12-month trends in health-related quality of life after hospitalization - comparison of tumor entities - Eichler, M.; Hornemann, B.; Hoenig, K.; Bergelt, C.; Faller, H.; Maatouk,; Stein, B.; Teufel, M.; Goerling, U.; Erim, Yesim; Geiser, F.; Niecke, A.; et al. (ONCOLOGY RESEARCH AND TREATMENT, 2022)
CRIS-Team WoS Importer:2022-11-18

2D:4D biomarker reliability and validity in a within-subject pregnancy-childhood-adolescence cohort - Eichler, Anna; Kaufmann, Franziska; Titzmann, Adriana; Fasching, Peter; Beckmann, Matthias; Gerlach, Jennifer; Kratz, Oliver; Moll, Gunther; Buchholz, Verena Nadine; Kornhuber, Johannes; Lenz, Bernd (Early Human Development, 2023)
Background: A lot of studies use the second-to-fourth digit length ratio (2D:4D) as a biomarker for intrauterine androgen load to predict behavioral and mental health problems. Thus, knowledge of 2D:4D's metric properties, namely reliability and validity, is essential. Method: 2D:4D handscans were available from 149 adolescents (M = 13.32 years, SD = 0.35) and their mothers. For 88 adolescents, there were also primary-school age handscans (M = 7.87 years, SD = 0.68). Prenatal risks for the 1st to 3rd trimesters were recorded during the 3rd trimester of pregnancy (alcohol exposition: meconium biomarker and maternal self-report; nicotine exposition: maternal self-report; maternal depressive symptoms and subjective stress: questionnaires). Results: The 2D:4D ratio was highly stable from childhood to early adolescence. However, both developmental and sex effects were present: The 2D:4D ratio increased with age and was higher in adolescent girls vs. boys. Significant 2D:4D mother-child associations were found for girls. Significant main effects could be found for the prenatal risk factors alcohol (self-report) and nicotine consumption. Conclusion: In line with earlier studies, the 2D:4D biomarker proved to be an inter-individually stable measure with an intra-individual increase from childhood to early adolescence. Sex differences in adolescence and associations with maternal prenatal health behaviour underline the validity of the biomarker. Findings on heritability emphasize the importance of interpreting 2D:4D results in a sex-specific manner.
CRIS-Team Scopus Importer:2023-04-28
Keywords: 2D:4D ratio; Alcohol; Androgen load; Biomarker; Construct validity; Heritability; Nicotine; Pregnancy risk; Prenatal; Retest reliability; Stability; Testosterone exposure

3-D gesture-based scene navigation in medical imaging applications using Time-of-Flight cameras - Soutschek, Stefan; Penne, Jochen; Hornegger, Joachim; Kornhuber, Johannes (2008 IEEE Computer Society Conference on Computer Vision and Pattern Recognition Workshops, CVPR Workshops, 2008)
For a lot of applications, and particularly for medical intra-operative applications, the exploration of and navigation through 3-D image data provided by sensors like ToF (Time-of-Flight) cameras, MUSTOF (Multisensor-Time-of- Flight) endoscopes or CT (Computed Tomography)[8], requires a user-interface which avoids physical interaction with an input device. Thus, we process a touchless userinterface based on gestures classified by the data provided by a ToF camera. Reasonable and necessary user interactions are described. For those interactions a suitable set of gestures is introduced. A user-interface is then proposed, which interprets the current gesture and performs the assigned functionality. For evaluating the quality of the developed user-interface we considered the aspects of classification rate, real-time applicability, usability, intuitiveness and training lime. The results of our evaluation show that our system, which provides a classification rate of 94.3% at a framerate of 11 frames per second, satisfactorily addresses all these quality requirements. © 2008 IEEE.

A 10-Year-Old Girl’s Dysfunctional ‘Self-Help’ in ADHD: Suppression of Hyperkinetic Symptoms via Self-Induced Weight Loss in the Context of Anorexia Nervosa—A Case Report - Mestermann, Stefan; Stonawski, Valeska; Böhm, Lea; Kratz, Oliver; Moll, Gunther; Horndasch, Stefanie (Children, 2023)
Anorexia Nervosa (AN) and Attention Deficit Hyperactivity Disorder (ADHD) are frequent mental disorders in child and adolescent psychiatry. Comorbidity of these disorders is, however, rare among minors. Thus, little is known about their mutual impact on illness development as well as diagnostic and therapeutic influencing factors. We report the case of a 10-year old girl with AN and massive underweight. At the age of 5, ADHD had been diagnosed. Application of ADHD-specific medication had been refused by her caregiver. As of 3rd grade, hyperkinetic symptoms were significantly reduced, which was later linked to beginning AN-induced weight loss. At inpatient admission, no clinically relevant ADHD-related symptoms were present. Accompanying weight gain, rather ‘sudden’ appearance of attention difficulties, motoric hyperactivity and impulsivity were reported, widely impairing our patient’s schoolwork and further daily life. Methylphenidate medication showed good clinical response and tolerability. We hypothesize that the former massive underweight had suppressed ADHD-specific behaviour. AN with significant weight loss could possibly mask hyperkinetic symptoms in children. Thus, sufficient clinical diagnostics and intense monitoring during ED treatment are required. Physicians and therapists should be sensitized for interactions in the joint occurrence of these mental disorders among minors.
CRIS-Team Scopus Importer:2023-10-06
Keywords: ADHD; anorexia nervosa; child and adolescent psychiatry; comorbidity; mental health; methylphenidate; weight loss

A bimodal neurophysiological study of motor control in attention-deficit hyperactivity disorder: a step towards core mechanisms? - Heinrich, Hartmut; Hoegl, Thomas; Moll, Gunther; Kratz, Oliver (Brain, 2014)
Knowledge about the core neural mechanisms of attention-deficit hyperactivity disorder, a pathophysiologically heterogeneous psychiatric disorder starting in childhood, is still limited. Progress may be achieved by combining different methods and levels of investigation. In the present study, we investigated neural mechanisms of motor control in 19 children with attention-deficit hyperactivity disorder (aged 9-14 years) and 21 age-matched typically developing children by relating neural markers of attention and response control (using event-related potentials) and measures of motor excitability/inhibition (evoked by transcranial magnetic stimulation). Thus, an interplay of processes at a subsecond scale could be studied. Using a monetary incentives-based cued Go/No-Go task, parameters that are well-known to be reduced in attention-deficit hyperactivity disorder were analysed: event-related potential components P3 (following cue stimuli; in Go and No-Go trials) and contingent negative variation as well as the transcranial magnetic stimulation-based short-interval intracortical inhibition measured at different latencies in Go and No-Go trials. For patient and control groups, different associations were obtained between performance, event-related potential and transcranial magnetic stimulation measures. In children with attention-deficit hyperactivity disorder, the P3 amplitude in Go trials was not correlated with reaction time measures but with short-interval intracortical inhibition at rest (r=0.56, P=0.01). In No-Go trials, P3 and short-interval intracortical inhibition after inhibiting the response (at 500 ms post-stimulus) were correlated in these children only (r=0.62; P=0.008). A classification rate of 90% was achieved when using short-interval intracortical inhibition (measured shortly before the occurrence of a Go or No-Go stimulus) and the amplitude of the P3 in cue trials as input features in a linear discriminant analysis. Findings indicate deviant neural implementation of motor control in children with attention-deficit hyperactivity disorder reflecting compensatory cognitive mechanisms as a result of a basal motor cortical inhibitory deficit (reduced activation of inhibitory intracortical interneurons). Both deviant inhibitory and attentional processes, which are not related to each other, seem to be characteristic for attention-deficit hyperactivity disorder at the neural level in motor control tasks. The underlying neural mechanisms, which are probably not restricted to the motor cortex and the posterior attention network, may play a key role in the pathophysiology of this child psychiatric disorder. The high classification rate can further be interpreted as a step towards the development of neural markers. In summary, the bimodal neurophysiological concept may contribute to developing an integrative framework for attention-deficit hyperactivity disorder.
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Ablation of the presynaptic organizer Bassoon in excitatory neurons retards dentate gyrus maturation and enhances learning performance - Annamneedi, Anil; Caliskan, Guersel; Mueller, Sabrina; Montag, Dirk; Budinger, Eike; Angenstein, Frank; Fejtová, Anna; Tischmeyer, Wolfgang; Gundelfinger, Eckart D.; Stork, Oliver (Brain Structure & Function, 2018)
Bassoon is a large scaffolding protein of the presynaptic active zone involved in the development of presynaptic terminals and in the regulation of neurotransmitter release at both excitatory and inhibitory brain synapses. Mice with constitutive ablation of the Bassoon (Bsn) gene display impaired presynaptic function, show sensory deficits and develop severe seizures. To specifically study the role of Bassoon at excitatory forebrain synapses and its relevance for control of behavior, we generated conditional knockout (Bsn cKO) mice by gene ablation through an Emx1 promoter-driven Cre recombinase. In these animals, we confirm selective loss of Bassoon from glutamatergic neurons of the forebrain. Behavioral assessment revealed that, in comparison to wild-type littermates, Bsn cKO mice display selectively enhanced contextual fear memory and increased novelty preference in a spatial discrimination/pattern separation task. These changes are accompanied by an augmentation of baseline synaptic transmission at medial perforant path to dentate gyrus (DG) synapses, as indicated by increased ratios of field excitatory postsynaptic potential slope to fiber volley amplitude. At the structural level, an increased complexity of apical dendrites of DG granule cells can be detected in Bsn cKO mice. In addition, alterations in the expression of cellular maturation markers and a lack of age-dependent decrease in excitability between juvenile and adult Bsn cKO mice are observed. Our data suggest that expression of Bassoon in excitatory forebrain neurons is required for the normal maturation of the DG and important for spatial and contextual memory.
EVALuna2:211603

Abrogating Native α-Synuclein Tetramers in Mice Causes a L-DOPA-Responsive Motor Syndrome Closely Resembling Parkinson's Disease - Nuber, Silke; Rajsombath, Molly; Minakaki, Georgia; Winkler, Jürgen; Müller, Christian P.; Ericsson, Maria; Caldarone, Barbara; Dettmer, Ulf; Selkoe, Dennis J. (Neuron, 2018)
α-Synuclein (αS) regulates vesicle exocytosis but forms insoluble deposits in Parkinson's disease (PD). Developing disease-modifying therapies requires animal models that reproduce cardinal features of PD. We recently described a previously unrecognized physiological form of αS, α-helical tetramers, and showed that familial PD-causing missense mutations shift tetramers to aggregation-prone monomers. Here, we generated mice expressing the fPD E46K mutation plus 2 homologous E→K mutations in adjacent KTKEGV motifs. This tetramer-abrogating mutant causes phenotypes similar to PD. αS monomers accumulate at membranes and form vesicle-rich inclusions. αS becomes insoluble, proteinase K-resistant, Ser129-phosphorylated, and C-terminally truncated, as in PD. These changes affect regions controlling motor behavior, including a decrease in nigrostriatal dopaminergic neurons. The outcome is a progressive motor syndrome including tremor and gait and limb deficits partially responsive to L-DOPA. This fully penetrant phenotype indicates that tetramers are required for normal αS homeostasis and that chronically shifting tetramers to monomers may result in PD, with attendant therapeutic implications.
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Absolute SPECT/CT quantification of cerebral uptake of 99mTc-HMPAO for patients with neurocognitive disorders - Welz, Friedrich; Sanders, James Chester; Kuwert, Torsten; Maler, Juan; Kornhuber, Johannes; Ritt, Philipp (Nuklearmedizin-Nuclear Medicine, 2016)
It was reported from planar imaging studies that the cerebral uptake of injected 99mTc-HMPAO activity is about 4-7% in humans. Recent work has shown that modern SPECT/CT devices are able to quantify the tissue concentration of radioactivity in vivo in absolute units (Bq/ml), while avoiding the limitations of planar techniques. The aims of this study were (a) to determine the cerebral uptake of 99mTc-HMPAO in absolute units in SPECT/CT, (b) to investigate potential differences in absolute tracer uptake for patients suspected of dementia.We performed 99mTc-HMPAO SPECT/CT in 65 patients with suspected dementia. 99mTc-HMPAO uptake was determined using a previously published quantitative SPECT/CT protocol. The absolute HMPAO uptake and the results of a regionalized analysis were compared for MMSE and NINCDS-ADRDA based patient groups.The mean absolute uptake of 99mTc-HMPAO for our patient population was 4.3 ± 0.8% of the injected dose. The uptake, as well as the regionalized analysis yielded significantly different results for low (<=23) and high (>23) MMSE groups and also for some of the NINCDS-ADRDA groups.Our results show that the absolute cerebral uptake of 99mTc-HMPAO is in the range of previously reported results, obtained by planar techniques. Absolute uptake is significantly different between the patient groups.
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Abuse potential and adverse cognitive effects of mitragynine (kratom) - Yusoff, Nurul H. M.; Suhaimi, Farah W.; Vadivelu, Raja K.; Hassan, Zurina; Rümler, Anne; Rotter, Andrea; Amato, Davide; Dringenberg, Hans C.; Mansor, Sharif M.; Navaratnam, Visweswaran; Müller, Christian P. (Addiction Biology, 2016)
Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug.
EVALuna2:23760

Access to Pain Management Programs: A Multifactorial Analysis of the Pathways of Care for Chronic Pain Patients in the University Clinic Erlangen - Dorscht, Lisa; Schön, Christoph; Geiss, Christa; Grässel, Elmar; Donath, Carolin (Gesundheitswesen, 2019)
BACKGROUND: Different treatment options are offered for patients suffering from chronic pain, which differ in intensity and costs: 1) monodisciplinary treatment, mostly in outpatient care and 2) interdisciplinary treatment with the option of participating in pain management programs as outpatients or inpatients. The present work investigates how patients at the University Clinic Erlangen receiving monodisciplinary treatment differ from those receiving interdisciplinary treatment (research question I) as well as how patients participating in a pain management program differ from those who do not (research question II). The aim is to generate insights into whether the differences between the patient groups under various treatment modalities reflect the officially defined criteria for the indication of chronic pain management programs. METHODS: Routine data of 1,833 patients treated from January 2008 to March 2013 at the University Clinic Erlangen were analyzed. After univariate preanalyses and checks for multicollinearity, the remaining variables were used for the final multivariate model (multiple binary logistic regression) for research question I and II. RESULTS: Research question I: Patients getting interdisciplinary treatment were more often employed, had higher affective experience of pain, more often regarded their pain as treatable, had more often participated in at least one pain-associated rehabilitation treatment in the past, were younger and rarely had application for retirement in consideration. Research question II: Patients who participated in a pain management program were more often female, more often employed, described their pain as mainly located at the upper part of the body, had more concomitant symptoms, were more often diagnosed with musculoskeletal pain and rarely had a retirement request pending. CONCLUSIONS: It could be shown that patients in the analyzed pathways of care mainly differed in demographic variables, and regarding pain management programs, also in the type of pain. Differences between patients in different treatment paths reflecting the officially defined indication criteria for chronic pain management programs were detectable only to a minor extent. Clearer and operational practical guidance should help support the clinical decision to assign patients to different treatment options and close the gap between theory and practice.
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Acculturation and depressive symptoms among Turkish immigrants in Germany - Morawa, Eva; Erim, Yesim (International Journal of Environmental Research and Public Health, 2014)
EVALuna2:24015

Acculturation, depressive Symptoms and Life Satisfaction among Migrants of Turkish Origin in Germany: Gender-specific and Generation-related Aspects - Morawa, Eva; Brand, Tilman; Dragano, Nico; Joeckel, Karl-Heinz; Moebus, Susanne; Erim, Yesim (ZEITSCHRIFT FUR PSYCHOSOMATISCHE MEDIZIN UND PSYCHOTHERAPIE, 2021)
CRIS-Team WoS Importer:2021-07-16

ACCURACY AND CONCORDANCE OF MEASUREMENT METHODS TO ASSESS NONADHERENCE AFTER RENAL TRANSPLANTATION - A PROSPECTIVE STUDY - Lieb, Marietta; Erim, Yesim (TRANSPLANT INTERNATIONAL, 2020)
CRIS-Team WoS Importer:2020-11-06

Accuracy and concordance of measurement methods to assess non-adherence after renal transplantation - A prospective study - Lieb, Marietta; Hepp, Tobias; Schiffer, Mario; Opgenoorth, Mirian; Erim, Yesim (BMC Nephrology, 2020)
Background: Non-adherence (NA) to immunosuppressants (IS) among renal transplant recipients (RTRs) is associated with higher risk of allograft rejection, graft loss, and mortality. A precise measurement of NA is indispensable, although its prevalence differs greatly depending on the respective measurement methods. The objective of this study was to assess the accuracy and concordance of different measurement methods of NA in patients after renal transplantation. Design and methods: This was a single-center prospective observational study. At baseline (T0), NA was measured via physicians' estimates (PE), self-reports (SR), and tacrolimus trough level variability (CV%) in 78 RTRs. A Visual Analogue Scale (VAS, 0-100%) was applied both for SR and PE. In addition, we used BAASIS© for SR and a 5-point Likert scale for PE. NA was measured prospectively via electronic monitoring (EM, VAICA©) during a three month period. Meanwhile, all participants received phone calls in a two week interval (T1-T6) during which SRs were given. Results: Seventy-eight RTRs participated in our study. At t0, NA rates of 6.4%, 28.6%, and 15.4% were found for PE, SR, and CV%, respectively. No correlation was found between these methods. During the study, the percentages of self-reported and electronically monitored adherence remained high, with a minimum mean of 91.2% for the strictest adherence measure (Timing Adherence ±30 min). Our results revealed a moderate to high association between SR and EM. In contrast to PE and CV%, SR significantly predicted electronically monitored adherence. Overall, a decreasing effect of electronically monitored adherence was found for both taking and timing adherence (±2 h, ±30 min) over the course of the study. Discussion: The moderate to high concordance of SR and EM suggests that both methods measure NA equally accurately. SR seems to be a method that can adequately depict electronically monitored NA and may represent a good and economical instrument to assess NA in clinical practice. The increased adherence at the beginning of the study and its subsequent decrease suggests an intervention effect. Surveillance of IS intake via EM with intermittent phone calls could improve adherence on a short-term basis. To establish long-term effects, further research is necessary.
CRIS-Team Scopus Importer:2020-04-14
Keywords: Accuracy; Adherence; Electronic monitoring; IS trough level variability; Measurement methods; Physicians' estimates; Prospective study; Renal transplant recipients; Self-report

A central role for the acid sphingomyelinase/ceramide system in neurogenesis and major depression - Gulbins, Erich; Walter, Silke; Becker, Katrin Anne; Halmer, Ramona; Liu, Yang; Reichel, Martin; Edwards, Michael J.; Müller, Christian P.; Fassbender, Klaus; Kornhuber, Johannes (Journal of Neurochemistry, 2015)
Major depressive disorder is a severe and chronic illness with high lifetime prevalence and a high incidence of suicide as the cause of death for patients with this diagnosis. Major depressive disorder is often treated with anti-depressants. Although these drugs have been used for many years, their exact mode of action is still unknown. It has been suggested that many anti-depressants act by increasing the concentrations of serotonergic transmitters in the synaptic space. However, recent studies have examined the effects of anti-depressants on neurogenesis in the hippocampus, the restoration of hippocampal neuronal networks that may be affected by major depression, and the regulation of the hypothalamic-pituitary-adrenal axis by immature neurons in the hippocampus. Here, we present and discuss a novel hypothesis suggesting that these events are regulated by the concentrations of sphingolipids, in particular ceramide, in the hippocampus. These concepts suggest that the acid sphingomyelinase/ceramide system plays a central role in the pathogenesis of major depression and may be a novel target for anti-depressants.
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Achtsamkeit in der entwicklungsorientierten Suchtprävention und -therapie: Rational, Design und Ziele des Forschungsverbundes IMAC-Mind - Arnaud, Nicolas; Banaschewski, Tobias; Nees, Frauke; Bucholz, Verena Nadine; Klein, Michael; Reis, Olaf; Legenbauer, Tanja; Zapf, Antonia; Thomasius, Rainer (Praxis der Kinderpsychologie und Kinderpsychiatrie, 2020)
Mindfulness in Development-oriented Approaches to Substance Use Prevention and Therapy: Rationale, Design and Objectives of the Research Consortium IMAC-Mind Substance use disorders (SUD) are a major contributor to morbidity and mortality. They are typically initiated during adolescence and can have fatal implications for healthy development. Despite substantial scientific advances, there remains a need to prioritize research directed at reducing risks for SUD, particularly in vulnerable periods and populations from a developmental perspective. Research indicates that reward sensitivity, impulsivity, deficient self-regulation, and stress reactivity develop markedly in childhood and adolescence and play an important role in the initiation and maintenance of SUD. A growing number of research results suggest that these factors can be favorably influenced by mindfulness-based interventions and that mindfulness-based exercises can be successfully integrated into established prevention and treatment programs. In this paper we summarize the conceptual relationships between the development and maintenance of addiction disorders and mindfulness, discuss existing empirical findings with regard to childhood and adolescence, and present the aims, study designs and intervention models of the subprojects from the ongoing research network "IMAC-Mind: Improving Mental Health and Reducing Addiction in Childhood and Adolescence through Mindfulness: Mechanisms, Prevention and Treatment".
CRIS-Team Scopus Importer:2020-07-17
Keywords: Achtsamkeit; children and adolescents; Entwicklungspsychopathologie; Kinder- und Jugendpsychiatrie; mindfulness; prevention; Selbstregulation; self-regulation; Substance Use Disorder; Substanzbezogene Störungen; therapy

Acid sphingomyelinase – a regulator of canonical transient receptor potential channel 6 (TRPC6) activity - Zeitler, Stefanie; Ye, Lian; Andreyeva, Aksana; Schumacher, Fabian; Monti, Juliana; Nürnberg, Bernd; Nowak, Gabriel; Kleuser, Burkhard; Reichel, Martin; Fejtová, Anna; Kornhuber, Johannes; Rhein, Cosima; et al. (Journal of neurochemistry, 2019)
Recent investigations propose the acid sphingomyelinase (ASM)/ceramide system as a novel target for antidepressant action. ASM catalyzes the breakdown of the abundant membrane lipid sphingomyelin to the lipid messenger ceramide. This ASM-induced lipid modification induces a local shift in membrane properties, which influences receptor clustering and downstream signaling. Canonical transient receptor potential channels 6 (TRPC6) are non-selective cation channels located in the cell membrane that play an important role in dendritic growth, synaptic plasticity and cognition in the brain. They can be activated by hyperforin, an ingredient of the herbal remedy St. John’s wort for treatment of depression disorders. Because of their role in the context of major depression, we investigated the crosstalk between the ASM/ceramide system and TRPC6 ion channels in a pheochromocytoma cell line 12 neuronal cell model (PC12 rat pheochromocytoma cell line). Ca2+ imaging experiments indicated that hyperforin-induced Ca2+ influx through TRPC6 channels is modulated by ASM activity. While antidepressants, known as functional inhibitors of ASM activity, reduced TRPC6-mediated Ca2+ influx, extracellular application of bacterial sphingomyelinase rebalanced TRPC6 activity in a concentration-related way. This effect was confirmed in whole-cell patch clamp electrophysiology recordings. Lipidomic analyses revealed a decrease in very long chain ceramide/sphingomyelin molar ratio after ASM inhibition, which was connected with changes in the abundance of TRPC6 channels in flotillin-1–positive lipid rafts as visualized by western blotting. Our data provide evidence that the ASM/ceramide system regulates TRPC6 channels likely by controlling their recruitment to specific lipid subdomains and thereby fine-tuning their physical properties. (Figure presented.).
CRIS-Team Scopus Importer:2019-08-30
Keywords: acid sphingomyelinase; antidepressants; ceramide; hyperforin; lipid rafts; TRPC6

Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs - Gulbins, Erich; Palmada, Monica; Reichel, Martin; Lueth, Anja; Boehmer, Christoph; Amato, Davide; Müller, Christian P.; Tischbirek, Carsten H.; Groemer, Teja W.; Tabatabai, Ghazaleh; Becker, Katrin A.; Tripal, Philipp; et al. (Nature Medicine, 2013)
Major depression is a highly prevalent severe mood disorder that is treated with antidepressants. The molecular targets of antidepressants require definition. We investigated the role of the acid sphingomyelinase (Asm)-ceramide system as a target for antidepressants. Therapeutic concentrations of the antidepressants amitriptyline and fluoxetine reduced Asm activity and ceramide concentrations in the hippocampus, increased neuronal proliferation, maturation and survival and improved behavior in mouse models of stress-induced depression. Genetic Asm deficiency abrogated these effects. Mice overexpressing Asm, heterozygous for acid ceramidase, treated with blockers of ceramide metabolism or directly injected with C16 ceramide in the hippocampus had higher ceramide concentrations and lower rates of neuronal proliferation, maturation and survival compared with controls and showed depression-like behavior even in the absence of stress. The decrease of ceramide abundance achieved by antidepressant-mediated inhibition of Asm normalized these effects. Lowering ceramide abundance may thus be a central goal for the future development of antidepressants.
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Acid sphingomyelinase controls dopamine activity and responses to appetitive stimuli in mice - Kalinichenko, Liubov; Hammad, Lara; Reichel, Martin; Kohl, Zacharias; Gulbins, Erich; Kornhuber, Johannes; Müller, Christian P. (Brain Research Bulletin, 2019)
Alcohol use disorder and depression show a high comorbidity at clinical level with no treatment available selectively for this condition. A hyperfunction of acid sphingomyelinase (ASM) and resulting ceramide overload were recently identified as one pathway into this comorbidity. Here we analyzed the involvement of ASM, one of the main enzymes involved in ceramide synthesis, in the molecular control of monoaminergic systems in their basal activity and in response to pharmacological and natural reinforcers. The effects of alcohol and a palatable food on the extracellular levels of dopamine (DA), serotonin (5-HT), and noradrenaline (NE) were measured by in-vivo microdialysis in ASM overexpressing mice (tgASM). We found reduced basal extracellular DA levels in the nucleus accumbens (Nac) and dorsal hippocampus (DH) of tgASM mice with little effect on 5-HT and NE levels. In contrast, ASM overexpression potentiated the DA response to alcohol (2 g/kg, i.p.) in the DH and Nac, but reduced NE responses. DA and NE responses to a food stimulus were not altered in tgASM mice, but the Nac 5-HT response was enhanced.
CRIS-Team WoS Importer:2019-03-15

Acid Sphingomyelinase Impacts Canonical Transient Receptor Potential Channels 6 (TRPC6) Activity in Primary Neuronal Systems - Zeitler, Stefanie; Schumacher, Fabian; Monti, Juliana; Anni, Daniela; Guhathakurta, Debarpan; Kleuser, Burkhard; Friedland, Kristina; Fejtová, Anna; Kornhuber, Johannes; Rhein, Cosima (Cells, 2020)
: The acid sphingomyelinase (ASM)/ceramide system exhibits a crucial role in the pathology of major depressive disorder (MDD). ASM hydrolyzes the abundant membrane lipid sphingomyelin to ceramide that regulates the clustering of membrane proteins via microdomain and lipid raft organization. Several commonly used antidepressants, such as fluoxetine, rely on the functional inhibition of ASM in terms of their antidepressive pharmacological effects. Transient receptor potential canonical 6 (TRPC6) ion channels are located in the plasma membrane of neurons and serve as receptors for hyperforin, a phytochemical constituent of the antidepressive herbal remedy St. John's wort. TRPC6 channels are involved in the regulation of neuronal plasticity, which likely contributes to their antidepressant effect. In this work, we investigated the impact of reduced ASM activity on the TRPC6 function in neurons. A lipidomic analysis of cortical brain tissue of ASM deficient mice revealed a decrease in ceramide/sphingomyelin molar ratio and an increase in sphingosine. In neurons with ASM deletion, hyperforin-mediated Ca2+-influx via TRPC6 was decreased. Consequently, downstream activation of nuclear phospho-cAMP response element-binding protein (pCREB) was changed, a transcriptional factor involved in neuronal plasticity. Our study underlines the importance of balanced ASM activity, as well as sphingolipidome composition for optimal TRPC6 function. A better understanding of the interaction of the ASM/ceramide and TRPC6 systems could help to draw conclusions about the pathology of MDD.
CRIS-Team Scopus Importer:2020-12-04
Keywords: acid sphingomyelinase; major depressive disorder; sphingolipids; trpc6

Acid Sphingomyelinase Is a Modulator of Contextual Fear - Zoicas, Iulia; Kornhuber, Johannes (International Journal of Molecular Sciences, 2022)
Acid sphingomyelinase (ASM) regulates a variety of physiological processes and plays an important role in emotional behavior. The role of ASM in fear-related behavior has not been investigated so far. Using transgenic mice overexpressing ASM (ASMtg) and ASM deficient mice, we studied whether ASM regulates fear learning and expression of cued and contextual fear in a classical fear conditioning paradigm, a model used to investigate specific attributes of post-traumatic stress disorder (PTSD). We show that ASM does not affect fear learning as both ASMtg and ASM deficient mice display unaltered fear conditioning when compared to wild-type littermates. However, ASM regulates the expression of contextual fear in a sex-specific manner. While ASM overexpression enhances the expression of contextual fear in both male and female mice, ASM deficiency reduces the expression of contextual fear specifically in male mice. The expression of cued fear, however, is not regulated by ASM as ASMtg and ASM deficient mice display similar tone-elicited freezing levels. This study shows that ASM modulates the expression of contextual fear but not of cued fear in a sex-specific manner and adds a novel piece of information regarding the involvement of ASM in hippocampal-dependent aversive memory.
CRIS-Team Scopus Importer:2022-04-01
Keywords: ASM; Contextual fear; Cued fear; Fear conditioning; Fear extinction; Fear learning; Knock-out mice; PTSD; Transgenic mice

A Climbing (Bouldering) Intervention to Increase the Psychological Well-Being of Adolescents in the Bekaa Valley in Lebanon-Study Protocol for a Controlled Trial - Luttenberger, Katharina; Najem, Charbel; Rosenbaum, Simon; Sifri, Charles; Kind, Leona; Baggenstos, Beat (International Journal of Environmental Research and Public Health, 2023)
(1) Background: Adolescent refugees in Lebanon and Lebanese youth are both at high risk of suffering from reduced psychological well-being. Sport is an evidence-based strategy for improving mental and physical health, and climbing is a type of sport that may positively impact both. The aim of this study is to test the effect of a manualized, psychosocial group climbing intervention on the well-being, distress, self-efficacy, and social cohesion of adolescents in Lebanon. In addition, the mechanisms behind psychological changes will be investigated. (2) Methods: In this mixed-methods waitlist-controlled study, we are allocating a minimum of 160 participants to an intervention (IG) or a control group (CG). The primary outcome is overall mental well-being (WEMWBS) after the 8-week intervention. Secondary outcomes include distress symptoms (K-6 Distress Scale), self-efficacy (General Self-Efficacy Scale; GSE), and social cohesion. Potential mechanisms of change and implementation factors are being investigated through qualitative interviews with a subgroup of 40 IG participants. (3) Conclusions: The results may contribute to knowledge of sports interventions and their effects on psychological well-being and will provide insights regarding low-intensity interventions for supporting adolescent refugees and host populations in conflict-affected settings. The study was prospectively registered at the ISRCTN platform (current-controlled trials). ISRCTN13005983.
CRIS-Team Scopus Importer:2023-03-24
Keywords: adolescent mental health; bouldering/climbing; intervention studies; physical activity; refugees

A combined miRNA-piRNA signature to detect Alzheimer's disease - Jain, Gaurav; Stuendl, Anne; Rao, Pooja; Berulava, Tea; Pena Centeno, Tonatiuh; Kaurani, Lalit; Burkhardt, Susanne; Delalle, Ivana; Kornhuber, Johannes; Hüll, Michael; Maier, Wolfgang; Peters, Oliver; et al. (Translational Psychiatry, 2019)
Alzheimer's disease (AD) is the most common neurodegenerative disorder causing huge emotional and economic burden to our societies. An effective therapy has not been implicated yet, which is in part also due to the fact that pathological changes occur years before clinical symptoms manifest. Thus, there is a great need for the development of a translatable biomarker. Recent evidence highlights microRNAs as candidate biomarkers. In this study, we use next-generation sequencing to study the small noncoding RNAome (sncRNAome) in exosomes derived from human cerebrospinal fluid (CSF). We show that the sncRNAome from CSF-derived exosomes is dominated not only by microRNAs (miRNAs) but also by PIWI-interacting RNAs (piRNAs). We define a combined signature consisting of three miRNAs and three piRNAs that are suitable to detect AD with an AUC of 0.83 in a replication cohort and furthermore predict the conversion of mild-cognitive impaired (MCI) patients to AD dementia with an AUC of 0.86 for the piRNA signature. When combining the smallRNA signature with pTau and Aβ 42/40 ratio the AUC reaches 0.98. Our study reports a novel exosomal small noncoding RNA signature to detect AD pathology and provides the first evidence that in addition to miRNAs, piRNAs should also be considered as a candidate biomarker for AD.
CRIS-Team Scopus Importer:2019-10-18

A comment on the paper 'Biomarkers in Multiple Sclerosis' by Sapko et al - Lewczuk, Piotr; Kornhuber, Johannes; Mroczko, Barbara (Neurologia I Neurochirurgia Polska, 2021)
CRIS-Team WoS Importer:2021-04-09

A Comparison of Operational Definitions for Mild Cognitive Impairment. - Polcher, Alexandra; Wolfsgruber, Steffen; Peters, Oliver; Froelich, Lutz; Wiltfang, Jens; Kornhuber, Johannes; Huell, Michael; Ruether, Eckart; Lewczuk, Piotr; Maier, Wolfgang; Jessen, Frank; Wagner, Michael (Journal of Alzheimer's Disease, 2022)
BACKGROUND: Consideration of many tests from different cognitive domains in defining mild cognitive impairment (MCI) is clinical routine, but guidelines for a neuropsychological operationalization of MCI are lacking. OBJECTIVE: Among different operational MCI criteria, to identify those which are best in predicting either conversion to dementia, or a biomarker profile indicative for Alzheimer's disease (AD). METHODS: Memory clinic patients without dementia (N = 558; mean age = 66; up to 3 years of follow-up; n = 360 with baseline CSF biomarkers) were included in an observational study using most liberal criteria of cognitive impairment. Four operational definitions of MCI were retrospectively applied: 1) amnestic MCI (CERAD word list delayed recall), 2) CERAD total score, 3) comprehensive criteria and 4) base rate corrected CERAD. We compared their accuracy in predicting incident all-cause dementia or AD dementia within three years, or a concurrent CSF Aβ42/tau-ratio indicative of AD. RESULTS: The four definitions overlapped considerably, classified 35-58% of the original sample as impaired and were associated with markedly increased PPVs regarding incident all-cause dementia (39-46% versus 26% of the original sample), AD dementia and AD biomarker positivity. The base rate corrected MCI definition had the highest prognostic accuracy. CONCLUSION: he operational criteria examined seem suitable to specify MCI in memory clinic settings, as they identify subjects at high risk of clinical progression. Depending on the neuropsychological battery in use, one or several of these criteria could help to calibrate the clinical judgment of test results, reduce false-positive decisions, and define risk-enriched groups for clinical trials.
EVALuna2:506089

A consistent eduation could clearly increase the disposition of organ donation with the population of Turkish-Islamic descent - Heuer, M.; Kaiser, G. M.; Saner, F. H.; Erim, Yesim; Wirges, U.; Paul, A.; Gerken, G.; Canbay, A. (MED WELT, 2009)
Keywords: Education; Organ donation; Immigrant; Religion

Activin Controls Ethanol Potentiation of Inhibitory Synaptic Transmission Through GABAA Receptors and Concomitant Behavioral Sedation - Zheng, Fang; Puppel, Anne; Hubert, Sabine E.; Link, Andrea; Eulenburg, Volker; van Brederode, Johannes; Müller, Christiane; Alzheimer, Christian (Neuropsychopharmacology, 2016)
Activin, a member of the transforming growth factor-? family, exerts multiple functions in the nervous system. Originally identified as a neurotrophic and -protective agent, increasing evidence implicates activin also in the regulation of glutamatergic and GABAergic neurotransmission in brain regions associated with cognitive and affective functions. To explore how activin impacts on ethanol potentiation of GABA synapses and related behavioral paradigms, we used an established transgenic model of disrupted activin receptor signaling, in which mice express a dominant-negative activin receptor IB mutant (dnActRIB) under the control of the CaMKII? promoter. Comparison of GABAA receptor currents in hippocampal neurons from dnActRIB mice and wild-type mice showed that all concentrations of ethanol tested (30-150 mM) produced much stronger potentiation of phasic inhibition in the mutant preparation. In dentate granule cells of dnActRIB mice, tonic GABA inhibition was more pronounced than in wild-type neurons, but remained insensitive to low ethanol (30 mM) in both preparations. The heightened ethanol sensitivity of phasic inhibition in mutant hippocampi resulted from both pre- and postsynaptic mechanisms, the latter probably involving PKC?. At the behavioral level, ethanol produced significantly stronger sedation in dnActRIB mice than in wild-type mice, but did not affect consumption of ethanol or escalation after withdrawal. We link the abnormal narcotic response of dnActRIB mice to ethanol to the excessive potentiation of inhibitory neurotransmission. Our study suggests that activin counteracts oversedation from ethanol by curtailing its augmenting effect at GABA synapses.
EVALuna2:4739

Acute stress responses of autonomous nervous system, HPA axis, and inflammatory system in posttraumatic stress disorder - von Majewski, Kristin; Kraus, Olga; Rhein, Cosima; Lieb, Marietta; Erim, Yesim; Rohleder, Nicolas (Translational Psychiatry, 2023)
Posttraumatic stress disorder (PTSD) does not only have direct consequences for well-being, but it also comes with a significant risk for severe somatic health consequences. A number of previous studies have pointed to alterations in stress systems in traumatized persons, as well as the inflammatory system, which might be important links in the pathway between trauma, PTSD, and health consequences. The aim of this study was to investigate acute stress responses in PTSD patients compared with healthy controls. Twenty-seven PTSD patients and 15 controls were exposed to the Trier Social Stress Test (TSST), and we measured salivary cortisol, salivary alpha-amylase (sAA), plasma interleukin-6 (IL-6), as well as heart rate and heart rate variability (HRV) at different time points before, during and after the stress test. Results revealed similar stress responses between patients and controls, but lower baseline cortisol levels and higher IL-6 baseline levels in PTSD patients. Increases in sAA stress responses were significantly lower in patients, while sAA concentrations were higher in the PTSD group during intervention. HRV was markedly decreased in patients and showed a significantly blunted acute stress response with a slower recovery after TSST. These results confirm previous findings of marked stress system dysregulations in PTSD and add to the literature on acute stress reactivity in PTSD which appears to show stress system-specific changes. Overall, these results have implications for our understanding of potential risk and resilience factors in the response to trauma.
CRIS-Team Scopus Importer:2023-02-10

Addiction Research: And the Growing Realization of the Magnitude of the Task - Müller, Christian P. (Sucht, 2021)
CRIS-Team WoS Importer:2021-09-03

Additional Data from Omitted Study in a Meta-analysis of the Association of Depression and Anxiety with Autoimmune Thyroiditis - Siegmann, Eva-Maria; Grömer, Teja Wolfgang (JAMA Psychiatry, 2019)
CRIS-Team Scopus Importer:2019-07-02

Additive sex-specific influence of common non-synonymous DISC1 variants on amygdala, basal ganglia, and white cortical surface area in healthy young adults - Mühle, Christiane; Kreczi, Jakob; Rhein, Cosima; Richter-Schmidinger, Tanja; Alexopoulos, Panagiotis; Dörfler, Arnd; Lenz, Bernd; Kornhuber, Johannes (Brain Structure & Function, 2017)
The disrupted-in-schizophrenia-1 (DISC1) gene is known for its role in the development of mental disorders. It is also involved in neurodevelopment, cognition, and memory. To investigate the association between DISC1 variants and brain morphology, we analyzed the influence of the three common non-synonymous polymorphisms in DISC1 on specific brain structures in healthy young adults. The volumes of brain regions were determined in 145 subjects by magnetic resonance imaging and automated analysis using FreeSurfer. Genotyping was performed by high resolution melting of amplified products. In an additive genetic model, rs6675281 (Leu607Phe), rs3738401 (Arg264Gln), and rs821616 (Ser704Cys) significantly explained the volume variance of the amygdala (p = 0.007) and the pallidum (p = 0.004). A higher cumulative portion of minor alleles was associated with larger volumes of the amygdala (p = 0.005), the pallidum (p = 0.001), the caudate (p = 0.024), and the putamen (p = 0.007). Sex-stratified analysis revealed a strong genetic effect of rs6675281 on putamen and pallidum in females but not in males and an opposite influence of rs3738401 on the white cortical surface in females compared to males. The strongest single association was found for rs821616 and the amygdala volume in male subjects (p < 0.001). No effect was detected for the nucleus accumbens. We report-to our knowledge-for the first time a significant and sex-specific influence of common DISC1 variants on volumes of the basal ganglia, the amygdala and on the cortical surface area. Our results demonstrate that the additive model of all three polymorphisms outperforms their single analysis.
EVALuna2:33147

ADHERENCE AND MENTAL HEALTH AFTER RENAL AND HEART TRANSPLANTATION - A STUDY PROTOCOL - Lieb, Marietta; Erim, Yesim (2018)
EVALuna2:214428

Adherence in transplantation medicine - special aspects after lung and heart transplantation - Erim, Yesim; Beckmann, M. B.; Marggraf, G.; Azhari, P.; Senf, W. (Psychotherapie Psychosomatik Medizinische Psychologie, 2009)

Adherence to Immunosuppressive Medication Following Organ Transplantation - Nöhre, Mariel; Erim, Yesim; Vitinius, Frank; Klewitz, Felix; Schiffer, Mario; De Zwaan, Martina (Psychotherapie Psychosomatik Medizinische Psychologie, 2018)

A Direct Performance Test for Assessing Activities of Daily Living in Patients with Mild Degenerative Dementia: The Development of the ETAM and Preliminary Results - Schmiedeberg-Sohn, Anke; Grässel, Elmar; Luttenberger, Katharina (Dementia and Geriatric Cognitive Disorders Extra, 2015)
There are currently only a few performance tests that assess the capacity to perform activities of daily living. These measures frequently require a long time to administer, are strongly cognition oriented, or have not been adequately validated.The Erlangen Test of Activities of Daily Living in Mild Dementia (ETAM) was developed in a 4-phase process that was based on the International Classification of Functioning, Disability, and Health (ICF). A pilot study was conducted on 30 subjects with mild dementia with a mean age of 80 years. The subjects' mean score on the MMSE was 21.5. Twenty-one of the 30 subjects were women.Ten items were developed and tested in the pilot study. The mean time required to complete the test was 26 min. The item analysis showed difficulties that ranged primarily from r = 0.28 to r = 0.79. The ETAM had a moderate correlation with the MMSE (rMMSE = 0.310) and a low correlation with the Geriatric Depression Scale-15 (GDS-15; rGDS-15 = 0.149).The preliminary version of the ETAM is quick and easy to use and has predominantly satisfactory item characteristics. There still is the need to revise the items 'giving directions' and 'making tea' with regard to standardisation.
EVALuna2:23692

A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter - Amato, Davide; Canneva, Fabio; Cumming, Paul; Maschauer, Simone; Groos, Dominik; Dahlmanns, Jana Katharina; Grömer, Teja W.; Chiofalo, Lisa; Dahlmanns, Marc; Zheng, Fang; Kornhuber, Johannes; Prante, Olaf; et al. (Molecular Psychiatry, 2018)
Antipsychotic drugs are effective interventions in schizophrenia. However, the efficacy of these agents often decreases over time, which leads to treatment failure and symptom recurrence. We report that antipsychotic efficacy in rat models declines in concert with extracellular striatal dopamine levels rather than insufficient dopamine D2 receptor occupancy. Antipsychotic efficacy was associated with a suppression of dopamine transporter activity, which was reversed during failure. Antipsychotic failure coincided with reduced dopamine neuron firing, which was not observed during antipsychotic efficacy. Synaptic field responses in dopamine target areas declined during antipsychotic efficacy and showed potentiation during failure. Antipsychotics blocked synaptic vesicle release during efficacy but enhanced this release during failure. We found that the pharmacological inhibition of the dopamine transporter rescued antipsychotic drug treatment outcomes, supporting the hypothesis that the dopamine transporter is a main target of antipsychotic drugs and predicting that dopamine transporter blockers may be an adjunct treatment to reverse antipsychotic treatment failure.
EVALuna2:35828

Adult alcohol drinking and emotional tone are mediated by neutral sphingomyelinase during development in males - Kalinichenko, Liubov; Mühle, Christiane; Jia, Tianye; Anderheiden, Felix; Datz, Maria; Eberle, Anna-Lisa; Eulenburg, Volker; Granzow, Jonas; Hofer, Martin Jürgen; Hohenschild, Julia; Huber, Sabine; Kämpf, Stefanie; et al. (Cerebral Cortex, 2022)
Alcohol use, abuse, and addiction, and resulting health hazards are highly sex-dependent with unknown mechanisms. Previously, strong links between the SMPD3 gene and its coded protein neutral sphingomyelinase 2 (NSM) and alcohol abuse, emotional behavior, and bone defects were discovered and multiple mechanisms were identified for females. Here we report strong sex-dimorphisms for central, but not for peripheral mechanisms of NSM action in mouse models. Reduced NSM activity resulted in enhanced alcohol consumption in males, but delayed conditioned rewarding effects. It enhanced the acute dopamine response to alcohol, but decreased monoaminergic systems adaptations to chronic alcohol. Reduced NSM activity increased depression- and anxiety-like behavior, but was not involved in alcohol use for the self-management of the emotional state. Constitutively reduced NSM activity impaired structural development in the brain and enhanced lipidomic sensitivity to chronic alcohol. While the central effects were mostly opposite to NSM function in females, similar roles in bone-mediated osteocalcin release and its effects on alcohol drinking and emotional behavior were observed. These findings support the view that the NSM and multiple downstream mechanism may be a source of the sex-differences in alcohol use and emotional behavior.
CRIS-Team WoS Importer:2022-04-15
Keywords: neutral sphingomyelinase; osteocalcin; depression; alcohol; anxiety

Advances in clinical pharmacy education in Germany: a quasi-experimental single-blinded study to evaluate a patient-centred clinical pharmacy course in psychiatry - Dircks, Monika; Mayr, Andreas; Freidank, Annette; Kornhuber, Johannes; Dörje, Frank; Friedland, Kristina (Bmc Medical Education, 2017)
BACKGROUND: The pharmacy profession has shifted towards patient-centred care. To meet the new challenges it is necessary to provide students with clinical competencies. A quasi-experimental single-blinded teaching and learning study was carried out using a parallel-group design to evaluate systematically the benefits of clinical teaching in pharmacy education in Germany. METHODS: A clinical pharmacy course on a psychiatric ward was developed and implemented for small student groups. The learning aims included: the improvement of patient and interdisciplinary communication skills and the identification and management of pharmaceutical care issues. The control group participated only in the preparation lecture, while the intervention group took part in the complete course. The effects were assessed by an objective structured clinical examination (OSCE) and a student satisfaction survey. RESULTS: The intervention group achieved significantly better overall results on the OSCE assessment (46.20 ± 10.01 vs. 26.58 ± 12.91 of a maximum of 90 points; p < 0.0001).The practical tasks had the greatest effect, as reflected in the outcomes of tasks 1-5 (34.94 ± 9.60 vs. 18.63 ± 10.24 of a maximum of 60 points; p < 0.0001). Students' performance on the theoretical tasks (tasks 6-10) was improved but unsatisfying in both groups considering the maximum score (11.50 ± 4.75 vs. 7.50 ± 4.00 of a maximum of 30 points; p < 0.0001). Of the students, 93% rated the course as practice-orientated, and 90% felt better prepared for patient contact. Many students suggested a permanent implementation and an extension of the course. CONCLUSIONS: The results suggest that the developed ward-based course provided learning benefits for clinical skills. Students' perception of the course was positive. Implementation into the regular clinical pharmacy curriculum is therefore advisable.
EVALuna2:33398

Advantages and disadvantages of the use of the CSF Amyloid β (Aβ) 42/40 ratio in the diagnosis of Alzheimer’s Disease - Hansson, Oskar; Lehmann, Sylvain; Otto, Markus; Zetterberg, Henrik; Lewczuk, Piotr (Alzheimer's Research and Therapy, 2019)
The cerebrospinal fluid (CSF) biochemical markers (biomarkers) Amyloidβ 42 (Aβ42), total Tau (T-tau) and Tau phosphorylated at threonine 181 (P-tau181) have proven diagnostic accuracy for mild cognitive impairment and dementia due to Alzheimer’s Disease (AD). In an effort to improve the accuracy of an AD diagnosis, it is important to be able to distinguish between AD and other types of dementia (non-AD). The concentration ratio of Aβ42 to Aβ40 (Aβ42/40 Ratio) has been suggested to be superior to the concentration of Aβ42 alone when identifying patients with AD. This article reviews the available evidence on the use of the CSF Aβ42/40 ratio in the diagnosis of AD. Based on the body of evidence presented herein, it is the conclusion of the current working group that the CSF Aβ42/40 ratio, rather than the absolute value of CSF Aβ42, should be used when analysing CSF AD biomarkers to improve the percentage of appropriately diagnosed patients.
CRIS-Team Scopus Importer:2019-05-02
Keywords: Alzheimer’s Disease; Amyloidβ Peptides; Aβ42/40 ratio; Biomarkers; Cerebrospinal Fluid

A EUROPEAN, MULTICENTRE, PHASE III, CLINICAL TRIAL OF HYPOTHERMIA FOR ACUTE ISCHAEMIC STROKE: EUROHYP-1 - Sprigg, N.; Smithson, J.; Bath, P.; Lees, K.; Macleod, M.; Van Der Worp, B.; Krieger, D.; Petersson, J.; Staykov, Dimitre; Schwab, Sibylle (2016)
EVALuna2:33132

A German climbing study on depression: A bouldering psychotherapeutic group intervention in outpatients compared with state-of-the-art cognitive behavioural group therapy and physical activation-study protocol for a multicentre randomised controlled trial - Dorscht, Lisa; Karg, Nina; Book, Stephanie; Grässel, Elmar; Kornhuber, Johannes; Luttenberger, Katharina (BMC Psychiatry, 2019)
Background: Besides classical approaches for treating depression, physical activity has been demonstrated to be an effective option. Bouldering psychotherapy (BPT) combines psychotherapeutic interventions with action-oriented elements from the field of climbing. The aim of this study is to investigate the effectiveness of BPT compared with a home-based exercise program (EP- A ctive control group, superiority trial) and state-of-the-art cognitive behavioural therapy (CBT-non-inferiority trial). Methods: The study is being conducted as a multicentre randomised controlled intervention trial at three locations in Germany. Participants are being randomised into three groups: BPT, CBT, or EP, each with a 10-week treatment phase. A power analysis indicated that about 240 people should initially be included. The primary outcome of the study is the Montgomery and Asberg Depression Rating Scale (MADRS) directly after the intervention. Additional measurement points are located three, six, and 12 months after the end of the intervention. The data are being collected via computer-assisted telephone interviews. Statistical analyses comprise regression analyses to test for the superiority of BPT over EP. To test for the non-inferiority of BPT and CBT, a non-inferiority margin of 1.9 points in the Patient Health Questionnaire (PHQ-9) and two non-inferiority margins for the MADRS (half of the two smallest Cohen's d values from the current meta-analyses) was predefined. The mean difference between CBT and EP is being used as a supplementary equivalence margin. Discussion: This is the first study to investigate the effect of a bouldering psychotherapy (BPT) on outpatients' depressive symptoms compared with mere physical activity (superiority analysis) and state-of-the-art cognitive behavioural therapy (CBT, non-inferiority analysis). Methodological strengths of the study are the elaborated, multicentred, randomised, controlled design. Assessors are blinded with regard to group allocation which leads to high objectivity. The study is conducted in a naturalistic setting, which leads to high external validity. Methodological limitations might be the clinical heterogeneity of the sample, which may dilute the intervention effects.
CRIS-Team Scopus Importer:2019-05-28
Keywords: Bouldering; Depression; Exercise program; Physical activity; Psychotherapy; Rock climbing; Sports

Agitation and aggression in people living with dementia and mild cognitive impairment in shared-housing arrangements – validation of a German version of the Cohen-Mansfield Agitation Inventory-Short Form (CMAI-SF) - Kratzer, André; Scheel-Barteit, Jennifer; Altona, Janissa; Wolf-Ostermann, Karin; Grässel, Elmar; Donath, Carolin (Health and Quality of Life Outcomes, 2023)
Background: The Cohen-Mansfield Agitation Inventory-Short Form (CMAI-SF) is a 14-item scale for assessing agitation and aggression, derived from the original 29-item CMAI, and completed by a proxy. Because the CMAI-SF has not yet been validated in German language, the aim of this study is to explore its construct validity. Methods: Baseline data from a cluster-randomized trial to evaluate a non-pharmacological complex intervention for people living with dementia (PlwD) and mild cognitive impairment (MCI) were analyzed. The study sample consisted of 97 shared-housing arrangements (SHAs) in Germany, comprising N = 341 residents with mild to severe dementia and MCI. Trained nursing staff collected data by proxy-rating the CMAI-SF, Neuropsychiatric Inventory-Nursing Home Version (NPI-NH), and QUALIDEM. They also conducted the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Results: In an exploratory factor analysis, three factors emerged: “aggressive behavior”, “verbally agitated behavior”, and “physically non-aggressive behavior”. The CMAI-SF total score showed good internal consistency (α =.85), and the factors themselves showed adequate internal consistency (α =.75/.76/.73). The CMAI-SF showed convergent validity with the NPI-NH agitation item (r =.66) and the NPI-NH “agitation & restless behavior” factor (r =.82). Discriminant validity was confirmed by a low (r =.28) correlation with the NPI-NH apathy item. Quality of life decreased significantly with agitation, as the CMAI-SF showed a moderate negative correlation with the QUALIDEM total score (r = -.35). Conclusions: The 14-item CMAI-SF is a time-efficient, reliable, and valid assessment instrument. Three factors emerged that were similar to those already found in nursing home samples for the original CMAI and the CMAI-SF and in day care samples for the CMAI-SF. The findings provide preliminary evidence that the CMAI-SF can be used instead of the CMAI to reduce time, costs, and burden in future trials. Trial registration: The DemWG study from which data were used to draft this manuscript was prospectively registered on 16 July 2019 at ISRCTN registry (ISRCTN89825211).
CRIS-Team Scopus Importer:2023-06-09
Keywords: Aggression; Agitation; CMAI; CMAI-SF; Cohen-Mansfield Agitation Inventory; Dementia; Mild cognitive impairment; Reliability; Shared-housing arrangements; Validity

A high risk of sleep apnea is associated with less postoperative cognitive dysfunction after intravenous anesthesia: results of an observational pilot study - Wagner, Sören; Quente, Jörg; Städtler, Sven; Koch, Katharina; Richter-Schmidinger, Tanja; Kornhuber, Johannes; Ihmsen, Harald; Schüttler, Jürgen (BMC Anesthesiology, 2018)
Background: The obstructive sleep apnea syndrome (OSAS) is characterized by temporary cerebral hypoxia which can cause cognitive dysfunction. On the other hand, hypoxia induced neurocognitive deficits are detectable after general anesthesia. The objective of this study was to evaluate the impact of a high risk of OSAS on the postoperative cognitive dysfunction after intravenous anesthesia. Methods: In this single center trial between June 2012 and June 2013 43 patients aged 55 to 80 years with an estimated hospital stay of at least 3 days undergoing surgery were enrolled. Patients were screened for a high risk of OSAS using the STOP-BANG test. The cognitive function was assessed using a neuropsychological test battery, including the DemTect test for cognitive impairment and the RMBT test for memory, the day before surgery and within 36 h after extubation. Results: Twenty-two of the 43 analyzed patients were identified as patients with a high risk of OSAS. Preoperatively, OSAS patients showed a significant worse performance only for the DemTect (p = 0.0043). However, when comparing pre- and postoperative test results, the OSAS patients did not show a significant loss in any test but significantly improved in RMBT test, whereas the control group showed a significant worse performance in three of eight tests. In five tests, we found a significant difference between the two groups with respect to the change from pre- to postoperative cognitive function. Conclusion: Patients with a high risk of OSAS showed a less impairment of memory function and work memory performance after intravenous anesthesia. This might be explained by a beneficial effect of intrinsic hypoxic preconditioning in these patients.
EVALuna2:35845

A language-based sum score for the course and therapeutic intervention in primary progressive aphasia - Semler, Elisa; Anderl-Straub, Sarah; Uttner, Ingo; Diehl-Schmid, Janine; Danek, Adrian; Einsiedler, Beate; Fassbender, Klaus; Fliessbach, Klaus; Huppertz, Hans-Jurgen; Jahn, Holger; Kornhuber, Johannes; Landwehrmeyer, Bernhard; et al. (Alzheimer's Research and Therapy, 2018)
With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions.We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials.Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures.Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies.
EVALuna2:54596

Alcohol abuse and cigarette smoking are associated with global DNA hypermethylation: results from the German Investigation on Neurobiology in Alcoholism (GINA) - Semmler, Alexander; Heese, Peter; Stoffel-Wagner, Birgit; Muschler, Marc; Heberlein, Annemarie; Bigler, Laurent; Prost, Jean-Christophe; Frieling, Helge; Kornhuber, Johannes; Banger, Markus; Bleich, Stefan; Hillemacher, Thomas; et al. (Alcohol, 2015)
Recent studies have shown that smoking and alcoholism may be associated with altered DNA methylation and that alcohol consumption might induce changes in DNA methylation by altering homocysteine metabolism. In this monocenter study, we included 363 consecutive patients referred for hospitalization for alcohol detoxification treatment. Blood samples were obtained on treatment days 1, 3, and 7 for measurement of global DNA methylation in leukocytes by liquid chromatography tandem mass spectrometry. Genomic DNA was used for genotyping the following seven genetic variants of homocysteine metabolism: cystathionine beta-synthase (CBS) c.844_855ins68, dihydrofolate-reductase (DHFR) c.594 + 59del19bp, methylenetetrahydrofolate-reductase (MTHFR) c.677C > T and c.1298A > C, methyltetrahydrofolate-transferase (MTR) c.2756A > G, reduced folate carrier 1 (RFC1) c.80G > A, and transcobalamin 2 c.776C > G. Multivariate linear regression showed a positive correlation of global DNA methylation with alcohol consumption and smoking on day 1 of hospitalization. DNA methylation was not correlated with homocysteine or vitamin plasma levels, nor with the tested genetic variants of homocysteine metabolism. This suggests a direct effect of alcohol consumption and smoking on DNA methylation, which is not mediated by effects of alcohol on homocysteine metabolism.
EVALuna2:23732

Alcohol abuse in the context of end stage liver disease and transplantation. Results of a comprehensive psychotherapeutic care program - Erim, Yesim; Beckmann, M.; Boettcher, M.; Paul, A.; Senf, W. (Journal of psychosomatic research, 2012)
Keywords: Ethyl glucuronide; liver transplantation; alcohol relates liver disease; psychotherapy; abstinence

Alcohol does not influence trust in others or oxytocin, but increases positive affect and risk-taking: a randomized, controlled, within-subject trial - Wenger, Leonard P.; Hamm, Oliver; Mühle, Christiane; Hoffmann, Sabine; Reinhard, Iris; Bach, Patrick; Kornhuber, Johannes; Alpers, Georg W.; Kiefer, Falk; Leménager, Tagrid; Lenz, Bernd (European archives of psychiatry and clinical neuroscience, 2023)
Background: Alcohol consumption to facilitate social interaction is an important drinking motive. Here, we tested whether alcohol influences trust in others via modulation of oxytocin and/or androgens. We also aimed at confirming previously shown alcohol effects on positive affect and risk-taking, because of their role in facilitating social interaction. Methods: This randomized, controlled, within-subject, parallel group, alcohol-challenge experiment investigated the effects of alcohol (versus water, both mixed with orange juice) on perceived trustworthiness via salivary oxytocin (primary and secondary endpoint) as well as testosterone, dihydrotestosterone, positive affect, and risk-taking (additional endpoints). We compared 56 male participants in the alcohol condition (1.07 ± 0.18 per mille blood alcohol concentration) with 20 in the control condition. Results: The group (alcohol versus control condition) × time (before [versus during] versus after drinking) interactions were not significantly associated with perceived trustworthiness (η2 < 0.001) or oxytocin (η2 = 0.003). Bayes factors provided also substantial evidence for the absence of these effects (BF01 = 3.65; BF01 = 7.53). The group × time interactions were related to dihydrotestosterone (η2 = 0.018 with an increase in the control condition) as well as positive affect and risk-taking (η2 = 0.027 and 0.007 with increases in the alcohol condition), but not significantly to testosterone. Discussion: The results do not verify alcohol effects on perceived trustworthiness or oxytocin in male individuals. However, they indicate that alcohol (versus control) might inhibit an increase in dihydrotestosterone and confirm that alcohol amplifies positive affect and risk-taking. This provides novel mechanistic insight into social facilitation as an alcohol-drinking motive.
CRIS-Team Scopus Importer:2023-09-22
Keywords: Alcohol; Oxytocin; Positive affect; Risk-taking; Social facilitation; Trustworthiness

Alcohol Reverses Depression/Anxiety State of Mice With Acid Sphingomyelinase Overexpression - Kalinichenko, Liubov; Hammad, Lara; Reichel, Martin; Kohl, Zacharias; Kornhuber, Johannes; Müller, Christian P. (BIOLOGICAL PSYCHIATRY, 2020)
CRIS-Team WoS Importer:2020-08-21

Alleged Detrimental Mutations in the SMPD1 Gene in Patients with Niemann-Pick Disease - Rhein, Cosima; Mühle, Christiane; Kornhuber, Johannes; Reichel, Martin (International Journal of Molecular Sciences, 2015)
Loss-of-function mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene are associated with decreased catalytic activity of acid sphingomyelinase (ASM) and are the cause of the autosomal recessive lysosomal storage disorder Niemann-Pick disease (NPD) types A and B. Currently, >100 missense mutations in SMPD1 are listed in the Human Gene Mutation Database. However, not every sequence variation in SMPD1 is detrimental and gives rise to NPD. We have analysed several alleged SMPD1 missense mutations mentioned in a recent publication and found them to be common variants of SMPD1 that give rise to normal in vivo and in vitro ASM activity. (Comment on Manshadi et al. Int. J. Mol. Sci. 2015, 16, 6668-6676).
EVALuna2:23703

A LONGITUDINAL DUAL ENERGY COMPUTED TOMOGRAPHY STUDY ON THE EFFECT OF URATE LOWERING THERAPIES ON THE REDUCTION OF TOPHUS BURDEN IN PATIENTS WITH CHRONIC GOUT - Ellmann, Hanna; Bayat, Sara; D'Oliveira, I.; Englbrecht, Matthias; Araujo, E.; Mendonca, S.; Lell, Michael; Manger, Bernhard; Schett, Georg; Rech, Jürgen; Cavallaro, Alexander Josef (2016)
EVALuna2:13439

Alpha-band oscillations reflect external spatial coding for tactile stimuli in sighted, but not in congenitally blind humans - Schubert, Jonathan T.W.; Buchholz, Verena N.; Föcker, Julia; Engel, Andreas K.; Röder, Brigitte; Heed, Tobias (Scientific Reports, 2019)
We investigated the function of oscillatory alpha-band activity in the neural coding of spatial information during tactile processing. Sighted humans concurrently encode tactile location in skin-based and, after integration with posture, external spatial reference frames, whereas congenitally blind humans preferably use skin-based coding. Accordingly, lateralization of alpha-band activity in parietal regions during attentional orienting in expectance of tactile stimulation reflected external spatial coding in sighted, but skin-based coding in blind humans. Here, we asked whether alpha-band activity plays a similar role in spatial coding for tactile processing, that is, after the stimulus has been received. Sighted and congenitally blind participants were cued to attend to one hand in order to detect rare tactile deviant stimuli at this hand while ignoring tactile deviants at the other hand and tactile standard stimuli at both hands. The reference frames encoded by oscillatory activity during tactile processing were probed by adopting either an uncrossed or crossed hand posture. In sighted participants, attended relative to unattended standard stimuli suppressed the power in the alpha-band over ipsilateral centro-parietal and occipital cortex. Hand crossing attenuated this attentional modulation predominantly over ipsilateral posterior-parietal cortex. In contrast, although contralateral alpha-activity was enhanced for attended versus unattended stimuli in blind participants, no crossing effects were evident in the oscillatory activity of this group. These findings suggest that oscillatory alpha-band activity plays a pivotal role in the neural coding of external spatial information for touch.
CRIS-Team Scopus Importer:2019-07-09

Alpha power decrease in quantitative EEG detects development of cerebral infarction after subarachnoid hemorrhage early - Müller, Tamara; Gollwitzer, Stephanie; Hopfengartner, Ruediger; Rampp, Stefan; Lang, Johannes; Stritzelberger, Jenny; Madzar, Dominik; Reindl, Caroline; Sprügel, Maximilian; Onugoren, Muejgan Dogan; Mühlen, Iris; Kuramatsu, Joji; et al. (Clinical Neurophysiology, 2021)
Objective: In subarachnoid hemorrhage (SAH), transcranial Doppler/color-coded-duplex sonography (TCD/TCCS) is used to detect delayed cerebral ischemia (DCI). In previous studies, quantitative electroencephalography (qEEG) also predicted imminent DCI. This study aimed to compare and analyse the ability of qEEG and TCD/TCCS to early identify patients who will develop later manifest cerebral infarction. Methods: We analysed cohorts of two previous qEEG studies. Continuous six-channel-EEG with artefact rejection and a detrending procedure was applied. Alpha power decline of ≥ 40% for ≥ 5 hours compared to a 6-hour-baseline was defined as significant EEG event. Median reduction and duration of alpha power decrease in each channel was determined. Vasospasm was diagnosed by TCD/TCCS, identifying the maximum frequency and days of vasospasm in each territory. Results: 34 patients were included (17 male, mean age 56 ± 11 years, Hunt and Hess grade: I–V, cerebral infarction: 9). Maximum frequencies in TCD/TCCS and alpha power reduction in qEEG were correlated (r = 0.43; p = 0.015). Patients with and without infarction significantly differed in qEEG parameters (maximum alpha power decrease: 78% vs 64%, p = 0.019; summed hours of alpha power decline: 236 hours vs 39 hours, p = 0.006) but showed no significant differences in TCD/TCCS parameters. Conclusions: There was a moderate correlation of TCD/TCCS frequencies and qEEG alpha power reduction but only qEEG differentiated between patients with and without cerebral infarction. Significance: qEEG represents a non-invasive, continuous tool to identify patients at risk of cerebral infarction.
CRIS-Team Scopus Importer:2021-06-04
Keywords: Delayed cerebral ischemia; Quantitative EEG; Subarachnoid hemorrhage; Vasospasm

Alpha-Synuclein RNA Expression is Increased in Major Depression - Rotter, Andrea; Lenz, Bernd; Pitsch, Ruben; Richter-Schmidinger, Tanja; Kornhuber, Johannes; Rhein, Cosima (International Journal of Molecular Sciences, 2019)
Alpha-synuclein (SNCA) is a small membrane protein that plays an important role in neuro-psychiatric diseases. It is best known for its abnormal subcellular aggregation in Lewy bodies that serves as a hallmark of Parkinson's disease (PD). Due to the high comorbidity of PD with depression, we investigated the role of SNCA in patients suffering from major depressive disorder (MDD). SNCA mRNA expression levels were analyzed in peripheral blood cells of MDD patients and a healthy control group. SNCA mRNA expression was positively correlated with severity of depression as indicated by psychometric assessment. We found a significant increase in SNCA mRNA expression levels in severely depressed patients compared with controls. Thus, SNCA analysis could be a helpful target in the search for biomarkers of MDD.
CRIS-Team Scopus Importer:2019-05-17
Keywords: alpha-synuclein; Hamilton Scale of Depression; major depression; SNCA

Alterations of plasma glycerophospholipid and sphingolipid species in male alcohol-dependent patients - Reichel, Martin; Hönig, Stefanie; Liebisch, Gerhard; Lueth, Anja; Kleuser, Burkhard; Gulbins, Erich; Schmitz, Gerd; Kornhuber, Johannes (BBA - Biochimica et Biophysica Acta, 2015)
Alcohol abuse is a major risk factor for somatic and neuropsychiatric diseases. Despite their potential clinical importance, little is known about the alterations of plasma glycerophospholipid (GPL) and sphingolipid (SPL) species associated with alcohol abuse.Plasma GPL and SPL species were quantified using electrospray ionization tandem mass spectrometry in samples from 23 male alcohol-dependent patients before and after detoxification, as well as from 20 healthy male controls.A comparison of alcohol-dependent patients with controls revealed higher phosphatidylcholine (PC; P-value=0.008) and phosphatidylinositol (PI; P-value=0.001) concentrations in patients before detoxification, and higher PI (P-value=0.001) and phosphatidylethanolamine (PE)-based plasmalogen (PE P; P-value=0.003) concentrations after detoxification. Lysophosphatidylcholines (LPC) were increased by acute intoxication (P-value=0.002). Sphingomyelin (SM) concentration increased during detoxification (P-value=0.011). The concentration of SM 23:0 was lower in patients (P-value=2.79×10(-5)), and the concentrations of ceramide Cer d18:1/16:0 and Cer d18:1/18:0 were higher in patients (P-value=2.45×10(-5) and 3.73×10(-5)). Activity of lysosomal acid sphingomyelinase (ASM) in patients correlated positively with the concentrations of eight LPC species, while activity of secreted ASM was inversely correlated with several PE, PI and PC species, and positively correlated with the molar ratio of PC to SM (Pearson's r=-0.432; P-value=0.039).Plasma concentrations of numerous GPL and SPL species were altered in alcohol-dependent patients. These molecules might serve as potential biomarkers to improve the diagnosis of patients and to indicate health risks associated with alcohol abuse. Our study further indicates that there are strong interactions between plasma GPL concentrations and SPL metabolism.
EVALuna2:23708

Altered frontal electroencephalography as a potential correlate of acute dissociation in dissociative disorders: Novel findings from a mirror confrontation study - Schäflein, Eva; Mertens, Yoki Linn; Lejko, Nena; Beutler, Sarah; Sattel, Heribert; Sack, Martin (British Journal of Psychiatry Open, 2022)
People suffering from chronic dissociation often experience stress and detachment during self-perception. We tested 18 people with dissociative disorders not otherwise specified (DDNOS; compared with a matched sample of 18 healthy controls) undergoing a stress-inducing facial mirror confrontation paradigm, and measured acute dissociation and frontal electroencephalography (measured with a four-channel system) per experimental condition (e.g. confrontation with negative cognition). Linear mixed models indicated a significant group×time×condition effect, with DDNOS group depicting less electroencephalography power than healthy controls at the beginning of mirror confrontation combined with negative and positive cognition. This discrepancy-most prominent in the negative condition-diminished in the second minute. Correlational analyses depicted a positive association between initial electroencephalography power and acute dissociation in the DDNOS group. These preliminary findings may indicate altered neural processing in DDNOS, but require further investigation with more precise electroencephalography measures.
CRIS-Team Scopus Importer:2022-11-25
Keywords: Dissociative disorders; electroencephalography; mirror; post-Traumatic stress disorder; self-perception

Alternative splicing of SMPD1 coding for acid sphingomyelinase in major depression - Rhein, Cosima; Reichel, Martin; Kramer, Marcel; Rotter, Andrea; Lenz, Bernd; Mühle, Christiane; Gulbins, Erich; Kornhuber, Johannes (Journal of Affective Disorders, 2017)
BACKGROUND: Major depressive disorder (MDD) is a psychiatric disorder characterized by key symptoms that include depressed mood and a loss of interest and pleasure. A recently developed pathogenic model of MDD involves disturbed neurogenesis in the hippocampus, where the acid sphingomyelinase (ASM)/ceramide system plays an important role and is proposed as a molecular target for antidepressant action. Because alternative splicing of SMPD1 mRNA, coding for ASM, is relevant for the regulation of ASM enzymatic activity, we investigated the frequency of alternatively spliced ASM isoforms in peripheral blood cells of MDD patients versus healthy controls. METHODS: Because the full-length transcript variant 1 of SMPD1 (termed ASM-1) is the only known form within the splicing pattern that encodes an enzymatically fully active ASM, we determined a fraction of splice isoforms deviating from ASM-1 using PCR amplification and capillary electrophoresis with laser-induced fluorescence analysis. RESULTS: ASM alternative splicing events occurred significantly less frequently in MDD patients compared to healthy subjects. After 5 days of antidepressant treatment, the frequency of alternatively spliced ASM isoforms decreased in those patients who were treated with a functional inhibitor of ASM activity (FIASMA) but remained constant in MDD patients treated with other antidepressant drugs. This effect was more pronounced when healthy male volunteers were treated with the FIASMAs fluoxetine or paroxetine, in contrast to a placebo group. LIMITATIONS: Patients were treated with different antidepressant drugs, depending on individual parameters and disease courses. CONCLUSIONS: This study shows that the ASM alternative splicing pattern could be a biological target with diagnostic relevance and could serve as a novel biomarker for MDD.
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Alzheimer’s Disease—Biochemical and Psychological Background for Diagnosis and Treatment - Beata, Bocwinska Kiluk; Wojciech, Jelski; Kornhuber, Johannes; Lewczuk, Piotr; Barbara, Mroczko (International Journal of Molecular Sciences, 2023)
There is a paucity of empirical research on the use of non-pharmacological interventions to both treat and curb the spread of Alzheimer’s disease (AD) across the globe. This paper examines the biochemical and clinical outlook and the social implications of the condition in relation to psychological aspects that may indicate a direction for further interventions. There is a scarcity of research on the effectiveness of using various psychological aspects of AD, a disease characterized by a process of transition from health and independence to a dependent state with a progressive loss of memory and functional skills. The paper investigates the biochemical and psychological aspects of AD and their significance for improving quality of life for patients with this disease. Psychological interventions based on, among other factors, biochemical studies, are conducted to improve the emotional wellbeing of AD patients and may assist in slowing down the progression of the disease. To date, however, no effective methods of AD treatment have been established.
CRIS-Team Scopus Importer:2023-02-03
Keywords: Alzheimer’s disease; diagnosis; psychological intervention; treatment

Alzheimer’s disease: history, ethics and medical humanities in the context of assisted suicide - Braun, Birgit; Demling, Joachim; Loew, Thomas Horst (Philosophy, Ethics, and Humanities in Medicine, 2022)
Introduction: Dementia diseases, especially Alzheimer’s disease (AD), are of considerable importance in terms of social policy and health economics. Moreover, against the background of the current Karlsruhe judgement on the legalisation of assisted suicide, there are also questions to be asked about medical humanities in AD. Methodology: Relevant literature on complementary forms of therapy and prognosis was included and discussed. Results: Creative sociotherapeutic approaches (art, music, dance) and validating psychotherapeutic approaches show promise for suitability and efficiency in the treatment of dementia, but in some cases still need to be scientifically tested. Biomarker-based early diagnosis of dementia diseases is increasingly becoming a subject of debate against the background of the Karlsruhe ruling. Discussion: Needs-oriented and resource-enhancing approaches can make a significant contribution to improving the quality of life of people with dementia. The discussion on the issue of “assisted suicide” should include questions of the dignity and value of a life with dementia. Outlook: The integrative dementia therapy model can be complemented by a religion- and spirituality-based approach. Appropriate forms of psychotherapy should be scientifically evaluated.
CRIS-Team Scopus Importer:2022-04-15
Keywords: Alzheimer dementia; Assisted suicide; Dignity; Ethics; Integrative dementia therapy model

Alzheimer's disease protease-containing plasma extracellular vesicles transfer to the hippocampus via the choroid plexus - Lee, Jung Hyun; Ostalecki, Christian; Oberstein, Timo; Schierer, Stefan; Zinser, Elisabeth; Eberhardt, Martin; Blume, Katja; Plosnita, Bianca; Stich, Lena; Bruns, Heiko; Coras, Roland; Vera González, Julio; et al. (EBioMedicine, 2022)
Background: Plasma extracellular vesicles (pEV) can harbor a diverse array of factors including active proteases and the amyloid-precursor-protein (APP) cleavage product Aβ, involved in plaque formation in Alzheimer`s diseases (AD). A potential role of such vesicles in AD pathology is unexplored. Methods: In a case-control study of randomly selected patients with AD and other neurological diseases (n = 14), and healthy controls (n = 7), we systematically analyzed the content of pEV, using different assay systems. In addition, we determined their entry path into brain tissue, employing animal (mice) injection experiments with ex vivo generated EV that were similar to AD-pEV, followed by multi antigen analysis (MAA) of brain tissue (n = 4 per condition). The results were compared with an IHC staining of human brain tissue in a small cohort of AD patients (n = 3) and controls with no neurodegenerative diseases (n = 3). Findings: We show that pEV levels are considerably upregulated in AD patients. Besides numerous inflammatory effectors, AD-pEV contained α-, β- and γ-secretases, able to cleave APP in in target cells. In vitro generated EV with similar characteristics as AD-pEV accumulated in the choroid plexus (CP) of injected animals and reached primarily hippocampal neurons. Corroborating findings were made in human brain samples. An inhibitor of hyaluronic-acid-synthetase (HAS) blocked uploading of proteases and Hyaluronan onto EV in vitro and abolished CP targeting in animal injection experiments. Interpretation: We conclude that protease-containing pEV could be part of a communication axis between the periphery and the brain that could be become detrimental depending on pEV concentration and duration of target cell impact.
CRIS-Team Scopus Importer:2022-03-04
Keywords: Alzheimer's disease; APP; Aβ; BACE; Choroid plexus; Hippocampus; Hyaluronan; Hyaluronic acid synthetase; Plasma extracellular vesicles; Secretases

Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment - Louwersheimer, Eva; Wolfsgruber, Steffen; Espinosa, Ana; Lacour, Andre; Heilmann-Heimbach, Stefanie; Alegret, Montserrat; Hernandez, Isabel; Rosende-Roca, Maitee; Tarraga, Lluis; Boada, Merce; Kornhuber, Johannes; Peters, Oliver; et al. (Alzheimers & Dementia, 2016)
We evaluated the effect of Alzheimer's disease (AD) susceptibility loci on endophenotypes closely related with AD pathology in patients with mild cognitive impairment (MCI).We selected 1730 MCI patients from four independent data sets. Weighted polygenic risk scores (PGS) were constructed of 18 non-apolipoprotein E (APOE) AD risk variants. In addition, we determined APOE genotype. AD endophenotypes were cognitive decline over time and cerebrospinal fluid (CSF) biomarkers (a?, tau, ptau).PGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (? ± SE:-0.24 ± 0.10; P = .012), and with CSF levels of tau and ptau (tau: 1.38 ± 0.36, P = 1.21 × 10(-4); ptau: 1.40 ± 0.36, P = 1.02 × 10(-4)).In MCI, we observed a joint effect of AD susceptibility loci on nonamyloid endophenotypes, suggesting a link of these genetic loci with neuronal degeneration in general rather than with Alzheimer-related amyloid deposition.
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A masked aversive odor cannot be discriminated from the masking odor but can be identified through odor quality ratings and neural activation patterns - Rodriguez-Raecke, Rea; Loos, Helene; Sijben, Rik; Singer, Marco; Beauchamp, Jonathan; Büttner, Andrea; Freiherr, Jessica (Frontiers in Neuroscience, 2019)
Odor masking is a very prominent problem in our daily routines, mainly concerning unpleasant sweat or toilet odors. In the current study we explored the effectiveness of odor masking both on a behavioral and neuronal level. By definition, participants cannot differentiate a fully masked unpleasant odor from the pleasant pure odor used as a masking agent on a behavioral level. We hypothesized, however, that one can still discriminate between a fully masked odor mixture and the pure masking odor on a neuronal level and that, using a reinforcing feedback paradigm, participants could be trained to perceive this difference. A pleasant, lemon-like odor (citral) and a mixture of citral and minor amounts of an unpleasant, goat-like odor (caproic acid) were presented to participants repeatedly using a computer-controlled olfactometer and participants had to decide whether two presented stimuli were the same or different. Accuracy of this task was incentivized with a possible monetary reward. Functional imaging was used throughout the task to investigate central processing of the two stimuli. The participants rated both stimuli as isopleasant and isointense, indicating that the unpleasant odor was fully masked by the pleasant odor. The isolated caproic acid component of the mixture was rated less pleasant than the pleasant odor in a prior experimental session. Although the masked and pure stimuli were not discriminated in the forced-choice task, quality ratings on a dimensional scale differed. Further, we observed an increased activation of the insula and ventral striatum/putamen for the pure in contrast to the fully masked odor, hence revealing a difference in neuronal processing. Our hypothesis that perceptual discrimination and neuronal processing can be enhanced using a reinforcing feedback paradigm is not supported by our data.
CRIS-Team Scopus Importer:2019-11-26
Keywords: FMRI; Odor masking; Odor mixture; Piriform cortex; Ventral striatum

A Modified Reading the Mind in the Eyes Test Predicts Behavioral Variant Frontotemporal Dementia Better Than Executive Function Tests - Schroeter, Matthias L.; Pawelke, Sarah; Bisenius, Sandrine; Kynast, Jana; Schuemberg, Katharina; Polyakova, Maryna; Anderl-Straub, Sarah; Danek, Adrian; Fassbender, Klaus; Jahn, Holger; Jessen, Frank; Kornhuber, Johannes; et al. (Frontiers in Aging Neuroscience, 2018)
Behavioral variant frontotemporal dementia (bvFTD) is characterized by deep alterations in behavior and personality. Although revised diagnostic criteria agree for executive dysfunction as most characteristic, impairments in social cognition are also suggested. The study aimed at identifying those neuropsychological and behavioral parameters best discriminating between bvFTD and healthy controls. Eighty six patients were diagnosed with possible or probable bvFTD according to Rascovsky et al. (2011) and compared with 43 healthy age-matched controls. Neuropsychological performance was assessed with a modified Reading the Mind in the Eyes Test (RMET), Stroop task, Trail Making Test (TMT), Hamasch-Five-Point Test (H5PT), and semantic and phonemic verbal fluency tasks. Behavior was assessed with the Apathy Evaluation Scale, Frontal Systems Behavioral Scale, and Bayer Activities of Daily Living Scale. Each test's discriminatory power was investigated by Receiver Operating Characteristic curves calculating the area under the curve (AUC). bvFTD patients performed significantly worse than healthy controls in all neuropsychological tests. Discriminatory power (AUC) was highest in behavioral questionnaires, high in verbal fluency tasks and the RMET, and lower in executive function tests such as the Stroop task, TMT and H5PT. As fluency tasks depend on several cognitive functions, not only executive functions, results suggest that the RMET discriminated better between bvFTD and control subjects than other executive tests. Social cognition should be incorporated into diagnostic criteria for bvFTD in the future, such as in the International Classification of Diseases (ICD)-11, as already suggested in the Diagnostic and Statistical Manual for Mental Disorders (DSM)-5.
EVALuna2:62186

A Multiple Piccolino-RIBEYE Interaction Supports Plate-Shaped Synaptic Ribbons in Retinal Neurons - Müller, Tanja; Gierke, Kaspar; Joachimsthaler, Anneka; Sticht, Heinrich; Izsvak, Zsuzsanna; Hamra, F. Kent; Fejtová, Anna; Ackermann, Frauke; Garner, Craig C.; Kremers, Jan; Brandstätter, Johann Helmut; Regus-Leidig, Hanna (Journal of Neuroscience, 2019)
Active zones at chemical synapses are highly specialized sites for the regulated release of neurotransmitters. Despite a high degree of active zone protein conservation in vertebrates, every type of chemical synapse expresses a given set of protein isoforms and splice variants adapted to the demands on neurotransmitter release. So far, we know little about how specific active zone proteins contribute to the structural and functional diversity of active zones. In this study, we explored the nanodomain organization of ribbon-type active zones by addressing the significance of Piccolino, the ribbon synapse-specific splice variant of Piccolo, for shaping the ribbon structure. We followed up on previous results, which indicated that rod photoreceptor synaptic ribbons lose their structural integrity in a knockdown of Piccolino. Here, we demonstrate an interaction between Piccolino and the major ribbon component RIBEYE that supports plate-shaped synaptic ribbons in retinal neurons. In a detailed ultrastructural analysis of three different types of retinal ribbon synapses in Piccolo/Piccolino-deficient male and female rats, we show that the absence of Piccolino destabilizes the superstructure of plate-shaped synaptic ribbons, although with variable manifestation in the cell types examined. Our analysis illustrates how the expression of a specific active zone protein splice variant (e.g., Piccolino) contributes to structural diversity of vertebrate active zones.
CRIS-Team WoS Importer:2019-04-12

A Multisensory Deficit in the Perception of Pleasantness in Parkinson's Disease. - Utz, Kathrin; Martini, Max; Mrochen, Anne; Lambrecht, Vera; Süß, Patrick; Renner, Bertold; Freiherr, Jessica; Schenk, Thomas; Winkler, Jürgen; Marxreiter, Franz (Journal of Parkinson's Disease, 2021)
BACKGROUND: There is growing interest in non-motor symptoms in Parkinson's disease (PD), due to the impact on quality of life. Anhedonia, the inability to experience joy and lust, has a prevalence of up to 46% in PD. The perception of pleasantness of an odor is reduced in anhedonia without PD. We previously showed a reduced hedonic olfactory perception in PD, i.e., patients evaluated odors as less pleasant or unpleasant compared to controls. This deficit correlated with anhedonia. OBJECTIVE: We aimed to confirm these findings. Moreover, we hypothesized that the perception of pleasantness in PD is affected on a multisensory level and correlates with anhedonia. Therefore, we assessed olfactory, visual and acoustic evaluation of pleasantness in PD and healthy individuals. METHODS: Participants had to rate the pleasantness of 22 odors, pictures, and sounds on a nine-point Likert scale. Depression, anhedonia, and apathy were assessed by means of questionnaires. Results of the pleasantness-rating were compared between groups and correlated to scores of the questionnaires. RESULTS: In particular pleasant and unpleasant stimuli across all three modalities are perceived less intense in PD, suggesting that a reduced range of perception of pleasantness is a multisensory phenomenon. However, only a reduction of visual hedonic perception correlated with anhedonia in PD. A correlation of reduced perception of pleasantness with apathy or depression was not present. CONCLUSION: We provide evidence for a multisensory deficit in the perception of pleasantness. Further studies should delineate the underlying neural circuity and the diagnostic value to detect neuropsychiatric symptoms in PD.
EVALuna2:470167

A Multisensory Deficit in the Perception of Pleasantness in Parkinson's Disease - Utz, Kathrin; Martini, Max; Mrochen, Anne; Lambrecht, Vera; Süß, Patrick; Renner, Bertold; Freiherr, Jessica; Schenk, Thomas; Winkler, Jürgen; Marxreiter, Franz (Journal of Parkinson's Disease, 2021)
Background: There is growing interest in non-motor symptoms in Parkinson's disease (PD), due to the impact on quality of life. Anhedonia, the inability to experience joy and lust, has a prevalence of up to 46% in PD. The perception of pleasantness of an odor is reduced in anhedonia without PD. We previously showed a reduced hedonic olfactory perception in PD, i.e., patients evaluated odors as less pleasant or unpleasant compared to controls. This deficit correlated with anhedonia. Objective: We aimed to confirm these findings. Moreover, we hypothesized that the perception of pleasantness in PD is affected on a multisensory level and correlates with anhedonia. Therefore, we assessed olfactory, visual and acoustic evaluation of pleasantness in PD and healthy individuals. Methods: Participants had to rate the pleasantness of 22 odors, pictures, and sounds on a nine-point Likert scale. Depression, anhedonia, and apathy were assessed by means of questionnaires. Results of the pleasantness-rating were compared between groups and correlated to scores of the questionnaires. Results: In particular pleasant and unpleasant stimuli across all three modalities are perceived less intense in PD, suggesting that a reduced range of perception of pleasantness is a multisensory phenomenon. However, only a reduction of visual hedonic perception correlated with anhedonia in PD. A correlation of reduced perception of pleasantness with apathy or depression was not present. Conclusion: We provide evidence for a multisensory deficit in the perception of pleasantness. Further studies should delineate the underlying neural circuity and the diagnostic value to detect neuropsychiatric symptoms in PD.
CRIS-Team Scopus Importer:2021-10-29
Keywords: affective pictures; anhedonia; apathy; depression; hyposmia; non-motor symptoms; Parkinson's disease; Sniffin' Sticks

Amyloid-beta levels and cognitive trajectories in non-demented pTau181-positive subjects without amyloidopathy - Oberstein, Timo; Schmidt, Manuel; Florvaag, Anna; Haas, Anna-Lena; Siegmann, Eva-Maria; Olm, Pauline; Utz, Janine; Spitzer, Philipp; Dörfler, Arnd; Lewczuk, Piotr; Kornhuber, Johannes; Maler, Juan Manuel (Brain, 2022)
In a long-term observational study, Oberstein et al. find that the biomarker constellation of increased pTau181, A beta 40 and A beta 42 in CSF is not associated with dementia. Further investigation of this biomarker profile may provide insights into the circumstances under which A beta becomes pathological.
CRIS-Team WoS Importer:2022-09-30

Amyloidogenic amyloid-?-peptide variants induce microbial agglutination and exert antimicrobial activity - Spitzer, Philipp; Condic, Mateja; Herrmann, Martin; Oberstein, Timo; Scharin-Mehlmann, Marina; Gilbert, Daniel; Friedrich, Oliver; Groemer, Teja; Kornhuber, Johannes; Lang, Roland; Maler, Juan Manuel (Scientific Reports, 2016)
Amyloid-? (A?) peptides are the main components of the plaques found in the brains of patients with Alzheimer's disease. However, A? peptides are also detectable in secretory compartments and peripheral blood contains a complex mixture of more than 40 different modified and/or N- and C-terminally truncated A? peptides. Recently, anti-infective properties of A? peptides have been reported. Here, we investigated the interaction of A? peptides of different lengths with various bacterial strains and the yeast Candida albicans. The amyloidogenic peptides A?1-42, A?2-42, and A?3p-42 but not the non-amyloidogenic peptides A?1-40 and A?2-40 bound to microbial surfaces. As observed by immunocytochemistry, scanning electron microscopy and Gram staining, treatment of several bacterial strains and Candida albicans with A? peptide variants ending at position 42 (A?x-42) caused the formation of large agglutinates. These aggregates were not detected after incubation with A?x-40. Furthermore, A?x-42 exerted an antimicrobial activity on all tested pathogens, killing up to 80% of microorganisms within 6 h. A?1-40 only had a moderate antimicrobial activity against C. albicans. Agglutination of A?1-42 was accelerated in the presence of microorganisms. These data demonstrate that the amyloidogenic A?x-42 variants have antimicrobial activity and may therefore act as antimicrobial peptides in the immune system.
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Amyloid β oligomers (AβOs) in Alzheimer's disease - Mroczko, Barbara; Groblewska, Magdalena; Litman-Zawadzka, Ala; Kornhuber, Johannes; Lewczuk, Piotr (Journal of Neural Transmission, 2018)
The causative role of amyloid β 1-42 (Aβ42) aggregation in the pathogenesis of Alzheimer's disease (AD) has been under debate for over 25 years. Primarily, scientific efforts have focused on the dyshomeostasis between production and clearance of Aβ42. This imbalance may result from mutations either in genes for the substrate, i.e., amyloid precursor protein or in genes encoding presenilin, the enzyme of the reaction that generates Aβ42. Currently, it is supposed that soluble oligomers of amyloid beta (AβOs) and not fibrillar Aβ42 within neuritic plaques may be the toxic factors acting on a very early stage of AD, perhaps even initiating pathological cascade. For example, soluble AβOs isolated from AD patients' brains reduced number of synapses, inhibited long-term potentiation, and enhanced long-term synaptic depression in brain regions responsible for memory in animal models of AD. Concentrations of AβOs in the cerebrospinal fluid (CSF) of AD patients are often reported higher than in non-demented controls, and show a negative correlation with mini-mental state examination scores. Furthermore, increased Aβ42/oligomer ratio in the CSF of AD/MCI patients indicated that the presence of soluble AβOs in CSF may be linked to lowering of natively measured monomeric Aβ42 by epitopes masking, and hence, concentrations of AβOs in the CSF are postulated to as useful AD biomarkers.
EVALuna2:35461

Analysis of hyperforin (St. John’s wort) action at TRPC6 channel leads to the development of a new class of antidepressant drugs - El Hamdaoui, Yamina; Zheng, Fang; Fritz, Nikolas; Ye, Lian; Tran, Mai Anh; Schwickert, Kevin; Schirmeister, Tanja; Braeuning, Albert; Lichtenstein, Dajana; Hellmich, Ute A.; Weikert, Dorothée; Heinrich, Markus; et al. (Molecular Psychiatry, 2022)
St. John’s wort is an herb, long used in folk medicine for the treatment of mild depression. Its antidepressant constituent, hyperforin, has properties such as chemical instability and induction of drug-drug interactions that preclude its use for individual pharmacotherapies. Here we identify the transient receptor potential canonical 6 channel (TRPC6) as a druggable target to control anxious and depressive behavior and as a requirement for hyperforin antidepressant action. We demonstrate that TRPC6 deficiency in mice not only results in anxious and depressive behavior, but also reduces excitability of hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. Using electrophysiology and targeted mutagenesis, we show that hyperforin activates the channel via a specific binding motif at TRPC6. We performed an analysis of hyperforin action to develop a new antidepressant drug that uses the same TRPC6 target mechanism for its antidepressant action. We synthesized the hyperforin analog Hyp13, which shows similar binding to TRPC6 and recapitulates TRPC6-dependent anxiolytic and antidepressant effects in mice. Hyp13 does not activate pregnan-X-receptor (PXR) and thereby loses the potential to induce drug-drug interactions. This may provide a new approach to develop better treatments for depression, since depression remains one of the most treatment-resistant mental disorders, warranting the development of effective drugs based on naturally occurring compounds.
CRIS-Team Scopus Importer:2022-10-21

Analysis of longitudinal data: Introduction to Special Issue - Stemmler, Mark Kurt; Lösel, Friedrich; Erzigkeit, Helmut (Methods of Psychological Research (MPR-online), 1998)

Analysis of motives and patient satisfaction in oncological second opinions provided by a certified university breast and gynecological cancer center - Löhberg, Christian; Meyer, Julia; Häberle, Lothar; Hack, Carolin; Jud, Sebastian; Hein, Alexander; Wunderle, Marius; Emons, Julius; Gaß, Paul; Fasching, Peter; Egloffstein, Sainab; Krebs, Jessica; et al. (Archives of Gynecology and Obstetrics, 2020)
Purpose: Second opinions in oncology are becoming increasingly important in an era of more complex treatments and a growing demand for information by patients. Therefore, we analyzed their effects and influencing factors like patients’ motives, subjective extent of information and satisfaction with communications. Methods: This prospective study evaluated second opinions for patients with breast cancer or gynecological malignancy. The patients received a questionnaire before and two months after, which inquired expectations, reasons, and satisfaction with the second opinion and the attending physicians. Results: A total of 164 patients were included and the majority had breast cancer (75.0%). Receiving the second opinion made 89.7% feel better informed, their need for information decreased (from 75.3% to 39.2%, P < 0.0001), and satisfaction with doctor–patient communications increased (from 61.9 to 91.8%, P = 0.0002). There were various reasons for requesting a second opinion, e.g., the extremely stressful situation of a cancer diagnosis, hope for change in the treatment recommendation or dissatisfaction with the initial physicians. Conclusions: Second opinions can lead to significantly greater patient satisfaction, meeting the need for information and leading to better management of patients in the extremely stressful situation of a cancer diagnosis. Doctor–patient communications play a key role.
CRIS-Team Scopus Importer:2020-04-28
Keywords: Breast cancer; Doctor–patient communication; Gynecological malignancy; Oncology center; Patient satisfaction; Second opinion

Analysis of Oncological Second Opinions in a Certified University Breast and Gynecological Cancer Center Regarding Consensus between the First and Second Opinion and Conformity with the Guidelines - Lux, Michael P.; Wasner, Sonja; Meyer, Julia; Häberle, Lothar; Hack, Carolin; Jud, Sebastian; Hein, Alexander; Wunderle, Marius; Emons, Julius; Gaß, Paul; Fasching, Peter; Egloffstein, Sainab; et al. (Breast Care, 2020)
Introduction: Oncological second opinions are becoming increasingly important in the era of complex treatments and established certified cancer centers. Oncological guidelines with the highest levels of evidence are available, but these can only be effective to the extent that they are implemented. Therefore, we analyzed the effects of second opinions with regard to their agreement with first opinions and conformity with guidelines. Methods: In 164 patients with a diagnosis of breast cancer or gynecological malignancy who requested a second opinion, the first and second opinions, established at the interdisciplinary tumor conference, and conformity with the guidelines were evaluated. Results: The first opinion was not in agreement with the guidelines in 34.8% (15.2% diagnosis, 12.8% surgical therapy, 13.4% systemic therapy, and 5.5% radiotherapy), and the recommendations were optimized in the second opinion in 56.7% (28.7% diagnosis, 15.9% surgical therapy, 30.5% systemic therapy, and 8.5% radiotherapy). Conclusions: Oncological second opinions showed significant effects and one-third of first opinions were not in conformity with the guidelines. In a significant proportion of cases, the existing treatment plan was changed or supplemented to allow modern and individualized treatment approaches.
CRIS-Team Scopus Importer:2020-09-04

Analysis of Surface Levels of IL-1 Receptors and Macrophage Scavenger Receptor I in Peripheral Immune Cells of Patients With Alzheimer Disease - Spitzer, Philipp; Weinbeer, Johannes; Herrmann, Martin; Oberstein, Timo; Condic, Mateja; Lewczuk, Piotr; Kornhuber, Johannes; Maler, Juan Manuel (Journal of Geriatric Psychiatry and Neurology, 2019)
Increased concentrations of interleukin 1 (IL-1) in the cerebrospinal fluid and serum of patients with Alzheimer disease (AD) reduced phagocytic capacity point to an inflammatory activation of mononuclear phagocytes in AD. Interleukin 1 receptors (IL-1R) and the macrophage scavenger receptor I (MSRI) are important players in IL-1 signaling and phagocytosis. In 20 patients with AD and 17 controls, IL-1RI, IL-1RII, and MSRI were assessed on peripheral blood mononuclear cells by flow cytometry. IL-1β, soluble IL-1 receptors, and IL-1R antagonist (IL-1Ra) were measured by enzyme-linked immunosorbent assay. The fraction of IL-1RI+ monocytes was increased by 10% and the expression of MSRI was reduced by 12% in AD. A 3.6% increased fraction of IL-1RI+ lymphocytes was accompanied by a 6.1% reduced expression of IL-1RII. The IL-1RI on monocytes and lymphocytes discriminated patients with AD with an accuracy of 0.79 and 0.75, respectively. The IL-1Ra was elevated in AD. Changes in the expression of IL-1 receptors and MSRI on peripheral blood cells fit to the concept of a proinflammatory state of the peripheral immune system. However, the observed differences are not strong enough to suggest their application as biomarkers for AD.
CRIS-Team Scopus Importer:2019-05-03
Keywords: Alzheimer disease; biomarker; dementia; IL-1RI; MSRI; neurodegeneration; neuroinflammation

An automatic version of a reading disorder test - Maier, Andreas; Hönig, Florian Thomas; Steidl, Stefan; Nöth, Elmar; Horndasch, Stefanie; Sauerhöfer, Elisabeth; Kratz, Oliver; Moll, Gunther (ACM Transactions on Speech and Language Processing, 2011)

ANDEXANET ALFA VERSUS USUAL CARE IN PATIENTS WITH DOAC ASSOCIATED INTRACEREBRAL HEMORRHAGE: A PROPENSITY-SCORE BASED HISTORICAL COMPARISON OF PATIENTS FROM ANNEXA4 AND RETRACEII - Huttner, Hagen; Gerner, Stefan; Connolly, S.; Middeldorp, S.; Milling, T.; Beyer-Westendorf, J.; Altevers, J.; Andersohn, F.; Yue, P.; Stross, L.; Schwab, Stefan (INTERNATIONAL JOURNAL OF STROKE, 2020)
CRIS-Team WoS Importer:2021-01-22

A New Approach to the Life and Oeuvre of Karl Leonhard: His Role as a Psychiatrist under National Socialism and the Influence of "Erlangen School" on his Scientific Position - Braun, Birgit; Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2022)
Aim The aim of this study was to present a new approach to the life and oeuvre of Karl Leonhard, focussing on his role as a psychiatrist during the period of national socialism and on his scientific affiliation to the "Erlangen school". Method For the first time, documents from Franconian archives have been evaluated. Results At the University Hospital of Psychiatry in Erlangen, Leonhard described psychopathological states in a very detailed manner as a main component of his phenomenological approach. Although Leonhard was classified as a "follower" during his denazification, temporarily he was "incriminated" due to a denunciation. Conclusion Leonhard as an opportunist supported the NS racial hygiene without any actual eugenic orientation. Further studies are needed to clarify Leonhard's proclaimed active opposition to NS "euthanasia".
CRIS-Team WoS Importer:2022-04-22

Angehörige erzählen. Vom Umgang mit Demenz: einige sozialmedizinische und narratologische Beobachtungen - Niefanger, Dirk; Grässel, Elmar (Alter(n) in Literatur und Kultur der Gegenwart, 2012)

Animal models of psychoactive drug use and addiction - Present problems and future needs for translational approaches - Müller, Christian P. (Behavioural Brain Research, 2018)
Drug addiction is a psychiatric disorder based on a dysfunction of the brain. It frequently develops from a controlled drug consumption and drug instrumentalization (DI). Thereby, DI is the use of a drug to improve specific non-drug related behaviors, beyond the drug's direct positive or negative reinforcing effects. Currently available pharmacotherapies for drug addiction show low effect size and rather limited long-term efficacy, which suggests that current theories on addiction are still insufficient in how they capture the phenomenon and how they allow predictions for highly efficient treatments. This opinion review attempts a critical analysis of some aspects of current addiction neuroscience using animal models. As a result, (1) animal models that cover previously neglected types of drug memories in controlled drug use are suggested. (2) Animal models for drug instrumentalization are warranted. Animal models of drug addiction should consider that addiction develops predominantly in individuals with mental and/or environmental challenges. It is suggested (3) to preferentially use animal models with similar mental and environmental challenges to model the transition of controlled to compulsive drug use. (4) Animal models should in the future also capture the important aspect of the motivation to self-medicate in order to ameliorate a negative emotional/physical state. Potential pharmaco-treatments of addiction, in order to later achieve compliance in humans, should be tested for their systemic self-administration in order to self-medicate a drug-induced aversive state. This may allow a better understanding of the fundamental differences between an organism that shows controlled psychoactive drug consumption as an integral part of a 'normal' behavioral repertoire and one in a pathological condition with compulsive drug abuse.
EVALuna2:36576

Antidepressants act by inducing autophagy controlled by sphingomyelin-ceramide - Gulbins, Anne; Schumacher, Fabian; Becker, Katrin Anne; Wilker, Barbara; Soddemann, Matthias; Boldrin, Francesco; Müller, Christian P.; Edwards, Michael J.; Goodman, Michael; Caldwell, Charles C.; Kleuser, Burkhard; Kornhuber, Johannes; et al. (Molecular Psychiatry, 2018)
Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autophagy in hippocampal neurons via the slow accumulation of sphingomyelin in lysosomes and Golgi membranes and of ceramide in the endoplasmic reticulum (ER). ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B. Although treatment with amitriptyline or fluoxetine requires at least 12 days to achieve sphingomyelin accumulation and the subsequent biochemical and cellular changes, direct inhibition of sphingomyelin synthases with tricyclodecan-9-yl-xanthogenate (D609) results in rapid (within 3 days) accumulation of ceramide in the ER, activation of autophagy, and reversal of biochemical and behavioral signs of stress-induced MDD. Inhibition of Beclin blocks the antidepressive effects of amitriptyline and D609 and induces cellular and behavioral changes typical of MDD. These findings identify sphingolipid-controlled autophagy as an important target for antidepressive treatment methods and provide a rationale for the development of novel antidepressants that act within a few days.
EVALuna2:211626

Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19 - Hoertel, Nicolas; Sanchez-Rico, Marina; Kornhuber, Johannes; Gulbins, Erich; Reiersen, Angela M.; Lenze, Eric J.; Fritz, Bradley A.; Jalali, Farid; Mills, Edward J.; Cougoule, Celine; Carpinteiro, Alexander; Mühle, Christiane; et al. (Journal of Clinical Medicine, 2022)
To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19. We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP-HP (Assistance Publique-Hopitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant use at admission (N = 1482). Antidepressant use was significantly less prevalent in inpatients with COVID-19 than in a matched control group of inpatients without COVID-19 (1.9% versus 4.8%; Odds Ratio (OR) = 0.38; 95%CI = 0.35-0.41, p < 0.001). Antidepressant use was significantly associated with reduced 28-day mortality among COVID-19 inpatients (12.8% versus 21.2%; OR = 0.55; 95%CI = 0.41-0.72, p < 0.001), particularly at daily doses of at least 40 mg fluoxetine equivalents. Antidepressants with high FIASMA (Functional Inhibitors of Acid Sphingomyelinase) activity seem to drive both associations. These treatments may reduce SARS-CoV-2 infections and COVID-19-related mortality in inpatients, and may be appropriate for prophylaxis and/or COVID-19 therapy for outpatients or inpatients.
CRIS-Team WoS Importer:2022-10-28

Antiseizure medication and perceived “fair” cost allocation: A factorial survey among neurologists, persons with epilepsy, their relatives, and a control group - Stritzelberger, Jenny; Walther, Katrin; Olmes, David; Gollwitzer, Stefanie; Graf, Wolfgang; Welte, Tamara; Lang, Johannes; Reindl, Caroline; Schwab, Stefan; Kriwy, Peter; Hamer, Hajo (Epilepsia, 2022)
Objective: Because resources are limited in modern health care systems, the decision on the allocation of expensive drugs can be supported by a public consent. This study examines how various factors influence subjectively perceived “fair” pricing of antiseizure medication (ASM) among four groups including physicians, persons with epilepsy (PWEs), their relatives, and a control group. Methods: We conducted a factorial survey. Vignettes featured a fictional PWE receiving a fictional ASM. The characteristics of the fictional PWE, ASM, and epilepsy varied. Participants were asked to assess the subjectively appropriate annual cost of ASM treatment per year for each scenario. Results: Fifty-seven PWEs (mean age (SD) 37.7 ± 12.3, 45.6% female), 44 relatives (age 48.4 ± 15.7, 51.1% female), 46 neurologists (age 37.1 ± 9.6, 65.2% female), and 47 persons in the control group (age 31.2 ± 11.2, 68.1% female) completed the questionnaire. The amount of money that respondents were willing to spend for ASM treatment was higher than currently needed in Germany and increased with disease severity among all groups. All groups except for PWEs accepted higher costs of a drug with better seizure control. Physicians and the control group, but not PWEs and their relatives, tended to do so also for minor or no side effects. Physicians reduced the costs for unemployed patients and the control group spent less money for older patients. Significance: ASM effectiveness appears to justify higher costs. However, the control group attributed less money to older PWEs and physicians allocated fewer drug costs to unemployed PWEs.
CRIS-Team Scopus Importer:2022-08-19

Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model - Pericat, David; Leon-Icaza, Stephen Adonai; Rico, Marina Sanchez; Mühle, Christiane; Zoicas, Iulia; Schumacher, Fabian; Planes, Remi; Mazars, Raoul; Gros, Germain; Carpinteiro, Alexander; Becker, Katrin Anne; Izopet, Jacques; et al. (International Journal of Molecular Sciences, 2022)
The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world’s population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19. In this report, we evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5. Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects. Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.
CRIS-Team Scopus Importer:2022-11-25
Keywords: anti-depressant; COVID-19; fluoxetine; inflammation; mouse model; SARS-CoV-2

Antonovskys Konzept der Salutogenese und ihre Implikationen in der Psychotherapie körperlich Kranker - Erim, Yesim (Psychotherapie im Dialog, 2013)

Anxiety and Depression Are Related to Higher Activity of Sphingolipid Metabolizing Enzymes in the Rat Brain - Zoicas, Iulia; Mühle, Christiane; Schmidtner, Anna K.; Gulbins, Erich; Neumann, Inga D.; Kornhuber, Johannes (Cells, 2020)
Changes in sphingolipid metabolism have been suggested to contribute to the pathophysiology of major depression. In this study, we investigated the activity of acid and neutral sphingomyelinases (ASM, NSM) and ceramidases (AC, NC), respectively, in twelve brain regions of female rats selectively bred for high (HAB) versus low (LAB) anxiety-like behavior. Concomitant with their highly anxious and depressive-like phenotype, HAB rats showed increased activity of ASM and NSM as well as of AC and NC in multiple brain regions associated with anxiety- and depressive-like behavior, including the lateral septum, hypothalamus, ventral hippocampus, ventral and dorsal mesencephalon. Strong correlations between anxiety-like behavior and ASM activity were found in female HAB rats in the amygdala, ventral hippocampus and dorsal mesencephalon, whereas NSM activity correlated with anxiety levels in the dorsal mesencephalon. These results provide novel information about the sphingolipid metabolism, especially about the sphingomyelinases and ceramidases, in major depression and comorbid anxiety.
CRIS-Team Scopus Importer:2020-05-29
Keywords: anxiety; ceramidase; depression; sphingolipids; sphingomyelinase

Anxiety Is Associated With DPPIV Alterations in Children With Selective Mutism and Social Anxiety Disorder: A Pilot Study - Golub, Yulia; Stonawski, Valeska; Plank, Anne-Christine; Eichler, Anna; Kratz, Oliver; Waltes, Regina; von Hörsten, Stephan; Roessner, Veit; Freitag, Christine M. (Frontiers in Psychiatry, 2021)
Background: Both selective mutism (SM) and social anxiety disorder (SAD) are severe pediatric anxiety disorders with the common trait of behavioral inhibition (BI). The underlying pathophysiology of these disorders remains poorly understood, however converging evidence suggests that alterations in several peripheral molecular pathways might be involved. In a pilot study, we investigated alterations in plasma molecular markers (dipeptidyl peptidase-4 [DPPIV], interleukin-6 [IL-6], tumor necrosis factor-beta [TNF-beta] and neuropeptide-Y [NPY]) in children with SM, SAD, and healthy controls, as well as the correlation of these markers to symptom severity.
CRIS-Team WoS Importer:2021-07-23

Anxiety, Posttraumatic Stress, and Fear of Cancer Progression in Patients with Melanoma in Cancer Aftercare - Erim, Yesim; Loquai, Carmen; Schultheis, Ulrike; Lindner, Marion; Beckmann, Mingo; Schadendorf, Corinna; Senf, Wolfgang (Onkologie, 2013)
Keywords: Anxiety; Fear of cancer progression; Melanoma; Posttraumatic stress

Anxiogenic-like behavior and deficient attention/working memory in rats expressing the human DISC1 gene - Wang, An-Li; Chao, Owen Y.; Yang, Yi-Mei; Trossbach, Svenja V.; Müller, Christian P.; Korth, Carsten; Huston, Joseph P.; De Souza Silva, Maria Angelica (Pharmacology Biochemistry and Behavior, 2019)
In humans, mutations in the Disrupted-in-schizophrenia 1 (DISC1) gene have been related to psychiatric disorders, including symptoms of abnormal cognitive and emotional behaviors. In our previous studies, overexpression of the human DISC1 gene in rats resulted in schizophrenia-like phenotypes showing deficits in motor learning, impaired cognitive function and dysfunctions of the dopamine system. Here we asked, whether the DISC1 overexpression affects locomotor activity in the open field (OF), anxiety in the elevated plus-maze (PPM), depression-related behavior in the forced swim test (FST), and attention-like/short-term working-memory in the spontaneous alternation behavior (SAB) in the T-maze in transgenic DISC1 (tgDISC1) rats and littermate controls (WT). TgDISC1 rats showed enhanced anxiety behavior in the EPM and an impairment in attention-like/short-term working-memory in the SAB. However, tgDISC1 animals showed no locomotor impairments or depression-like behavior in the OF and FST. These results suggest that DISC1 overexpression leads to higher anxiety level and an attention-like/working-memory deficit. These findings may expand the causal role of DISC1 in its contribution to multiple symptom dimensions of psychiatric disorders.
CRIS-Team WoS Importer:2019-04-30

Apathy in patients with Alzheimer's disease is a cost-driving factor - Kruse, Christopher; Maier, Franziska; Spottke, Annika; Bach, Jan-Philipp; Bartels, Claudia; Buerger, Katharina; Fellgiebel, Andreas; Fliessbach, Klaus; Frolich, Lutz; Hausner, Lucrezia; Hellmich, Martin; Kloppel, Stefan; et al. (Alzheimers & Dementia, 2023)
BackgroundApathy is the most frequent neuropsychiatric symptom in patients with dementia of the Alzheimer's type (DAT). We analyzed the influence of apathy on the resource use of DAT patients and their caregivers. MethodsIncluded were baseline data of 107 DAT patients from a randomized clinical trial on apathy treatment. The Resource Utilization in Dementia (RUD) instrument assessed costs over a 1-month period prior to baseline. Cost predictors were determined via a least absolute shrinkage and selection operator (LASSO). ResultsOn average, total monthly costs were euro3070, of which euro2711 accounted for caregivers' and euro359 for patients' costs. An increase of one point in the Apathy Evaluation Scale resulted in a 4.1% increase in total costs. DiscussionApathy is a significant cost driving factor for total costs in mild to moderate DAT. Effective treatment of apathy might be associated with reduced overall costs in DAT.
CRIS-Team WoS Importer:2023-01-27

A Phenotyping Platform to Characterize Healthy Individuals Across Four Stages of Life - The Enable Study - Brandl, Beate; Skurk, Thomas; Rennekamp, Rachel; Hannink, Anne; Kießwetter, Eva; Freiherr, Jessica; Ihsen, Susanne; Roosen, Jutta; Klingenspor, Martin; Haller, Dirk; Krautwurst, Dietmar; Hofmann, Thomas; et al. (Frontiers in Nutrition, 2020)
Introduction: Nutritional habits and requirements are changing over the lifespan, but the dynamics of nutritional issues and the diet-health relationship in the major stages of the human life cycle are not sufficiently understood. A human phenotyping research platform for nutrition studies was established to recruit and phenotype selected population groups across different stages of life. The project is the backbone of the highly interdisciplinary enable competence cluster of nutrition research aiming to identify dietary determinants of a healthy life throughout the lifespan and to develop healthier and tasty convenience foods with high consumer acceptance. Methods: The phenotyping program included anthropometry, body composition analysis, assessment of energy metabolism, health and functional status, multisensory perception, metabolic phenotyping, lifestyle, sociodemography, chronobiology, and assessment of dietary intake including food preferences and aversions. Results: In total, 503 healthy volunteers at four defined phases of life including 3–5-year old children (n = 44), young adults aged 18–25 years (n = 94), adults aged 40–65 years (“middle agers,” n = 205), and older adults aged 75–85 years (n = 160) were recruited and comprehensively phenotyped. Plasma, serum, buffy coat, urine, feces and saliva samples were collected and stored at −80°C. Significant differences in anthropometric and metabolic parameters between the four groups were found. A major finding was the decrease in fat-free mass and the concomitant increase in % body fat in both sexes across the adult lifespan. Conclusions: The dataset will provide novel information on differences in diet-related parameters over the lifespan and is available for targeted analyses. We expect that this novel platform approach will have implications for the development of innovative food products tailored to promote healthy eating throughout life. Trial registration: DRKS, DRKS00009797. Registered on 20 January 2016, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&_ID=DRKS00009797.
CRIS-Team Scopus Importer:2020-11-20
Keywords: biosamples; cohort; enable-cluster; metabolic phenotyping; nutrition

APOBEC3 enzymes restrict marginal zone B cells - Beck-Engeser, Gabriele B.; Winkelmann, Rebecca; Wheeler, Matthew L.; Shansab, Maryam; Yu, Philipp; Wuensche, Sarah; Walchhuetter, Anja; Metzner, Mirjam; Vettermann, Christian; Eilat, Dan; Defranco, Anthony; Jäck, Hans-Martin; et al. (European Journal of Immunology, 2015)
In general, a long-lasting immune response to viruses is achieved when they are infectious and replication competent. In the mouse, the neutralizing antibody response to Friend murine leukemia virus is contributed by an allelic form of the enzyme Apobec3 (abbreviated A3). This is counterintuitive because A3 directly controls viremia before the onset of adaptive antiviral immune responses. It suggests that A3 also affects the antibody response directly. Here, we studied the relative size of cell populations of the adaptive immune system as a function of A3 activity. We created a transgenic mouse that expresses all seven human A3 enzymes and compared it to WT and mouse A3-deficient mice. A3 enzymes decreased the number of marginal zone B cells, but not the number of follicular B or T cells. When mouse A3 was knocked out, the retroelement hitchhiker-1 and sialyl transferases encoded by genes close to it were overexpressed three and two orders of magnitude, respectively. We suggest that A3 shifts the balance, from the fast antibody response mediated by marginal zone B cells with little affinity maturation, to a more sustained germinal center B-cell response, which drives affinity maturation and, thereby, a better neutralizing response.
EVALuna2:13616

App-based maintenance treatment for alcohol use disorder after acute inpatient treatment: Study protocol for a multicentre randomized controlled trial - Saur, Sebastian; Weisel, Kiona; Lang, Catharina; Fuhrmann, Lukas; Steins-Loeber, Sabine; Enewoldsen, Niklas; Reichl, Daniela; Zink, Mathias; Jakobi, Fabian; Rudolph, Melanie; Ahnert, Andreas; Braunwarth, Wolf Dietrich; et al. (Internet Interventions, 2022)
Background: Alcohol use disorder, a prevalent and disabling mental health problem, is often characterized by a chronic disease course. While effective inpatient and aftercare treatment options exist, the transferal of treatment success into everyday life is challenging and many patients remain without further assistance. App-based interventions with human guidance have great potential to support individuals after inpatient treatment, yet evidence on their efficacy remains scarce. Objectives: To develop an app-based intervention with human guidance and evaluate its usability, efficacy, and cost-effectiveness. Methods: Individuals with alcohol use disorder (DSM-5), aged 18 or higher, without history of schizophrenia, undergoing inpatient alcohol use disorder treatment (N = 356) were recruited in eight medical centres in Bavaria, Germany, between December 2019 and August 2021. Participants were randomized in a 1:1 ratio to either receive access to treatment as usual plus an app-based intervention with human guidance (intervention group) or access to treatment as usual plus app-based intervention after the active study phase (waitlist control/TAU group). Telephone-based assessments are conducted by diagnostic interviewers three and six weeks as well as three and six months after randomization. The primary outcome is the relapse risk during the six months after randomization assessed via the Timeline Follow-Back Interview. Secondary outcomes include intervention usage, uptake of aftercare treatments, AUD-related psychopathology, general psychopathology, and quality of life. Discussion: This study will provide further insights into the use of app-based interventions with human guidance as maintenance treatment in individuals with AUD. If shown to be efficacious, the intervention may improve AUD treatment by assisting individuals in maintaining inpatient treatment success after returning into their home setting. Due to the ubiquitous use of smartphones, the intervention has the potential to become part of routine AUD care in Germany and countries with similar healthcare systems.
CRIS-Team Scopus Importer:2022-03-11
Keywords: Alcohol use disorder; App-based intervention; Germany; Human guidance; Maintenance treatment; RCT

Application of multiplexing technology to the analysis of the intrathecally released immunoglobulins against B. burgdorferi antigens in neuroborreliosis - Zajkowska, Joanna; Lelental, Natalia; Kulakowska, Alina; Mroczko, Barbara; Pancewicz, Slawomir; Bucki, Robert; Kornhuber, Johannes; Lewczuk, Piotr (Immunology Letters, 2015)
Lyme neuroborreliosis (LNB) is an infectious disease of the nervous system caused by the tick-borne spirochete Borrelia burgdorferi. The presence of B. burgdorferi specific antibodies in cerebrospinal fluid (CSF), with evidence of intrathecal production, is the traditional diagnostic standard, although has limitations it such as low sensitivity in the very early phase. In the current study, 27 patients with possible neuroborreliosis suffered from clinically defined Bannwarth syndrome. The control group (CON) consisted of 6 patients. The analyses included function of the blood-CSF barrier (QAlb) as well as intrathecal synthesis of total IgG and IgM, (QIgG, and QIgM). Multiplexing analyses of the specific antibodies (IgG and IgM) against B.burgdorferi antigens were performed with the Microgen assay (Neuried, Germany). The ASI antibodies (Antibody Synthesis Index) specific to particular B. burgdorferi antigens (VlsE, OspC, etc.) were calculated analogously as QIgG and QIgM for separate antibody. All but one patient with NB had pathologic ASI-IgG against B. burgdorferi (median 6.3). Out of 27 NB patients, 13 had measurable ASI-IgM, and all these indices were pathologic. None of the CON subjects had pathologic ASI in either IgG or IgM class. Furthermore, NB patients showed dysfunction of the blood-CSF barrier (average QAlb in the NB and CON groups: 13.8 and 5.6, respectively, p<0.01). Twenty-one of 27 NB patients had at least one positive (>1.5) IgG-ASI against either VlsE, p100, p58, p39, p18, or OspC, and none of these patients showed positive OspA-IgG-ASI. Interestingly, the NB patient with negative IgG ASI on ELISA had the highest p100 IgG ASI on multiplexing (270.8). Among the 13 NB patients with detectable IgM-ASI on ELISA, nine showed measurable IgM-ASI against at least one antigen; however, in one of these cases, the OspC ASI was normal (0.6). In addition, one subject with non-measurable IgM ASI on ELISA had highly pathologic (19.7) index for OspC B. g. on multiplexing. The control subjects with measurable ASI-IgG on ELISA (two cases) had measurable, but normal, indices for VlsE in the IgG class also on multiplexing. None of the control subjects had measurable indices for any of the antigens in the IgM class. The simultaneous analysis of a panel of antibodies against different B. burgdorferi antigens makes multiplexing technology a very interesting supplement to the classic ELISA by providing more specific, antigen-related indices to the general, antigen-unspecific ASI. Whether this additional information proves to be diagnostically relevant will be certainly a matter of further studies.
EVALuna2:23700

A Practical Guide to Immunoassay Method Validation - Andreasson, Ulf; Perret-Liaudet, Armand; Van Doorn, Linda J. C. Van Waalwijk; Blennow, Kaj; Chiasserini, Davide; Engelborghs, Sebastiaan; Fladby, Tormod; Genc, Sermin; Kruse, Niels; Kuipenj, H. Bea; Kulic, Luka; Lewczuk, Piotr; et al. (Frontiers in Neurology, 2015)
Biochemical markers have a central position in the diagnosis and management of patients in clinical medicine, and also in clinical research and drug development, also for brain disorders, such as Alzheimer's disease. The enzyme-linked immunosorbent assay (ELISA) is frequently used for measurement of low-abundance biomarkers. However, the quality of ELISA methods varies, which may introduce both systematic and random errors. This urges the need for more rigorous control of assay performance, regardless of its use in a research setting, in clinical routine, or drug development. The aim of a method validation is to present objective evidence that a method fulfills the requirements for its intended use. Although much has been published on which parameters to investigate in a method validation, less is available on a detailed level on how to perform the corresponding experiments. To remedy this, standard operating procedures (SOPs) with step-by-step instructions for a number of different validation parameters is included in the present work together with a validation report template, which allow for a well-ordered presentation of the results. Even though the SOPs were developed with the intended use for immunochemical methods and to be used for multicenter evaluations, most of them are generic and can be used for other technologies as well.
EVALuna2:23722

A rare heterozygous TREM2 coding variant identified in familial clustering of dementia affects an intrinsically disordered protein region and function of TREM2 - Karsak, Meliha; Glebov, Konstantin; Scheffold, Marina; Bajaj, Thomas; Kawalia, Amit; Karaca, Ilker; Rading, Sebastian; Kornhuber, Johannes; Peters, Oliver; Diez-Fairen, Monica; Froelich, Lutz; Huell, Michael; et al. (Human Mutation, 2019)
Rare coding variants in the triggering receptor expressed on myeloid cells-2 (TREM2) gene have been associated with Alzheimer disease (AD) and homozygous TREM2 loss-of-function variants have been reported in families with monogenic frontotemporal-like dementia with/without bone abnormalities. In a whole-exome sequencing study of a family with probable AD-type dementia without pathogenic variants in known autosomal dominant dementia disease genes and negative for the apolipoprotein E (APOE) epsilon 4 allele, we identified an extremely rare TREM2 coding variant, that is, a glycine-to-tryptophan substitution at amino acid position 145 (NM_018965.3:c.433G>T/p.[Gly145Trp]). This alteration is found in only 1 of 251,150 control alleles in gnomAD. It was present in both severely affected as well as in another putatively affected and one 61 years old as yet unaffected family member suggesting incomplete penetrance and/or a variable age of onset. Gly145 maps to an intrinsically disordered region (IDR) of TREM2 between the immunoglobulin-like and transmembrane domain. Subsequent cellular studies showed that the variant led to IDR shortening and structural changes of the mutant protein resulting in an impairment of cellular responses upon receptor activation. Our results, suggest that a p.(Gly145Trp)-induced structural disturbance and functional impairment of TREM2 may contribute to the pathogenesis of an AD-like form of dementia.
CRIS-Team WoS Importer:2019-10-01

Arc controls alcohol cue relapse by a central amygdala mechanism - Pagano, Roberto; Salamian, Ahmad; Zielinski, Janusz; Beroun, Anna; Nalberczak-Skóra, Maria; Skonieczna, Edyta; Cały, Anna; Tay, Nicole; Banaschewski, Tobias; Desrivières, Sylvane; Grigis, Antoine; Garavan, Hugh; et al. (Molecular Psychiatry, 2022)
Alcohol use disorder (AUD) is a chronic and fatal disease. The main impediment of the AUD therapy is a high probability of relapse to alcohol abuse even after prolonged abstinence. The molecular mechanisms of cue-induced relapse are not well established, despite the fact that they may offer new targets for the treatment of AUD. Using a comprehensive animal model of AUD, virally-mediated and amygdala-targeted genetic manipulations by CRISPR/Cas9 technology and ex vivo electrophysiology, we identify a mechanism that selectively controls cue-induced alcohol relapse and AUD symptom severity. This mechanism is based on activity-regulated cytoskeleton-associated protein (Arc)/ARG3.1-dependent plasticity of the amygdala synapses. In humans, we identified single nucleotide polymorphisms in the ARC gene and their methylation predicting not only amygdala size, but also frequency of alcohol use, even at the onset of regular consumption. Targeting Arc during alcohol cue exposure may thus be a selective new mechanism for relapse prevention.
CRIS-Team Scopus Importer:2022-11-25

Are 10,000 steps per day enough? - Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2017)
EVALuna2:33497

Are perinatal measures associated with adolescent mental health? A retrospective exploration with original data from psychiatric cohorts - Basedow, Lukas A.; Kuitunen-Paul, Sören; Roessner, Veit; Moll, Gunther; Golub, Yulia; Eichler, Anna (BMC Psychiatry, 2022)
Background: Perinatal markers of prenatal development are associated with offspring psychiatric symptoms. However, there is little research investigating the specificity of perinatal markers for the development of specific disorders. This study aimed to explore if perinatal markers are specifically associated with adolescent substance use disorder (SUDs). Methods: Adolescent participants from two study centers, one for SUD patients (n = 196) and one for general psychopathology (n = 307), were recruited for participation. Since the SUD participants presented with a number of comorbid disorders, we performed a 1-on-1 matching procedure, based on age, gender, and specific pattern of comorbid disorders. This procedure resulted in n = 51 participants from each group. From all participants and their mothers we recorded perinatal markers (mode of birth, weeks of completed pregnancy, birth weight, Apgar score after 5 min) as well as intelligence quotient (IQ). The SUD sample additionally filled out the Youth Safe Report (YSR) as well as the PQ-16 and the DUDIT. We aimed to distinguish the two groups (SUD sample vs. general psychiatric sample) based on the perinatal variables via a logistic regression analysis. Additionally, linear regressions were performed for the total group and the subgroups to assess the relationship between perinatal variables and IQ, YSR, DUDIT and PQ-16. Results: The perinatal variables were not able to predict group membership (X2 [4] = 4.77, p =.312, Cox & Snell R² = 0.053). Odds ratios indicated a small increase in probability to belonging to the general psychiatric sample instead of the SUD sample if birth was completed via C-section. After Bonferroni-correction, the linear regression models showed no relation between perinatal markers and IQ (p =.60, R² = 0.068), YSR (p =.09, R² = 0.121), DUDIT (p =.65, R² = 0.020), and PQ-16 (p =.73, R² =0.021). Conclusion: Perinatal markers were not able to distinguish SUD patients from patients with diverse psychopathologies. This pattern contradicts previous findings, perhaps because our chosen markers reflect general processes instead of specific mechanistic explanations. Future studies should take care to investigate specific prenatal markers and associate them with psychopathology on the symptom level.
CRIS-Team Scopus Importer:2022-11-11
Keywords: Addiction; Adolescents; Apgar; Birth; Mental Disorders; Perinatal

Are Protective Activities and Limitations in Practical Skills of Daily Living Associated with the Cognitive Performance of People with Mild Cognitive Impairment? Baseline Results from the BrainFit-Nutrition Study - Scheerbaum, Petra; Grässel, Elmar; Bösl, Sophia; Hanslian, Etienne; Kessler, Christian S.; Scheuermann, Julia-Sophia (Nutrients, 2023)
Limitations in daily living have not yet been described adequately for mild cognitive impairment (MCI). In this study, we investigated first, time spent on protective activities (social, mental, and physical) and second, limitations in practical skills of daily living, both for people with MCI. We used baseline data from 270 individuals who participated in the randomized controlled trial BrainFit-Nutrition. The Montreal Cognitive Assessment (MoCA) was used to identify people with MCI. Participants were asked how much time they spent engaged in social, mental, and physical activities each week. Furthermore, the Bayer-ADL scale was used to quantify deficits in activities of daily living (ADLs). Regarding protection, the number of hours spent engaged in the three activity areas was significantly correlated with the cognitive performance in people with MCI. Social activities were positively associated with current cognitive performance. Concerning the limitations in practical skills of daily living, older and more cognitively impaired individuals were affected. Memory and orientation appear to be among the first practical skills of daily living that become impaired in people with MCI. Treatment recommendations for people with MCI include an increase in social, mental, and physical activities as well as the promotion of a healthy lifestyle.
CRIS-Team Scopus Importer:2023-09-08
Keywords: chronic diseases; dementia; integrative medicine; lifestyle medicine; mild cognitive impairment

"As Good as it Gets at Home" - Reasons for Institutionalisation in Dementia - Grau, Hannes; Berth, H.; Lauterberg, J.; Holle, R.; Grässel, Elmar (Gesundheitswesen, 2016)
What are the reasons for institutionalising community-dwelling persons with dementia?A written survey of family caregivers and general practitioners was undertaken.Within 2 years 47 of 351 people with dementia (13%) were institutionalised. The person with dementia was involved in the decision in only 1/3 of the cases. The 3 most common reasons were: ensuring the best possible care, high expenditure of care-giving time at home, deterioration of the health of the care-receiver.From the ethical point of view the exclusion of the persons with dementia from the decision-making with regard to institutionalisation has to be examined critically. The often given reason of ensuring the best possible care through institutionalisation could be counteracted by the improvement of community-based care.
EVALuna:34132

A Specific Reduction in Aβ1-42 vs. a Universal Loss of Aβ Peptides in CSF Differentiates Alzheimer's Disease From Meningitis and Multiple Sclerosis - Spitzer, Philipp; Lang, Roland; Oberstein, Timo; Lewczuk, Piotr; Ermann, Natalia; Huttner, Hagen; Masouris, Ilias; Kornhuber, Johannes; Koedel, Uwe; Maler, Juan M. (Frontiers in Aging Neuroscience, 2018)
A reduced concentration of Aβ1-42 in CSF is one of the established biomarkers of Alzheimer's disease. Reduced CSF concentrations of Aβ1-42 have also been shown in multiple sclerosis, viral encephalitis and bacterial meningitis. As neuroinflammation is one of the neuropathological hallmarks of Alzheimer's disease, an infectious origin of the disease has been proposed. According to this hypothesis, amyloid pathology is a consequence of a microbial infection and the resulting immune defense. Accordingly, changes in CSF levels of amyloid-β peptides should be similar in AD and inflammatory brain diseases. Aβ1-42 and Aβ1-40 levels were measured in cerebrospinal fluid by ELISA and Western blotting in 34 patients with bacterial meningitis (n = 9), multiple sclerosis (n = 5) or Alzheimer's disease (n = 9) and in suitable controls (n = 11). Reduced concentrations of Aβ1-42 were detected in patients with bacterial meningitis, multiple sclerosis and Alzheimer's disease. However, due to a concurrent reduction in Aβ1-40 in multiple sclerosis and meningitis patients, the ratio of Aβ1-42/Aβ1-40 was reduced only in the CSF of Alzheimer's disease patients. Urea-SDS-PAGE followed by Western blotting revealed that all Aβ peptide variants are reduced in bacterial meningitis, whereas in Alzheimer's disease, only Aβ1-42 is reduced. These results have two implications. First, they confirm the discriminatory diagnostic power of the Aβ1-42/Aβ1-40 ratio. Second, the differential pattern of Aβ peptide reductions suggests that the amyloid pathology in meningitis and multiple sclerosis differs from that in AD and does not support the notion of AD as an infection-triggered immunopathology.
EVALuna2:36428

A sphingolipid mechanism for behavioral extinction - Huston, Joseph P.; Kornhuber, Johannes; Mühle, Christiane; Japtok, Lukasz; Komorowski, Mara; Mattern, Claudia; Reichel, Martin; Gulbins, Erich; Kleuser, Burkhard; Topic, Bianca; Silva, Maria A. De Souza; Müller, Christian P. (Journal of Neurochemistry, 2016)
Reward-dependent instrumental behavior must continuously be re-adjusted according to environmental conditions. Failure to adapt to changes in reward contingencies may incur psychiatric disorders like anxiety and depression. When an expected reward is omitted, behavior undergoes extinction. While extinction involves active re-learning, it is also accompanied by emotional behaviors indicative of frustration, anxiety, and despair (extinction-induced depression). Here, we report evidence for a sphingolipid mechanism in the extinction of behavior. Rapid extinction, indicating efficient re-learning, coincided with a decrease in the activity of the enzyme acid sphingomyelinase (ASM), which catalyzes turnover of sphingomyelin to ceramide, in the dorsal hippocampus of rats. The stronger the decline in ASM activity, the more rapid was the extinction. Sphingolipid-focused lipidomic analysis showed that this results in a decline of local ceramide species in the dorsal hippocampus. Ceramides shape the fluidity of lipid rafts in synaptic membranes and by that way can control neural plasticity. We also found that aging modifies activity of enzymes and ceramide levels in selective brain regions. Aging also changed how the chronic treatment with corticosterone (stress) or intranasal dopamine modified regional enzyme activity and ceramide levels, coinciding with rate of extinction. These data provide first evidence for a functional ASM-ceramide pathway in the brain involved in the extinction of learned behavior. This finding extends the known cellular mechanisms underlying behavioral plasticity to a new class of membrane-located molecules, the sphingolipids, and their regulatory enzymes, and may offer new treatment targets for extinction- and learning-related psychopathological conditions. Sphingolipids are common lipids in the brain which form lipid domains at pre- and postsynaptic membrane compartments. Here we show a decline in dorsal hippocampus ceramide species together with a reduction of acid sphingomyelinase activity during extinction of conditioned behavior in rats. This reduction was associated with expression of re-learning-related behavior, but not with emotional behaviors. Read the Editorial Highlight for this article on page 485.
EVALuna2:23768

Assay to measure sphingomyelinase and ceramidase activities efficiently and safely - Mühle, Christiane; Kornhuber, Johannes (Journal of Chromatography A, 2017)
As part of the sphingomyelin pathway, sphingomyelinases and ceramidases have attracted much attention in basic as well as clinical research. However, current assays still often rely on a radioactive substrate, extensive manual purification steps, and hazardous solvents for chromatographic analysis. We here show the equivalence of a fluorescent sphingomyelin substrate and present a new versatile solvent replacing the chloroform/methanol mixture. By further modifications including the omission of the manual extraction steps, chloroform and methanol are eliminated from the entire procedure and render the assay flexible to repeated analyses at multiple time intervals. These improvements allow for the rapid detection of both enzymes in a high throughput microtiter format. Moreover, we demonstrate the relevance of the plastic assay material and the interchangeability between serum and different plasma sources.
EVALuna2:33502

Assessing behavioral changes in antidementia therapy: Perspectives of an international ADL-Project - Erzigkeit, Helmut; Overall, John E.; Stemmler, Mark; Steinwachs, Klaus; Lehfeld, Hartmut; Hulla, Franz (Aging, Health, and Healing, 1995)

Assessing comfort in the epilepsy monitoring unit: Psychometric testing of an instrument - Egger-Rainer, Andrea; Trinka, Eugen; Zimmermann, Georg; Arnold, Stephan; Boßelmann, Christian; Hamer, Hajo; Hengsberger, Anna; Lang, Johannes; Lerche, Holger; Noachtar, Soheyl; Pataraia, Ekaterina; Schulze-Bonhage, Andreas; et al. (Epilepsy & Behavior, 2020)
Purpose: The purpose of the study was to evaluate the psychometric properties of the newly developed Epilepsy Monitoring Unit Comfort Questionnaire (EMUCQ) according to the consensus-based standards for the selection of health measurements instruments (COSMIN). Moreover, we aimed to assess changes in comfort-levels. Methods: From October 2018 to November 2019, a total of 267 patients participated in a quantitative study in ten epilepsy centers in Austria and southern Germany. For basic item analysis, descriptive analysis and correlational analysis were computed. An exploratory factor analysis (EFA) was undertaken to detect the factor structure. Reliability was checked through internal consistency (Cronbach's alpha) and the measurement error. In the validity domain, convergent validity and structural validity were estimated. t-Tests were used to detect changes in comfort-levels. Results: Due to unfavorable statistical properties, two items were removed. Exploratory factor analysis showed a three-factorial solution. The EMUCQ was found to be a reliable instrument (Cronbach's alpha 0.77–0.81 for the subscales, 0.88 for the scale total comfort); convergent validity could be supported, too. Confirmatory factor analysis (CFA) supported the hypothesis that structural validity for the three subscales holds. The patients' comfort levels were lower at the end of the stay than at the beginning and lower in nonseizure-free patients compared with seizure-free patients. Conclusion: Validity and reliability are supported for the 42-item EMUCQ in the three-factorial solution. Owing to the item reduction and modifications made in the CFA, a new test should be carried out on a different sample.
CRIS-Team Scopus Importer:2020-10-02
Keywords: Comfort; Epilepsy monitoring unit; Questionnaire; Validation study

Assessing Professional Caregivers’ Intention to Use and Relatives’ Support of Use for a Mobile Service Robot in Group Therapy for Institutionalized People with Dementia – A Standardized Assessment Using an Adapted Version of UTAUT - Wasic, Catharina; Bahrmann, Frank; Vogt, Stefan; Böhme, Hans Joachim; Grässel, Elmar (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 2022)
Introduction: Care settings for people with dementia involve not only the individuals who are being cared for but also professional caregivers and relatives. Therefore, the use of a social robot also depends on professional caregivers’ and relatives’ acceptance of the robot. Methods: We surveyed 29 relatives and 18 professional caregivers of institutionalized people with dementia in a nursing home in Germany. To assess acceptance, we used an adapted version of the Unified Theory of Acceptance and Use of Technology and the Almere model. Results: Intention to use the robot by professional caregivers correlates positively with attitude, facilitating conditions and perceived usefulness as well as negatively with anxiety. Support of use by relatives correlates positively with attitude, perceived usefulness, facilitating conditions and social influence. Intention to use and support of use significantly differ between professional caregivers and relatives. Conclusion: For professional caregivers and relatives that are not the primary users of the robot and only indirectly affected by the employment of a robot, perceived usefulness and attitude have a significant influence on the acceptance. Professional caregivers are more skeptical about social robots and have lower acceptance values compared to relatives.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Acceptance; Caregivers; Dementia; Residential facilities; Robotics

Assessing the commutability of reference material formats for the harmonization of amyloid-? measurements - Bjerke, Maria; Andreasson, Ulf; Kuhlmann, Julia; Portelius, Erik; Pannee, Josef; Lewczuk, Piotr; Umek, Robert M.; Vanmechelen, Eugeen; Vanderstichele, Hugo; Stoops, Erik; Lewis, Jennifer; Vandijck, Manu; et al. (Clinical Chemistry and Laboratory Medicine, 2016)
The cerebrospinal fluid (CSF) amyloid-? (A?42) peptide is an important biomarker for Alzheimer's disease (AD). Variability in measured A?42 concentrations at different laboratories may be overcome by standardization and establishing traceability to a reference system. Candidate certified reference materials (CRMs) are validated herein for this purpose.Commutability of 16 candidate CRM formats was assessed across five CSF A?42 immunoassays and one mass spectrometry (MS) method in a set of 48 individual clinical CSF samples. Promising candidate CRM formats (neat CSF and CSF spiked with A?42) were identified and subjected to validation across eight (Elecsys, EUROIMMUN, IBL, INNO-BIA AlzBio3, INNOTEST, MSD, Simoa, and Saladax) immunoassays and the MS method in 32 individual CSF samples. Commutability was evaluated by Passing-Bablok regression and the candidate CRM termed commutable when found within the prediction interval (PI). The relative distance to the regression line was assessed.The neat CSF candidate CRM format was commutable for almost all method comparisons, except for the Simoa/MSD, Simoa/MS and MS/IBL where it was found just outside the 95% PI. However, the neat CSF was found within 5% relative distance to the regression line for MS/IBL, between 5% and 10% for Simoa/MS and between 10% and 15% for Simoa/MSD comparisons.The neat CSF candidate CRM format was commutable for 33 of 36 method comparisons, only one comparison more than expected given the 95% PI acceptance limit. We conclude that the neat CSF candidate CRM can be used for value assignment of the kit calibrators for the different A?42 methods.
EVALuna2:23763

Assessment of parental stress using the "Eltern-Belastungs-Screening zur Kindeswohlgefährdung" (EBSK) - association with emotional and behavioral problems in children - Eichler, Anna; Glaubitz, Katharina; Hartmann, Luisa Carla; Spangler, Gottfried (Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2014)
Parental stress is increased in clinical contexts (e.g., child psychiatry) and correlates with behavioral and emotional problems of children. In addition, parental stress can result in a biased parental perception of child's behavior and emotions. These interrelations were examined in a normal (N = 320) and a clinical (N = 75) sample. The "Eltern-Belastungs-Screening zur Kindeswohlgefährdung" (EBSK; Deegener, Spangler, Körner & Becker, 2009) was used for the assessment of parental stress. As expected, increased EBSK scores were overrepresented in the clinical sample. In both samples stressed parents reported having children with more behavioral and emotional problems. Children of stressed parents in turn reported significantly less problems than their parents did. The rating of independent third persons, e.g. teachers, was not available and should be added in future research. Restrictions in methodology and conclusions for practice are discussed.
EVALuna2:23886

Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study - Hoertel, Nicolas; Sanchez-Rico, M.; Gulbins, E.; Kornhuber, Johannes; Vernet, R.; Beeker, N.; Neuraz, A.; Blanco, C.; Olfson, M.; Airagnes, G.; Lemogne, C.; Alvarado, J. M.; et al. (Epidemiology and Psychiatric Sciences, 2022)
AIMS: To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospitalised for COVID-19. A total of 686 (4.8%) inpatients received a BZRA at hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (standard deviation (s.d.) = 25.4). The study baseline was the date of admission, and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, medical comorbidities and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW). RESULTS: Over a mean follow-up of 14.5 days (s.d. = 18.1), the primary endpoint occurred in 186 patients (27.1%) who received BZRAs and in 1134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (hazard ratio (HR) = 3.20; 95% confidence interval (CI) = 2.74-3.74; p < 0.01) and in the IPW analysis (HR = 1.61; 95% CI = 1.31-1.98, p < 0.01), with a significant dose-dependent relationship (HR = 1.55; 95% CI = 1.08-2.22; p = 0.02). This association remained significant in sensitivity analyses. Exploratory analyses indicate that most BZRAs may be associated with an increased mortality among patients hospitalised for COVID-19, except for diazepam, which may be associated with a reduced mortality compared with any other BZRA treatment. CONCLUSIONS: BZRA use may be associated with an increased mortality among patients hospitalised for COVID-19, suggesting the potential benefit of decreasing dose or tapering off gradually these medications when possible.
CRIS-Team Scopus Importer:2022-04-15
Keywords: Benzodiazepine; COVID-19; mortality; SARS-CoV-2

Association between FIASMA psychotropic medications and reduced risk of intubation or death in individuals with psychiatric disorders hospitalized for severe COVID-19: an observational multicenter study - Hoertel, Nicolas; Sánchez-Rico, Marina; Gulbins, Erich; Kornhuber, Johannes; Carpinteiro, Alexander; Abellán, Miriam; de la Muela, Pedro; Vernet, Raphaël; Beeker, Nathanaël; Neuraz, Antoine; Delcuze, Aude; Alvarado, Jesús M.; et al. (Translational Psychiatry, 2022)
The acid sphingomyelinase (ASM)/ceramide system may provide a useful framework for better understanding SARS-CoV-2 infection and the repurposing of psychotropic medications functionally inhibiting the acid sphingomyelinase/ceramide system (named FIASMA psychotropic medications) against COVID-19. We examined the potential usefulness of FIASMA psychotropic medications in patients with psychiatric disorders hospitalized for severe COVID-19, in an observational multicenter study conducted at Greater Paris University hospitals. Of 545 adult inpatients, 164 (30.1%) received a FIASMA psychotropic medication upon hospital admission for COVID-19. We compared the composite endpoint of intubation or death between patients who received a psychotropic FIASMA medication at baseline and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, psychiatric and other medical comorbidity, and other medications. FIASMA psychotropic medication use at baseline was significantly associated with reduced risk of intubation or death in both crude (HR = 0.42; 95%CI = 0.31-0.57; p < 0.01) and primary inverse probability weighting (IPW) (HR = 0.50; 95%CI = 0.37-0.67; p < 0.01) analyses. This association was not specific to one FIASMA psychotropic class or medication. Patients taking a FIASMA antidepressant at baseline had a significantly reduced risk of intubation or death compared with those taking a non-FIASMA antidepressant at baseline in both crude (HR = 0.57; 95%CI = 0.38-0.86; p < 0.01) and primary IPW (HR = 0.57; 95%CI = 0.37-0.87; p < 0.01) analyses. These associations remained significant in multiple sensitivity analyses. Our results show the potential importance of the ASM/ceramide system framework in COVID-19 and support the continuation of FIASMA psychotropic medications in these patients and the need of large- scale clinical trials evaluating FIASMA medications, and particularly FIASMA antidepressants, against COVID-19.
CRIS-Team Scopus Importer:2022-03-11

Association Between FIASMAs and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID-19: An Observational Multicenter Study - Hoertel, Nicolas; Sanchez-Rico, Marina; Gulbins, Erich; Kornhuber, Johannes; Carpinteiro, Alexander; Lenze, Eric J.; Reiersen, Angela M.; Abellan, Miriam; De La Muela, Pedro; Vernet, Raphael; Blanco, Carlos; Cougoule, Celine; et al. (Clinical Pharmacology & Therapeutics, 2021)
Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the ASM/ceramide system may be central to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe coronavirus disease 2019 (COVID-19) in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking an FIASMA medication at the time of their hospital admission. The primary end point was a composite of intubation and/or death. We compared this end point between patients taking vs. not taking an FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD = 12.5), the primary end point occurred in 104 patients (37.5%) receiving an FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.58-0.87, P < 0.001) and primary IPW (HR = 0.58, 95%CI = 0.46-0.72, P < 0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one particular FIASMA class or medication. These results show the potential importance of the ASM/ceramide system in COVID-19 and support the continuation of FIASMA medications in these patients. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.
CRIS-Team WoS Importer:2021-07-09

Association between infection with Helicobacter pylori and Chlamydia pneumoniae and risk of ischemic stroke subtypes: Results from a population-based case-control study - Maass, Matthias; Faller, Gerhard; Gesslein, Markus; Neureiter, Daniel; Neundörfer, Bernhard; Craiovan, Benjamin; Beck, Georg; Kolominsky-Rabas, Peter; Heuschmann, Peter U. (2001)
Background and Purpose - Helicobacter pylori and Chlamydia pneumoniae have been associated epidemiologically and pathogenetically with coronary atherosclerosis. However, population-based data on chronic infection and stroke are lacking. Therefore, we investigated the association of both bacterial pathogens and ischemic stroke subtypes in a population-based case-control study. Methods - Patients with first ischemic stroke in the population-based Erlangen Stroke Project were collected as cases. Neighborhood controls were drawn from the study population, matched for age, sex, and place of residence. IgG antibodies to H pylori were measured by enzyme immunoassay, and IgG antibodies to C pneumoniae were measured by microimmunofluorescence technique. Conditional logistic regression was used. Analyses were stratified for etiologic stroke subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results - A total of 145 case and 260 control subjects were included. Chronic H pylori infection was associated with a higher risk of stroke caused by small-artery occlusion (adjusted odds ratio, 3.31; 95% CI, 1.15 to 9.56) and a lower risk of cardioembolic stroke (adjusted odds ratio, 0.21; 95% CI, 0.06 to 0.71). Overall, elevated H pylori as well as elevated C pneumoniae antibodies were not associated with ischemic stroke. Conclusions - Our population-based study does not provide evidence of any strong association between the immune response to C pneumoniae as a marker of prior infection and ischemic stroke. Further studies are required to reveal the role of chronic H pylori infection as an independent risk factor for the subgroup small-artery occlusion.
Created from Fastlane, Scopus look-up
Keywords: Chlamydia pneumoniae; Helicobacter pylori; Seroepidemiologic studies; Stroke

Association of a CAMK2A genetic variant with logical memory performance and hippocampal volume in the elderly - Rhein, Cosima; Mühle, Christiane; Lenz, Bernd; Richter-Schmidinger, Tanja; Kogias, Georgios; Boix, Fernando; Lourdusamy, Anbarasu; Dörfler, Arnd; Peters, Oliver; Ramirez, Alfredo; Jessen, Frank; Maier, Wolfgang; et al. (Brain Research Bulletin, 2020)
Calcium/Calmodulin-dependent kinase alpha (αCaMKII) has been shown to play an essential role in synaptic plasticity and in learning and memory in animal models. However, there is little evidence for an involvement in specific memories in humans. Here we tested the potential involvement of the αCaMKII coding gene CAMK2A in verbal logical memory in two Caucasian populations from Germany, in a sample of 209 elderly people with cognitive impairments and a sample of 142 healthy adults. The association of single nucleotide polymorphisms (SNPs) located within the genomic region of CAMK2A with verbal logical memory learning and retrieval from the Wechsler Memory Scale was measured and hippocampal volume was assessed by structural MRI. In the elderly people, we found the minor allele of CAMK2A intronic SNP rs919741 to predict a higher hippocampal volume and better logical memory retrieval. This association was not found in healthy adults. The present study may provide evidence for an association of a genetic variant of the CAMK2A gene specifically with retrieval of logical memory in elderly humans. This effect is possibly mediated by a higher hippocampal volume.
CRIS-Team Scopus Importer:2020-05-22
Keywords: adults; CAMK2A; elderly; hippocampus; logical memory; αCaMKII

Association of CamK2A genetic variants with transition time from occasional to regular heroin use in a sample of heroin-dependent individuals - Eirich, Antonia; Biermann, Teresa; Müller, Christian P.; Kornhuber, Johannes; Benyamin, Beben; Hulse, Gary K.; Wildenauer, Dieter B.; Schwab, Sibylle (Psychiatric Genetics, 2019)
Objectives Susceptibility to heroin dependence is strongly influenced by genetic factors with heritability estimates as high as 0.7. A number of genes, as well as environmental factors, are likely to contribute to its etiology. Not all individuals who have ever tried heroin at some stage during their lifetime become dependent on heroin. It has been suggested that genetic factors might be more important in the transition stage to heroin dependence rather than in environmental exposures and experimenting with heroin. As the features of substance dependence and memory formation have been found to be strikingly similar, we have focused on a key enzyme involved in long-term potentiation and synaptic plasticity, namely the calcium-dependent/calmodulin-dependent protein kinase IIa (CAMKIIa). We hypothesized, that CamK2A genetic variation may play a role in the transition from occasional to regular heroin use.
CRIS-Team WoS Importer:2019-02-27

Association of Cerebral Amyloid-? Aggregation With Cognitive Functioning in Persons Without Dementia - Jansen, Willemijn J.; Ossenkoppele, Rik; Tijms, Betty M.; Fagan, Anne M.; Hansson, Oskar; Klunk, William E.; Van Der Flier, Wiesje M.; Villemagne, Victor L.; Frisoni, Giovanni B.; Fleisher, Adam S.; Lleo, Alberto; Mintun, Mark A.; et al. (JAMA Psychiatry, 2018)
Cerebral amyloid-? aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-? aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score <=27 or memory z score<=-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample - Mobascher, A.; Diaz-Lacava, A.; Wagner, Michael; Gallinat, J.; Wienker, T. F.; Drichel, D.; Becker, T.; Steffens, M.; Dahmen, N.; Gruender, G.; Thürauf, Norbert; Kiefer, F.; et al. (PLoS ONE, 2016)
Variation in genes coding for nicotinic acetylcholine receptor (nAChR) subunits affect cognitive processes and may contribute to the genetic architecture of neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in the CHRNA4 gene that codes for the alpha4 subunit of alpha4/beta2-containing receptors have previously been implicated in aspects of (mostly visual) attention and smoking-related behavioral measures. Here we investigated the effects of six synonymous but functional CHRNA4 exon 5 SNPs on the N100 event-related potential (ERP), an electrophysiological endophenotype elicited by a standard auditory oddball. A total of N = 1,705 subjects randomly selected from the general population were studied with electroencephalography (EEG) as part of the German Multicenter Study on nicotine addiction. Two of the six variants, rs1044396 and neighboring rs1044397, were significantly associated with N100 amplitude. This effect was pronounced in females where we also observed an effect on reaction time. Sequencing of the complete exon 5 region in the population sample excluded the existence of additional/functional variants that may be responsible for the observed effects. This is the first large-scale population-based study investigation the effects of CHRNA4 SNPs on brain activity measures related to stimulus processing and attention. Our results provide further evidence that common synonymous CHRNA4 exon 5 SNPs affect cognitive processes and suggest that they also play a role in the auditory system. As N100 amplitude reduction is considered a schizophrenia-related endophenotype the SNPs studied here may also be associated with schizophrenia outcome measures.
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Association of cultural origin and migration status with work-related mental health of migrants and refugees in Europe: a systematic review protocol - Herold, Regina; Wuchenauer, Frederik; Kandler, Anja; Morawa, Eva; Unverzagt, Susanne; Voss, Amanda; Erim, Yesim (BMJ Open, 2022)
IntroductionMigrants make up a significant proportion of the European working population. Previous studies have already shown that migrants and refugees often suffer from poor work-related conditions in the host country, which might have an impact on mental health. Thus, the main objective of this systematic review is to analyse and summarise existing research on work-related conditions of migrants and refugees in Europe and to investigate the relationship of these conditions with their mental health. METHODS AND ANALYSIS: Three electronic databases (PubMed/MEDLINE, PsycINFO and CINAHL) will be systematically searched for eligible articles using quantitative study designs (randomised controlled trials, cohort, case-control and cross-sectional studies with and without control groups) written in English, German, French, Italian, Polish, Spanish or Turkish and published from 1st January 2016 onwards. The primary health outcomes will be diagnosed psychiatric and psychological disorders, suicide and suicide attempts, psychiatric and psychological symptoms, and perceived distress. The secondary health outcomes will be more general concepts of mental health such as well-being, life satisfaction and quality of life. Outcome measures must have been assessed by validated questionnaires. Screening of all articles, reference lists of included studies and relevant reviews as well as data extraction will be performed independently by two review authors. Methodological quality of primary studies will be assessed and discussed. The results of the primary studies will be summarised descriptively. Migrants and natives, migrants and refugees, migrants of different cultural backgrounds and migrants living in different host countries will be compared in terms of the association between their work-related conditions and their mental health. ETHICS AND DISSEMINATION: This systematic review is excluded from ethical approval because it will use previously approved published data from primary studies. The results of this review will be submitted to a related peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021244840.
CRIS-Team Scopus Importer:2022-02-04
Keywords: mental health; occupational & industrial medicine; psychiatry; public health

Association of Depression and Anxiety Disorders With Autoimmune Thyroiditis: A Systematic Review and Meta-analysis - Siegmann, Eva-Maria; Müller, Helge H.O.; Luecke, Caroline; Philipsen, Alexandra; Kornhuber, Johannes; Groemer, Teja W. (JAMA Psychiatry, 2018)
Importance: With a prevalence of 4% to 13% in the United States, autoimmune thyroiditis (AIT) is a major health problem. Besides somatic complications, patients with AIT can also experience psychiatric disorders. The extent of these organic psychiatric diseases in patients with AIT, however, is so far not commonly known. Objective: To provide meta-analytic data on the association of depression and anxiety with AIT. Data Sources: Google Scholar, the EBSCO Host databases, the Web of Knowledge, and PubMed were searched from inception through December 5, 2017. Articles identified were reviewed and reference lists were searched manually. Study Selection: Case-control studies that reported the association between AIT and either depression or anxiety disorders or both were included. Data Extraction and Synthesis: Data extraction was performed by multiple observers following the PRISMA guidelines. Two univariate random-effects meta-analyses were performed, and moderators were tested with Bonferroni-corrected meta-regression analysis. Heterogeneity was assessed with the I2 statistic. Sensitivity analyses tested the robustness of the results. Small study effects were assessed with funnel plots and the Egger test. Main Outcomes and Measures: The odds ratio of patients with AIT and depression compared with a healthy control group, as well as the odds ratio of patients with AIT and anxiety disorders compared with a healthy control group. Results: Nineteen studies comprising 21 independent samples were included, with a total of 36 174 participants (35 168 for depression and 34 094 for anxiety). Patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had significantly higher scores on standardized depression instruments, with an odds ratio of 3.56 (95% CI, 2.14-5.94; I2 = 92.1%). For anxiety disorders, patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had an odds ratio of 2.32 (95% CI, 1.40-3.85; I2 = 89.8%). Funnel plot asymmetry was detected for studies of depression. Study quality assessed with the Newcastle-Ottawa Scale for case-control studies (mean [SD] score: anxiety, 5.77 [1.17]; depression, 5.65 [1.14]; of a possible maximum score of 9) and proportion of females did not modulate the meta-analytic estimate, whereas mean age did. Conclusions and Relevance: This meta-analysis establishes the association between AIT and depression and anxiety disorders. Patients with AIT exhibit an increased chance of developing symptoms of depression and anxiety or of receiving a diagnosis of depression and anxiety disorders. This finding has important implications for patients and could lead to the choice of early treatment-and not only psychotherapeutic treatment-of the organic disorder.
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Association of impulsivity with quality of life and well-being after alcohol withdrawal treatment - Reichl, Daniela; Enewoldsen, Niklas; Weisel, Kiona; Fuhrmann, Lukas; Lang, Catharina; Saur, Sebastian; Berking, Matthias; Zink, Mathias; Ahnert, Andreas; Falkai, Peter; Kraus, Thomas; Hillemacher, Thomas; et al. (Journal of Clinical Psychology, 2022)
Objectives Impulsivity is related to a higher risk of relapse in alcohol use disorders. However, besides drinking behavior, other recovery outcomes like physical and mental health-related quality of life are at least as important. The present study aimed to fill a research gap regarding the association of different impulsivity facets with health-related quality of life and well-being in alcohol use disorder. Methods Individuals with a primary alcohol use disorder diagnosis (n = 167) were interviewed with standardized self-report measures at the progressed stage of their withdrawal treatment and 6 weeks thereafter. Multiple regression models were calculated to examine the association of impulsivity, craving, and drinking patterns with health-related quality of life and well-being 6 weeks after withdrawal treatment, as well as the predictive role of impulsivity assessed during withdrawal for these two outcomes. Results Craving was associated with health-related quality of life and well-being 6 weeks after withdrawal. Likewise, non-planning and attentional impulsivity were associated with well-being 6 weeks after withdrawal. Motor impulsivity during withdrawal treatment predicted health-related quality of life 6 weeks thereafter. Conclusion Impulsivity seems to be negatively related to health-related quality of life and well-being in the first weeks after alcohol withdrawal treatment, probably to a higher extent than drinking patterns, but differentiating between its facets seems to be important. These findings emphasize the importance of treatment approaches aiming at reduced impulsivity in the early recovery process.
CRIS-Team WoS Importer:2022-02-04

Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis. - Kuramatsu, Joji; Gerner, Stefan; Ziai, Wendy; Bardutzky, Juergen; Sembill, Jochen; Sprügel, Maximilian; Mrochen, Anne; Kölbl, Kathrin; Ram, Malathi; Avadhani, Radhika; Falcone, Guido J.; Selim, Magdy H.; et al. (Stroke, 2022)
BACKGROUND: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. METHODS: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). RESULTS: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. CONCLUSIONS: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.
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Association of Maternal Smoking during Pregnancy with Neurophysiological and ADHD-Related Outcomes in School-Aged Children - Jansone, Karina; Eichler, Anna; Fasching, Peter; Kornhuber, Johannes; Kaiser, Anna; Millenet, Sabina; Banaschewski, Tobias; Nees, Frauke; On Behalf Of The Imac-Mind Consortium, (International Journal of Environmental Research and Public Health, 2023)
Data of a longitudinal cohort study were analyzed to investigate the association between prenatal tobacco exposure and electroencephalographical (EEG) power spectrum in healthy, school-aged children as well as its relationship with attention deficit hyperactivity disorder (ADHD)-related symptoms. Group comparisons (exposed, non-exposed) were performed to test whether prenatal tobacco exposure was associated with brain activity and ADHD symptoms, with adjustments made for covariates including child's sex, child's age, maternal age, maternal smoking habit before pregnancy, alcohol consumption during pregnancy, gestation age, and maternal psychopathology. Tobacco-exposed children showed higher brain activity in the delta and theta frequency bands. This effect was independent of the considered covariates. However, the effects on hyperactivity were found to significantly depend on maternal age and alcohol consumption during pregnancy, but not on the amount of exposure. In summary, smoking during pregnancy significantly affected the resting-state brain activity in children, independent of socio-demographic factors, indicating potential long-lasting effects on brain development. Its impact on ADHD-related behavior was shown to be influenced by socio-demographic confounding factors, such as maternal alcohol consumption and the age of the mother.
CRIS-Team Scopus Importer:2023-04-07
Keywords: ADHD; EEG; hyperactivity; maternal smoking; pregnancy; resting-state brain activity

Association of prenatal alcohol exposure and prenatal maternal depression with offspring low-grade inflammation in early adolescence - Maschke, Janina; Roetner, Jakob; Bösl, Sophia; Plank, Anne-Christine; Rohleder, Nicolas; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kratz, Oliver; Moll, Gunther; Lenz, Bernd; Kornhuber, Johannes; et al. (International Journal of Environmental Research and Public Health, 2021)
(1) This longitudinal study aimed to investigate the link between prenatal alcohol exposure and prenatal maternal depression with the offspring’s low-grade inflammatory status. (2) Prenatal alcohol exposure was determined via maternal self-report during the 3rd trimester of pregnancy (self-report+: n = 29) and the meconium alcohol metabolite Ethyl Glucuronide (EtG), collected at birth (≥30 ng/g: n = 23). The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for prenatal maternal depressive symptoms during the 3rd trimester (≥10: n = 35). Fifteen years later, 122 adolescents (M = 13.32 years; 48.4% female) provided blood samples for the analysis of high sensitivity C-reactive protein (hsCRP; M = 0.91; SD = 1.28). (3) Higher hsCRP levels were found in EtG positive adolescents (p = 0.036, ηp2 = 0.04) and an inverse non-significant dose–response relation with hsCRP (r = −0.35, p = 0.113). For maternal self-reported prenatal alcohol consumption (p = 0.780, ηp2 = 0.00) and prenatal depressive symptoms (p = 0.360, ηp2 = 0.01) no differences for hsCRP levels between the affected and unaffected groups were found. (4) Adolescents with prenatal alcohol exposure are at risk for low-grade systemic inflammation. The EtG biomarker may be more accurate compared to self-reports. The findings suggest that prenatal maternal depression does not evoke low-grade systemic inflammation.
CRIS-Team Scopus Importer:2021-08-06
Keywords: Early adolescence; High-sensitivity C-reactive protein (hsCRP); Low-grade systemic inflammation; Maternal self-report; Meconium ethyl glucuronide (EtG); Pregnancy; Prenatal alcohol exposure (PAE); Prenatal depression

Association of systemic inflammation markers with the presence and extent of coronary artery calcification - Raaz-Schrauder, Dorette; Klinghammer, Lutz; Baum, Christina; Frank, Thomas; Lewczuk, Piotr; Achenbach, Stephan; Cicha, Iwona; Stumpf, Christian; Wiltfang, Jens; Kornhuber, Johannes; Daniel, Werner; Garlichs, Christoph (Cytokine, 2012)
Background: Coronary artery calcification (CAC) is a marker for the presence and extent of coronary atherosclerotic plaques and can be detected non-invasively by multi-detector row CT (MDCT). Well known predictors of CAC are age, gender, and the classical atherogenic risk factors. CAC is associated with atherosclerotic plaque burden, but it is still elusive if atherosclerosis-relevant cytokines and chemokines are also associated with CAC. Methods: We conducted a clinical study among 455 consecutive individuals who underwent coronary calcium assessment performed by MDCT. Before MDCT, blood was drawn and subsequently analyzed for 20 different atherosclerosis-relevant cytokines and chemokines using a Luminex-laser-based fluorescence analysis. Results: Using univariate analyses, CAC patients revealed significantly higher levels of the chemokines IP-10 (P=0.047) and eotaxin (P=0.031) as compared to non-CAC patients. In multivariate analyses using common thresholds for calcium burden, the three cytokines interleukin-6 (P=0.028), interleukin-8 (P=0.009), and interleukin-13 (P=0.024) were associated with high coronary calcium levels after adjustment for classical variables and risk factors. Conclusions: In a large group of individuals with atypical chest pain and a low to intermediate likelihood for coronary artery disease elevated plasma levels of IL-6 and reduced levels of IL-8 and IL-13 were predictive for distinct coronary artery calcification. These findings support a specific role of these cytokines in coronary calcification. © 2011 Elsevier Ltd.
CRIS-Team Scopus Importer:2023-07-10
Keywords: Atherosclerosis; Cardiac computed tomography; Coronary calcification; Cytokines; Inflammation

Association of testosterone and BDNF serum levels with craving during alcohol withdrawal - Heberlein, Annemarie; Lenz, Bernd; Opfermann, Birgitt; Groschl, Michael; Janke, Eva; Stange, Katrin; Groh, Adrian; Kornhuber, Johannes; Frieling, Helge; Bleich, Stefan; Hillemacher, Thomas (Alcohol, 2016)
Preclinical and clinical studies show associations between testosterone and brain-derived neurotrophic growth factor (BDNF) serum levels. BDNF and testosterone have been independently reported to influence alcohol consumption. Therefore, we aimed to investigate a possible interplay of testosterone and BDNF contributing to alcohol dependence. Regarding possible interplay of testosterone and BDNF and the activity of the hypothalamic pituitary axis (HPA), we included cortisol serum levels in our research. We investigated testosterone and BDNF serum levels in a sample of 99 male alcohol-dependent patients during alcohol withdrawal (day 1, 7, and 14) and compared them to a healthy male control group (n = 17). The testosterone serum levels were significantly (p < 0.001) higher in the patients' group than in the control group and decreased significantly during alcohol withdrawal (p < 0.001). The decrease of testosterone serum levels during alcohol withdrawal (days 1-7) was significantly associated with the BDNF serum levels (day 1: p = 0.008). In a subgroup of patients showing high cortisol serum levels (putatively mirroring high HPA activity), we found a significant association of BDNF and testosterone as well as with alcohol craving measured by the Obsessive and Compulsive Drinking Scale (OCDS). Our data suggest a possible association of BDNF and testosterone serum levels, which may be relevant for the symptomatology of alcohol dependence. Further studies are needed to clarify our results.
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Association of Testosterone Levels and Steroid 5-Alpha-Reductase 2 Polymorphisms with Opioid Craving - Janke, Eva; Groh, Adrian; Mühle, Christiane; Dürsteler-Macfarland, Kenneth M.; Wiesbeck, Gerhard A.; Kornhuber, Johannes; Jahn, Kirsten; Groeschl, Michael; Lichtinghagen, Ralf; Frieling, Helge; Bleich, Stefan; Hillemacher, Thomas; et al. (Neuropsychobiology, 2020)
Background/Aims: Opioid dependence is a severe disease which is associated with a high risk of relapse, even in cases of successful withdrawal therapy. Studies have shown alterations of the hypothalamic-pituitary-gonadal axis in opioid-dependent patients, such as decreased testosterone serum levels in affected males. Sex hormones and the steroid 5-alpha-reductase 2 (SRD5A2) V89L polymorphism are associated with craving during alcohol withdrawal, but little is known about their impact on symptomatology of opioid dependence. Methods: In this study, we analyzed 2 independent male cohorts of opioid-dependent patients for possible alterations in testosterone serum levels compared to non-opioid-dependent controls. In one of the cohorts, we additionally investigated associations of testosterone serum levels and 3 SRD5A2 polymorphisms with symptoms of opioid dependence, measured by the Heroin Craving Questionnaire (HCQ). Results: In the patient groups, we found significantly decreased testosterone serum levels compared to the control groups. Furthermore, we found significant associations of both the testosterone serum levels and the SRD5A2 V89L polymorphism with opioid craving assessed by the HCQ. Conclusion: Our data show a possible role of testosterone metabolism in opioid dependence, which may be relevant for the establishment of future treatment strategies.
CRIS-Team Scopus Importer:2020-07-31

Associations Between Acculturation, Depressive Symptoms, and Life Satisfaction Among Migrants of Turkish Origin in Germany: Gender- and Generation-Related Aspects - Morawa, Eva; Brand, Tilman; Dragano, Nico; Jockel, Karl-Heinz; Moebus, Susanne; Erim, Yesim (Frontiers in Psychiatry, 2020)
Objective: The aim of the present study was to investigate the degree of depressive symptoms and life satisfaction (LS) as well as the association between acculturation and depressive symptoms among a large sample of persons with Turkish migration background in Germany, taking into account gender- and migration-related differences. Methods: This study was part of a pretest for a large national epidemiological cohort study in Germany. Acculturation was measured using the Frankfurt Acculturation Scale (FRACC). Based on the median split of the two subscales, four acculturative styles according to Berry (integration, assimilation, separation and marginalization) were determined. Depressive symptoms were assessed with the depression module (PHQ-9) from the Patient Health Questionnaire. LS was assessed with a single item on a scale from 1 = bad to 5 = excellent. Differences in levels of depressive symptoms and LS in relation to gender and generation of migration were tested with analysis of covariance, controlling for age. Gender-stratified multiple linear regression analyses were also conducted for depressive symptoms as criterion variable. Results: 328 Turkish migrants participated (61.3% women). The cut-off-value of ≥10 for the PHQ-9 was achieved by 33.2% of the women and 26.4% of the men (p=0.209, φ=0.071). In female migrants, the age-adjusted mean score for depressive symptoms was 7.81 (SD=6.42), in males 6.70 (SD=6.41) (p=0.137, η2=0.007). After controlling for unemployment status, women showed a trend for being more frequently depressed than men (p=0.055, φ=0.117) and also demonstrated a trend for higher levels of depressive symptoms (p=0.072, η2=0.012). No significant gender-specific difference was found concerning age-adjusted mean score for LS (p=0.547, η2=0.001), also when controlled for unemployment status (p=0.322, η2=0.004). In both sexes, the second generation demonstrated a significantly higher age-adjusted mean score for LS of small/medium effect size than the first generation. In women, separation as acculturation style (linear regression coefficient (B=4.42, 95% CI=1.68, 7.17, p=0.002; reference: integration), having no partnership (B=2.56, 95% CI=0.26, 4.86, p=0.03) and lower education (B=-2.28, 95% CI=-4.54, -0.02, p=0.048) were associated with higher severity of depressive symptoms; in men, separation as acculturation style (B=4.01, 95% CI=0.70, 7.31, p=0.018; reference: integration) and employment status (B=-3.32, 95% CI=-5.71, -0.92, p=0.007) were related to depression levels. Conclusions: Separation as acculturation style is associated with higher levels of depressive symptoms (for both genders). Gender-sensitive health promotion programs should target separated migrants to improve their integration into the German society.
CRIS-Team Scopus Importer:2020-09-11
Keywords: depression; life satisfaction; mental health; migrants; Turkish

Associations between APOE-, COMT Val108/158Met- and BDNF Val66Met polymorphisms and variations in depressive and anxiety symptoms, sense of coherence and vital exhaustion in the real-life setting of mandatory basic military training - Alexopoulos, Panagiotis; Papanastasiou, Anastasios D.; Εconomou, Polychronis; Beis, Pavlos; Niforas, Michail; Dassios, Theodore G.; Kormpaki, Aggeliki; Zarkadis, Ioannis K.; Reichel, Martin; Kornhuber, Johannes; Perneczky, Robert; Gourzis, Philippos (Journal of Neural Transmission, 2021)
Apolipoprotein E (APOE) ε, catechol-O-methytranferase (COMT) Val108/158Met and brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphisms (SNPs) were shown to affect stress perception and response. The present study explored possible associations between these SNPs and changes in subclinical anxiety- and depressive symptoms, sense of coherence (SOC) and vital exhaustion (VE) during compulsory basic military training. The study encompassed 179 conscripts of a training base in Greece. The neuropsychiatric assessment was based on the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Antonovsky SOC scale and the Maastricht Questionnaire. It was conducted at three time points of the 19-day basic military training: on day one (baseline), day six (follow-up I) and day 13 (follow-up II). Statistical analyses included Mann–Whitney test, Chi-square test and cross-sectional time series regression models based on the Skillings–Mack statistic. APOE ε4 non-carriers encountered significant changes in anxiety- and depressive symptoms and SOC (in all cases P < 0.001) over the observation period, whilst ε4 carriers did not. The changes in anxiety, depressive symptoms and SOC attained statistical significance in both BDNF Met66 carriers (in all cases P < 0.001) and non-carriers (P = 0.036; < 0.001; < 0.001, respectively) as well as in COMT Met108/158 carriers (P = 0.004; < 0.001; < 0.001, respectively) and non-carriers (P = 0.02; 0.01; 0.021, respectively. Changes over time in VE were not significant (P > 0.05). The observed resistance of APOE ε4 carriers vs non-carriers to changes in anxiety- and depressive symptoms and SOC when exposed to a stressful environment may point to superior coping capacities of healthy young men carrying the ε4 allele.
CRIS-Team Scopus Importer:2021-01-15
Keywords: BDNFVal66Met; COMT Val108/158Met; Sense of coherence; Subclinical depressive and anxiety symptoms; Vital exhaustion

Associations of prenatal depressive symptoms with DNA methylation of HPA axis-related genes and diurnal cortisol profiles in primary school-aged children - Stonawski, Valeska; Frey, Stefan; Golub, Yulia; Rohleder, Nicolas; Kriebel, Jennifer; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Kratz, Oliver; Moll, Gunther; Heinrich, Hartmut; et al. (Development and Psychopathology, 2018)

Associations of prenatal depressive symptoms with DNA methylation of HPA axis-related genes and diurnal cortisol profiles in primary school-aged children - Stonawski, Valeska; Frey, Stefan; Golub, Yulia; Rohleder, Nicolas; Kriebel, Jennifer; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Kratz, Oliver; Heinrich, Hartmut; Moll, Gunther; et al. (Development and Psychopathology, 2019)
Epigenetic DNA modifications in genes related to the hypothalamic-pituitary-adrenal (HPA) axis are discussed as a mechanism underlying the association between prenatal depression and altered child HPA activity. In a longitudinal study, DNA methylation changes related to prenatal depressive symptoms were investigated in 167 children aged 6 to 9 years. At six candidate genes, 126 cytosine-guanine dinucleotides were considered without correcting for multiple testing due to the exploratory nature of the study. Further associations with the basal child HPA activity were examined. Children exposed to prenatal depressive symptoms exhibited lower bedtime cortisol (p = .003, ηp2 = 0.07) and a steeper diurnal slope (p = .023, ηp2 = 0.06). For total cortisol release, prenatal exposure was related to lower cortisol release in boys, and higher release in girls. Furthermore, prenatal depressive symptoms were associated with altered methylation in the glucocorticoid receptor gene (NR3C1), the mineralocorticoid receptor gene (NR3C2), and the serotonin receptor gene (SLC6A4), with some sex-specific effects (p = .012-.040, ηp2 = 0.03-0.04). In boys, prenatal depressive symptoms predicted bedtime cortisol mediated by NR3C2 methylation, indirect effect = -0.07, 95% confidence interval [-0.16, -0.02]. Results indicate relations of prenatal depressive symptoms to both child basal HPA activity and DNA methylation, partially fitting a mediation model, with exposed boys and girls being affected differently.
EVALuna2:36373

Associations of the Intellectual Disability Gene MYT1L with Helix-Loop-Helix Gene Expression, Hippocampus Volume and Hippocampus Activation During Memory Retrieval - Kepa, Agnieszka; Medina, Lourdes Martinez; Erk, Susanne; Srivastava, Deepak P.; Fernandes, Alinda; Toro, Roberto; Levi, Sabine; Ruggeri, Barbara; Fernandes, Cathy; Degenhardt, Franziska; Witt, Stephanie H.; Meyer-Lindenberg, Andreas; et al. (Neuropsychopharmacology, 2017)
The fundamental role of the brain-specific myelin transcription factor 1-like (MYT1L) gene in cases of intellectual disability and in the etiology of neurodevelopmental disorders is increasingly recognized. Yet, its function remains under-investigated. Here, we identify a network of helix-loop-helix (HLH) transcriptional regulators controlled by MYT1L, as indicated by our analyses in human neural stem cells and in the human brain. Using cell-based knockdown approaches and microarray analyses we found that (1) MYT1L is required for neuronal differentiation and identified ID1, a HLH inhibitor of premature neurogenesis, as a target. (2) Although MYT1L prevented expression of ID1, it induced expression of a large number of terminal differentiation genes. (3) Consistently, expression of MYT1L in the human brain coincided with neuronal maturation and inversely correlated with that of ID1 and ID3 throughout the lifespan. (4) Genetic polymorphisms that reduced expression of MYT1L in the hippocampus resulted in increased expression of ID1 and ID3, decreased levels of the proneural basic HLH (bHLH) transcriptional regulators TCF4 and NEUROD6 and decreased expression of genes involved in long-term potentiation and synaptic transmission, cancer and neurodegeneration. Furthermore, our neuroimaging analyses indicated that MYT1L expression associated with hippocampal volume and activation during episodic memory recall, as measured by blood-oxygen-level-dependent (BOLD) signals. Overall, our findings suggest that MYT1L influences memory-related processes by controlling a neuronal proliferation/differentiation switch of ID-bHLH factors.
EVALuna2:33378

A Stearoyl–Coenzyme A Desaturase Inhibitor Prevents Multiple Parkinson Disease Phenotypes in α-Synuclein Mice - Nuber, Silke; Nam, Alice Y.; Rajsombath, Molly M.; Cirka, Haley; Hronowski, Xiaoping; Wang, Junmin; Hodgetts, Kevin; Kalinichenko, Liubov; Müller, Christian P.; Lambrecht, Vera; Winkler, Jürgen; Weihofen, Andreas; et al. (Annals of neurology, 2020)
Objective: Parkinson disease (PD) has useful symptomatic treatments that do not slow the neurodegenerative process, and no significant disease-modifying treatments are approved. A key therapeutic target in PD is α-synuclein (αS), which is both genetically implicated and accumulates in Lewy bodies rich in vesicles and other lipid membranes. Reestablishing αS homeostasis is a central goal in PD. Based on previous lipidomic analyses, we conducted a mouse trial of a stearoyl–coenzyme A desaturase (SCD) inhibitor (“5b”) that prevented αS-positive vesicular inclusions and cytotoxicity in cultured human neurons. Methods: Oral dosing and brain activity of 5b were established in nontransgenic mice. 5b in drinking water was given to mice expressing wild-type human αS (WT) or an amplified familial PD αS mutation (E35K + E46K + E61K ["3K"]) beginning near the onset of nigral and cortical neurodegeneration and the robust PD-like motor syndrome in 3K. Motor phenotypes, brain cytopathology, and SCD-related lipid changes were quantified in 5b- versus placebo-treated mice. Outcomes were compared to effects of crossing 3K to SCD1−/− mice. Results: 5b treatment reduced αS hyperphosphorylation in E46K-expressing human neurons, in 3K neural cultures, and in both WT and 3K αS mice. 5b prevented subtle gait deficits in WT αS mice and the PD-like resting tremor and progressive motor decline of 3K αS mice. 5b also increased αS tetramers and reduced proteinase K-resistant lipid-rich aggregates. Similar benefits accrued from genetically deleting 1 SCD allele, providing target validation. Interpretation: Prolonged reduction of brain SCD activity prevented PD-like neuropathology in multiple PD models. Thus, an orally available SCD inhibitor potently ameliorates PD phenotypes, positioning this approach to treat human α-synucleinopathies. ANN NEUROL 2020.
CRIS-Team Scopus Importer:2020-10-30

Astrocytes and microglia but not neurons preferentially generate N-terminally truncated A? peptides - Oberstein, Timo; Spitzer, Philipp; Klafki, Hans-Wolfgang; Linning, Philipp; Neff, Florian; Knoelker, Hans-Joachim; Lewczuk, Piotr; Wiltfang, Jens; Kornhuber, Johannes; Maler, Juan Manuel (Neurobiology of Disease, 2015)
The neuropathological hallmarks of Alzheimer's disease include extracellular neuritic plaques and neurofibrillary tangles. The neuritic plaques contain ?-amyloid peptides (A? peptides) as the major proteinaceous constituent and are surrounded by activated microglia and astrocytes as well as dystrophic neurites. N-terminally truncated forms of A? peptides are highly prevalent in neuritic plaques, including A? 3-x beginning at Glu eventually modified to pyroglutamate (A? N3pE-x), A? 2-x, A? 4-x, and A? 5-x. The precise origin of the different N-terminally modified A? peptides currently remains unknown. To assess the contribution of specific cell types to the formation of different N-terminally truncated A? peptides, supernatants from serum-free primary cell cultures of chicken neurons, astrocytes, and microglia, as well as human astrocytes, were analyzed by A?-ELISA and one- and two-dimensional SDS-urea polyacrylamide gel electrophoresis followed by immunoblot analysis. To evaluate the contribution of ?- and ?-secretase to the generation of N-terminally modified A?, cultured astrocytes were treated with membrane-anchored "tripartite ?-secretase (BACE1) inhibitors" and the ?-secretase inhibitor DAPT. Neurons, astrocytes, and microglia each exhibited cell type-specific patterns of secreted A? peptides. Neurons predominantly secreted A? peptides that begin at Asp1, whereas those released from astrocytes and microglia included high proportions of N-terminally modified A? peptides, presumably including A? 2/3-x and 4/5-x. The inhibition of BACE1 reduced the amount of A? 1-x in cell culture supernatants but not the amount of A? 2-x.
EVALuna2:23718

A Taxonomy for Psycho-Oncological Intervention Techniques in an Acute Care Hospital in Germany - Madl, Martina; Lieb, Marietta; Schieber, Katharina; Hepp, Tobias; Erim, Yesim (Oncology Research and Treatment, 2021)
Background: Due to the establishment of a nationwide certification system for cancer centers in Germany, the availability of psycho-oncological services for cancer patients has increased substantially. However, little is known about the specific intervention techniques that are applied during sessions in an acute care hospital, since a standardized taxonomy is lacking. With this study, we aimed at the investigation of psycho-oncological intervention techniques and the development of a comprehensive and structured taxonomy thereof. Methods: In a stepwise procedure, a team of psycho-oncologists generated a data pool of interventions and definitions that were tested in clinical practice during a pilot phase. After an adaptation of intervention techniques, interrater reliability (IRR) was attained by rating 10 previously recorded psycho-oncological sessions. A classification of interventions into superordinate categories was performed, supported by cluster analysis. Results: Between April and June 2017, 980 psycho-oncological sessions took place. The experts agreed on a total number of 22 intervention techniques. An IRR of 89% for 2 independent psycho-oncological raters was reached. The 22 techniques were classified into 5 superordinate categories. Discussion/Conclusion: We developed a comprehensive and structured taxonomy of psycho-oncological intervention techniques in an acute care hospital that provides a standardized basis for systematic research and applied care. We expect our work to be continuously subjected to further development: future research should evaluate and expand our taxonomy to other contexts and care settings.
CRIS-Team WoS Importer:2021-07-30

A time-efficient screening tool for activities of daily living functions in Parkinson’s disease dementia - Sulzer, Patricia; Liebig, Luise; Csoti, Ilona; Grässel, Elmar; Wurster, Isabel; Berg, Daniela; Liepelt-Scarfone, Inga (Journal of Clinical and Experimental Neuropsychology, 2020)
Instruction: In Parkinson’s disease (PD), activities of daily living (ADL) impairments are crucial for diagnosis of dementia (PDD). Performance-based tests are promising tools to discriminate between different levels of cognitive impairment in PD; however, the value of those tests for diagnosis of PDD is only sparsely investigated. Therefore, we evaluated the Erlangen Test of Activities of Daily Living (E-ADL), a time-efficient performance-based ADL test, in PD. Method: In this cross-sectional study, 40 PD patients with normal cognition (PD-NC), 45 patients with mild cognitive impairment (PD-MCI) and 21 patients with PDD were assessed with a comprehensive ADL and cognitive test battery. Results: Interrater reliability (rs =.86) indicated high consistency of the standardized E-ADL scoring system between raters. The E-ADL correlated significantly with other tests of ADL functions (p <.01), highest with an alternative performance-based ADL test (rs = −.52), and lowest with self-ratings and a physician-rated scale. The E-ADL was also associated with cognitive impairment (p <.01), but also with motor impairment. A binary logistic regression model verified that the E-ADL (p =.04) was an independent predictor of PDD, in addition to motor impairment explaining 53.3% of variance. Receiver operating characteristic curve analysis of the E-ADL revealed an area under the curve of 0.78, a specificity of 77%, and a sensitivity of 67% for diagnosis PDD. Conclusions: The standardized, easy, and quick to administer E-ADL showed acceptable levels of reliability, and validity in PD and measures cognitive-driven ADL functions. Therefore, it might be a suitable test to support diagnosis of PDD in the clinical daily routine.
CRIS-Team Scopus Importer:2021-04-19
Keywords: activities of daily living; cognition; dementia; Parkinson’s disease; performance-based assessment

Ätiologie der Vergiftungen am Beispiel der Universitätskinderklinik in Istanbul - Oelschlegel, A.; Erim, Yesim; Zakaryan, K.; Asik, A.; Apak, S. (Der Kinderarzt, 1984)

A translational systems biology approach in both animals and humans identifies a functionally related module of accumbal genes involved in the regulation of reward processing and binge drinking in males - Stacey, David; Lourdusamy, Anbarasu; Ruggeri, Barbara; Maroteaux, Matthieu; Jia, Tianye; Cattrell, Anna; Nymberg, Charlotte; Banaschewski, Tobias; Bhattacharyya, Sohinee; Band, Hamid; Barker, Gareth; Bokde, Arun; et al. (Journal of Psychiatry & Neuroscience, 2016)
The mesolimbic dopamine system, composed primarily of dopaminergic neurons in the ventral tegmental area that project to striatal structures, is considered to be the key mediator of reinforcement-related mechanisms in the brain. Prompted by a genome-wide association meta-analysis implicating the Ras-specific guanine nucleotide-releasing factor 2 (RASGRF2) gene in the regulation of alcohol intake in men, we have recently shown that male Rasgrf2(-/-) mice exhibit reduced ethanol intake and preference accompanied by a perturbed mesolimbic dopamine system. We therefore propose that these mice represent a valid model to further elucidate the precise genes and mechanisms regulating mesolimbic dopamine functioning.Transcriptomic data from the nucleus accumbens (NAcc) of male Rasgrf2(-/-) mice and wild-type controls were analyzed by weighted gene coexpression network analysis (WGCNA). We performed follow-up genetic association tests in humans using a sample of male adolescents from the IMAGEN study characterized for binge drinking (n = 905) and ventral striatal activation during an fMRI reward task (n = 608).The WGCNA analyses using accumbal transcriptomic data revealed 37 distinct "modules," or functionally related groups of genes. Two of these modules were significantly associated with Rasgrf2 knockout status: M5 (p < 0.001) and M6 (p < 0.001). In follow-up translational analyses we found that human orthologues for the M5 module were significantly (p < 0.01) enriched with genetic association signals for binge drinking in male adolescents. Furthermore, the most significant locus, originating from the EH-domain containing 4 (EHD4) gene (p < 0.001), was also significantly associated with altered ventral striatal activity in male adolescents performing an fMRI reward task (pempirical < 0.001).It was not possible to determine the extent to which the M5 module was dysregulated in Rasgrf2(-/-) mice by perturbed mesolimbic dopamine signalling or by the loss of Rasgrf2 function in the NAcc.Taken together, our findings indicate that the accumbal M5 module, initially identified as being dysregulated in male Rasgrf2(-/-) mice, is also relevant for human alcohol-related phenotypes potentially through the modulation of reinforcement mechanisms in the NAcc. We therefore propose that the genes comprising this module represent important candidates for further elucidation within the context of alcohol-related phenotypes.
EVALuna2:23770

Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia - Teipel, Stefan; Raiser, Theresa; Riedl, Lina; Riederer, Isabelle; Schroeter, Matthias L.; Bisenius, Sandrine; Schneider, Anja; Kornhuber, Johannes; Fliessbach, Klaus; Spottke, Annilza; Grothe, Michel J.; Prudlo, Johannes; et al. (Cortex, 2016)
Primary progressive aphasia (PPA) is characterized by profound destruction of cortical language areas. Anatomical studies suggest an involvement of cholinergic basal forebrain (BF) in PPA syndromes, particularly in the area of the nucleus subputaminalis (NSP). Here we aimed to determine the pattern of atrophy and structural covariance as a proxy of structural connectivity of BF nuclei in PPA variants. We studied 62 prospectively recruited cases with the clinical diagnosis of PPA and 31 healthy older control participants from the cohort study of the German consortium for frontotemporal lobar degeneration (FTLD). We determined cortical and BF atrophy based on high-resolution magnetic resonance imaging (MRI) scans. Patterns of structural covariance of BF with cortical regions were determined using voxel-based partial least square analysis. We found significant atrophy of total BF and BF subregions in PPA patients compared with controls [F(1, 82) = 20.2, p < .001]. Atrophy was most pronounced in the NSP and the posterior BF, and most severe in the semantic variant and the nonfluent variant of PPA. Structural covariance analysis in healthy controls revealed associations of the BF nuclei, particularly the NSP, with left hemispheric predominant prefrontal, lateral temporal, and parietal cortical areas, including Broca's speech area (p < .001, permutation test). In contrast, the PPA patients showed preserved structural covariance of the BF nuclei mostly with right but not with left hemispheric cortical areas (p < .001, permutation test). Our findings agree with the neuroanatomically proposed involvement of the cholinergic BF, particularly the NSP, in PPA syndromes. We found a shift from a structural covariance of the BF with left hemispheric cortical areas in healthy aging towards right hemispheric cortical areas in PPA, possibly reflecting a consequence of the profound and early destruction of cortical language areas in PPA.
EVALuna2:23764

Atrophy in the Thalamus But Not Cerebellum Is Specific for FTD and ALS Patients - An Atlas-Based Volumetric MRI Study - Schoenecker, Sonja; Neuhofer, Christiane; Otto, Markus; Ludolph, Albert; Kassubek, Jan; Landwehrmeyer, Bernhard; Anderl-Straub, Sarah; Semler, Elisa; Diehl-Schmid, Janine; Prix, Catharina; Vollmar, Christian; Fortea, Juan; et al. (Frontiers in Aging Neuroscience, 2018)
The neuropathology of patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS) due to a mutation is characterized by two distinct types of characteristic protein depositions containing either TDP-43 or so-called dipeptide repeat proteins that extend beyond frontal and temporal regions. Thalamus and cerebellum seem to be preferentially affected by the dipeptide repeat pathology unique to mutation carriers. This study aimed to determine if mutation carriers showed an enhanced degree of thalamic and cerebellar atrophy compared to sporadic patients or healthy controls. Atlas-based volumetry was performed in 13 affected FTD, ALS and FTD/ALS patients, 45 sporadic FTD and FTD/ALS patients and 19 healthy controls. Volumes and laterality indices showing significant differences between mutation carriers and sporadic patients were subjected to binary logistic regression to determine the best predictor of mutation carrier status. Compared to sporadic patients, mutation carriers showed a significant volume reduction of the thalamus, which was most striking in the occipital, temporal and prefrontal subregion of the thalamus. Disease severity measured by mini mental status examination (MMSE) and FTD modified Clinical Dementia Rating Scale Sum of Boxes (FTD-CDR-SOB) significantly correlated with volume reduction in the aforementioned thalamic subregions. No significant atrophy of cerebellar regions could be detected. A logistic regression model using the volume of the prefrontal and the laterality index of the occipital subregion of the thalamus as predictor variables resulted in an area under the curve (AUC) of 0.88 while a model using overall thalamic volume still resulted in an AUC of 0.82. Our data show that thalamic atrophy in mutation carriers goes beyond the expected atrophy in the prefrontal and temporal subregion and is in good agreement with the cortical atrophy pattern described in mutation carriers, indicating a retrograde degeneration of functionally connected regions. Clinical relevance of the detected thalamic atrophy is illustrated by a correlation with disease severity. Furthermore, the findings suggest MRI volumetry of the thalamus to be of high predictive value in differentiating mutation carriers from patients with sporadic FTD.
EVALuna2:62169

Attempted suicide during an episode of lycanthropy - A case report and review of literature - Groh, Adrian; Heberlein, Annemarie; Thürauf, Norbert; Garlipp, Petra; Kornhuber, Johannes; Frieling, Helge; Bleich, Stefan; Hillemacher, Thomas (Psychiatry Research, 2020)
EVALuna2:211730

Attention, cognitive control and motivation in ADHD: Linking event-related brain potentials and DNA methylation patterns in boys at early school age - Heinrich, Hartmut; Grunitz, Juliane; Stonawski, Valeska; Frey, Silke; Wahl, Simone; Albrecht, Bjoern; Goecke, Tamme W.; Beckmann, Matthias; Kornhuber, Johannes; Fasching, Peter; Moll, Gunther; Eichler, Anna (Scientific Reports, 2017)
In order to better understand the underpinnings of attention-deficit/hyperactivity disorder (ADHD), we targeted the relationship of attentional, cognitive control and motivational processes with DNA methylation patterns of 60 candidate genes in boys at early school age. Participants (6 to 8 years; N = 82) were selected from a German longitudinal cohort (FRANCES). ADHD-related behaviour was assessed via maternal ratings. Performance and event-related potential measures (inter alia Cue-P3 and Nogo-P3), which were recorded in a motivational go/nogo task, indicated diminished attentional orienting, reduced inhibitory response control and a larger motivational effect on performance in ADHD already at this relatively young age. Methylation patterns were analysed in buccal cell DNA with the Illumina HumanMethylation 450K array. For CpG sites at genes of the dopaminergic (COMT, ANKK1) and the neurotrophic (BDNF, NGFR) system, associations with the Nogo-P3 as well as ADHD symptom severity were found suggesting that these systems are involved in response control deficits in ADHD. Methylation effects related to both functional aspects and ADHD behaviour were also observed for DPP10 and TPH2. Epigenetic mechanisms may play a role in ADHD-associated deficits but findings need to be replicated in larger samples and are limited by the fact that only peripheral methylation could be considered.
EVALuna2:33560

Attention towards food: Conflicting mechanisms in anorexia nervosa - Horndasch, Stefanie; Oschmann, Stephanie; Graap, Holmer; Heinrich, Hartmut; Moll, Gunther; Kratz, Oliver (Appetite, 2020)
In Anorexia nervosa (AN) attentional biases towards, as well as away from, food cues have been found using different paradigms. In the current study, adult and adolescent AN patients and control participants performed two tasks while their eye movements were recorded. The tasks involved viewing and rating: 1. Single photographs of food items; 2. Pairs of pictures consisting of one picture of high calorie and one of low calorie food. Girls and women suffering from AN rated pictures of high calorie food as more negative than control participants. In the task showing single food pictures, reduced fixation times within Regions of Interest of low calorie food were seen in AN; during the task using picture pairs, a visual attentional bias towards low calorie and away from high calorie stimuli for AN was demonstrated. There is evidence for heightened visual attentional capture by high calorie stimuli when presented alone as well as attraction of attention by low calorie stimuli when shown next to high calorie stimuli, possibly facilitated by avoidance of the latter. Different attentional mechanisms seem to be activated when only one stimulus is shown compared to when two stimuli are competing for the viewer's attention.
CRIS-Team Scopus Importer:2020-08-21
Keywords: Adolescents; Eating disorders; Eye-tracking

Attitudes toward persons with epilepsy as friends: Results of a factorial survey - Walther, Katrin; Kriwy, Peter; Stritzelberger, Jenny; Graf, Wolfgang; Gollwitzer, Stefanie; Lang, Johannes; Reindl, Caroline; Schwab, Stefan; Welte, Tamara; Hamer, Hajo (Epilepsia, 2023)
Objective: Discrimination against persons with epilepsy (PWEs) may persist. The aim of this study was to examine whether epilepsy is an obstacle to desired friendship.Methods: A factorial survey (vignettes), which is less biased by social desirability, was applied to PWEs, their relatives, and lay persons. The vignettes described a person who was varied by the dimensions of age (younger, same age, older), gender (male, female), disease (healthy, mild epilepsy, severe epilepsy [generalized toni-clonic seizures], diabetes), origin (German, non-German), contact (phone/internet, activities at home, activities outside), frequency of contacts (weekly, monthly), and distance (around the corner, 10 km away). Respondents rated their willingness to befriend the person on a 10-point Likert scale. Multivariate regression determined the contribution of each dimension on the judgment.Results: Participants were 64 PWEs (age = 37.1 +/- 14.0 years), 64 relatives of PWEs (age = 45.1 +/- 13.6 years), and 98 controls without contact with PWEs (age = 24.4 +/- 10.1 years). Controls were less interested in a friendship with a PWE with mild epilepsy (-3.4%) and even more avoided PWEs with severe epilepsy (-11.7%), whereas in PWEs with toni-clonic seizures, a mild form of epilepsy was actually conducive to friendship (+7.0%). Controls preferred females (+5.0%) and disliked younger people (-12.3%) and contacts via the internet or telephone (-7.3%). PWEs were also less interested in younger people (-5.8%), and relatives of PWEs had a lower preference for friendships with longer distance (-2.3%).Significance: PWEs still suffer from a risk of social avoidance, and this becomes more evident with generalized motor seizures.
CRIS-Team WoS Importer:2023-02-03

Audio-visual and olfactory-visual integration in healthy participants and subjects with autism spectrum disorder - Stickel, Susanne; Weismann, Pauline; Kellermann, Thilo; Regenbogen, Christina; Habel, Ute; Freiherr, Jessica; Chechko, Natalya (Human Brain Mapping, 2019)
The human capacity to integrate sensory signals has been investigated with respect to different sensory modalities. A common denominator of the neural network underlying the integration of sensory clues has yet to be identified. Additionally, brain imaging data from patients with autism spectrum disorder (ASD) do not cover disparities in neuronal sensory processing. In this fMRI study, we compared the underlying neural networks of both olfactory–visual and auditory–visual integration in patients with ASD and a group of matched healthy participants. The aim was to disentangle sensory-specific networks so as to derive a potential (amodal) common source of multisensory integration (MSI) and to investigate differences in brain networks with sensory processing in individuals with ASD. In both groups, similar neural networks were found to be involved in the olfactory–visual and auditory–visual integration processes, including the primary visual cortex, the inferior parietal sulcus (IPS), and the medial and inferior frontal cortices. Amygdala activation was observed specifically during olfactory–visual integration, with superior temporal activation having been seen during auditory–visual integration. A dynamic causal modeling analysis revealed a nonlinear top-down IPS modulation of the connection between the respective primary sensory regions in both experimental conditions and in both groups. Thus, we demonstrate that MSI has shared neural sources across olfactory–visual and audio–visual stimulation in patients and controls. The enhanced recruitment of the IPS to modulate changes between areas is relevant to sensory perception. Our results also indicate that, with respect to MSI processing, adults with ASD do not significantly differ from their healthy counterparts.
CRIS-Team Scopus Importer:2019-08-02
Keywords: auditory–visual integration; autism spectrum disorder; dynamic causal modeling; fMRI; multisensory integration; olfactory–visual integration

Audio-Visual Feedback System for Reward-Based Training Sessions of Elderly People in a Home Environment - Soutschek, Stefan; Maier, Andreas; Hönig, Florian Thomas; Spiegl, Werner; Steidl, Stefan; Hornegger, Joachim; Erzigkeit, Helmut; Kornhuber, Johannes (Proceedings of the 5th Russian-Bavarian Conference on Biomedical Engineering, 2009)

Ausrichtung innovativer Versorgungskonzepte für multimorbide Patienten - Grässel, Elmar; Hollederer, Alfons; Drexler, Hans; Kolominsky-Rabas, Peter (Public Health Forum, 2016)
Innovative care concepts for multimorbid patients should be oriented towards eliminating healthcare deficits. These are inappropriate care, different health care providers acting in isolation, failure to involve family caregivers in intervention planning, regional differences in healthcare and failure to take into account the specific care needs of people with dementia. An outline for an innovative healthcare concept is presented.
CRIS-Team Scopus Importer:2020-05-11
Keywords: care concept; dementia; healthcare provision; multimorbid patients; regional differences in healthcare

Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (Nature Genetics, (2019), 51, 3, (414-430), 10.1038/s41588-019-0358-2) - Kunkle, Brian W.; Grenier-Boley, Benjamin; Sims, Rebecca; Bis, Joshua C.; Damotte, Vincent; Naj, Adam C.; Boland, Anne; Vronskaya, Maria; van der Lee, Sven J.; Amlie-Wolf, Alexandre; Bellenguez, Céline; Frizatti, Aura; et al. (Nature Genetics, 2019)
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
CRIS-Team Scopus Importer:2019-08-27

Automated ASPECT scoring in acute ischemic stroke: comparison of three software tools - Hölter, Philip; Mühlen, Iris; Gölitz, Philipp; Beuscher, Vanessa; Schwab, Stefan; Dörfler, Arnd (Neuroradiology, 2020)
Purpose: Various software applications offer support in the diagnosis of acute ischemic stroke (AIS), yet it remains unclear whether the performance of these tools is comparable to each other. Our study aimed to evaluate three fully automated software applications for Alberta Stroke Program Early CT (ASPECT) scoring (Syngo.via Frontier ASPECT Score Prototype V2, Brainomix e-ASPECTS® and RAPID ASPECTS) in AIS patients. Methods: Retrospectively, 131 patients with large vessel occlusion (LVO) of the middle cerebral artery or the internal carotid artery, who underwent endovascular therapy (EVT), were included. Pre-interventional non-enhanced CT (NECT) datasets were assessed in random order using the automated ASPECT software and by three experienced neuroradiologists in consensus. Interclass correlation coefficient (ICC), Bland-Altman, and receiver operating characteristics (ROC) were applied for statistical analysis. Results: Median ASPECTS of the expert consensus reading was 8 (7–10). Highest correlation was between the expert read and Brainomix (r = 0.871 (0.818, 0.909), p < 0.001). Correlation between expert read and Frontier V2 (r = 0.801 (0.719, 0.859), p < 0.001) and between expert read and RAPID (r = 0.777 (0.568, 0.871), p < 0.001) was high, respectively. There was a high correlation among the software tools (Frontier V2 and Brainomix: r = 0.830 (0.760, 0.880), p < 0.001; Frontier V2 and RAPID: r = 0.847 (0.693, 0.913), p < 0.001; Brainomix and RAPID: r = 0.835 (0.512, 0.923), p < 0.001). An ROC curve analysis revealed comparable accuracy between the applications and expert consensus reading (Brainomix: AUC = 0.759 (0.670–0.848), p < 0.001; Frontier V2: AUC = 0.752 (0.660–0.843), p < 0.001; RAPID: AUC = 0.734 (0.634–0.831), p < 0.001). Conclusion: Overall, there is a convincing yet developable grade of agreement between current ASPECT software evaluation tools and expert evaluation with regard to ASPECT assessment in AIS.
CRIS-Team Scopus Importer:2020-05-15
Keywords: Acute ischemic stroke; Aspects; Diagnostics; Software anylsis

Automated Evaluation of Standardized Dementia Screening Tests - Braun, F.; Förstel, M.; Oppermann, B.; Erzigkeit, Andreas; Hillemacher, T.; Lehfeld, H.; Riedhammer, K. (Proceedings of the Annual Conference of the International Speech Communication Association, INTERSPEECH, 2022)
For dementia screening and monitoring, standardized tests play a key role in clinical routine since they aim at minimizing subjectivity by measuring performance on a variety of cognitive tasks. In this paper, we report a study consisting of a semi-standardized history taking followed by two standardized neuropsychological tests, namely the SKT and the CERAD-NB. The tests include basic tasks such as naming objects, learning word lists, but also widely used tools such as the MMSE. Most of the tasks are performed verbally and should thus be suitable for automated scoring based on transcripts. For the first batch of 30 patients, we analyze the correlation between expert manual evaluations and automatic evaluations based on manual and automatic transcriptions. For both SKT and CERAD-NB, we observe high to perfect correlations using manual transcripts; for certain tasks with lower correlation, the automatic scoring is stricter than the human reference since it is limited to the audio. Using automatic transcriptions, correlations drop as expected and are related to recognition accuracy; however, we still observe high correlations of up to 0.98 (SKT) and 0.85 (CERAD-NB). We show that using word alternatives helps to mitigate recognition errors and subsequently improves correlation with expert scores.
CRIS-Team Scopus Importer:2022-10-28
Keywords: dementia screening; neuropsychological tests

Automatic Classification of Reading Disorders in a Single Word Reading Test - Maier, Andreas; Horndasch, Stefanie; Nöth, Elmar (Workshop on Child, Computer, and Interaction 2009, 2009)

Autophagy modulates SNCA/?-synuclein release, thereby generating a hostile microenvironment - Pöhler, Anne-Maria; Xiang, Wei; Spitzer, Philipp; May, Verena Elisabeth Luise; Meixner, Holger; Rockenstein, Edward; Chutna, Oldriska; Outeiro, Tiago Fleming; Winkler, Jürgen; Masliah, Eliezer; Klucken, Jochen; Klucken, Jochen (Autophagy, 2014)
SNCA/?-synuclein aggregation plays a crucial role in synucleinopathies such as Parkinson disease and dementia with Lewy bodies. Aggregating and nonaggregating SNCA species are degraded by the autophagy-lysosomal pathway (ALP). Previously, we have shown that the ALP is not only responsible for SNCA degradation but is also involved in the intracellular aggregation process of SNCA. An additional role of extracellular SNCA in the pathology of synucleinopathies substantiating a prion-like propagation hypothesis has been suggested since released SNCA species and spreading of SNCA pathology throughout neural cells have been observed. However, the molecular interplay between intracellular pathways, SNCA aggregation, release, and response of the local microenvironment remains unknown. Here, we attributed SNCA-induced toxicity mainly to secreted species in a cell culture model of SNCA aggregation and in SNCA transgenic mice: We showed that ALP inhibition by bafilomycinA1 reduced intracellular SNCA aggregation but increased secretion of smaller oligomers that exacerbated microenvironmental response including uptake, inflammation, and cellular damage. Low-aggregated SNCA was predominantly released by exosomes and RAB11A-associated pathways whereas high-aggregated SNCA was secreted by membrane shedding. In summary, our study revealed a novel role of the ALP by linking protein degradation to nonclassical secretion for toxic SNCA species. Thus, impaired ALP in the diseased brain not only limits intracellular degradation of misfolded proteins, but also leads to a detrimental microenvironmental response due to enhanced SNCA secretion. These findings suggest that the major toxic role of SNCA is related to its extracellular species and further supports a protective role of intracellular SNCA aggregation.
EVALuna2:4698

A wearable real-time activity tracker - Jensen, Ulf; Leutheuser, Heike; Hofmann, Steffen; Schüpferling, Benno; Suttner, Gerald; Seiler, Kristin; Kornhuber, Johannes; Eskofier, Björn (Biomedical Engineering Letters, 2015)
Keywords: activity tracking; wearable computing; MET levels; accelerometers; mental health

Aβ1-16 controls synaptic vesicle pools at excitatory synapses via cholinergic modulation of synapsin phosphorylation - Anni, Daniela; Weiss, Eva-Maria; Guhathakurta, Debarpan; Akdas, Enes Yagiz; Klueva, Julia; Zeitler, Stefanie; Andres-Alonso, Maria; Huth, Tobias; Fejtová, Anna (Cellular and Molecular Life Sciences, 2021)
Amyloid beta (Aβ) is linked to the pathology of Alzheimer’s disease (AD). At physiological concentrations, Aβ was proposed to enhance neuroplasticity and memory formation by increasing the neurotransmitter release from presynapse. However, the exact mechanisms underlying this presynaptic effect as well as specific contribution of endogenously occurring Aβ isoforms remain unclear. Here, we demonstrate that Aβ1-42 and Aβ1-16, but not Aβ17-42, increased size of the recycling pool of synaptic vesicles (SV). This presynaptic effect was driven by enhancement of endogenous cholinergic signalling via α7 nicotinic acetylcholine receptors, which led to activation of calcineurin, dephosphorylation of synapsin 1 and consequently resulted in reorganization of functional pools of SV increasing their availability for sustained neurotransmission. Our results identify synapsin 1 as a molecular target of Aβ and reveal an effect of physiological concentrations of Aβ on cholinergic modulation of glutamatergic neurotransmission. These findings provide new mechanistic insights in cholinergic dysfunction observed in AD.
CRIS-Team Scopus Importer:2021-05-07
Keywords: Alpha7 nicotinic acetylcholine receptor; Amyloid beta; Synapsin 1; Synaptic vesicle dynamics

BACE1 modulates gating of KCNQ1 (Kv7.1) and cardiac delayed rectifier KCNQ1/KCNE1 (IKs) - Agsten, Marianne; Heßler, Sabine; Lehnert, Sandra; Volk, Tilmann; Rittger, Andrea; Hartmann, Stephanie; Raab, Christian; Kim, Doo Yeon; Groemer, Teja W.; Schwake, Michael; Alzheimer, Christian; Huth, Tobias (Journal of Molecular and Cellular Cardiology, 2015)
KCNQ1 (Kv7.1) proteins form a homotetrameric channel, which produces a voltage-dependent K(+) current. Co-assembly of KCNQ1 with the auxiliary ?-subunit KCNE1 strongly up-regulates this current. In cardiac myocytes, KCNQ1/E1 complexes are thought to give rise to the delayed rectifier current IKs, which contributes to cardiac action potential repolarization. We report here that the type I membrane protein BACE1 (?-site APP-cleaving enzyme 1), which is best known for its detrimental role in Alzheimer's disease, but is also, as reported here, present in cardiac myocytes, serves as a novel interaction partner of KCNQ1. Using HEK293T cells as heterologous expression system to study the electrophysiological effects of BACE1 and KCNE1 on KCNQ1 in different combinations, our main findings were the following: (1) BACE1 slowed the inactivation of KCNQ1 current producing an increased initial response to depolarizing voltage steps. (2) Activation kinetics of KCNQ1/E1 currents were significantly slowed in the presence of co-expressed BACE1. (3) BACE1 impaired reconstituted cardiac IKs when cardiac action potentials were used as voltage commands, but interestingly augmented the IKs of ATP-deprived cells, suggesting that the effect of BACE1 depends on the metabolic state of the cell. (4) The electrophysiological effects of BACE1 on KCNQ1 reported here were independent of its enzymatic activity, as they were preserved when the proteolytically inactive variant BACE1 D289N was co-transfected in lieu of BACE1 or when BACE1-expressing cells were treated with the BACE1-inhibiting compound C3. (5) Co-immunoprecipitation and fluorescence recovery after photobleaching (FRAP) supported our hypothesis that BACE1 modifies the biophysical properties of IKs by physically interacting with KCNQ1 in a ?-subunit-like fashion. Strongly underscoring the functional significance of this interaction, we detected BACE1 in human iPSC-derived cardiomyocytes and murine cardiac tissue and observed decreased IKs in atrial cardiomyocytes of BACE1-deficient mice.
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Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats - Yusoff, Nurul H. M.; Mansor, Sharif M.; Müller, Christian P.; Hassan, Zurina (Behavioural Brain Research, 2018)
Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABAB receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABAB receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABAB receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABAB receptor.
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Basic Human Body Dimensions Relate to Alcohol Dependence and Predict Hospital Readmission - Lenz, Bernd; Köllner, Martin; Mühle, Christiane; Weinland, Christian; Kornhuber, Johannes (Journal of Clinical Medicine, 2019)
Alcohol dependence is a severe mental illness and there is a need for more effective preventive and therapeutic strategies. Translational research suggests that intrauterine sex hormone exposure modulates the risk and course of alcohol dependence during adulthood. During development, sex hormones permanently shape sexually dimorphic body dimensions. Thus, these dimensions may provide insight into sex hormone organization. Here, we compared body measurements (absolute, relative to, and residualized on height) between 200 alcohol-dependent in-patients and 240 age-matched healthy control subjects and investigated how these measurements associate with the patients' prospective 12- and 24-month outcome. The results show that alcohol dependence is related to lower absolute, relative, and residualized body measurements for height and weight, head circumference, bitragion head arc, lip-chin distance, hip, thigh, and calf circumference, and foot length and breadth. In male alcohol-dependent in-patients, higher risk, shorter latency, and more alcohol-related readmissions were predicted by higher absolute, relative, and residualized thigh and calf circumferences. The second-to-fourth finger length ratio, a putative proxy for prenatal sex hormone organization, was not convincingly correlated with the body dimensions, suggesting that the results represent pubertal (or later) effects. The study's findings have implications for further research. The body measurements' high accessibility may facilitate the future transition into clinical settings.
CRIS-Team WoS Importer:2020-01-28

Basic presynaptic functions in hippocampal neurons are not affected by acute or chronic lithium treatment - Lüke, Katharina; Kaiser, Tobias; Svetlitchny, Alexei; Welzel, Oliver; Wenzel, Eva M.; Tyagarajan, Shiva; Kornhuber, Johannes; Groemer, Teja W. (Journal of Neural Transmission, 2014)
Lithium is an effective mood-stabilizer in the treatment of bipolar affective disorder. While glycogen synthase kinase 3-mediated and inositol depletion-dependent effects of lithium have been described extensively in literature, there is very little knowledge about the consequences of lithium treatment on vesicle recycling and neurotransmitter availability. In the present study we have examined acute and chronic effects of lithium on synaptic vesicle recycling using primary hippocampal neurons. We found that exocytosis of readily releasable pool vesicles as well as recycling pool vesicles was unaffected by acute and chronic treatment within the therapeutic range or at higher lithium concentrations. Consistent with this observation, we also noticed that the network activity and number of active synapses within the network were also not significantly altered after lithium treatment. Taken together, as lithium treatment does not affect synaptic vesicle release at even high concentrations, our data suggest that therapeutic effects of lithium in bipolar affective disorder are not directly related to presynaptic function.
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Bassoon controls synaptic vesicle release via regulation of presynaptic phosphorylation and cAMP - Montenegro-Venegas, Carolina; Guhathakurta, Debarpan; Pina-Fernandez, Eneko; Andres-Alonso, Maria; Plattner, Florian; Gundelfinger, Eckart D.; Fejtova, Anna (EMBO Reports, 2022)
Neuronal presynaptic terminals contain hundreds of neurotransmitter-filled synaptic vesicles (SVs). The morphologically uniform SVs differ in their release competence segregating into functional pools that differentially contribute to neurotransmission. The presynaptic scaffold bassoon is required for neurotransmission, but the underlying molecular mechanisms are unknown. We report that glutamatergic synapses lacking bassoon feature decreased SV release competence and increased resting pool of SVs as assessed by imaging of SV release in cultured neurons. CDK5/calcineurin and cAMP/PKA presynaptic signalling are dysregulated, resulting in an aberrant phosphorylation of their downstream effectors synapsin1 and SNAP25, well-known regulators of SV release competence. An acute pharmacological restoration of physiological CDK5 and cAMP/PKA activity fully normalises the SV pools in neurons lacking bassoon. Finally, we demonstrate that CDK5-dependent regulation of PDE4 activity interacts with cAMP/PKA signalling and thereby controls SV release competence. These data reveal that bassoon organises SV pools in glutamatergic synapses via regulation of presynaptic phosphorylation and cAMP homeostasis and indicate a role of CDK5/PDE4/cAMP axis in the control of neurotransmitter release.
CRIS-Team Scopus Importer:2022-07-08
Keywords: Bassoon; neuromodulation; neurotransmission; PDE4; synaptic vesicle recycling

Bassoon inhibits proteasome activity via interaction with PSMB4 - Montenegro-Venegas, Carolina; Fienko, Sandra; Anni, Daniela; Pina-Fernandez, Eneko; Frischknecht, Renato; Fejtova, Anna (Cellular and Molecular Life Sciences, 2020)
Abstract: Proteasomes are protein complexes that mediate controlled degradation of damaged or unneeded cellular proteins. In neurons, proteasome regulates synaptic function and its dysfunction has been linked to neurodegeneration and neuronal cell death. However, endogenous mechanisms controlling proteasomal activity are insufficiently understood. Here, we describe a novel interaction between presynaptic scaffolding protein bassoon and PSMB4, a β subunit of the 20S core proteasome. Expression of bassoon fragments that interact with PSMB4 in cell lines or in primary neurons attenuates all endopeptidase activities of cellular proteasome and induces accumulation of several classes of ubiquitinated and non-ubiquitinated substrates of the proteasome. Importantly, these effects are distinct from the previously reported impact of bassoon on ubiquitination and autophagy and might rely on a steric interference with the assembly of the 20S proteasome core. In line with a negative regulatory role of bassoon on endogenous proteasome we found increased proteasomal activity in the synaptic fractions prepared from brains of bassoon knock-out mice. Finally, increased activity of proteasome and lower expression levels of synaptic substrates of proteasome could be largely normalized upon expression of PSMB4-interacting fragments of bassoon is the name of the protein bassoon in neurons derived from bassoon deficient mice. Collectively, we propose that bassoon interacts directly with proteasome to control its activity at presynapse and thereby it contributes to a compartment-specific regulation of neuronal protein homeostasis. These findings provide a mechanistic explanation for the recently described link of bassoon is the name of the protein bassoon to human diseases associated with pathological protein aggregation. Graphic Abstract: Presynaptic cytomatrix protein bassoon (Bsn) interacts with PSMB4, the β7 subunit of 20S core proteasome, via three independent interaction interfaces. Bsn inhibits proteasomal proteolytic activity and degradation of different classes of proteasomal substrates presumably due to steric interference with the assembly of 20S core of proteasome. Upon Bsn deletion in neurons, presynaptic substrates of the proteasome are depleted, which can be reversed upon expression of PSMB4-interacting interfaces of Bsn. Taken together, bsn controls the degree of proteasome degradation within the presynaptic compartment and thus, contributes to the regulation of synaptic proteome[Figure not available: see fulltext.]
CRIS-Team Scopus Importer:2020-07-24
Keywords: Cytomatrix at the active zone; Protein degradation; Proteostasis; Synapse; Ubiquitin–proteasome system

Bassoon proteinopathy drives neurodegeneration in multiple sclerosis - Schattling, Benjamin; Engler, Jan Broder; Volkmann, Constantin; Rothammer, Nicola; Woo, Marcel S.; Petersen, Meike; Winkler, Iris; Kaufmann, Max; Rosenkranz, Sina C.; Fejtová, Anna; Thomas, Ulrich; Bose, Aparajita; et al. (Nature Neuroscience, 2019)
Multiple sclerosis (MS) is characterized by inflammatory insults that drive neuroaxonal injury. However, knowledge about neuron-intrinsic responses to inflammation is limited. By leveraging neuron-specific messenger RNA profiling, we found that neuroinflammation leads to induction and toxic accumulation of the synaptic protein bassoon (Bsn) in the neuronal somata of mice and patients with MS. Neuronal overexpression of Bsn in flies resulted in reduction of lifespan, while genetic disruption of Bsn protected mice from inflammation-induced neuroaxonal injury. Notably, pharmacological proteasome activation boosted the clearance of accumulated Bsn and enhanced neuronal survival. Our study demonstrates that neuroinflammation initiates toxic protein accumulation in neuronal somata and advocates proteasome activation as a potential remedy.
CRIS-Team Scopus Importer:2019-05-02

BDNF serum levels and promoter methylation of BDNF exon I, IV and VI in depressed patients receiving electroconvulsive therapy - Kleimann, Alexandra; Kotsiari, Alexandra; Sperling, Wolfgang; Groeschl, Michael; Heberlein, Annemarie; Kahl, Kai G.; Hillemacher, Thomas; Bleich, Stefan; Kornhuber, Johannes; Frieling, Helge (Journal of Neural Transmission, 2015)
We examined potential changes in brain-derived neurotrophic factor (BDNF) serum levels and promoter methylation of the BDNF gene in 11 patients with treatment-resistant major depressive disorder during a series of electroconvulsive therapy (ECT). Blood samples were taken before, 1 and 24 h after ECT treatment sessions 1, 4, 7 and 10. Patients remitting under ECT had significantly lower mean promoter methylation rates, especially concerning the exon I promoter, compared to non-remitters (both p < 0.002). These findings may point to a depression subtype in which ECT is particularly beneficial.
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Becoming a Teenager after Early Surgical Ventricular Septal Defect (VSD) Repair: Longitudinal Biopsychological Data on Mental Health and Maternal Involvement - Lang, Laura; Gerlach, Jennifer; Plank, Anne-Christine; Purbojo, Ariawan; Cesnjevar, Robert; Kratz, Oliver; Moll, Gunther; Eichler, Anna (Journal of Clinical Medicine, 2022)
Beside somatic strains of congenital heart diseases (CHD), affected children often show developmental impairments in the long term. Ventricular septal defect (VSD) is the most common congenital heart defect and early surgical repair is associated with positive somatic outcomes. However, psychological adjustment is of lifelong relevance. We investigated 24 children with a surgically-corrected isolated VSD and their mothers from primary school (6–9 years) to adolescence (10–14 years) and compared them to controls. Both times, mothers reported child internalizing/externalizing problems, mothers and children rated child quality of life, and children performed neurodevelopmental tests. Adolescents also rated internalizing/externalizing problems themselves, and their hair cortisol levels were analyzed. Maternal anxiety and proactive parenting behavior were considered as moderators. Results revealed no group differences in child neurodevelopment (language, cognition), externalizing problems, and cortisol levels at any time. In reports from mothers, internalizing problems (depression, anxiety) were elevated in children with a VSD at both times—when mothers reported anxiety symptoms themselves. In adolescent reports, VSD patients’ quality of life was increased and internalizing problems were decreased—proactive parenting behavior went along with decreased symptoms in VSD-affected adolescents and with increased symptoms in controls. The findings pronounce the crucial role of parenting behavior and the influence of maternal anxieties on child mental health after surgical VSD repair and might highlight the need for parent-centered interventions.
CRIS-Team Scopus Importer:2022-12-23
Keywords: adolescence; child development; congenital heart disease; cortisol; longitudinal study; mental health; psychological adjustment; quality of life; stress; ventricular septal defect

Behavioral Addictions in Psychosomatic Care - Woelfling, Klaus; Zeeck, Almut; Te Wildt, Bert; Resmark, Gaby; Morawa, Eva; Kersting, Anette; Von Wietersheim, Joern; Mueller, Astrid (Psychotherapie Psychosomatik Medizinische Psychologie, 2021)
Zusammenfassung
CRIS-Team WoS Importer:2021-12-03

Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models - Chestnykh, Daria; Graßl, Fabian; Pfeifer, Conrad; Dülk, Jonas; Ebner, Chiara; Walters, Mona; von Hörsten, Stephan; Kornhuber, Johannes; Kalinichenko, Liubov; Heinrich, Markus; Müller, Christian P. (Psychopharmacology, 2023)
Rationale: The dopamine D4 receptors (DRD4) play a key role in numerous brain functions and are involved in the pathogenesis of various psychiatric disorders. DRD4 ligands have been shown to moderate anxiety, reward and depression-like behaviours, and cognitive impairments. Despite a series of promising but ambiguous findings, the therapeutic advantages of DRD4 stimulation remain elusive. Objectives: The investigation focused on the behavioural effects of the recently developed DRD4 agonist, APH199, to evaluate its impact on anxiety, anhedonia, behavioural despair, establishment and retrieval of alcohol reinforcement, and amphetamine (AMPH)-induced symptoms. Methods: Male C57BL/6 J mice and Sprague–Dawley rats were examined in five independent experiments. We assessed APH199 (0.1–5 mg/kg, i.p.) effects on a broad range of behavioural parameters in the open field (OF) test, conditioned place preference test (CPP), elevated plus maze (EPM), light–dark box (LDB), novelty suppressed feeding (NSF), forced swim test (FST), sucrose preference test (SPT), AMPH-induced hyperlocomotion test (AIH), and prepulse inhibition (PPI) of the acoustic startle response in AMPH-sensitized rats. Results: APH199 caused mild and sporadic anxiolytic and antidepressant effects in EPM and FST, but no remarkable impact on behaviour in other tests in mice. However, we found a significant increase in AMPH-induced hyperactivity, suggesting an exaggeration of the psychotic-like responses in the AMPH-sensitized rats. Conclusions: Our data challenged the hypothesis of the therapeutic benefits of DRD4 agonists, pointing out a possible aggravation of psychosis. We suggest a need for further preclinical studies to ensure the safety of antipsychotics with DRD4 stimulating properties.
CRIS-Team Scopus Importer:2023-03-10
Keywords: Alcohol; Anxiety; APH199; Depression; DRD4 agonist; Psychosis; Schizophrenia

Bereitschaft zur COVID-19-Impfung unter Beschäftigten im Gesundheitswesen in Deutschland - Schug, Caterina; Erim, Yesim; Geiser, Franziska; Hiebel, Nina; Beschoner, Petra; Jerg-Bretzke, Lucia; Albus, Christian; Weidner, Kerstin; Steudte-Schmiedgen, Susann; Borho, Andrea; Lieb, Marietta; Morawa, Eva (Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz, 2021)
Background: The COVID-19 pandemic is a continuing burden on society and the health system. The vaccination willingness among healthcare workers is of particular interest, as these groups play a key role in the pandemic response. Objectives: The present study investigated how the willingness of healthcare workers in Germany to get vaccinated depends on sociodemographic, occupational, and COVID-19-specific characteristics, as well as mental health. Methods: Between November 2020 and January 2021, 6217 employees in the German healthcare system were questioned about their vaccination willingness, sociodemographic, occupational, COVID-19-specific, and psychosocial characteristics using the online VOICE survey within the framework of the University Medicine Network (NUM). Results: The vaccination willingness of the sample group was 65.3%. A higher vaccination willingness was associated with male gender; age > 40 years; having no children or no migration background; not working in direct patient care; belonging to a COVID-19 risk group or professional group of physicians and psychologists in comparison with nursing staff; feeling sufficiently informed about COVID-19 and protected by the measures of the national or local authorities and the employer; fear of infection; and lack of signs of depression. Physicians showed the highest willingness to get vaccinated. Conclusions: During the study period, an overall moderate vaccination willingness against COVID-19 in the health sector was described. Information about the disease and vaccination, especially for younger people, females, and non-physicians, adequate protective measures and prevention of depressive symptoms could increase the vaccination willingness.
CRIS-Team Scopus Importer:2021-10-08
Keywords: Acceptance; COVID-19-vaccination; Healthcare workers; Mental burden; Predictors

Beurteilung und Förderung der arbeitsbezogenen Selbstwirksamkeitserwartung in der Psychotherapie: Ergebnisse einer Sekundäranalyse einer randomisiert-kontrollierten Studie - Hansmann, Marieke; Angerer, Peter; Brenner, Lorena; Brezinski, Jolanda; Erim, Yesim; Feisst, Manuel; Hander, Nicole; Herold, Regina; Kilian, Reinhold; Köllner, Volker; Kohl, Fiona; Rothermund, Eva; et al. (Verhaltenstherapie, 2024)
Background: Occupational self-efficacy expectations (OSE) are considered a relevant predictor for successful return-to-work in employees with mental disorders. However, specific interventions to promote OSE do not exist. The present study investigated whether a newly developed cognitive-imaginative OSE-module is suitable for (1) generating imaginative coping experiences (ICE), (2) preparing real coping efforts (behavioural relevance; BR) and (3) addressing OSE. Methods: The OSE-module was conducted and videotaped during a short-term work-focused intervention (N = 22). Using videorecordings, independent raters assessed OSE and indicators for ICE and for BR. Self-assessments of OSE were made before treatment and at the time of the OSE-module. Results: All ICE-indicators (cooperation, vividness, emotional involvement, cognitive flexibility) were rather high. Means of BR-indicators showed that cognitive gains were moderate, intentions for behaviour change were rather high and identification of models was low. Observer-rated OSE was positively associated to self-rated OSE before treatment (r = 0.47, p = 0.025) and during OSE-module (r = 0.51, p = 0.014). Conclusion: The results imply that in the OSE-module (1) ICE were generated, (2) intentions for behaviour change were promoted and (3) self-efficacy relevant cognitions were activated. The OSE-module appears to be a suitable approach to cognitive-motivational priming of coping efforts. Future studies should investigate the effects of the OSE-module on real coping experiences and OSE change.
CRIS-Team Scopus Importer:2024-01-26
Keywords: Imagination; Observer rating; Occupational self-efficacy

Beyond Functional Impairment: Redefining Favorable Outcome in Patients with Subarachnoid Hemorrhage - Custal, Christina; Koehn, Julia; Borutta, Matthias; Mrochen, Anne; Brandner, Sebastian; Eyupoglu, Ilker Y.; Lücking, Hannes; Hölter, Philip; Kuramatsu, Joji; Kornhuber, Johannes; Schwab, Stefan; Huttner, Hagen; et al. (Cerebrovascular Diseases, 2021)
Background: For outcome assessment in patients surviving subarachnoid hemorrhage (SAH), the modified Rankin scale (mRS) represents the mostly established outcome tool, whereas other dimensions of outcome such as mood disorders and impairments in social life remain unattended so far. Objective: The aim of our study was to correlate 12-month functional and subjective health outcomes in SAH survivors. Methods: All SAH patients treated over a 5-year period received outcome assessment at 12 months, including functional scores (mRS and Barthel Index [BI]), subjective health measurement (EQ-5D), and whether they returned to work. Analyses - including utility-weighted mRS - were conducted to detect associations and correlations among different outcome measures, especially in patients achieving good functional outcome (i.e., mRS 0-2) at 12 months. Results: Of 351 SAH survivors, 287 (81.2%) achieved favorable functional outcome at 12 months. Contrary to the BI, the EQ-5D visual analog scale (VAS) showed a strong association with different mRS grades, accentuated in patients with favorable functional outcome. Despite favorable functional outcome, patients reported a high rate of impairments in activities (24.0%), pain (33.4%), and anxiety/depression (42.5%). Further, multivariable analysis revealed (i) impairments in activities (odds ratio [OR] [95% confidence interval CI]: 0.872 [0.817-0.930]), (ii) presence of depression or anxiety (OR [95% CI]: 0.836 [0.760-0.920]), and (iii) return to work (OR [95% CI]: 1.102 [0.1.013-1.198]) to be independently associated with self-reported subjective health. Conclusion: Established stroke scores mainly focusing on functional outcomes do poorly reflect the high rate of subjective impairments reported in SAH survivors, specifically in those achieving good functional outcome. Further studies are needed to investigate whether psychoeducational approaches aiming at improving coping mechanisms and perceived self-efficacy may result in higher subjective health in these patients.
CRIS-Team WoS Importer:2021-08-06

Biochemical markers of neurodegeneration in hereditary diffuse leucoencephalopathy with spheroids - Spitzer, Philipp; Kohl, Zacharias; Gölitz, Philipp; Coras, Roland; Blümcke, Ingmar; Brueck, Wolfgang; Dörfler, Arnd; Maihöfner, Christian (BMJ Case Reports, 2014)
Hereditary diffuse leucoencephalopathy with spheroids (HDLS) is a rare autosomal dominantly inherited disease with unknown pathophysiology. Diagnosis of neurodegenerative diseases is increasingly based on biomarkers. Although lumbar puncture is routinely performed during the diagnostic workup of HDLS, reports on alterations of neurodegeneration-specific biochemical markers have not been documented so far. We report a 35-year-old woman with clinical, radiological and neuropathological signs of HDLS. She suffered from a rapidly progressive frontal lobe syndrome. Brain MRI revealed diffuse leucoencephalopathy with predominant involvement of the periventricular white matter and corpus callosum. Although she was severely impaired and leucoencephalopathy was prominent, only cerebrospinal fluid total-? was moderately elevated. Other markers of neuronal (NSE) and astrocytic (S100B) damage were within normal range. Therefore, biochemical markers of central nervous system damage are not helpful in the diagnosis of HDL
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Bioimpedance Body Measures and Serum Lipid Levels in Masculine Depression - von Zimmermann, Claudia; Brückner, Lena; Mühle, Christiane; Weinland, Christian; Kornhuber, Johannes; Lenz, Bernd (Frontiers in Psychiatry, 2022)
Background: Major depressive disorder (MDD) is a main reason for suicide, and serum lipids are involved in both affective disorders and related suicidal behavior. Moreover, masculine depression has been suggested as a subtype of depression with an increased risk for suicide. Here, we studied the relationship between body measures, serum lipids, suicidal thoughts, and masculine depression. Methods: Depressed patients (44% women) were divided by a sex-separated median-split into a group of 81 “patients with masculine depression” (mean age ± standard error: 36.4 ± 1.6 years) and a group of 82 “patients with non-masculine depression” (age 45.7 ± 1.6 years) according to the Male Depression Risk Scale. We compared body measures, serum lipid levels, and past suicidal ideation between these groups and explored differences between these groups and 176 healthy controls (51% women; age 37.2 ± 1.0 years). Results: Patients with masculine depression did not significantly differ from patients with non-masculine depression in any of the body measures, lipid markers, or suicidal thoughts. Compared to healthy controls, both patient groups showed significantly higher body fat (B[masculine depression] = 0.041 and B[non–masculine depression] = 0.050), lower high-density lipoprotein (HDL) cholesterol (B = –0.045 and –0.044), and a higher risk for suicidal thoughts (B = 3.927 and 2.663) than healthy controls. Suicidal thoughts were significantly associated with lower low-density lipoprotein (LDL)/HDL ratios (B = –0.455) in patients with depression and with higher LDL cholesterol levels (B = 0.020) in healthy controls subjects. Limitation: Correlational study design and focus on in-patients. Conclusion: In the studied cohort, masculine depression was not significantly associated with the analyzed parameters of body measures, serum lipids, or suicidal thoughts in in-patients with depression.
CRIS-Team Scopus Importer:2022-08-12
Keywords: body fat; cholesterol; masculine depression; serum lipids; suicidal behavior

Biological Evidence for Paradoxical Improvement of Psychiatric Disorder Symptoms by Addictive Drugs - Müller, Christian P.; Kornhuber, Johannes (Trends in Pharmacological Sciences, 2017)
Addiction biology has focused on the mechanisms of the positive and negative reinforcing actions of addictive drugs but neglected potential benefits. Two new studies provide the first insights into a neurobiology of psychoactive drug instrumentalization. This may help us design better models for addiction neuroscience and opens a new dimension for the development of personalized pharmacotherapy of drug addiction.
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Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study - van Maurik, Ingrid S.; Vos, Stephanie J.; Bos, Isabelle; Bouwman, Femke H.; Teunissen, Charlotte E.; Scheltens, Philip; Barkhof, Frederik; Frolich, Lutz; Kornhuber, Johannes; Wiltfang, Jens; Maier, Wolfgang; Peters, Oliver; et al. (Lancet Neurology, 2019)
Background: Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia. Methods: In this modelling study, we included people with mild cognitive impairment (MCI) from single-centre and multicentre cohorts in Europe and North America: the European Medical Information Framework for Alzheimer's Disease (EMIF-AD; n=883), Alzheimer's Disease Neuroimaging Initiative (ADNI; n=829), Amsterdam Dementia Cohort (ADC; n=666), and the Swedish BioFINDER study (n=233). Inclusion criteria were a baseline diagnosis of MCI, at least 6 months of follow-up, and availability of a baseline Mini-Mental State Examination (MMSE) and MRI or CSF biomarker assessment. The primary endpoint was clinical progression to any type of dementia. We evaluated performance of previously developed risk prediction models—a demographics model, a hippocampal volume model, and a CSF biomarkers model—by evaluating them across cohorts, incorporating different biomarker measurement methods, and determining prognostic performance with Harrell's C statistic. We then updated the models by re-estimating parameters with and without centre-specific effects and evaluated model calibration by comparing observed and expected survival. Finally, we constructed a model combining markers for amyloid deposition, tauopathy, and neurodegeneration (ATN), in accordance with the National Institute on Aging and Alzheimer's Association research framework. Findings: We included all 2611 individuals with MCI in the four cohorts, 1007 (39%) of whom progressed to dementia. The validated demographics model (Harrell's C 0·62, 95% CI 0·59–0·65), validated hippocampal volume model (0·67, 0·62–0·72), and updated CSF biomarkers model (0·72, 0·68–0·74) had adequate prognostic performance across cohorts and were well calibrated. The newly constructed ATN model had the highest performance (0·74, 0·71–0·76). Interpretation: We generated risk models that are robust across cohorts, which adds to their potential clinical applicability. The models could aid clinicians in the interpretation of CSF biomarker and hippocampal volume results in individuals with MCI, and help research and clinical settings to prepare for a future of precision medicine in Alzheimer's disease. Future research should focus on the clinical utility of the models, particularly if their use affects participants' understanding, emotional wellbeing, and behaviour. Funding: ZonMW-Memorabel.
CRIS-Team Scopus Importer:2019-10-15

Biomarkers for dementia and other neurodegenerative diseases : Current developments - Wiltfang, J.; Lewczuk, Piotr; Otto, M. (Der Nervenarzt, 2016)
Cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) support the early and differential diagnosis of dementia, most importantly the diagnosis of early or preclinical Alzheimer's dementia (AD). Meanwhile CSF-NDD are now recommended for improved exclusion and positive diagnostics of AD by the German national neuropsychiatry S3 dementia guidelines ( www.DGPPN.de ). Meta-analyses of independent international multicenter studies have shown that a combined CSF analysis of amyloid-beta 1-42 (A? 1-42, decreased), total tau proteins (increased) and phospho-tau proteins (increased) offers a sensitivity and specificity of 80-90 % for the early and differential diagnosis of AD (AD versus all other). Generally, CSF-NDD should be combined with blood-based routine diagnostics and should be part of routine CSF diagnostics, e. g. cell count and cell differentiation (if applicable), intrathecal antibody synthesis and blood-CSF barrier analysis. The CSF-NDD are most valuable for the improved differentiation between reversible dementia syndromes and irreversible neurodegenerative dementia, e. g. cognitive deficits due to late onset depression (pseudodementia due to depression) or AD. Combined with extended psychometric neuropsychological evaluation and neuroimaging methods, such as magnetic resonance imaging (MRI), dopamine transporter scanning (DaTscan) by single photon emission computed tomography (SPECT), 18F-fluorodeoxyglucose positron emission tomography (glucose-PET) and amyloid-PET, CSF-NDD also significantly improve the differential diagnostics within the heterogeneous group of primary neurodegenerative dementias. Meanwhile, several independent studies have indicated that the A? 1-42:A? 1-40 ratio is superior to the determination of A? 1-42 alone. Currently, several international research initiatives have been launched to further harmonize and optimize preanalytical procedures and CSF-NDD biomarker assays.
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Biomarkers for the Diagnosis of Alzheimer's Disease in Clinical Practice: The Role of CSF Biomarkers during the Evolution of Diagnostic Criteria. - Dulewicz, Maciej; Kulczynska-Przybik, Agnieszka; Mroczko, Piotr; Kornhuber, Johannes; Lewczuk, Piotr; Mroczko, Barbara (International Journal of Molecular Sciences, 2022)
Alzheimer's disease (AD) is a progressive condition and the most common cause of dementia worldwide. The neuropathological changes characteristic of the disorder can be successfully detected before the development of full-blown AD. Early diagnosis of the disease constitutes a formidable challenge for clinicians. CSF biomarkers are the in vivo evidence of neuropathological changes developing in the brain of dementia patients. Therefore, measurement of their concentrations allows for improved accuracy of clinical diagnosis. Moreover, AD biomarkers may provide an indication of disease stage. Importantly, the CSF biomarkers of AD play a pivotal role in the new diagnostic criteria for the disease, and in the recent biological definition of AD by the National Institute on Aging, NIH and Alzheimer's Association. Due to the necessity of collecting CSF by lumbar puncture, the procedure seems to be an important issue not only from a medical, but also a legal, viewpoint. Furthermore, recent technological advances may contribute to the automation of AD biomarkers measurement and may result in the establishment of unified cut-off values and reference limits. Moreover, a group of international experts in the field of AD biomarkers have developed a consensus and guidelines on the interpretation of CSF biomarkers in the context of AD diagnosis. Thus, technological advancement and expert recommendations may contribute to a more widespread use of these diagnostic tests in clinical practice to support a diagnosis of mild cognitive impairment (MCI) or dementia due to AD. This review article presents up-to-date data regarding the usefulness of CSF biomarkers in routine clinical practice and in biomarkers research.
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Biomarkers of Alzheimer's disease and mild cognitive impairment: a current perspective - Lewczuk, Piotr; Mroczko, Barbara; Fagan, Anne; Kornhuber, Johannes (Advances in Medical Sciences, 2015)
A growing body of evidence supports the application of the neurochemical dementia diagnostics (NDD) biomarkers for the diagnosis of dementing conditions. Biomarkers of Alzheimer's disease (AD) were recently classified as these reflecting amyloid ? pathology (decreased CSF concentrations of A?42 and/or positive A? PET scan) and these reflecting neurodegeneration (increased CSF Tau concentrations, decreased uptake of FDG on FDG-PET, and cerebral atrophy on structural MRI). Particularly important seems the role of the biomarkers in the early diagnosis of AD, as the first pathophysiologic events observable in the CSF and amyloid ?-PET occur years and perhaps decades before the onset of the earliest clinical symptoms. Therefore, the NDD tools enable the diagnosis of AD already in the early preclinical stage. This review summarizes pathophysiology underlying the CSF biomarkers, following a discussion of their role in the current guidelines for the diagnostic procedures.
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BKPYV-SPECIFIC T CELLS REDUCE VIRAL LOAD IN A PRIMARY TUBULAR CELL MODEL - Wasielewski, E.; Lippler, Susanne; Knaup, Karl; Gary, Regina; Aigner, Michael; Kremer, Anna-Lena; Pfister, Felix; Amann, Kerstin Ute; Schiffer, Mario; Mackensen, Andreas; Wiesener, Michael (TRANSPLANT INTERNATIONAL, 2021)
CRIS-Team WoS Importer:2021-10-15

Blind - without noticing - Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2019)
CRIS-Team WoS Importer:2019-03-15

Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic - O'Bryant, Sid E.; Mielke, Michelle M.; Rissman, Robert A.; Lista, Simone; Vanderstichele, Hugo; Zetterberg, Henrik; Lewczuk, Piotr; Posner, Holly; Hall, James; Johnson, Leigh; Fong, Yiu-Lian; Luthman, Johan; et al. (Alzheimers & Dementia, 2017)
The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state of the art. In addition, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and toward clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional handoff model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases.
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Bloody olfaction? Confounding associations of sex and age on the influence of blood parameters and body weight on odor identification performance in healthy adults - Schicker, Doris; Karacan, Brid; Brandl, Beate; Skurk, Thomas; Volkert, Dorothee; Hauner, Hans; Freiherr, Jessica (Physiology & behavior, 2022)
Olfactory function and nutrition are closely related and may influence each other via metabolic parameters. However, the relationship between nutritional blood parameters and olfactory performance is still unclear. Inconclusive findings exist for specific blood parameters. In this extensive analysis, we examined the relationship between olfactory performance, measured with MONEX-40, as well as intensity and pleasantness ratings with 38 metabolic blood parameters, age, sex, and the anthropometric measurements body mass index (BMI) and body fat percentage (BFP). Therefore, we included data of 418 healthy, well-phenotyped Caucasians of the Enable cohort. We replicated age-dependent olfactory identification scores (p < 0.001) and found slight evidence for a body fat dependence measured with BFP (BF10 = 10.466). We further identified a sex difference only in middle-aged adults (p < 0.001) that could be explained by environmental factors. Several blood parameters correlated significantly with the MONEX-40 score (p < 0.05 – p < 0.001). However, these effects diminished after adjusting for sex and age (p > 0.9) that were identified as confounders. The same applies for BFP. In addition, no parameters were identified to correlate significantly with perceived olfactory intensity or pleasantness score if controlled for sex and age (p > 0.08). Our results suggest that metabolic blood parameters are not related to olfactory identification performance in a relevant manner and highlight the importance of controlling for sex and age in chemosensory research.
CRIS-Team Scopus Importer:2022-08-19
Keywords: Age; Blood parameter; Body weight; Nutrition; Olfaction; Sex

Body dysmorphic disorder: symptoms, models and treatment - Kollei, Ines; Martin, Alexandra; Erim, Yesim (Psychotherapie Psychosomatik Medizinische Psychologie, 2014)
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Body mass index and craving predict 24-month hospital readmissions of alcohol-dependent in-patients following withdrawal - Weinland, Christian; Mühle, Christiane; Kornhuber, Johannes; Lenz, Bernd (Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2019)
OBJECTIVE: Addictive alcohol drinking, craving, and overeating share common etiopathological mechanisms. We investigated whether body mass index (BMI) and craving predict outcome of alcohol-dependent in-patients. METHOD: The prospective study included 101 male and 72 female early-abstinent alcohol-dependent in-patients. Craving was quantified by Obsessive-Compulsive Drinking Scale (OCDS) scores. We documented alcohol-related readmissions over 24 months. RESULTS: In males, a higher BMI was associated with alcohol-related hospital readmission (median 26.1 vs. 23.1 kg/m2, P = .007) and correlated with more (ρ = 0.286, P = .004) and earlier readmissions (ρ = -0.256, P = .010). These associations were stronger in the subgroup of active smokers (n = 79; median 25.9 vs. 22.3 kg/m2, P = .005; ρ = 0.350, P = .002; ρ = -0.340, P = .002). BMI did not significantly predict outcome in females. Males with at least one readmission reported higher OCDS scores than those without (OCDS-total, OCDS-obsessive, OCDS-compulsive, P < .040), and the OCDS scores correlated with more readmissions (males: OCDS-total, OCDS-obsessive, OCDS-compulsive, ρ > 0.244, P < .014; females: OCDS-compulsive, ρ = 0.341, P = .003) and fewer days to first readmission (males: OCDS-total, OCDS-compulsive, ρ < -0.195, P < .050; females: OCDS-compulsive, ρ = -0.335, P = .004). The OCDS scores explained 9 to 19% of the relationship between BMI and outcome in males. CONCLUSION: BMI and craving are easily accessible outcome predictors of alcohol-related readmission following in-patient withdrawal treatment. They might be used to individualize relapse prevention in the future.
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Body mass index and serum levels of soluble leptin receptor are sex-specifically related to alcohol binge drinking behavior - Bouna-Pyrrou, Polyxeni; Mühle, Christiane; Kornhuber, Johannes; Weinland, Christian; Lenz, Bernd (Psychoneuroendocrinology, 2021)
Objective: Binge drinking is a highly prevalent behavior in adolescents and young adults and a risk factor to develop alcohol use disorder. Body mass index (BMI) and blood levels of leptin peptide and its soluble receptor have been implicated in alcohol use disorder; however, their role in binge drinking remains to be investigated. Method: We studied associations of BMI, serum levels of soluble leptin receptor (ObRe) and leptin as well as the free leptin index with binge drinking in 93 male and 99 female young adults. Results: In men, binge drinkers showed significantly higher BMI (kg/m2) than non-binge drinkers (23.67 vs. 22.08) and higher BMI correlated significantly with more severe binge drinking episodes (ρ = 0.251). In women, we found significantly higher ObRe (ng/ml) / BMI (kg/m2) values in binge drinkers than in non-binge drinkers (0.52 vs. 0.44) and ObRe/BMI values correlated significantly with more severe binge drinking episodes (ρ = 0.210). Conclusion: This study confirms that higher BMI associates with binge drinking in men and shows for the first time a role of ObRe/BMI in binge drinking in women. Our data emphasize the importance of further research in the ﬁeld of metabolic markers and implications in neurobiological processes of binge drinking.
CRIS-Team Scopus Importer:2021-04-09
Keywords: Alcohol binge drinking; Body mass index; Leptin; Soluble leptin receptor

Bouldering psychotherapy is effective in enhancing perceived self-efficacy in people with depression: results from a multicenter randomized controlled trial - Kratzer, André; Luttenberger, Katharina; Karg-Hefner, Nina; Weiss, Maren; Dorscht, Lisa (BMC Psychology, 2021)
Background: Recent studies have suggested that therapeutic climbing/bouldering may have positive effects on perceived self-efficacy. Nevertheless, there is still an urgent need for high-quality studies, as many existing studies have suffered from methodological problems. Therefore, the current work was aimed at investigating the effect of a manualized bouldering psychotherapy (BPT) on perceived self-efficacy in people with depression, compared with a home-based physical exercise program (EP) and state-of-the-art cognitive behavioral group therapy (CBT). Methods: In a prospective, multicenter, randomized controlled trial, 233 people with depression were randomly assigned to one group (BPT, EP, or CBT). Perceived self-efficacy was assessed at baseline (t0) and directly after the 10-week intervention period (t1) with the GSE. In addition, depression was assessed with the PHQ-9 and the MADRS. We computed t tests, analyses of variance (ANOVAs), confounder-adjusted hierarchical regression analyses, mediation analyses, and several sensitivity analyses. Results: BPT participants showed a significantly larger increase in perceived self-efficacy on the GSE compared with the EP (an increase of 3.04 vs. 1.26 points, p =.016, Cohen’s d = 0.39). In the confounder-adjusted hierarchical multiple regression analysis, group allocation (BPT vs. EP) was found to be the only significant predictor of the postintervention GSE score (β =.16, p =.014) besides the baseline GSE score (β =.69, p <.001). No differences were found between BPT and CBT participants regarding the effect on perceived self-efficacy. Only in the CBT group, the relationship between depression at baseline and postintervention was partially mediated (23%) by perceived self-efficacy. Conclusions: Participation in the manualized BPT in a group setting leads to a clinically relevant enhancement of perceived self-efficacy in people with depression. This effect is superior to that of physical exercise alone. The results provide also initial indications that BPT is comparable to CBT in enhancing perceived self-efficacy, suggesting a strong case for a broader use of BPT as a supplement to existing health services. Future studies should focus on the modes of action of BPT and its effect on perceived self-efficacy in people with other mental or physical disorders. Trial registration ISRCTN12457760, registered partly retrospectively, 26 July 2017.
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Keywords: Bouldering; Depression; Physical Exercise; Psychotherapy; Self Efficacy; Therapeutic climbing

Bouldering psychotherapy is more effective in the treatment of depression than physical exercise alone: Results of a multicentre randomised controlled intervention study - Karg, Nina; Dorscht, Lisa; Kornhuber, Johannes; Luttenberger, Katharina (BMC Psychiatry, 2020)
Background: Recent scientific studies have suggested that climbing/bouldering is effective in alleviating depression when the comparison group was a waitlist control group, even when physical activity and other therapeutic approaches were controlled for. In the present study, we aimed to investigate the effectiveness of a manualised psychotherapeutic bouldering intervention for depressed individuals, compared with an active control group performing physical exercise alone. Methods: In a multicentre randomised controlled intervention trial, 133 outpatients with depression were assigned to either a bouldering psychotherapy (BPT) group or a home-based supervised exercise programme (EP). Severity of depression as the primary outcome was assessed at baseline and directly after a ten-week intervention period using the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary outcomes included anxiety, coping skills, self-esteem, body image, and interpersonal sensitivity. We applied t-tests to test for differences within the groups (t0 vs. t1) and between the BPT and the EP and a multiple regression analysis with the post-intervention MADRS score as the dependent variable. The robustness of estimates was investigated with a sensitivity analyses. Results: Patients in the BPT group showed a significantly larger decrease in depression scores compared with the EP on the MADRS (drop of 8.4 vs. 3.0 points, p =.002, Cohen's d = 0.55). In the confounder-adjusted regression analyses, group allocation was found to be the only significant predictor of the post-intervention MADRS score ( =-5.60, p =.001) besides the baseline MADRS score. Further significant differences in change scores between the BPT and the EP were found for anxiety (p =.046, d = 0.35), body image (p =.018, d = 0.42), and global self-esteem (p =.011, d = 0.45). Conclusions: The study provides evidence that the manualised BPT is not only effective in alleviating depressive symptoms but even goes beyond the effect of mere physical exercise. Based on these findings, the BPT should be considered as a complementary therapeutic approach. Trial registration: Trial identification number: ISRCTN12457760: Study KuS (Klettern und Stimmung-Climbing and Mood) combined boulder and psychotherapy against depression, registered retrospectively on July 26th, 2017.
CRIS-Team Scopus Importer:2020-03-27
Keywords: Bouldering; Depression; Physical exercise; Psychotherapy

Bouldering psychotherapy is not inferior to cognitive behavioural therapy in the group treatment of depression: A randomized controlled trial - Luttenberger, Katharina; Berking, Matthias; Kind, Leona; Weiss, Maren; Kornhuber, Johannes; Dorscht, Lisa; Karg-Hefner, Nina (British Journal of Clinical Psychology, 2021)
Objectives: Bouldering has shown promising results in the treatment of various health problems. In previous research, bouldering psychotherapy (BPT) was shown to be superior to a waitlist control group and to physical exercise with regard to reducing symptoms of depression. The primary aim of this study was to compare group BPT with group cognitive behavioural psychotherapy (CBT) to test the hypothesis that BPT would be equally as effective as CBT. Design: We conducted a randomized, controlled, assessor-blinded non-inferiority trial in which 156 outpatients meeting the criteria of a depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) were randomly assigned to one of the two intervention groups (CBT: N = 77, BPT: N = 79). Methods: Intervention groups were manualized and treated for 10 weeks with a maximum of 11 participants and two therapists. The primary outcome was depressive symptom severity assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Patient Health questionnaire (PHQ-9) at the beginning and end of the treatment phase as well as one year after the end of treatment. Result: In both groups, depressive symptoms improved significantly by an average of one severity level, moving from moderate to mild depressive symptoms after therapy (MADRS difference scores: BPT −8.06, 95% CI [−10.85, −5.27], p <.001; CBT −5.99, 95% CI [−8.55, −3.44], p <.001). The non-inferiority of BPT in comparison with CBT was established on the basis of the lower bound of the 95% confidence interval falling above all of the predefined margins. BPT was found to be effective in both the short (d = 0.89) and long term (d = 1.15). Conclusion: Group BPT was found to be equally as effective as group CBT. Positive effects were maintained until at least 12 months after the end of therapy. Thus, BPT is a promising approach for broadening the therapeutic field of therapies for depression. Practitioner points: Physical activity is effective in the treatment of depression and current guidelines explicitly recommend it as a complementary method for the treatment of depression. Nevertheless, body-related interventions are still underrepresented in current treatments for depression. Bouldering psychotherapy (BPT) combines physical activity with psychotherapeutic content. Its concept relies on proven effective factors from CBT such as exposure training, problem solving and practicing new functional behaviours and is thus an enrichment and implementation of CBT methods on the bouldering wall. The positive effect of group bouldering psychotherapy (BPT) in reducing depressive symptoms in outpatients with depression is not inferior to the effect of group cognitive behavioural therapy (CBT). Additionally the 10-weeks BPT-programme significantly improved symptoms of anxiety and interpersonal sensitivity as well as health-related quality of life, coping, body image, self-efficacy, and global self-esteem.
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Keywords: bouldering; cognitive behavioural therapy; depression; exercise; Group; physical activity; psychotherapy; rock climbing; sports

Bouldering psychotherapy reduces depressive symptoms even when general physical activity is controlled for: A randomized controlled trial - Stelzer, Eva-Maria; Book, Stephanie; Grässel, Elmar; Hofner, Benjamin; Kornhuber, Johannes; Luttenberger, Katharina (Heliyon, 2018)
Background: Bouldering psychotherapy (BPT) combines psychotherapeutic elements with physical activity (PA). It might be effective for reducing symptoms of depression, but so far, no study has assessed individuals' levels of PA to control for whether positive effects on depression can also be found when adjusting for participants' levels of PA. This is important because PA itself has been proven effective in reducing depression and therefore might be an important variable to account for - especially in therapies using sport as one therapeutic mechanism. Methods: Using a waitlist control group design, outpatients with depression were assessed at baseline and after eight, 16, and 24 weeks. The intervention group took part in an eight-week bouldering psychotherapy which met once a week for three hours. Self-report measures before and after the intervention included the Symptom Checklist-90-R (SCL-90-R), the Beck Depression Inventory (BDI-II), and the questionnaire on resources and self-management skills (FERUS). PA was assessed during the first 16-week period via FitBit Zip accelerometers. Results: Altogether, 47 complete cases (20 men and 27 women) were included in the final analyses. Depression scores dropped by up to 6.74 (CI 2.80-10.67) points on the SCL-90-R depression scale and by up to 8.26 (CI 4.21-12.31) points on the BDI-II during the BPT intervention, the control group remained stable (SCL-90-R Cohen's d = 0.60; BDI-II: Cohen's d = .50). All Participants accrued an average of 6,515 steps per day, which is considered "low-active." Participants of the BPT intervention were significantly more likely to reduce their depressive symptoms (p = .025) than participants of the control group, even when PA was controlled for in a regression analysis. Limitations: Limitations of the study are the relatively small number of patients and the assessment of outcome scores via self-report. Conclusions: This study provides evidence that short-term BPT can be effective for reducing symptoms of depression even if controlled for other therapeutically active confounders including antidepressant medication, psychotherapy and general level of PA.
EVALuna2:211633

Brain-derived neurotrophic factor, Val66Met single nucleotide polymorphism is not associated with alcohol dependence - Muschler, Marc Andre Nicolas; Heberlein, Annemarie; Frieling, Helge; Vogel, Nicolas; Becker, Cord-Michael; Kornhuber, Johannes; Bleich, Stefan; Hillemacher, Thomas (Psychiatric Genetics, 2011)
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Brain membrane lipids in major depression and anxiety disorders - Müller, Christian P.; Reichel, Martin; Mühle, Christiane; Rhein, Cosima; Gulbins, Erich; Komhuber, Johannes (BBA - Biochimica et Biophysica Acta, 2015)
Major depression and anxiety disorders have high prevalence rates and are frequently comorbid. The neurobiological bases for these disorders are not fully understood, and available treatments are not always effective. Current models assume that dysfunctions in neuronal proteins and peptide activities are the primary causes of these disorders. Brain lipids determine the localization and function of proteins in the cell membrane and in doing so regulate synaptic throughput in neurons. Lipids may also leave the membrane as transmitters and relay signals from the membrane to intracellular compartments or to other cells. Here we review how membrane lipids, which play roles in the membrane's function as a barrier and a signaling medium for classical transmitter signaling, contribute to depression and anxiety disorders and how this role may provide targets for lipid-based treatment approaches. Preclinical findings have suggested a crucial role for the membrane-forming n-3 polyunsaturated fatty acids, glycerolipids, glycerophospholipids, and sphingolipids in the induction of depression- and anxiety-related behaviors. These polyunsaturated fatty acids also offer new treatment options such as targeted dietary supplementation or pharmacological interference with lipid-regulating enzymes. While clinical trials support this view, effective lipid-based therapies may need more individualized approaches. Altogether, accumulating evidence suggests a crucial role for membrane lipids in the pathogenesis of depression and anxiety disorders; these lipids could be exploited for improved prevention and treatment. This article is part of a Special Issue entitled Brain Lipids.
EVALuna2:23702

Brain region-dependent effects of neuropeptide y on conditioned social fear and anxiety-like behavior in male mice - Kornhuber, Johannes; Zoicas, Iulia (International Journal of Molecular Sciences, 2021)
Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We have previously shown that the intracerebroventricular administration of NPY reduces the expression of social fear in a mouse model of social fear conditioning (SFC). In the present study, we aimed to identify the brain regions that mediate these effects of NPY. We show that NPY (0.1 nmol/0.2 µL/side) reduces the expression of SFC-induced social fear in a brain-region-dependent manner. In more detail, NPY reduced the expression of social fear when administered into the dorsolateral septum (DLS) and central amygdala (CeA), but not when administered into the dorsal hippocampus (DH), medial amygdala (MeA) and basolateral amygdala (BLA). We also investigated whether the reduced expression of social fear might partly be due to a reduced anxiety-like behavior, and showed that NPY exerted anxiolytic-like effects when administered into the DH, DLS, CeA and BLA, but not when administered into the MeA. This study identifies the DLS and the CeA as brain regions mediating the effects of NPY on the expression of social fear and suggests that partly distinct neural circuitries mediate the effects of NPY on the expression of social fear and on anxiety-like behavior.
CRIS-Team Scopus Importer:2021-04-19
Keywords: Anxiety; Central amygdala; Conditioned fear; Dorsolateral septum; Elevated plus-maze; Fear expression; Neuropep-tide Y; SFC; Social fear

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group - Walton, Esther; Bernardoni, Fabio; Batury, Victoria Luise; Bahnsen, Klaas; Larivière, Sara; Abbate-Daga, Giovanni; Andres-Perpiña, Susana; Bang, Lasse; Bischoff-Grethe, Amanda; Brooks, Samantha J.; Campbell, Iain C.; Cascino, Giammarco; et al. (Biological Psychiatry, 2022)
Background: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. Methods: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). Results: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. Conclusions: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.
CRIS-Team Scopus Importer:2022-09-09
Keywords: BMI; Cortical thickness; MRI; Subcortical volume; Surface area

Brief telephone counselling is effective for caregivers who do not experience any major life events - Caregiver-related outcomes of the German day-care study - Behrndt, Elisa-Marie; Straubmeier, Melanie; Seidl, Hildegard; Vetter, Chiara; Luttenberger, Katharina; Grässel, Elmar (BMC Health Services Research, 2019)
Background: To date, there has been a dearth of scientifically tested, established intervention concepts focussed on supporting informal caregivers and embedded in routine health care structures. The aim of this study was to assess effects of a brief telephone intervention for caregivers of persons with cognitive impairment (PCIs) on caregivers' depressiveness and subjective burden. Methods: A two-arm cluster-randomised controlled intervention study was carried out at 32 German day-care centres. During the six-month intervention period, informal caregivers in the intervention group (n = 205) received counselling in three phone calls focussed on stress reduction, development of self-management strategies, and how to deal with challenging behaviours. Both the control group (n = 154) and the intervention group were free to take part in any support programmes offered by the German Health Care System (TAU). Caregivers' subjective burden and depressiveness were measured with the Burden Scale for Family Caregivers - short version (BSFC-s) and the WHO-5 Well-Being Index (WHO-5). Outcomes were assessed by means of computer-assisted telephone interviews (CATIs) at baseline and at the end of the six-month intervention phase. Multiple regression analyses were used to show the influence of group allocation. Results: After the intervention phase, group allocation was not found to significantly predict caregivers' subjective burden or depressiveness. The baseline scores (p < 0.001) were the only significant predictors of change in both outcomes. However, sensitivity analyses for caregivers who did not experience any events that they felt were major (in a negative or positive sense) during the six months (n = 271) showed that group allocation (p < 0.05) was a significant predictor of positive change in both outcomes (BSFC-s: Δ-1.3, [- 2.4, - 0.3], Cohen's d = 0.27; WHO-5: Δ1.5, [0.4, 2.7], Cohen's d = 0.26). Effect sizes were highest in the subgroup of caregivers of people with mild dementia (BSFC-s: Cohen's d = 0.43; WHO-5: Cohen's d = 0.42). Conclusions: A "low-dose" psychoeducative telephone intervention designed to empower caregivers is effective, especially in an early stage, if the overlap between the effect of the intervention and the effect of events that are experienced as major events in the caregiver's life is considered. Trial registration: Identifier: ISRCTN16412551 (Registration date: 30 July 2014, registered retrospectively).
CRIS-Team Scopus Importer:2019-05-09
Keywords: Day-care; Dementia; MCI; Informal caregivers; Telephone intervention

Bupropion for the Treatment of Apathy in Alzheimer Disease: A Randomized Clinical Trial - Maier, Franziska; Spottke, Annika; Bach, Jan Philipp; Bartels, Claudia; Buerger, Katharina; Dodel, Richard; Fellgiebel, Andreas; Fliessbach, Klaus; Frölich, Lutz; Hausner, Lucrezia; Hellmich, Martin; Klöppel, Stefan; et al. (JAMA Network Open, 2020)
Importance: Apathy is a frequent neuropsychiatric symptom in dementia of Alzheimer type and negatively affects the disease course and patients' and caregivers' quality of life. Effective treatment options are needed. Objective: To examine the efficacy and safety of the dopamine and noradrenaline reuptake inhibitor bupropion in the treatment of apathy in patients with dementia of Alzheimer type. Design, Setting, and Participants: This 12-week, multicenter, double-blind, placebo-controlled, randomized clinical trial was conducted in a psychiatric and neurological outpatient setting between July 2010 and July 2014 in Germany. Patients with mild-to-moderate dementia of Alzheimer type and clinically relevant apathy were included. Patients with additional clinically relevant depressed mood were excluded. Data analyses were performed between August 2018 and August 2019. Interventions: Patients received either bupropion or placebo (150 mg for 4 weeks plus 300 mg for 8 weeks). In case of intolerability of 300 mg, patients continued to receive 150 mg throughout the study. Main Outcomes and Measures: Change on the Apathy Evaluation Scale-Clinician Version (AES-C) (score range, 18-72 points) between baseline and week 12 was the primary outcome parameter. Secondary outcome parameters included measures of neuropsychiatric symptoms, cognition, activities of daily living, and quality of life. Outcome measures were assessed at baseline and at 4, 8, and 12 weeks. Results: A total of 108 patients (mean [SD] age, 74.8 [5.9] years; 67 men [62%]) were included in the intention-to-treat analysis, with 54 randomized to receive bupropion and 54 randomized to receive placebo. The baseline AES-C score was comparable between the bupropion group and the placebo group (mean [SD], 52.2 [8.7] vs 50.4 [8.2]). After controlling for the baseline AES-C score, site, and comedication with donepezil or galantamine, the mean change in the AES-C score between the bupropion and placebo groups was not statistically significant (mean change, 2.22; 95% CI, -0.47 to 4.91; P = .11). Results on secondary outcomes showed statistically significant differences between bupropion and placebo in terms of total neuropsychiatric symptoms (mean change, 5.52; 95% CI, 2.00 to 9.04; P = .003) and health-related quality of life (uncorrected for multiple comparisons; mean change, -1.66; 95% CI, -3.01 to -0.31; P = .02) with greater improvement in the placebo group. No statistically significant changes between groups were found for activities of daily living (mean change, -2.92; 95% CI, -5.89 to 0.06; P = .05) and cognition (mean change, -0.27; 95% CI, -3.26 to 2.73; P = .86). The numbers of adverse events (bupropion group, 39 patients [72.2%]; placebo group, 33 patients [61.1%]) and serious adverse events (bupropion group, 5 patients [9.3%]; placebo group, 2 patients [3.7%]) were comparable between groups. Conclusions and Relevance: Although it is safe, bupropion was not superior to placebo for the treatment of apathy in patients with dementia of Alzheimer type in the absence of clinically relevant depressed mood. Trial Registration: EU Clinical Trials Register Identifier: 2007-005352-17.
CRIS-Team Scopus Importer:2020-06-09

CAGn repeat of the androgen receptor is linked to proopiomelanocortin promoter methylation-relevance for craving of male alcohol-dependent patients? - Muschler, Marc Andre Nicolas; Lenz, Bernd; Hillemacher, Thomas; Kraus, Cornelia; Kornhuber, Johannes; Frieling, Helge; Bleich, Stefan (Psychopharmacology, 2014)
Previous findings of the Franconian Alcoholism Research Studies showed that both the CAGn of the androgen receptor (AR) and the promoter methylation of the hypothalamic peptide proopiomelanocortin (POMC) were associated with craving of male alcohol-dependent patients.Based on the strong interactions between the hypothalamic-pituitary-gonadal (HPG) and the hypothalamic-pituitary-adrenal axis (HPA), this study investigated the relationships between the CAGn repeat of the AR, POMC promoter methylation and craving of male alcohol-dependent patients.This analysis covers 84 male patients with a diagnosis of alcohol dependence (DSM-IV). We sequenced the POMC gene promoter using bisulfite modified DNA to display the methylation status. Furthermore, we sequenced the CAGn repeat within exon 1 of the AR gene. Craving was quantified by the Obsessive Compulsive Drinking Scale.We found an inverse correlation between the number of CAGn repeats of the AR and the POMC methylation status in this study. Altogether, the POMC promoter methylation accounted for 33 % of the relationship between CAGn AR polymorphism and craving.This work shows that the AR and the POMC gene might functionally interact with each other and subsequently mediate craving in alcohol-dependent patients. The paper discusses different mechanisms which might underlie our findings involving sex hormones' and sex determining region of Y-gene's regulatory function on DNA-methyltransferase activity. In conclusion, the results give insight in the interaction between HPG and HPA axis. This study is a further step on the way to a better understanding of genetic and non-genetic factors underlying craving for alcohol.
EVALuna2:9197

?CaMKII autophosphorylation mediates neuronal activation in the hippocampal dentate gyrus after alcohol and cocaine in mice - Schöpf, Isabella; Easton, Alanna C.; Solati, Jalal; Golub, Yulia; Kornhuber, Johannes; Giese, K. Peter; Müller, Christiane (Neuroscience Letters, 2015)
Psychoactive drug-induced cellular activation is a key mechanism to promote neuronal plasticity and addiction. Alpha Ca(2+)/calmodulin-dependent protein kinase II (?CaMKII) and its autophosphorylation play a key role in the development of drug use associated behaviours. It has been suggested that ?CaMKII autophosphorylation is necessary for drug-induced neuronal activation in the mesolimbic system. Here, we show an alcohol- and cocaine-induced increase in c-fos expression in the hippocampal dentate gyrus, which is absent in ?CaMKII(T286A) autophosphorylation deficient mice. These findings may suggest a role in hippocampal ?CaMKII autophosphorylation in the acute neuroplastic effects of alcohol and cocaine.
EVALuna2:23636

?CaMKII controls the establishment of cocaine's reinforcing effects in mice and humans - Easton, A. C.; Lourdusamy, Anbarasu; Havranek, M.; Mizuno, K.; Solati, Jalal; Golub, Yulia; Clarke, T-K; Vallada, Homero; Laranjeira, R.; Desrivieres, Sylvane; Moll, Gunther; Moessner, R.; et al. (Translational Psychiatry, 2014)
Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca(2+)/calmodulin-dependent protein kinase-II (?CaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. The autophosphorylation of ?CaMKII was shown to accelerate learning. Thus, we investigated the role of ?CaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that ?CaMKII autophosphorylation-deficient ?CaMKII(T286A) mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg(-1), intraperitoneal). In vivo microdialysis revealed that ?CaMKII(T286A) mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg(-1), intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in ?CaMKII(T286A) mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n=688) and Switzerland (n=141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that ?CaMKII controls the speed for the establishment of cocaine's reinforcing effects.
EVALuna2:23639

CaMKII is activated in opioid induced conditioned place preference, but αCaMKII Thr286 autophosphorylation is not necessary for its establishment - Andersen, Jannike M.; Opdal, Siri H.; Müller, Christian P.; Boix, Fernando (Behavioural Brain Research, 2020)
Activation of calcium/calmodulin-dependent protein kinase II (CaMKII), particularly its α isoform, is known to be important for neuronal processes central for learning and memory and has also been implicated in the maladaptive learning involved in drug addiction.Thr286 autophosphorylation of αCaMKII has been shown to be indispensable for establishment of cocaine-induced CPP (Easton et al., 2014). To study the contribution of CaMKII in opioid induced conditioned learning, we examined how establishment of conditioned place preference (CPP) induced by 10 or 30 μmol/kg morphine or its active metabolite morphine-6-glucuronide (M6G) affects the levels and Thr286 autophosphorylation of the α- and β-isoforms of CaMKII, as well as β-actin levels, in dorsal and ventral striatum and in hippocampus of mice. An acute and a sub-chronic treatment were used as controls. Whereas an acute single administration of morphine or M6G caused increases in CaMKII levels and phosphorylation at Thr286 and β-actin in striatal areas, CPP induced by these opioids was accompanied primarily by an increase in the protein levels of both CaMKII isoforms and β-actin in dorsal striatum and hippocampus. Decreases in CaMKII Thr286 phosphorylation were observed in dorsal striatum after the sub-chronic pharmacological treatment. Despite the changes observed in αCaMKII activity in wild type mice, morphine-induced CPP was not affected in αCaMKIIT286A autophosphorylation-deficient mice. These results indicate that opioid-induced CPP is accompanied by activation of α- and βCaMKII in striatum and hippocampus, but, in opposition to what has been observed with cocaine, αCaMKII autophosphorylation is not essential for establishment of opioid-induced CPP.
CRIS-Team Scopus Importer:2020-06-02
Keywords: CaMKII; Conditioned place preference; Morphine; Morphine-6-glucuronide; Opioids; Synaptic plasticity

CaM Kinases: From Memories to Addiction - Müller, Christian P.; Quednow, Boris B.; Lourdusamy, Anbarasu; Kornhuber, Johannes; Schumann, Gunter; Giese, Peter (Trends in Pharmacological Sciences, 2016)
Drug addiction is a major psychiatric disorder with a neurobiological basis that is still insufficiently understood. Initially, non-addicted, controlled drug consumption and drug instrumentalization are established. They comprise highly systematic behaviours acquired by learning and the establishment of drug memories. Ca(2+)/calmodulin-dependent protein kinases (CaMKs) are important Ca(2+) sensors translating glutamatergic activation into synaptic plasticity during learning and memory formation. Here we review the role of CaMKs in the establishment of drug-related behaviours in animal models and in humans. Converging evidence now shows that CaMKs are a crucial mechanism of how addictive drugs induce synaptic plasticity and establish various types of drug memories. Thereby, CaMKs are not only molecular relays for glutamatergic activity but they also directly control dopaminergic and serotonergic activity in the mesolimbic reward system. They can now be considered as major molecular pathways translating normal memory formation into establishment of drug memories and possibly transition to drug addiction.
EVALuna2:23777

Can brief telephone interventions reduce caregiver burden and depression in caregivers of people with cognitive impairment? - Long-term results of the German day-care study (RCT) - Donath, Carolin; Luttenberger, Katharina; Grässel, Elmar; Scheel, Jennifer Felicia; Pendergrass, Anna; Behrndt, Elisa-Marie (BMC Geriatrics, 2019)
Background: Day-care and telephone counseling have been discussed as effective support measures for caregivers of people with cognitive impairment. Methods: In a two-arm cluster-randomized trial involving multicomponent therapy for cognitively impaired persons in day-care centers and telephone counseling for their caregivers versus treatment as usual (TAU), we investigated long-term effects on caregivers' burden and depressiveness. Person-caregiver dyads involving home-dwelling persons with MCI, mild dementia, or moderate dementia were eligible. Day-care centers were randomized into an intervention group (IG) or a control group (CG). Outcome assessors were blinded. Out of 359 caregivers who had completed a 6-month intervention phase (nIG = 205, nCG = 154), a total of 304 of them were available at the 12-month follow-up (nIG = 173, nCG = 131). Instruments for assessing were the Burden Scale for Family Caregivers - short version (BSFC-s) (caregiver burden) and the Well-Being Index Score (WHO-5) (depressiveness). Mixed ANOVAs were used for the main analyses; descriptive statistics and subgroup analyses were additionally performed; secondary analyses involved multiple linear regressions for the main outcomes that were significant in the unadjusted main analysis. Results: At follow-up, crude mean differences showed a nonsignificant advantage for the IG in caregiver burden [IG: -.20 (SD = 5.39) vs. CG:.76 (SD = 5.49), p =.126, d =.177] and depressiveness (reverse scored) [IG: -.05 (SD = 5.17) vs. CG: -.98 (SD = 5.65), p =.136, d =.173]. For caregiver burden, a mixed ANOVA resulted in significant main effects of group (F (1, 302) = 4.40; p =.037) and time (F (1.88, 568.96) = 3.56; p =.032) but not a significant interaction. The largest effects were found for the "mild dementia" subgroup (d =.443 for caregiver burden and d =.520 for depressiveness). Discussion: Positive long-term effects of a combined intervention involving telephone counseling for caregivers and multicomponent activation for patients were observed especially for mild dementia. However, the treatment effects washed out after the intervention ended. Trial registration: ISRCTN16412551 (date: 30 July 2014, retrospectively).
CRIS-Team Scopus Importer:2019-08-06
Keywords: Day-care; Dementia; MCI; Informal caregivers; Telephone intervention

Can flat-detector CT after successful endovascular treatment predict long-term outcome in patients with large vessel occlusion? An Alberta Stroke Programme Early CT Score–based study - Knott, Michael; Hölter, Philip; Hock, Stefan; Mühlen, Iris; Gerner, Stefan; Sprügel, Maximilian; Huttner, Hagen; Schwab, Stefan; Engelhorn, Tobias; Dörfler, Arnd (Neurological Sciences, 2022)
Purpose: Recent studies postulate a high prognostic value of the Alberta Stroke Programme Early CT Score (ASPECTS) applied on non-contrast whole-brain flat-detector CT (FDCT) after successful endovascular treatment (EVT). The aim of this study was the evaluation of long-term patient outcome after endovascular treatment using postinterventional FDCT. Methods: Using a local database (Stroke Research Consortium in Northern Bavaria, STAMINA), 517 patients with successful endovascular treatment (modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2B) due to acute ischaemic stroke (AIS) and large vessel occlusion (LVO) of the anterior circulation were recruited retrospectively. In all cases, non-contrast FDCT after EVT was analysed with special focus at ASPECTS. These results were correlated with the functional outcome in long-term (modified Rankin Scale (mRS) shift from pre-stroke to 90 days after discharge). Results: A significant difference in FDCT-ASPECTS compared to the subgroup of favourable vs. unfavourable outcome (Δ mRS) (median ASPECTS 10 (10–9) vs. median ASPECTS 9 (10–7); p = 0,001) could be demonstrated. Multivariable regression analysis revealed FDCT-ASPECTS (OR 0.234, 95% CI − 0.102–0.008, p = 0.022) along with the NHISS at admission (OR 0.169, 95% CI 0.003–0.018, p = 0.008) as independent factors for a favourable outcome. Cut-off point for a favourable outcome (Δ mRS) was identified at an ASPECTS ≥ 8 (sensitivity 90.6%, specificity 35%). Conclusion: For patients with LVO and successful EVT, FDCT-ASPECTS was found to be highly reliable in predicting long-term outcome.
CRIS-Team Scopus Importer:2022-12-02
Keywords: ASPECTS; Endovascular treatment; Flat-detector CT; Stroke

Capturing schizophrenia-like prodromal symptoms in a spinocerebellar ataxia-17 transgenic rat - Amato, Davide; Canneva, Fabio; Huu Phuc Nguyen,; Bauer, Peter; Riess, Olaf; von Hörsten, Stephan; Müller, Christian P. (Journal of Psychopharmacology, 2017)
RATIONALE: The polyglutamine disease spinocerebellar ataxia type 17 (SCA17) is a neurodegenerative disease leading to severe neurological symptoms during development. Additionally, patients affected by SCA17 display psychosis earlier than their motor disorders. OBJECTIVE: Here the putative psychotic phenotype and endophenotype of transgenic SCA17 rats was examined. METHODS: The expression of schizophrenia-like symptoms was evaluated over a longitudinal period before and after the onset of neurological symptoms in SCA17. To this end, transgenic SCA17 rats' monoamine neurotransmission was investigated along with their locomotion at baseline and in response to amphetamine using in-vivo microdialysis in free moving conditions, their sensorimotor gating using pre-pulse inhibition of startle reaction, and their object memory using the novel object recognition test as an index of cognitive impairments. RESULTS: Presymptomatic SCA17 rats displayed dysregulated monoamine levels at baseline and in response to amphetamine compared with control wild-type (wt) rats. At that stage, neither amphetamine-induced hyperlocomotion nor sensorimotor gating differed from that in wt rats. Symptomatic SCA17 rats developed sensorimotor gating deficits and also showed an impaired object memory, while their monoaminergic responses remained supersensitive to amphetamine. CONCLUSIONS: The data of the present study demonstrate a neurochemical endophenotype in SCA17 rats resembling that of prodromal schizophrenia. These findings suggest that a sensitization of the monoamine systems arises early in adulthood in SCA17 rats and may predispose them to express schizophrenia-like symptoms later in life.
EVALuna2:32791

Cardiac Surgery is Associated with Biomarker Evidence of Neuronal Damage - Alifier, Marek; Olsson, Bob; Andreasson, Ulf; Cullen, Nicholas C.; Czyżewska, Jolanta; Jakubów, Piotr; Sieśkiewicz, Andrzej; Stasiak-Barmuta, Anna; Hirnle, Tomasz; Kornhuber, Johannes; Zetterberg, Henrik; Lewczuk, Piotr; et al. (Journal of Alzheimer's Disease, 2020)
Background: Anesthesia and surgery is commonly associated with central nervous system sequelae and cognitive symptoms, which may be caused by neuronal injury. Neuronal injury can be monitored by plasma concentrations of the neuronal biomarkers tau and neurofilament light protein (NFL). Currently, there are no studies examining whether neuronal injury varies between surgical procedures. Objective: Our aim was to investigate if neuronal damage is more frequent after cardiac than after otolaryngeal surgery, as estimated by tau and NFL concentrations in plasma. Methods: Blood samples were drawn before, during, and after surgery and concentrations of tau, NFL, Aβ40, and Aβ42 were measured in 25 patients undergoing cardiac surgery (9 off-pump and 16 on-pump) and 26 patients undergoing otolaryngeal surgery. Results: Tau increased during surgery (1752%, p=0.0001) and NFL rose seven days post-surgery (1090%, p<0.0001) in patients undergoing cardiac surgery; even more in patients on-pump than off-pump. No changes were observed in patients undergoing otolaryngeal surgery and only minor fluctuations were observed for Aβ40 and Aβ42. Conclusion: Cardiac surgery is associated with neuronal injury, which is aggravated by extracorporeal circulation. Analyses of NFL and tau in blood may guide development of surgical procedures to minimize neuronal damage, and may also be used in longitudinal clinical studies to assess the relationship of surgery with future neurocognitive impairment or dementia.
CRIS-Team Scopus Importer:2020-05-05
Keywords: Cardiac surgery; cognitive impairment; dementia; extracorporeal circulation; neurofilament light protein; plasma; tau

Cardiovascular autonomic dysfunction in patients with posterior circulation ischemic stroke - Wang, Ruihao; Macha, Kosmas; Koehn, Julia; Siedler, Gabriela; Winder, Klemens; Gerner, Stefan; Schwab, Stefan; Kohrmann, Martin; Hilz, Max-Josef; Kallmünzer, Bernd (JOURNAL OF THE NEUROLOGICAL SCIENCES, 2021)
CRIS-Team WoS Importer:2021-12-03

CARDIOVASCULAR AUTONOMIC MODULATION THREE MONTHS POST STROKE IMPROVES IN PATIENTS WITH ISCHEMIA IN THE RIGHT MIDDLE CEREBRAL ARTERY TERRITORY - Wang, Ruihao; Macha, Kosmas; Köhn, Julia; Marsch, Armin; Winder, Klemens; Gerner, Stefan; Koehrmann, M.; Schwab, Stefan; Kallmünzer, Bernd; Hilz, Max-Josef (INTERNATIONAL JOURNAL OF STROKE, 2020)
CRIS-Team WoS Importer:2021-01-22