Temporal Dynamics of Antidepressant Ketamine Effects on Glutamine Cycling Follow Regional Fingerprints of AMPA and NMDA Receptor Densities - Li, Meng; Demenescu, Liliana Ramona; Colic, Lejla; Metzger, Coraline Danielle; Heinze, Hans-Jochen; Steiner, Johann; Speck, Oliver; Fejtová, Anna; Salvadore, Giacomo; Walter, Martin (Neuropsychopharmacology, 2017)
The anterior cingulate cortex (ACC) has shown decreased glutamate levels in patients with major depressive disorder. Subanesthetic doses of ketamine were repeatedly shown to improve depressive symptoms within 24 h after infusion and this antidepressant effect was attributed to increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) throughput. To elucidate ketamine's mechanism of action, we tested whether the clinical time course of the improvement is mirrored by the change of glutamine/glutamate ratio and if such effects show a regional and temporal specificity in two distinct subdivisions of ACC with different AMPA/N-methyl-D-aspartate receptor profiles. In a double-blind, placebo-controlled intravenous infusion study of ketamine, we measured glutamate and glutamine in the pregenual ACC (pgACC) and the anterior midcingulate cortex at 1 and 24 h post infusion with magnetic resonance spectroscopy at 7 T. A significant interaction of time, region, and treatment was found for the glutamine/glutamate ratios (placebo, n=14; ketamine, n=12). Post-hoc analyses revealed that the glutamine/glutamate ratio increased significantly in the ketamine group, compared with placebo, specifically in the pgACC after 24 h. The glutamine/glutamate increase in the pgACC caused by ketamine at 24 h post infusion was reproduced in an enlarged sample (placebo, n=24; ketamine, n=20). Our results support a significant temporal and regional response in glutamine/glutamate ratios to a single subanesthetic dose of ketamine, which mirrors the time course of the antidepressant response and reversal of the molecular deficits in patients and which may be associated with the histoarchitectonical receptor fingerprints of the ACC subregions.
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The 4th Schizophrenia International Research Society Conference, 5-9 April 2014, Florence, Italy: a summary of topics and trends - Abayomi, Olukayode; Amato, Davide; Bailey, Candace; Bitanihirwe, Byron; Bowen, Lynneice; Burshtein, Shimon; Cullen, Alexis; Fuste, Montserrat; Herrmann, Ana P.; Khodaie, Babak; Kilian, Sanja; Lang, Qortni A.; et al. (Schizophrenia Research, 2014)
The 4th Schizophrenia International Research Society Conference was held in Florence, Italy, April 5-9, 2014 and this year had as its emphasis, "Fostering Collaboration in Schizophrenia Research". Student travel awardees served as rapporteurs for each oral session, summarized the important contributions of each session and then each report was integrated into a final summary of data discussed at the entire conference by topic. It is hoped that by combining data from different presentations, patterns of interest will emerge and thus lead to new progress for the future. In addition, the following report provides an overview of the conference for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.
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The acid sphingomyelinase/ceramide system in COVID-19 - Kornhuber, Johannes; Hoertel, Nicolas; Gulbins, Erich (Molecular Psychiatry, 2021)
Acid sphingomyelinase (ASM) cleaves sphingomyelin into the highly lipophilic ceramide, which forms large gel-like rafts/platforms in the plasma membrane. We showed that SARS-CoV-2 uses these platforms for cell entry. Lowering the amount of ceramide or ceramide blockade due to inhibitors of ASM, genetic downregulation of ASM, anti-ceramide antibodies or degradation by neutral ceramidase protected against infection with SARS-CoV-2. The addition of ceramide restored infection with SARS-CoV-2. Many clinically approved medications functionally inhibit ASM and are called FIASMAs (functional inhibitors of acid sphingomyelinase). The FIASMA fluvoxamine showed beneficial effects on COVID-19 in a randomized prospective study and a prospective open-label real-world study. Retrospective and observational studies showed favorable effects of FIASMA antidepressants including fluoxetine, and the FIASMA hydroxyzine on the course of COVID-19. The ASM/ceramide system provides a framework for a better understanding of the infection of cells by SARS-CoV-2 and the clinical, antiviral, and anti-inflammatory effects of functional inhibitors of ASM. This framework also supports the development of new drugs or the repurposing of "old" drugs against COVID-19.
CRIS-Team WoS Importer:2021-10-15

The Alzheimer’s Disease Activities of Daily Living International Scale (ADL-IS) - Reisberg, Barry; Finkel, Sanford; Overall, John; Schmidt-Gollas, Norbert; Kanowski, Siegfried; Lehfeld, Hartmut; Hulla, Franz; Sclan, Steven G.; Wilms, Hans-Ulrich; Heininger, Kurt; Hindmarch, Ian; Stemmler, Mark; et al. (International Psychogeriatrics, 2001)
Background: Activities of daily living (ADL) deficits are integral components of dementia disorders, and ADL measures are among the most robust markers of the course of Alzheimer's disease (AD). Despite this acknowledged importance, no clearly useful ADL instrument for cross-cultural application in pharmacologic trials in the early stages of AD had been available. Method: An international effort was launched to develop an ADL scale for pharmacologic trials in early AD. Steps taken from 1990 to the present included: (1) international scientific working group meetings and reviews, (2) reviews of existing measures, (3) collating of existent, nonredundant items, (4) querying experts for new items, (5) interviews with informants and subjects in the USA, France, and Germany, toward the identification of potential new items, (6) identification of an item pool based upon these procedures, (7) creation of a trial instrument, (8) piloting of this instrument, and (9) refinement of the scale based upon statistical analysis of the pilot data. Final item selection was based upon: (1) relevance for [greater-than-or-equal] 80% of subjects in severity-stratified USA and German samples; (2) absence of gender and national biases; (3) significant (p < .05) discrimination between (a) normal versus mildly impaired and (b) mildly impaired versus moderately to moderately severely impaired subjects; and (4) Global Deterioration Scale (GDS) scores accounting for [greater-than-or-equal] 12% of variance in the item after controlling for age and gender. Results: An ADL scale consisting of 40 items that correlate with the global and cognitive progress of AD is developed for international usage in pharmacologic trials in incipient, mild, moderate, and moderately severe AD. The scale contains 40 items falling within 13 ADL categories. The 40-item scale is shown to have .81 correlation with GDS staging,.81 with mental status assessment (Mini-Mental State Examination), and .81 with a psychometric test (the SKT) (p values < .001). Conclusion: This scale can be used to measure therapeutic response in AD.

The AMDS system for the documentation of symptoms and signs ﻿associated with﻿ pain - Gromer, Teja W.; Kaefferlein, Wolfgang; Menger, Bjoern; Dohrenbusch, Ralf; Kappis, Bernd; Maihoefner, Christian; Kornhuber, Johannes; Philipsen, Alexandra; Mueller, Helge H. O. (Schmerz, 2017)
The authors present a system for nomenclature and documentation of symptoms and signs associated with pain. The system was compiled in a staged process by the study group for methods and documentation of pain-associated symptoms and signs (Arbeitsgemeinschaft für Methodik und Dokumentation von Schmerzbefunden [AMDS]). The suggested items were elaborated from terms used in current national and international guidelines and classifications and in part integrated into superordinate terms. The items that were built up by this approach aim to reflect the broad spectrum of pain diseases. The items for the description of pain-associated symptoms and signs are divided into the areas of algesiomotor, psychoalgesiological and somatoalgesiological findings. The aim is the documentation of a multidimensional algesiological description of findings with defined terminology, which can serve as a comparable and unified standard, particularly in the field of pain assessment. The AMDS system should enable a systematic description of pain, which is a reliable foundation for diagnostics, therapy planning and expert case evaluation.
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The androgen model of suicide completion - Lenz, Bernd; Röther, Mareike; Bouna-Pyrrou, Polyxeni; Mühle, Christiane; Tektas, Ozan Y.; Kornhuber, Johannes (Progress in Neurobiology, 2019)
Suicide is a devastating public health issue that imposes severe psychological, social, and economic burdens not only for the individuals but also for their relatives, friends, clinicians, and the general public. Among the different suicidal behaviors, suicide completion is the worst and the most relevant outcome. The knowledge of biological etiopathological mechanisms involved in suicide completion is limited. Hitherto, no objective markers, either alone or in combination, can reliably predict who will complete a suicide. However, such parameters are strongly needed to establish and optimize prediction and prevention. We introduce here a novel ideation-to-completion framework in suicide research and discuss the problems of studies aiming at identifying and validating clinically useful markers. The male gender is a specific risk factor for suicide, which suggests that androgen effects are implicated in the transition from suicidal ideation to suicide completion. We present multiple lines of direct and indirect evidence showing that both an increased prenatal androgen load (with subsequent permanent neuroadaptations) and increased adult androgen activity are involved in suicide completion. We also review data arguing that modifiable maternal behavioral traits during pregnancy contribute to the offspring's prenatal androgen load and increase the risk for suicide completion later in life. We conclude that in utero androgen exposure and adult androgen levels facilitate suicide completion in an synergistic manner. The androgen model of suicide completion provides the basis for the development of novel predictive and preventive strategies in the future.
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The antidepressant fluoxetine mobilizes vesicles to the recycling pool of rat hippocampal synapses during high activity - Jung, Jasmin; Loy, Kristina; Schilling, Eva-Maria; Röther, Mareike; Brauner, Jan M.; Huth, Tobias; Schlötzer-Schrehardt, Ursula; Alzheimer, Christian; Kornhuber, Johannes; Welzel, Oliver; Groemer, Teja W. (Molecular Neurobiology, 2014)
Effects of the antidepressant fluoxetine in therapeutic concentration on stimulation-dependent synaptic vesicle recycling were examined in cultured rat hippocampal neurons using fluorescence microscopy. Short-term administration of fluoxetine neither inhibited exocytosis nor endocytosis of RRP vesicular membranes. On the contrary, acute application of the drug markedly increased the size of the recycling pool of hippocampal synapses. This increase in recycling pool size was corroborated using the styryl dye FM 1-43, antibody staining with ?Syt1-CypHer(TM)5E and overexpression of synapto-pHluorin, and was accompanied by an increase in the frequency of miniature postsynaptic currents. Analysis of axonal transport and fluorescence recovery after photobleaching excluded vesicles originating from the synapse-spanning superpool as a source, indicating that these new release-competent vesicles derived from the resting pool. Super resolution microscopy and ultrastructural analysis by electron microscopy revealed that short-term incubation with fluoxetine had no influence on the number of active synapses and synaptic morphology compared to controls. These observations support the idea that therapeutic concentrations of fluoxetine enhance the recycling vesicle pool size and thus the recovery of neurotransmission from exhausting stimuli. The change in the recycling pool size is consistent with the plasticity hypothesis of the pathogenesis of major depressive disorder as stabilization of the vesicle recycling might be responsible for neural outgrowth and plasticity.
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The applause sign in frontotemporal lobar degeneration and related conditions - Schoenecker, Sonja; Hell, Franz; Boetzel, Kai; Wlasich, Elisabeth; Ackl, Nibal; Suessmair, Christine; Otto, Markus; Anderl-Straub, Sarah; Ludolph, Albert; Kassubek, Jan; Huppertz, Hans-Juergen; Diehl-Schmid, Janine; et al. (Journal of Neurology, 2019)
The applause sign, i.e., the inability to execute the same amount of claps as performed by the examiner, was originally reported as a sign specific for progressive supranuclear palsy (PSP). Recent research, however, has provided evidence for the occurrence of the applause sign in various conditions. The aim of this study was to determine the prevalence of the applause sign and correlate its presence with neuropsychological and MRI volumetry findings in frontotemporal lobar degeneration and related conditions. The applause sign was elicited with the three clap test (TCT), with a higher score indicating poorer performance. Data were recorded from 272 patients from the cohort of the German consortium for frontotemporal lobar degeneration (FTLDc): 111 with behavioral variant frontotemporal dementia (bvFTD), 98 with primary progressive aphasia (PPA), 30 with progressive supranuclear palsy Richardson's syndrome, 17 with corticobasal syndrome (CBS) and 16 with amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD). For comparison, 29 healthy elderly control subjects (HC) were enrolled in the study. All subjects underwent detailed language and neuropsychological assessment. In a subset of 156 subjects, atlas-based volumetry was performed. The applause sign occurred in all patient groups (40% in PSP, 29.5% in CBS, 25% in ALS/FTD, 13.3% in PPA and 9.0% in bvFTD) but not in healthy controls. The prevalence was highest in PSP patients. It was significantly more common in PSP as compared to bvFTD, PPA and HC. The comparison between the other groups failed to show a significant difference regarding the occurrence of the applause sign. The applause sign was highly correlated to a number of neuropsychological findings, especially to measures of executive, visuospatial, and language function as well as measures of disease severity. TCT scores showed an inverse correlation with the volume of the ventral diencephalon and the pallidum. Furthermore the volume of the ventral diencephalon and pallidum were significantly smaller in patients displaying the applause sign. Our study confirms the occurrence of the applause sign in bvFTD, PSP and CBS and adds PPA and ALS/FTD to these conditions. Although still suggestive of PSP, clinically it must be interpreted with caution. From the correlation with various cognitive measures we suggest the applause sign to be indicative of disease severity. Furthermore we suggest that the applause sign represents dysfunction of the pallidum and the subthalamic nucleus, structures which are known to play important roles in response inhibition.
CRIS-Team WoS Importer:2019-02-21

The association between prenatal alcohol consumption and preschool child stress system disturbance - Grimm, Jennifer; Stemmler, Mark; Golub, Yulia; Schwenke, Eva; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kratz, Oliver; Moll, Gunther; Kornhuber, Johannes; Eichler, Anna (Developmental Psychobiology, 2021)
Background: Drinking alcohol during pregnancy is considered a risk factor for child development; however, child biomarkers of prenatal alcohol exposure have been rarely studied. We examined whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with child cortisol concentrations at primary school age. Methods: For 137 children, prenatal alcohol exposure was operationalized by the meconium biomarker EtG and by maternal self-reports during pregnancy. Two EtG cut-offs (EtG ≥10 ng/g and EtG ≥112 ng/g) were applied. Cortisol concentrations were measured in saliva and hair samples. Results: Children with EtG ≥10 ng/g showed significantly reduced hair cortisol concentrations (HCCs) (p =.050, (Formula presented.) = 0.042). For children with EtG ≥112 ng/g, the cortisol awakening response (CAR) was significantly decreased (p =.025, (Formula presented.) = 0.070). These effects were also present in correlational analyses with continuous EtG data, speaking for partly dose-dependent effects. Especially, within the EtG ≥112 ng/g group, the basal (CAR: rp = −.642, p =.120) and cumulative (HCC: rp = −.660, p =.107) cortisol parameters were associated with child emotional symptoms at medium effect size. Conclusions: The present study showed both the biological association of intrauterine alcohol exposure with the cortisol stress system, partly dose-dependent, and the functional association with emotional and behavioral symptoms.
CRIS-Team Scopus Importer:2020-10-16
Keywords: alcohol; biomarker; child; cortisol stress system; ethyl glucuronide; hypothalamus-pituitary-adrenal axis; intrauterine alcohol exposure; meconium; pregnancy

The association of leptin secretion with cognitive performance in patients with eating disorders - Wollenhaupt, Carina; Wilke, Leonhard; Erim, Yesim; Rauh, Manfred; Steins-Loeber, Sabine; Paslakis, Georgios (Psychiatry Research, 2019)
This study is an investigation of neuropsychological performance in patients with anorexia nervosa, bulimia nervosa, and binge eating disorder and hormonal secretion patterns for ghrelin, leptin, insulin, and glucose. An oral glucose tolerance test (OGTT)was performed in a cohort of n = 30 female patients suffering from eating disorders as well as n = 20 control females. All participants underwent the Wisconsin Card Sorting Test (WCST), the Trail Making Test (TMT), and a go/no-go task using food vs. neutral stimuli. Patients with anorexia nervosa differed from controls in their leptin response to the OGTT. While the four groups under investigation did not differ in neuropsychological performance, we found leptin responses to the OGTT to be associated with performance in the food-specific go/no-go task. These preliminary results may indicate a putative association between leptin concentrations and neuropsychological performance, particularly in measures of inhibitory control. Further studies investigating the role of leptin in impulsive behaviors in eating disorders would be useful.
CRIS-Team Scopus Importer:2019-05-28
Keywords: Eating disorder; Ghrelin; Go/no-go test; Leptin; Neuropsychological performance; Oral glucose tolerance test

THE ASSOCIATION OF METHYLATION OF THE PROMOTER AND ANTIDEPRESSANTS IN TRANSCRIPTIONAL REGULATION OF THE BRAIN-DERIVED NEUROTROPHIC FACTOR EXON IV - Pathak, Hansi; Frieling, Helge (EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2019)
CRIS-Team WoS Importer:2019-04-09

The beer component hordenine inhibits alcohol addiction-associated behaviours in mice - Li, Yan; Vogel, Christina; Kalinichenko, Liubov; Hübner, Harald; Weikert, Dorothée; Schaefer, Natascha; Gmeiner, Peter; Villmann, Carmen; Pischetsrieder, Monika; Müller, Christian P. (Addiction Biology, 2023)
Alcohol consumption is a widespread behaviour that may eventually result in the development of alcohol use disorder (AUD). Alcohol, however, is rarely consumed in pure form but in fruit- or corn-derived preparations, like beer. These preparations add other compounds to the consumption, which may critically modify alcohol intake and AUD risk. We investigated the effects of hordenine, a barley-derived beer compound on alcohol use-related behaviours. We found that the dopamine D2 receptor agonist hordenine (50 mg/kg) limited ongoing alcohol consumption and prophylactically diminished relapse drinking after withdrawal in mice. Although not having reinforcing effects on its own, hordenine blocked the establishment of alcohol-induced conditioned place preference (CPP). However, it independently enhanced alcohol CPP retrieval. Hordenine had a dose-dependent inhibitory effect on locomotor activity. Chronic hordenine exposure enhanced monoamine tissue levels in many brain regions. Further characterization revealed monoaminergic binding sites of hordenine and found a strong binding on the serotonin and dopamine transporters, and dopamine D3, and adrenergic α1A and α2A receptor activation but no effects on GABAA receptor or glycinergic signalling. These findings suggest that natural ingredients of beer, like hordenine, may work as an inhibitory and use-regulating factor by their modulation of monoaminergic signalling in the brain.
CRIS-Team Scopus Importer:2023-08-11
Keywords: addiction; alcohol; conditioned preference; drinking; hordenine

The behavioral profile of spice and synthetic cannabinoids in humans - Mueller, Helge H.; Kornhuber, Johannes; Sperling, Wolfgang (Brain Research Bulletin, 2016)
The use of synthetic cannabinoids (spice) is increasing. The number of descriptions of (new) clinical side effects is also increasing. We screened relevant publications for articles about spice with a focus on the clinical manifestations of the use of this drug. Spice creates diffuse psychiatric and somatic effects that are only partially similar to those of natural cannabinoids. Most of the observed effects are related to sympathomimetic-cardiac effects and neuropsychiatric manifestations. Clinical treatment is primarily based on intensive apparative and laboratory monitoring and supportive therapy. Because the exact active ingredients of spice are often difficult to determine with standard specific toxicology testing, the assessment and analysis of consumed substances by specialized laboratories is recommended.
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The Benefit of a Retrospective Pregnancy Anamnesis in Child and Adolescent Psychiatry: The Reliability of Maternal Self-Report during Childhood Development - Mestermann, Stefan; Fasching, Peter; Beckmann, Matthias; Gerlach, Jennifer; Kratz, Oliver; Moll, Gunther; Kornhuber, Johannes; Eichler, Anna (Children, 2023)
Pregnancy anamnesis is a crucial part of child and adolescent psychiatry diagnostics. In previous works, the reliability of retrospective maternal self-report on perinatal characteristics was heterogeneous. This prospective longitudinal study aimed to evaluate women’s recall of prenatal events in a within-subject design. A sample of 241 women gave a self-report on prenatal alcohol, smoking, partnership quality, pregnancy satisfaction, and obstetric complications during the 3rd trimester (t0), childhood (t1, 6–10 y), and adolescence (t2, 12–14 y). The intra-individual agreement was examined. The t0–t1–(t2) agreement was poor to substantial; this was highest for smoking and worst for obstetric complications, followed by alcohol (Fleiss’ κ = 0.719 to −0.051). There were significant t0–t1–(t2) differences for all pregnancy variables (p < 0.017), except for 3rd trimester satisfaction (p = 0.256). For alcohol (t0 25.8%, t1 17.4%, t2 41.0%) and smoking (t0 11.9%, t1 16.4%, t2 22.6%), the highest self-reported rates were found during adolescence. During childhood, fewer obstetric complications (t0 84.9%, t1 42.2%) and worse partnerships were reported (t0 M = 8.86, t1 M = 7.89). Thought to be due to social stigmata and memory effects, pregnancy self-reports cannot be precisely reproduced. Creating a respectful and trusting atmosphere is essential for mothers to give honest self-reports that are in the best interest of their children.
CRIS-Team Scopus Importer:2023-06-30
Keywords: alcohol; partnership; pregnancy; pregnancy satisfaction; prenatal; retrospective; risk perceptions; self-report; smoking

The Ca2+ sensor protein swiprosin-1/EFhd2 is present in neurites and involved in kinesin-mediated transport in neurons - Purohit, Pavitra; Perez-Branguli, Francesc; Prots, Iryna; Borger, Eva; Gunn-Moore, Frank; Welzel, Oliver; Loy, Kristina; Wenzel, Eva Maria; Groemer, Teja W.; Brachs, Sebastian; Holzer, Max; Buslei, Rolf; et al. (PLoS ONE, 2014)
Swiprosin-1/EFhd2 (EFhd2) is a cytoskeletal Ca2+ sensor protein strongly expressed in the brain. It has been shown to interact with mutant tau, which can promote neurodegeneration, but nothing is known about the physiological function of EFhd2 in the nervous system. To elucidate this question, we analyzed EFhd2-/-/lacZ reporter mice and showed that lacZ was strongly expressed in the cortex, the dentate gyrus, the CA1 and CA2 regions of the hippocampus, the thalamus, and the olfactory bulb. Immunohistochemistry and western blotting confirmed this pattern and revealed expression of EFhd2 during neuronal maturation. In cortical neurons, EFhd2 was detected in neurites marked by MAP2 and co-localized with pre- and post-synaptic markers. Approximately one third of EFhd2 associated with a biochemically isolated synaptosome preparation. There, EFhd2 was mostly confined to the cytosolic and plasma membrane fractions. Both synaptic endocytosis and exocytosis in primary hippocampal EFhd2-/- neurons were unaltered but transport of synaptophysin-GFP containing vesicles was enhanced in EFhd2-/- primary hippocampal neurons, and notably, EFhd2 inhibited kinesin mediated microtubule gliding. Therefore, we found that EFhd2 is a neuronal protein that interferes with kinesin-mediated transport.
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The Central Biobank and Virtual Biobank of BIOMARKAPD: A Resource for Studies on Neurodegenerative Diseases - Reijs, Babette L. R.; Teunissen, Charlotte E.; Goncharenko, Nikolai; Betsou, Fay; Blennow, Kaj; Baldeiras, Ines; Brosseron, Frederic; Cavedo, Enrica; Fladby, Tormod; Froelich, Lutz; Gabryelewicz, Tomasz; Gurvit, Hakan; et al. (Frontiers in Neurology, 2015)
Biobanks are important resources for biomarker discovery and assay development. Biomarkers for Alzheimer's and Parkinson's disease (BIOMARKAPD) is a European multicenter study, funded by the EU Joint Programme-Neurodegenerative Disease Research, which aims to improve the clinical use of body fluid markers for the diagnosis and prognosis of Alzheimer's disease (AD) and Parkinson's disease (PD). The objective was to standardize the assessment of existing assays and to validate novel fluid biomarkers for AD and PD. To support the validation of novel biomarkers and assays, a central and a virtual biobank for body fluids and associated data from subjects with neurodegenerative diseases have been established. In the central biobank, cerebrospinal fluid (CSF) and blood samples were collected according to the BIOMARKAPD standardized pre-analytical procedures and stored at Integrated BioBank of Luxembourg. The virtual biobank provides an overview of available CSF, plasma, serum, and DNA samples at each site. Currently, at the central biobank of BIOMARKAPD samples are available from over 400 subjects with normal cognition, mild cognitive impairment (MCI), AD, frontotemporal dementia (FTD), vascular dementia, multiple system atrophy, progressive supranuclear palsy, PD, PD with dementia, and dementia with Lewy bodies. The virtual biobank contains information on over 8,600 subjects with varying diagnoses from 21 local biobanks. A website has been launched to enable sample requests from the central biobank and virtual biobank.
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The ceramide system as a novel antidepressant target - Kornhuber, Johannes; Müller, Christiane; Becker, Katrin Anne; Reichel, Martin; Gulbins, Erich (Trends in Pharmacological Sciences, 2014)
Major depression is a systems disorder which impairs not only central nervous system aspects of mood and behavior but also peripheral organ systems. Current views on the pathogenesis and treatment of depression are predominantly based on proteins and transmitters and thus are difficult to reconcile central with peripheral pathomechanisms. Recent research showed that there is also a lipid-based pathway involved in the pathology of depression, which is activated by psychosocial stress, oxidative stress, or inflammation. Inducible dysfunction of the ceramide pathway, which is abundant in the brain as well as in peripheral organs, may account for mood disorder, behavioral symptoms, and further promote inflammation and oxidative stress in peripheral systems. As such, the lipid ceramide pathway may provide the missing link between brain dysfunction and somatic symptoms of depression. Pharmacological interventions that reduce ceramide abundance also show antidepressant action and may promise a better treatment of major depression.
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The clinical use of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: a consensus paper from the Alzheimer's Biomarkers Standardization Initiative - Luis Molinuevo, Jose; Blennow, Kaj; Dubois, Bruno; Engelborghs, Sebastiaan; Lewczuk, Piotr; Perret-Liaudet, Armand; Teunissen, Charlotte E.; Parnetti, Lucilla (Alzheimers & Dementia, 2014)
Cerebrospinal fluid (CSF) biomarkers ?-amyloid 1-42 (A?1-42), also expressed as A?1-42:A?1-40 ratio, T-tau, and P-tau181P, have proven diagnostic accuracy for mild cognitive impairment and Alzheimer's disease (AD). How to use, interpret, and disclose biomarker results drives the need for standardization.Previous Alzheimer's Biomarkers Standardization Initiative meetings discussed preanalytical issues affecting A?1-42 and tau in CSF. This second round of consensus meetings focused on issues related to clinical use of AD CSF biomarkers.Consensus was reached that lumbar puncture for AD CSF biomarker analysis be considered as a routine clinical test in patients with early-onset dementia, at the prodromal stage or with atypical AD. Moreover, consensus was reached on which biomarkers to use, how results should be interpreted, and potential confounding factors.Changes in A?1-42, T-tau, and P-tau181P allow diagnosis of AD in its prodromal stage. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up.
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The common acid sphingomyelinase polymorphism p.G508R is associated with self-reported allergy - Reichel, Martin; Richter-Schmidinger, Tanja; Mühle, Christiane; Rhein, Cosima; Alexopoulos, Panagiotis; Schwab, Sibylle; Gulbins, Erich; Kornhuber, Johannes (Cellular Physiology and Biochemistry, 2014)
Acid sphingomyelinase (ASM) is a key regulator of ceramide-dependent signalling pathways. Among others, activation of ASM can be induced by CD95 or cytokine signalling and by cellular stress resulting from inflammation or infection. Increased ASM activity was observed in a variety of human diseases including inflammatory and neuropsychiatric disorders. We hypothesized that basal ASM activity might influence the susceptibility for common human diseases.The general health condition of 100 young people was assessed using a questionnaire. The ASM polymorphism rs1050239 (c.1522G>A; encoding p.G508R) was determined from genomic DNA. Activities of secretory (S-) and lysosomal (L-) ASM were measured in blood plasma and peripheral blood cells respectively.The polymorphism rs1050239 was significantly associated with self-reported allergy (p=4.68×10(-4); adjusted p-value for multiple testing 0.007). Allergy was more prevalent in carriers of the minor A allele compared to non-carriers (p=0.00015; odds ratio=6.5, 95% CI 2.15-21.7). S-ASM activity was significantly associated with rs1050239 (p=5.3×10(-7)) and decreased with the number of A alleles in a gene-dosage dependent manner. In allergic patients, S-ASM activity was moderately decreased (p=0.034). L-ASM activity was significantly lower in subjects homozygous for the minor A allele (p=0.025) but not different between allergic and non-allergic subjects (p=0.318).Our analysis provides evidence for an involvement of ASM in the pathophysiology of allergy, which is in line with previous reports addressing the role of sphingolipids in this disorder. Further studies should clarify the mechanism linking rs1050239 to allergy. The ASM pathway might be useful for predicting allergic disposition and disease course and as a therapeutic target.
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The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study - Müller, Christian P.; Chu, Congying; Qin, Liya; Liu, Chunyu; Xu, Bing; Gao, He; Ruggeri, Barbara; Hieber, Saskia; Schneider, Julia; Jia, Tianye; Tay, Nicole; Akira, Shizuo; et al. (Cerebral Cortex, 2019)
Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-κB activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 × 10-19) and regional methylation (P = 5.90 × 10-25). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-κB. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.
CRIS-Team Scopus Importer:2019-05-02
Keywords: alcohol; anxiety; drinking; insular cortex; NF-κB; TANK

The Cost of Early Diagnosis of Cognitive Decline in German Memory Clinics - Onurl, Oezguer A.; Wolff-Menzler, Claus; Von Arnim, Christine A. F.; Jessen, Frank; Fink, Gereon R.; Wiltfang, Jens; Laske, Christoph; Schneider, Anja; Levinl, Johannes; Oberstein, Timo; Kornhuber, Johannes; Oberhauser, Felix; et al. (Fortschritte der Neurologie - Psychiatrie, 2022)
Dementias are expensive diseases: the net annual cost in European healthcare is about euro 28.000 per case with a strong stage dependency, of which medical care accounts for about 19%. Diagnostic costs, on the other hand, account for only a small proportion of the total costs. With changes in the guidelines, biomarker tests are becoming increasingly important. At present, the concrete economic impact of biomarker-based diagnosis is largely unknown. To determine the actual costs of diagnostic procedures based on guidelines, we conducted a survey among the members of the German Memory Clinic Network (DNG). From 15 expert centres, the staff engagement time for all procedures was collected. Based on the individual engagement times of the different professions, the total of personnel costs for diagnostics was calculated using current gross personnel costs. The total sum of diagnostic costs (personnel plus procedures) was calculated for three different scenarios e. g. euro 633,97 for diagnostics without biomarkers, euro 1.214,90 for diagnostics with CSF biomarkers and euro 4.740,58 euro for diagnostics with FDG- plus Amyloid-PET. In addition, the actual diagnostic costs of the current practice in expert memory clinics were estimated, taking into account personnel costs, costs for the different procedures and the frequency of their use across all patients. This results in total average costs of euro 1.394,43 per case as the mean across all centres (personnel costs euro 351,72, costs for diagnostic procedures euro 1.042,71). The results show that state-of-the-art diagnosis of dementia and pre-dementia states, such as mild cognitive impairment (MCI) requires financial resources, which are currently not fully reimbursed in Germany. The need for a biomarker-based etiological diagnosis of dementia and pre-dementia states will increase, due to availability of disease-modifying treatments. Therefore, the current gap of reimbursement must be filled by new models of compensation.
CRIS-Team WoS Importer:2022-07-29

The course of cancer-related insomnia: don't expect it to disappear after cancer treatment - Schieber, Katharina; Niecke, Alexander; Geiser, Franziska; Erim, Yesim; Bergelt, Corinna; Büttner-Teleaga, Antje; Maatouk, Imad; Stein, Barbara; Teufel, Martin; Wickert, Martin; Wuensch, Alexander; Weis, Joachim (Sleep Medicine, 2019)
Objective: The study aimed to examine the 12-month course of cancer-related insomnia (CRI) and to identify possible predictors for the prevalence and persistence of CRI. Methods: This longitudinal multicenter study included N = 405 patients with cancer (56% females, mean age: 58.6 years). CRI was measured by the Insomnia Severity Index (ISI). Socio-demographic and clinical data, as well as psychological parameters (Distress Thermometer, PHQ-9, GAD-7, and EORTC-Fatigue), were assessed at baseline (T1) and 12 months later (T2). Results: In our sample, a high prevalence of relevant insomnia symptoms (49.4%, ISI > 7) was found, while a clinical insomnia diagnosis was verified in 12.8% (ISI > 14). When insomnia was present at T1, this problem was persistent after one year in 64%. At T2, however, significantly more women suffered from insomnia symptoms (53.3% women vs. 39.3% men; p = 0.003). Insomnia was associated with many clinical and psychological parameters, especially with fatigue (r = 0.5). Multiple regression analysis revealed that, in women, only insomnia at T1 was a significant predictor for insomnia at T2 (R2 = 0.40; F(5) = 12.5; p < 0.001), whereas in men insomnia, depressive symptoms and the use of psychotropic drugs at T1 predicted the extent of insomnia at T2 (R2 = 0.28; F(7) = 9.5; p < 0.001). In all participants, levels of distress, depression, and anxiety decreased from T1 to T2 (p's < 0.016). Conclusion: Insomnia is a common disorder in cancer patients. Although medical and psychological parameters improved during the 12-month course of cancer treatment, our results show that insomnia is highly persistent, especially in women. This indicates that adequate support for those affected is needed. Clinical Trial Registration Number: DRKS00004860.
CRIS-Team Scopus Importer:2019-06-04
Keywords: Cancer; Gender-specific predictors; Insomnia; Prevalence; Psychological distress; Sleep disorder

The Dementia Assessment of Service Needs (DEMAND): Development and Validation of a Standardized Needs Assessment Instrument - Dietzel, Nikolas; Grässel, Elmar; Kürten, Lara; Meuer, Sebastian; Klaas-Ickler, Dorothee; Hladik, Markus; Chmelirsch, Christina; Kolominsky-Rabas, Peter (Journal of Alzheimer's Disease, 2022)
BACKGROUND: Dementia is one of the main triggers for care dependency among older adults who are predominantly cared for at home by relatives. To provide support in the care situation, health systems need valid information about the central needs of the affected people. OBJECTIVE: The present study aimed to develop a research instrument to assess the most important needs of people with dementia and their family caregivers. METHODS: The development of the 'Dementia Assessment of Service Needs (DEMAND)' took place within the project 'Digital Dementia Registry Bavaria (digiDEM Bayern)'. A focus group and an online survey with dementia experts were conducted to identify the most relevant support services and to develop the design of the instrument. The questionnaire was deployed in the digiDEM baseline data collection. Participants were asked to evaluate the comprehensibility of the questionnaire. Readability was assessed using the Flesch reading ease score. RESULTS: Seventeen experts participated in the focus group and 59 people in the online survey. The final questionnaire included 13 support services. One hundred eighty-three participants (50 people with dementia and 133 family caregivers) completed the questionnaire at baseline. The mean comprehensibility score was 3.6 (SD = 2.3). The Flesch reading ease score result was 76. CONCLUSION: A research instrument could be developed, enabling people with dementia and family caregivers to directly express their individual needs for specific support services. Results show that the DEMAND is easy to understand and short in execution. Therefore, supply gaps can be identified and transformed into a specific health care plan.
CRIS-Team Scopus Importer:2022-10-21
Keywords: Demand; dementia; digiDEM; health services research; needs; resource use

The DemWG study: reducing the risk of hospitalisation through a complex intervention for people with dementia and mild cognitive impairment (MCI) in German shared-housing arrangements: study protocol of a prospective, mixed-methods, multicentre, cluster-randomised controlled trial - Kratzer, André; Scheel, Jennifer; Wolf-Ostermann, Karin; Schmidt, Annika; Ratz, Katrin; Donath, Carolin; Grässel, Elmar (BMJ Open, 2020)
INTRODUCTION: Shared-housing arrangements (SHAs) are small, home-like care environments in Germany. Residents are predominantly people with dementia. The risk for all-cause hospitalisation is consistently higher for people with dementia compared with people without dementia and there is currently no evidence-based intervention to reduce the risk of hospitalisation. Thus, the DemWG study investigates whether a complex intervention is effective in reducing hospitalisation (primary outcome), behavioural and psychological symptoms of dementia and falls and for stabilising cognitive functioning and quality of life in people with dementia and mild cognitive impairment (MCI) in German SHAs. METHODS AND ANALYSIS: Based on the UK Medical Research Council framework 'Developing and evaluating complex interventions', a prospective, mixed-methods, multicentre, cluster-randomised controlled trial combining primary and secondary data analyses as well as quantitative and qualitative research methods is being conducted. The intervention consists of three parts: (A) education of nursing staff in SHAs; (B) awareness raising and continuing medical education (CME) of general practitioners; (C) multicomponent non-pharmacological group intervention MAKS-mk+ ('m'=motor training; 'k'=cognitive training; '+'=fall prevention) for people with dementia and MCI. Randomisation is stratified by the German federal states and type of setting (rural vs urban). Neither the trained professionals nor the participants are blinded. Data are collected at baseline and after 6, 12 and 18 months with standardised instruments. Quantitative data will be analysed by multivariate analyses according to the general linear model, qualitative data using qualitative content analysis. Recruitment is still ongoing until 31 December 2020. ETHICS AND DISSEMINATION: All procedures were approved by the Ethics Committee of the University of Bremen (Ref. 2019-18-06-3). Informed consent will be obtained before enrolment of participants. Due to findings of previous randomised controlled trials, serious adverse events are not expected. Results will be disseminated in peer-reviewed journal publications and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN89825211.
CRIS-Team Scopus Importer:2020-12-11
Keywords: delirium & cognitive disorders; dementia; geriatric medicine

The dopamine D1 receptor antagonist SCH-23390 blocks the acquisition, but not expression of mitragynine-induced conditioned place preference in rats - Japarin, Rima Atria; Harun, Norsyifa; Hassan, Zurina; Müller, Christian P. (Behavioural Brain Research, 2023)
Mitragynine (MG) is the primary active constituent of Mitragyna speciosa Korth (kratom), a psychoactive Southeast Asian plant with potential therapeutic use. Numerous studies support roles of dopaminergic system in drug reward. However, the involvement of the dopaminergic system in mediating MG reward and drug-seeking is poorly understood. Using conditioned place preference (CPP) paradigm, the present study aims to evaluate the roles of the dopamine (DA) D1 receptor in the acquisition and expression of MG-induced CPP in rats. The effects of SCH-23390, a selective DA D1 receptor antagonist, on the acquisition of MG-induced CPP were first investigated. Rats were pre-treated systemically with SCH-23390 (0, 0.1 and 0.3 mg/kg, i.p.) prior to MG (10 mg/kg) conditioning sessions. Next, we tested the effects of the DA D1 receptor antagonist on the expression of MG-induced CPP. Furthermore, the effects of a MG-priming dose (5 mg/kg) on the reinstatement of extinguished CPP were tested. The results showed that SCH-23390 dose-dependently suppressed the acquisition of a MG-induced CPP. In contrast, SCH-23390 had no effect on the expression of a MG-induced CPP. The findings of this study suggested a crucial role of the DA D1 receptor in the acquisition, but not the expression of the rewarding effects of MG in a CPP test. Furthermore, blockade of the D1-like receptor during conditioning did not prevent MG priming effects on CPP reinstatement test, suggesting no role for the DA D1 receptor in reinstatement sensitivity.
CRIS-Team Scopus Importer:2023-09-08
Keywords: Conditioned-place Preference; Dopamine; Kratom; Mitragynine; Opioid; Rats

The Dysmorphic Concern Questionnaire in the German General Population: Psychometric Properties and Normative Data - Schieber, Katharina; Kollei, Ines; Zwaan, Martina De; Martin, Alexandra (Aesthetic Plastic Surgery, 2018)
BACKGROUND: The Dysmorphic Concern Questionnaire (DCQ) is a widely used screening instrument assessing dysmorphic concerns ranging from a mild to an excessive level. It is often used in the setting of plastic and aesthetic surgery. The present study aimed at examining the psychometric properties of the DCQ in a random general population sample. METHODS: A representative sample of the German general population (N = 2053, aged between 18 and 65 years, 54% females) completed the DCQ as well as questionnaires on depression and appearance concerns. RESULTS: The DCQ showed a good internal consistency with Cronbach's α = 0.81. Its one-factor model structure was confirmed. Normative data were stratified according to gender and age. Women reported more dysmorphic concerns than men, but also within females the DCQ scores differed between age classes. Overall, 4.0% of the sample reported excessive dysmorphic concerns based on a previously defined cutoff sum score ≥ 11. CONCLUSION: The DCQ is a valid and reliable screening tool to identify individuals with excessive dysmorphic concerns. Excessive concerns may indicate also the presence of body dysmorphic disorder, but for verifying a final diagnosis the use of a structured clinical interview is necessary. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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The effect object paradigm - a means to support medication safety with clinical decision support - Patapovas, Andrius; Pfistermeister, Barbara; Tarkhov, Aleksey; Terfloth, Lothar; Maas, Renke; Fromm, Martin; Kornhuber, Johannes; Prokosch, Hans-Ulrich; Bürkle, Thomas (Studies in health technology and informatics, 2014)
In many countries, officially approved drug information known as summary of product characteristics (SPC) is mostly available in text form, which cannot be used for Clinical Decision Support Systems (CDSS). It may be essential however to substantiate CDSS advice with such legally binding text snippets. In an attempt to link various drug data sources including SPC towards a CDSS to support medication safety in psychiatric patients we arrived at the notion of an effect object.A requirements analysis revealed data items and data structure which are needed from the patient and from the drug information source for the CDSS functionality. Published drug data modelling approaches were analyzed and found unsuitable. A conceptional database modeling approach using top down and bottom up modeling was performed.The schema based data model implemented within the django framework centered on SPC "effect objects" which comprise all SPC data required for the respective CDSS function such as search for contraindications in the proposed medication. Today six effect objects have been defined for contraindications and warnings, missing indications, adverse effects, drug-drug interactions, dosing and pharmacokinetics.The transformation of SPC data to a database-driven "effect objects" structure permits decoupling between the CDSS functions and different underlying data sources and supports the design of reusable, stable and verified CDSS functions.
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The Effect of Digital Mindfulness Interventions on Depressive, Anxiety, and Stress Symptoms in Pregnant Women: A Systematic Review and Meta-Analysis - Mefrouche, Monique L.; Siegmann, Eva-Maria; Böhme, Stephanie; Berking, Matthias; Kornhuber, Johannes (European Journal of Investigation in Health, Psychology and Education, 2023)
Introduction. Pregnancy is a unique time in a woman’s life that can be both exciting and challenging. It is also a period that can be associated with significant stress, anxiety, and depression, which can have negative consequences for both the mother and the baby. Mindfulness interventions are known to be a well-suited treatment and prevention method for psychiatric symptoms in pregnancy, and web-based applications have been explored. We here present an up-to-date systematic review and meta-analysis of randomized–controlled trials to investigate the effect of digital-based mindfulness interventions on depressive, anxiety, and stress symptoms during pregnancy. Methods. The systematic literature search and data extraction was performed by two independent raters. It resulted in 13 eligible studies overall comprising 1373 participants. We conducted random-effects meta-analyses for depressive, anxiety, and stress symptoms after completion of a digital mindfulness intervention (compared to a control group). Results. Digital mindfulness intervention methods were significantly able to reduce depression (g = −0.47, 95% CI [−0.9; −0.09]) and anxiety symptoms (g = −0.41, 95% CI [−0.77; −0.05]), but not stress symptoms. These effects were moderated by the attrition rate (βDepression = 0.025, pDepression < 0.01; βAnxiety = 0.022, pAnxiety < 0.01; βStress = 0.022, pStress < 0.01). Primiparity also had a significant influence on the intervention effect regarding depression symptoms (β = 0.033, p = 0.024). Conclusions. Digital mindfulness interventions are a promising method to reduce mental health symptoms in pregnant women. We identified certain parameters moderating this effect, for example, primiparity and the attrition rate.
CRIS-Team Scopus Importer:2023-10-27
Keywords: anxiety; depression; digital; meta-analysis; mindfulness; pregnancy; stress

The effect of dronabinol in a male patient with anorexia nervosa suffering from severe acute urge to be physically active. - Graap, Holmer; Erim, Yesim; Paslakis, Georgios (International Journal of Eating Disorders, 2018)

The effect of the degree of relationship on the mental sensitivities of donors within the framework of live liver donation (LDLT) - Erim, Yesim; Beckmann, M. B.; Kroencke, S.; Senf, W.; Schulz, K. H. (Psychotherapie Psychosomatik Medizinische Psychologie, 2009)

The Effects of a Normal Rate versus a Slow Intervalled Rate of Oral Nutrient Intake and Intravenous Low Rate Macronutrient Application on Psychophysical Function - Two Pilot Studies - Denzer-Lippmann, Melanie; Bachlechner, Stephan; Wielopolski, Jan; Fischer, Marie; Büttner, Andrea; Dörfler, Arnd; Schöfl, Christof; Muench, Gerald; Kornhuber, Johannes; Thürauf, Norbert (Frontiers in Psychology, 2017)
Stomach distension and energy per time are factors influencing satiety. Moreover, different rates of nutrient intake induce different stomach distension. The goal of our studies was to elucidate the influence of different oral rates of nutrient intake (normal rate versus slow intervalled rate; study I) and intravenous low rate macronutrient application (protein, carbohydrate, fat) or placebo (study II) on psychophysical function. The pilot studies investigated the effects of 1) study I: a mixed nutrient solution (1/3 protein, 1/3 fat, 1/3 carbohydrates) 2) study II: intravenous macronutrient infusions (protein, carbohydrate, fat) or placebo on psychophysical function (mood, hunger, food craving, alertness, smell intensity ratings and hedonic ratings) in human subjects. In study I 10 male subjects (age range: 21-30 years) completed the study protocol participating in both test conditions and in study II 20 male subjects (age range: 19-41 years) completed the study protocol participating in all test conditions. Additionally, metabolic function was analyzed and cognitive and olfactory tests were conducted twice starting 100 min before the beginning of the intervention and 240 min after. Psychophysical (mood, hunger, fat-, protein-, carbohydrate-, sweets- and vegetable-craving), alertness and metabolic function tests were performed seven times on each examination day. Greater effects on hunger and food cravings were observed for normal rate of intake compared to slow intervalled rate of intake and intravenous low rate macronutrient application. Our findings potentially confirm that volume of the food ingested and a higher rate of energy per time contribute to satiety during normal rate of food intake, while slow intervalled rate of food intake and intravenous low rate macronutrient application showed no effects on satiation. Our results motivate the view that a certain amount of volume of the food ingested and a certain energy per time ratio are necessary to reduce hunger and food craving.
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Keywords: food ingestion; food intake; rate of food intake; psychophysical function; food craving; parenteral food administration; parenteral food intake

The effects of an overnight holding of whole blood at room temperature on haemoglobin modification and in vitro markers of red blood cell aging - Eckstein, Markus; Zimmermann, Rüdiger; Roth, T.; Hauck-Dlimi, B.; Strasser, E. F.; Xiang, Wei (Vox Sanguinis, 2015)
Some effects of the red blood cell (RBC) storage lesion are well documented whereas others are not. Whether a period of room temperature hold (RTH) during RBC production enhances the RBC storage lesion has remained controversial. In this study, we compared whole blood (WB)-derived RBCs produced after 24-h RTH with rapidly cooled (RC) RBCs and tested them for classical metabolic markers and signs of oxidative damage.SAGM-RBCs were prepared from mixed and split pairs (n = 12) of WB units. RBCs prepared after a 24-h period of RTH on day+1 after collection (RTH-RBCs) were compared with RC-RBCs. All RBCs were stored at 4°C for 42 days with assay of in vitro variables on days+1, +15, +22, +29 and +42. The study examined standard quality parameters, glutathione, catalase and superoxide dismutase (SOD) activities, and indicative markers of oxidative cell damage including post-translational haemoglobin modification, malondialdehyde (MDA), and phosphatidylserine expression.RTH-RBCs exhibited decreased levels of potassium (1·98 ± 0·26 vs. 5·23 ± 0·65 mmol/l) and of 2,3-diphosphoglycerate (2,3-DPG) on day+1 compared with RC-RBCs. Haemolysis rate on day+42 was higher in RTH-RBCs than in RC-RBCs (0·52 ± 0·13 vs. 0·37 ± 0·12%). The phosphatidylserine expression amounted to 0·25 ± 0·20% in RTH-RBCs and 0·07 ± 0·12% in RC-RBCs. Haemoglobin modification was not different between both RBC groups. RTH-RBCs showed slightly higher MDA concentration on days +29 and +42.RC-RBCs and RTH-RBCs show only small differences of classical in vitro parameters and no relevant differences in antioxidative metabolism and oxidative haemoglobin modification. These findings do not explain the loss observed in in vivo survival studies with RBCs.
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The effects of chronic mitragynine (Kratom) exposure on the EEG in rats - Suhaimi, Farah Wahida; Hassan, Zurina; Mansor, Sharif Mahsufi; Müller, Christian P. (Neuroscience Letters, 2021)
Mitragynine is the main alkaloid isolated from the leaves of Mitragyna speciosa Korth (Kratom). Kratom has been widely used to relieve pain and opioid withdrawal symptoms in humans but may also cause memory deficits. Here we investigated the changes in brain electroencephalogram (EEG) activity after acute and chronic exposure to mitragynine in freely moving rats. Vehicle, morphine (5 mg/kg) or mitragynine (1, 5 and 10 mg/kg) were administered for 28 days, and EEG activity was repeatedly recorded from the frontal cortex, neocortex and hippocampus. Repeated exposure to mitragynine increased delta, but decreased alpha powers in both cortical regions. It further decreased delta power in the hippocampus. These findings suggest that acute and chronic mitragynine can have profound effects on EEG activity, which may underlie effects on behavioral activity and cognition, particularly learning and memory function.
CRIS-Team Scopus Importer:2021-01-29
Keywords: EEG; Kratom; Mitragynine; Morphine

The Effects of Different Isocaloric Oral Nutrient Solutions on Psychophysical, Metabolic, Cognitive, and Olfactory Function in Young Male Subjects - Bachlechner, Stephan; Denzer-Lippmann, Melanie Y.; Wielopolski, Jan; Fischer, Marie; Büttner, Andrea; Dörfler, Arnd; Schöfl, Christof; Muench, Gerald; Kornhuber, Johannes; Thürauf, Norbert (Frontiers in Psychology, 2017)
Food intake influences human cognition, olfaction, hunger, and food craving. However, little research has been done in this field to elucidate the effects of different nutrients. Thus, the goal of our study was to investigate the effects of oral ingestion of different nutrient solutions on olfactory, cognitive, metabolic and psychophysical function. Twenty healthy men participated in our study employing a double-blind, cross-over, repeated measurement design. Participants were tested on four different study days. Each day participants received, in randomized order, one of three isocaloric (protein, carbohydrate or fat 600 kcal, 1,500mL) solutions or a placebo. Olfactory and cognitive tests (monitoring only) were conducted three times, i.e., 60min before the beginning of nutrient intake, following oral ingestion of the solution and 60, and 240min after. Psychophysical and metabolic function tests (active grehlin, desacyl ghrelin, insulin, glucagon, glucose, triglyceride, urea) were performed 7 times on each examination day (observation period: -60min, 0 = solution intake, +60, +120, +180, +240, and +300min). Ratings of hunger and food craving significantly differed over the observation period with lowest ratings following application of the protein solution. Highest ratings of craving were found following placebo intake. We further observed a significant positive correlation of active grehlin with hunger and fat, protein and sweets craving for each nutrient solution. Active grehlin significantly correlated with carbohydrate craving for carbohydrate and fat solution and with vegetable craving for fat solution only. Hunger hormone levels, hunger and food craving ratings demonstrated that the hierarchical order that appears in satiating efficiencies of isovolumetric-isocaloric ingested macronutrients is protein > fat > carbohydrate. Our study reveals that the type of nutrient exerts a significant influence on metabolic parameters, hunger and food craving.
Keywords: food ingestion; food intake; oral intake; olfaction; psychophysical function

The effects of exercise programs on cognition, activities of daily living, and neuropsychiatric symptoms in community-dwelling people with dementia-a systematic review - Steichele, Kathrin; Keefer, Anne; Dietzel, Nikolas; Grässel, Elmar; Prokosch, Hans-Ulrich; Kolominsky-Rabas, Peter (Alzheimer's Research and Therapy, 2022)
Background: The prevalence of dementia is expected to increase dramatically. Due to a lack of pharmacological treatment options for people with dementia, non-pharmacological treatments such as exercise programs have been recommended to improve cognition, activities of daily living, and neuropsychiatric symptoms. However, inconsistent results have been reported across different trials, mainly because of the high heterogeneity of exercise modalities. Thus, this systematic review aims to answer the questions whether exercise programs improve cognition, activities of daily living as well as neuropsychiatric symptoms in community-dwelling people with dementia.
CRIS-Team WoS Importer:2022-08-05

The Epigenetic Regulation of GATA4-Dependent Brain Natriuretic Peptide Expression during Alcohol Withdrawal - Glahn, Alexander; Rhein, Mathias; Heberlein, Annemarie; Muschler, Marc; Kornhuber, Johannes; Frieling, Helge; Bleich, Stefan; Hillemacher, Thomas (Neuropsychobiology, 2016)
Natriuretic peptides participate in the collection of metabolic effects during alcohol withdrawal. Having witnessed modulation of other natriuretic peptides in alcohol-dependent patients during alcohol withdrawal, we were interested in the relation of brain natriuretic peptide (BNP) methylation with protein expression and craving in this longitudinal study.Ninety-nine male patients were compared to 101 healthy controls concerning epigenetic regulation and protein expression during detoxification treatment.With BNP expression being GATA4 dependent, we observed a correlation of GATA4 binding site methylation and protein expression. BNP serum levels and Obsessive Compulsive Drinking Scale scores are significantly decreased during withdrawal. Focusing on the two CpGs that are between GATA transcription factor binding sites, statistical analysis revealed a reversely proportional methylation pattern, significantly increasing with ongoing detoxification and thereby supporting the observed serum level changes.Without the functional knowledge about regulation of BNP expression via the GATA transcription factor, it would have been easy to take the mean results of the global CpG data and propose a direct relationship between methylation and expression. Thus, these findings are a voice for functionally and mechanistically approved results. There was no causal relationship between protein expression levels and epigenetic changes. Further research is needed which includes protein expression and other approaches.
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The "Erlangen System" of open care: a tribute to Gustav Kolb (1870-1938) - Braun, B.; Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2014)
This year marks the 80th anniversary of the forced retirement (1st March 1934) of Gustav Kolb (1870 - 1938). He is considered the founder of the "Erlangen System" of open care. The following article pays tribute to Gustav Kolb's "life's work", by delineating the formation, active period and the fall of his "Erlangen system" in its historical context.Relevant archive materials and secondary literature were assessed.Beginning in 1914, Gustav Kolb, as Director of the Mental Asylum in Erlangen (1911 - 1934) introduced the care of the emotionally ill in their own families. In 1930, 4200 of the 770 000 residents in a catchment area covering about 3200 square kilometers were being treated in open care. The "Erlangen system" was the largest organisation of its kind in Germany. Although Gustav Kolb was inspired by eugenic ideas, he opposed the national-socialist health politics. Kolb withdrew professionally in 1933 and died five years later.The situation in the tense area of open care between helping institutions for and controlling bodies over emotionally ill people was relatively balanced in the Weimar Republic. Later, Gustav Kolb's organisational thoroughness, with its creation of a central register of people under open care in the Erlangen system, provided considerable biogenetic information. Tragically, this was abused as an important source in carrying out the national-socialist law for prevention of genetically-impaired offspring (14.7.1933). Several aspects contributed to the misfortune that Kolb's liberal system could be distorted to a recording instrument by the National Socialists. Final Comment: Individual efforts to reestablish open care facilities after 1945 were not implemented. It was not until during the socio-psychiatric movement of the 1960 s that Kolb's concept could achieve a renaissance, although it was unnamed and unrecognised at the time.
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The Erlangen test of activities of daily living in persons with mild dementia or mild cognitive impairment (ETAM) - an extended validation - Book, Stephanie; Luttenberger, Katharina; Stemmler, Mark; Meyer, Sebastian; Grässel, Elmar (BMC Psychiatry, 2018)
BACKGROUND: The ability to perform activities of daily living (ADLs) is a central marker in the diagnosis and progression of the dementia syndrome. ADLs can be identified as basic ADLs (BADLs), which are fairly easy to perform, or instrumental ADLs (IADLs), which involve more complex activities. Presently, the only performance-based assessment of IADL capabilities in persons with cognitive impairment is the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM). The aim of the present study was to revalidate the ETAM in persons with mild cognitive impairment (MCI) or mild dementia and to analyze its application to persons with moderate dementia. METHODS: We used baseline data from a cluster randomized controlled trial involving a sample of 443 users of 34 day-care centers in Germany. We analyzed groups of persons with MCI, mild dementia, and moderate dementia, categorized on the basis of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). An item analysis was performed, and new discriminant validities were calculated. We computed a confirmatory factor analysis (CFA) to examine the postulated theoretical model of the ETAM with all six items loading on a single IADL factor. This was the first time that the ETAM's sensitivity to change was analyzed after a time period of 6 months. RESULTS: The overall sample scored on average 17.3 points (SD = 7.2) on the ETAM (range: 0-30 points). Persons with MCI scored on average 23.2 points, persons with mild dementia scored 18.4 points, and persons with moderate dementia scored 12.9 points, p < .001 (ANOVA). The item analysis yielded good difficulty indices and discrimination powers. The CFA indicated a good fit between the model and the observed data. After 6 months, both the ETAM score at baseline and the change in MMSE score (t0-t1) were significant predictors of the ETAM score at t1. CONCLUSIONS: The ETAM is a valid and reliable instrument for assessing IADL capabilities in persons with MCI or mild dementia. It is sensitive to changes in cognitive abilities. The test parameters confirm its application to persons with moderate dementia. TRIAL REGISTRATION: Identifier: ISRCTN16412551 (Registration date: 30 July 2014, registered retrospectively).
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The Essen Trauma Inventory - A screening instrument for the identification of traumatic events and post-traumatic disorders - Tagay, Sefik; Erim, Yesim; Stoelk, Babette; Möllering, Andrea; Mewes, Ricarda; Senf, Wolfgang (Zeitschrift für Psychotraumatologie, Psychotherapiewissenschaft, psychologische Medizin, 2007)

The evaluation of new psychoactive drugs - Müller, Christian P.; Hassan, Zurina (Brain Research Bulletin, 2016)
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The Father’s Part: A Pilot Evaluation of a Father-Centered Family Intervention Group in Child and Adolescent Psychiatry - Mestermann, Stefan; Kleinöder, Jonas; Arndt, Marie; Krämer, Josef; Eichler, Anna; Kratz, Oliver (Behavioral Sciences, 2024)
Changes in parental roles have renewed the focus on a father’s involvement in an offspring’s psychological development. However, fathers are still under-represented in family research. There are only a few structured father-centered intervention programs in child and adolescent psychiatry. In a German population sample, a pilot father-centered family intervention program with n = 16 participants, conducted in person (n = 8) and online (n = 8), in a child and adolescent psychiatry inpatient/day clinic setting was evaluated by comparing paternal stress, PSE, and child-rated paternal competence in a pre–post design. Participating fathers showed significant decreases in child-related parenting stress (presence: p = 0.042, online: p = 0.047) and significant increases in PSE (p = 0.006/0.012). Parent-related stress and child-rated paternal competence were unaffected (p = 0.108/0.171; p = 0.167/0.101), while small-to-medium effect size measures pointed in the direction of our hypothesis (d = 0.48/0.36; d = 0.37/0.50). Participant satisfaction was higher in person than online (p = 0.008). As social and biological fathers have important influences on child and adolescent well-being and development, they should be included more frequently in prevention and intervention programs. Fathers seem to benefit from gender-specific intervention programs with regard to stress reduction, as well as experiencing competence- and PSE-increasing effects.
CRIS-Team Scopus Importer:2024-03-08
Keywords: child development; parent-centered interventions; parental behavior; parenting stress; parent–child-relation

The Father’s Part: Influences of Paternal Psychopathology and Parenting Behavior on Child and Adolescent Well-Being - Mestermann, Stefan; Arndt, Marie; Fasching, Peter; Beckmann, Matthias; Kratz, Oliver; Moll, Gunther; Kornhuber, Johannes; Eichler, Anna (Healthcare, 2023)
Family influences on child quality of life (QoL) are increasingly understood. Parenting behavior and parent individual psychopathology are among the established predictors of offspring mental health. However, literature often addresses these factors as ‘parental’, lacking further gender-specific differentiation while predominantly studying maternal aspects. Social and biological fathers are still underrepresented in family research. The aim of this study was to analyze paternal contributions to child well-being. A total of 197 father/mother-dyads gave a standardized self-report on parenting behavior and their own psychopathology at child primary school age (t1; 6–10 y). Ratings were compared mutually and associated with child self-rated QoL at t1 and adolescence (t2; 12–14 y). Fathers and mothers differed in psychopathology and most parenting behavior dimensions (positive parenting, involvement, responsible parenting, poor monitoring, and corporal punishment). Father psychopathology made a relevant predictive contribution to girls’ QoL at t2. Boys’ t1 QoL was significantly influenced by maternal parenting factors (positivity and corporal punishment). Compared to mothers, fathers are faced with different individual stressors; paternal parenting behavior is different, while fathers’ influences are significant, particularly for daughters. Father-addressed pre- and intervention programs in child psychotherapeutic treatment are of high relevance.
CRIS-Team Scopus Importer:2023-08-25
Keywords: child development; father; parent-child-relations; parental influence; parenting; parenting behavior; resilience

The Forebrain-Specific Overexpression of Acid Sphingomyelinase Induces Depressive-Like Symptoms in Mice - Zoicas, Iulia; Schumacher, Fabian; Kleuser, Burkhard; Reichel, Martin; Gulbins, Erich; Fejtová, Anna; Kornhuber, Johannes; Rhein, Cosima (Cells, 2020)
Human and murine studies identified the lysosomal enzyme acid sphingomyelinase (ASM) as a target for antidepressant therapy and revealed its role in the pathophysiology of major depression. In this study, we generated a mouse model with overexpression of Asm (Asm-tgfb) that is restricted to the forebrain to rule out any systemic effects of Asm overexpression on depressive-like symptoms. The increase in Asm activity was higher in male Asm-tgfb mice than in female Asm-tgfb mice due to the breeding strategy, which allows for the generation of wild-type littermates as appropriate controls. Asm overexpression in the forebrain of male mice resulted in a depressive-like phenotype, whereas in female mice, Asm overexpression resulted in a social anxiogenic-like phenotype. Ceramides in male Asm-tgfb mice were elevated specifically in the dorsal hippocampus. mRNA expression analyses indicated that the increase in Asm activity affected other ceramide-generating pathways, which might help to balance ceramide levels in cortical brain regions. This forebrain-specific mouse model offers a novel tool for dissecting the molecular mechanisms that play a role in the pathophysiology of major depression.
CRIS-Team Scopus Importer:2020-06-05
Keywords: acid sphingomyelinase; anxiety-like behavior; ceramide; depressive-like behavior; forebrain; Smpd1

The frequency and influence of dementia risk factors in prodromal Alzheimer's disease - Bos, Isabelle; Vos, Stephanie J.; Froelich, Lutz; Kornhuber, Johannes; Wiltfang, Jens; Maier, Wolfgang; Peters, Oliver; Ruether, Eckhart; Engelborghs, Sebastiaan; Niemantsverdriet, Ellis; De Roeck, Ellen Elisa; Tsolaki, Magda; et al. (Neurobiology of Aging, 2017)
We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity, and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared with those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with mild cognitive impairment. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e., preclinical) of AD.
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The German day-care study: multicomponent non-drug therapy for people with cognitive impairment in day-care centres supplemented with caregiver counselling (DeTaMAKS) - study protocol of a cluster-randomised controlled trial - Behrndt, Elisa-Marie; Straubmeier, Melanie; Seidl, Hildegard; Book, Stephanie; Grässel, Elmar; Luttenberger, Katharina (BMC Health Services Research, 2017)
BACKGROUND: It is the wish of both people with cognitive impairment and their informal caregivers for the impaired person to live at home for as long as possible. This is also in line with economic arguments about health. The existing structure of day-care services for the elderly can be used to achieve this. Due to the current lack of empirical evidence in this field, most day-care centres do not offer a scientifically evaluated, structured intervention, but instead offer a mixture of individual activities whose efficacy has not yet been established. Informal caregivers of people with dementia use day-care centres primarily to relieve themselves of their care tasks and as a support service. METHODS/DESIGN: The present study therefore investigates the effectiveness of a combination of a multicomponent activation therapy for people with mild cognitive impairment (MCI) or mild to moderate dementia at day-care centres and a brief telephone intervention for their informal caregivers. The study is conducted as a cluster-randomised intervention trial at 34 day-care centres in Germany with a 6-month treatment phase. The centres in the waitlist control group provide "care as usual". A power analysis indicated that 346 people should initially be included in the study. The primary endpoints of the study include the ability to perform activities of daily living (ADL) and cognitive capacities on the side of the day-care centre users and the subjectively perceived burden and well-being of the informal caregivers. The total duration of the study is 3 years, during which data are collected both by the psychometric testing of the people with cognitive impairment and by telephone interviews with informal caregivers. DISCUSSION: The project has three distinctive quality features. First, it is embedded in real care situations since the day-care services have already been established for this target group. Second, due to the large number of cases and the fact that the participating day-care centres are spread across the entire country, the results can be expected to be generalisable. Third, the interventions can be assumed to be implementable as they required only a one-day training event for the staff already working at the centres. TRIAL REGISTRATION: ISRCTN16412551 (Registration date: 30 July 2014, registered retrospectively).
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The Health Economic Impact of Resource use in Dementia: the Erlanger Dementia Registry (EDR). - Schaller, S. U.; Marinova-Schmidt,; Gobin, J.; Luttenberger, Katharina; Richter-Schmidinger, T.; Grässel, Elmar; Maler, Juan Manuel; Kornhuber, Johannes; Kolominsky-Rabas, Peter (Value in Health, 2014)
Dementia patients are in need of more extensive personal care compared to other long-term care users. This Results in a high economic impact of dementia on patients, families and healthcare systems. Due to the increasing prevalence of dementia worldwide, combined with limited healthcare expenditures, a better understanding of resource use in dementia care is needed. Therefore the aim of our study is the assessment of resource use in dementia in the most common setting: home-based care (informal caregivers).<br
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The hedonics of olfactory induced memories - a new model for the analyses of emotional blunting - Thürauf, Norbert; Sollmann, Manuel; Fuchs, Michael; Jäger, Jakob; Mettang, Melissa; Reich, Karin; Kornhuber, Johannes; Sperling, Wolgang; Freiherr, Jessica (CHEMICAL SENSES, 2020)
CRIS-Team WoS Importer:2020-06-23

The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review - Hansson, Oskar; Mikulskis, Alvydas; Fagan, Anne M.; Teunissen, Charlotte; Zetterberg, Henrik; Vanderstichele, Hugo; Molinuevo, Jose Luis; Shaw, Leslie M.; Vandijck, Manu; Verbeek, Marcel M.; Savage, Mary; Mattsson, Niklas; et al. (Alzheimers & Dementia, 2018)
INTRODUCTION: Cerebrospinal fluid (CSF) biomarkers have the potential to improve the diagnostic accuracy of Alzheimer's disease, yet there is a lack of harmonized preanalytical CSF handling protocols. METHODS: This systematic review summarizes the current literature on the influence of preanalytical variables on CSF biomarker concentration. We evaluated the evidence for three core CSF biomarkers: β-amyloid 42, total tau, and phosphorylated tau. RESULTS: The clinically important variables with the largest amount of conflicting data included the temperature at which samples are stored, the time nonfrozen samples can be stored, and possible effects of additives such as detergents, blood contamination, and centrifugation. Conversely, we discovered that there is consensus that tube material has a significant effect. DISCUSSION: A unified CSF handling protocol is recommended to reduce preanalytical variability and facilitate comparison of CSF biomarkers across studies and laboratories. In future, experiments should use a gold standard with fresh CSF collected in low binding tubes.
EVALuna2:202451

The impact of the coronavirus disease (COVID-19) pandemic on outpatient epilepsy care: An analysis of physician practices in Germany - Müller, Tamara; Kostev, Karel; Gollwitzer, Stephanie; Lang, Johannes; Stritzelberger, Jenny; Westermayer, Vivien; Reindl, Caroline; Hamer, Hajo (Epilepsy & Behavior, 2021)
Objective: To gain insight into epilepsy care during coronavirus disease (COVID-19) pandemic, we analyzed prescription data of a large cohort of persons with epilepsy (PWE) during lockdown in Germany. Methods: Information was obtained from the Disease Analyzer database, which collects anonymous demographic and medical data from practice computer systems of general practitioners (GP) and neurologists (NL) throughout Germany. We retrospectively compared prescription data for anti-seizure medication (ASM) and physicians’ notes of “known” and “new” PWE from January 2020 until May 2020 with the corresponding months in the three preceding years 2017–2019. Adherence was estimated by calculating the proportion of patients with follow-up prescriptions within 90 days after initial prescriptions in January or February. We additionally analyzed hospital referrals of PWE. The significance level was set to 0.01 to adjust for multiple comparisons. Results: A total of 52,844 PWE were included. Anti-seizure medication prescriptions for known PWE increased in March 2020 (GP + 36%, NL + 29%; P < 0.01). By contrast, a decrease in prescriptions to known and new PWE was observed in April and significantly in May 2020 ranging from −16% to −29% (P < 0.01). The proportion of PWE receiving follow-up prescriptions was slightly higher in 2020 (73.5%) than in 2017–2019 (70.7%, P = 0.001). General practitioners and NL referred fewer PWE to hospitals in March 2020 (GP: −30%, P < 0.01; NL: −12%), April 2020 (GP: −29%, P < 0.01; NL: −37%), and May 2020 (GP: −24%, P < 0.01; NL: −16%). Conclusion: Adherence of known PWE to ASM treatment appeared to remain stable during lockdown in Germany. However, this study revealed findings which point to reduced care for newly diagnosed PWE as well as fewer hospital admissions. These elements may warrant consideration during future lockdown situations.
CRIS-Team Scopus Importer:2021-03-05
Keywords: Anti-seizure drugs; COVID-19; Epilepsy care

The impact of the COVID-19 pandemic on pediatric developmental services: a cross-sectional study on overall burden and mental health status - Borusiak, Peter; Mazheika, Yuliya; Bauer, Susanne; Haberlandt, Edda; Krois, Ilona; Fricke, Christian; Simon, Liane; Beschoner, Petra; Jerg-Bretzke, Lucia; Geiser, Franziska; Hiebel, Nina; Weidner, Kerstin; et al. (Archives of Public Health, 2022)
Background The COVID-19 outbreak has taken a heavy toll on the mental well-being of healthcare workers, even those who have not been directly involved in the care of acutely ill patients. The aims of this study were to identify the overall burden and mental health status of healthcare workers in pediatric developmental services under the influence of the COVID-19 pandemic, and to identify the risk and protective factors associated with mental health. Methods This cross-sectional web-based study was part of a large multicenter VOICE study conducted among employees ((neuro-)pediatricians, psychologists, speech therapists, occupational therapists, etc.) from various pediatric developmental services between June and July 2020. A total of 1291 questionnaires regarding overall burden, mental health status (depression, generalized anxiety disorder and emotional exhaustion) and risk and protective factors for mental health (working conditions, potential problems during the COVID-19 pandemic and psychological resources) were analyzed. Descriptive statistics and multiple linear regression were used for data analysis. Results A total of 44.5% (574/1291) participants felt a high or very high overall burden during the COVID-19 pandemic. Of all the participants, 14.6% (171/1173) reported clinically significant levels of depressive symptoms, 17.0% (199/1173) reported generalized anxiety disorder symptoms and 44.6% (532/1192) reported emotional exhaustion. Multiple linear regression analyses identified several common risk and protective factors for mental health status variables. The burden of an increase in the quantity of work, fear of work and fear of becoming infected showed the strongest negative associations, whereas psychological resources and sufficient relaxation in leisure time exhibited the strongest positive associations. Conclusion Employees who were not directly involved in the care of acutely ill patients were also exposed to considerable stress, some of which was not different from that experienced by professionals who were directly affected. These employees should not be lost sight of and must be offered appropriate support.
CRIS-Team WoS Importer:2022-04-29

The impact of the COVID-19 pandemic on the mental health of medical staff considering the interplay of pandemic burden and psychosocial resources-A rapid systematic review - Hannemann, Julian; Abdalrahman, Alan; Erim, Yesim; Morawa, Eva; Jerg-Bretzke, Lucia; Beschoner, Petra; Geiser, Franziska; Hiebel, Nina; Weidner, Kerstin; Steudte-Schmiedgen, Susann; Albus, Christian (PLoS ONE, 2022)
Background In times of the global corona pandemic health care workers (HCWs) fight the disease at the frontline of healthcare services and are confronted with an exacerbated load of pandemic burden. Psychosocial resources are thought to buffer adverse effects of pandemic stressors on mental health. This rapid review summarizes evidence on the specific interplay of pandemic burden and psychosocial resources with regard to the mental health of HCWs during the COVID-19 pandemic. The goal was to derive potential starting points for supportive interventions. Methods We conducted a rapid systematic review following the recommendations of the Cochrane Rapid Reviews Methods Group. We searched 7 databases in February 2021 and included peer-reviewed quantitative studies, that reported related data on pandemic stressors, psychosocial resources, and mental health of HCWs. Results 46 reports were finally included in the review and reported data on all three outcomes at hand. Most studies (n = 41) applied a cross-sectional design. Our results suggest that there are several statistically significant pandemic risk factors for mental health problems in HCWs such as high risk and fear of infection, while resilience, active and emotion-focused coping strategies as well as social support can be considered beneficial when protecting different aspects of mental health in HCWs during the COVID-19 pandemic. Evidence for patterns of interaction between outcomes were found in the context of coping style when facing specific pandemic stressors. Conclusions Our results indicate that several psychosocial resources may play an important role in buffering adverse effects of pandemic burden on the mental health of HCWs in the context of the COVID-19 pandemic. Nevertheless, causal interpretations of mentioned associations are inadequate due to the overall low study quality and the dominance of cross-sectional study designs. Prospective longitudinal studies are required to elucidate the missing links.
CRIS-Team Scopus Importer:2022-03-04

The impact of the temporal sequence of cranial radiotherapy and platin-based chemotherapy on hearing impairment in pediatric and adolescent CNS and head-and-neck cancer patients: A report from the PanCareLIFE consortium - Scobioala, Sergiu; Parfitt, Ross; Matulat, Peter; Byrne, Julianne; Langer, Thorsten; Troschel, Fabian M.; Hesping, Amélie E.; Clemens, Eva; Kaatsch, Peter; Grabow, Desiree; Kaiser, Melanie; Spix, Claudia; et al. (International Journal of Cancer, 2023)
The impact of the temporal sequence by which cranial radiotherapy (CRT) and platin-based chemotherapy (PCth) are administered on sensorineural hearing loss (SNHL) in pediatric and adolescent central nervous system (CNS) and head-and-neck (HN) cancer patients has not yet been studied in detail. We examined the ototoxic effects of sequentially applied CRT and PCth. This study included children and adolescents with CNS and HN tumors who participated in the multicountry PanCareLIFE (PCL) consortium. Audiological outcomes were compared between patients who received CRT prior to PCth and those who received it afterwards. The incidence, degree and posttreatment progression of SNHL, defined as Muenster classification grade ≥MS2b, were evaluated in 141 patients. One hundred and nineteen patients were included in a time-to-onset analysis. Eighty-eight patients received CRT prior to PCth (Group 1) and 53 patients received PCth before CRT (Group 2). Over a median follow-up time of 1.6 years, 72.7% of patients in Group 1 experienced SNHL ≥ MS2b compared to 33.9% in Group 2 (P <.01). A time-to-onset analysis was performed for 74 patients from Group 1 and 45 patients from Group 2. Median time to hearing loss (HL) ≥ MS2b was 1.2 years in Group 1 and 4.4 years in Group 2 (P <.01). Thus, audiological outcomes were better for patients who received CRT after PCth than before. This finding should be further evaluated and considered within clinical practice in order to minimize hearing loss in children and adolescents with CNS and HN tumors.
CRIS-Team Scopus Importer:2023-09-29
Keywords: cranial radiotherapy; PanCareLIFE project; platin-based chemotherapy; posttreatment hearing loss; therapy sequence

The influence of patient-related factors on the frequency and duration of psycho-oncological sessions in a university cancer center - Madl, Martina; Lieb, Marietta; Schieber, Katharina; Erim, Yesim (Journal of Psychosocial Oncology, 2021)
Objective The present study aimed at identifying factors that are associated with the frequency and duration of psycho-oncological sessions. Design In a retrospective single-center study, data of all patients who made use of the psycho-oncological service (POS) at the University Hospital Erlangen from April 2017 - March 2018 were registered. Sample Over the course of one year, N = 1601 patients made use of the POS. Methods In the hospital's digital documentation system, relevant data such as frequency of sessions, duration of sessions, gender, age, family status, preexisting mental disorder, prior psychotherapy, cancer entity (type of cancer) and treatment modality were recorded. Socio-demographic and clinical parameters were analyzed to predict frequency and duration of the psycho-oncology sessions. Findings Regression analyses revealed that among POS users, women, younger patients, patients with a longer hospital stay and those with a preexisting mental disorder attended significantly more sessions than other patients (p < .001). Patients with skin cancer had significantly fewer POS sessions than those with a hematological diagnosis. Also, patients who had undergone surgery had significantly fewer sessions than patients with pharmacological treatment. Younger age and a longer hospital stay significantly predicted longer sessions (p < .001). In the regression model, patients with brain tumors and lung cancer had significantly longer sessions than patients with skin cancer. Implications With the identification of specific risk groups that require more and longer sessions, we can provide the basis for more patient-tailored intervention approaches and better scheduling according to the patients' needs. However, our results also suggest that the frequency and duration of POS sessions also depend on illness- and treatment-related criteria, e.g. the length of the hospital stay.
CRIS-Team WoS Importer:2021-12-10

The influence of prenatal risks on attachment, emotion regulation and emotional and behavioral problems in middle childhood: A prospective longitudinal study - Ziegler, Clara; Zalan, Vera; Eichler, Anna; Heinrich, Hartmut; Moll, Gunther; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Lenz, Bernd; Spangler, Gottfried (International Attachment Conference, 2017)

The influence of the setting on alcohol self-reports: a comparison of the setting of liver transplantation and rehabilitation therapy - Schieber, Katharina; Lindner, M.; Sowa, J. P.; Gerken, G.; Scherbaum, N.; Kahraman, A.; Canbay, A.; Erim, Yesim (Transplant International, 2014)

The interplay between adverse childhood experiences, COVID-19 associated burden and emotional exhaustion: Results of the egePan - VOICE Study - Kempf, Maximilian; Clemens, Vera; Beschoner, Petra; Weimer, Katja; Morawa, Eva; Geiser, Franziska; Albus, Christian; Steudte-Schmiedgen, Susan; Gundel, Harald; Fegert, Jorg M.; Jerg-Bretzke, Lucia (EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY, 2021)
CRIS-Team WoS Importer:2021-12-10

The interrelation between perceived discrimination, depressiveness, and health related quality of life in immigrants of Turkish and Polish origin - Morawa, Eva; Erim, Yesim (Psychiatrische Praxis, 2014)
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The Latent Dementia Phenotype ? is Associated with Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Predicts Conversion to Dementia in Subjects with Mild Cognitive Impairment - Koppara, Alexander; Wolfsgruber, Steffen; Kleineidam, Luca; Schmidtke, Klaus; Frölich, Lutz; Kurz, Alexander; Schulz, Stefanie; Hampel, Harald; Heuser, Isabella; Peters, Oliver; Reischies, Friedel M; Jahn, Holger; et al. (Journal of Alzheimer's Disease, 2015)
The recently proposed latent variable ? is a new tool for dementia case finding. It is built in a structural equation modeling framework of cognitive and functional data and constitutes a novel endophenotype for Alzheimer's disease (AD) research and clinical trials.To investigate the association of ? with AD biomarkers and to compare the prediction of ? with established scales for conversion to dementia in patients with mild cognitive impairment (MCI).Using data from a multicenter memory clinic study, we examined the external associations of the latent variable ? and compared ? with well-established cognitive and functional scales and cognitive-functional composite scores. For that purpose, logistic regressions with cerebrospinal fluid (CSF) biomarkers and conversion to dementia as dependent variables were performed with the investigated scores. The models were tested for significant differences.In patients with MCI, ? based on a broad range of cognitive scales (including the ADAS-cog, the MMSE, and the CERAD neuropsychological battery) predicted an abnormal CSF A?42/tau ratio indicative of AD (n = 340, AUC = 0.78, p < 0.001), and predicted incident dementia within 1-3 years of follow-up (n = 525, AUC = 0.84, p < 0.001). These associations were generally stronger than for any other scale or cognitive-functional composite examined. Homologs of ? based on reduced test batteries yielded somewhat lower effects.These findings support the interpretation of ? as a construct capturing the disease-related "essence" of cognitive and functional impairments in patients with MCI and dementia, and suggest that ? might become an analytical tool for dementia research.
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The MAKS-s study: multicomponent non-pharmacological intervention for people with severe dementia in inpatient care – study protocol of a randomised controlled trial - Diehl, Kristina; Kratzer, André; Grässel, Elmar (BMC Geriatrics, 2020)
Background: Nursing homes accommodate a large number of people with severe dementia. More than 80% of residents with dementia suffer from behavioural and psychological symptoms, that can have consequences on the perceived burden of the formal caregivers. Internationally, the number of studies on non-pharmacological interventions for people with severe dementia is very small. One way to reduce these symptoms is to meet the needs of people with severe dementia. The non-pharmacological group intervention MAKS-s, which we will investigate in this study, is intended to reduce the behavioural and psychological symptoms and to improve the quality of life of such people. Additionally, we will investigate the effects on the burden carried by formal caregivers. Methods: With the present study, we will investigate the effectiveness of a multicomponent non-pharmacological intervention for people with severe dementia living in nursing homes (primary target group). A power analysis indicated that 144 dementia participants should initially be included. In addition, a secondary target group (nursing home staff) will be examined with respect to their dementia-related stress experiences. The study will be conducted as a cluster randomised controlled trail in Germany with a 6-month intervention phase. The nursing homes in the waitlist control group will provide “care as usual.” The primary endpoints of the study will be the behavioural and psychological symptoms of dementia and the quality of life of people with severe dementia. The total duration of the study will be 18 months. Data will be collected by using observer rating scales. Discussion: The project has some outstanding quality features. The external validity is high, because it is situated in a naturalistic setting in nursing homes and is being carried out with available nursing employees. Due to this fact, a permanent implementation also seems to be possible. Since the participating nursing homes are disseminated across several German federal states and rural and urban regions, the results should be transferable to the entire population. Trial registration: ISRCTN15722923 (Registration date: 07 August 2019).
CRIS-Team Scopus Importer:2020-10-30
Keywords: Behavioural and psychological symptoms of dementia; Nursing home; Psychosocial intervention; Quality of life; RCT; Severe dementia

The Male Brain - Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2016)
EVALuna2:23789

The mediating role of COVID-19-related burden in the association between adverse childhood experiences and emotional exhaustion: results of the egePan - VOICE study - Clemens, Vera; Beschoner, Petra; Jarczok, Marc N.; Weimer, Katja; Kempf, Maximilian; Morawa, Eva; Geiser, Franziska; Albus, Christian; Steudte-Schmiedgen, Susan; Guendel, Harald; Fegert, J. M.; Jerg-Bretzke, Lucia (European Journal of Psychotraumatology, 2021)
Background Adverse childhood experiences (ACEs) increase the risk for mental health problems. However, there is a lack of data targeting the role of ACEs for one of the most prevalent mental health problems in health-care professionals: burnout. Objective We aimed to assess the relationship between ACEs and the core burnout dimension 'emotional exhaustion' (EE). As health-care professionals have been facing particular challenges during the COVID-19 pandemic, we furthermore aimed to assess the role of COVID-19 associated burden in the interplay between ACEs and EE. Methods During the first lockdown in Germany, a total of 2500 medical healthcare professionals were questioned in a cross-sectional online survey. Questions targeted, among others, sociodemographics, ACEs, COVID-19-associated problems (e.g. increase of workload, worries about relatives and patients) and emotional exhaustion, measured by the respective dimension of the Maslach Burnout Inventory (MBI). Results In German health-care professionals, ACEs were associated with a higher EE score. The number of experienced ACEs was associated with the majority of assessed COVID-19-associated problems. An increasing number of ACEs predicted higher EE scores, controlling for gender. The association between ACEs and EE was mediated significantly by COVID-19-associated problems. These included maladaptive coping strategies such as increased smoking, drinking and use of antidepressants/tranquilizers, feeling less protected by measures of the employee or the state, a greater feeling of being burdened by COVID-19-associated problems and greater exhaustion and sleep problems. Conclusion Our findings suggest ACEs as significant risk factor for EE in German health-care professionals. The current pandemic means a significant burden that further pronounces this risk.
CRIS-Team WoS Importer:2021-10-15

The multicenter effectiveness study of inpatient and day hospital treatment in departments of psychosomatic medicine and psychotherapy in Germany. - Doering, Stephan; Herpertz, Stephan; Pape, Magdalena; Hofmann, Tobias; Rose, Matthias; Imbierowicz, Katrin; Geiser, Franziska; Bierling, Antonie Louise; Weidner, Kerstin; Rademacher, Jörg; Michalek, Silke; Morawa, Eva; et al. (Frontiers in Psychiatry, 2023)
BACKGROUND: Reliable outcome data of psychosomatic inpatient and day hospital treatment with a focus on psychotherapy are important to strengthen ecological validity by assessing the reality of mental health care in the field. This study aims to evaluate the effectiveness of inpatient and day hospital treatment in German university departments of Psychosomatic Medicine and Psychotherapy in a prospective, naturalistic, multicenter design including structured assessments. METHODS: Structured interviews were used to diagnose mental disorders according to ICD-10 and DSM-IV at baseline. Depression, anxiety, somatization, eating disorder and posttraumatic stress disorder (PTSD) symptoms, as well as personality functioning were assessed by means of questionnaires on admission and at discharge. RESULTS: 2,094 patients recruited by 19 participating university hospitals consented to participation in the study. Effect sizes for each of the outcome criteria were calculated for 4-5 sub-groups per outcome domain with differing severity at baseline. Pre-post effect sizes for patients with moderate and high symptom severity at baseline ranged from d = 0.78 to d = 3.61 with symptoms of PTSD, depression, and anxiety showing the largest and somatization as well as personality functioning showing somewhat smaller effects. CONCLUSIONS: Inpatient and day hospital treatment in German university departments of Psychosomatic Medicine and Psychotherapy is effective under field conditions. CLINICAL TRIAL REGISTRATION: https://drks.de/search/de/trial/DRKS00016412, identifier: DRKS00016412.
EVALuna2:540873

The Pathological Buying Screener: Validation in a Clinical Sample - Mueller, Astrid; Trotzke, Patrick; Laskowski, Nora M.; Brederecke, Jan; Georgiadou, Ekaterini; Tahmassebi, Nadja; Hillemacher, Thomas; De Zwaan, Martina; Brand, Matthias (Psychotherapie Psychosomatik Medizinische Psychologie, 2020)
Aim The aim of the study was to evaluate the psychometric properties of the 13-item Pathological Buying Screener (PBS, [1]) in a clinical sample.
CRIS-Team WoS Importer:2020-12-11

The perceptions of trauma, complaints, somatization, and coping strategies among syrian refugees in germany—a qualitative study of an at‐risk population - Zbidat, Ali; Georgiadou, Ekaterini; Borho, Andrea; Erim, Yesim; Morawa, Eva (International Journal of Environmental Research and Public Health, 2020)
Background: A high prevalence of mental distress, especially posttraumatic stress disorder, has been widely confirmed among refugees. In order to establish adequate interventions in psychotherapy, however, it must first be examined whether refugees have similar ideas and concepts of stress, trauma, and healing. This study, therefore, aimed to analyze the representations of trauma, self‐reported complaints, indications of somatization, and coping strategies among a refugee population. Methods: Semi‐structured interviews based on the Cultural Formulation Interview (CFI) of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) were conducted with Syrian refugees who have residence permission in Germany. The interviews were audio‐recorded, transcribed, and analyzed according to the qualitative content analysis of Mayring. The foci of interest were determined on the basis of the predefined interview guideline, and inductive subcategories were extracted from the transcripts. Results: Sixteen refugees participated (50% women; mean age: 35.5 years, SD = 11.2; the mean duration of stay in Germany: 23.3 months, SD = 6.6). War experiences were the most frequently reported subjective perceptions of trauma. Frequently reported complaints included sleeping disturbance, cardiovascular symptoms, rumination, and pain. Among half of the participants, we found indications of somatization. We identified the following coping strategies: Activity, cognitive coping, social coping, religious coping, avoidance, and emotional coping. Conclusions: War‐related traumatic events are the most common trauma perceptions among Syrian refugees. The self-reported complaints demonstrate somatoform, depressive, and posttraumatic symptoms. Syrian refugees should be screened for somatization, depression, and posttraumatic stress disorder and should receive targeted interventions that consider and support individual coping resources.
CRIS-Team Scopus Importer:2020-02-04
Keywords: Coping; refugees; Somatization; Symptoms; Syria; Trauma

The pH probe CypHer™5E is effectively quenched by FM dyes - Welzel, Oliver; Loy, Kristina; Tischbirek, Carsten H.; Tabor, Alina; Gmeiner, Peter; Kornhuber, Johannes; Groemer, Teja W. (Journal of Fluorescence, 2013)
Concurrent imaging of spectrally distinct fluorescence probes has become an important method for live-cell microscopy experiments in many biological disciplines. The technique enables the identification of a multitude of causal relationships. However, interactions between fluorescent dyes beyond an obvious overlap of their fluorescent spectra are often neglected. Here we present the effects of the well-established fluorescent dyes FM®2-10 or FM®1-43 on the recently introduced pH-dependent probe CypHer™5E. Spectrophotometry as well as live-cell fluorescence microscopy revealed that both FM dyes are effective quenchers of CypHer™5E. Control experiments indicated that this effect is reversible and not due to bleaching. We conclude that, in general, parallel measurements of both dyes are possible, with low FM dye concentrations. Nevertheless, our results implicate that special care has to be taken in such dual colour experiments especially when analysing dynamic CypHer™5E signals in live-cell microscopy. © 2013 Springer Science+Business Media New York.

The preliminary study suggests an association between NF-ĸB pathway activation and increased plasma 20S proteasome activity in intracranial aneurysm patients - Kamińska, Joanna; Tylicka, Marzena; Sutkowska, Kinga; Gacuta, Karolina Marta; Sawicka, Magdalena Maria; Kowalewska, Ewa; Ćwiklińska-Dworakowska, Magdalena; Maciejczyk, Mateusz; Łysoń, Tomasz; Kornhuber, Johannes; Lewczuk, Piotr; Matowicka-Karna, Joanna; et al. (Scientific Reports, 2024)
The significant role of increased activation of 20S proteasomes in the development of abdominal aortic aneurysms has been well-established in a mouse model. The available literature lacks similar studies concerning brain aneurysms. The aim of the study was to verify the hypothesis that patients with unruptured intracranial aneurysms (UIA) have increased 20S proteasome ChT-L activity compared to the control group of individuals without vascular lesions in the brain. In the next step, the relationship between the activity of 20S proteasomes ChT-L and precursor proteins from the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family, namely NF-κB1 (p105), NF-κB2 (p100), NF-κB p65, and the inflammatory chemokine MCP-1, was examined. Patients with UIA had significantly higher 20S ChT-L proteasome activity compared to the control group. Patients with multiple aneurysms had significantly higher 20S proteasome ChT-L activity compared to those with single aneurysms. In patients with UIA, the activity of the 20S proteasome ChT-L negatively correlated with the concentration of NF-κB1 (p105) and NF-κB p65 precursor proteins and positively correlated with the concentration of the cerebrospinal fluid chemokine MCP-1. Our results may suggest that increased 20S proteasome ChT-L activity in UIA patients modulates inflammation in the cerebral arterial vessel via the MCP-1 chemokine as a result of activation of the canonical NF-κB pathway.
CRIS-Team Scopus Importer:2024-03-01
Keywords: 20S proteasome; Canonical NF-κB pathway; Intracranial aneurysms (IA); NF-κB p65; NF-κB1; NF-κB2

The prevalence and risk factors for mental distress among Syrian refugees in Germany: a register-based follow-up study - Borho, Andrea; Viazminsky, Andre; Morawa, Eva; Schmitt, Gregor Martin; Georgiadou, Ekaterini; Erim, Yesim (BMC Psychiatry, 2020)
Background: Mental disorders among refugees as well as their risk factors are already well documented in cross-sectional reports. However, longitudinal follow-up designs are widely lacking. Therefore, the aim of this study was to examine the change of the prevalence of mental disorders among Syrian refugees with German residence permission, taking into account their increasing length of stay in Germany, and to uncover the change in their relationship to pre- and post-migration risk factors. Methods: This study formed part of a register-based follow-up study with two measurement points in Erlangen (Germany). At the first time of recruitment in 2017, 200 of the 518 Syrian refugees with residence permission living in Erlangen took part. During the second survey timeframe 1.5 years later, in 2019, 108 of the former 200 Syrian refugees participated again and formed the total sample for this follow-up study. The survey instruments included demographics, migration-related variables and symptoms of post-traumatic stress (Essen Trauma Inventory, ETI), depression (Patient Health Questionnaire - PHQ-9) and generalized anxiety disorder (GAD-7). Results: At the time of the first survey, 26.9% of the participants exceeded the cut-off for a clinically relevant depression diagnosis, 16.7% for an anxiety disorder and 13.9% for a PTSD diagnosis. At the second measurement point, it was 30.6% for depression, 15.7% for an anxiety disorder and 13.0% for PTSD. No significant changes between the measurement points were found for any of the disorders. In multiple linear regression analyses, higher perceived discrimination, a higher number of traumatic experiences and a shorter duration of residence permission were shown to be the most important pre- and post-migration predictors of psychological stress independent of the time of measurement. Conclusions: There is strong empirical evidence that the prevalence rates of mental distress among refugees are significantly higher compared to the overall population. However, it has not yet become clear how these prevalence rates change with an increasing length of stay in the host countries. The results of our study indicate that the psychological burden on this refugee population remains consistently high over time, despite partly improved living conditions, and confirm the importance of therapeutic interventions.
CRIS-Team Scopus Importer:2020-07-24
Keywords: Depression; Follow-up; Generalized anxiety disorder; Germany; Mental distress; Mental health; Post-traumatic stress disorder; Register-based; Syrian refugees

The prevalence of effort-reward imbalance and its associations with working conditions, psychosocial resources and burden among health care workers during the COVID-19 pandemic: Results of the egePan-Voice study - Beschoner, Petra; Jerg-Bretzke, Lucia; Erim, Yesim; Geiser, Franziska; Baranowski, Andreas M.; Weidner, Kerstin; Albus, Christian; Schug, Caterina; Limbrecht-Ecklundt, Kerstin; Weimer, Katja; Jarczok, Marc N.; Kempf, Maximilian; et al. (PLoS ONE, 2023)
OBJECTIVE: The association between a measure of effort-reward imbalance (ERI) and profession as well as gender in a sample of health care workers (HCW) during the first wave of the COVID-19 pandemic in Germany using the egePan-Voice study. In addition, we examined, which factors are associated with an effort-reward imbalance ratio (ERI ratio) >1. METHODS: In a large sample of HCW (N = 6174) we assessed occupational stress with the short version of the effort-reward imbalance (ERI) questionnaire, working conditions, COVID-19-related problems and psychosocial resources (ENRICHD Social Support Inventory, ESSI; Sense of Coherence Scale, SOC-3 and optimism, SOP2). RESULTS: The prevalence of a ERI ratio >1 among HCW was 50.9%. The prevalence's of an ERI ratio >1 were statistically significant different between gender as well as the occupational profession. The proportion of women (51.8%) with ERI ratio >1 was significantly higher than among men (47.8%). The highest ERI imbalance was found among nurses (62.8%), followed by medical technical assistants (MTA) (58.8%), while psychologists/psychotherapists revealed the lowest value (37.8%), followed by physicians (41.8%). In the total sample, most essential factors reported at this time for increased ERI ratio were: insufficient staff for the current work load, insufficient recovery, feeling insufficiently protected by measures taken by the hospital/the employer, high occupancy rate of the wards, insufficient trust in colleagues and being a nurse as compared with being a physician. CONCLUSION: The findings indicate a high proportion of HCW with effort-reward imbalance and substantial profession-related differences. Preventive interventions should be offered to vulnerable groups among the HCW to decrease the imbalance measured by work stress.
CRIS-Team Scopus Importer:2023-09-01

The priority aim is to survive the intensive care unit but that alone is not sufficient: The neurological and mental sequelae of intensive medical care treatment - Kapfhammer, H. -P.; Schwab, Sibylle (Der Nervenarzt, 2016)
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The psychophysical assessment of odor valence: does an anchor stimulus influence the hedonic evaluation of odors? - Clepce, Marion; Neumann, Konrad; Martus, Peter; Nitsch, Marie; Wielopolski, Jan; Koch, Anna Maria; Kornhuber, Johannes; Reich, Karin; Thürauf, Norbert (Chemical Senses, 2014)
Olfactory stimuli are experienced primarily in terms of their hedonic tone and the assessment of olfactory hedonic estimates is a prevalent task in scientific and industrial contexts. However, measuring conditions are poorly standardized. Our study aims to fill this gap, focusing on the influence of anchor stimuli on olfactory hedonic evaluations, frequency of anchor presentation, and temporal stability of results. In n = 31 subjects, hedonic estimates for the 16 odors of the Sniffin' Sticks identification task were assessed on a visual analog rating scale under 4 measuring conditions (nonanchor, pleasant anchor, neutral anchor, unpleasant anchor). To test for stability over time, n = 10 subjects were reassessed 2, 4, and 6 months after original testing. To analyze for possible effects of single versus repeated anchor presentation, n = 15 subjects were retested 2 months after the original session in a multiple anchor presentation format. Statistical analysis revealed significant differences between the 4 anchor conditions, thus highlighting the necessity of specifying assessment methods in scientific research. No significant differences between timepoints were observed, indicating a high temporal stability of olfactory hedonic evaluations, especially from timepoint T2 onward. No overall significant effects of single versus multiple anchor presentation were detected. Findings might help to further standardize testing procedures.
EVALuna2:23574

Therapierefraktäre erstmalige Depression im mittleren Lebensalter - Grotemeyer, Alexander; Kornhuber, Johannes; Spitzer, Philipp (Der Nervenarzt, 2023)
CRIS-Team Scopus Importer:2023-09-22

The relevance of accuracy of heartbeat perception in noncardiac and cardiac chest pain - Schroeder, Stefanie; Gerlach, Alexander L.; Achenbach, Stephan; Martin, Alexandra (International Journal of Behavioral Medicine, 2015)
The development and course of noncardiac chest pain are assumed to be influenced by interoceptive processes.It was investigated whether heartbeat perception was enhanced in patients suffering from noncardiac chest pain and to what degree it was associated with self-reported cognitive-perceptual features and chest pain characteristics.A total of 42 patients with noncardiac chest pain (NCCP), 35 patients with cardiac chest pain, and 52 healthy controls were recruited. Heartbeat perception was assessed using the Schandry task and a modified Brener-Kluvitse task. Self-report measures assessed anxiety sensitivity, somatosensory amplification, heart-focused anxiety, and chest pain characteristics.Heartbeat perception was not more accurate in patients with NCCP, compared to patients with cardiac chest pain and healthy controls. However, in patients with NCCP, the error score (Schandry task) was significantly associated with stronger chest pain impairment, and the response bias (Brener-Kluvitse task) was associated with lower chest pain intensity.Against assumptions of current etiological models, heartbeat perception was not enhanced in patients with NCCP. Chest pain characteristics and particularly their appraisal as threatening might be more relevant to NCCP than the perceptional accuracy of cardiac sensations and should be focused in psychological interventions. However, associations with chest pain impairment suggest cardiac interoception to influence the course of NCCP.
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The role of AMPA and NMDA receptors in mitragynine effects on hippocampal synaptic plasticity - Effendy, Mohamad Azmeer; Yunusa, Suleiman; Mat, Noorul Hamizah; Has, Ahmad Tarmizi Che; Müller, Christian P.; Hassan, Zurina (Behavioural Brain Research, 2023)
Mitragynine, an indole alkaloid from the plant Mitragyna speciosa (Kratom), has been reported to modify hippocampal synaptic transmission. However, the role of glutamatergic neurotransmission modulating synaptic plasticity in mitragynine-induced synaptic changes is still unknown. Here, we determined the role of AMPA- and NMDA glutamate receptors in mitragynine-induced synaptic plasticity in the hippocampus. Male Sprague Dawley rats received either vehicle or mitragynine (10 mg/kg), with or without the AMPA receptor antagonist, NBQX (3 mg/kg), or the NMDA receptor antagonist, MK-801 (0.2 mg/kg). Field excitatory postsynaptic potentials (fEPSP) during baseline, paired-pulse facilitation (PPF) and long-term potentiation (LTP) were recorded in-vivo in the hippocampal CA1 area of anaesthetised rats. Basal synaptic transmission and LTP were significantly impaired after mitragynine, NBQX, and MK-801 alone, without an effect on PPF. Combined effects suggest a weak functional AMPA- as well as NMDA receptor antagonist action of mitragynine.
CRIS-Team Scopus Importer:2022-11-04
Keywords: AMPAR; LTP; Mitragynine; MK-801; NBQX; NMDAR; Synaptic plasticity

The Role of Cathepsin B in the Degradation of Aβ and in the Production of Aβ Peptides Starting With Ala2 in Cultured Astrocytes - Oberstein, Timo; Utz, Janine; Spitzer, Philipp; Klafki, Hans Wolfgang; Wiltfang, Jens; Lewczuk, Piotr; Kornhuber, Johannes; Maler, Juan Manuel (Frontiers in Molecular Neuroscience, 2021)
Astrocytes may not only be involved in the clearance of Amyloid beta peptides (Aβ) in Alzheimer's disease (AD), but appear to produce N-terminally truncated Aβ (Aβn−x) independently of BACE1, which generates the N-Terminus of Aβ starting with Asp1 (Aβ1−x). A candidate protease for the generation of Aβn−x is cathepsin B (CatB), especially since CatB has also been reported to degrade Aβ, which could explain the opposite roles of astrocytes in AD. In this study, we investigated the influence of CatB inhibitors and the deletion of the gene encoding CatB (CTSB) using CRISPR/Cas9 technology on Aβ2−x and Aβ1−x levels in cell culture supernatants by one- and two-dimensional Urea-SDS-PAGE followed by immunoblot. While the cell-permeant inhibitors E64d and CA-074 Me did not significantly affect the Aβ1−x levels in supernatants of cultured chicken and human astrocytes, they did reduce the Aβ2−x levels. In the glioma-derived cell line H4, the Aβ2−x levels were likewise decreased in supernatants by treatment with the more specific, but cell-impermeant CatB-inhibitor CA-074, by CA-074 Me treatment, and by CTSB gene deletion. Additionally, a more than 2-fold increase in secreted Aβ1−x was observed under the latter two conditions. The CA-074 Me-mediated increase of Aβ1−x, but not the decrease of Aβ2−x, was influenced by concomitant treatment with the vacuolar H+-ATPase inhibitor Bafilomycin A1. This indicated that non-lysosomal CatB mediated the production of Aβ2−x in astrocytes, while the degradation of Aβ1−x seemed to be dependent on lysosomal CatB in H4 cells, but not in primary astrocytes. These findings highlight the importance of considering organelle targeting in drug development to promote Aβ degradation.
CRIS-Team Scopus Importer:2021-02-05
Keywords: Alzheimer's disease; amyloid beta; astrocytes; cathepsin B; lysosomal; N-terminus

The role of ceramide in major depressive disorder - Kornhuber, Johannes; Reichel, Martin; Tripal, Philipp; Groemer, Teja W.; Henkel, Andreas W.; Mühle, Christiane; Gulbins, Erich (European archives of psychiatry and clinical neuroscience, 2009)
Major depression is a severe mood disorder with a lifetime prevalence of more than 10%. The pharmacokinetic hypothesis claims that a slow accumulation of antidepressant drugs by acid trapping mainly into lysosomes is responsible for the therapeutic latency and that a lysosomal target mediates the antidepressant effects. The lysosomal lipid metabolizing enzyme acid sphingomyelinase (ASM) cleaves sphingomyelin into ceramide and phosphorylcholine. In a pilot study, the activity of this enzyme was increased in peripheral blood cells of patients with major depressive disorder (MDD), making the ASM an interesting molecular target of antidepressant drugs. Indeed, several antidepressant drugs functionally inhibit ASM. The ASM/ceramide pathway might be a missing link unifying independent findings in neurobiology and the treatment of MDD such as therapeutic latency, oxidative stress, immune activation and increased risk of cardiovascular disease. © 2009 Springer-Verlag.
Created from Fastlane, Scopus look-up
Keywords: Acid sphingomyelinase; Amitriptyline; Ceramide; Fluoxetine; Lysosomes; Major depressive disorder; Neuroplasticity hypothesis; Pharmacokinetic hypothesis; Sphingolipids

The role of coping strategies in post-traumatic growth among syrian refugees: A structural equation model - Acar, Busra; Acar, İbrahim H. and Alhiraki, Omar A. and Fahham, Ola and Erim, Yesim and Acarturk, Ceren (International Journal of Environmental Research and Public Health, 2021)
The Syrian conflict has led to a mass migration of Syrians to other countries and exposed them to many possible traumatic events and stressors in their country of origin and in the resettlement process. The possibility of positive psychological effects of adverse life events is less documented among Syrian refugees. Thus, the current study aimed to develop preliminary evidence for the identifying factors: traumatic experiences, post-migration stressors and coping strategies that are associated with post-traumatic growth (PTG) of Syrian refugees residing in Turkey. Structural equation modeling (SEM) was used in the current study to assess the associations among these factors. Data were obtained from Syrian refugees residing in the governorates of Hatay and Mardin. A total of 528 Syrians, aged between 18–77 years (M = 35.60, SD = 11.65) participated in this cross-sectional study. Results from the SEM indicated that past traumatic experiences and post-migration stressors were indirectly related to PTG. The results from the current study provide support for that the association between refugees’ traumatic experiences, post-migration stressors and PTG appear to be explained through the presence of coping strategies which could be addressed in the psychotherapies and psychosocial interventions for refugees to promote positive psychological change. Future studies should address the effects of post-migration stressors on PTG in detail.
CRIS-Team Scopus Importer:2021-08-27
Keywords: Coping; Post-migration stressors; Post-traumatic growth; Refugees; Syrian conflict

The role of metabotropic glutamate receptors in social behavior in Rodents - Zoicas, Iulia; Kornhuber, Johannes (International Journal of Molecular Sciences, 2019)
The appropriate display of social behavior is critical for the well-being and survival of an individual. In many psychiatric disorders, including social anxiety disorder, autism spectrum disorders, depression and schizophrenia social behavior is severely impaired. Selective targeting of metabotropic glutamate receptors (mGluRs) has emerged as a novel treatment strategy for these disorders. In this review, we describe some of the behavioral paradigms used to assess different types of social behavior, such as social interaction, social memory, aggressive behavior and sexual behavior. We then focus on the effects of pharmacological modulation of mGluR1-8 on these types of social behavior. Indeed, accumulating evidence indicates beneficial effects of selective ligands of specific mGluRs in ameliorating innate or pharmacologically-induced deficits in social interaction and social memory as well as in reducing aggression in rodents. We emphasize the importance of future studies investigating the role of selective mGluR ligands on different types of social behavior to provide a better understanding of the neural mechanisms involved which, in turn, might promote the development of selective mGluR-targeted tools for the improved treatment of psychiatric disorders associated with social deficits.
CRIS-Team Scopus Importer:2019-05-02
Keywords: Aggression; Animal models; Anxiety; Metabotropic glutamate receptors; MGluR agonists; MGluR antagonists; Social investigation; Social recognition

The Role of Prefrontal Inhibition in Regulating Facial Expressions of Pain: A Repetitive Transcranial Magnetic Stimulation Study - Karmann, Anna Julia; Maihoefner, Christian; Lautenbacher, Stefan; Sperling, Wolfgang; Kornhuber, Johannes; Kunz, Miriam (Journal of Pain, 2016)
Although research on facial expressions of pain has a long history, little is known about the cerebral mechanisms regulating these expressions. It has been suggested that the medial prefrontal cortex (mPFC) might be involved in regulating/inhibiting the degree to which pain is facially displayed. To test whether such a prefrontal regulation does indeed take place, we reduced medial prefrontal excitability via repetitive transcranial magnetic stimulation (rTMS) and assessed its effect on facial expressions. In a within-subject design, facial and subjective responses to experimental pain as well as "situational" pain catastrophizing were assessed in 35 healthy participants; once after receiving low-frequency rTMS over the mPFC (1 Hz) and once after sham stimulation. Compared with sham stimulation, rTMS over the mPFC resulted in enhanced facial expressions of pain, whereas self-report and pain catastrophizing did not change. The current data show that reducing medial prefrontal excitability (via low-frequency rTMS) makes individuals facially more expressive to pain. This finding indicates that the mPFC is crucially involved in the inhibition of facial expressions of pain. Because this effect was independent of changes in self-report and pain catastrophizing suggests that this inhibitory mechanism is mainly governing the facial expression and not the underlying experience of pain.Using rTMS, it was shown that the mPFC is causally involved in the downregulation or silencing of one's facial expression of pain. This might explain why individuals with low mPFC functioning (eg, patients with dementia) are facially more expressive in response to pain.
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The role of serotonin in alcohol use and abuse - Müller, Christian P.; Schumann, Gunter; Kornhuber, Johannes; Kalinichenko, Liubov (Handbook of Behavioral Neuroscience, 2020)
Alcohol is a widely used and abused psychoactive drug in Western societies. Long-term consumption may lead to alcohol addiction, a severe psychiatric disorder. The serotonergic system of the brain is a key regulator of reinforcement learning and behavioral plasticity and has long been considered as an important mediator of alcohol-related physiological and behavioral adaptations. In this chapter we review the action of alcohol on the serotonergic system, and how components of the system contribute to the establishment and expression of alcohol consumption, alcohol instrumentalization and alcohol addiction-related behaviors in animal models and in humans. Altogether, accumulating evidence suggests that a prominent activation of the serotonergic system after alcohol exposure is reversed after chronic alcohol consumption. The serotonergic system contributes essentially to the establishment of controlled alcohol consumption and may also be involved in distinct ways of alcohol instrumentalization. Long-term adaptations after chronic alcohol consumption in the serotonergic system may contribute to the transition from controlled to compulsive consumption and addiction. Although no serotonin-based pharmacotherapy for alcohol addiction has emerged yet, serotonin receptors still offer interesting targets for potential therapeutic approaches.
CRIS-Team Scopus Importer:2020-02-04
Keywords: Addiction; Addiction treatment; Alcohol; Animal models; Ethanol; Instrumentalization; Serotonin

The role of sphingolipids in psychoactive drug use and addiction - Kalinichenko, Liubov; Gulbins, Erich; Kornhuber, Johannes; Müller, Christian P. (Journal of Neural Transmission, 2018)
Psychoactive drug use is a common behavior in many societies worldwide, frequently associated with drug instrumentalization. Regular use may develop into drug addiction, which is a severe psychiatric disorder with multiple pathological effects to virtually all organ systems. Treatment strategies for addiction are often insufficient with no broadly working pharmaco-treatment available. Recently, lipids, and particularly sphingolipids, have been considered as new mediators in the pathogenic pathways and as possible therapeutic targets for the treatment of addictive states. In our review, we discuss the contribution of sphingolipids in the development of addictive states including alcohol consumption, nicotine, amphetamine, morphine, and cocaine dependencies. Recent data show that the involvement of various classes of sphingolipids, such as sphingomyelins, ceramides, globosides, sulfatides, and cerebrosides, might explain the development of some specific features of addictive states, for example, apoptotic neurodegeneration induced by psychoactive substances. On the other hand, protective effects of sphingolipids are discussed. Sphingolipids might be a key mechanism in the development of beneficial effects of moderate alcohol consumption. Therefore, sphingolipid systems emerge as possible new pathways involved in the development of addiction and its pathophysiological consequences. However, further analysis is still needed to investigate the exact mechanisms of sphingolipid contribution and possibility of using of sphingolipids as new therapeutic targets.
EVALuna2:211638

The role of the n-methyl-d-aspartate receptors in social behavior in rodents - Zoicas, Iulia; Kornhuber, Johannes (International Journal of Molecular Sciences, 2019)
The appropriate display of social behaviors is essential for the well-being, reproductive success and survival of an individual. Deficits in social behavior are associated with impaired N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. In this review, we describe recent studies using genetically modified mice and pharmacological approaches which link the impaired functioning of the NMDA receptors, especially of the receptor subunits GluN1, GluN2A and GluN2B, to abnormal social behavior. This abnormal social behavior is expressed as impaired social interaction and communication, deficits in social memory, deficits in sexual and maternal behavior, as well as abnormal or heightened aggression. We also describe the positive effects of pharmacological stimulation of the NMDA receptors on these social deficits. Indeed, pharmacological stimulation of the glycine-binding site either by direct stimulation or by elevating the synaptic glycine levels represents a promising strategy for the normalization of genetically-induced, pharmacologically-induced or innate deficits in social behavior. We emphasize on the importance of future studies investigating the role of subunit-selective NMDA receptor ligands on different types of social behavior to provide a better understanding of the underlying mechanisms, which might support the development of selective tools for the optimized treatment of disorders associated with social deficits.
CRIS-Team Scopus Importer:2019-11-19
Keywords: Inter-male aggression; Maternal aggression; Maternal care; Mating behavior; NMDAR agonists; NMDAR antagonists; Social investigation; Social recognition; Ultrasonic vocalizations

The scent of the other women: Body odor-induced behavioral and physiological effects on face categorization - Mutic, Smiljana; Freiherr, Jessica; Cavazzana, Annachiara; Rocha, Marta; Soares, Sandra C.; Parma, Valentina (Physiology & behavior, 2019)
In body odor research, the interaction of female donors and receivers is scarcely investigated. With the aim to investigate effects of female body odor in a competitive context, we tested 51 women divided into two groups (i.e., a competitive and a non-competitive group, based on verbal instructions). Between groups, we explored whether female body odor exposure (vs. masker odor) modulates emotion categorization (via RT variance and distribution) and physiological reactions (via instantaneous heart rate) in a task with dynamic male and female faces as either angry or happy. Women in the competitive group reported to feel more competitive and performed more accurately. They gathered more emotional information to categorize dynamic faces and when additionally exposed to female body odor, they showed a resistance to cardiac deceleration. Lapses of attention (via RT distribution) occurred irrespective of body odor exposure. Our results support the idea that female body odors, presented in a competitive context, contrast cardiac deceleration and, by tendency, modulate emotion categorization. Data are discussed in the context of chemosignaling and social interactions among women.
CRIS-Team Scopus Importer:2019-08-06
Keywords: Chemosensation; Chemosignal; Heart rate; Intrasexual competition; Olfaction; Smell

The selective FKBP51 inhibitor SAFit2 reduces alcohol consumption and reinstatement of conditioned alcohol effects in mice - König, Loretta; Kalinichenko, Liubov; Huber, Sabine; Voll, Andreas M.; Bauder, Michael; Kornhuber, Johannes; Hausch, Felix; Müller, Christian P. (Addiction Biology, 2019)
There is still no widely effective pharmacotherapy for alcohol addiction available in the clinic. FK506-binding protein 51 (FKBP51) is a negative regulator of the glucocorticoid receptor signaling pathway that regulates the stress-induced glucocorticoid feedback circuit. Here we asked whether selective inhibitors of FKBP51, exemplified by SAFit2, may serve as a new pharmacological strategy to reduce alcohol consumption and conditioned alcohol effects in a mouse model. We report that a relatively short treatment with SAFit2 (20 mg/kg, ip) reduces ongoing 16 vol% alcohol consumption when administered during free access to alcohol in a two-bottle free-choice test. SAFit2 was also able to reduce alcohol consumption when given during an abstinence period immediately before relapse. In contrast, SAFit2 did not affect alcohol consumption when given during a relapse period after repeated withdrawal from alcohol. SAFit2 (10 and 20 mg/kg, ip) showed no effects when used in an intermittent drinking schedule. When 20 vol% alcohol was only available every other day, SAFit2 had no effect on drinking, no matter whether given during a drinking episode or the day before. SAFit2 (2 and 20 mg/kg, ip) did not affect the expression of an alcohol-induced conditioned place preference (CPP). However, SAFit2 was able to inhibit alcohol-induced reinstatement of an extinguished CPP in a dose-dependent way. Altogether, these data may suggest pharmacological inhibition of FKBP51 as a viable strategy to reduce alcohol seeking and consumption.
CRIS-Team Scopus Importer:2019-06-25
Keywords: alcohol; conditioned place preference; drinking; FKBP51; SAFit2

The subjective burden of informal caregivers of persons with dementia: extended validation of the German language version of the Burden Scale for Family Caregivers (BSFC) - Grau, Hannes; Grässel, Elmar; Berth, H. (Aging & Mental Health, 2015)
In research as well as in the practice of caregiver counselling, the subjective burden of family caregivers is considered an important characteristic of home care. The objective of the present study was to provide an extended validation of the German language version of the Burden Scale for Family Caregivers (BSFC) published in 2001.Extended validation was performed using medical, interview, and health insurance data of 351 informal caregivers and their relatives who had dementia. Cronbach's alpha was calculated to assess the internal consistency of the items, and an exploratory factor analysis was conducted to determine the structure of the BSFC. The discriminatory power and item difficulties of the 28 BSFC items were examined. Five research questions addressed construct validity. Question six addressed the BSFC score as a potential predictor of institutionalization at a follow-up time of 2.5 years (predictive validity).Exploratory factor analysis indicated that the BSFC had a single-factor structure. Cronbach's alpha for the total scale was 0.93. A significant increase in the BSFC score was observed when the severity of cognitive impairment increased, persons with dementia showed disturbing behaviour, caregivers were diagnosed with depression, care requirements increased, or the family caregiver and the person with dementia lived together. Caregiver burden emerged as a significant predictor of institutionalization. The validity of the BSFC was confirmed by the results.The BSFC score allows for a valid assessment of the total caregiver burden in both research and practice. The BSFC is available for free in 20 languages ( http://www.caregiver-burden.eu ).
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The system's genetics of depression and its somatic and mental comorbidities - Kalinichenko, Liubov; Kornhuber, Johannes; Müller, Christian P. (Translational Neuroscience, 2022)
Depression is a common mood disorder characterised by high comorbidity with other mental and somatic diseases. New studies reveal a shared genetic base for mental core symptoms and somatic comorbidities. Functional analyses showed multiple brain-body pathways involved. This may help considering new therapeutic approaches for depression as a system's disorder.
CRIS-Team WoS Importer:2022-08-05

Theta/beta neurofeedback in children with ADHD: Feasibility of a short-term setting and plasticity effects. - Van Doren, Jessica; Heinrich, Hartmut; Bezold, Mareile; Reuter, Nina; Kratz, Oliver; Horndasch, Stefanie; Berking, Matthias; Ros, Thomas; Gevensleben, Holger; Moll, Gunther; Studer, Petra (International Journal of Psychophysiology, 2016)
Neurofeedback (NF) is increasingly used as a therapy for attention-deficit/hyperactivity disorder (ADHD), however behavioral improvements require 20 plus training sessions. More economic evaluation strategies are needed to test methodological optimizations and mechanisms of action. In healthy adults, neuroplastic effects have been demonstrated directly after a single session of NF training. The aim of our study was to test the feasibility of short-term theta/beta NF in children with ADHD and to learn more about the mechanisms underlying this protocol. Children with ADHD conducted two theta/beta NF sessions. In the first half of the sessions, three NF trials (puzzles as feedback animations) were run with pre- and post-reading and picture search tasks. A significant decrease of the theta/beta ratio (TBR), driven by a decrease of theta activity, was found in the NF trials of the second session demonstrating rapid and successful neuroregulation by children with ADHD. For pre-post comparisons, children were split into good vs. poor regulator groups based on the slope of their TBR over the NF trials. For the reading task, significant EEG changes were seen for the theta band from pre- to post-NF depending on individual neuroregulation ability. This neuroplastic effect was not restricted to the feedback electrode Cz, but appeared as a generalized pattern, maximal over midline and right-hemisphere electrodes. Our findings indicate that short-term NF may be a valuable and economical tool to study the neuroplastic mechanisms of targeted NF protocols in clinical disorders, such as theta/beta training in children with ADHD.

"Time is brain" in relapsing remitting multiple sclerosis : Current treatment concepts in immunotherapy - Linker, Ralf; Kallmann, B. -A.; Kleinschnitz, C.; Rieckmann, P.; Maeurer, M.; Schwab, Sibylle (Der Nervenarzt, 2015)
Despite highly divergent time scales of disease evolution in multiple sclerosis (MS) and ischemic stroke, clear analogies are apparent that may point the way to optimization of MS treatment. Inflammatory disease activity and neurodegeneration may induce potentially irreversible damage to central nervous system structures and thus lead to permanent disability. For the treatment of MS early detection of disease activity and early immunotherapy or treatment optimization are pivotal determinants of long-term outcomes. Such therapeutic concepts may be described with the catchy phrase "time is brain" as coined for the acute thrombolytic treatment of ischemic stroke.For MS a "time is brain" concept would comprise an early initiation of first line therapy as well as sensitive and structured monitoring of disease activity under therapy in conjunction with a low threshold for timely treatment optimization to achieve sustained freedom from measurable disease activity. This approach may substantially improve the long-term outcome in patients who show insufficient response to platform therapies. The intersectorial collaboration in regional MS care networks involving office-based neurologists and specialized MS centers may facilitate the timely use of highly active therapies with their specific benefit-risk profiles thus supporting sustained stabilization of patient quality of life.
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Timing of sequential use of double-balloon catheter and oral misoprostol for induction of labor - Kehl, Sven; Böhm, Lea; Weiss, Christel; Heimrich, Jutta; Dammer, Ulf; Baier, Friederike; Suetterlin, Marc; Beckmann, Matthias; Faschingbauer, Florian (Journal of Obstetrics and Gynaecology Research, 2016)
AIM: The best time to commence cervical ripening with a balloon catheter is unknown. The aim of this study was to evaluate whether application of a balloon catheter in the morning or in the evening is better when sequential prostaglandin application is planned. METHODS: This multicenter historical cohort study included 415 women with an unfavorable cervix undergoing labor induction at term. Labor was induced with a double-balloon catheter and the sequential use of oral misoprostol if necessary. The balloon catheter was placed in the morning group between 02:00-15:00 and in the evening group between 15:00-02:00. The primary outcome measure was the cesarean section rate. Secondary outcome measures included failed labor induction (no vaginal delivery within 72 h). RESULTS: The cesarean section rate did not differ between the groups (morning 26.9%, evening 24.3%; P = 0.5553); however, more women in the morning group did not deliver within 72 h (8.8% vs 3.1%; P = 0.0138). In nulliparous women, labor induction failed more often in the morning group (12% vs. 4%, P = 0.043). In parous women, the induction-to-delivery interval was longer in the morning group (1756 vs. 1349 min; P = 0.046), and there were fewer deliveries within 24 h (35% vs. 56%, P = 0.016). CONCLUSIONS: When sequential use of a double-balloon catheter and oral misoprostol for labor induction is planned, the preferable time for catheter placement is in the evening. This resulted in fewer failed inductions in nulliparous women and a shorter induction-to-delivery interval and more deliveries within 24 h in parous women.
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TNF-? and IL-6 serum levels: neurobiological markers of alcohol consumption in alcohol-dependent patients? - Heberlein, Annemarie; Kaeser, Marius; Lichtinghagen, Ralf; Rhein, Mathias; Lenz, Bernd; Kornhuber, Johannes; Bleich, Stefan; Hillemacher, Thomas (Alcohol, 2014)
We investigated the serum levels of IL-6 and TNF-? in 30 male alcohol-dependent patients during withdrawal (day 1, 7, and 14) and compared them with the levels obtained from 18 healthy male controls. IL-6 (day 1: T = 2,593, p = 0.013; day 7: T = 2,315, p = 0.037; day 14: T = 1,650, p = 0.112) serum levels were significantly increased at the beginning of alcohol withdrawal. TNF-? (T = 3,202, p = 0.03) serum levels were significantly elevated in the patients' group during the whole period of withdrawal. IL-6 serum levels decreased significantly during withdrawal (F = 16.507, p < 0.001), whereas TNF-? levels did not change significantly (day 1-14). IL-6 serum levels were directly associated with alcohol consumption (r = 0.392, p = 0.047) on day 1. Moreover, the IL-6 serum levels were associated with alcohol craving (PACS total score day 1: r = -0.417, p = 0.022, the score of the obsessive subscale of the OCDS on day 14 [r = -0.549, p = 0.022]), depression (r = -0.507, p = 0.005), and trait anxiety (r = -0.674, p < 0.001) on day 1. We found an association with the duration of active drinking following the last period of abstinence and the TNF-? serum levels (day 1:r = 0.354, p = 0.009; day 7: r = 0.323, p = 0.022; day 14: r = 0.303, p = 0.034) as well as an association with the severity of alcohol dependence measured by the SESA scale (r = 0.454, p = 0.015). Moreover, we found a significant association between the BDNF serum levels and the TNF-? serum levels (r = -0.426, p = 0.021). Our results support an association between alterations in TNF-? and IL-6 serum levels and alcohol consumption.
EVALuna2:23652

Tonic activin signaling shapes cellular and synaptic properties of CA1 neurons mainly in dorsal hippocampus - Dahlmanns, Marc; Valero-Aracama, Maria Jesus; Dahlmanns, Jana; Zheng, Fang; Alzheimer, Christian (iScience, 2023)
Dorsal and ventral hippocampus serve different functions in cognition and affective behavior, but the underpinnings of this diversity at the cellular and synaptic level are not well understood. We found that the basal level of activin A, a member of the TGF-β family, which regulates hippocampal circuits in a behaviorally relevant fashion, is much higher in dorsal than in ventral hippocampus. Using transgenic mice with a forebrain-specific disruption of activin receptor signaling, we identified the pronounced dorsal-ventral gradient of activin A as a major factor determining the distinct neurophysiologic signatures of dorsal and ventral hippocampus, ranging from pyramidal cell firing, tuning of frequency-dependent synaptic facilitation, to long-term potentiation (LTP), long-term depression (LTD), and de-potentiation. Thus, the strong activin A tone in dorsal hippocampus appears crucial to establish cellular and synaptic phenotypes that are tailored specifically to the respective network operations in dorsal and ventral hippocampus.
CRIS-Team Scopus Importer:2023-10-20
Keywords: Cellular neuroscience; Neuroscience

Tonic Control of Secretory Acid Sphingomyelinase Over Ventral Hippocampal Synaptic Transmission and Neuron Excitability - Lin, Chih-Hung; Kornhuber, Johannes; Zheng, Fang; Alzheimer, Christian (Frontiers in Cellular Neuroscience, 2021)
The acid sphingomyelinase (ASM) converts sphingomyelin into ceramide. Recent work has advanced the ASM/ceramide system as a major player in the pathogenesis of major depressive disorder (MDD). Indeed, ASM activity is enhanced in MDD patients and antidepressant drugs like fluoxetine act as functional inhibitors of ASM. Here, we employed the specific ASM inhibitor ARC39 to explore the acute effects of the enzyme on hippocampal synaptic transmission and cell excitability in adult mouse brain slice preparations. In both field potential and whole-cell recordings, ARC39 (1-3 mu M) enhanced excitatory synaptic input onto ventral hippocampal CA1 pyramidal cells. The specificity of drug action was demonstrated by its lacking effect in slices from ASM knockout mice. In control condition, ARC39 strongly reduced firing in most CA1 pyramidal cells, together with membrane hyperpolarization. Such pronounced inhibitory action of ARC39 on soma excitability was largely reversed when GABA(A) receptors were blocked. The idea that ARC39 recruits GABAergic inhibition to dampen cell excitability was further reinforced by the drug's ability to enhance the inhibitory synaptic drive onto pyramidal cells. In pyramidal cells that were pharmacologically isolated from synaptic input, the overall effect of ARC39 on cell firing was inhibitory, but some neurons displayed a biphasic response with a transient increase in firing, suggesting that ARC39 might alter intrinsic firing properties in a cell-specific fashion. Because ARC39 is charged at physiological pH and exerted all its effects within minutes of application, we propose that the neurophysiological actions reported here are due to the inhibition of secretory rather than lysosomal ASM. In summary, the ASM inhibitor ARC39 reveals a tonic control of the enzyme over ventral hippocampal excitability, which involves the intrinsic excitability of CA1 pyramidal cells as well as their excitatory and inhibitory synaptic inputs.
CRIS-Team WoS Importer:2021-04-30

Too hot to handle: Mood states moderate implicit approach vs. avoidance tendencies toward food cues in patients with obesity and active binge eating disorder - Krehbiel, Johannes; Halbeisen, Georg; Kühn, Simone; Erim, Yesim; Paslakis, Georgios (Journal of Psychiatric Research, 2021)
Patients with binge eating disorder (BED) display recurring episodes of eating large amounts of food in a short period of time, especially during negative mood states. However, the psychological processes linking negative mood to binge eating behavior have not been sufficiently explored. This study investigated the effects of experimentally inducing a negative (sad) mood state upon reaction times in a computerized Approach-Avoidance-Task (AAT) using images of foods and compared to a neutral control procedure in which negative mood was not induced. Differences in reaction times between “pulling” and “pushing away” food cues in the AAT were considered surrogates for fast, automatic (i.e., implicit) preferences (“bias”) for either the approach or avoidance of foods. Obese patients with BED (n = 40), weight-matched (obese) individuals (n = 40), and norm-weight controls (n = 29) were asked to approach (“pull”) or avoid (“push”) images of high- and low-calorie foods following the induction of a negative mood state vs. the neutral control procedure. Sample size was within the common range of previous investigations of the kind. Similar to previous findings, obese patients with BED exhibited an avoidance bias (i.e., faster reaction times in “pushing” compared to “pulling”) during the neutral control condition. However, a contrast analysis revealed that negative mood was associated with decreased avoidance bias in obese patients with BED, but not in obese and norm-weight controls. Mood status exerted no effect on BED patients’ self-reported (i.e., explicit) ratings of the urge to consume foods. These findings may help to advance current understanding of how negative (sad) mood states may affect binge eating behaviors. Implications of these findings for developing novel treatment approaches are discussed.
CRIS-Team Scopus Importer:2021-10-01
Keywords: Approach avoidance task; Binge eating disorder; Eating disorder; Implicit bias; Psychotherapy

Touchscreen ohne Touch - Berührungslose 3D Gesten-Interaktion für den Operationssaal (Touchscreen without Touch - Touchless 3D Gesture Interaction for the Operation Room) - Penne, Jochen; Soutschek, Stefan; Stürmer, Michael; Schaller, Christian; Placht, Simon; Kornhuber, Johannes; Hornegger, Joachim (i-com : Zeitschrift für interaktive und kooperative Medien, 2009)

Towards the Automatic Classification of Reading Disorders in Continuous Text Passages - Maier, Andreas; Bocklet, Tobias; Hönig, Florian Thomas; Horndasch, Stefanie; Nöth, Elmar (Text, Speech and Dialogue, 2009)

Transcranial magnetic stimulation (TMS), inhibition processes and attention deficit/hyperactivity disorder (ADHD) - an overview - Hoegl, Thomas; Bender, Stephan; Buchmann, Johannes; Kratz, Oliver; Moll, Gunther; Heinrich, Hartmut (Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2014)
Motor system excitability can be tested by transcranial magnetic stimulation CFMS). In this article, an overview of recent methodological developments and research findings related to attention deficit/hyperactivity disorder (ADHD) is provided. Different TMS parameters that reflect the function of interneurons in the motor cortex may represent neurophysiological markers of inhibition in ADHD, particularly the so-called intracortical inhibition. In children with a high level of hyperactivity and impulsivity, intracortical inhibition was comparably low at rest as shortly before the execution of a movement. TMS-evoked potentials can also be measured in the EEG so that investigating processes of excitability is not restricted to motor areas in future studies. The effects of methylphenidate on motor system excitability may be interpreted in the sense of a 'fine-tuning' with these mainly dopaminergic effects also depending on genetic parameters (DAT1 transporter). A differentiated view on the organization of motor control can be achieved by a combined analysis of TMS parameters and event-related potentials. Applying this bimodal approach, strong evidence for a deviant implementation of motor control in children with ADHD and probably compensatory mechanisms (with involvement of the prefrontal cortex) was obtained. These findings, which contribute to a better understanding of hyperactivity/impulsivity, inhibitory processes and motor control in ADHD as well as the mechanisms of medication, underline the relevance of TMS as a neurophysiological method in ADHD research.
EVALuna2:23888

Transcriptomic Profiling Reveals the Antiapoptosis and Antioxidant Stress Effects of Fos in Ischemic Stroke - Mu, Qiancheng; Zhang, Yuxuan; Gu, Long; Gerner, Stefan; Qiu, Xiancheng; Tao, Qianke; Pang, Jinwei; Dipritu, Ghosh; Zhang, Lifang; Yin, Shigang; Jiang, Yong; Peng, Jianhua (Frontiers in Neurology, 2021)
Arterial hypertension is considered the most prevalent risk factor for stroke. Both pathophysiologic and clinical data previously acquired suggest a strong correlation between the hemodynamic nature of arterial hypertension and an increase in the risk of ischemic insult to tissues. However, the knowledge of specific molecular interactions between hypertension and ischemic stroke (IS) is limited. In this study, we performed systematic bioinformatics analysis of stroke-prone spontaneous hypertensive brain tissue samples of rats (GSE41452), middle cerebral artery occlusion of brain tissue samples of rats (GSE97537), and peripheral blood array data of IS patients (GSE22255). We identified that Fos, an immediate-early gene (IEG) that responds to alterations in arterial blood pressure, has a strong correlation with the occurrence and prognosis of IS. To further evaluate the potential function of Fos, the oxygen–glucose deprivation model and RNA sequencing of HT22 neuronal cells were performed. Consistent with the sequencing results, real-time quantitative PCR and Western blot indicate that Fos was elevated at 3 h and returned to normal levels at 6 h after oxygen–glucose deprivation. Knock-down of Fos by lentivirus significantly increased the oxidative stress level, neuronal apoptosis, and inhibited the mitochondrial function. In conclusion, Fos acts as an important link between hypertension and IS. Furthermore, Fos can be used as a potential biomarker for target therapy in the prevention of stroke among hypertensive patients and also potential treatment targeting apoptosis and oxidative stress after its onset.
CRIS-Team Scopus Importer:2021-11-19
Keywords: apoptosis; Fos; hypertension; ischemic stroke; mitochondria; oxidative stress; oxygen-glucose deprivation

Transient Confinement of CaV2.1 Ca2+-Channel Splice Variants Shapes Synaptic Short-Term Plasticity - Heck, Jennifer; Parutto, Pierre; Ciuraszkiewicz, Anna; Bikbaev, Arthur; Freund, Romy; Mitlöhner, Jessica; Andres-Alonso, Maria; Fejtová, Anna; Holcman, David; Heine, Martin (Neuron, 2019)
The precision and reliability of synaptic information transfer depend on the molecular organization of voltage-gated calcium channels (VGCCs) within the presynaptic membrane. Alternative splicing of exon 47 affects the C-terminal structure of VGCCs and their affinity to intracellular partners and synaptic vesicles (SVs). We show that hippocampal synapses expressing VGCCs either with exon 47 (CaV2.1+47) or without (CaV2.1Δ47) differ in release probability and short-term plasticity. Tracking single channels revealed transient visits (∼100 ms) of presynaptic VGCCs in nanodomains (∼80 nm) that were controlled by neuronal network activity. Surprisingly, despite harboring prominent binding sites to scaffold proteins, CaV2.1+47 persistently displayed higher mobility within nanodomains. Synaptic accumulation of CaV2.1 was accomplished by optogenetic clustering, but only CaV2.1+47 increased transmitter release and enhanced synaptic short-term depression. We propose that exon 47-related alternative splicing of CaV2.1 channels controls synapse-specific release properties at the level of channel mobility-dependent coupling between VGCCs and SVs.
CRIS-Team Scopus Importer:2019-07-09
Keywords: calcium channel; localization microscopy; nanodomain; presynapse; short-term plasticity; single particle tracking; surface mobility; synapse; synaptic transmission; vesicular release

Translating satisfaction determination from health care to the automotive industry - Meinzer, Stefan; Prenninger, Johann; Vesel, Patrick; Kornhuber, Johannes; Volmer, Judith; Hornegger, Joachim; Eskofier, Björn (Service Business, 2015)
This study is based on the case of BMW, and aims to improve the determination of perceived consumer satisfaction in the automotive industry by transferring existing knowledge from the health care sector. A literature analysis of the health care sector and the automotive industry was conducted to identify the common concepts of determining satisfaction. These were the service encounter, situational factors, and sociodemographics. The practical application was tested by analyzing a contemporary survey from BMW. Based on the findings, managers responsible for customer satisfaction in after-sales services in the automotive industry could improve measurement of customer satisfaction.
UnivIS-Import:2015-10-26:Pub.2015.tech.IMMD.IMMD5.transl
Keywords: Automotive industry; BMW; Customer satisfaction; Health care; Patient satisfaction

Traumaerlebnisse, Posttraumatische Belastungsstörung und Kohärenzgefühl bei türkischsprachigen Patienten einer psychosomatischen Universitätsambulanz - Erim, Yesim; Morawa, Eva; Atay, Halil; Tagay, Sefik; Aygün, Sanem; Senf, Wolfgang (Zeitschrift für Medizinische Psychologie, 2009)
Keywords: Immigrants; Essen Trauma Inventory; Sense of coherence; PTSD; Trauma

Traumatic events and posttraumatic stress disorder in Turkish-speaking patients in primary care - Tagay, Sefik; Zararsiz, Rasit; Erim, Yesim; Duellmann, Sonja; Schlegl, Sandra; Braehler, Elmar; Senf, Wolfgang (Psychotherapie Psychosomatik Medizinische Psychologie, 2008)
Keywords: migration; PTSD; trauma; primary care; Essen Trauma Inventory

Traumatic Events, Posttraumatic Stress Disorder and Utilization of Psychotherapy in Immigrants of Polish Origin in Germany - Morawa, Eva; Erim, Yesim (Psychotherapie Psychosomatik Medizinische Psychologie, 2016)
EVALuna2:24043

Traumatische Kindheitserlebnisse bei behandlungsaufsuchenden Patientinnen mit pathologischem Kaufen - eine Pilotstudie - Laskowski, Nora M.; Gockeln, Laura; Tahmassebi, Nadja; Georgiadou, Ekaterini; Hillemacher, Thomas; Zwaan, Martina De; Moller, Astrid (Verhaltenstherapie und Verhaltensmedizin, 2019)
This pilot study investigated the breadth of childhood trauma exposure in treatment-seeking patients with buying-shopping disorder n = 97) compared to patients with gambling disorder (n = 44), alcohol use disorder (n = 47) and consecutive inpatients with other mental health disorders (n = 93). All patients answered the German version of the Adverse Childhood Experiences Questionnaire (ACE-D). The results indicate a high level of ACEs in all four groups, which is higher than in population-based samples. There were no significant group differences in the mean number of reported ACE categories. It appears that exposure to childhood trauma is an unspecific rather than a specific risk factor for buying-shopping disorder. The results should be taken into consideration regarding treatment approaches.
CRIS-Team Scopus Importer:2020-02-21
Keywords: Adverse childhood experience ques-tionnaire; Buying-shopping disorder; Childhood trauma; Compulsive buying

Treadmill exercise intervention improves gait and postural control in alpha-synuclein mouse models without inducing cerebral autophagy - Minakaki, Georgia; Canneva, Fabio; Chevessier, Frederic; Bode, Frederik; Menges, Stefanie; Timotius, Ivanna; Kalinichenko, Liubov; Meixner, Holger; Müller, Christian P.; Eskofier, Björn; Casadei, Nicolas; Riess, Olaf; et al. (Behavioural Brain Research, 2019)
Gait and postural control dysfunction are prototypical symptoms compromising quality of life for patients with Parkinson’s disease (PD). Hallmarks of cellular pathology are dopaminergic degeneration and accumulation of the cytosolic protein alpha-synuclein, linked to impaired autophagy-lysosome pathway (ALP) clearance. Physical exercise improves gait in PD patients and motor function in rodent lesion models. Moreover, exercise is considered neuroprotective and ALP induction has been reported, e.g. in human skeletal muscle, rodent peripheral and cerebral tissues. A combined analysis of how distinct exercise paradigms affect motor and central biochemical aspects of PD could maximize benefits for patients. Here we examine the effect of 4 weeks treadmill exercise intervention in 7-8 month non-lesioned mice on a) distinct gait categories, b) ALP activity, c) dopaminergic and alpha-synuclein homeostasis. The study includes wild type, alpha-synuclein knockout, and mice exclusively expressing human alpha-synuclein. Parameters of gait regularity and stability, activity, and dynamic postural control during unforced walk, were assessed by an automated system (CatWalk XT). At baseline, alpha-synuclein mouse models exhibited irregular and less active gait, with impaired dynamic postural control, compared to wild type mice. Treadmill exercise particularly improved speed and stride length, while increasing dual diagonal versus three-paw body support in both the alpha-synuclein knockout and transgenic mice. Biochemical analyses showed higher striatal tyrosine hydroxylase immuno-reactivity and reduced higher-order alpha-synuclein species in the cerebral cortex. However, no significant cerebral ALP induction was measured. In summary, treadmill exercise improved gait activity and postural stability, and promoted dopaminergic and alpha-synuclein homeostasis, without robustly inducing cerebral ALP.<br
Keywords: alpha-synuclein; autophagy; instrumented gait analysis; mouse gait pattern; Parkinson´s disease; treadmill exercise

Treating depression in an outpatient setting: Predictors of patient response to bouldering psychotherapy, cognitive behavioural therapy or exercise alone - Luttenberger, Katharina; Donath, Carolin; Grässel, Elmar; Kornhuber, Johannes; Schlüter, Annika; Dorscht, Lisa; Kind, Leona (Clinical Psychology & Psychotherapy, 2023)
Background: Bouldering psychotherapy (BPT) for depression has proven effective, but nothing is known about its potential predictors of response. This study should identify predictors of response to BPT, cognitive behavioural therapy (CBT) and an active control (home-based exercise programme; EP) using a literature-based model. Methods: In a multicentre randomised controlled trial, 233 outpatients were assigned to BPT, CBT or EP. Response (reduction of at least 46% on the Montgomery–Åsberg Depression Rating Scale [MADRS]) and remission (≤7 MADRS points) were defined as suggested by the literature. Predictors of response were identified twofold: (1) univariate analyses followed by logistic regression analyses in each group with all predictors yielding a univariate p-value <.20 and (2) a backward regression analysis with all potential predictors. Only variables that emerged as predictors in both types of analyses were interpreted. Results: There was a significantly greater proportion of responders (p =.035) in the BPT than in the EP. The chance of response in the BPT was higher for patients with a higher health-related quality of life. In the EP, response was higher for patients with lower interpersonal sensitivity, suffering from their first episode and living with a partner. Conclusions: Response rates in BPT are similar to or even higher than in other outpatient psychotherapy group therapies. BPT and CBT are suitable for a wide range of patients, but patients with higher functionality could start with psychoeducation and exercise.
CRIS-Team Scopus Importer:2023-09-15
Keywords: bouldering; cognitive behavioural therapy; depression; exercise; group psychotherapy; psychotherapy

Treatment escalation in patients not responding to pharmacotherapy, psychotherapy, and electro-convulsive therapy: experiences from a novel regimen using intravenous S-ketamine as add-on therapy in treatment-resistant depression - Kallmünzer, Bernd; Volbers, Bastian; Karthaus, Anne; Tektas, Ozan Yueksel; Kornhuber, Johannes; Mueller, Helge H. (Journal of Neural Transmission, 2016)
A lack of response despite maximum therapy is common in patients fulfilling criteria of treatment-resistant depression. Therefore, innovative strategies for treatment escalation are warranted. Here, we report the clinical experiences associated with a novel therapeutic regimen combining electroconvulsive therapy and repeated intravenous S-ketamine treatment in three patients. The combined therapy was feasible and had no serious side effects. All patients responded to the new treatment option. The augmentative effect of sub-anesthetic S-ketamine on ECT is discussed.
EVALuna2:22270

Treatment of stroke - Koehrmann, M.; Schwab, Sibylle (Medizinische Klinik - Intensivmedizin und Notfallmedizin, 2017)
EVALuna2:33130

Trigeminal Stimulus Menthol Masks Bitter Off-Flavor of Artificial Sweetener Acesulfame-K - Buechner, Kai; Haagen, Jana; Sastrosubroto, Ashtri; Kerpes, Roland; Freiherr, Jessica; Becker, Thomas (Foods, 2022)
Consumer health concerns and regulatory policies lead to a growing demand for sugar-sweetened beverage alternatives. A reduced energy content can be achieved using artificial sweeteners, which often also convey a metallic or bitter off-flavor. Therefore, the alteration of sweetness perception and masking of potential off-flavors are paramount for improving sweet beverages. Trigeminal stimuli, such as capsaicin (spicy) or menthol (cooling), have been used to influence taste perception in food items, although their use in beverages has not yet been systematically investigated. Here, the influence of menthol on sweetness perception in an aqueous solution is examined both on the sensory and psychophysiological level. The addition of menthol had no sensory effect on sweetness perception; however, psychophysiological measurements suggest a boost in the physiological response to cold perception through the addition of sugar. Moreover, menthol addition shifted the recognition threshold of unpleasant bitterness of the sweetener acesulfame-K from 21.35 to 36.93 mg/L, masking the off-flavor. These findings illuminate the complexity of trigeminal perception influences on taste. Further investigation of these effects can render trigeminal stimuli an effective tool to enhance beverage aroma and flavor.
CRIS-Team Scopus Importer:2022-10-07
Keywords: artificial sweetener; menthol; nervus trigeminus; off-flavor; psychophysiology

Trimodal processing of complex stimuli in inferior parietal cortex is modality-independent - Porada, Danja K.; Regenbogen, Christina; Freiherr, Jessica; Seubert, Janina; Lundström, Johan N. (Cortex, 2021)
In humans, multisensory mechanisms facilitate object processing through integration of sensory signals that match in their temporal and spatial occurrence as well as their meaning. The generalizability of such integration processes across different sensory modalities is, however, to date not well understood. As such, it remains unknown whether there are cerebral areas that process object-related signals independently of the specific senses from which they arise, and whether these areas show different response profiles depending on the number of sensory channels that carry information. To address these questions, we presented participants with dynamic stimuli that simultaneously emitted object-related sensory information via one, two, or three channels (sight, sound, smell) in the MR scanner. By comparing neural activation patterns between various integration processes differing in type and number of stimulated senses, we showed that the left inferior frontal gyrus and areas within the left inferior parietal cortex were engaged independently of the number and type of sensory input streams. Activation in these areas was enhanced during bimodal stimulation, compared to the sum of unimodal activations, and increased even further during trimodal stimulation. Taken together, our findings demonstrate that activation of the inferior parietal cortex during processing and integration of meaningful multisensory stimuli is both modality-independent and modulated by the number of available sensory modalities. This suggests that the processing demand placed on the parietal cortex increases with the number of sensory input streams carrying meaningful information, likely due to the increasing complexity of such stimuli.
CRIS-Team Scopus Importer:2021-05-21
Keywords: Auditory-visual-olfactory; Inferior parietal cortex; Intraparietal sulcus; Multisensory integration; Object information; Trimodal

Türkischstämmige Patientinnen mit masochistischen Persönlichkeitsanteilen und ein türkisches Märchen als therapeutisches Instrument: Der Einsatz von Märchen als kultursensible Intervention. - Erim, Yesim; Senf, Wolfgang (Psychotherapie & Sozialwissenschaft, 2007)

Two of a kind? Mapping the psychopathological space between obesity with and without binge eating disorder - Sommer, Laura Marie; Halbeisen, Georg; Erim, Yesim; Paslakis, Georgios (Nutrients, 2021)
(1) Background: Obesity (OB) is a frequent co-morbidity in Binge Eating Disorder (BED), suggesting that both conditions share phenotypical features along a spectrum of eating-related behaviors. However, the evidence is inconsistent. This study aimed to comprehensively compare OB-BED patients against OB individuals without BED and healthy, normal-weight controls in general psychopathological features, eating-related phenotypes, and early life experiences. (2) Methods: OB-BED patients (n = 37), OB individuals (n = 50), and controls (n = 44) completed a battery of standardized questionnaires. Responses were analyzed using univariate comparisons and dimensionality reduction techniques (linear discriminant analysis, LDA). (3) Results: OB-BED patients showed the highest scores across assessments (e.g., depression, emotional and stress eating, food cravings, food addiction). OB-BED patients did not differ from OB individuals in terms of childhood traumatization or attachment styles. The LDA revealed a two-dimensional solution that distinguished controls from OB and OB-BED in terms of increasing problematic eating behaviors and attitudes, depression, and childhood adversities, as well as OB-BED from OB groups in terms of emotional eating tendencies and self-regulation impairments. (4) Conclusions: Findings support the idea of a shared spectrum of eating-related disorders but also highlight important distinctions relevant to identifying and treating BED in obese patients.
CRIS-Team Scopus Importer:2021-11-05
Keywords: Binge eating disorder; Childhood trauma questionnaire; Emotional eating; Food addiction; Impulsivity; Obesity; Psychotherapy

Überlegungen zur professionellen Versorgung transsexueller Menschen - Erim, Yesim; Feldmann, Christiane; Ghiassi, Valerie; Senf, Wolfgang (Psychotherapie im Dialog, 2009)

Under What Conditions Can People With Severe Dementia in Nursing Homes Benefit From a Multicomponent Psychosocial Intervention? - Diehl, Kristina; Kratzer, André; Grässel, Elmar (Gesundheitswesen, Supplement, 2023)
Background The majority of psychosocial interventions are considered effective in the treatment of dementia symptoms. However, there are hardly any evaluated concepts for people with severe dementia. An RCT study of patients with severe dementia in nursing homes during the Covid-19 pandemic found no effect of the newly developed multi-component intervention MAKS-s (motor, activities of daily living, cognitive, social version for persons with severe dementia) on patients quality of life, behavioural and psychological symptoms. Material and methods At the end of the controlled phase, 6 months after beginning of the study, the nursing staff of the control groups were also trained in MAKS-s. They were then free to decide whether and how often they wanted to use MAKS-s (open phase). By means of a written follow-up survey, conconducted with trained therapists, after another 6 months, predictors for positive effects of the intervention on people with severe dementia were to be identified. The survey also aimed to identify predictors of therapy fidelity. Data acquisition based on a self-developed questionnaire, assessing the therapists' subjective ratings of the three areas of structure, process and outcome quality of the MAKS-s intervention. Apart from descriptive evaluations, the predictors of benefit for people with severe dementia were analysed using a linear regression model and the predictors of therapy fidelity by using a binary logistic regression model. Results The more pronounced the normative restrictions due to the Covid-19 pandemic were, the more frequently manual deviations were observed. Fewer deviations from the manual were significantly associated with positive effects on people with severe dementia. Conclusion The results indicate the importance of therapy fidelity for the success of MAKS-s intervention. Therapy fidelity is decisive for the extent of the positive effects of MAKS-s, experienced by the therapists. Furthermore, the survey results show that activity-restricting pandemic policies in nursing homes negatively influenced the perceived effectiveness.
CRIS-Team Scopus Importer:2023-10-20
Keywords: Covid-19; dementia; nursing homes; psychosocial intervention; Treatment adherence and compliance

Unraveling corticobasal syndrome and alien limb syndrome with structural brain imaging - Albrecht, Franziska; Mueller, Karsten; Ballarini, Tommaso; Lampe, Leonie; Diehl-Schmid, Janine; Fassbender, Klaus; Fliessbach, Klaus; Jahn, Holger; Jech, Robert; Kassubek, Jan; Kornhuber, Johannes; Landwehrmeyer, Bernhard; et al. (Cortex, 2019)
Alien limb phenomenon is a rare syndrome associated with a feeling of non-belonging and disowning toward one's limb. In contrast, anarchic limb phenomenon leads to involuntary but goal-directed movements. Alien/anarchic limb phenomena are frequent in corticobasal syndrome (CBS), an atypical parkinsonian syndrome characterized by rigidity, akinesia, dystonia, cortical sensory deficit, and apraxia. The structure–function relationship of alien/anarchic limb was investigated in multi-centric structural magnetic resonance imaging (MRI) data. Whole-group and single-subject comparisons were made in 25 CBS and eight CBS-alien/anarchic limb patients versus controls. Support vector machine was used to see if CBS with and without alien/anarchic limb could be distinguished by structural MRI patterns. Whole-group comparison of CBS versus controls revealed asymmetric frontotemporal atrophy. CBS with alien/anarchic limb syndrome versus controls showed frontoparietal atrophy including the supplementary motor area contralateral to the side of the affected limb. Exploratory analysis identified frontotemporal regions encompassing the pre-/and postcentral gyrus as compromised in CBS with alien limb syndrome. Classification of CBS patients yielded accuracies of 79%. CBS-alien/anarchic limb syndrome was differentiated from CBS patients with an accuracy of 81%. Predictive differences were found in the cingulate gyrus spreading to frontomedian cortex, postcentral gyrus, and temporoparietoocipital regions. We present the first MRI-based group analysis on CBS-alien/anarchic limb. Results pave the way for individual clinical syndrome prediction and allow understanding the underlying neurocognitive architecture.
CRIS-Team Scopus Importer:2019-05-02
Keywords: Alien limb syndrome; Anarchic limb syndrome; Corticobasal syndrome; Diagnosis prediction; Support vector machine

Update on structured pain assessment for the documentation of diagnosis-independent symptoms and signs associated with pain - Grömer, Teja W.; Atasever, André T.; Käfferlein, Wolfgang; Janoschka, Jonas; Moeller, Sebastian; Dohrenbusch, Ralf; Kappis, Bernd; Maihöfner, Christian; Lücke, Caroline; Kornhuber, Johannes; Philipsen, Alexandra; Müller, Helge H.O. (Schmerz, 2019)
Concerning the diagnosis and therapy of pain syndromes, standardized descriptions similar to those used in the examination of psychopathological findings via the system produced by the AMDP (“Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie”, i. e., the working group establishing standardized methodology and documentation within psychiatry) are still lacking. Therefore, the authors of this article have founded a working group to establish standardized methodology and documentation for symptoms and signs associated with pain, although not at a diagnosis-specific level, in order to promote standardization in the documentation of pain and rating of the symptoms associated with a given set of medical results. This article presents a system for documenting the symptoms and signs associated with pain globally and independently of the diagnosis (Structured Pain Assessment System) with nomenclature that is inspired by the AMDP system. The objective of this working group is to develop documentation for a uniform multidimensional pain assessment (with defined terminology) that serves as a comparable and unified standard in the field.
CRIS-Team Scopus Importer:2019-06-07
Keywords: Assessment of pain; Classification; Diagnostic tool; Pain syndromes; Standardization

Up to a Third of Renal Transplant Recipients Have Deficiencies in Cognitive Functioning - Stößel, Lisa; Schieber, Katharina; Jank, Sabine; Reber, Sandra Therese; Grundmann, Franziska; Lüker, Christine; Vitinius, Frank; Paslakis, Georgios; Eckardt, Kai-Uwe; Erim, Yesim (Progress in Transplantation, 2017)

Urinary ethyl glucuronide testing detects alcohol consumption in alcoholic liver disease patients awaiting liver transplantation - Erim, Yesim; Böttcher, Michael; Dahmen, Uta; Beck, Olof; Broelsch, Christoph E.; Helander, Anders (Liver Transplantation, 2007)

Usability evaluation of an offline electronic data capture app in a prospective multicenter dementia registry (digidem bayern): Mixed method study - Reichold, Michael; Heß, Miriam; Kolominsky-Rabas, Peter; Grässel, Elmar; Prokosch, Hans-Ulrich (JMIR Formative Research, 2021)
Background: Digital registries have been shown to provide an efficient way of gaining a better understanding of the clinical complexity and long-term progression of diseases. The paperless method of electronic data capture (EDC) during a patient interview saves both time and resources. In the prospective multicenter project "Digital Dementia Registry Bavaria (digiDEM Bayern)," interviews are also performed on site in rural areas with unreliable internet connectivity. It must be ensured that EDC can still be performed in such a context and that there is no need to fall back on paper-based questionnaires. In addition to a web-based data collection solution, the EDC system REDCap (Research Electronic Data Capture) offers the option to collect data offline via an app and to synchronize it afterward. Objective: The aim of this study was to evaluate the usability of the REDCap app as an offline EDC option for a lay user group and to examine the necessary technology acceptance of using mobile devices for data collection. The feasibility of the app-based offline data collection in the digiDEM Bayern dementia registry project was then evaluated before going live. Methods: An exploratory mixed method design was employed in the form of an on-site usability test with the "Thinking Aloud" method combined with an online questionnaire including the System Usability Scale (SUS). The acceptance of mobile devices for data collection was surveyed based on five categories of the technology acceptance model. Results: Using the "Thinking Aloud" method, usability issues were identified and solutions were accordingly derived. Evaluation of the REDCap app resulted in a SUS score of 74, which represents "good" usability. After evaluating the technology acceptance questionnaire, it can be concluded that the lay user group is open to mobile devices as interview tools. Conclusions: The usability evaluation results show that a lay user group generally agree that data collecting partners in the digiDEM project can handle the REDCap app well. The usability evaluation provided statements about positive aspects and could also identify usability issues relating to the REDCap app. In addition, the current technology acceptance in the sample showed that heterogeneous groups of different ages with diverse experiences in handling mobile devices are also ready for the use of app-based EDC systems. Based on these results, it can be assumed that the offline use of an app-based EDC system on mobile devices is a viable solution for collecting data in a decentralized registry-based research project.
CRIS-Team Scopus Importer:2021-11-19
Keywords: Dementia; Digital health; Electronic data collection; Evaluation; Mobile app; Mobile device; Offline; Registry; Usability; Usability testing

Usefulness of a Tailored eHealth Service for Informal Caregivers and Professionals in the Dementia Treatment and Care Setting: The eHealthMonitor Dementia Portal - Schaller, Sandra; Marinova-Schmidt, Velislava; Setzer, Manuela; Kondylakis, Haridimos; Griebel, Lena; Sedlmayr, Martin; Grässel, Elmar; Maler, Juan Manuel; Kirn, Stefan; Kolominsky-Rabas, Peter (JMIR Research Protocols, 2016)
The European eHealthMonitor project (eHM) developed a user-sensitive and interactive Web portal for the dementia care setting called the eHM Dementia Portal (eHM-DP). It aims to provide targeted support for informal caregivers of persons with dementia and professionals.The objective of this study was to assess the usefulness and impact of the eHM-DP service in the dementia care setting from two user perspectives: informal caregivers and professionals.The evaluation study was conducted from June to September 2014 and followed a before-after, user-participatory, mixed-method design with questionnaires and interviews. The used intervention was the eHM-DP: an interactive Web portal for informal caregivers and professionals that was tested for a 12-week period. Primary outcomes for caregivers included empowerment, quality of life, caregiver burden, decision aid, as well as perceived usefulness and benefits of the eHM-DP. Primary outcomes for professionals involved decision aid, perceived usefulness, and benefits of the eHM-DP.A total of 25 informal caregivers and 6 professionals used the eHM-DP over the 12-week study period. Both professionals and informal caregivers indicated perceived benefits and support by the eHM-DP. In total, 65% (16/25) of informal caregivers would use the eHM-DP if they had access to it. Major perceived benefits were individualized information acquisition, improved interaction between informal caregivers and professionals, access to support from home, and empowerment in health-related decisions (PrepDM Score: 67.9). Professionals highlighted the improved treatment and care over the disease course (83%, 5/6) and improved health care access for people living in rural areas (67%, 4/6). However, there was no improvement in caregiver burden (Burden Scale for Family Caregivers) and quality of life (EuroQol-5D-5L) over the study period.Our study provides insight into the different user perspectives on an eHealth support service in the dementia treatment and care setting. These results are of importance for future developments and the uptake of eHealth solutions in the dementia domain and reinforce the importance of early user involvement. Turning to the primary target of the eHM-DP service, our findings suggest that the eHM-DP service proved to be a valuable post-diagnostic support service, in particular for the home-based care setting. Further research on a larger scale is needed to enhance the implementation in existing health care infrastructures.
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Utility of the Repeat and Point Test for Subtyping Patients with Primary Progressive Aphasia - Seckin, Mustafa; Ricard, Ingrid; Raiser, Theresa; Heitkamp, Nari; Ebert, Anne; Prix, Catharina; Levin, Johannes; Diehl-Schmid, Janine; Riedl, Lina; Roßmeier, Carola; Hoen, Nora; Schroeter, Matthias L.; et al. (Alzheimer Disease & Associated Disorders, 2022)
Background: Primary progressive aphasia (PPA) may present with three distinct clinical sybtypes: semantic variant PPA (svPPA), nonfluent/agrammatic variant PPA (nfvPPA), and logopenic variant PPA (lvPPA). Objective: The aim was to examine the utility of the German version of the Repeat and Point (R&P) Test for subtyping patients with PPA. Method: During the R&P Test, the examiner reads out aloud a noun and the participants are asked to repeat the word and subsequently point to the corresponding picture. Data from 204 patients (68 svPPA, 85 nfvPPA, and 51 lvPPA) and 33 healthy controls were analyzed. Results: Controls completed both tasks with >90% accuracy. Patients with svPPA had high scores in repetition (mean=9.2±1.32) but low scores in pointing (mean=6±2.52). In contrast, patients with nfvPPA and lvPPA performed comparably in both tasks with lower scores in repetition (mean=7.4±2.7 for nfvPPA and 8.2±2.34 for lvPPA) but higher scores in pointing (mean=8.9±1.41 for nfvPPA and 8.6±1.62 for lvPPA). The R&P Test had high accuracy discriminating svPPA from nfvPPA (83% accuracy) and lvPPA (79% accuracy). However, there was low accuracy discriminating nfvPPA from lvPPA (<60%). Conclusion: The R&P Test helps to differentiate svPPA from 2 nonsemantic variants (nfvPPA and lvPPA). However, additional tests are required for the differentiation of nfvPPA and lvPPA.
CRIS-Team Scopus Importer:2022-02-11
Keywords: Agrammatism; Classification; Primary progressive aphasia; Repetition; Single-word comprehension

Vagus Nerve Stimulation As an Adjunctive Neurostimulation Tool in Treatment-resistant Depression - Moeller, Sebastian; Luecke, Caroline; Heinen, Christian; Bewernick, Bettina H.; Aydin, Merve; Lam, Alexandra P.; Groemer, Teja W.; Philipsen, Alexandra; Mueller, Helge H. O. (Journal of Visualized Experiments, 2019)
Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression (TRD). VNS exhibits antidepressive and stabilizing effects. This method is particularly useful as a long-term treatment, in which up to two-thirds of patients respond. The vagus nerve stimulator is positioned on the left vagus nerve during a surgical procedure and is activated telemetrically by a wand connected to a handheld computerized device. The treating physician can perform various adjustments of the vagus nerve stimulator during in-office visits (e.g., by modifying stimulation intensity or stimulation frequency) to achieve maximum therapeutic effects with low side effects. Set-up of the device usually takes several months. Typical side effects include wound infection, temporary salivation, coughing, paralysis of the vocal cords, bradycardia, or even asystole. The patient can stop the VNS by placing a magnet over the generator. The current protocol describes delivery of the specific stimulation tool and methods for adjusting the tuning parameters to achieve the best remission rates in patients with TRD.
CRIS-Team WoS Importer:2019-02-21

Valence-dependent effects of neuropeptide Y on the expression of conditioned fear and anxiety-like behavior: Involvement of the bed nucleus of the stria terminalis - Kornhuber, Johannes; Zoicas, Iulia (Neuropharmacology, 2024)
Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We have previously shown that intracerebroventricular administration of NPY reduces the expression of social fear via simultaneous activation of Y1 and Y2 receptors in a mouse model of social fear conditioning (SFC). In the present study, we investigated whether the anteroventral bed nucleus of the stria terminalis (BNSTav) mediates these effects of NPY, given the important role of BNSTav in regulating anxiety- and fear-related behaviors. We show that while NPY (0.1 nmol/0.2 μl/side) did not reduce the expression of SFC-induced social fear in male CD1 mice, it reduced the expression of both cued and contextual fear by acting on Y2 but not on Y1 receptors within the BNSTav. Prior administration of the Y2 receptor antagonist BIIE0246 (0.2 nmol/0.2 μl/side) but not of the Y1 receptor antagonist BIBO3304 trifluoroacetate (0.2 nmol/0.2 μl/side) blocked the effects of NPY on the expression of cued and contextual fear. Similarly, NPY exerted non-social anxiolytic-like effects in the elevated plus maze test but not social anxiolytic-like effects in the social approach avoidance test by acting on Y2 receptors and not on Y1 receptors within the BNSTav. These results suggest that administration of NPY within the BNSTav exerts robust Y2 receptor-mediated fear-reducing and anxiolytic-like effects specifically in non-social contexts and add a novel piece of evidence regarding the neural underpinnings underlying the effects of NPY on conditioned fear and anxiety-like behavior.
CRIS-Team Scopus Importer:2024-01-26
Keywords: Anxiety; BNSTav; Contextual fear; Cued fear; Neuropeptide Y; NPY receptor antagonist

Validation of the Benefits of Being a Caregiver Scale (BBCS) – further development of an independent characteristic of informal caregiving - Pendergrass, Anna; Weiß, Saskia; Rohleder, Nicolas; Grässel, Elmar (BMC Geriatrics, 2023)
Background: Although larger amounts of scientific attention have been directed toward the concept of positive aspects of caregiving (PAC) in recent years, a globally uniform definition and a suitable, scientifically valid questionnaire for all informal caregivers have yet to be developed. On the basis of the questionnaires that already exist for measuring PAC, the authors aimed to (a) concretize the concept and (b) develop a new scale by focusing only on items that show that family caregivers experience a benefit for themselves and that the benefit they experience is the result of their caregiving activities. Methods: The Benefits of Being a Caregiver Scale (BBCS) was validated on data from 961 informal caregivers. Cronbach's alpha was calculated to assess the internal consistency of the items, and a factor analysis was conducted to determine the structure of the BBCS. The discriminatory power and item difficulties were examined. Construct validity was established by testing four hypotheses. Results: The factor analysis confirmed the single-factor structure of the BBCS. Cronbach's alpha for the total scale was 0.922. One of the 15 items did not show good to very good discriminatory power and was excluded from the final version of the scale. A higher BBCS score was observed if the caregiver experienced more positive aspects of caregiving and tended to have better general coping skills and a positive relationship with the care-receiver. The BBCS score was not associated with the subjective burden of the caregiver. Results confirmed the validity of the BBCS. Conclusion: The BBCS is a valid assessment instrument for measuring the benefits that caregivers experience from their caregiving work and can easily be used in research and practice. The BBCS is available free of charge in English and German (http://www.caregiver-benefits.de).
CRIS-Team Scopus Importer:2023-01-27
Keywords: Benefits of Being a Caregiver Scale; Discriminatory power; Factor analysis; Item difficulty; Positive aspects of caregiving; Reliability; Validity

Validation of the Erlangen Score Algorithm for Differential Dementia Diagnosis in Autopsy-Confirmed Subjects - Somers, Charisse; Lewczuk, Piotr; Sieben, Anne; Van Broeckhoven, Christine; De Deyn, Peter Paul; Kornhuber, Johannes; Martin, Jean-Jacques; Bjerke, Maria; Engelborghs, Sebastiaan (Journal of Alzheimer's Disease, 2019)
Background: Despite decades of research on the optimization of the diagnosis of Alzheimer's disease (AD), its biomarker-based diagnosis is being hampered by the lack of comparability of raw biomarker data. In order to overcome this limitation, the Erlangen Score (ES), among other approaches, was set up as a diagnostic-relevant interpretation algorithm.
CRIS-Team WoS Importer:2019-04-23

Validation of the Erlangen Score Algorithm for the Prediction of the Development of Dementia due to Alzheimer's Disease in Pre-Dementia Subjects - Lewczuk, Piotr; Kornhuber, Johannes; Toledo, Jon B.; Trojanowski, John Q.; Knapik-Czajka, Malgorzata; Peters, Oliver; Wiltfang, Jens; Shaw, Leslie M. (Journal of Alzheimer's Disease, 2015)
In previous studies, a dichotomous stratification of subjects into "cerebrospinal fluid (CSF) normal" and "CSF pathologic" was used to investigate the role of biomarkers in the prediction of progression to dementia in pre-dementia/mild cognitive impairment subjects. With the previously published Erlangen Score Algorithm, we suggested a division of CSF patterns into five groups, covering all possible CSF result combinations based on the presence of pathologic tau and/or amyloid-? CSF values.This study aimed to validate the Erlangen Score diagnostic algorithm based on the results of biomarkers analyses obtained in different patients cohorts, with different pre-analytical protocols, and with different laboratory analytical platforms.We evaluated the algorithm in two cohorts of pre-dementia subjects: the US-Alzheimer's Disease Neuroimaging Initiative and the German Dementia Competence Network.In both cohorts, the Erlangen scores were strongly associated with progression to Alzheimer's disease. Neither the scores of the progressors nor the scores of the non-progressors differed significantly between the two projects, in spite of significant differences in the cohorts, laboratory methods, and the samples treatment.Our findings confirm the utility of the Erlangen Score algorithm as a useful tool in the early neurochemical diagnosis of Alzheimer's disease.
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Validation of the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM) - Luttenberger, Katharina; Reppermund, Simone; Schmiedeberg-Sohn, Anke; Book, Stephanie; Grässel, Elmar (BMC Geriatrics, 2016)
There are currently no valid, fast, and easy-to-administer performance tests that are designed to assess the capacities to perform activities of daily living in persons with mild dementia and mild cognitive impairment (MCI). However, such measures are urgently needed for determining individual support needs as well as the efficacy of interventions. The aim of the present study was therefore to validate the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia and Mild Cognitive Impairment (ETAM), a performance test that is based on the International Classification of Functioning and Health (ICF), which assesses the relevant domains of living in older adults with MCI and mild dementia who live independently.The 10 ICF-based items on the research version of the ETAM were tested in a final sample of 81 persons with MCI or mild dementia. The items were selected for the final version in accordance with 6 criteria: 1) all domains must be represented and have equal weight, 2) all items must load on the same factor, 3) item difficulties and item discriminatory powers, 4) convergent validity (Bayer Activities of Daily Living Scale [B-ADL]) and discriminant validity (Mini Mental State Examination [MMSE], Geriatric Depression Scale 15 [GDS-15]), 5) inter-rater reliabilities of the individual items, 6) as little material as possible. Retest reliability was also examined. Cohen's ds were calculated to determine the magnitudes of the differences in ETAM scores between participants diagnosed with different grades of severity of cognitive impairment.The final version of the ETAM consists of 6 items that cover the five ICF domains communication, mobility, self-care, domestic life (assessed by two 3-point items), and major life areas (specifically, the economic life sub-category) and load on a single factor. The maximum achievable score is 30 points (6 points per domain). The average administration time was 35 min, 19 of which were needed for pure item performance. The internal consistency was ? = .71. The three-week test-retest reliability was r = .78, and the inter-rater reliability was r = .97. The ETAM also provided satisfactory discrimination between healthy individuals and persons with MCI or mild dementia as well as between persons with mild and moderate dementia.The 6-item final version of the ETAM shows satisfactory psychometric characteristics and can be administered quickly. It is therefore suitable for use in both clinical practice and research.
EVALuna2:23761

Validation of the Turkish version of the Screening for Somatoform Disorders (SOMS) - Erim, Yesim; Beckmann, Mingo; Tagay, Sefik; Ayguen, Sanem; Gencoglu, Peykan Goekalp; Senf, Wolfgang (Diagnostica, 2012)
Keywords: migration; somatization; medically unexplained symptoms; validation; screening

Validierter SKT als Multimodale Telemedizinische Applikation - Soutschek, Stefan; Spiegl, Werner; Gropp, Martin; Steidl, Stefan; Nöth, Elmar; Erzigkeit, Hellmut; Hornegger, Joachim; Kornhuber, Johannes (Tagungsband zum 2. deutschen AAL-Kongress (2. Deutscher AAL (Ambient Assisted Living)-Kongress Berlin), 2009)
Ziel dieser Arbeit ist die Verringerung von Beurteilereinflüssen bei psychometrischen Tests, wie dem Syndrom-Kurztest (SKT), d.h. die Steigerung intersubjektiver Übereinstimmung der Beurteiler, durch die Erfassung validitätssteigernder Variablen mit Hilfe multimodaler Sensoren. Beispiele für solche Sensoren sind Mikrofone, Eyetracker oder Touch-Screens. Die Messung kognitiver Leistungsdefizite nimmt insbesondere bei der Diagnose und Therapiekontrolle altersassoziierter Erkrankungen – zu denen etwa die Demenzen zu zählen sind – einen wichtigen Stellenwert ein. Im Rahmen eines von der Bayerischen Forschungsstiftung (BFS) geförderten Forschungsprojektes (FitForAge) wird untersucht, ob es gelingt, ein interaktives Testsystem zur Erfassung von kognitiven Leistungsstörungen zu konstruieren, das für den Einsatz im telemedizinischen Bereich geeignet ist und vom Patienten weitestgehend selbständig ausgeführt werden kann. Als Grundlage für diese Messungen soll der SKT dienen. Der SKT ist ein international validierter Test zur Erfassung von Gedächtnis- und Aufmerksamkeitsstörungen.

Vascular and Neurogenic Rejuvenation in Aging Mice by Modulation of ASM - Park, Min Hee; Lee, Ju Youn; Park, Kang Ho; Jung, In Kyung; Kim, Kyoung-Tae; Lee, Yong-Seok; Ryu, Hyun-Hee; Jeong, Yong; Kang, Minseok; Schwaninger, Markus; Gulbins, Erich; Reichel, Martin; et al. (Neuron, 2018)
Although many reports have revealed dysfunction of endothelial cells in aging, resulting in blood-brain barrier (BBB) breakdown, the underlying mechanism or mechanisms remain to be explored. Here, we find that acid sphingomyelinase (ASM) is a critical factor for regulating brain endothelial barrier integrity. ASM is increased in brain endothelium and/or plasma of aged humans and aged mice, leading to BBB disruption by increasing caveolae-mediated transcytosis. Genetic inhibition and endothelial-specific knockdown of ASM in mice ameliorated BBB breakdown and neurocognitive impairment during aging. Using primary mouse brain endothelial cells, we found that ASM regulated the caveolae-cytoskeleton interaction through protein phosphatase 1-mediated ezrin/radixin/moesin (ERM) dephosphorylation and apoptosis. Moreover, mice with conditional ASM overexpression in brain endothelium accelerated significant BBB impairment and neurodegenerative change. Overall, these results reveal a novel role for ASM in the control of neurovascular function in aging, suggesting that ASM may represent a new therapeutic target for anti-aging.
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Ventricular and lumbar cerebrospinal fluid concentrations of Alzheimer's disease biomarkers in patients with normal pressure hydrocephalus and posttraumatic hydrocephalus - Brandner, Sebastian; Thaler, Christian; Lelental, Natalia; Buchfelder, Michael; Kleindienst, Andrea; Maler, Juan Manuel; Kornhuber, Johannes; Lewczuk, Piotr (Journal of Alzheimer's Disease, 2014)
Little information is available on the rostro-caudal concentration gradient of Alzheimer's disease (AD) biomarkers.We studied the concentrations of amyloid-? (A?) peptides 1-42 and 1-40 as well as the Tau and pTau proteins in simultaneously collected ventricular and lumbar cerebrospinal fluid (CSF) samples.The samples were simultaneously collected from the ventricle and the lumbar spinal canal in two groups of patients: 10 subjects being treated for normal pressure hydrocephalus (NPH) by the placement of a ventriculo-peritoneal shunt and 5 patients treated simultaneously with an external ventricular drain and a lumbar CSF drain due to posttraumatic hydrocephalus (PTH).The ventricular-lumbar (V/L) concentration ratio for A?1-40 was 0.81 in NPH patients and 0.71 in PTH patients. The V/L-ratio for A?1-42 was 0.84 in NPH, reflecting significantly higher concentrations in lumbar CSF than in ventricular CSF, and 1.02 in PTH patients. The V/L-ratios for Tau and pTau differed significantly depending on the diagnostic group: the median V/L-ratio for Tau was 6.83 in NPH patients but only 0.97 in PTH patients. The median V/L-ratio for pTau was 2.36 in NPH patients and 0.91 in PTH patients.We conclude that the rostro-caudal concentration gradient for brain-derived proteins (Tau and pTau in this study) depends on the diagnosis and clinical status of the patient, which were largely neglected in the previously postulated models.
EVALuna2:22827

Verbesserte Qualität gelagerter Erythrozytenkonzentrate durch maschinelle Autotransfusion - Münch, Frank; Purbojo, Ariawan; Wenzel, F.; Kohl, M.; Dittrich, Sven; Rauh, Manfred; Zimmermann, Rüdiger; Kwapil, Nicola (Die Anaesthesiologie, 2022)
Background The transfusion of packed red blood cells (PRBC) is associated with various side effects, including storage damage to PRBCs. The cells change their structure, releasing potassium as well as lactate. Mechanical rinsing, available in many hospitals, is able to remove toxic substances and possibly minimizes the negative side effects of transfusion. Objective The primary aim of our study was to improve the quality of PRBCs before transfusion. The effects of different washing solutions on PRBC quality were analyzed. Material and methods This in vitro study compares 30 mechanically washed PRBCs. They were either processed with standard normal saline 0.9% (n = 15, N group) or a hemofiltration solution containing 4 mmol/l potassium (n = 15, HF group) by a mechanical rinsing device (Xtra, LivaNova, Munich, Germany). A subgroup analysis was performed based on the storage duration of the processed PRBCs (7, 14, 37 days). Samples were taken before washing (EKpra), immediately after washing (EKpost) and 10 h later (EKpost10h), after storage in the "wash medium" at room temperature. Concentrations of ATP (probability of survival in transfused erythrocytes), lactate, citrate and electrolytes (potassium, sodium, chloride, calcium) were tested. Results and conclusion Mechanical rinsing improves pretransfusion quality of PRBC. Washing with a hemofiltration solution results in a more physiological electrolyte composition. Even 10 h after mechanical rinsing with a hemofiltration solution, the quality of 37-day-old PRBC is comparable to young PRBC that have been stored for 7 days and have not been washed. Washing stored PRBC increases the ATP content, which subsequently leads to an increased probability of survival of red cells after transfusion.
CRIS-Team WoS Importer:2022-08-26

Versorgungsbedarf in einer psychosomatischen Spezialambulanz für Geflüchtete an einem Universitätsklinikum - Beyer, Thomas; Morawa, Eva; Graemer, Katrin; Erim, Yesim (Nervenheilkunde, 2021)
Background After the migration movement of the year 2015, it was often found that the offered psychotherapeutic services were not sufficient to address the expected demand. Objectives The aim of this study was to use a questionnaire to analyze the treatments carried out in a special outpatient clinic at a regular care facility, and to determine their specific aspects. Materials and methods The flow and contents of psychotherapeutic consultations with refugees were discussed in the research team. On this basis, expected settings and interventions were summarized in a questionnaire. This served as a retrospective study of the treatments carried out. The data were evaluated descriptively. Results 60 treatments of refugees were evaluated. Our results provide a differentiated overview of the contents of the treatments in a group of patients with high mental stress. For example, the seating arrangement in an interpreted conversation was carried out in 56 cases, psychoeducation in 43 cases, regulation of affect and stress in 32 cases, treatment with psycho-pharmaceuticals in 24 cases and the discussion of religious aspects in 28 cases. Conclusions The contents of the examined treatments can be categorized into interventions, special settings, medical-psychotherapeutic treatment, and the attention paid to cultural and religious aspects. It can be argued that in the case of refugees, the establishment and maintenance of the framework conditions of safety, goal clarification, time management and relationship are of great importance. Our results illustrate that in the examined treatments stabilizing interventions took place, but also intercultural and religious aspects were addressed. Especially the establishment of a stable relationship with the refugees is interfered by intercultural and religious aspects and the specificity of the presence of an interpreter and the translation process.
CRIS-Team Scopus Importer:2021-11-19
Keywords: Interventions; Psychotherapy; Refugees; Specialized outpatient unit; Standard care facility

Virtual reality jogging as a novel exposure paradigm for the acute urge to be physically active in patients with eating disorders: Implications for treatment - Paslakis, Georgios; Fauck, Vanessa; Roeder, Kathrin; Rauh, Elisabeth; Rauh, Manfred; Erim, Yesim (International Journal of Eating Disorders, 2017)
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Visualization and ligand-induced modulation of dopamine receptor dimerization at the single molecule level - Tabor, Alina; Weisenburger, S; Banerjee, Ashutosh; Purkayastha, Nirupam; Kaindl, Jonas; Hübner, Harald; Wei, Luxi; Groemer, Teja W.; Kornhuber, Johannes; Tschammer, Nuska; Birdsall, Nigel J.M.; Mashanov, Gregory I.; et al. (Scientific Reports, 2016)
G protein-coupled receptors (GPCRs), including dopamine receptors, represent a group of important pharmacological targets. An increased formation of dopamine receptor D-2 homodimers has been suggested to be associated with the pathophysiology of schizophrenia. Selective labeling and ligand-induced modulation of dimerization may therefore allow the investigation of the pathophysiological role of these dimers. Using TIRF microscopy at the single molecule level, transient formation of homodimers of dopamine receptors in the membrane of stably transfected CHO cells has been observed. The equilibrium between dimers and monomers was modulated by the binding of ligands; whereas antagonists showed a ratio that was identical to that of unliganded receptors, agonist-bound D-2 receptor-ligand complexes resulted in an increase in dimerization. Addition of bivalent D-2 receptor ligands also resulted in a large increase in D2 receptor dimers. A physical interaction between the protomers was confirmed using high resolution cryogenic localization microscopy, with ca. 9 nm between the centers of mass.

Visualization of ligand-induced dopamine D2S and D2L receptor internalization by TIRF microscopy - Tabor, Alina; Möller, Dorothee; Hübner, Harald; Kornhuber, Johannes; Gmeiner, Peter (Scientific Reports, 2017)

Visual selective attention in body dysmorphic disorder, bulimia nervosa and healthy controls - Kollei, Ines; Horndasch, Stefanie; Erim, Yesim; Martin, Alexandra (Journal of psychosomatic research, 2017)
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Vitamin B-Can it prevent cognitive decline? A systematic review and meta-analysis - Behrens, Annika; Grässel, Elmar; Pendergrass, Anna; Donath, Carolin (Systematic Reviews, 2020)
BACKGROUND: Development of cognitive decline represents substantial issues in today's society, steadily gaining importance with increasing life expectancy. One potential approach to preventing cognitive decline is to lower homocysteine by administering vitamin B. In this systematic review and meta-analysis, we address this topic and investigate whether oral supplementation of vitamin B can successfully prevent cognitive decline in cognitively unimpaired individuals. METHODS: A computerized systematic literature search was conducted using the electronic databases PubMed, Embase, and the Cochrane Library. Eligibility criteria included oral supplementation with vitamin B (B1, B6, folic acid, and B12) and the absence of cognitive impairment. A meta-analysis was conducted with "global cognition" as the primary outcome of this review. Secondary outcomes were changes in cognitive function in other cognitive domains reported in the included studies. Risk of bias was assessed according to the Cochrane Risk of Bias tool and the GRADE approach to establish the overall certainty of the evidence. RESULTS: The meta-analysis did not yield a significant overall effect of supplementation with vitamin B on cognitive function (Z = 0.87; p = 0.39; SMD, 0.02; 95% CI, - 0.034, 0.08). A sensitivity analysis focusing on specific risk factors did not alter this result. Some studies reported isolated significant effects of the intervention on secondary outcomes. However, these findings were outnumbered by the number of cognitive tests that did not yield significant effects. DISCUSSION: We found no overall evidence that oral vitamin B supplementation prevented cognitive decline. The isolated significant effects that were reported could be attributed to methodological issues. The results of this review do not provide evidence that population groups with certain risk factors would profit more from the intervention than others. Our findings do not apply to forms of administration other than oral supplementation nor do they offer information regarding the treatment of cognitively impaired individuals via the administration of vitamin B. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017071692.
CRIS-Team Scopus Importer:2020-05-29
Keywords: Cognition[Mesh]; Dementia[Mesh]; Folic Acid[Mesh]; Prevention; Vitamin B12[Mesh]; Vitamin B6[Mesh]

Voice handicap index and voice-related quality of life in small laryngeal carcinoma - Kasper, Claudia; Schuster, Maria; Psychogios, Georgios; Zenk, Johannes; Ströbele, Anika; Rosanowski, Frank; Grässel, Elmar; Haderlein, Tino (European Archives of Oto-Rhino-Laryngology, 2011)

Vulnerable in the end – Longitudinal study among medical students on mental health and personal and work-related resources over a 5.5-year-period - Schneider, Kurt; Breuer, G.; Luibl, Lena; Paulsen, F.; Scholz, Michael; Burger, P. H.M. (Annals of Anatomy-Anatomischer Anzeiger, 2023)
Background: Mental health problems are common in medical professionals and their development already starts at the undergraduate level. Studies on medical students can replicate higher prevalence for depression and burnout in this group, but they normally compare semester cohorts in an anonymized, cross-sectional approach and without a preventive perspective. Methods: We surveyed medical students at the beginning and end of their medical curriculum and collected data on burnout, depressivity, work related experience and salutogenesis parameters with validated self-administered questionnaires. Most remarkably we obtained the data from the same 58 individuals after 5.5 years, representing data of the highest quality in order to compare the mental health status at the beginning and the end of our students´ medical curriculum. Results: Our results not only show a severe exacerbation of physical, mental and emotional burnout in the participants at the end of their studies. The students also do not seem to have sufficient personal (resilience) or social resources (e.g. experience of social support) for coping with their mental health problems around the time of their graduation. Conclusions: Our participants reflect a development of mental health during their medical studies at university that is paving the way to the devastating prevalence of mental disorders and suicide in health professionals. From our results we derive an urgent need to integrate self-care and active coping in the learning goals of medical curricula.
CRIS-Team Scopus Importer:2023-09-29
Keywords: Burnout; Healthcare Professional; Mental Health; Resilience

Was will die MFA? Eine Befragung zu der Arbeitszufriedenheit und den Wünschen von medizinischen Fachangestellten im ambulanten Bereich - Scheerbaum, Petra; Scheerbaum, Martin; Schöffski, Oliver (Gesundheitsökonomie und Qualitätsmanagement, 2024)
Aim Every sixth female entrant to a job-training in Germany pursues employment as a medical assistant. However, there is still insufficient data on the wishes of this group so far. Therefore, we want to investigate this subject. Method Using a regional digital survey, medical assistants in outpatient practices in Middle Franconia and Upper Franconia were asked about the wishes and preferences in their everyday work life. Results Overall, medical assistants are very satisfied related to their workplace as well as to the work with patients. Less approval was given to the areas of communication in the team, leadership behaviour as well as further training opportunities. Conclusion Employers should focus on an open and transparent form of discussion with their medical assistants concerning questions of decisions and personal development.
CRIS-Team Scopus Importer:2024-03-08
Keywords: healthcare professionals; job satisfaction; medical assistant; outpatient sector

Web-based data collection yielded an additional response bias - but had no direct effect on outcome scales - Mayr, Andreas; Gefeller, Olaf; Prokosch, Hans-Ulrich; Pirkl, Anna; Fröhlich, Antje; de Zwaan, Matina (Journal of Clinical Epidemiology, 2012)
Objective: To assess and to evaluate possible effects arising from Web-based data collection on the results of a study. Study Design and Setting: We analyzed participants of the German Weight Control Registry (GWCR) of whom 328 chose to use Web-based questionnaires and 139 preferred to participate via a traditional postal survey. Furthermore, we included data of 212 individuals sampled independently from the general population who fulfilled the study's inclusion criteria - giving us the chance to differentiate between response bias (concerning Web-based data collection) and general selection bias (concerning participation in the GWCR). Results: In addition to selection bias (GWCR participants are overall better educated, more likely to live in a partnership, more often female, and older than the general population), we also found a substantial response bias: Participants using the Internet were younger, better educated, and more often male compared with participants preferring the paper-and-pencil version. However, after adjusting for these differences, we found no additional direct effect of Web-based data collection on any of the outcome variables. Conclusion: Web-based epidemiologic studies still do not attract the same participants as postal surveys, even in highly industrialized countries. However, after adjusting for this bias, the same results can be expected. © 2012 Elsevier Inc. All rights reserved.
UnivIS-Import:2015-04-14:Pub.2012.tech.IMMD.infome.webbas
Keywords: Bias; Data collection; Epidemiologic methods; Internet; Questionnaires; Registries

Web-based mindfulness and skills-based distress reduction for patients with cancer: study protocol of the multicentre, randomised, controlled confirmatory intervention trial Reduct - Baeuerle, Alexander; Martus, Peter; Erim, Yesim; Schug, Caterina; Heinen, Jana; Krakowczyk, Julia Barbara; Steinbach, Jasmin; Damerau, Mirjam; Bethge, Wolfgang; Dinkel, Andreas; Dries, Sebastian; Mehnert-Theuerkauf, Anja; et al. (BMJ Open, 2022)
Introduction Many patients with cancer experience severe psychological distress, but as a result of various barriers, few of them receive psycho-oncological support. E-mental health interventions try to overcome some of these barriers and the limitation of healthcare offers, enabling patients with cancer to better cope with psychological distress. In the proposed trial, we aim to assess the efficacy and cost-effectiveness of the manualised e-mental health intervention Make It Training- Mindfulness-Based and Skills-Based Distress Reduction in Oncology. Make It Training is a self-guided and web-based psycho-oncological intervention, which includes elements of cognitive behavioural therapy, mindfulness-based stress reduction and acceptance and commitment therapy. The training supports the patients over a period of 4 months. We expect the Make It Training to be superior to treatment as usual optimised (TAU-O) in terms of reducing distress after completing the intervention (T1, primary endpoint). Methods and analysis The study comprises a multicentre, prospective, randomised controlled confirmatory interventional trial with two parallel arms. The proposed trial incorporates four distinct measurement time points: the baseline assessment before randomisation, a post-treatment assessment and 3 and 6 month follow-up assessments. We will include patients who have received a cancer diagnosis in the past 12 months, are in a curative treatment setting, are 18-65 years old, have given informed consent and experience high perceived psychological distress (Hospital Anxiety and Depression Scale >= 13) for at least 1 week. Patients will be randomised into two groups (Make It vs TAU-O). The aim is to allocate 600 patients with cancer and include 556 into the intention to treat analysis. The primary endpoint, distress, will be analysed using a baseline-adjusted ANCOVA for distress measurement once the intervention (T1) has been completed, with study arm as a binary factor, baseline as continuous measurement and study centre as an additional categorical covariate. Ethics and dissemination The Ethics Committee of the Medical Faculty Essen has approved the study (21-10076-BO). Results will be published in peer-reviewed journals, conference presentations, the project website, and among self-help organisations.
CRIS-Team WoS Importer:2022-06-24

Web-based MINDfulness and Skills-based distress reduction in cancer (MINDS): study protocol for a multicentre observational healthcare study - Bäuerle, Alexander; Teufel, Martin; Schug, Caterina; Skoda, Eva Maria; Beckmann, Mingo; Schäffeler, Norbert; Junne, Florian; Erim, Yesim; Zipfel, Stephan; Graf, Johanna (BMJ Open, 2020)
INTRODUCTION: Although a high percentage of patients with cancer experience severe psychological distress, few of them receive psycho-oncological care, largely due to barriers on the side of patients and healthcare providers that pose great challenges to delivering such care. In response, low-threshold, self-guided eHealth interventions can enable patients with cancer to deal independently and effectively with disease-related challenges and distress. Mindfulness and Skills-Based Distress Reduction in Oncology Training, nicknamed Make It Training, is one such innovative, self-guided eHealth intervention. In our study, we propose to assess different characteristics of such patients in order to define target populations for Make It Training, evaluate the intervention in terms of its usability, feasibility and sustainability and gather longitudinal data concerning the intervention's efficacy. METHODS AND ANALYSIS: Self-guided and web-based Make It Training consists of eight 30 min modules involving the use of techniques of mindfulness therapy, cognitive-behavioural therapy and acceptance and commitment therapy to be completed in a 4-month period. In our observational study, adult patients with cancer who possess adequate German language skills and provide their informed consent will be recruited at Essen, Erlangen and Tübingen University Hospitals at outpatient oncological institutions and via online channels. Patients will undergo a baseline online assessment (T0), an assessment directly after completing the intervention (T1) and assessments 3 and 6 months later (T2 and T3, respectively). With the results of those assessments, we will perform descriptive analyses of their sociodemographic and medical data, compare means and conduct regression analyses. ETHICS AND DISSEMINATION: The Ethics Committees of the University Hospitals Essen, Erlangen and Tübingen have approved the study (19-8643-BO, 27_19 B, 293/2018BO1). Results will be published in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: DRKS00017119.
CRIS-Team Scopus Importer:2020-08-28
Keywords: mental health; oncology; telemedicine

Wenn es nicht mehr alleine geht – Inanspruchnahme ambulanter Unterstützungsangebote von Menschen mit Demenz: der Bayerische Demenz Survey (BayDem) - Karrer, Linda; Dietzel, Nikolas; Wolff, Franziska; Kratzer, André; Hess, Manuela; Grässel, Elmar; Kolominsky-Rabas, Peter (Gesundheitswesen, 2020)
Background The increasing prevalence of dementia raises challenges concerning the care of people with dementia (pwd). The care of pwd is mainly conducted by informal caregivers who are faced with several burdens; however, use of care services is generally low. The aim of this study was to identify predictors of the use of outpatient care services. Methods The Bavarian Dementia Survey (BayDem) is a multi-centre, longitudinal study that was conducted at 3 different sites in Bavaria, Germany. Participants were people with dementia (pwd) (according to ICD-10) and their informal caregivers. Data were collected by standardised face-to-face interviews using well-designed instruments in cooperation with local partners. Logistic regression analysis was carried out in order to identify predictors of the use of outpatient care services. Results In total, 364 pwd and 339 informal caregivers were included at the beginning of the study BayDem. The use of supportive care services was generally low. One-third of all participants used outpatient care services. In the logistic regression analysis, the following significant predictors for the use of outpatient care services 6 months after baseline were identified: severity of cognitive impairment of the pwd; use of outpatient care at the beginning of the study. Conclusion The low use of outpatient care services is a well-known paradoxical phenomenon. Such services can help give relief to informal caregivers. In order to enhance the use of supportive outpatient care services, there should be more focus on innovative health service delivery models with a low access threshold barrier. Besides more public campaigns, more guidance for existing offers is needed.
CRIS-Team Scopus Importer:2020-02-04
Keywords: informal caregivers; outpatient care; People with dementia; Resource Utilization in Dementia (RUD); use of care services

What Kind of Patients Receive Inpatient and Day-Hospital Treatment in Departments of Psychosomatic Medicine and Psychotherapy in Germany? - Doering, Stephan; Herpertz, Stephan; Hofmann, Tobias; Rose, Matthias; Imbierowicz, Katrin; Geiser, Franziska; Croy, Ilona; Weidner, Kerstin; Rademacher, Jörg; Michalek, Silke; Morawa, Eva; Erim, Yesim; et al. (Psychotherapy and Psychosomatics, 2023)
Introduction: Germany is one of the few countries with a medical specialty of psychosomatic medicine and psychotherapy and many treatment resources of this kind. Objective: This observational study describes the psychosomatic treatment programs as well as a large sample of day-hospital and inpatients in great detail using structured diagnostic interviews. Methods: Mental disorders were diagnosed according to ICD-10 and DSM-IV by means of Mini-DIPS and SCID-II. In addition to the case records, a modified version of the CSSRI was employed to collect demographic data and service use. The PHQ-D was used to assess depression, anxiety, and somatization. Results: 2,094 patients from 19 departments participated in the study after giving informed consent. The sample consisted of a high proportion of "complex patients"with high comorbidity of mental and somatic diseases, severe psychopathology, and considerable social and occupational dysfunction including more than 50 days of sick leave per year in half of the sample. The most frequent diagnoses were depression, somatoform and anxiety disorders, eating disorders, personality disorders, and somato-psychic conditions. Conclusions: Inpatient and day-hospital treatment in German university departments of psychosomatic medicine and psychotherapy is an intensive multimodal treatment for complex patients with high comorbidity and social as well as occupational dysfunction.
CRIS-Team Scopus Importer:2023-02-10
Keywords: Day-hospital; Diagnosis; Inpatient treatment; Psychosomatic medicine; Psychotherapy

What should we eat? - Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2014)
EVALuna2:23634

Which Protective Factors Are Associated with the Mental Health of Syrian Students in Germany? A Register-Based Cross-Sectional Study - Hosari, Remy Rahim; Borho, Andrea; Morawa, Eva; Erim, Yesim (International Journal of Environmental Research and Public Health, 2022)
The aim of this online, register-based cross-sectional study was to investigate the frequency of psychological distress and protective factors among 136 Syrian students in Germany. The survey measured depression and anxiety (Patient Health Questionnaire-4), post-traumatic stress (Impact of Event-Scale-6), as well as resources social support (ENRICHD Social Support Instrument), optimism (Optimism–Pessimism-2 Scale) and religiosity (Duke Religion Index). A total of 26.50% of the sample were female. A total of 38.93% met criteria for clinically relevant depressive respectively generalized anxiety symptoms and 15.72% showed prominent PTSD scores. Participants screened positive for mental distress reported significantly less social support (p = 0.001) and less optimism (p = 0.002) than participants without mental distress. In multiple regression analyses, higher levels of feeling welcome in Germany, social support and intrinsic religiosity were significantly associated with lower levels of depression and generalized anxiety. Significant associations with lower PTSD levels were found with higher levels of social support and optimism. The results show that Syrian students in Germany are more psychologically burdened compared to other Syrian refugee samples, except for PTSD. This suggests that besides the stress caused by flight and trauma, stressors such as studying and social isolation could be considered as additional impediments for mental health and require intervention measures.
CRIS-Team Scopus Importer:2022-12-23
Keywords: depression; generalized anxiety disorder; mental health; post-traumatic stress disorder; protective factors; Syrian students; university

White paper by the Society for CSF Analysis and Clinical Neurochemistry: Overcoming barriers in biomarker development and clinical translation - Teunissen, Charlotte E.; Otto, Markus; Engelborghs, Sebastiaan; Herukka, Sanna-Kaisa; Lehmann, Sylvain; Lewczuk, Piotr; Lleo, Alberto; Perret-Liaudet, Armand; Tumani, Hayrettin; Turner, Martin R.; Verbeek, Marcel M.; Wiltfang, Jens; et al. (Alzheimer's Research and Therapy, 2018)
Body fluid biomarkers have great potential for different clinical purposes, including diagnosis, prognosis, patient stratification and treatment effect monitoring. This is exemplified by current use of several excellent biomarkers, such as the Alzheimer's disease cerebrospinal fluid (CSF) biomarkers, anti-neuromyelitis optica antibodies and blood neurofilament light. We still, however, have a strong need for additional biomarkers and several gaps in their development and implementation should be filled. Examples of such gaps are i) limited knowledge of the causes of neurological diseases, and thus hypotheses about the best biomarkers to detect subclinical stages of these diseases; ii) the limited success translating discoveries obtained by e.g. initial mass spectrometry proteomic low-throughput studies into immunoassays for widespread clinical implementation; iii) lack of interaction among all stakeholders to optimise and adapt study designs throughout the biomarker development process to medical needs, which may change during the long period needed for biomarker development.The Society for CSF Analysis and Clinical Neurochemistry (established in 2015) has been founded as a concerted follow-up of large standardisation projects, including BIOMARKAPD and SOPHIA, and the BioMS-consortium.The main aims of the CSF society are to exchange high level international scientific experience, to facilitate the incorporation of CSF diagnostics into clinical practice and to give advice on inclusion of CSF analysis into clinical guidelines. The society has a broad scope, as its vision is that the gaps in development and implementation of biomarkers are shared among almost all neurological diseases and thus they can benefit from the activities of the society.
EVALuna2:62188

Why are suicides of inpatients so burdensome? - Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2018)
EVALuna2:211635

Winner takes it all: addiction as an example for selfish goal dominance - Müller, Christiane; Amato, Davide (Behavioral and Brain Sciences, 2014)
Here we argue that the selfish goal concept may well be suitable to explain inconsistencies not only in micro-behaviors, but also in the gross behavioral repertoire of an individual, which is often associated with psychopathologies, such as addiction. Neurophysiological evidence for pathological conditions like addiction emerged, and this evidence may also serve as an explanatory model for normal behaviors.
EVALuna2:23663

Wnt/?-catenin signaling via Axin2 is required for myogenesis and, together with YAP/Taz and Tead1, active in IIa/IIx muscle fibers - Huraskin, Danyil; Eiber, Nane; Reichel, Martin; Zidek, Laura M.; Kravic, Bojana; Bernkopf, Dominic; von Maltzahn, Julia; Behrens, Jürgen; Hashemolhosseini, Said (Development, 2016)
Canonical Wnt/?-catenin signaling plays an important role in myogenic differentiation, but its physiological role in muscle fibers remains elusive. Here, we studied activation of Wnt/?-catenin signaling in adult muscle fibers and muscle stem cells in an Axin2 reporter mouse. Axin2 is a negative regulator and a target of Wnt/?-catenin signaling. In adult muscle fibers, Wnt/?-catenin signaling is only detectable in a subset of fast fibers that have a significantly smaller diameter than other fast fibers. In the same fibers, immunofluorescence staining for YAP/Taz and Tead1 was detected. Wnt/?-catenin signaling was absent in quiescent and activated satellite cells. Upon injury, Wnt/?-catenin signaling was detected in muscle fibers with centrally located nuclei. During differentiation of myoblasts expression of Axin2, but not of Axin1, increased together with Tead1 target gene expression. Furthermore, absence of Axin1 and Axin2 interfered with myoblast proliferation and myotube formation, respectively. Treatment with the canonical Wnt3a ligand also inhibited myotube formation. Wnt3a activated TOPflash and Tead1 reporter activity, whereas neither reporter was activated in the presence of Dkk1, an inhibitor of canonical Wnt signaling. We propose that Axin2-dependent Wnt/?-catenin signaling is involved in myotube formation and, together with YAP/Taz/Tead1, associated with reduced muscle fiber diameter of a subset of fast fibers.
EVALuna2:4993

Women-only versus mixed-gender groups in multimodal, day clinic treatment of trauma-related disorders - Philipps, Anke; Hepp, Tobias; Silbermann, Andrea; Morawa, Eva; Stemmler, Mark; Erim, Yesim (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2022)
Background: In the German healthcare system benefits include inpatient and day clinic psychotherapy of trauma-related disorders, which are often provided in gender specific groups. Despite this widespread practice, the actual impact and potential outcome have been studied relatively scarcely and are still open to debate. The present study therefore examines whether the therapeutic relationships in the group vary depending on the group composition and whether this has an effect on therapy outcome. Methods: 66 patients (N = 55 women) were treated in our multimodal, day clinic groupbased treatment program and filled out symptom questionnaires (ETI, BDI-II, PHQ-15, Questionnaire on social support) at admission and discharge and the Group Questionnaire (GQ; including subscales positive bonding, positive working and negative relationships) at the end of each of the eight weeks of treatment. Patients took part in five women-only and six mixed-gender groups and underwent therapy in a closed group format, so that they began and ended therapy within the same group. All patients were diagnosed with trauma-related disorders, which included PTSD, cPTSD, depression, somatoform disorders and further mental diseases. Outcome data were examined using functional regression analysis and linear mixed models. Results: In women-only groups, positive bonding and positive working relationship were significantly higher than in mixed-gender groups. Negative relationship ratings were significantly lower in women-only groups, especially in the middle phase of treatment. However, no effect of an exclusively female group composition on treatment outcome was found, except for the higher increase of perceived social support for patients treated in women-only groups. Conclusions: Group relationships were considered more pleasant in women-only groups than in mixed-gender groups, but this had no effect on the symptom-based therapy outcome. To enhance feelings of safety and comfort, traumatized women should have the possibility to choose whether to be treated in a women-only or a mixed-gender group.
CRIS-Team Scopus Importer:2022-12-23
Keywords: Day Clinic; Group Relationships; PTSD; Trauma; Women-Only Groups

Working conditions and mental health of migrants and refugees in Europe considering cultural origin– a systematic review - Herold, Regina; Lieb, Marietta; Borho, Andrea; Voss, Amanda; Unverzagt, Susanne; Morawa, Eva; Rothermund, Eva; Erim, Yesim (BMC Public Health, 2024)
Background: Migrants and refugees/asylum seekers, as a large part of the European work force, are often confronted with unfavorable working conditions in the host country. Main aim of this systematic review was to compare the association of these working conditions with mental health between migrants and refugees/asylum seekers due to their diverse migration experiences and cultural origins, and between different European host countries. Methods: Systematic search for eligible primary studies was conducted in three electronic databases (PubMed/MEDLINE, PsycINFO and CINAHL) using quantitative study designs written in English, German, French, Italian, Polish, Spanish or Turkish and published from January 1, 2016 to October 27, 2022. Primary health outcomes were diagnosed psychiatric and psychological disorders, suicide and suicide attempts, psychiatric and psychological symptoms, and perceived distress. Secondary health outcomes were more general concepts of mental health such as well-being, life satisfaction and quality of life. Two reviewers independently completed screening, data extraction and the methodological quality assessment of primary studies using the Newcastle-Ottawa-Scale. Descriptive summary of primary studies on working conditions and their relationship with mental health were conducted, comparing migrants and refugees/asylum seekers, migrants and refugees/asylum seekers of different cultural backgrounds (collectivistic and individualistic) and migrants and refugees/asylum seekers living in different host countries. Results: Inclusion criteria were met by 19 primary studies. Voluntary migrants are more likely to experience overqualification in the host country than refugees. In all examined host countries, migrants and refugees suffer from unfavorable working conditions, with migrants from collectivistic countries being slightly at risk compared to migrants from individualistic countries. Most unfavorable working conditions are related to poor mental health, regardless of migrant status, cultural origin or host country. Conclusions: Although the results should be interpreted with caution due to the small number of studies, it is evident that to maintain both the mental health and labor force of migrants and refugees/asylum seekers, their working conditions in host countries should be controlled and improved. Special attention should be paid to specific subgroups such as migrants from collectivistic societies. Ethics and dissemination: This systematic review is excluded from ethical approval because it used previously approved published data from primary studies. Trial registration number: CRD42021244840.
CRIS-Team Scopus Importer:2024-03-15
Keywords: Collectivism; Cultural origin; Europe; Individualism; Mental health; Migrants; Refugees; Well-being; Working conditions

Yes, I can - maybe … Effects of placebo-related instructions on neuroregulation in children with ADHD - Gevensleben, Holger; Schmiedeke, David; Heinrich, Hartmut; Rothenberger, Aribert (Journal of Neural Transmission, 2020)
Neurofeedback training (NFT) provides strategies for children with ADHD to achieve changes on the neurophysiological and behavioral level to attenuate ADHD symptoms. We assume self-efficacy (an “active attitude”), a core variable in successful NFT. In a randomized, double-blind controlled study, we investigated the impact of a “placebo instruction” on the EEG-regulation performance during two sessions of Theta-Beta-NFT in children with ADHD (age 8–12 years). Children receiving the information “this might be a placebo-training” showed inferior neuroregulation (n = 10) compared to children receiving a standard instruction (n = 12). Results of our pilot study are discussed in view of factors necessary for a valid training (ensuring maximal self-efficacy in the participants) and the fidelity of placebo-controlled trials in NFT-research.
CRIS-Team Scopus Importer:2020-05-19
Keywords: Attention-deficit/hyperactivity disorder (ADHD); Neurofeedback; Neuroregulation; Placebo; Theta-beta-training

Zeitgerechte Diagnosestellung bei Menschen mit Demenz: der Bayerische Demenz Survey (BayDem) - Wolff, Franziska; Dietzel, Nikolas; Karrer, Linda; Kratzer, André; Hess, Manuela; Grässel, Elmar; Kolominsky-Rabas, Peter (Gesundheitswesen, 2020)
Background In many cases, people with dementia (PWD) receive their first diagnosis at an advanced stage of the disease. A timely diagnosis, however, is crucial for the utilization of therapies and support services for PWD and their caregivers. So far, only a few international studies have analysed predictors of the time lapse between the first perceived symptoms and diagnosis. The aim of this study was to assess the time span from the first symptoms of dementia until the first dementia diagnosis and to identify predictors of a timely diagnosis. Methods The Bavarian Dementia Survey (BayDem) is a multi-centre, longitudinal study at 3 different sites in Bavaria, Germany. Participants were PWD as defined by ICD-10 and their informal caregivers. Data was collected by standardized face-to-face interviews in cooperation with local actors. For the analysis of potential sociodemographic predictors of a timely diagnosis within 9 months after the perception of the first symptoms, binary logistic regressions were used. Results The median length from the perception of the first symptoms until diagnosis was 16 months. Predictors of a timely diagnosis for male PWD were age at the time of the first perceived symptoms and education. There was no association between a timely diagnosis and the place of residence or living situation of the PWD. Conclusions Diagnosis of dementia is often made with a huge delay. Therefore, it is necessary to enhance structured access routes to a timely diagnosis in primary care.
CRIS-Team Scopus Importer:2020-02-04
Keywords: dementia; diagnostic delay; time to diagnosis; timely diagnosis

Zu welchen Themen suchen Angehörige von Demenzbetroffenen telefonische oder emailbasierte Beratung auf? Aktuelle Ergebnisse des bundesweiten Beratungsangebots der Deutschen Alzheimer Gesellschaft e.V. - Pendergrass, Anna; Weiß, Saskia; Grässel, Elmar (Gesundheitswesen, 2019)
BACKGROUND: Since 15 years, the Alzheimer 's Telephone of the German Alzheimer Society (Deutsche Alzheimer Gesellschaft e.V.; DAlzG), a nationwide psychosocial counseling service, has been offering support for people with dementia (PwD) and their families. The aim of this study was to evaluate: a) why informal PwD caregivers seek telephone counseling, b) whether these telephone calls are one-time counseling or long-term support, and c) whether the telephone inquiries differ from the email-based inquiries with regard to the addressed issues. MATERIALS AND METHODS: The data are based on the inquiries of 3,744 informal caregivers, which consulted the DAlzG in 2015. Sociodemographic data on the informal caregivers and the PwD, the characteristics of the telephone call, and the topics addressed in the email inquiries were collected. RESULTS: 70.3% of the callers were female. Most of them (59.9%) were the children (in-law) of and half of them (49.7%) lived with PwD. More than two-thirds of the callers (70%) were seeking help in dealing with the person with dementia (e. g. challenging behavior) and 36.5% of the relatives needed recommendations for further local help and assistance. In the third place, the calls were related to financial and legal topics (23.5%). 92.2% of the calls were one-time consultations. The addressed issues in the email inquiries did not significantly differ from the topics discussed over the telephone. DISCUSSION: On many topics there is a need for further "on site" consultation. Doctors and other health professionals should therefore be actively involved in counseling relatives of PwD.
CRIS-Team Scopus Importer:2019-12-20

α-Synuclein oligomers induce early axonal dysfunction in human iPSC-based models of synucleinopathies - Prots, Iryna; Grosch, Janina; Brazdis, Razvan-Marius; Simmnacher, Katrin; Veber, Vanesa; Havlicek, Steven; Hannappel, Christian; Krach, Florian; Krumbiegel, Mandy; Schuetz, Oliver; Reis, André; Wrasidlo, Wolfgang; et al. (Proceedings of the National Academy of Sciences of the United States of America, 2018)
α-Synuclein (α-Syn) aggregation, proceeding from oligomers to fibrils, is one central hallmark of neurodegeneration in synucleinopathies. α-Syn oligomers are toxic by triggering neurodegenerative processes in in vitro and in vivo models. However, the precise contribution of α-Syn oligomers to neurite pathology in human neurons and the underlying mechanisms remain unclear. Here, we demonstrate the formation of oligomeric α-Syn intermediates and reduced axonal mitochondrial transport in human neurons derived from induced pluripotent stem cells (iPSC) from a Parkinson's disease patient carrying an α-Syn gene duplication. We further show that increased levels of α-Syn oligomers disrupt axonal integrity in human neurons. We apply an α-Syn oligomerization model by expressing α-Syn oligomer-forming mutants (E46K and E57K) and wild-type α-Syn in human iPSC-derived neurons. Pronounced α-Syn oligomerization led to impaired anterograde axonal transport of mitochondria, which can be restored by the inhibition of α-Syn oligomer formation. Furthermore, α-Syn oligomers were associated with a subcellular relocation of transport-regulating proteins Miro1, KLC1, and Tau as well as reduced ATP levels, underlying axonal transport deficits. Consequently, reduced axonal density and structural synaptic degeneration were observed in human neurons in the presence of high levels of α-Syn oligomers. Together, increased dosage of α-Syn resulting in α-Syn oligomerization causes axonal transport disruption and energy deficits, leading to synapse loss in human neurons. This study identifies α-Syn oligomers as the critical species triggering early axonal dysfunction in synucleinopathies.
EVALuna2:34623
Keywords: alpha-synuclein; oligomers; axonal transport; synucleinopathies; neurodegeneration

Aberrant neuronal activity-induced signaling and gene expression in a mouse model of RASopathy - Altmueller, Franziska; Pothula, Santosh; Annamneedi, Anil; Nakhei-Rad, Saeideh; Montenegro-Venegas, Carolina; Pina-Fernandez, Eneko; Marini, Claudia; Santos, Monica; Schanze, Denny; Montag, Dirk; Ahmadian, Mohammad R.; Stork, Oliver; et al. (PLoS Genetics, 2017)
Noonan syndrome (NS) is characterized by reduced growth, craniofacial abnormalities, congenital heart defects, and variable cognitive deficits. NS belongs to the RASopathies, genetic conditions linked to mutations in components and regulators of the Ras signaling pathway. Approximately 50% of NS cases are caused by mutations in PTPN11. However, the molecular mechanisms underlying cognitive impairments in NS patients are still poorly understood. Here, we report the generation and characterization of a new conditional mouse strain that expresses the overactive Ptpn11D61Y allele only in the forebrain. Unlike mice with a global expression of this mutation, this strain is viable and without severe systemic phenotype, but shows lower exploratory activity and reduced memory specificity, which is in line with a causal role of disturbed neuronal Ptpn11 signaling in the development of NS-linked cognitive deficits. To explore the underlying mechanisms we investigated the neuronal activity-regulated Ras signaling in brains and neuronal cultures derived from this model. We observed an altered surface expression and trafficking of synaptic glutamate receptors, which are crucial for hippocampal neuronal plasticity. Furthermore, we show that the neuronal activity-induced ERK signaling, as well as the consecutive regulation of gene expression are strongly perturbed. Microarray-based hippocampal gene expression profiling revealed profound differences in the basal state and upon stimulation of neuronal activity. The neuronal activity-dependent gene regulation was strongly attenuated in Ptpn11D61Y neurons. In silico analysis of functional networks revealed changes in the cellular signaling beyond the dysregulation of Ras/MAPK signaling that is nearly exclusively discussed in the context of NS at present. Importantly, changes in PI3K/AKT/mTOR and JAK/STAT signaling were experimentally confirmed. In summary, this study uncovers aberrant neuronal activity-induced signaling and regulation of gene expression in Ptpn11D61Y mice and suggests that these deficits contribute to the pathophysiology of cognitive impairments in NS.
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A comparison of suicides in psychiatric in-patients, after discharge and in not recently hospitalized individuals - Deisenhaminer, Eberhard A.; Behrndt, Elisa-Marie; Kemrnler, Georg; Haring, Christian; Miller, Carl (Comprehensive Psychiatry, 2016)
Time of in-patient treatment and the first weeks after hospital discharge have repeatedly been described as periods of increased suicide risk. This study compared demographic, clinical and suicide related factors between in-patient, post-discharge and not recently hospitalized suicides.Suicide data from the Tyrol Suicide Register were linked with registers of three psychiatric hospitals in the state of Tyrol, Austria. Suicide cases then were categorized as in-patient suicides, post-discharge suicides (suicide within 12weeks after discharge) or never/not within 12weeks before death hospitalized suicides. Data were collected between 2004 and 2011.Of the total of 711 cases, 30 were in-patient, 89 post-discharge and 592 not recently hospitalized suicides. The three groups differed with regard to male-to-female ratio (lower in both hospitalized groups), marital status, suicide method used (jumping in in-patients, hanging in not recently hospitalized suicides), history of attempted suicide and suicide threats (highest in in-patients) and whether suicides had been in psychiatric or general practitioner treatment shortly before death. In most variables with significant differences there was a gradual increase/decrease with post-discharge suicides taking the middle place between the two other groups.The three suicide populations differed in a number of variables. Varying factors appear to influence suicide risk and choice of method differently in in-patient, post-discharge and not hospitalized suicides.
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Belief of agency changes dynamics in sensorimotor networks - Buchholz, Verena N.; David, Nicole; Sengelmann, Malte; Engel, Andreas K. (Scientific Reports, 2019)
Controlling an event through one's own action usually induces a sense of agency, a feeling that arises when an expected outcome matches the intention. The neural correlates of this feeling remain controversial however, as experimental manipulation of the action-outcome chain often introduces mismatch or prediction errors that strongly correlate with the sense of agency. Here, we took a different approach and manipulated the causal belief (self-attribution vs. computer-attribution) by external cues during matched visuo-motor tapping conditions. With magneto-encephalography, we studied the sense of agency from a network perspective, investigating in source space the modulation of local population activity and changes in functional connectivity with motor cortex. Our results show that during the belief of agency primary motor cortex (M1) shows stronger functional connectivity (mediated by the beta band) to inferior parietal lobe and right middle temporal gyrus (MTG). Furthermore, the local feed-forward activity (gamma band power) in extrastriate body area and MTG disappears with that belief. After changes in action context, left M1 shows stronger connectivity in the alpha band with right premotor cortex and left insular-temporal cortex a network that might support active inference in social action context. Finally, a better tapping performance in this rhythmic task was related to alpha power modulations in the bilateral cerebellum and bilateral fusiform body-area, with power suppression during a more precise performance. These findings highlight the role of multiple networks supporting the sense of agency by changing their relative contribution for different causal beliefs.
CRIS-Team WoS Importer:2019-02-27

Do Caregiver Characteristics Affect Caregiver Burden Differently in Different Countries? - Konerding, Uwe; Bowen, Tom; Forte, Paul; Karampli, Eleftheria; Malmstrom, Tomi; Pavi, Elpida; Torkki, Paulus; Grässel, Elmar (American Journal of Alzheimers Disease and Other Dementias, 2019)
The relationships between caregiver burden as measured with the Burden Scale for Family Caregivers-short form and 6 characteristics of caregivers caring for patients with dementia were investigated for caregivers from England (n = 36), Finland (n = 42), and Greece (n = 46) using survey data. In all 3 countries, caregiver burden increases with physical problems of the caregiver, emotional problems of the caregiver, and weekly hours of care. Hence, in all 3 countries, special support for informal care is required when these characteristics are at high levels. When the caregiver is a spouse or long-term partner of the person with dementia, lives in the same house as this person, or spends fewer than 20 h/wk for other duties than care, this is associated with less caregiver burden in England but with more caregiver burden in Greece. Accordingly, special support is required for Greek caregivers with these characteristics, but the opposite is true for English caregivers.
CRIS-Team WoS Importer:2019-04-30

ELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones - Kawabe, Hiroshi; Mitkovski, Miso; Kaeser, Pascal S.; Hirrlinger, Johannes; Opazo, Felipe; Nestvogel, Dennis; Kalla, Stefan; Fejtova, Anna; Verrier, Sophie E.; Bungers, Simon R.; Cooper, Benjamin H.; Varoqueaux, Frederique; et al. (The Journal of Cell Biology, 2017)
Presynaptic active zones (AZs) are unique subcellular structures at neuronal synapses, which contain a network of specific proteins that control synaptic vesicle (SV) tethering, priming, and fusion. Munc13s are core AZ proteins with an essential function in SV priming. In hippocampal neurons, two different Munc13s-Munc13-1 and bMunc13-2-mediate opposite forms of presynaptic short-term plasticity and thus differentially affect neuronal network characteristics. We found that most presynapses of cortical and hippocampal neurons contain only Munc13-1, whereas ∼10% contain both Munc13-1 and bMunc13-2. Whereas the presynaptic recruitment and activation of Munc13-1 depends on Rab3-interacting proteins (RIMs), we demonstrate here that bMunc13-2 is recruited to synapses by the AZ protein ELKS1, but not ELKS2, and that this recruitment determines basal SV priming and short-term plasticity. Thus, synapse-specific interactions of different Munc13 isoforms with ELKS1 or RIMs are key determinants of the molecular and functional heterogeneity of presynaptic AZs.
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Epidemiology of suicidal ideation, suicide attempts, and direct self-injurious behavior in adolescents with a migration background: a representative study - Donath, Carolin; Bergmann, Marie Christine; Kliem, Soeren; Hillemacher, Thomas; Baier, Dirk (BMC Pediatrics, 2019)
BackgroundData on the prevalence of suicidal ideation, suicide attempts, and direct self-injurious behavior in adolescents with a migration background are scarce. There are hints that this population is at risk. The aim of the study is to investigate the epidemiology of suicidal ideation, suicide attempts, and direct self-injurious behavior in adolescents with a migration background in Germany while taking gender-specific differences into consideration.MethodsA representative study with N=10,638 students (mean age 14.91years, SD=.73).) in the state of Lower Saxony in Germany was conducted. In the 2014-2015 school year, 672 classes were selected by randomly sampling different school types. The participation rate was 84.1%, excluding any classes for which the director refused to provide consent. A total of 49.8% were female adolescents, and 23.3% of the participants had a migration background. Target variables were assessed with items from the Ottawa Self-Injury Inventory, the Self-Harm Behavior Questionnaire and the Self-Harm Inventory, partly adapted.ResultsOf all students, 7.6% had a lifetime history of suicide attempts, and 36.6% answered with a rating of at least rarely when asked to rate the lifetime prevalence of suicidal ideation. The 12-month prevalence of direct self-injurious behavior was 17.8%. Adolescents with a migration background showed a significantly higher prevalence of all three constructs (p=.006; p<.001; p=.006). Male students with a migration background reported a significantly higher lifetime prevalence of suicide attempts (4.7% vs. 3.1%) than native males (p=.009). Female students with a migration background reported a significantly higher lifetime prevalence of suicide attempts (15.9% vs. 10.4%) and suicidal ideation (often 12.1% vs. 8.9%) than native female students (p<.001; p=.008).ConclusionOur assessment indicates an elevated risk for suicidal behaviors in adolescents with a migration background. From research on adults, it is known that the dominant motives for suicidal behavior in migrants are associated with their migration history/situation. As suggested by Cramer and Kapusta's (Front Psychol 8:1756, 2017) theoretical model, the Social-Ecological Framework of Theory, Assessment, and Prevention, there is a need for culturally sensitive preventions that take into account the specific reasons for suicide attempts in migrants.
CRIS-Team WoS Importer:2019-02-21

Hyaluronic acid based extracellular matrix regulates surface expression of GluN2B containing NMDA receptors - Schweitzer, Barbara; Singh, Jeet; Fejtova, Anna; Groc, Laurent; Heine, Martin; Frischknecht, Renato (Scientific Reports, 2017)
Cortical areas of the juvenile rodent brain display a high degree of structural and functional plasticity, which disappears later in development. Coincident with the decline of plasticity 1) the hyaluronic acid-based extracellular matrix (ECM) of the brain, which stabilizes synapses and neuronal circuit is formed and 2) N-methyl-D-aspartate subtype of ionotropic glutamate receptors (NMDARs) implied in synaptic plasticity switch from mainly GluN2B to GluN2A subunit-containing receptors. Here we tested the hypothesis that ECM influences the NMDAR subunit composition in dissociated neuronal cultures. Experimental removal of ECM using hyaluronidase induced an increase in surface expression of GluN2B. This was due to decreased endocytosis of surface GluNB-containing receptors. We further found a reduction in phosphorylation at Tyr1472, which negatively regulates their binding to the endocytotic AP2 complex. We propose that maturation of ECM could induce switch in NMDAR composition necessary for normal adult synaptic plasticity and that increased expression of GluN2B contributes to rejuvenation of plasticity after ECM removal in vivo.
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Investigating burden of informal caregivers in England, Finland and Greece: an analysis with the short form of the Burden Scale for Family Caregivers (BSFC-s) - Konerding, Uwe; Bowen, Tom; Forte, Paul; Karampli, Eleftheria; Malmström, Tomi; Pavi, Elpida; Torkki, Paulus; Grässel, Elmar (Aging & Mental Health, 2016)
The burden of informal caregivers might show itself in different ways in different cultures. Understanding these differences is important for developing culture-specific measures aimed at alleviating caregiver burden. Hitherto, no findings regarding such cultural differences between different European countries were available. In this paper, differences between English, Finnish and Greek informal caregivers of people with dementia are investigated.A secondary analysis was performed with data from 36 English, 42 Finnish and 46 Greek caregivers obtained with the short form of the Burden Scale for Family Caregivers (BSFC-s). The probabilities of endorsing the BSFC-s items were investigated by computing a logit model with items and countries as categorical factors. Statistically significant deviation of data from this model was taken as evidence for country-specific response patterns.The two-factorial logit model explains the responses to the items quite well (McFadden's pseudo-R-square: 0.77). There are, however, also statistically significant deviations (p < 0.05). English caregivers have a stronger tendency to endorse items addressing impairments in individual well-being; Finnish caregivers have a stronger tendency to endorse items addressing the conflict between the demands resulting from care and demands resulting from the remaining social life and Greek caregivers have a stronger tendency to endorse items addressing impairments in physical health.Caregiver burden shows itself differently in English, Finnish and Greek caregivers. Accordingly, measures for alleviating caregiver burden in these three countries should address different aspects of the caregivers' lives.
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N-truncated Aβ2-X starting with position two in sporadic Alzheimer's disease cases and two Alzheimer mouse models - Savastano, Adriana; Klafki, Hans; Haussman, Ute; Oberstein, Timo; Muller, Petr; Wirths, Oliver; Wiltfang, Jens; Bayer, Thomas A. (Journal of Alzheimer's Disease, 2016)
According to the modified amyloid hypothesis, the key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of neurotoxic amyloid ?-peptides (A?s) in plaques and cerebral blood vessels. Additionally to full-length peptides, a great diversity of N-truncated A? variants is derived from the larger amyloid-? protein precursor (A?PP). Vast evidence suggests that A?x-42 isoforms play an important role in triggering neurodegeneration due to their high abundance, amyloidogenic propensity and toxicity. Although N-truncated A? peptides and A?x-42 species appear to be the crucial players in AD etiology, the A?2-X isoforms did not receive much attention yet. The present study is the first to show immunohistochemical evidence of A?2-X in cases of AD and its distribution in A?PP/PS1KI and 5XFAD transgenic mouse models using a novel antibody pAB77 that has been developed using A?2-14 as antigen. Positive plaques and congophilic amyloid angiopathy (CAA) were observed in AD cases and in both mouse models. While in AD cases, abundant CAA and less pronounced plaque pathology was evident, the two mouse models showed predominantly extracellular A? deposits and minor CAA staining. Western blotting and a capillary isoelectric focusing immunoassay demonstrated the high specificity of the antibody pAb77 against A?-variants starting with the N-terminal Alanine-2.
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Performance-Based Assessment of Instrumental Activities of Daily Living: Validation of the Sydney Test of Activities of Daily Living in Memory Disorders (STAM) - Reppermund, Simone; Birch, Rachael C.; Crawford, John D.; Wesson, Jacqueline; Draper, Brian; Kochan, Nicole A.; Trollor, Julian N.; Luttenberger, Katharina; Brodaty, Henry; Sachdev, Perminder S. (Journal of the American Medical Directors Association, 2017)
OBJECTIVES: The distinction between dementia and mild cognitive impairment (MCI) relies upon the evaluation of independence in instrumental activities of daily living (IADL). Self- and informant reports are prone to bias. Clinician-based performance tests are limited by long administration times, restricted access, or inadequate validation. To close this gap, we developed and validated a performance-based measure of IADL, the Sydney Test of Activities of Daily Living in Memory Disorders (STAM). DESIGN: Prospective cohort study (Sydney Memory and Ageing Study). SETTING: Eastern Suburbs, Sydney, Australia. PARTICIPANTS: 554 community-dwelling individuals (54% female) aged 76 and older with normal cognition, MCI, or dementia. MEASUREMENTS: Activities of daily living were assessed with the STAM, administered by trained psychologists, and the informant-based Bayer-Activities of Daily Living Scale (B-ADL). Depressive symptoms were measured with the Geriatric Depression Scale (15-item version). Cognitive function was assessed with a comprehensive neuropsychological test battery. Consensus diagnoses of MCI and dementia were made independently of STAM scores. RESULTS: The STAM showed high interrater reliability (r = 0.854) and test-retest reliability (r = 0.832). It discriminated significantly between the diagnostic groups of normal cognition, MCI, and dementia with areas under the curves ranging from 0.723 to 0.948. A score of 26.5 discriminated between dementia and nondementia with a sensitivity of 0.831 and a specificity of 0.864. Correlations were low with education (r = 0.230) and depressive symptoms (r = -0.179), moderate with the B-ADL (r = -0.332), and high with cognition (ranging from r = 0.511 to r = 0.594). The mean time to complete the STAM was 16 minutes. CONCLUSIONS: The STAM has good psychometric properties. It can be used to differentiate between normal cognition, MCI, and dementia and can be a helpful tool for diagnostic classification both in clinical practice and research.
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Pharmacological modulation of metabotropic glutamate receptor subtype 5 and 7 impairs extinction of social fear in a time-point-dependent manner - Slattery, David A.; Neumann, Inga D.; Flor, Peter J.; Zoicas, Iulia (Behavioural Brain Research, 2017)
Pharmacological modulation of metabotropic glutamate receptor subtype 5 (mGluR5) and 7 (mGluR7) was shown to attenuate the acquisition and to facilitate the extinction of cued and contextual, non-social, fear. Using the allosteric mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and the allosteric mGluR7 agonist N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082), we aimed to study how pharmacological blockade of mGluR5 and activation of mGluR7 influence acquisition and extinction of social fear in mice. We could show that when administered before social fear conditioning, neither MPEP nor AMN082 affected acquisition and extinction of social fear, suggesting that mGluR5 inactivation and mGluR7 activation do not alter social fear. However, when administered before social fear extinction, both MPEP and AMN082 impaired social fear extinction and extinction recall. These findings suggest that mGluR5 inactivation and mGluR7 activation are unlikely to prevent the formation of traumatic social memories. Furthermore, medication strategies aimed at augmenting exposure-based therapies for psychiatric disorders associated with social deficits via modulation of mGluR5 and mGluR7 must be pursued cautiously because of their potential to delay social fear extinction processes.
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Predictors of health-related quality of life in stroke patients after neurological inpatient rehabilitation: a prospective study - Katona, Mirjam; Schmidt, Ralf; Schupp, Wilfried; Grässel, Elmar (Health and Quality of Life Outcomes, 2015)
The goal of the study was to investigate the long-term course of health-related quality of life (HRQoL) in stroke survivors during and up to 2.5 years after inpatient neurological rehabilitation and to identify predictors of HRQoL.HRQoL was determined in 152 stroke survivors in a single-centre prospective cohort study at four time points: upon admission to inpatient rehabilitation, at discharge, and one and 2.5 years after discharge. Their HRQoL was determined by administering the EQ-5D at all four measurement points. During inpatient rehabilitation, the SF-36 was administered in addition to the EQ-5D. Predictors were identified through multiple regression analysis.During inpatient rehabilitation, the "European Index" of the EQ-5D rose significantly (p < 0.001) from 45.4 to 66.7. The change in HRQoL on the SF-36 was convergent. The HRQoL of the stroke patients living at home remained at the same level for 2.5 years following discharge. In the multiple regression analysis, the EQ-5D Index at discharge (p = 0.049), the risk of falls as defined by Runge and Rehfeld (p = 0.001), and the change in emotional quality of life on the SF-36 during inpatient rehabilitation (p = 0.048) predicted HRQoL 2.5 years following discharge.On the basis of our results, we conclude that the long-term health-related quality of life of stroke survivors can be positively influenced by reducing the risk of falls and improving emotional well-being during neurological inpatient rehabilitation.
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Professional Care Team Burden (PCTB) scale - reliability, validity and factor analysis - Auer, Stefanie; Grässel, Elmar; Viereckl, Carmen; Kienberger, Ursula; Span, Edith; Luttenberger, Katharina (Health and Quality of Life Outcomes, 2015)
There is growing concern about how to provide care for persons with dementia in institutions such as nursing homes, day care centers, mobile services and hospitals. Care teams (formal caregivers) have to meet specific expectations from different sides: the Person with Dementia herself, the institution, and from different family members. Out of this situation, considerable burden can emerge hindering the professional development of care team members and counteracting quality of care of care recipients. So far there are very few specific reliable and valid scales measuring burden in care team members. Based on the theoretical concept of subjectively perceived burden, organizationally based factors of burden and structural factors of burden, we report on the construction of a care team burden scale and its scale quality criteria.Based on the theoretical three assumed sources of burden, a structured interview guide was developed. Interviews were held with professional caregivers. Through qualitative data analysis, an item pool consisting of 40 Items was constructed. Experts selected 19 items found most appropriate to measure the three theoretically based domains of burden. The Perceived Stress Scale (PSS) was chosen as a criterion in order to test discriminant validity. An exploratory factor analysis was performed.The stepwise scale analysis revealed a 10 item solution. The Cronbach's alpha was 0.785. The Pearson correlation between the PCTB 10 Item scale (mean score 10.2, SD = 5.0) and the PSS (mean score 13.0, SD = 5.9) was 0.46 (p < 0.001). All included items could clearly be assigned to one of three factors.The 10 item PCTB scale provides a valid and reliable means of obtaining ratings of burden from formal care teams working in nursing homes in order to evaluate different interventions targeted at the reduction of burden in care teams.
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Psychotherapy and pharmacotherapy for harmful tobacco use and tobacco dependency - Batra, A.; Petersen, K. U.; Hoch, E.; Mann, K.; Kroeger, C.; Schweizer, C.; Jaehne, A.; Ruether, T.; Thürauf, Norbert; Muehlig, S. (Der Nervenarzt, 2016)
Tobacco consumption is one of the major preventable health risk factors. In Germany approximately 110,000 people prematurely die from tobacco-related diseases and approximately 50% of regular smokers are considered to be tobacco dependent. Nevertheless, motivation to quit smoking is low and the long-term abstinence rates after attempts to stop smoking without professional support are far below 10%. As part of the S3 treatment guidelines 78 recommendations for motivation and early interventions for smokers unwilling to quit as well as psychotherapeutic and pharmacological support for smokers willing to quit were formulated after an systematic search of the current literature. More than 50 professional associations adopted the recommendations and background information in a complex certification process. In this article the scientific evidence base regarding the psychotherapeutic and pharmacological treatment options as well as recommendations and further information about indications and treatment implementation are presented. By following these guidelines for treatment of heavy smokers who are willing to quit combined with individual and group therapies on the basis of behavioral treatment strategies and pharmacological support, long-term success rates of almost 30% can be achieved.
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Schlaganfallpatienten nach stationärer neurologischer Rehabilitation: Eine prospektive Studie zur Ermittlung von Prädiktoren für das Überleben zuhause bis 5 Jahre nach Entlassung - Grässel, Elmar; Schupp, Wilfried; Schmidt, Ralf (Rehabilitation (Germany), 2019)
Purpose To identify factors influencing the long-term survival at home in stroke patients after neurological inpatient rehabilitation. Methods The study was conducted as a prospective cohort study in 204 stroke patients who were treated in the course of one year in the Herzogenaurach Rehabilitation Hospital (rehabilitation phases C and B). The social data and clinical data were collected during inpatient rehabilitation. The outcome variable was assessed up to 5 years after discharge. Differences between groups were analysed with t-tests or chi-square tests. Binary logistic regression analyses were carried out for multivariate predictor analyses. Results The regression analysis resulted in a prediction model consisting of 5 variables for living at home 2.5 years after discharge (vs. institutionalization or death): a greater increase in health-related quality of life during inpatient rehabilitation, better health-relate quality of life at discharge, a greater increase in functional independence during inpatient rehabilitation, a higher body-mass index and fewer comorbidity conditions associated with a mortality risk. 5 years after discharge the prediction model consists of 3 variables: lower age, fewer comorbidity conditions associated with a mortality risk and lower risk for falls at discharge from neurological rehabilitation. Conclusion Up to 2.5 years after discharge the extent of functional improvement and the improvement of health related quality of life, which are both correlated with therapeutic effects, are predictors for survival and living at home. On the other hand, 5 years after discharge biological factors as age and comorbidities are prognostically dominating.
CRIS-Team Scopus Importer:2019-11-01
Keywords: inpatient neurological rehabilitation; longitudinal study; predictors for living at home; stroke

Serotonin Transporter and Tryptophan Hydroxylase Gene Variations Mediate Working Memory Deficits of Cocaine Users - Havranek, Michael M.; Vonmoos, Matthias; Müller, Christiane; Buetiger, Jessica R.; Tasiudi, Eve; Hulka, Lea M.; Preller, Katrin H.; Moessner, Rainald; Gruenblatt, Edna; Seifritz, Erich; Quednow, Boris B. (Neuropsychopharmacology, 2015)
Cocaine users consistently develop working memory (WM) impairments but the mediating molecular mechanisms are unknown so far. Recent evidence suggests that the serotonin (5-HT) system is altered by chronic cocaine use, while also being involved in WM processing. Thus, we investigated the effects of genetic variations impacting 5-HT activity and of peripheral 5-HT transporter (5-HTT) mRNA expression on WM performance in cocaine users and stimulant naive controls. Two hundred twenty participants (126 cocaine users, 94 controls) were assessed with visuospatial, spatial, and verbal WM tasks, genotyped for the length polymorphism in the promoter region of the 5-HTT (5-HTTLPR), the variable number of tandem repeats in the second intron of the 5-HTT (VNTR In2), two single-nucleotide polymorphisms (rs4570625 and rs1386497) in the tryptophan hydroxylase-2 (TPH2) gene and quantified for peripheral 5-HTT mRNA expression in whole-blood samples. Several significant gene × environment interactions between 5-HT genotypes and cocaine use on WM emerged: in cocaine users, the long/long (5-HTTLPR), 9+10/9+10 (VNTR In2) and C/C (TPH2 rs1386497) genotypes were risk alleles for WM impairments, whereas in healthy controls these polymorphisms were associated with improved WM performance. Analogously, high 5-HTT mRNA levels were associated with worse executive WM performance in cocaine users but with increased performance in controls. These gene × environment interactions suggest that the 5-HT system has an important role in the development of cognitive deficits in chronic cocaine users. Hence, pharmacological compounds targeting 5-HT neurotransmission might be promising for the treatment of cognitive deficits in cocaine dependence.
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Validation of a core patient-reported-outcome measure set for operationalizing success in multimodal pain therapy: useful for depicting long-term success? - Donath, Carolin; Geiss, Christa; Schoen, Christoph (BMC Health Services Research, 2018)
BACKGROUND: The study aims to validate a previously developed and published combined success criterion for patients after multimodal pain therapy (Donath et al., BMC Health Serv Res 15:272, 2015). The criterion classifies treated patients as successful in the long term on the basis of pain severity, disability through pain, depressiveness, and health-related quality of life. METHODS: Routine longitudinal data of 135 pain patients treated with multimodal pain therapy in 2014-2015 at the Interdisciplinary Pain Center of the University Clinic Erlangen were available at baseline, therapy start, therapy end, and 12 months after treatment. Patients were, on average, 51.0 (SD 11.1) years old and to 63.7% female, two thirds were employed (66.7%). We conducted an analysis of concurrent validity (with: pain severity, disability through pain, depressiveness, mental and physical quality of life), criterion validity (with disability days, self-rated success), convergent validity (with stress, anxiety, well-being), and discriminant validity (with chronicity of pain, comorbidity), objectivity, and reliability. Statistically, descriptive and inference statistics, graphical methods and MANOVAs were used. RESULTS: Patients classified as successful had significantly better values on the 5 variables demonstrating concurrent validity (all p < .001), significantly fewer Disability days (M = 15.31 (SD = 23.15) vs. M = 26.75 (SD = 29.15)); t (133) = 2.308; p = .024, less Anxiety (Pillai-Spur: F (3, 131) = 2.972, p = .034), less Stress (Pillai-Spur: F (3, 131) = 9.907, p < .001), and better Well-being (Pillai-Spur: F (3, 131) = 9.594, p < .001) 12 months after treatment than patients classified as not successful. The Spearman correlation between success classification and Chronicity stage was .094 (p = .280). CONCLUSION: We demonstrated the validity of the combined success criterion with long-term data in addition to confirming the reliability and objectivity of the criterion. Future research might consider identifying predictors of success in multi-modal pain therapy.
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