Caregiver intervention studies : Recommendations on endpoints and outcome measures for cognitively impaired care recipients - Albrecht, D.; Pendergrass, Anna; Becker, C.; Hautzinger, M.; Pfeiffer, K. (Zeitschrift für Gerontologie und Geriatrie, 2018)
BACKGROUND: Even though the intervention effects on cognitively impaired care recipients are of interest, the evaluation in dementia caregiver studies on caregiver outcomes is often limited. Furthermore, the comparison of studies and interventions is difficult because of the large variance of endpoints and assessments used in this field. OBJECTIVE: The aim of this study was to give an overview on the most prevalent outcomes for cognitively impaired care recipients and expert based recommendations for assessment. MATERIAL AND METHODS: A written Delphi survey was carried out on 16 assessments from 5 dimensions with 14 experts working in different disciplines in German healthcare and research institutes. RESULTS: The most important outcomes and best rated assessments were 1) for problem behavior: revised memory and behavior problem checklist and neuropsychiatric inventory Q, 2) for depressive symptoms: geriatric depression scale, 3) for quality of life: quality of life in Alzheimer's disease, 4) for cognition: mini mental state examination and 5) for ADL/IADL: Katz activities of daily living and Lawton instrumental activities of daily living. CONCLUSION: Due to the varying experiences of the experts with particular assessments, the ratings were in some cases relatively heterogeneous. Overall previous international recommendations could be confirmed. There is particular need of German validation studies on internationally used instruments within the dimensions of problem behavior and quality of life.
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Caring for dependent children impacts practical and emotional problems and need for support, but not perceived distress among cancer patients - Fugmann, Dominik; Richter, Peter; Karger, André; Ernstmann, Nicole; Hönig, Klaus; Bergelt, Corinna; Faller, Hermann; Maatouk, Imad; Hornemann, Beate; Stein, Barbara; Teufel, Martin; Goerling, Ute; et al. (Psycho-Oncology, 2023)
Objective: More than one in 10 cancer patients care for dependent children. It is unclear whether this status makes a difference in terms of the distress and associated problems they experience, or whether it is linked to differences in the need for or utilization of psychosocial support. Methods: Secondary analysis of a cross-sectional German study in National Comprehensive Cancer Centers using self-report standardized questionnaires administered to inpatients. Patients living with dependent children (n = 161) were matched by age and sex with a subsample of 161 cancer patients not living with dependent children. The resulting sample was tested for between-group differences in Distress Thermometer (DT) scores and the corresponding DT Problem List. Additionally, between-group differences in measures of the need for and utilization of psychosocial support were examined. Results: More than 50% of all patients suffered from clinically relevant distress. Patients living with dependent children reported significantly more practical (p < 0.001, η2p = 0.04), family (p < 0.001, η2p = 0.03), and emotional problems (p < 0.001, η2p = 0.01). Although reporting a greater need for psychological support, parents with cancer were not found to more frequently utilize any type of psychosocial support. Conclusions: The specific problems and needs of parents with cancer who care for dependent children are currently not sufficiently addressed in the clinical care pathways. All families should be helped to establish open and honest communication as well as understand the available support systems and what they can provide. Tailored interventions should be implemented for highly distressed families.
CRIS-Team Scopus Importer:2023-07-07
Keywords: cancer; child; family; oncology; parents; psycho-oncology; psychological distress; psychosocial support systems; psychotherapy

CD133-Positive Membrane Particles in Cerebrospinal Fluid of Patients with Inflammatory and Degenerative Neurological Diseases - Bobinger, Tobias; May, Lisa-Sophie; Lücking, Hannes; Kloska, Stephan; Burkardt, Petra; Spitzer, Philipp; Maler, Juan M.; Corbeil, Denis; Huttner, Hagen (Frontiers in Cellular Neuroscience, 2017)
Background: Analysis of cerebrospinal fluid (CSF) is a frequently used diagnostic tool in a variety of neurological diseases. Recent studies suggested that investigating membrane particles enriched with the stem cell marker CD133 may offer new avenues for studying neurological disease. In this study, we evaluated the amount of membrane particle-associated CD133 in human CSF in neuroinflammatory and degenerative diseases. Methods: We compared the amount of membrane particle-associated CD133 in CSF samples collected from 45 patients with normal pressure hydrocephalus, parkinsonism, dementia, and cognitive impairment, chronic inflammatory diseases and 10 healthy adult individuals as controls. After ultracentrifugation of CSF, gel electrophoresis and immunoblotting using anti-CD133 monoclonal antibody 80B258 were performed. Antigen-antibody complexes were detected using chemiluminescence. Results: The amount of membrane particle-associated CD133 was significantly increased in patients with normal pressure hydrocephalus (p < 0.001), parkinsonism (p = 0.011) as well as in patients with chronic inflammatory disease (p = 0.008). Analysis of CSF of patients with dementia and cognitive impairment revealed no significant change compared with healthy individuals. Furthermore, subgroup analysis of patients with chronic inflammatory diseases demonstrated significantly elevated levels in individuals with relapsing-remitting multiple sclerosis (p = 0.023) and secondary progressive multiple sclerosis (SPMS; p = 0.010). Conclusion: Collectively, our study revealed elevated levels of membrane particle-associated CD133 in patients with normal pressure hydrocephalus, parkinsonism as well as relapsing-remitting and SPMS. Membrane glycoprotein CD133 may be of clinical value for several neurological diseases.
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CD161a-positive natural killer (NK) cells and α-smooth muscle actin-positive myofibroblasts were upregulated by extrarenal DPP4 in a rat model of acute renal rejection - Schmid, Franziska; Mayer, Carolin; Büttner-Herold, Maike; von Hörsten, Stephan; Amann, Kerstin Ute; Daniel, Christoph (Diabetes Research and Clinical Practice, 2021)
Aims: Systemic inhibition of dipeptidyl peptidase 4 (DPP4) showed a protective effect in several transplant models. Here we assessed the specific role of extrarenal DPP4 in renal transplant rejection. Methods: Kidneys from wildtype (wt) F344 rats were either transplanted in wt Dark Agouti or congenic rats not expressing DPP4. The remaining, not transplanted donor kidney served as healthy controls. To investigate early inflammatory events rats were sacrificed 3 days after transplantation and kidneys were evaluated for inflammatory cells, capillary rarefaction, proliferation, apoptosis and myofibroblasts by immunohistochemistry. Results: Capillary ERG-1-positive endothelial cells were significantly more abundant in renal cortex when transplanted into DPP4 deficient compared to wt recipients. In contrast, TGF-ß and myofibroblasts were reduced by more than 25% in kidneys transplanted into DPP4 deficient compared to wt recipients. Numbers of CD161a-positive NK-cells were significantly lower in allografts in DPP4 deficient compared to wt recipients. Numbers of all other investigated immune cells were not affected by the lack of extrarenal DPP4. Conclusion: In early transplant rejection extrarenal DPP4 is involved in the recruitment of NK-cells and early fibrosis. Beneficial effects were less pronounced than reported for systemic DPP4 inhibition, indicating that renal DPP4 is an important player in transplantation-mediated injury.
CRIS-Team Scopus Importer:2021-03-05
Keywords: Extrarenal DPP4; Fibrosis; Inflammation; Renal transplantation

Cellular Receptors of Amyloid β Oligomers (AβOs) in Alzheimer's Disease - Mroczko, Barbara; Groblewska, Magdalena; Litman-Zawadzka, Ala; Kornhuber, Johannes; Lewczuk, Piotr (International Journal of Molecular Sciences, 2018)
It is estimated that Alzheimer’s disease (AD) affects tens of millions of people, comprising not only suffering patients, but also their relatives and caregivers. AD is one of age-related neurodegenerative diseases (NDs) characterized by progressive synaptic damage and neuronal loss, which result in gradual cognitive impairment leading to dementia. The cause of AD remains still unresolved, despite being studied for more than a century. The hallmark pathological features of this disease are senile plaques within patients’ brain composed of amyloid beta (Aβ) and neurofibrillary tangles (NFTs) of Tau protein. However, the roles of Aβ and Tau in AD pathology are being questioned and other causes of AD are postulated. One of the most interesting theories proposed is the causative role of amyloid β oligomers (AβOs) aggregation in the pathogenesis of AD. Moreover, binding of AβOs to cell membranes is probably mediated by certain proteins on the neuronal cell surface acting as AβO receptors. The aim of our paper is to describe alternative hypotheses of AD etiology, including genetic alterations and the role of misfolded proteins, especially Aβ oligomers, in Alzheimer’s disease. Furthermore, in this review we present various putative cellular AβO receptors related to toxic activity of oligomers.
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Ceramide and Its Related Neurochemical Networks as Targets for Some Brain Disorder Therapies - Brodowicz, Justyna; Przegalinski, Edmund; Müller, Christian P.; Filip, Malgorzata (Neurotoxicity Research, 2018)
Correlational and causal comparative research link ceramide (Cer), the precursor of complex sphingolipids, to some psychiatric (e.g., depression, schizophrenia (SZ), alcohol use disorder, and morphine antinociceptive tolerance) and neurological (e.g., Alzheimer's disease (AD), Parkinson disease (PD)) disorders. Cer generation can occur through the de novo synthesis pathway, the sphingomyelinase pathways, and the salvage pathway. The discoveries that plasma Cer concentration increase during depressive episodes in patients and that tricyclic and tetracyclic antidepressants functionally inhibit acid sphingomyelinase (ASM), the enzyme that catalyzes the degradation of sphingomyelin to Cer, have initiated a series of studies on the role of the ASM-Cer system in depressive disorder. Disturbances in the metabolism of Cer or SM are associated with the occurrence of SZ and PD. In both PD and SZ patients, the elevated levels of Cer or SM in the brain regions were associated with the disease. AD patients showed also an abnormal metabolism of brain Cer at early stages of the disease which may suggest Cer as an AD biomarker. In plasma of AD patients and in AD transgenic mice, ASM activity was increased. In contrast, partial ASM inhibition of Aβ deposition improved memory deficits. Furthermore, in clinical and preclinical research, ethanol enhanced activation of ASM followed by Cer production. Limited data have shown that Cer plays an important role in the development of morphine antinociceptive tolerance. In summary, clinical and preclinical findings provide evidence that targeting the Cer system should be considered as an innovative translational strategy for some brain disorders.
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Ceramide bei Depression - Kornhuber, Johannes (Drug Research, 2017)
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Ceramide levels in blood plasma correlate with major depressive disorder severity and its neutralization abrogates depressive behavior in mice - Schumacher, Fabian; Edwards, Michael J.; Mühle, Christiane; Carpinteiro, Alexander; Wilson, Greg C.; Wilker, Barbara; Soddemann, Matthias; Keitsch, Simone; Scherbaum, Norbert; Müller, Bernhard W.; Lang, Undine E.; Linnemann, Christoph; et al. (Journal of Biological Chemistry, 2022)
Major depressive disorder (MDD) is a severe disease of unknown pathogenesis that will affect ∼10% of people during their lifetime. Therapy for MDD requires prolonged treatment and often fails, predicating a need for novel treatment strategies. Here, we report increased ceramide levels in the blood plasma of MDD patients and in murine stress-induced models of MDD. These blood plasma ceramide levels correlated with the severity of MDD in human patients and were independent of age, sex, or body mass index. In addition, intravenous injection of anti-ceramide antibodies or neutral ceramidase rapidly abrogated stress-induced MDD, and intravenous injection of blood plasma from mice with MDD induced depression-like behavior in untreated mice, which was abrogated by ex vivo preincubation of the plasma with anti-ceramide antibodies or ceramidase. Mechanistically, we demonstrate that ceramide accumulated in endothelial cells of the hippocampus of stressed mice, evidenced by the quantitative measurement of ceramide in purified hippocampus endothelial cells. We found ceramide inhibited the activity of phospholipase D (PLD) in endothelial cells in vitro and in the hippocampus in vivo and thereby decreased phosphatidic acid in the hippocampus. Finally, we show intravenous injection of PLD or phosphatidic acid abrogated MDD, indicating the significance of this pathway in MDD pathogenesis. Our data indicate that ceramide controls PLD activity and phosphatidic acid formation in hippocampal endothelial cells and thereby mediates MDD. We propose that neutralization of plasma ceramide could represent a rapid-acting targeted treatment for MDD.
CRIS-Team Scopus Importer:2022-08-05
Keywords: behavior; ceramide; endothelial cells; major depression; neurogenesis; phosphatidic acid; PLD

Ceramides affect alcohol consumption and depressive-like and anxiety-like behavior in a brain region- and ceramide species-specific way in male mice - Zoicas, Iulia; Huber, Sabine; Kalinichenko, Liubov; Gulbins, Erich; Müller, Christian P.; Kornhuber, Johannes (Addiction Biology, 2019)
Depression and alcohol dependence are associated with increased plasma ceramide concentrations in humans. Pharmacological increase in C16 ceramide concentrations in the dorsal hippocampus (DH) induced a depressive-like phenotype in naïve mice. However, the effects of C16 ceramide on alcohol consumption and anxiety-like behavior as well as the behavioral effects of other ceramide species are yet unknown. Therefore, we investigated whether repeated infusion of ceramides with different fatty acid chain lengths (C8, C16, and C20) into the DH and the basolateral amygdala (BLA) alter alcohol consumption, emotional behavior, and tissue monoamine levels. Our results revealed that C16, but not C8 and C20, ceramide altered alcohol drinking and emotional behavior in a brain region–specific way without altering tissue noradrenaline, dopamine, and serotonin levels in the prefrontal cortex, ventral striatum, and dorsal mesencephalon. In more detail, C16 ceramide increased alcohol consumption when infused into the BLA, but not when infused into the DH. Furthermore, C16 ceramide induced a depressive-like phenotype when infused into the DH, but a predominantly anxiogenic-like phenotype (in a non-social, but not a social context) when infused into the BLA. In turn, alcohol drinking normalized C16 ceramide-induced depressive-like and anxiogenic-like phenotypes. This study demonstrates a complex ceramide species-specific and brain region-specific modulation of alcohol consumption and emotional behavior in mice and provides the framework for future studies investigating the involvement of distinct ceramide species in the regulation of emotional behavior.
CRIS-Team Scopus Importer:2019-12-24
Keywords: alcohol consumption; basolateral amygdala; C16 ceramide; dorsal hippocampus; emotional behavior

Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry - Lewczuk, Piotr; Riederer, Peter; O'Bryant, Sid E.; Verbeek, Marcel M.; Dubois, Bruno; Visser, Pieter Jelle; Jellinger, Kurt A.; Engelborghs, Sebastiaan; Ramirez, Alfredo; Parnetti, Lucilla; Jack, Clifford R.; Teunissen, Charlotte E.; et al. (World Journal of Biological Psychiatry, 2018)
In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.
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Cerebrospinal Fluid Aβ42/40 Corresponds Better than Aβ42 to Amyloid PET in Alzheimer's Disease - Lewczuk, Piotr; Matzen, Anja; Blennow, Kaj; Parnetti, Lucilla; Molinuevo, Jose Luis; Eusebi, Paolo; Kornhuber, Johannes; Morris, John C.; Fagan, Anne M. (Journal of Alzheimer's Disease, 2017)
BACKGROUND: Decreased concentrations of amyloid-β 1-42 (Aβ42) in cerebrospinal fluid (CSF) and increased retention of Aβ tracers in the brain on positron emission tomography (PET) are considered the earliest biomarkers of Alzheimer's disease (AD). However, a proportion of cases show discrepancies between the results of the two biomarker modalities which may reflect inter-individual differences in Aβ metabolism. The CSF Aβ42/40 ratio seems to be a more accurate biomarker of clinical AD than CSF Aβ42 alone. OBJECTIVE: We tested whether CSF Aβ42 alone or the Aβ42/40 ratio corresponds better with amyloid PET status and analyzed the distribution of cases with discordant CSF-PET results. METHODS: CSF obtained from a mixed cohort (n = 200) of cognitively normal and abnormal research participants who had undergone amyloid PET within 12 months (n = 150 PET-negative, n = 50 PET-positive according to a previously published cut-off) was assayed for Aβ42 and Aβ40 using two recently developed immunoassays. Optimal CSF cut-offs for amyloid positivity were calculated, and concordance was tested by comparison of the areas under receiver operating characteristic (ROC) curves (AUC) and McNemar's test for paired proportions. RESULTS: CSF Aβ42/40 corresponded better than Aβ42 with PET results, with a larger proportion of concordant cases (89.4% versus 74.9%, respectively, p < 0.0001) and a larger AUC (0.936 versus 0.814, respectively, p < 0.0001) associated with the ratio. For both CSF biomarkers, the percentage of CSF-abnormal/PET-normal cases was larger than that of CSF-normal/PET-abnormal cases. CONCLUSION: The CSF Aβ42/40 ratio is superior to Aβ42 alone as a marker of amyloid-positivity by PET. We hypothesize that this increase in performance reflects the ratio compensating for general between-individual variations in CSF total Aβ.
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Cerebrospinal Fluid Biomarkers and Clinical Progression in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment - Wolfsgruber, Steffen; Polcher, Alexandra; Koppara, Alexander; Kleineidam, Luca; Froelich, Lutz; Peters, Oliver; Huell, Michael; Ruether, Eckart; Wiltfang, Jens; Maier, Wolfgang; Kornhuber, Johannes; Lewczuk, Piotr; et al. (Journal of Alzheimer's Disease, 2017)
BACKGROUND: There is very limited data on the prevalence of abnormal cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and their predictive value for clinical progression in memory clinic patients with subjective cognitive decline (SCD). OBJECTIVE: To assess the frequency of abnormal CSF biomarkers of AD and their predictive value for clinical progression in memory clinic patients with SCD in comparison to patients with mild cognitive impairment (MCI) from the same cohort. METHODS: We analyzed prospective data from memory clinic patients of the German Competence Network Dementia cohort with a baseline diagnosis of SCD (n = 82) or MCI (n = 134), distinguished by actuarial neuropsychological MCI criteria ("Jak-Bondi criteria"). Risk of clinical progression during 3-year follow-up was evaluated with Cox-Proportional-Hazard models. RESULTS: Prevalence of abnormal values in CSF markers of tau-mediated neurodegeneration (67.8% versus 46.3%) but not of amyloid deposition (40.3% versus 35.4%) was significantly higher in MCI compared to SCD. The rate of incident AD dementia (26.1% versus 12.2%) was also significantly higher in MCI. In SCD, additional 22% progressed to MCI during follow-up. Combined amyloid/tau abnormality was the strongest predictor of clinical progression in both groups. CONCLUSION: High prevalence of biomarker abnormality and clinical progression, together with the predictive value of CSF biomarkers, in memory clinic patients with SCD support the validity and usefulness of this condition as a "pre-MCI" at risk stage of AD.
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CEREBROSPINAL FLUID BIOMARKERS FOR CEREBRAL AMYLOID ANGIOPATHY - Sembill, Jochen; Lusse, C.; Linnerbauer, Mathias; Sprügel, Maximilian; Mrochen, Anne; Knott, Michael; Hölter, Philip; Engelhorn, Tobias; Schmidt, M.; Dörfler, Arnd; Oberstein, Timo; Maler, Juan Manuel; et al. (INTERNATIONAL JOURNAL OF STROKE, 2022)
CRIS-Team WoS Importer:2022-11-18

Cerebrospinal fluid biomarkers for cerebral amyloid angiopathy - Sembill, Jochen; Lusse, Christoph; Linnerbauer, Mathias; Sprügel, Maximilian; Mrochen, Anne; Knott, Michael; Engelhorn, Tobias; Schmidt, Manuel; Dörfler, Arnd; Oberstein, Timo; Maler, Juan Manuel; Kornhuber, Johannes; et al. (Brain Communications, 2023)
Integrating cerebrospinal fluid-biomarkers into diagnostic workup of patients with sporadic cerebral amyloid angiopathy may support early and correct identification. We aimed to identify and validate clinical- and cerebrospinal fluid-biomarkers for in vivo diagnosis of cerebral amyloid angiopathy. This observational cohort study screened 2795 consecutive patients admitted for cognitive complaints to the academic departments of neurology and psychiatry over a 10-year period (2009–2018). We included 372 patients with available hemosiderin-sensitive MR imaging and cerebrospinal fluid-based neurochemical dementia diagnostics, i.e. Aβ40, Aβ42, t-tau, p-tau. We investigated the association of clinical- and cerebrospinal fluid-biomarkers with the MRI-based diagnosis of cerebral amyloid angiopathy, applying confounder-adjusted modelling, receiver operating characteristic and unsupervised cluster analyses. We identified 67 patients with cerebral amyloid angiopathy, 76 patients with Alzheimer’s disease, 75 patients with mild cognitive impairment due to Alzheimer’s disease, 76 patients with mild cognitive impairment with unlikely Alzheimer’s disease and 78 healthy controls. Patients with cerebral amyloid angiopathy showed a specific cerebrospinal fluid pattern: average concentration of Aß40 [13 792 pg/ml (10 081–18 063)] was decreased compared to all controls (P < 0.05); Aß42 [634 pg/ml (492–834)] was comparable to Alzheimer’s disease and mild cognitive impairment due to Alzheimer’s disease (P = 0.10, P = 0.93) but decreased compared to mild cognitive impairment and healthy controls (both P < 0.001); p-tau [67.3 pg/ml (42.9–91.9)] and t-tau [468 pg/ml (275–698)] were decreased compared to Alzheimer’s disease (P < 0.001, P = 0.001) and mild cognitive impairment due to Alzheimer’s disease (P = 0.001, P = 0.07), but elevated compared to mild cognitive impairment and healthy controls (both P < 0.001). Multivariate modelling validated independent clinical association of cerebral amyloid angiopathy with older age [odds-ratio: 1.06, 95% confidence interval (1.02–1.10), P < 0.01], prior lobar intracerebral haemorrhage [14.00 (2.64–74.19), P < 0.01], prior ischaemic stroke [3.36 (1.58–7.11), P < 0.01], transient focal neurologic episodes (TFNEs) [4.19 (1.06–16.64), P = 0.04] and gait disturbance [2.82 (1.11–7.15), P = 0.03]. For cerebrospinal fluid-biomarkers per 1 pg/ml, both lower Aß40 [0.9999 (0.9998–1.0000), P < 0.01] and lower Aß42 levels [0.9989 (0.9980–0.9998), P = 0.01] provided an independent association with cerebral amyloid angiopathy controlled for all aforementioned clinical confounders. Both amyloid biomarkers showed good discrimination for diagnosis of cerebral amyloid angiopathy among adjusted receiver operating characteristic analyses (area under the receiver operating characteristic curves, Aß40: 0.80 (0.73–0.86), P < 0.001; Aß42: 0.81 (0.75–0.88), P < 0.001). Unsupervised Euclidian clustering of all cerebrospinal fluid-biomarker-profiles resulted in distinct segregation of cerebral amyloid angiopathy patients from all controls. Together, we demonstrate that a distinctive set of cerebrospinal fluid-biomarkers effectively differentiate cerebral amyloid angiopathy patients from patients with Alzheimer’s disease, mild cognitive impairment with or without underlying Alzheimer’s disease, and healthy controls. Integrating our findings into a multiparametric approach may facilitate diagnosing cerebral amyloid angiopathy, and may aid clinical decision-making, but warrants future prospective validation.
CRIS-Team Scopus Importer:2023-07-21
Keywords: biomarker; cerebral amyloid angiopathy; cerebrospinal fluid; dementia; small vessel disease

Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases - Lleo, Alberto; Cavedo, Enrica; Parnetti, Lucilla; Vanderstichele, Hugo; Herukka, Sanna Kaisa; Andreasen, Niels; Ghidoni, Roberta; Lewczuk, Piotr; Jeromin, Andreas; Winblad, Bengt; Tsolaki, Magda; Mroczko, Barbara; et al. (Nature Reviews Neurology, 2015)
Alzheimer disease (AD) and Parkinson disease (PD) are the most common neurodegenerative disorders. For both diseases, early intervention is thought to be essential to the success of disease-modifying treatments. Cerebrospinal fluid (CSF) can reflect some of the pathophysiological changes that occur in the brain, and the number of CSF biomarkers under investigation in neurodegenerative conditions has grown rapidly in the past 20 years. In AD, CSF biomarkers are increasingly being used in clinical practice, and have been incorporated into the majority of clinical trials to demonstrate target engagement, to enrich or stratify patient groups, and to find evidence of disease modification. In PD, CSF biomarkers have not yet reached the clinic, but are being studied in patients with parkinsonism, and are being used in clinical trials either to monitor progression or to demonstrate target engagement and downstream effects of drugs. CSF biomarkers might also serve as surrogate markers of clinical benefit after a specific therapeutic intervention, although additional data are required. It is anticipated that CSF biomarkers will have an important role in trials aimed at disease modification in the near future. In this Review, we provide an overview of CSF biomarkers in AD and PD, and discuss their role in clinical trials.
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Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer's type - Popp, Julius; Wolfsgruber, Steffen; Heuser, Isabella; Peters, Oliver; Huell, Michael; Schroeder, Johannes; Moeller, Hans-Juergen; Lewczuk, Piotr; Schneider, Anja; Jahn, Holger; Luckhaus, Christian; Perneczky, Robert; et al. (Neurobiology of Aging, 2015)
Increased peripheral and central nervous system cortisol levels have been reported in Alzheimer's disease (AD) and may reflect dysfunction of cerebral components of the hypothalamic-pituitary-adrenal (HPA) axis. However, brain exposure to high cortisol concentrations may also accelerate disease progression and cognitive decline. The objectives of this study were to investigate whether HPA-axis dysregulation occurs at early clinical stages of AD and whether plasma and CSF cortisol levels are associated with clinical disease progression. Morning plasma and CSF cortisol concentrations were obtained from the subjects with AD dementia, mild cognitive impairment of AD type (MCI-AD), MCI of other type (MCI-O), and controls with normal cognition included in a multicenter study from the German Dementia Competence Network. A clinical and neuropsychological follow-up was performed in a subgroup of participants with MCI-AD, MCI-O, and AD dementia. CSF cortisol concentrations were increased in the subjects with AD dementia or MCI-AD compared with subjects with MCI-O or normal cognition. After controlling for possible confounders including CSF measures of amyloid beta1-42 and total tau, higher baseline CSF cortisol levels were associated with faster clinical worsening and cognitive decline in MCI-AD. The findings suggest that HPA-axis dysregulation occurs at the MCI stage of AD and may accelerate disease progression and cognitive decline.
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Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate, Alzheimer’s Disease Pathology, and Cognitive Decline - Ouanes, Sami; Clark, Christopher; Richiardi, Jonas; Marechal, Benedicte; Lewczuk, Piotr; Kornhuber, Johannes; Kirschbaum, Clemens; Popp, Julius (Frontiers in Aging Neuroscience, 2022)
Introduction: Elevated cortisol levels have been reported in Alzheimer’s disease (AD) and may accelerate the development of brain pathology and cognitive decline. Dehydroepiandrosterone sulfate (DHEAS) has anti-glucocorticoid effects and it may be involved in the AD pathophysiology. Objectives: To investigate associations of cerebrospinal fluid (CSF) cortisol and DHEAS levels with (1) cognitive performance at baseline; (2) CSF biomarkers of amyloid pathology (as assessed by CSF Aβ levels), neuronal injury (as assessed by CSF tau), and tau hyperphosphorylation (as assessed by CSF p-tau); (3) regional brain volumes; and (4) clinical disease progression. Materials and Methods: Individuals between 49 and 88 years (n = 145) with mild cognitive impairment or dementia or with normal cognition were included. Clinical scores, AD biomarkers, brain MRI volumetry along with CSF cortisol and DHEAS were obtained at baseline. Cognitive and functional performance was re-assessed at 18 and 36 months from baseline. We also assessed the following covariates: apolipoprotein E (APOE) genotype, BMI, and education. We used linear regression and mixed models to address associations of interest. Results: Higher CSF cortisol was associated with poorer global cognitive performance and higher disease severity at baseline. Cortisol and cortisol/DHEAS ratio were positively associated with tau and p-tau CSF levels, and negatively associated with the amygdala and insula volumes at baseline. Higher CSF cortisol predicted more pronounced cognitive decline and clinical disease progression over 36 months. Higher CSF DHEAS predicted more pronounced disease progression over 36 months. Conclusion: Increased cortisol in the CNS is associated with tau pathology and neurodegeneration, and with decreased insula and amygdala volume. Both CSF cortisol and DHEAS levels predict faster clinical disease progression. These results have implications for the identification of patients at risk of rapid decline as well as for the development of interventions targeting both neurodegeneration and clinical manifestations of AD.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Alzheimer’s disease; cerebrospinal fluid; cognitive decline; cortisol; DHEAS; neurodegeneration

Cerebrospinal fluid in Borna disease virus 1 (BoDV-1) encephalitis - Neumann, Bernhard; Hierl, Andreas; Wunderlich, Silke; Meier, Helen; Bauer, Christina; Gerner, Stefan; Rieder, Georg; Geis, Tobias; Kunkel, Jürgen; Bauswein, Markus; Niller, Hans Helmut; Schmidt, Barbara; et al. (Journal of the Neurological Sciences, 2023)
Borna disease virus 1 (BoDV-1) has been recognized as a rare cause of very severe encephalitis with rapid onset in central Europe. Data on cerebrospinal fluid (CSF) analysis have not yet been analyzed in detail. Here, we present the first study on CSF changes in BoDV-1 encephalitis. We retrospectively analyzed CSFs from 18 BoDV-1 encephalitis cases from Bavaria, Germany, an endemic region, from 1996 to 2021. Data were obtained through review of medical records and institutional databases. We found that white blood cell count (WBC) in CSF is elevated in 13 of our 18 patients at first examination (average 83.2 ± 142.3 leukocytes/μl) and cytology showed predominance of lymphocytes. Patients with typical symptoms of meningoencephalitis had higher WBC in first CSF analyzation (133.5 ± 163.1 vs 4.0 ± 3.2/μl; p = 0.065). BoDV-1 PCR of CSF is not always positive when tested (7 of 9 cases). Four of five patients tested showed a polyvalent reaction against multiple viruses in the CSF suggesting that BoDV1 may trigger autoimmune mechanisms. CSF changes in BoDV-1 encephalitis seem similar to those of other viral encephalitis and at the beginning WBC can be normal in up to 28%, making the diagnosis even more challenging. All in all, BoDV-1 should be included in the diagnostic workup of patients with rapidly evolving and/or severe encephalitis and patients with severe neuropathy and secondary encephalopathy with and without CSF changes. Repeated CSF examinations as well as BoDV-1 serology and CSF PCR have to be considered in endemic areas.
CRIS-Team Scopus Importer:2023-02-10
Keywords: Borna disease virus 1 (BoDV-1); Cerebrospinal fluid; Viral encephalitis

Cerebrospinal Fluid of Patients With Alzheimer's Disease Contains Increased Percentages of Synaptophysin-Bearing Microvesicles - Utz, Janine; Berner, Judith; Munoz, Luis Enrique; Oberstein, Timo; Kornhuber, Johannes; Herrmann, Martin; Maler, Juan Manuel; Spitzer, Philipp (Frontiers in Aging Neuroscience, 2021)
Introduction In Alzheimer's disease, the severity of symptoms is linked to a loss of synaptic density and the spread of pathologically hyperphosphorylated tau. The established cerebrospinal fluid markers A beta, tau and phospho-tau reflect the histopathological hallmarks of Alzheimer's disease but do not indicate disease progression. Such markers are of special interest, especially for trials of disease modifying drugs. Microvesicles are produced by stressed cells and reflect part of the metabolism of their cells of origin. Therefore, we investigated microvesicles of neuronal origin in cerebrospinal fluid. Materials and Methods We used flow cytometry to analyze microvesicles carrying tau, phospho-tau-Thr181, phospho-tau-Ser202Thr205, synaptophysin, and SNAP-25 in the cerebrospinal fluid of 19 patients with Alzheimer's disease and 15 non-inflammatory neurological disease controls. Results The percentages of synaptophysin-bearing microvesicles were significantly higher in the cerebrospinal fluid of patients with Alzheimer's disease than in the CSF of non-inflammatory neurological disease controls. Tau, phospho-tau-Thr181, phospho-tau-Ser202Thr205, and SNAP-25 did not differ between the groups. The percentages of synaptophysin-bearing vesicles distinguished patients with Alzheimer's disease from the controls (AUC = 0.81). Conclusion The loss of synapses in Alzheimer's disease may be reflected by synaptophysin-bearing microvesicles in the cerebrospinal fluid. Future studies are needed to investigate the possibility of using these MVs as a marker to determine the activity of Alzheimer's disease.
CRIS-Team WoS Importer:2021-07-30

Cerebrospinal fluid α synuclein concentrations in patients with positive AD biomarkers and extrapyramidal symptoms - Winkel, Izabela; Ermann, Natalia; Zelwetro, Agnieszka; Sambor, Bozydar; Mroczko, Barbara; Kornhuber, Johannes; Paradowski, Boguslaw; Lewczuk, Piotr (Journal of Neural Transmission, 2021)
Extrapyramidal symptoms (EP) are not uncommon in Alzheimer’s Disease (AD); when present, they negatively influence the course of the disorder. A large proportion of AD patients shows concomitant Lewy bodies’ pathology post mortem. Total α Synuclein (αSyn) concentrations are frequently increased in the cerebrospinal fluid (CSF) of AD patients, but are decreased in Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). αSyn CSF concentrations in AD patients with EP (EP+) have not been reported so far. αSyn and the four Neurochemical Dementia Diagnostics (NDD) CSF biomarkers, (Aβ1-42, Aβ42/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm, were measured in patients with positive NDD results and presence of extrapyramidal symptoms (NDD + / EP+; n = 26), in patients with positive NDD results and absence of extrapyramidal symptoms (NDD+ / EP−; n = 54), and in subjects with negative NDD results (NDD−; n = 34). Compared to the NDD− controls (379.8 ± 125.2 pg/mL), NDD+ patients showed, on average, highly significantly increased CSF αSyn (519 ± 141.3 pg/mL, p < 0.01), but without differences between NDD+ / EP+ and NDD+ / EP− subgroups (p = 0. 38). Moderate but highly significant association was observed between concentrations of αSyn and Tau (r = 0.47, p < 0.01) and pTau181 (r = 0.65, p < 0.01). Adjusted for diagnoses, age, and sex, subjects with more advanced neurodegeneration on neuroimaging showed significantly lower αSyn concentrations (p < 0.02). In the setting AD versus controls, the area under the receiver operating characteristic (ROC) curve was 0.804 [0.712; 0.896] with the sensitivity and the specificity of 0.863 and 0.618, respectively. αSyn in AD patients does not differentiate between subjects with- and without EP. Its increased average concentration reflects probably neurodegenerative process, and is not specific for any pathophysiologic mechanisms. Further studies are necessary to explain the role of CSF αSyn as a potential biomarker.
CRIS-Team Scopus Importer:2021-06-04
Keywords: Alzheimer’s disease; Biomarker; Cerebrospinal fluid; Extrapyramidal symptoms; α Synuclein

Cerebrovascular complications of immunologically mediated heparin-induced thrombocytopenia - Macha, K.; Kloska, Stephan; Dörfler, Arnd; Raaz-Schrauder, D.; Schwab, Sibylle; Köhrmann, Martin; Seifert, Frank (Fortschritte der Neurologie - Psychiatrie, 2014)
Immunologically mediated heparin-induced thrombocytopenia (HIT) is a thrombotic disease caused by antibodies occurring after heparin exposure. Thrombocytopenia occurs within a few days after heparin exposure, about half of HIT-patients develop venous or arterial thrombotic complications. Neurological complications of HIT are mainly ischaemic stroke and sinus vein thrombosis. To ensure the primary clinical diagnosis functional and immunological assays for antibody detection are available. The probability for the occurrence of HIT depends on the nature of heparin employed (LMWH vs. UFH) and individual patient characteristics such as gender and primary disease (medical vs. surgical patients). In the case of suspected HIT heparin administration should be discontinued immediately and replaced by an alternative anticoagulation to prevent the expansion or development of further thrombotic complications. Herein we report a case of a patient suffering from HIT-associated embolic cerebral ischaemic stroke.
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Changing focus of symptoms: A rare case report of Munchhausen's syndrome - Hagen, Melanie; Faust, Beatrice; Kunzelmann, Nina; Tektas, Ozan Y.; Kornhuber, Johannes; Mueller, Helge H. O. (Mental Illness, 2017)
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Characterization of a Neutral Sphingomyelinase Activity in Human Serum and Plasma - Mühle, Christiane; Kornhuber, Johannes (International Journal of Molecular Sciences, 2023)
Alterations of sphingolipids and their metabolizing enzymes play a role in various diseases. However, peripheral biomarkers for such changes are limited. Particularly, in the increasingly reported involvement of neutral sphingomyelinase (NSM) with four described isoforms in tissues or cells, a peripheral marker is lacking. We here describe the detection of an NSM activity in human serum and plasma samples which hydrolyses fluorescently labeled sphingomyelin to ceramide in a time- and volume-dependent manner. Reaction rates were linear up to 10 days, and serum volumes above 2 vol-% were inhibitory. Biochemical properties were different from acid sphingomyelinase (ASM) with respect to detergent specificity (sodium deoxycholate), pH profile (pH 7–9), and cation dependence: Serum NSM activity was inhibited by EDTA ≥ 1 µM and restored in EDTA-anticoagulated plasma with the addition of ≥ 100 µM Co2+. It was independent of Mg2+, the typical cofactor of cellular NSM species, and even inhibited by [Mg2+] ≥ 20 mM. Serum NSM activity was not correlated with ASM activity and was independent of sex and age in 24 healthy adults. Since human peripheral NSM activity is very low and activities in rodents are even lower or undetectable, future research should aim to increase the reaction rate and determine the source of this enzymatic activity. The established activity could serve as a future biomarker or therapeutic target in diseases affected by sphingolipid derangements.
CRIS-Team Scopus Importer:2023-02-24
Keywords: blood biomarker; ceramide; cobalt cofactor; EC 3.1.4.12; enzyme inhibitors; NSM; SMPD3; sphingolipid metabolism; sphingomyelin; sphingomyelin phosphodiesterase

Chemotherapeutic xCT inhibitors sorafenib and erastin unraveled with the synaptic optogenetic function analysis tool - Dahlmanns, Marc; Yakubov, Eduard; Chen, Daishi; Sehm, Tina; Rauh, Manfred; Savaskan, Nicolai; Wrosch, Jana Katharina (Cell Death Discovery, 2017)
In the search for new potential chemotherapeutics, the compounds' toxicity to healthy cells is an important factor. The brain with its functional units, the neurons, is especially endangered during the radio- and chemotherapeutic treatment of brain tumors. The effect of the potential compounds not only on neuronal survival but also neuronal function needs to be taken into account. Therefore, in this study we aimed to comprehend the biological effects of chemotherapeutic xCT inhibition on healthy neuronal cells with our synaptic optogenetic function analysis tool (SOFA). We combined common approaches, such as investigation of morphological markers, neuronal function and cell metabolism. The glutamate-cystine exchanger xCT (SLC7A11, system Xc-) is the main glutamate exporter in malignant brain tumors and as such a relevant drug target for treating deadly glioblastomas (WHO grades III and IV). Recently, two small molecules termed sorafenib (Nexavar) and erastin have been found to efficiently block xCT function. We investigated neuronal morphology, metabolic secretome profiles, synaptic function and cell metabolism of primary hippocampal cultures (containing neurons and glial cells) treated with sorafenib and erastin in clinically relevant concentrations. We found that sorafenib severely damaged neurons already after 24 h of treatment. Noteworthy, also at a lower concentration, where no morphological damage or metabolic disturbance was monitored, sorafenib still interfered with synaptic and metabolic homeostasis. In contrast, erastin-treated neurons displayed mostly inconspicuous morphology and metabolic rates. Key parameters of proper neuronal function, such as synaptic vesicle pool sizes, were however disrupted following erastin application. In conclusion, our data revealed that while sorafenib and erastin effectively inhibited xCT function they also interfered with essential neuronal (synaptic) function. These findings highlight the particular importance of investigating the effects of potential neurooncological and general cancer chemotherapeutics also on healthy neuronal cells and their function as revealed by the SOFA tool.
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Child neurodevelopment and mental health after surgical ventricular septal defect repair: risk and protective factors - Eichler, Anna; Kohler-Jonas, Nicola; Stonawski, Valeska; Purbojo, Ariawan; Moll, Gunther; Heinrich, Hartmut; Cesnjevar, Robert; Kratz, Oliver (Developmental Medicine and Child Neurology, 2019)
Aim This case-control study examined the long-term consequences of surgical correction for ventricular septal defect (VSD; the most common congenital heart defect) in infancy. It assessed children who had undergone VSD surgery and the factors related to maternal conditions, surgery, and hospital stay. Method Thirty-nine children (23 females, 16 males; age range 6y 1mo-9y 7mo [mean 7y 4mo, SD 1y]) with repaired isolated, non-syndromic, non-genetic VSD were compared with 39 typically developing children (22 females, 17 males; age range 6y-9y 2mo [mean 7y 3mo, SD 10mo]). The children completed behavioural tests of neurodevelopment and a quality of life (QoL) questionnaire. Mothers rated children's emotional/behavioural symptoms and QoL. Measures of maternal parenting behaviour and psychopathology were treated as moderators. Results Affected children showed reduced language skills (p=0.002) unless mothers reported high parenting behaviour subscale scores (p=0.04). Children's anxiety symptoms were elevated when mothers had anxiety symptoms (p=0.01). Longer hospital stay was associated with lower intelligence (p=0.003) and psychomotor scores (p=0.006). Longer scars predicted elevated child anxiety (p=0.008), and age at surgery and QoL were inversely related (p=0.01). Interpretation Impairments could be mitigated if VSD repair was performed early in life with a relatively small scar and uncomplicated hospital stay. This outcome depends on maternal parenting behaviour and anxiety symptoms. What this paper adds
CRIS-Team WoS Importer:2019-02-21

Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression - Steinacker, Petra; Verde, Federico; Fang, Lubin; Feneberg, Emily; Oeckl, Patrick; Roeber, Sigrun; Anderl-Straub, Sarah; Danek, Adrian; Diehl-Schmid, Janine; Fassbender, Klaus; Fliessbach, Klaus; Foerstl, Hans; et al. (Journal of Neurology Neurosurgery and Psychiatry, 2018)
OBJECTIVES: Neurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1). METHODS: Altogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con). CHIT1 and neurofilament levels were determined in cerebrospinal fluid (CSF) and blood and analysed with regard to diagnostic sensitivity and specificity and prognostic performance. Additionally, postmortem tissue was analysed for CHIT1 expression. RESULTS: In ALS, CHIT1 CSF levels were higher compared with Con (p<0.0001), DCo (p<0.05) and neurodegenerative diseases (AD p<0.05, PD p<0.01, FTLD p<0.0001) except CJD. CHIT1 concentrations were correlated with ALS disease progression and severity but not with the survival time, as did neurofilaments. Serum CHIT1 levels were not different in ALS compared with any other study group. In the spinal cord of patients with ALS, but not Con, AD or CJD cases, CHIT1 was expressed in the corticospinal tract and CHIT1 staining colocalised with markers of microglia (IBA1) and macrophages (CD68). CONCLUSIONS: CHIT1 concentrations in the CSF of patients with ALS may reflect the extent of microglia/macrophage activation in the white matter of the spinal cord. CHIT1 could be a potentially useful marker for differential diagnosis and prediction of disease progression in ALS and, therefore, seems suitable as a supplemental marker for patient stratification in therapeutic trials.
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Cholesterol metabolites and plant sterols in cerebrospinal fluid are associated with Alzheimer's cerebral pathology and clinical disease progression - Jahn, Tabea; Clark, Christopher; Kerksiek, Anja; Lewczuk, Piotr; Lütjohann, Dieter; Popp, Julius (Journal of Steroid Biochemistry and Molecular Biology, 2021)
Background and Purpose: Altered cholesterol metabolism is associated with increased risk of neurodegeneration and in particular with the development of Alzheimer's disease (AD). Here, we investigate whether non-cholesterol sterols and oxysterols in the central nervous system are associated with (i) the presence of cerebral AD pathology, (ii) distinct aspects of AD pathology, i.e. amyloid pathology, neuronal injury, and tau pathology, and (iii) cognitive decline over time. Experimental Approach: One hundred forty-two elder subjects with normal cognition, mild cognitive impairment, or mild dementia participating in a cohort study on cognitive decline and AD were included. Clinical and neuropsychological assessments were performed at inclusion and repeated at follow-up visits at 18 and 36 months. Concentrations of cholesterol, non-cholesterol sterols, and cholesterol metabolites were measured in cerebrospinal fluid (CSF), along with CSF beta-amyloid (Aβ)1−42; Aβ1−42/Aβ1−40 ratio, total-tau (tau), and tau phosphorylated at threonine 181 (p-tau) as markers of amyloid pathology, neuronal injury and tau pathology, respectively. Cognitive decline was assessed by changes in Mini-Mental State Examination and Clinical Dementia Rating sum of boxes at follow-up visits. Key Results: CSF 24S-hydroxycholesterol (24S−OHC) and the 24S−OHC/27−OHC ratio were higher in subjects with AD pathology. CSF desmosterol correlated with Aβ1−42 levels. The 24S−OHC levels, the 24S−OHC/27−OHC ratio and the plant sterols campesterol and sitosterol were associated with the tau and p-tau levels. Both plant sterol concentrations along with the 24S−OHC/27−OHC ratio at baseline predicted cognitive decline at follow-up visits. Conclusions and Implications: We show the importance of CSF levels of several non-cholesterol sterols and oxysterols to AD and core AD biomarkers. The plant sterols campesterol and sitosterol appear to be involved in tau pathology and neurodegeneration. CSF desmosterol level indicates CNS cholesterol synthesis and might be of relevance for clinical disease severity. Therefore these non-cholesterol sterols may represent intervention targets to slow down disease progression.
CRIS-Team Scopus Importer:2020-11-27
Keywords: Alzheimer's disease; Brain cholesterol metabolism; Cerebrospinal fluid; Cholesterol synthesis; Lipids; Neurodegeneration; Oxysterols

Chronic antipsychotic treatment targets GIRK current suppression, loss of long-term synaptic depression and behavioural sensitization in a mouse model of amphetamine psychosis - Groos, Dominik; Zheng, Fang; Rauh, Manfred; Quinger, Benedikt; Kornhuber, Johannes; Müller, Christian P.; Alzheimer, Christian (Journal of Psychopharmacology, 2018)
BACKGROUND:: Antipsychotic drugs (APDs) are the mainstay of the pharmacological treatment of psychotic disorders like schizophrenia. While the clinical efficacy of APDs has long since been established, the neurobiological mechanisms underlying their therapeutic benefits are still not well understood. METHODS:: Here, we used an escalating amphetamine regimen to induce a psychosis-like state in mice. To achieve clinically relevant drug concentrations in amphetamine-pretreated mice, the typical APD haloperidol or the atypical APD olanzapine were chronically administered via subcutaneously implanted osmotic mini-pumps. RESULTS:: Demonstrating their therapeutic efficacy, both drugs dampened amphetamine-induced hyperlocomotion and restored normal behaviour in the light-induced activity test. Whole-cell recordings from dopaminergic neurons of the ventral tegmental area (VTA) in ex vivo brain slices revealed two pronounced aberrations associated with the psychosis-like state: Strongly enhanced spontaneous firing and a substantial loss of G protein-gated inwardly rectifying potassium (GIRK) current upon activation of GABAB receptors with baclofen. Chronic haloperidol and olanzapine restored normal firing and partially rescued the GIRK current response to baclofen. In ex vivo slices containing the nucleus accumbens, which receives a dopaminergic projection from the VTA, abrogation of long-term synaptic depression (LTD) and enhanced excitatory drive onto medium spiny neurons were identified as synaptic consequences of amphetamine-induced psychosis. Again, both alterations proved amenable to chronic APD treatment. CONCLUSION:: Our data provide evidence for aberrant neuronal function and plasticity in the mesolimbic dopamine system during an induced psychotic state and identify these alterations as targets of chronic APD treatment.
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Chronic cerebral hypoperfusion-induced memory impairment and hippocampal long-term potentiation deficits are improved by cholinergic stimulation in rats - Damodaran, Thenmoly; Müller, Christian P.; Hassan, Zurina (Pharmacological Reports, 2019)
Background: Chronic cerebral hypoperfusion (CCH) can induce the accumulation of reactive oxygen species, which leads to oxidative damage, neuronal injury, and central cholinergic dysfunction in vulnerable regions of the brain, such as the hippocampus and cerebral cortex. These effects can lead to significant cognitive impairments in clinical populations of vascular dementia (VaD). The present studies aimed to investigate the role of the cholinergic system in memory functions and hippocampal long-term potentiation (LTP) impairments induced by CCH in rats. Methods: Male Sprague Dawley rats were subjected to permanent bilateral occlusion of common carotid arteries (PBOCCA) or sham surgery. Then, PBOCCA rats received ip injections with, either vehicle (control group), the muscarinic receptor agonist oxotremorine (0.1 mg/kg), or the acetylcholinesterase inhibitor physostigmine (0.1 mg/kg). Cognitive functions were evaluated using a passive avoidance task and the Morris water maze test. In addition, hippocampal LTP was recorded in vivo under anaesthesia. Results: The PBOCCA rats exhibited significant deficits in passive avoidance retention and spatial learning and memory tests. They also showed a suppression of LTP formation in the hippocampus. Oxotremorine and physostigmine significantly improved the learning and memory deficits as well as the suppression of LTP in PBOCCA rats. Conclusions: The present data suggest that the cholinergic system plays an important role in CCH-induced cognitive deficits and could be an effective therapeutic target for the treatment of VaD.
CRIS-Team Scopus Importer:2019-05-02
Keywords: LTP; Memory; Morris water maze; Passive avoidance; PBOCCA; Vascular dementia

Chronic corticosterone treatment enhances extinction-induced depression in aged rats - Huston, Joseph P.; Komorowski, Mara; Silva, Maria A. De Souza; Lamounier-Zepter, Valeria; Nikolaus, Susanne; Mattern, Claudia; Müller, Christian P.; Topic, Bianca (Hormones and Behavior, 2016)
Withdrawal and avoidance behavior are common symptoms of depression and can appear as a consequence of absence of reward, i.e. extinction-induced depression (EID). This is particularly relevant for the aged organism subjected to pronounced loss of former rewards. Avoidance of the former site of reward and increased withdrawal into a distant compartment accompany extinction of food-rewarded behavior in rodent models. During extinction, behavioral markers for re-learning dissociate from indicators of extinction-induced depression. Here we examined the effect of a chronic treatment with corticosterone (CORT), a well-known inducer of depression-related behavior, on EID in adult and aged rats. Adult (3-4months) and aged (18months) male rats were treated with CORT via drinking water for 3weeks prior to extinction of a cued food-reward task. CORT treatment increased the distance from the site of reward and decreased goal tracking behavior during extinction, especially in the aged rats. Plasma hormone levels measured before and after restraint stress showed a decline in basal ACTH- and CORT-levels after chronic CORT treatment in aged animals. The treatment significantly impaired the HPA-axis activation after acute stress in both, adult and aged animals, alike. Altogether, these findings show an enhancement of EID after chronic CORT treatment in the aged organism, which may be mediated by an impaired HPA-axis sensitivity. These findings may have special relevance for the investigation of human geriatric depression.
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Chronic mitragynine (kratom) enhances punishment resistance in natural reward seeking and impairs place learning in mice - Ismail, Nurul Iman W.; Jayabalan, Nanthini; Mansor, Sharif Mahsufi; Müller, Christian P.; Muzaimi, Mustapha (Addiction Biology, 2017)
Kratom (Mitragyna speciosa) is a widely abused herbal drug preparation in Southeast Asia. It is often consumed as a substitute for heroin, but imposing itself unknown harms and addictive burdens. Mitragynine is the major psychostimulant constituent of kratom that has recently been reported to induce morphine-like behavioural and cognitive effects in rodents. The effects of chronic consumption on non-drug related behaviours are still unclear. In the present study, we investigated the effects of chronic mitragynine treatment on spontaneous activity, reward-related behaviour and cognition in mice in an IntelliCage® system, and compared them with those of morphine and Δ-9-tetrahydrocannabinol (THC). We found that chronic mitragynine treatment significantly potentiated horizontal exploratory activity. It enhanced spontaneous sucrose preference and also its persistence when the preference had aversive consequences. Furthermore, mitragynine impaired place learning and its reversal. Thereby, mitragynine effects closely resembled that of morphine and THC sensitisation. These findings suggest that chronic mitragynine exposure enhances spontaneous locomotor activity and the preference for natural rewards, but impairs learning and memory. These findings confirm pleiotropic effects of mitragynine (kratom) on human lifestyle, but may also support the recognition of the drug's harm potential.
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Chronic Psychosocial Stress in Mice Is Associated With Increased Acid Sphingomyelinase Activity in Liver and Serum and With Hepatic C16:0-Ceramide Accumulation - Reichel, Martin; Rhein, Cosima; Hofmann, Lena M.; Monti, Juliana; Japtok, Lukasz; Langgartner, Dominik; Fuechsl, Andrea M.; Kleuser, Burkhard; Gulbins, Erich; Hellerbrand, Claus; Reber, Stefan O.; Kornhuber, Johannes (Frontiers in Psychiatry, 2018)
Chronic psychosocial stress adversely affects human morbidity and is a risk factor for inflammatory disorders, liver diseases, obesity, metabolic syndrome, and major depressive disorder (MDD). In recent studies, we found an association of MDD with an increase of acid sphingomyelinase (ASM) activity. Thus, we asked whether chronic psychosocial stress as a detrimental factor contributing to the emergence of MDD would also affect ASM activity and sphingolipid (SL) metabolism. To induce chronic psychosocial stress in male mice we employed the chronic subordinate colony housing (CSC) paradigm and compared them to non-stressed single housed control (SHC) mice. We determined Asm activity in liver and serum, hepatic SL concentrations as well as hepatic mRNA expression of genes involved in SL metabolism. We found that hepatic Asm activity was increased by 28% (P = 0.006) and secretory Asm activity by 47% (P = 0.002) in stressed mice. C16:0-Cer was increased by 40% (P = 0.008). Gene expression analysis further revealed an increased expression of tumor necrosis factor (TNF)-α (P = 0.009) and of several genes involved in SL metabolism (Cers5, P = 0.028; Cers6, P = 0.045; Gba, P = 0.049; Gba2, P = 0.030; Ormdl2, P = 0.034; Smpdl3B; P = 0.013). Our data thus provides first evidence that chronic psychosocial stress, at least in mice, induces alterations in SL metabolism, which in turn might be involved in mediating the adverse health effects of chronic psychosocial stress and peripheral changes occurring in mood disorders.
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Classification of body dysmorphic disorder - What is the advantage of the new DSM-5 criteria? - Schieber, Katharina; Kollei, Ines; De Zwaan, Martina; Martin, Alexandra (Journal of psychosomatic research, 2015)
In DSM-5 the diagnosis of body dysmorphic disorder (BDD) has been subjected to two important changes: Firstly, BDD has been assigned to the category of obsessive-compulsive and related disorders. Secondly, a new criterion has been defined requiring the presence of repetitive behaviors or mental acts in response to appearance concerns. The aims of this study were to report the prevalence rates of BDD based on a DSM-5 diagnosis, and to evaluate the impact of the recently introduced DSM-5 criteria for BDD by comparing the prevalence rates (DSM-5 vs.BDD-criteria (DSM-IV/DSM-5), dysmorphic concerns, and depressive symptoms, were assessed in a representative sample of the German general population (N=2129, aged 18-65years).The association between BDD case identification based on DSM-IV and DSM-5 was strong (Phi=.95, p<.001), although point prevalence of BDD according to DSM-5 was slightly lower (2.9%, n=62 vs. 3.2%, n=68). Approximately one third of the identified BDD (DSM-5) cases reported time-consuming behavioral acts in response to appearance concerns. In detail, 0.8% of the German general population fulfilled the BDD criteria and reported repetitive acts of at least one hour/day.The revised criteria of BDD in DSM-5 do not seem to have an impact on prevalence rates. However, the recently added B-criterion reflects more precisely the clinical symptoms of BDD, and may be useful for distinguishing between various severity levels related to repetitive behaviors/mental acts.
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Classifying primary progressive aphasias individually with support vector machine approaches in MRI data - Bisenius, S.; Mueller, K.; Diehl-Schmid, J.; Fassbender, K.; Jessen, F.; Kassubek, Jan; Kornhuber, Johannes; Schneider, A.; Stuke, K.; Danek, A.; Otto, M.; Schroeter, M. L. (2016)
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Clinical and Cost-Effectiveness of PSYCHOnlineTHERAPY: Study Protocol of a Multicenter Blended Outpatient Psychotherapy Cluster Randomized Controlled Trial for Patients With Depressive and Anxiety Disorders - Baumeister, Harald; Bauereiss, Natalie; Zarski, Anna-Carlotta; Braun, Lina; Buntrock, Claudia; Hoherz, Christian; Idrees, Abdul Rahman; Kraft, Robin; Meyer, Pauline; Nguyen, Tran Bao Dat; Pryss, Rudiger; Reichert, Manfred; et al. (Frontiers in Psychiatry, 2021)
Introduction: Internet- and mobile-based interventions (IMIs) and their integration into routine psychotherapy (i.e., blended therapy) can offer a means of complementing psychotherapy in a flexible and resource optimized way. Objective: The present study will evaluate the non-inferiority, cost-effectiveness, and safety of two versions of integrated blended psychotherapy for depression and anxiety compared to standard cognitive behavioral therapy (CBT). Methods: A three-armed multicenter cluster-randomized controlled non-inferiority trial will be conducted comparing two implementations of blended psychotherapy (PSYCHOnlineTHERAPYfix/flex) compared to CBT. Seventy-five outpatient psychotherapists with a CBT-license will be randomized in a 1:1:1 ratio. Each of them is asked to include 12 patients on average with depressive or anxiety disorders resulting in a total sample size of N = 900. All patients receive up to a maximum of 16 psychotherapy sessions, either as routine CBT or alternating with Online self-help sessions (fix: 8/8; flex: 0–16). Assessments will be conducted at patient study inclusion (pre-treatment) and 6, 12, 18, and 24 weeks and 12 months post-inclusion. The primary outcome is depression and anxiety severity at 18 weeks post-inclusion (post-treatment) using the Patient Health Questionnaire Anxiety and Depression Scale. Secondary outcomes are depression and anxiety remission, treatment response, health-related quality of life, patient satisfaction, working alliance, psychotherapy adherence, and patient safety. Additionally, several potential moderators and mediators including patient characteristics and attitudes toward the interventions will be examined, complemented by ecological day-to-day digital behavior variables via passive smartphone sensing as part of an integrated smart-sensing sub-study. Data-analysis will be performed on an intention-to-treat basis with additional per-protocol analyses. In addition, cost-effectiveness and cost-utility analyses will be conducted from a societal and a public health care perspective. Additionally, qualitative interviews on acceptance, feasibility, and optimization potential will be conducted and analyzed. Discussion: PSYCHOnlineTHERAPY will provide evidence on blended psychotherapy in one of the largest ever conducted psychotherapy trials. If shown to be non-inferior and cost-effective, PSYCHOnlineTHERAPY has the potential to innovate psychotherapy in the near future by extending the ways of conducting psychotherapy. The rigorous health care services approach will facilitate a timely implementation of blended psychotherapy into standard care. Trial Registration: The trial is registered in the German Clinical Trials Register (DRKS00023973; date of registration: December 28th 2020).
CRIS-Team Scopus Importer:2021-06-11
Keywords: anxiety; blended therapy; depression; E-Mental-Health; implementation; psychotherapy; routine care

Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview - Delaby, Constance; Teunissen, Charlotte E.; Blennow, Kaj; Alcolea, Daniel; Arisi, Ivan; Amar, Elodie Bouaziz; Beaume, Anne; Bedel, Aurelie; Bellomo, Giovanni; Bigot-Corbel, Edith; Bjerke, Maria; Blanc-Quintin, Marie-Celine; et al. (Alzheimers & Dementia, 2021)
Introduction: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of resultsmay differ, which can lead tomisunderstandings and raises questions about the commutability of tests.
CRIS-Team WoS Importer:2021-12-31

Clinical significance of fluid biomarkers in Alzheimer’s Disease - Lewczuk, Piotr; Łukaszewicz-Zając, Marta; Mroczko, Piotr; Kornhuber, Johannes (Pharmacological Reports, 2020)
Abstract: The number of patients with Alzheimer’s Disease (AD) and other types of dementia disorders has drastically increased over the last decades. AD is a complex progressive neurodegenerative disease affecting about 14 million patients in Europe and the United States. The hallmarks of this disease are neurotic plaques consist of the Amyloid-β peptide (Aβ) and neurofibrillary tangles (NFTs) formed of hyperphosphorylated Tau protein (pTau). Currently, four CSF biomarkers: Amyloid beta 42 (Aβ42), Aβ42/40 ratio, Tau protein, and Tau phosphorylated at threonine 181 (pTau181) have been indicated as core neurochemical AD biomarkers. However, the identification of additional fluid biomarkers, useful in the prognosis, risk stratification, and monitoring of drug response is sorely needed to better understand the complex heterogeneity of AD pathology as well as to improve diagnosis of patients with the disease. Several novel biomarkers have been extensively investigated, and their utility must be proved and eventually integrated into guidelines for use in clinical practice. This paper presents the research and development of CSF and blood biomarkers for AD as well as their potential clinical significance. Graphic abstract: Upper panel: Aβ peptides are released from transmembrane Amyloid Precursor Protein (APP) under physiological conditions (blue arrow). In AD, however, pathologic accumulation of Aβ monomers leads to their accumulation in plaques (red arrow). This is reflected in decreased concentration of Aβ1-42 and decreased Aβ42/40 concentration ratio in the CSF. Lower panel: Phosphorylated Tau molecules maintain axonal structures; hyperphosphorylation of Tau (red arrow) in AD leads to degeneration of axons, and release of pTau molecules, which then accumulate in neurofibrillary tangles. This process is reflected by increased concentrations of Tau and pTau in the CSF. [Figure not available: see fulltext.].
CRIS-Team Scopus Importer:2020-05-15
Keywords: Alzheimer's Disease; Amyloid; Biomarkers; Cerebrospinal fluid; Tau

Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer's disease - Blennow, Kaj; Dubois, Bruno; Fagan, Anne M.; Lewczuk, Piotr; De Leon, Mony J.; Hampel, Harald (Alzheimers & Dementia, 2015)
Several potential disease-modifying drugs for Alzheimer's disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-? (A?1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF biomarkers for both clinical trials and routine clinical diagnosis of AD.
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Clinico-genetic findings in 509 frontotemporal dementia patients - Wagner, Matias; Lorenz, Georg; Volk, Alexander E.; Brunet, Theresa; Edbauer, Dieter; Berutti, Riccardo; Zhao, Chen; Anderl-Straub, Sarah; Bertram, Lars; Danek, Adrian; Deschauer, Marcus; Dill, Veronika; et al. (Molecular Psychiatry, 2021)
Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. To which extent genetic aberrations dictate clinical presentation remains elusive. We investigated the spectrum of genetic causes and assessed the genotype-driven differences in biomarker profiles, disease severity and clinical manifestation by recruiting 509 FTD patients from different centers of the German FTLD consortium where individuals were clinically assessed including biomarker analysis. Exome sequencing as well as C9orf72 repeat analysis were performed in all patients. These genetic analyses resulted in a diagnostic yield of 18.1%. Pathogenic variants in C9orf72 (n = 47), GRN (n = 26), MAPT (n = 11), TBK1 (n = 5), FUS (n = 1), TARDBP (n = 1), and CTSF (n = 1) were identified across all clinical subtypes of FTD. TBK1-associated FTD was frequent accounting for 5.4% of solved cases. Detection of a homozygous missense variant verified CTSF as an FTD gene. ABCA7 was identified as a candidate gene for monogenic FTD. The distribution of APOE alleles did not differ significantly between FTD patients and the average population. Male sex was weakly associated with clinical manifestation of the behavioral variant of FTD. Age of onset was lowest in MAPT patients. Further, high CSF neurofilament light chain levels were found to be related to GRN-associated FTD. Our study provides large-scale retrospective clinico-genetic data such as on disease manifestation and progression of FTD. These data will be relevant for counseling patients and their families.
CRIS-Team Scopus Importer:2021-10-08

Cloninger Type 2 Score and Lesch Typology Predict Hospital Readmission of Female and Male Alcohol-Dependent Inpatients During a 24-Month Follow-Up - Weinland, Christian; Braun, Birgit; Mühle, Christiane; Kornhuber, Johannes; Lenz, Bernd (Alcoholism-Clinical and Experimental Research, 2017)
BACKGROUND: Relapse after detoxification treatment is a common problem in alcohol dependence. However, its prediction still lacks reliability. We here investigated whether the easily accessible clinical Cloninger and Lesch classifications predict alcohol-related hospital readmission following inpatient withdrawal treatment. METHODS: In this bicentric prospective clinical study, 67 female and 84 male alcohol-dependent inpatients were characterized according to the Cloninger items and the Lesch typology. The patients' records were followed for 24 months. Because of the well-established sex differences in alcohol dependence, we studied females and males separately. RESULTS: Overall, 54% of the female patients and 67% of the male patients sustained at least 1 alcohol-related hospital readmission during the follow-up. Readmission was related to a higher Cloninger type 2 score than nonreadmission (females, p = 0.007, males p = 0.044). In females, the Cloninger type 2 score correlated with the number of readmissions (ρ = 0.384, p = 0.001) and the days to first readmission (ρ = -0.333, p = 0.006). The effects were stronger in patients with age at onset of alcohol dependence over 25 years. We found gender dimorphisms concerning the Cloninger items. In female patients, the 4 Lesch subtypes differed in their risk (p = 0.010), the number (p = 0.040), and the days to first readmission (p = 0.031). Lesch type 1 was associated with an increased risk (OR = 4.83, p = 0.041) and Lesch type 2 with a reduced risk (OR = 0.07, p = 0.004). In addition, the number of previous inpatient alcohol withdrawals predicted the patients' outcomes (p < 0.05). CONCLUSIONS: The Cloninger type 2 score and the Lesch typology are promising tools for the prediction of alcohol-related readmissions. Our findings provide the basis to optimize relapse prevention in alcohol dependence.
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Cluster C Personality Accentuation in Patients with Takotsubo Cardiomyopathy Personality Traits Mark Vulnerability - Mueller, Helge H.; Sperling, Wolfgang; Kornhuber, Johannes (Psychiatria Danubina, 2017)
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c-MRI findings after crystal meth abuse - Möbius, Cornelia; Kustermann, Andreas; Struffert, Tobias; Kornhuber, Johannes; Mueller, Helge H. (Journal of Addiction Medicine, 2014)
We describe a case of intoxication with N-methylamphetamine (Crystal-METH) after withdrawal. Crystal-METH abuse was associated with persisting neurological symptoms and impressive structural white matter alterations. Magnetic resonance imaging should be recommended to document the possible extensive changes in amphetamine abuse, which increases dramatically.
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Cocaine attenuates acid sphingomyelinase activity during establishment of addiction-related behavior—A translational study in rats and monkeys - Frankowska, Małgorzata; Jesus, Fernando M.; Mühle, Christiane; Pacheco, Jéssica V.N.; Maior, Rafael S.; Sadakierska-Chudy, Anna; Smaga, Irena; Piechota, Marcin; Kalinichenko, Liubov; Gulbins, Erich; Kornhuber, Johannes; Filip, Małgorzata; et al. (Addiction Biology, 2020)
Cocaine addiction is a severe psychiatric condition for which currently no effective pharmacotherapy is available. Brain mechanisms for the establishment of addiction-related behaviors are still not fully understood, and specific biomarkers for cocaine use are not available. Sphingolipids are major membrane lipids, which shape neuronal membrane composition and dynamics in the brain. Here, we investigated how chronic cocaine exposure during establishment of addiction-related behaviors affects the activity of the sphingolipid rheostat controlling enzymes in the brain of rats. As we detected specific effects on several enzymes in the brain, we tested whether the activity of selected enzymes in the blood may serve as potential biomarker for cocaine exposure in non-human primates (Callithrix penicillata). We found that intravenous cocaine self-administration led to a reduced mRNA expression of Cers1, Degs1 and Degs2, and Smpd1 in the prefrontal cortex of rats, as well as a reduction of Cers4 expression in the striatum. These effects reversed after 10 days of abstinence. Monkeys showed a robust cocaine-induced place preference (CPP). This coincided with a reduction in blood acid sphingomyelinase (ASM) activity after CPP establishment. This effect normalized after 15 days of abstinence. Altogether, these findings suggest that the establishment of cocaine addiction-related behaviors coincides with changes in the activity of sphingolipid controlling enzymes. In particular, blood ASM levels may serve as a translational biomarker for recent cocaine exposure.
CRIS-Team Scopus Importer:2020-08-14
Keywords: cocaine; conditioned place preference; monkeys; rats; self-administration; sphingolipids; sphingomyelinase

Cognitive impairments and mental health of patients with post-COVID-19: A cross-sectional study - Morawa, Eva; Krehbiel, Johannes; Borho, Andrea; Herold, Regina; Lieb, Marietta; Schug, Caterina; Erim, Yesim (Journal of Psychosomatic Research, 2023)
Background: Persistent cognitive complaints belong to the most frequent symptoms after COVID-19. This study explored the neuropsychological profile, mental health and risk factors for cognitive impairment in post-COVID-19 patients. Methods: The patients were recruited consecutively in the Post COVID Center of the University Hospital of Erlangen between 12/2022 and 05/2023. They underwent an extensive neuropsychological assessment including the Verbal Learning Memory Test (VLMT), the digit span backwards from the Wechsler Memory Scale-Revised (WMS-R), the Trail Making Test (TMT) Part A and B, the d2 Test of Attention and the Regensburger Verbal Fluency Test (RWT). For each cognitive domain we calculated the frequency of age-adjusted scores below the measure-specific norms. Depressive symptoms were measured with the Patient-Health-Questionnaire-9 (PHQ-9). Logistic regression analyses were computed. Results: In 110 patients (mean age: 42.5 ± 11.9 years; 68.2% women), the most frequent cognitive deficits were observed for verbal fluency, working speed, delayed recall and attention. In almost every cognitive domain high education levels were associated with a decreased risk for cognitive impairment. Higher age was a risk factor for working speed and delayed recall and a protective factor for verbal fluency. Clinically relevant depressive symptoms were associated with an elevated risk for an impairment regarding some cognitive functions. Conclusion: Cognitive dysfunctions were common among the post-COVID-19 patients. Differentiated exploration of cognitive impairments is crucial for a proper characterization of the post-COVID syndrome. In future research parameters of cognitive impairment should be correlated to alterations in biological markers of the disease like markers of immunological and microcirculation change.
CRIS-Team Scopus Importer:2023-08-18
Keywords: Cognitive deficits; Cognitive impairment; COVID-19; Depression; Mental health; Neurocognitive function; Post-COVID-19

Cognitive profiles of patients with mild cognitive impairment due to Alzheimer's versus Parkinson's disease defined using a base rate approach: Implications for neuropsychological assessments - Ophey, Anja; Wolfsgruber, Steffen; Roeske, Sandra; Polcher, Alexandra; Spottke, Annika; Frolich, Lutz; Hull, Michael; Jessen, Frank; Kornhuber, Johannes; Maier, Wolfgang; Peters, Oliver; Ramirez, Alfredo; et al. (Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring, 2021)
Introduction Large studies on cognitive profiles of patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD-MCI) compared to Parkinson's disease (PD-MCI) are rare. Methods Data from two multicenter cohort studies in AD and PD were merged using a unified base rate approach for the MCI diagnosis. Cognitive profiles were compared using scores derived from the Consortium to Establish a Registry for Alzheimer's Disease battery. Results Patients with AD-MCI showed lower standardized scores on all memory test scores and a language test. Patients with PD-MCI showed lower standardized scores in a set-shifting measure as an executive task. A cross-validated logistic regression with test scores as predictors was able to classify 72% of patients correctly to AD-MCI versus PD-MCI. Discussion The applied test battery successfully discriminated between AD-MCI and PD-MCI. Neuropsychological test batteries in clinical practice should always include a broad spectrum of cognitive domains to capture any cognitive changes.
CRIS-Team WoS Importer:2021-09-24

Cognitive subtypes of probable Alzheimer's disease robustly identified in four cohorts - Scheltens, Nienke M. E.; Tijms, Betty M.; Koene, Teddy; Barkhof, Frederik; Teunissen, Charlotte E.; Wolfsgruber, Steffen; Wagner, Michael; Kornhuber, Johannes; Peters, Oliver; Cohn-Sheehy, Brendan I.; Rabinovici, Gil D.; Miller, Bruce L.; et al. (Alzheimers & Dementia, 2017)
INTRODUCTION: Patients with Alzheimer's disease (AD) show heterogeneity in profile of cognitive impairment. We aimed to identify cognitive subtypes in four large AD cohorts using a data-driven clustering approach. METHODS: We included probable AD dementia patients from the Amsterdam Dementia Cohort (n = 496), Alzheimer's Disease Neuroimaging Initiative (n = 376), German Dementia Competence Network (n = 521), and University of California, San Francisco (n = 589). Neuropsychological data were clustered using nonnegative matrix factorization. We explored clinical and neurobiological characteristics of identified clusters. RESULTS: In each cohort, a two-clusters solution best fitted the data (cophenetic correlation >0.9): one cluster was memory-impaired and the other relatively memory spared. Pooled analyses showed that the memory-spared clusters (29%-52% of patients) were younger, more often apolipoprotein E (APOE) ɛ4 negative, and had more severe posterior atrophy compared with the memory-impaired clusters (all P < .05). CONCLUSIONS: We could identify two robust cognitive clusters in four independent large cohorts with distinct clinical characteristics.
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Combination therapy with peginterferon alpha-2B and ribavirin in liver transplant recipients with recurrent HCV infection: Preliminary results of an open prospective study - Beckebaum, Susanne; Cicinnati, Vito; Zhang, Xin; Malago, Massimo; Dirsch, Olaf; Erim, Yesim; Frilling, Andrea; Broelsch, Christoph E.; Gerken, Guido (Transplantation Proceedings, 2004)

Common network effect-patterns after monoamine reuptake inhibition in dissociated hippocampus cultures - Trepl, Julia; Dahlmanns, Marc; Kornhuber, Johannes; Groemer, Teja W.; Dahlmanns, Jana (Journal of Neural Transmission, 2022)
The pharmacological treatment of major depressive disorder with currently available antidepressant drugs is still unsatisfying as response to medication is delayed and in some patients even non-existent. To understand complex psychiatric diseases such as major depressive disorder and their treatment, research focus is shifting from investigating single neurons towards a view of the entire functional and effective neuronal network, because alterations on single synapses through antidepressant drugs may translate to alterations in the entire network. Here, we examined the effects of monoamine reuptake inhibitors on in vitro hippocampal network dynamics using calcium fluorescence imaging and analyzing the data with means of graph theoretical parameters. Hypothesizing that monoamine reuptake inhibitors operate through changes of effective connectivity on micro-scale neuronal networks, we measured the effects of the selective monoamine reuptake inhibitors GBR-12783, Sertraline, Venlafaxine, and Amitriptyline on neuronal networks. We identified a common pattern of effects of the different tested monoamine reuptake inhibitors. After treatment with GBR-12783, Sertraline, and Venlafaxine, the connectivity degree, measuring the number of existing connections in the network, was significantly decreased. All tested substances led to networks with more submodules and a reduced global efficiency. No monoamine reuptake inhibitor did affect network-wide firing rate, the characteristic path length, or the network strength. In our study, we found that monoamine reuptake inhibition in neuronal networks in vitro results in a sharpening of the network structure. These alterations could be the basis for the reorganization of a large-scale miswired network in major depressive disorder.
CRIS-Team Scopus Importer:2022-03-04
Keywords: Antidepressants; Connectivity; Hippocampal networks; Hippocampus culture; Monoamine reuptake inhibitors

Common strength and localization of spontaneous and evoked synaptic vesicle release sites - Loy, Kristina; Welzel, Oliver; Kornhuber, Johannes; Groemer, Teja W. (Molecular Brain, 2014)
Different pools and functions have recently been attributed to spontaneous and evoked vesicle release. Despite the well-established function of evoked release, the neuronal information transmission, the origin as well as the function of spontaneously fusing synaptic vesicles have remained elusive. Recently spontaneous release was found to e.g. regulate postsynaptic protein synthesis or has been linked to depressive disorder. Nevertheless the strength and cellular localization of this release form was neglected so far, which are both essential parameters in neuronal information processing.Here we show that the complete recycling pool can be turned over by spontaneous trafficking and that spontaneous fusion rates critically depend on the neuronal localization of the releasing synapse. Thereby, the distribution equals that of evoked release so that both findings demonstrate a uniform regulation of these fusion modes.In contrast to recent works, our results strengthen the assumption that identical vesicles are used for evoked and spontaneous release and extended the knowledge about spontaneous fusion with respect to its amount and cellular localization. Therefore our data supported the hypothesis of a regulatory role of spontaneous release in neuronal outgrowth and plasticity as neurites secrete neurotransmitters to initiate process outgrowth of a possible postsynaptic neuron to form a new synaptic connection.
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Comorbid medical conditions are a key factor to understand the relationship between psychiatric disorders and COVID-19-related mortality: Results from 49,089 COVID-19 inpatients - Hoertel, Nicolas; Sanchez-Rico, Marina; Jose Herrera-Morueco, Juan; De La Muela, Pedro; Gulbins, Erich; Kornhuber, Johannes; Carpinteiro, Alexander; Becker, Katrin Anne; Cougoule, Celine; Limosin, Frederic (Molecular Psychiatry, 2021)
CRIS-Team WoS Importer:2021-12-03

Comparative analysis of machine learning algorithms for multi-syndrome classification of neurodegenerative syndromes - Lampe, Leonie; Niehaus, Sebastian; Huppertz, Hans-Juergen; Merola, Alberto; Reinelt, Janis; Mueller, Karsten; Anderl-Straub, Sarah; Fassbender, Klaus; Fliessbach, Klaus; Jahn, Holger; Kornhuber, Johannes; Lauer, Martin; et al. (Alzheimer's Research and Therapy, 2022)
Importance The entry of artificial intelligence into medicine is pending. Several methods have been used for the predictions of structured neuroimaging data, yet nobody compared them in this context. Objective Multi-class prediction is key for building computational aid systems for differential diagnosis. We compared support vector machine, random forest, gradient boosting, and deep feed-forward neural networks for the classification of different neurodegenerative syndromes based on structural magnetic resonance imaging. Design, setting, and participants Atlas-based volumetry was performed on multi-centric T1-weighted MRI data from 940 subjects, i.e., 124 healthy controls and 816 patients with ten different neurodegenerative diseases, leading to a multi-diagnostic multi-class classification task with eleven different classes. Interventions N.A. Main outcomes and measures Cohen's kappa, accuracy, and F1-score to assess model performance. Results Overall, the neural network produced both the best performance measures and the most robust results. The smaller classes however were better classified by either the ensemble learning methods or the support vector machine, while performance measures for small classes were comparatively low, as expected. Diseases with regionally specific and pronounced atrophy patterns were generally better classified than diseases with widespread and rather weak atrophy. Conclusions and relevance Our study furthermore underlines the necessity of larger data sets but also calls for a careful consideration of different machine learning methods that can handle the type of data and the classification task best.
CRIS-Team WoS Importer:2022-05-13

Comparing self-report and parental report of psychopathologies in adolescents with substance use disorders - Kuitunen-Paul, Sören; Eichler, Anna; Wiedmann, Melina; Basedow, Lukas A.; Roessner, Veit; Golub, Yulia (European Child & Adolescent Psychiatry, 2021)
Both internalizing and externalizing psychopathologies interfere with the treatment of substance use disorders (SUD) in adolescents. Self-reports of psychopathologies are likely biased and may be validated with parental reports. We compared N = 70 standardized self-reports of adolescents entering outpatient SUD treatment (13.2–18.6 years old, 43% female) to parental reports on the same psychopathologies, and explored biases due to gender, age, SUD diagnoses and SUD severity. Bivariate bootstrapped Pearson correlation coefficients revealed several small to moderate correlations between both reporting sources (r = 0.29–0.49, all pcorrected ≤ 0.039). A repeated measures MANOVA revealed moderately stronger parental reports of adolescent psychopathologies compared to adolescent self-reports for most externalizing problems (dissocial and aggressive behaviors, p ≤ 0.016, η2part = 0.09–0.12) and social/attention problems (p ≤ 0.012, η2part = 0.10), but no differences for most internalizing problems (p ≥ 0.073, η2part = 0.02–0.05). Differences were not associated with other patient or parental characteristics including age, gender, number of co-occurring diagnoses or presence/absence of a certain SUD (all puncorrected ≥ 0.088). We concluded that treatment-seeking German adolescents with SUD present with a multitude of extensive psychopathologies. The relevant deviation between self- and parental reports indicate that the combination of both reports might help to counteract dissimulation and other reporting biases. The generalizability of results to inpatients, psychiatry patients in general, or adolescents without SUD, as well as the validity of self- and parental reports in comparison to clinical judgements remain unknown.
CRIS-Team Scopus Importer:2021-09-10
Keywords: Addiction; Behavioral problems; Emotional problems; Inter-rater agreement; Questionnaire; Substance use disorder

Comparing the effects of isocaloric oral and i.v. application of nutrient solutions on olfactory functioning - Bachlechner, Stephan; Denzer-Lippmann, M.; Wielopolski, Jan; Fische, Mr; Büttner, Andrea; Dörfler, Arnd; Schöfl, Christof; Münch, Georg; Kornhuber, Johannes; Thürauf, Norbert (2016)
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Comparing tomographic EEG neurofeedback and EMG biofeedback in children with attention-deficit/hyperactivity disorder - Maurizio, Stefano; Liechti, Martina Daniela; Heinrich, Hartmut; Jaencke, Lutz; Steinhausen, Hans-Christoph; Walitza, Susanne; Brandeis, Daniel; Drechsler, Renate (Biological Psychology, 2014)
Two types of biofeedback (BF), tomographic electroencephalogram (EEG) neurofeedback (NF) and electromyographic biofeedback (EMG-BF), both with phasic and tonic protocols, were compared for treatment effects and specificity in attention-deficit/hyperactivity disorder (ADHD). Thirteen children with ADHD trained their brain activity in the anterior cingulate cortex (ACC), and twelve trained activity of arm muscles involved in fine motor skills. In each training session, resting state 24-channel EEG and training performances were recorded. Both groups showed similar behavioral improvements and artifact reduction in selected conditions, with no significant advantages despite medium effect sizes on primary outcomes for NF. Only the EMG-BF group, however, showed clear improvement in training regulation performance, and specific motor coordination effects. The NF group tended to present individual normalization of trained frequency bands in the ACC during rest across training. The results provide evidence for some specific effects in our small sample, albeit only to a small extent.
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Comparison of a new microscopic system for the measurement of residual leucocytes in apheresis platelets with flow cytometry and manual counting - Strobel, Joachim; Antos, U.; Zimmermann, Rüdiger; Eckstein, Reinhold; Zingsem, Jürgen (Vox Sanguinis, 2014)
Since 2001, all blood components in Germany must be leucocyte depleted. Recently, a new method for quality control of depletion was introduced. Our study aimed at the validation of the method for routine use in apheresis platelet concentrates.We compared the new ADAM-rWBC device with manual counting in the Nageotte chamber and flow cytometry, two standard methods, by measuring residual leucocytes in 40 units of apheresis platelet concentrates and in six geometrical dilution series.Cell counts of residual leucocytes in the 40 units were below 10(6) cells per component with all methods, although mean cell counts were approximately 5 and 6 times higher in flow cytometry and ADAM-rWBC, respectively, compared to the Nageotte chamber. No unit with <10(6) leucocytes was regarded as contaminated. The dilution series showed acceptable accuracy, especially in the range around the cut-off (approximately 4·5 cells/?l in components with a volume of 220 ml) for regarding a concentrate as contaminated with leucocytes. No sample spiked with more than 4·5 cells/?l was counted as having less.In comparison with manual counting and flow cytometry, the ADAM-rWBC device performed equally. The method is suitable for routine screening of leucocyte contamination of apheresis platelets.
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Comparison of C-Reactive Protein in Dried Blood Spots and Saliva of Healthy Adolescents - Plank, Anne-Christine; Maschke, Janina; Rohleder, Nicolas; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Eichler, Anna; Moll, Gunther; Kratz, Oliver (Frontiers in Immunology, 2021)
Background/AimDetermining C-reactive protein (CRP) by non-invasive methods is of great interest for research addressing inflammation in young people. However, direct comparisons of such methods applied in children and adolescents are lacking so far. This study aimed to evaluate the association between CRP measured in dried blood spots (DBS CRP) and in saliva (sCRP), two less invasive alternatives to venipuncture, in 12- to 14-year-old adolescents. To evaluate the validity of both measurements in the context of biobehavioral studies, the potential of DBS CRP and sCRP to discriminate between defined BMI subgroups was assessed. Materials and MethodsCRP levels in DBS and saliva collected from 87 healthy adolescents (M = 13.25 years, SD = 0.30, 51.7% females) were determined using high sensitive CRP ELISA for serum and salivary CRP ELISA, respectively. Characteristics and correlation of both measurements were assessed for the total sample and for three subgroups classified by BMI percentile ranges (A: <= 25; B: 26-74; C: >= 75). ResultsIn the total sample, DBS CRP and sCRP were significantly associated (r = 0.59, p < 0.001). Splitting the sample into BMI-dependent subgroups revealed similarly strong associations of DBS CRP with sCRP for all three groups (A: r = 0.51; B: r = 0.61; C: r = 0.53). However, comparing the mean CRP values per BMI subgroup, one-way ANOVA reported significant differences for DBS CRP, but not for sCRP mean values. ConclusionsThe significant correlation of DBS CRP with sCRP was independent of the investigated BMI range groups, yet BMI-dependent distinction was only provided by DBS CRP mean values. Overall, our results suggest that DBS CRP is likely to reflect systemic inflammation more precisely. Salivary CRP can be alternatively determined in studies with adolescents when conditions require it, given the oral health status is assessed. Considering that DBS CRP and sCRP share only 35% of common variance, further studies should examine their specific validity.
CRIS-Team WoS Importer:2022-01-14

Comparison of Different Matrices as Potential Quality Control Samples for Neurochemical Dementia Diagnostics - Lelental, Natalia; Brandner, Sebastian; Kofanova, Olga; Blennow, Kaj; Zetterberg, Henrik; Andreasson, Ulf; Engelborghs, Sebastiaan; Mroczko, Barbara; Gabryelewicz, Tomasz; Teunissen, Charlotte; Mollenhauer, Brit; Parnetti, Lucilla; et al. (Journal of Alzheimer's Disease, 2016)
Assay-vendor independent quality control (QC) samples for neurochemical dementia diagnostics (NDD) biomarkers are so far commercially unavailable. This requires that NDD laboratories prepare their own QC samples, for example by pooling leftover cerebrospinal fluid (CSF) samples.To prepare and test alternative matrices for QC samples that could facilitate intra- and inter-laboratory QC of the NDD biomarkers.Three matrices were validated in this study: (A) human pooled CSF, (B) A? peptides spiked into human prediluted plasma, and (C) A? peptides spiked into solution of bovine serum albumin in phosphate-buffered saline. All matrices were tested also after supplementation with an antibacterial agent (sodium azide). We analyzed short- and long-term stability of the biomarkers with ELISA and chemiluminescence (Fujirebio Europe, MSD, IBL International), and performed an inter-laboratory variability study.NDD biomarkers turned out to be stable in almost all samples stored at the tested conditions for up to 14 days as well as in samples stored deep-frozen (at - 80°C) for up to one year. Sodium azide did not influence biomarker stability. Inter-center variability of the samples sent at room temperature (pooled CSF, freeze-dried CSF, and four artificial matrices) was comparable to the results obtained on deep-frozen samples in other large-scale projects.Our results suggest that it is possible to replace self-made, CSF-based QC samples with large-scale volumes of QC materials prepared with artificial peptides and matrices. This would greatly facilitate intra- and inter-laboratory QC schedules for NDD measurements.
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Comparison of illness concepts and coping strategies among cancer patients of Turkish and German origin - Thein, Katja; Erim, Yesim; Morawa, Eva (International Journal of Environmental Research and Public Health, 2020)
Background: The aim of this study was to compare illness concepts and coping strategies among native German cancer patients and those with a Turkish migration background. Methods: Guideline-based, semi-structured interviews were conducted with 11 German (♂: 8, ♀: 3) and 11 Turkish (♂: 2, ♀: 9) cancer patients. The transcripts were evaluated using a qualitative content analysis in accordance with Mayring. Results: We identified eight categories of illness concepts: stressful life events, environmental influences, the will of God, medical factors, fate, trauma, health behaviour, and psychological causes. German patients frequently attributed their illness to environmental influences, persistent stress, or medical factors, whereas Turkish patients blamed persistent stress, the will of God, or trauma. The last two categories are not found among German patients. We classified the coping strategies into 11 main categories: social support, activity, patient competence, fighting spirit/positive thinking, use of health services/alternative healing methods, lifestyle, emotional coping, cognitive coping, religious coping, spiritual coping, and culture-specific methods for patients of Turkish origin. For German patients, activities as well as social support played primary roles in coping. Turkish patients also often used social support. However, in contrast to the German patients, they are less active and use much more religious coping and culture-specific means. In addition, negative emotions occur more often when processing the illness than in the German patients. Conclusion: Common illness representations and coping strategies could be found for Turkish and German patients, but also specific ones for the respective group. It is particularly noticeable that German patients attach more importance to medical factors and try more actively to cope with the illness. For Turkish patients, cultural and religious factors play an important role, which should also be considered in treatment.
CRIS-Team Scopus Importer:2020-08-14
Keywords: Cancer; Coping strategies; Illness beliefs; Illness concepts; Migrants; Turkish

Compatibility of Work and Family Life of Employees in the Healthcare Sector: An Issue in Health Services Research - Lukasczik, Matthias; Ahnert, Jutta; Stroebl, Veronika; Vogel, Heiner; Donath, Carolin; Enger, Ilka; Grässel, Elmar; Heyelmann, Lena; Lux, Heidemarie; Maurer, Jochen; Özbe, Dominik; Spieckenbaum, Stefanie; et al. (Gesundheitswesen, 2018)
BACKGROUND: Healthcare professionals are confronted with specific work-related demands that influence work-family relations and might indirectly affect the quality of healthcare. This paper seeks to provide an overview of the current state of research on this topic of relevance to health services research. The overview may serve as a starting point for modifying structures in the healthcare system (especially in rural regions) with the aim of improving work-family compatibility. METHODS: A systematic national and international literature search was conducted in terms of a scoping review. The following criteria/contents to be covered in publications were defined: work-family compatibility; work-family interface and work-family conflict in employees working in healthcare; healthcare professions in rural areas and links with work-family issues; interventions to improve work-family compatibility. 145 publications were included in the overview. RESULTS: The available literature focuses on physicians and nursing staff while publications on other professions are largely lacking. The methodological quality of existing studies is mostly low, including a lack of meta-analyses. Several studies document dissatisfaction in physicians and nursing staff regarding reconciliation of work and family life. Only few intervention studies were found that seek to improve work-life compatibility; few of them focus on employees in healthcare. There are also deficits with respect to linking work-family issues with aspects of healthcare in rural areas. CONCLUSIONS: There is a shortage of systematic national and international research regarding work-family compatibility, especially when it comes to the evaluation of interventions. The overview provides starting points for improving work-family compatibility in healthcare.
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Compromised cardiovascular autonomic modulation in patient with acute ischemic stroke improves after three & six months - Wang, Ruihao; Macha, Kosmas; Köhn, Julia; Köhn, Julia; Siedler, Gabriela; Winder, Klemens; Gerner, Stefan; Schwab, Stefan; Koehrmann, M.; Kallmünzer, Bernd; Hilz, Max-Josef (EUROPEAN JOURNAL OF NEUROLOGY, 2021)
CRIS-Team WoS Importer:2021-07-23

Computer-assisted prediction of clinical progression in the earliest stages of AD - Rhodius-Meester, Hanneke F.M.; Liedes, Hilkka; Koikkalainen, Juha; Wolfsgruber, Steffen; Coll-Padros, Nina; Kornhuber, Johannes; Peters, Oliver; Jessen, Frank; Kleineidam, Luca; Molinuevo, José Luis; Rami, Lorena; Teunissen, Charlotte E.; et al. (Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring, 2018)
Introduction: Individuals with subjective cognitive decline (SCD) are at increased risk for clinical progression. We studied how combining different diagnostic tests can help to identify individuals who are likely to show clinical progression. Methods: We included 674 patients with SCD (46% female, 64 ± 9 years, Mini-Mental State Examination 28 ± 2) from three memory clinic cohorts. A multivariate model based on the Disease State Index classifier incorporated the available baseline tests to predict progression to MCI or dementia over time. We developed and internally validated the model in one cohort and externally validated it in the other cohorts. Results: After 2.9 ± 2.0 years, 151(22%) patients showed clinical progression. Overall performance of the classifier when combining cognitive tests, magnetic resonance imagining, and cerebrospinal fluid showed a balanced accuracy of 74.0 ± 5.5, with high negative predictive value (93.3 ± 2.8). Discussion: We found that a combination of diagnostic tests helps to identify individuals at risk of progression. The classifier had particularly good accuracy in identifying patients who remained stable.
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Computer Based Body Exposure in Adolescents With Anorexia Nervosa: A Study Protocol - Stonawski, Valeska; Sasse, Lena; Moll, Gunther; Kratz, Oliver; Horndasch, Stefanie (Frontiers in Psychiatry, 2022)
Body dissatisfaction is a core feature of eating disorders (EDs) and plays an essential role in the development and maintenance of anorexia nervosa (AN). In the current study, a computer based body exposure intervention is conducted and evaluated regarding short-term effects on body dissatisfaction, psychopathology, viewing patterns, and stress reactivity. Within a randomized controlled trial (RCT) female adolescents and young women with AN are either receiving the intervention or treatment as usual (TAU). Furthermore, in a transdiagnostic approach, a highly body-dissatisfied group of clinical control participants obtaining the intervention will be surveyed to identify AN-specific processes. The standardized four-session body exposure intervention using photographs of the own body is adapted from a manualized body image treatment program for computer use. Psychopathology (body dissatisfaction, body image avoidance, body checking, depression, anxiety) is assessed via standardized questionnaires before and after the intervention. During each session, attentional biases regarding one's own body are measured via eye tracking, stress levels are measured via subjective ratings, heart rate variability, as well as salivary cortisol and alpha amylase. Between- and within-subject effects will be assessed. The pilot study aims to identify short-term effects of the intervention on body dissatisfaction and attentional bias, as well as to investigate the potential underlying mechanism of physiological habituation.
CRIS-Team WoS Importer:2022-02-18

Computerised cognitive training tools and online nutritional group counselling for people with mild cognitive impairment: study protocol of a completely digital, randomised, controlled trial. - Scheerbaum, Petra; Book, Stephanie; Jank, Michael; Hanslian, Etienne; Dello'Ro, Melanie; Schneider, Julia; Scheuermann, Julia-Sophia; Bösl, Sophia; Jeitler, Michael; Kessler, Christian; Grässel, Elmar (BMJ Open, 2022)
INTRODUCTION: People with mild cognitive impairment (MCI) are at increased risk of decreasing cognitive functioning. Computerised cognitive training (CCT) and nutrition have been shown to improve the cognitive capacities of people with MCI. For each variable, we developed two kinds of interventions specialised for people with MCI (CCT: 'individualised' CCT; nutrition: a whole-food, plant-based diet). Additionally, there are two kinds of active control measures (CCT: 'basic' CCT; nutrition: a healthy diet following the current guidelines of the German Nutrition Society). The aim of this study is to investigate the effects of the two interventions on cognition in people with MCI in a 2×2 randomised controlled trial with German participants. METHODS AND ANALYSIS: Participants will be community-dwelling individuals with a psychometric diagnosis of MCI based on the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination. With N=200, effects with an effect size of f≥0.24 (comparable to Cohen's d≥0.48) can be detected. Screening, baseline, t6 and t12 testing will be conducted via a videoconferencing assessment, telephone, and online survey. Participants will be randomly allocated to one of four groups and will receive a combination of CCT and online nutritional counselling. The CCT can be carried out independently at home on a computer, laptop, or tablet. Nutrition counselling includes 12 online group sessions every fortnight for 1.5 hours. The treatment phase is 6 months with follow-ups after six and 12 months after baseline. ETHICS AND DISSEMINATION: All procedures were approved by the Friedrich-Alexander-Universität Erlangen-Nürnberg Ethics Committee (Ref. 21-318-1-B). Written informed consent will be obtained from all participants. Results will be published in peer-reviewed scientific journals, conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN10560738.
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Concentrations of matrix metalloproteinases and their tissue inhibitors in the cerebrospinal fluid of patients with Alzheimer's disease - Mroczko, Barbara; Groblewska, Magdalena; Zboch, Marzena; Kulczynska, Agnieszka; Koper, Olga M.; Szmitkowski, Maciej; Kornhuber, Johannes; Lewczuk, Piotr (Journal of Alzheimer's Disease, 2014)
A growing body of evidence shows the involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in neurodegeneration processes, but reports of their concentrations in the cerebrospinal fluid (CSF) are inconsistent.Therefore, the aim of our study was to evaluate the CSF concentrations of MMP-2, MMP-3, MMP-9, and their inhibitors (TIMP-1 and TIMP-2) in carefully selected groups of patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and non-demented controls, whose clinical and neuropsychological diagnoses were confirmed by the corresponding CSF biomarkers of neurochemical dementia diagnostics: decreased concentrations of A?1-42 and/or A?42/40 ratio, and increased concentrations of Tau and pTau181 proteins.The study included 33 AD patients, 15 subjects with MCI, and 18 elderly individuals without cognitive deficits. The CSF concentrations of MMPs and TIMPs were determined with ELISAs.CSF concentrations of MMP-9 were significantly lower, and the concentrations of MMP-3 significantly higher in AD patients compared to the controls. Neither MMP-2 nor TIMPs showed significant changes among the groups investigated.Altered concentrations of two out of three MMPs investigated in this study suggest that this family of biomolecules may play a role in the AD pathophysiology. Further studies are needed to establish their potential diagnostic utility.
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Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part II: Cognition, neuroimaging and genetics - Schmitt, Andrea; Rujescu, Dan; Gawlik, Micha; Hasan, Alkomiet; Hashimoto, Kenji; Iceta, Sylvain; Jarema, Marek; Kambeitz, Joseph; Kasper, Siegfried; Keeser, Daniel; Kornhuber, Johannes; Koutsouleris, Nikolaos; et al. (World Journal of Biological Psychiatry, 2016)
OBJECTIVES: Schizophrenia is a group of severe psychiatric disorders with high heritability but only low odds ratios of risk genes. Despite progress in the identification of pathophysiological processes, valid biomarkers of the disease are still lacking. METHODS: This comprehensive review summarises recent efforts to identify genetic underpinnings, clinical and cognitive endophenotypes and symptom dimensions of schizophrenia and presents findings from neuroimaging studies with structural, functional and spectroscopy magnetic resonance imaging and positron emission tomography. The potential of findings to be biomarkers of schizophrenia is discussed. RESULTS: Recent findings have not resulted in clear biomarkers for schizophrenia. However, we identified several biomarkers that are potential candidates for future research. Among them, copy number variations and links between genetic polymorphisms derived from genome-wide analysis studies, clinical or cognitive phenotypes, multimodal neuroimaging findings including positron emission tomography and magnetic resonance imaging, and the application of multivariate pattern analyses are promising. CONCLUSIONS: Future studies should address the effects of treatment and stage of the disease more precisely and apply combinations of biomarker candidates. Although biomarkers for schizophrenia await validation, knowledge on candidate genomic and neuroimaging biomarkers is growing rapidly and research on this topic has the potential to identify psychiatric endophenotypes and in the future increase insight on individual treatment response in schizophrenia.
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Coping styles and causal attributions of Turkish and German patients with cancer: A qualitative study - Morawa, Eva; Erim, Yesim (2017)
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Correction to: Common network effect‑patterns after monoamine reuptake inhibition in dissociated hippocampus cultures (Journal of Neural Transmission, (2022), 129, 3, (261-275), 10.1007/s00702-022-02477-6) - Trepl, Julia; Dahlmanns, Marc; Kornhuber, Johannes; Grömer, Teja Wolfgang; Dahlmanns, Jana (Journal of Neural Transmission, 2022)
The Acknowledgements section was missing from this article and should have read: The present work was performed in (partial) fulfillment of the requirements for obtaining the degree "Dr. med."/"Dr. med. dent. The original article has been corrected.
CRIS-Team Scopus Importer:2022-10-21

Correction to: Out of the woods: psychophysiological investigations on wood odors to estimate their suitability as ambient scents (Wood Science and Technology, (2020), 54, 5, (1385-1400), 10.1007/s00226-020-01216-y) - Schreiner, Linda; Karacan, Brid; Blankenagel, Sonja; Packhaeuser, Kai; Freiherr, Jessica; Loos, Helene (Wood Science and Technology, 2021)
The article [Out of the woods: psychophysiological investigations on wood odors to estimate their suitability as ambient scents], written by [Linda Schreiner, Brid Karacan, Sonja Blankenagel, Kai Packhaeuser, Jessica Freiherr and Helene M. Loos], was originally published Online First without Open Access. After publication in volume [54], issue [5], page [1385–1400] the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © [The Author(s)] [2021] and this article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The original article has been corrected.
CRIS-Team Scopus Importer:2021-12-17

Correlates and Predictors of PTSD Symptoms Among Healthcare Workers During the COVID-19 Pandemic: Results of the egePan-VOICE Study - Steudte-Schmiedgen, Susann; Stieler, Lisa; Erim, Yesim; Morawa, Eva; Geiser, Franziska; Beschoner, Petra; Jerg-Bretzke, Lucia; Albus, Christian; Hiebel, Nina; Weidner, Kerstin (Frontiers in Psychiatry, 2021)
Background: The COVID-19 pandemic has led to ongoing challenges for healthcare systems across the world. Previous research has provided evidence for an increased prevalence of depression and anxiety as well as post-traumatic stress disorder (PTSD). In Germany, however, only scarce data on correlates and predictors for PTSD symptomatology in the context of the COVID-19 pandemic among healthcare workers (HCW) are available. Methods: This research is part of a large prospective web-based survey (egePan-VOICE study) among HCW in Germany. The current sample (N = 4,724) consisted of physicians (n = 1,575), nurses (n = 1,277), medical technical assistants (MTA, n = 1,662), and psychologists (n = 210). PTSD symptomatology was measured using the abbreviated version of the Impact of Event Scale (IES-6). In addition, sociodemographic, occupational, COVID-19-related, psychological (e.g., depressive symptoms and generalized anxiety), as well as work-related variables were assessed. Results: Our findings revealed significant higher PTSD symptoms with medium effect sizes among HCW reporting an increased self-report burden during the pandemic, increased fear of becoming infected or infecting relatives with the virus, sleep problems, feeling physically or mentally exhausted, as well as increased levels of depressiveness and generalized anxiety. According to multiple linear regression analysis, the most relevant predictors for higher IES-6 scores were increased level of generalized anxiety and depressiveness, increased fear of infecting relatives, as well as medical profession (MTA compared to physicians). Conclusion: Despite the cross-sectional design of our study, the here identified associations with PTSD symptomatology may provide a basis for future preventive interventions.
CRIS-Team Scopus Importer:2021-09-17
Keywords: anxiety; COVID-19; depression; healthcare; mental health; post-traumatic stress disorder

Correlation between coping strategies and subjective assessment of the voice-related quality of life of patients after resection of T1 and T2 laryngeal tumours - Seiferlein, Eva; Haderlein, Tino; Schuster, Maria; Grässel, Elmar; Bohr, Christopher (European Archives of Oto-Rhino-Laryngology, 2012)

Correlation of CSF- and MRI-Biomarkers and Progression of Cognitive Decline in an Open Label MCI Trial - Joachim, L. K.; Froelich, L.; Ruether, E.; Wiltfang, J.; Maier, W.; Kornhuber, Johannes; Bauer, C.; Heuser,; Peters, O. (The Journal of Prevention of Alzheimer's Disease, 2018)
BACKGROUND: In several randomized controlled trials (RCT) acetylcholinesterase-inhibitors (AChE-I) were tested in patients with mild cognitive impairment (MCI) but were ineffective in delaying disease progression as determined by neuropsychological testing only. Here we present data from an open label observational extension of a multicenter RCT in order to assess if biomarkers are providing useful additional information about a drug's efficacy. We followed 83 amnestic MCI patients and performed correlational analyses of A beta 1-42 and total-Tau in the cerebrospinal fluid (CSF), hippocampal and amygdala volume at baseline, the total duration of blinded and open label AChE-I treatment and the outcome 24 months after inclusion into the RCT. Twelve out of 83 amnestic MCI (14%) had progressed to Alzheimer's disease (AD). Overall, worsening and disease progression as measured by the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) and Clinical Dementia Rating (CDR) did not correlate with the duration of AChE-I treatment. However, a specific multidimensional biomarker profile at baseline indicated more reliably than cognitive testing alone progression to AD. We conclude that pharmacological RCTs testing symptomatic treatment effects in MCI should include biomarker assessment.
CRIS-Team WoS Importer:2019-04-04

Corrigendum: Feasibility and Diagnostic Accuracy of Ischemic Stroke Territory Recognition Based on Two-dimensional Projections of Three-dimensional Diffusion MRI Data - Wrosch, Jana Katharina; Volbers, Bastian; Gölitz, Philipp; Gilbert, Daniel; Schwab, Stefan; Dörfler, Arnd; Kornhuber, Johannes; Groemer, Teja Wolfgang (Frontiers in Neurology, 2017)
[This corrects the article on p. 239 in vol. 6, PMID: 26635717.].
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Corrigendum to “Cross-reinstatement of mitragynine and morphine place preference in rats” [Behav. Brain Res. 399 (2021) 113021] (Behavioural Brain Research (2021) 399, (S0166432820307208), (10.1016/j.bbr.2020.113021)) - Japarin, Rima Atria; Yusoff, Nurul Hasnida; Hassan, Zurina; Müller, Christian P.; Harun, Norsyifa (Behavioural Brain Research, 2023)
The authors regret “that did not include the post conditioning data in the figures and results section”. [Formula presented] Fig. 2. Drug priming reinstatement of a conditioned place preference following extinction A) Conditioned place preference. Data represents (mean ± SEM) of time spent in drug-paired side during pre-conditioning, post-conditioning, extinction and reinstatement test B) Locomotor activity in the conditioning compartment during pre-conditioning, post-conditioning, extinction and reinstatement test. Data represents (mean ± SEM) of distance travelled in drug-paired side during pre-conditioning, post-conditioning, extinction and reinstatement test C) Entries into conditioning compartment during pre-conditioning, post-conditioning, extinction and reinstatement test. Data represents (mean ± SEM) of number of entries in drug-paired side during pre-conditioning, post-conditioning, extinction and reinstatement test. (T-80, Tween-80; MOR, morphine 5, 10 mg/kg; METH, methamphetamine 0.5, 1 mg/kg; MG, mitragynine 5, 10, 15, 30 mg/kg; n = 10–12/group; *p < 0.05; ***p < 0.001 vs. extinction test; @p < 0.05 vs. post-conditioning test; ##p < 0.01 vs. pre conditioning test. [Formula presented] Fig. 3. Cross-reinstatement of a morphine conditioned place preference by mitragynine (MG) (A) Time spent in drug-paired side during reinstatement of a previously extinguished morphine-induced CPP with priming doses of MG. All animals were conditioned with 10 mg/kg of morphine and after extinction, were reinstated with the following doses of MG (0, 3, 10 and 30 mg/kg; n = 6–10/group) B) Locomotor activity in the conditioning compartment during reinstatement of a previously extinguished morphine-induced CPP with priming doses of MG C) Entries into conditioning compartment during reinstatement of a previously extinguished morphine-induced CPP with priming doses of MG (***p < 0.001, **p < 0.01, *p < 0.05 vs. extinction; ###p < 0.001, ##P < 0.01, #p < 0.05 vs. pre conditioning test). [Formula presented] Fig. 4. Cross-reinstatement of a mitragynine (MG) conditioned place preference by morphine (MOR) A) Time spent in drug-paired side during reinstatement of a previously extinguished MG-induced CPP with priming doses of MOR. All animals were conditioned with 30 mg/kg MG and after extinction, were reinstated with the following doses of MOR (0, 1, 3 and 10 mg/kg; n = 6–10/group) B) Locomotor activity in the conditioning compartment during reinstatement of a previously extinguished MG-induced CPP with priming doses of MOR C) Entries into conditioning compartment during reinstatement of a previously extinguished MG-induced CPP with priming doses of MOR (***p < 0.001, **P < 0.01, *p < 0.05 vs. extinction; ###p < 0.001, ##p < 0.01, #p < 0.05 vs. pre conditioning test). 3.1. Reinstatement of previously extinguished MG and morphine place preference effects Following the acquisition of a CPP, all treatment groups underwent an extinction training and reinstatement. A two-way ANOVA for the time spent in the drug-paired compartment revealed a significant effect on tests (F3, 174 = 7.02, p = 0.0002) and doses (F4, 174 = 2.71, p = 0.0316) with no significant effect on interaction (F12, 174 = 1.59, p = 0.0981). The time spent in the drug-paired compartment became similar to those of pre-conditioning phase (p > 0.05) for all treatment groups following extinction training (Fig. 2A). Subsequently, the extinguished drug-induced CPP was reinstated in rats treated with the corresponding conditioning drugs at half of the dose administered during conditioning phase (MOR, morphine 5 mg/kg; METH, methamphetamine 0.5 mg/kg; MG, mitragynine 5, 15 mg/kg in the reinstatement test), as shown by the increased time spent in the drug-associated chamber during reinstatement test compared to the extinction test (MOR 10 mg/kg: p < 0.05, MG 10 mg/kg: p < 0.05). In addition, morphine-treated rats exhibited an increased time spent in the drug-paired chamber during reinstatement compared to the pre-conditioning test (MOR 10 mg/kg: p < 0.05). On the other hand, rats reinstated with methamphetamine exhibited no significant effect on time spent in the drug-paired chamber relative to the pre-conditioning test (METH 1 mg/kg: p > 0.05) and extinction test (METH 1 mg/kg: p > 0.05). A two-way repeated measures ANOVA for locomotor activity in the drug-paired compartment for the reinstatement groups (Fig. 2B) revealed a significant effect on tests (F3,200 = 6.889, p = 0.0002) and doses (F4,200 = 2.873, p = 0.0241) but no significant effect on interaction (F12,200 = 1.008, p = 0.4425). Only the morphine group exhibited a significant hyperlocomotion effect after a priming drug injection when compared to pre-conditioning test (MOR 10 mg/kg: p < 0.001) and extinction test (MOR 10 mg/kg: p < 0.01). Meanwhile, no changes were observed for other treatment groups during reinstatement when compared to pre-conditioning test (METH 1 mg/kg: p > 0.05, MG 10 mg/kg: p > 0.05, MG 30 mg/kg: p > 0.05) and extinction test (METH 1 mg/kg: p > 0.05, MG 10 mg/kg: p > 0.05, MG 30 mg/kg: p > 0.05) (Fig. 2B). The reinstatement doses of morphine caused an increase in the number of entries into the drug-associated compartment between pre-conditioning and reinstatement, however, it did not reach statistical significance (Fig. 2C). There was no difference in the number of entries throughout the experiment for reinstatement doses of the other treatment groups between pre-conditioning and reinstatement (METH 1 mg/kg: p > 0.05, MG 10 mg/kg: p > 0.05, MG 30 mg/kg: p > 0.05) and extinction and reinstatement (MOR 10 mg/kg: p > 0.05, METH 1 mg/kg: p > 0.05, MG 10 mg/kg: p > 0.05, MG 30 mg/kg: p > 0.05). A two-way repeated measures ANOVA for the number of entries into the drug-paired side showed no significant effect on tests (F3, 208 = 2.28, p = 0.0803), doses (F4, 208 = 1.06, p = 0.3753) and interaction (F12, 208 = 0.38, p = 0.9695) (Fig. 2C). 3.2. Effects of MG priming doses on a previously extinguished place preference induced by morphine MG induces reinstatement of a previously extinguished morphine CPP (Fig. 3A). A two-way ANOVA for the time spent in the drug-paired compartment revealed a significant effect on tests (F3, 111 = 30.05, p < 0.0001) and interaction (F9,111 = 2.08, p = 0.0375) with no significant doses effect (F3, 111 = 2.67, p = 0.0509). Post-hoc comparisons showed that all rats conditioned with morphine (10 mg/kg) exhibited a CPP effect during the post-conditioning (reinstatement dose: vehicle: p < 0.05, MG 3 mg/kg: p < 0.01, MG 10 mg/kg: p < 0.001, MG 30 mg/kg: p < 0.001) when compared to the pre-conditioning test. In addition, post-hoc comparisons showed that all reinstatement doses of MG completely reinstated the morphine-induced CPP as seen by the increased time spent in the drug-associated chamber during the reinstatement compared to pre-conditioning test (MG 3 mg/kg: p < 0.001, MG 10 mg/ kg: p < 0.001, MG 30 mg/kg: p < 0.001). A two-way ANOVA for locomotor activity of the extinguished morphine-induced CPP group (Fig. 3B) showed a significant effect on MG reinstatement doses (F3,113 = 6.45, p = 0.0005) and tests (F3,113 = 16.73, p < 0.0001), with no significant effect on dose x tests interaction (F9,113 = 1.22, p = 0.2896). The reinstatement dose of MG at the highest dose exhibited significant hypolocomotion (MG 30 mg/kg: p < 0.05) following administration of the priming drug injection but no changes were noted for other MG doses. The highest reinstatement dose of MG exhibited a greater significant decrease in the number of entries into the drug-paired chamber between extinction and reinstatement (MG 30 mg/kg: p < 0.05; Fig. 3C). In addition, the reinstatement doses of MG caused a significant decrement in the number of entries into the drug-paired chamber between pre-conditioning and reinstatement (MG 10 mg/kg: p < 0.05, MG 30 mg/kg: p < 0.001). A two-way ANOVA revealed significant effects for the reinstatement doses (F3,130 = 4.24, p = 0.0068) and dose x tests interaction (F9,130 = 3.01, p = 0.0027) but no significant effect of tests (F3,130 = 2.37, p = 0.0733). 3.3 Effects of morphine priming doses on a previously extinguished place preference induced by MG Morphine induces reinstatement of a previously extinguished MG CPP (Fig. 4A). A two-way ANOVA for the time spent in the drug-paired side showed a significant effect on doses (F3,74 = 3.64, p = 0.0166), tests (F3,74 = 27.21, p < 0.0001) and interactions (F9,74 = 4.35, p = 0.0001). Post-hoc comparisons showed that all rats conditioned with MG (30 mg/kg) showed a significant CPP effect, as all the groups spent more time in the drug-paired chamber during post-conditioning than in the pre-conditioning session (reinstatement doses: vehicle: p < 0.01, MOR 1 mg/kg: p < 0.001, MOR 3 mg/kg: p < 0.001, MOR 10 mg/kg: p < 0.01). Post hoc comparisons also revealed that morphine at all doses (1, 3, 10 mg/kg) reinstated the extinguished MG-induced CPP as shown by an increase time spent in the drug-paired chamber compared to pre-conditioning test (MOR 1 mg/kg: p < 0.001, MOR 3 mg/kg: p < 0.001, MOR 10 mg/kg: p < 0.001). Meanwhile, a significant hypolocomotor activity was observed for the reinstatement of extinguished MG-induced CPP with morphine at all doses when compared with pre-conditioning (MOR 1 mg/kg: p < 0.01; MOR 3 mg/kg: p < 0.001; MOR 10 mg/kg: p < 0.01; Fig. 4B) and extinction (MOR 1 mg/kg: p < 0.05; MOR 3 mg/kg: p < 0.01; MOR 10 mg/kg: p < 0.05; Fig. 4B). Meanwhile, only rats reinstated with morphine at 1 mg/kg exhibited a significant hyperlocomotor effect during the post-conditioning test when compared with the pre-conditioning test (p < 0.001). A two-way ANOVA for the activity showed a significant effect of tests (F3,70 = 24.18, p < 0.0001), dose (F3,70 = 2.97, p = 0.0376) and interaction (F9,70 = 3.96, p = 0.0004). The reinstatement doses of morphine caused a significant decrease in the number of entries into the drug-associated compartment between pre-conditioning and reinstatement (3 mg/kg: p < 0.001; 10 mg/kg: p < 0.01; Fig. 4C). A two-way ANOVA showed a significant effect of tests (F3,86 = 10.21, p < 0.0001), but no effect of reinstatement dose (F3,86 = 2.04, p = 0.1142) or interaction (F9,86 = 0.78, p = 0.6386). The authors would like to apologise for any inconvenience caused.
CRIS-Team Scopus Importer:2022-10-28

Corrigendum to: More Than Smell-COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis. - Parma, Valentina; Ohla, Kathrin; Veldhuizen, Maria G.; Niv, Masha Y.; Kelly, Christine E.; Bakke, Alyssa J.; Cooper, Keiland W.; Bouysset, Cedric; Pirastu, Nicola; Dibattista, Michele; Kaur, Rishemjit; Liuzza, Marco Tullio; et al. (Chemical Senses, 2021)
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Cost-effectiveness of a non-pharmacological treatment vs. "care as usual" in day care centers for community-dwelling older people with cognitive impairment: results from the German randomized controlled DeTaMAKS-trial - Steinbeisser, Kathrin; Schwarzkopf, Larissa; Grässel, Elmar; Seidl, Hildegard (European Journal of Health Economics, 2020)
Background Cognitive impairment in older adults causes a high economic and societal burden. This study assesses the cost-effectiveness of the multicomponent, non-pharmacological MAKS treatment vs. "care as usual" in German day care centers (DCCs) for community-dwelling people with mild cognitive impairment (MCI) or mild to moderate dementia over 6 months. Methods The analysis was conducted from the societal perspective alongside the cluster-randomized controlled, multicenter, prospective DeTaMAKS-trial with waitlist group design. Outcomes were Mini-Mental Status Examination (MMSE) and Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM) of 433 individuals in 32 DCCs. Incremental differences in MMSE and ETAM were calculated via a Gaussian-distributed and incremental cost difference via a Gamma-distributed Generalized Linear Model. Cost-effectiveness was assessed via cost-effectiveness planes and cost-effectiveness acceptability curves (CEAC). Results At 6 months, MMSE (adjusted mean difference = 0.92; 95% confidence interval (CI): 0.17 to 1.67; p = 0.02) and ETAM (adjusted mean difference = 1.00; CI: 0.14 to 1.85; p = 0.02) were significantly better in the intervention group. The adjusted cost difference was - euro938.50 (CI: - 2733.65 to 763.13; p = 0.31). Given the CEAC, MAKS was cost-effective for 78.0% of MMSE and 77.4% for ETAM without a need for additional costs to payers. Conclusions MAKS is a cost-effective treatment to stabilize the ability to perform activities of daily living and cognitive abilities of people with MCI or mild to moderate dementia in German DCCs. Thus, MAKS should be implemented in DCCs.
CRIS-Team WoS Importer:2020-04-10

Creativity and mental disorder - Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2015)
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CRISPR/Cas9-mediated generation of hESC lines with homozygote and heterozygote p.R331W mutation in CTBP1 to model HADDTS syndrome - Akdas, Enes Yagiz; Turan, Sören; Guhathakurta, Debarpan; Ekici, Arif Bülent; Salar, Seda; Lie, Dieter Chichung; Winner, Beate; Fejtová, Anna (Stem Cell Research, 2023)
C-terminal Binding Protein 1 (CTBP1) is a ubiquitously expressed transcriptional co-repressor and membrane trafficking regulator. A recurrent de novo c.991C>T mutation in CTBP1 leads to expression of p.R331W CTBP1 and causes hypotonia, ataxia, developmental delay, and tooth enamel defects syndrome (HADDTS), a rare early onset neurodevelopmental disorder. We generated hESCs lines with heterozygote and homozygote c.991C>T in CTBP1 using CRISPR/Cas9 genome editing and validated them for genetic integrity, off-target mutations, and pluripotency. They will be useful for investigation of HADDTS pathophysiology and for screening for potential therapeutics.
CRIS-Team Scopus Importer:2023-01-20

CRISPR/Cas9-mediated generation of hESC lines with homozygote and heterozygote p.R331W mutation in CTBP1 to model HADDTS syndrome. - Winner, Beate; Akdas, Enes Yagiz; Turan, Sören; Guhathakurta, Debarpan; Ekici, Arif Bülent; Salar, Seda; Lie, Dieter Chichung; Fejtová, Anna (Stem Cell Research, 2023)
C-terminal Binding Protein 1 (CTBP1) is a ubiquitously expressed transcriptional co-repressor and membrane trafficking regulator. A recurrent de novo c.991C>T mutation in CTBP1 leads to expression of p.R331W CTBP1 and causes hypotonia, ataxia, developmental delay, and tooth enamel defects syndrome (HADDTS), a rare early onset neurodevelopmental disorder. We generated hESCs lines with heterozygote and homozygote c.991C>T in CTBP1 using CRISPR/Cas9 genome editing and validated them for genetic integrity, off-target mutations, and pluripotency. They will be useful for investigation of HADDTS pathophysiology and for screening for potential therapeutics.

Crossed Eye/Hand Laterality and Left-Eyedness Predict a Positive 24-Month Outcome in Alcohol-Dependent Patients - Weinland, Christian; Mühle, Christiane; Kornhuber, Johannes; Lenz, Bernd (Alcoholism-Clinical and Experimental Research, 2019)
Background: Available predictors of hospital readmission following withdrawal in alcohol-dependent patients are limited. However, such parameters are needed to optimize individualized treatment strategies. This study investigated whether crossed eye/hand laterality, eyedness, and handedness may predict outcomes in alcohol dependence. Methods: The prospective study included 200 early-abstinent alcohol-dependent inpatients (n[males] = 113, n[females] = 87) and 240 control subjects (n[males] = 133, n[females] = 107). We assessed eyedness and handedness using the hole-in-the-card and Shimizu tests and documented alcohol-related readmissions over 12 and 24 months. Results: Crossed eye/hand laterality and left-eyedness were associated with a reduced risk for alcohol-related readmission (12-month: odds ratios [OR] = 0.41, p = 0.008, OR = 0.42, p = 0.004; 24-month: OR = 0.57, p = 0.097, OR = 0.47, p = 0.016), fewer median readmissions (12-month: 0 vs. 1, p = 0.005, 0 vs. 1, p = 0.005; 24-month: 1 vs. 2, p = 0.014, 1 vs. 2, p = 0.006), and more mean days to the first readmission (12-month: 270 vs. 209, p = 0.007, 269 vs. 207, p = 0.003; 24-month: 462 vs. 335, p = 0.039, 461 vs. 323, p = 0.005). They also interacted with treatment and alcohol drinking history to predict the outcome. In sex-specific analyses, most of these effects remained significant in males but not in females. Handedness alone did not significantly predict outcome. Moreover, the laterality markers did not significantly differ between alcohol-dependent patients and control subjects. Conclusions: Determining crossed eye/hand laterality and eyedness may help to individualize relapse prevention in the future. Both are easily accessible predictors of alcohol-related readmission following inpatient withdrawal treatment.
CRIS-Team Scopus Importer:2019-06-04
Keywords: Alcohol Dependence; Crossed Eye/Hand Laterality; Eyedness; Relapse Prediction

Cross-national gender variations of digit ratio (2D:4D) correlate with life expectancy, suicide rate, and other causes of death - Lenz, Bernd; Kornhuber, Johannes (Journal of Neural Transmission, 2018)
The second-to-fourth finger length ratio (2D:4D) is an indication of prenatal sex hormone exposure, and has sex-specifically been associated with several lethal illnesses including ischemic heart disease, diverse cancers, and suicide. Our primary aim was to verify that 2D:4D sex-specifically relates to life expectancy and suicide numbers on a national level (23 countries). We also used a hypothesis-free approach to investigate associations with other causes of death [p value adjustment for multiple hypothesis testing using the false discovery rate procedure (FDR)]. All parameters were normalized to the national mean (of males and females) and analyzed across nations. Normalized male 2D:4D correlated positively with normalized male life expectancy (at birth, r = 0.46, p = 0.029; at the age of 60, r = 0.44, p = 0.038) and negatively with normalized male suicide rates (r = - 0.49, p = 0.017). In the exploratory analyses, the normalized male 2D:4D values were negatively associated with the normalized male deaths rates from communicable, maternal, perinatal, and nutritional conditions [r = - 0.65, p(FDR) = 0.011], respiratory infections [r = - 0.69, p(FDR) = 0.008], asthma [r = - 0.65, p(FDR) = 0.011], neurological conditions [r = - 0.56, p(FDR) = 0.046], and Alzheimer's disease and other dementias [r = - 0.59, p(FDR) = 0.036]. The normalized female parameters showed the same cross-national correlations. In line with the previous individual level findings, the results suggest that prenatal sex hormone effects are sex-specifically involved in suicide and neurological conditions. Moreover, we provide novel national level evidence that prenatal sex hormone priming may sex-specifically influence life expectancy and death risk from respiratory diseases.
EVALuna2:35462

Cross-reinstatement of mitragynine and morphine place preference in rats - Japarin, Rima Atria; Yusoff, Nurul Hasnida; Hassan, Zurina; Müller, Christian P.; Harun, Norsyifa (Behavioural Brain Research, 2021)
Kratom is a medicinal plant that exhibits promising results as an opiate substitute. However, there is little information regarding the abuse profile of its main psychoactive constituent, mitragynine (MG), particularly in relapse to drug abuse. Using the place conditioning procedure as a model of relapse, this study aims to evaluate the ability of MG to induce conditioned place preference (CPP) reinstatement in rats. To evaluate the cross-reinstatement effects, MG and morphine were injected to rats that previously extinguished a morphine- or MG-induced CPP. Following a CPP acquisition induced by either MG (10 and 30 mg/kg, i.p.) or morphine (10 mg/kg, i.p.), rats were subjected to repeated CPP extinction sessions. A low dose priming injection of MG or morphine produced a reinstatement of the previously extinguished CPP. In the second experiment of this study, a priming injection of morphine (1, 3 and 10 mg/kg, i.p.) dose-dependently reinstated an MG-induced CPP. Likewise, a priming injection of MG (3, 10 and 30 mg/kg, i.p.) was able to dose-dependently reinstate a morphine-induced CPP. The present study demonstrates a cross-reinstatement effect between MG and morphine, thereby suggesting a similar interaction in their rewarding motivational properties. The findings from this study also suggesting that a priming exposure to kratom and an opioid may cause relapse for a previously abused drug.
CRIS-Team Scopus Importer:2020-12-11
Keywords: Conditioned place preference; Kratom; Mitragynine; Opioid; Rats; Reinstatement

Cross-Sectional and Longitudinal Evaluation of the Social Network Use Disorder and Internet Gaming Disorder Criteria - Bouna-Pyrrou, Polyxeni; Aufleger, Birte; Braun, Simona; Gattnar, Manja; Kallmayer, Sofia; Wagner, Helena; Kornhuber, Johannes; Mühle, Christiane; Lenz, Bernd (Frontiers in Psychiatry, 2018)
Background: The inclusion of internet gaming disorder (IGD) as a condition warranting more research in the DSM-5 has led to a rapid increase of research on addictive internet activities. Further evaluation of the criteria for IGD and social network disorder (SND) is needed. Objective: To assess the internal consistency, construct validity, retest-reliability, and long-term stability of SND and IGD criteria in German-speaking cohorts. Method: We conducted total and sex-specific analyses on data from two cross-sectional and longitudinal studies, one sample of 192 participants enriched for internet use and another community-based sample of 2316 individuals. Results: First, independent from assessment setting (online, telephone, on-site) and gender, we found acceptable to good internal consistency for SND and IGD criteria (Cronbach's α 0.690-0.774 for SND and 0.743-0.866 for IGD, respectively). Second, positive Spearman correlations between the sum of affirmed criteria and established scales of pathological internet use (ρ 0.395-0.783) and time spent on the social networking sites or internet gaming (ρ 0.317-0.761) confirmed convergent validity. Moreover, the sum of affirmed criteria related positively to attentional impulsivity (ρmax 0.311), urgency (ρ 0.124-0.200), and neuroticism (ρmax 0.210), and negatively to perseverance (ρ -0.245- -0.098) and conscientiousness (ρmin -0.257). Finally, SND and IGD criteria showed high retest stability (SND ρ 0.653-0.826, IGD ρ 0.714-0.825, respectively). However, participants scored higher on SND and IGD scales during the online compared to the on-site assessment. The 2-year follow-up revealed an increase in affirmed SND and IGD criteria. Conclusion: Our data support good psychometric properties of the SND and IGD criteria and outline the addictive potential of social networking sites.
EVALuna2:211611

CSF Aβ1-42- an excellent but complicated Alzheimer's biomarker - a route to standardisation - Kuhlmann, Julia; Andreasson, Ulf; Pannee, Josef; Bjerke, Maria; Portelius, Erik; Leinenbach, Andreas; Bittner, Tobias; Korecka, Magdalena; Jenkins, Rand G.; Vanderstichele, Hugo; Stoops, Erik; Lewczuk, Piotr; et al. (Clinica Chimica Acta, 2017)
The 42 amino acid form of amyloid β (Aβ1-42) in cerebrospinal fluid (CSF) has been widely accepted as a central biomarker for Alzheimer's disease. Several immunoassays for CSF Aβ1-42are commercially available, but can suffer from between laboratory and batch-to-batch variability as well as lack of standardisation across assays. As a consequence, no general cut-off values have been established for a specific context of use (e.g., clinical diagnostics) and selection of individuals for enrolment in clinical trials (patient stratification) remains challenging. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has initiated a working group for CSF proteins (WG-CSF) to facilitate standardisation of CSF Aβ1-42measurement results. The efforts of the IFCC WG-CSF include the development of certified reference materials (CRMs) and reference measurement procedures (RMPs) for key biomarkers. Two candidate RMPs for quantification of Aβ1-42in CSF based on liquid chromatography tandem mass spectrometry have been developed and tested in two ring trials. Furthermore, two commutability studies including native CSF pools, artificial CSF and spiked materials have been completed. On the basis of these studies, human CSF pools containing only endogenous Aβ1-42at three concentrations were selected as the format for future CRMs that are now being processed.
EVALuna2:33582

CSF nonphosphorylated Tau as a biomarker for the discrimination of AD from CJD - Ermann, Natalia; Lewczuk, Piotr; Schmitz, Matthias; Lange, Peter; Knipper, Tobias; Goebel, Stefan; Kornhuber, Johannes; Zerr, Inga; Llorens, Franc (Annals of Clinical and Translational Neurology, 2018)
Creutzfeldt-Jakob disease and Alzheimer's disease are characterized by the presence of elevated total-Tau cerebrospinal fluid concentrations while the presence of hyperphosphorylated Tau forms in the cerebrospinal fluid is rather a hallmark of Alzheimer's disease. Here we aimed to investigate potential contribution of nonphospho-Tau epitopes (non-P-Tau) in the discrimination between both diseases. Non-P-Tau cerebrospinal fluid concentration was highly increased in Creutzfeldt-Jakob disease (n = 57, 3683 ± 3599 pg/mL) compared to Alzheimer's disease (n = 41, 148 ± 219 pg/mL) and neurological controls (n = 56, 62 ± 40 pg/mL), and significantly improved the proportion of correctly classified patients (99%) compared to that achieved by total-Tau (90%), P-Tau (62%) and 14-3-3 (91%).
EVALuna2:211627

CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles - Ivanova, Daniela; Imig, Cordelia; Camacho, Marcial; Reinhold, Annika; Guhathakurta, Debarpan; Montenegro-Venegas, Carolina; Cousin, Michael A.; Gundelfinger, Eckart D.; Rosenmund, Christian; Cooper, Benjamin; Fejtova, Anna (Cell Reports, 2020)
Compensatory endocytosis of released synaptic vesicles (SVs) relies on coordinated signaling at the lipid-protein interface. Here, we address the synaptic function of C-terminal binding protein 1 (CtBP1), a ubiquitous regulator of gene expression and membrane trafficking in cultured hippocampal neurons. In the absence of CtBP1, synapses form in greater density and show changes in SV distribution and size. The increased basal neurotransmission and enhanced synaptic depression could be attributed to a higher vesicular release probability and a smaller fraction of release-competent SVs, respectively. Rescue experiments with specifically targeted constructs indicate that, while synaptogenesis and release probability are controlled by nuclear CtBP1, the efficient recycling of SVs relies on its synaptic expression. The ability of presynaptic CtBP1 to facilitate compensatory endocytosis depends on its membrane-fission activity and the activation of the lipid-metabolizing enzyme PLD1. Thus, CtBP1 regulates SV recycling by promoting a permissive lipid environment for compensatory endocytosis. Ivanova et al. demonstrate a dual role of CtBP1 in synaptic transmission. Nuclear CtBP1 restricts synaptogenesis and vesicular release probability, whereas presynaptic CtBP1 promotes compensatory endocytosis via activation of the lipid enzyme PLD1. Phosphorylation by Pak1 controls the redistribution of CtBP1 from active zones toward endocytic sites linking presynaptic exo- and endocytosis.
CRIS-Team Scopus Importer:2020-02-25
Keywords: Bassoon; compensatory endocytosis; CtBP1; exo-endocytosis coupling; membrane fission; Pak1; PLD1; presynapse; synaptic vesicle pools; synaptic vesicle recycling

Cue reactivity towards bodies in anorexia nervosa - common and differential effects in adolescents and adults - Horndasch, Stefanie; Kratz, Oliver; Van Doren, Jessica; Graap, Holmer; Kramer, Robert; Moll, Gunther; Heinrich, Hartmut (Psychological Medicine, 2018)
BACKGROUND: Aberrant reward mechanisms with regard to slim body shapes are discussed in patients with anorexia nervosa (AN). The aim of the present study was to examine of cue reactivity toward body shapes in AN via the late positive potential (LPP), an event-related electroencephalography (EEG) component. By including adolescents and adults, aspects of development and chronification could be studied (2 × 2 design). METHODS: Thirty-two female AN patients (19 adolescents and 13 adults) and 37 control participants (16 adolescents and 21 adults) were included. Standardized photographic stimuli showing women's bodies in underwear from five body mass index (BMI) categories (extremely underweight to extremely overweight) were presented. During picture evaluation, EEG activity was recorded (10-20 system). The LPP was measured in two time windows characterized by different topographies (450-700 ms: posterior; 1000-1300 ms: central). RESULTS: Regarding the posterior component, LPP amplitudes were clearly reduced in adult but not in adolescent patients; for both time windows the LPP showed differential patterns over BMI categories for patients and controls. Regarding the central component, a highly significant linear decrease from extremely underweight to extremely overweight body shapes was revealed in patients and no significant modulation in control participants. CONCLUSIONS: Adolescent and adult patients show increased sustained attention toward extremely underweight bodies. In chronically ill patients, this bias appears to be accompanied by generally reduced automatic attention. The LPP findings provide a differentiated picture of aberrant cue reactivity which could be interpreted as motivated attention toward body shapes in AN.
EVALuna2:33525

Current status of the intercultural opening at hospitals and rehabilitation centres for psychosomatic medicine and psychotherapy in Bavaria - Weber, Alexander; Erim, Yesim; Georgiadou, Ekaterini (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2019)
Objectives: Intercultural opening of the health care system is supposed to optimize health services for migrants. It is part of the National Integration Plan and promoted by medical societies in Germany. This study examines its state of implementation at hospitals and rehabilitation centres for psychosomatic medicine and psychotherapy in Bavaria.
CRIS-Team WoS Importer:2020-03-17

Current status of the intercultural opening at hospitals and rehabilitation centres for psychosomatic medicine and psychotherapy in Bavaria. - Weber, Alexander; Erim, Yesim; Georgiadou, Ekaterini (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2020)
Objectives: Intercultural opening of the health care system is supposed to optimize health services for migrants. It is part of the National Integration Plan and promoted by medical societies in Germany. This study examines its state of implementation at hospitals and rehabilitation centres for psychosomatic medicine and psychotherapy in Bavaria. Methods: A written survey was conducted using a modified version of the questionnaire for the implementation of intercultural opening in the mental health care system IKÖ-P (Penka et al. 2012a). Results: Altogether 18 institutions responded. Migrants were underrepresented among patients and employees excluding physicians. Specialized psychotherapeutic interventions for migrants were rarely available, but frequently used when offered. Conclusions: Intercultural opening was poorly implemented in a structural level. Due to the low response-rate of 21.7 % the survey is not representative. Participation of institutions interested in intercultural opening could have led to biased results. To provide adequate psychosomatic medical care for migrants, intercultural opening should be further developed.
EVALuna2:421126

Current trends in live liver donation - Nadalin, Silvio; Malago, Massimo; Radtke, Arnold; Erim, Yesim; Saner, F. H.; Valentin-Gamazo, Camino; Schröder, Tobias; Schaffer, Randolph; Sotiropoulos, Georgios C.; Li, Jun; Frilling, Andrea; Broelsch, Christoph E. (Transplant International, 2007)
Keywords: complication; donor; ethics; living donor liver transplantation; outcome; psychology

Cyclin‐Dependent Kinases (CDKs) and the Human Cytomegalovirus‐Encoded CDK Ortholog pUL97 Represent Highly Attractive Targets for Synergistic Drug Combinations - Wild, Markus; Hahn, Friedrich; Brückner, Nadine; Schütz, Martin; Wangen, Christina; Wagner, Sabrina; Sommerer, Markus; Strobl, Stefan; Marschall, Manfred (International Journal of Molecular Sciences, 2022)
Human cytomegalovirus (HCMV) is a pathogenic human herpesvirus associated with serious, potentially life‐threatening symptoms in the immunocompromised or immunonaïve host. The limitations encountered by antiviral therapy options currently available include a narrow panel of accessible targets, the induction of viral drug resistance as well as severe drug dosage‐mediated side‐effects. Improved drug‐targeting strategies to resolve these issues are the focus of our investigations. In particular, pharmaceutical kinase inhibitors (PKIs), either directed to host kinases or directed to the viral protein kinase pUL97, have been considered to overcome these restrictions. Recently, we reported the identification of a synergistic combination of two PKIs directed to host cyclin‐dependent kinase 7 (CDK7) and viral CDK ortholog pUL97. Here, we substantiate these findings with the following results: (i) true drug synergy was exhibited by various chemical classes of PKI pairs directed to pUL97 and CDK7; (ii) no putative amplification of cytotoxicity by these drug combinations was observed; (iii) a reduction in drug dosage levels for synergistic combinations was defined on a quantitative basis and compared to monotreatments; (iv) the quantities of target proteins CDK7 and pUL97 expressed in HCMV‐infected cells were assessed by confocal imaging, indicating a strong down‐modulation of CDK7 levels as a result of synergistic drug treatment; (v) the functional importance of these target kinases, both binding to cyclin H, was illustrated by assessing HCMV replication under the viral genomic deletion of ORF‐UL97 or cellular cyclin knock‐out; (vi) new combinations of HCMV‐specific drug synergy were demonstrated for solely host‐directed treatments using PKIs against CDK2, CDK7, CDK8 and/or CDK9 and (vii) a triple PKI combination provided further support for the synergy approach. With these combined findings, this study highlights the potential of therapeutic drug combinations of approved, developmental and preclinical PKIs for expanding future options for anti‐HCMV therapy.
CRIS-Team Scopus Importer:2022-03-04
Keywords: Antiviral drug; Antiviral drug synergism; Cyclin‐dependent kinase (CDK); Direct‐acting antiviral (DAA); Drug combinations; Host‐directed antiviral (HDA); Human cytomegalovirus; New synergistic drug‐target combinations; Pharmaceutical kinase inhibitor (PKI); Viral CDK pUL97 (vCDK)

Cytomegalovirus cyclin-dependent kinase ortholog vCDK/pUL97 undergoes regulatory interaction with human cyclin H and CDK7 to codetermine viral replication efficiency - Schütz, Martin; Wangen, Christina; Sommerer, Markus; Kögler, Melanie; Eickhoff, Jan; Degenhart, Carsten; Klebl, Bert; Naing, Zin; Egilmezer, Ece; Hamilton, Stuart T.; Rawlinson, William D.; Sticht, Heinrich; et al. (Virus Research, 2023)
Human cytomegalovirus (HCMV) infection is shaped by a tightly regulated interplay between viral and cellular proteins. Distinct kinase activities, such as the viral cyclin-dependent kinase ortholog (vCDK) pUL97 and cellular CDK7 are both crucial for efficient viral replication. Previously, we reported that both kinases, vCDK/pUL97 and CDK7, interact with cyclin H, thereby achieving an enhanced level of kinase activity and overall functionality in viral replication. Here we provide a variety of novel results, as generated on a methodologically extended basis, and present a concept for the codetermination of viral replication efficiency through these kinase activities: (i) cyclin H expression, in various human cell types, is substantially upregulated by strains of HCMV including the clinically relevant HCMV Merlin; (ii) vCDK/pUL97 interacts with human cyclin H in both HCMV-infected and plasmid-transfected cell systems; (iii) a doxycycline-inducible shRNA-dependent knock-down (KD) of cyclin H significantly reduces pUL97 activity (qSox in vitro kinase assay); (iv) accordingly, pUL97 in vitro kinase activity is seen significantly increased upon addition of recombinant cyclin H; (v) as a point of specific importance, human CDK7 activity shows an increase by vCDK/pUL97-mediated trans-stimulation (whereas pUL97 is not stimulated by CDK7); (vi) phosphosite-specific antibodies indicate an upregulated CDK7 phosphorylation upon HCMV infection, as mediated through a pUL97-specific modulatory effect (i.e. shown by pUL97 inhibitor treatment or pUL97-deficient viral mutant); (vii) finally, an efficient KD of cyclin H in primary fibroblasts generally results in an impaired HCMV replication efficiency as measured on protein and genomic levels. These results show evidence for the codetermination of viral replication by vCDK/pUL97, cyclin H and CDK7, thus supporting the specific importance of cyclin H as a central regulatory factor, and suggesting novel targeting options for antiviral drugs.
CRIS-Team Scopus Importer:2023-09-08
Keywords: Codetermination of viral replication; Cyclin H knock-down; Functional importance of cyclin H; Human cytomegalovirus; Modulation of vCDK/pUL97 activity in vitro; Options for antiviral drug targeting; pUL97-mediated CDK7 trans-stimulation; vCDK/pUL97–cyclin binding; Viral cyclin-dependent kinase (CDK) ortholog

Dabigatran Plasma Levels in Acute Cerebrovascular Events - Volbers, Bastian; Köhrmann, Martin; Kallmünzer, Bernd; Kurka, Natalia; Breuer, Lorenz; Ringwald, Juergen; Schwab, Stefan (Journal of Stroke and Cerebrovascular Diseases, 2016)
Oral anticoagulation with dabigatran was shown to be effective for stroke prevention in patients with nonvalvular atrial fibrillation without the need for laboratory monitoring. However, a recent publication based on data of the Randomized Evaluation of Long-Term Anticoagulation Therapy study reported that ischemic stroke and bleeding outcomes are correlated with dabigatran plasma concentration (DPC). DPC was determined at a prespecified time point and correlated with cardiovascular events at any time during follow-up. Because of the known variability of DPC, among others depending on renal function, this approach might compromise data evaluation. We report on dabigatran plasma levels in acute cerebrovascular events.Consecutive patients with acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH) while taking dabigatran were retrospectively identified if admission DPC was available. DPC was determined using the diluted thrombin time (Hemoclot (HYPHEN BioMed, Neuville sur Oise, France)). Creatinine clearance (CrCl) was determined by measuring creatinine in plasma and 24-hour urine.Fifteen AIS and 4 ICH patients were included. Median DPC on admission was significantly higher in ICH patients than in AIS patients (135 ng/mL [interquartile range IQR 79-218] and 69.1 ng/mL [IQR 20.6-85.0], respectively; P = .035). Increased CrCl (values above published normal range) was correlated with lower median DPC (60 ng/mL [IQR 10-69] versus 100 ng/mL [IQR 79-157] in patients with normal CrCl, P = .01).Higher DPC was found in ICH patients than in AIS patients in temporal proximity to the event. Both decreased and increased renal functions seem to have an important influence on DPC.
EVALuna2:15996

Daily interferon alpha-2B and ribavirin combination therapy for liver transplant patients with chronic hepatitis C infection - Beckebaum, Susanne; Cicinnati, Vito; Karliova, Marc; Dirsch, Olaf; Erim, Yesim; Frilling, Andrea; Malago, Massimo; Broelsch, Christoph E.; Treichel, Ulrich; Gerken, Guido (Transplantation Proceedings, 2003)

Das Eltern-Belastungs-Inventar (EBI) Einsatz und Nutzen in der Kinder- und Jugendpsychiatrie und –psychotherapie - Irlbauer-Müller, Viktoria; Eichler, Anna; Donhauser, Johanna; Poehlmann, Nina E.; Stemmler, Mark; Moll, G.H.; Kratz, Oliver (Diagnostica, 2017)
Keywords: Elterliche Belastung; psychisch/verhaltensauffällige Kinder/Jugendliche; KJP; Diagnostik; Behandlung

Das Internet als Informationsquelle für pflegende Angehörige eines Demenzpatienten - Grässel, Elmar; Bleich, Stefan; Meyer-Wegener, Klaus; Schmidt, Ute; Kornhuber, Johannes; Prokosch, Hans-Ulrich (Psychiatrische Praxis, 2009)
Objective: What significance has the Internet as a source of information for family caregivers of dementia patients? Methods: In Middle Franconia (Germany), 391 family caregivers were requested to participate in a questionnaire-based postal survey about the significance of the Internet and other sources of information on dementia. The family caregivers in question were the relatives of patients of the Memory Clinic at Erlangen University Psychiatric Hospital, members of the Alzheimer's Society of Middle Franconia or the Nuremberg Family Counselling Society. Results: Younger and better-educated family caregivers more often own a computer with Internet access than older ones. The Internet is in 4th place on their list of sources of information. Although doctors are by far the most important source, counselling centres and literature are rated only just before the Internet. Conclusions: The Internet is particularly significant for the younger better-educated family caregivers, independent of gender, as a source of information on the diagnosis and treatment of dementia. © Georg Thieme Verlag KG Stuttgart.
UnivIS-Import:2015-03-09:Pub.2009.tech.IMMD.IMMD6.dasint
Keywords: Dementia; Family caregivers; Internet use; Sources of information

Deep Learning-based automatic longitudinal volumetric Analysis in Acoustic Neuroma - Putz, Florian; Chen, Hui-fen; Huang, Yixing; Weissmann, Thomas; Mansoorian, Sina; Schmidt, M.; Semrau, Sabine; Lettmaier, Sebastian; Bert, Christoph; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Default mode network connectivity change corresponds to ketamine's delayed glutamatergic effects - Li, Meng; Woelfer, Marie; Colic, Lejla; Safron, Adam; Chang, Catie; Heinze, Hans Jochen; Speck, Oliver; Mayberg, Helen S.; Biswal, Bharat B.; Salvadore, Giacomo; Fejtová, Anna; Walter, Martin (European archives of psychiatry and clinical neuroscience, 2018)
Ketamine exerts rapid antidepressant effects peaking 24 h after a single infusion, which have been suggested to be reflected by both reduced functional connectivity (FC) within default mode network (DMN) and altered glutamatergic levels in the perigenual anterior cingulate cortex (pgACC) at 24 h. Understanding the interrelation and time point specificity of ketamine-induced changes of brain circuitry and metabolism is thus key to future therapeutic developments. We investigated the correlation of late glutamatergic changes with FC changes seeded from the posterior cingulate cortex (PCC) and tested the prediction of the latter by acute fractional amplitude of low-frequency fluctuations (fALFF). In a double-blind, randomized, placebo-controlled study of 61 healthy subjects, we compared effects of subanesthetic ketamine infusion (0.5 mg/kg over 40 min) on resting-state fMRI and MR-Spectroscopy at 7 T 1 h and 24 h post-infusion. FC decrease between PCC and dorsomedial prefrontal cortex (dmPFC) was found at 24 h post-infusion (but not 1 h) and this FC decrease correlated with glutamatergic changes at 24 h in pgACC. Acute increase in fALFF was found in ventral PCC at 1 h which was not observed at 24 h and inversely correlated with the reduced dPCC FC towards the dmPFC at 24 h. The correlation of metabolic and functional markers of delayed ketamine effects and their temporal specificity suggest a potential mechanistic relationship between glutamatergic modulation and reconfiguration of brain regions belonging to the DMN.
EVALuna2:211604

Dementia as a predictor of care-related quality of life in informal caregivers: a cross-sectional study to investigate differences in health-related outcomes between dementia and non-dementia caregivers - Karg, Nina; Grässel, Elmar; Randzio, Ottilie; Pendergrass, Anna (BMC Geriatrics, 2018)
BACKGROUND: The objectives of this study with a large sample of informal caregivers (CG) were a) to compare health-related outcomes of CGs caring for a patient with dementia and those caring for a relative with another chronic disease and b) to check whether dementia is a predictor of CG's care-related quality of life (QoL) in CarerQoL-7D. METHODS: This cross-sectional study involved self-reported data from 386 informal CGs who applied for an initial grade or upgrade of the care level of the care recipient at the Medical Service of Compulsory Health Insurance Funds of Bavaria (Germany). By obtaining data this way, systematic biases often associated with the acquisition of CGs were prevented. Bivariate and multiple analyses were conducted using a univariate covariance model (ANCOVA). RESULTS: Bivariate analyses showed significantly higher levels of subjective burden and lower QoL in the dementia group. No significant differences were found in terms of physical health and depressiveness, though there was a tendency suggesting higher levels of depressiveness in dementia CGs. Multiple analysis explaining QoL by dementia status after controlling for CG's sex, age and employment status revealed a significant effect of dementia, suggesting caregiving for a dementia patient was associated with lower QoL. CONCLUSIONS: Results of the study suggest that caring for a relative with dementia is associated with poorer health, i.e. greater levels of subjective burden and depressiveness, and predicts lower QoL in CGs. These findings emphasize the importance of specific interventions aiming to support informal CGs of dementia patients.
EVALuna2:211608

Dementia Competence Network. Results and outlook - Peters, Oliver; Heuser, Isabella; Froelich, Lutz; Ruether, Eckart; Rienhoff, Otto; Kornhuber, Johannes; Wiltfang, Jens; Maier, Wolfgang (Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz, 2016)
The Dementia Competence Network (DCN) is represented by academic memory clinics and has three major aims: (1) To facilitate the development of diagnostic tools including neuropsychology, biomarkers, imaging and genetics. (2) To implement clinical trials in mild cognitive impairment and dementia and (3) to improve standard care for dementia in Germany.This article summarizes the achievements of the DCN so far and highlights future perspectives.The DCN has built up two multicentre cohorts. Within the first cohort, patients with mild cognitive impairment or mild dementia were examined longitudinally using multiple neuropsychological assessments and numerous different biomarkers. In a subgroup of the first cohort, patients were treated with antidementive drugs in two placebo-controlled clinical trials. The second cohort included cognitively healthy older people and examined repetitively clinical, neuropsychological and psychosocial parameters for ten years.The DCN has generated a large data and biomaterial bank. Numerous publications have helped to develop further diagnostic procedures and treatment of cognitive disorders and dementia. The DCN has contributed to end stigmatisation of dementia.
EVALuna2:23785

Demenzdiagnostik - Stemmler, Mark; Kornhuber, Johannes (Hogrefe, 2018)

DemWG - Improving the Care of People with Dementia in outpatient assisted Living Communities - Donath, Carolin; Kratzer, André; Scheel, Jennifer Felicia; Schmidt, A.; Friedrich, A-C; Stiefler, S.; Wolf-Ostermann, K.; Grässel, Elmar (GESUNDHEITSWESEN, 2021)
CRIS-Team WoS Importer:2022-05-20

DemWG - Reduction of the Risk for Hospital Admissions in People with Dementia in community-managed Residential Communities - Wolf-Ostermann, K.; Ratz, K.; Grässel, Elmar; Kratzer, André (ZEITSCHRIFT FUR GERONTOLOGIE UND GERIATRIE, 2019)
CRIS-Team WoS Importer:2019-09-06

Depression and attempted suicide under pregabalin therapy - Kustermann, Andreas; Möbius, Cornelia; Oberstein, Timo; Mueller, Helge H.; Kornhuber, Johannes (Annals of General Psychiatry, 2014)
Originally developed for the treatment of epilepsy, pregabalin has become a compound with a wide spectrum of indications comprising anxiety disorders and chronic pain and is therefore largely prescribed. Thus, it is important for clinicians to be aware of rare, but serious adverse effects. The following report illustrates the case of a 20-year-old male with a severe depressive syndrome following pregabalin medication which even led to a suicide attempt.
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Depression and protective factors of mental health in people with hepatitis C: A questionnaire survey - Erim, Yesim; Tagay, Sefik; Beckmann, Mingo; Bein, Sabine; Cicinnati, Vito; Beckebaum, Susanne; Senf, Wolfgang; Schlaak, Joerg F. (International Journal of Nursing Studies, 2010)
Keywords: Hepatitis; Depression; Sense of coherence; Social support; Psychological distress

Depression, Anxiety, Resilience and Coping Pre and Post Kidney Transplantation - Initial Findings from the Psychiatric Impairments in Kidney Transplantation (PI-KT)-Study - Mueller, Helge H.; Englbrecht, Matthias; Wiesener, Michael S.; Titze, Stephanie; Heller, Katharina; Groemer, Teja W.; Schett, Georg; Eckardt, Kai-Uwe; Kornhuber, Johannes; Maler, Juan Manuel (PLoS ONE, 2015)
Depression/anxiety, impaired Health-Related Quality of Life (HRQoL) and coping and resilience structures, are associated with increased mortality/poor outcome in chronic kidney disease (CKD) patients before (CKD/pre-KT) and after kidney (CKD-T) transplantation. Less is known about prevalence rates of psychiatric symptoms and impaired HRQoL of non-transplanted compared with transplanted patients.In a cross-sectional study comparing 101 CKD/pre-KT patients with 151 cadaveric-transplanted (CKD-T) patients, we examined prevalence of depression/anxiety (HADS questionnaire) and coping, resilience and HRQoL (SF-12, Resilience-Scale and FKV-questionnaire).The prevalence of both depressive and anxiety symptoms was not significantly different between different pre-/and CKD-T patient groups. In CKD-T no significant relations of coping strategies with kidney function were identified. Furthermore, the Resilience Scales for acceptance and competence did not suggest any differences between the CKD/pre-KT and CKD-T subgroup. In the CKD/pre-KT patients, significant correlations were identified between the acceptance subscale and partnership, as well as between the competence subscale and older age/partnership.Both the CKD/pre-KT and CKD-T patients exhibited notable impairments in the HRQoL which which showed a comparable pattern of results. KT itself does not appear to be the main risk factor for the development of mental impairments.
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Depressive and anxiety symptoms in the course of the COVID-19 pandemic among physicians in hospitals: results of the longitudinal, multicenter VOICE-EgePan survey over two years - Morawa, Eva; Adler, Werner; Schug, Caterina; Geiser, Franziska; Beschoner, Petra; Jerg-Bretzke, Lucia; Albus, Christian; Weidner, Kerstin; Baranowski, Andreas M.; Erim, Yesim (BMC Psychology, 2023)
Background: This longitudinal, multicenter web-based study explored the trajectories of depressive and anxiety symptoms during the COVID-19 pandemic among physicians over two years. Methods: At four measurement points between 4/2020 and 5/2022 depressive (Patient Health Questionnaire-2, PHQ-2) and anxiety symptoms (Generalized Anxiety Disorder Scale-2, GAD-2) among physicians in German hospitals were assessed. Time, gender and age effects were analyzed with linear mixed regression models. Comparisons with norm values for the German population during the COVID-19 pandemic were also performed and frequencies of probable depression and anxiety are reported. Results: The physicians (N = 340) showed a significant increase of depressive symptoms from T1 (M = 1.35, SD = 1.33) to T4 (M = 1.64, SD = 1.34) (p <.001) and of anxiety symptoms from T1 (M = 1.35, SD = 1.42) to T2 (M = 1.59, SD = 1.43) (p =.024). The main effect of gender was only significant for anxiety symptoms (p =.001): women demonstrated higher scores than men. A significant age class difference was observed only for depressive symptoms: the youngest age group (18–40 years) revealed higher values than the oldest group (> 50 years, p =.003). As compared to the general population, the physicians reported significantly elevated PHQ-2 (T1: M = 1.35, SD = 1.33; T2: M = 1.53, SD = 1.37; T3: M = 1.55, SD = 1.40; T4: M = 1.64, SD = 1.34) and GAD-2 scores (T1: M = 1.35, SD = 1.42; T2: M = 1.59, SD = 1.43; T3: M = 1.61, SD = 1.57; T4: M = 1.49, SD = 1.46) for all measurement points (all p <.001). The frequencies of probable depression (PHQ-2 ≥ 3) and anxiety (GAD-2 ≥ 3) were: 14.1% and 17.0% (T1), 16.5% and 21.9% (T2), 17.8% and 22.6% (T3) and 18.5% and 17.3% (T4), respectively. Conclusions: Mental distress of physicians in German hospitals has increased in the course of the COVID-19 pandemic with gender and age-related differences. Possible causes should be explored and regular monitoring of mental health and prevention programmes for physicians should be established. Trial registration: The study was registered on ClinicalTrials (DRKS-ID: DRKS00021268) on 9.4.2020.
CRIS-Team Scopus Importer:2023-10-20
Keywords: Anxiety; COVID-19; Depression; Health care workers; Hospital; Mental health; Physicians

Depressive complaints and utilization of mental health services: Comparison of adult cancer survivors of different ethnic origin - Morawa, Eva; Erim, Yesim (Journal of psychosomatic research, 2020)
Objective: To investigate depressive symptoms and mental health care utilization in adult cancer survivors (CS) of different ethnic origin. Methods: Mental health care utilization in dependence of depression (Patient Health Questionnaire, PHQ-9 ≥ 10) was analyzed in native German CS (GE) and in CS with Turkish (TR) or Polish (PL) migration background, recruited by a cancer registry. Frequencies and odds ratios (OR) were calculated. Results: 135 native German and 50 CS belonging to the first migration generation (TR: n = 25 and PL: n = 25) participated. TR showed the highest rate of depression (36.0%), followed by PL (32.0%), while GE revealed the lowest frequency (20.9%). The frequency of the utilization of mental health services was 17.4% (TR), 4.5% (PL) and 8.1% (GE). After adjusting for sociodemographic and clinical variables, no significant differences between the migrants and German CS were detected for the risk of being depressed, however a tendency for an increased risk in the migrant group was observed (OR = 2.53, CI = 0.96–6.65, p = .061). Female gender (OR = 3.88, CI = 1.29–11.68, p = .016) and prior psychological/psychiatric treatment (OR = 4.35, CI = 1.86–10.18, p = .001) were significantly associated with a higher risk of being depressed. Conclusion: Contrastingly to numerous surveys, our results indicate no substantial differences between migrants and native CS, when adjusted for important confounders. High levels of migrants´ acculturation (good language proficiency, German citizenship/unlimited residence permit, long duration of stay in Germany) may contribute to eliminate inequalities caused by migration status in depressive symptomatology and mental health care utilization in CS.
CRIS-Team Scopus Importer:2020-01-10
Keywords: Cancer; Depression; Mental health care utilization; Migrants; Polish; Turkish

Derivatization of common antidepressant drugs increases inhibition of acid sphingomyelinase and reduces induction of phospholipidosis - Rhein, Cosima; Löber, Stefan; Gmeiner, Peter; Gulbins, Erich; Tripal, Philipp; Kornhuber, Johannes (Journal of Neural Transmission, 2018)
Keywords: Desipramine; Fluoxetine; Acid sphingomyelinase; Major depression; Phospholipidosis; Functional inhibitors of ASM activity (FIASMAs); Imipramine

Der Rettungsanker am Unfallort: Erste Erkenntnisse einer qualitativen Studie über das Erleben kollegialer Erstbetreuung nach potenziell traumatisierenden Ereignissen - Wrenger, Nina; Staples, Ronald; Grässel, Elmar; Drexler, Hans; Clarner, Annika (Arbeitsmedizin, Sozialmedizin, Umweltmedizin, 2015)
Objectives: Health care experts recommend prompt low-threshold psychosocial assistance for employees who have experienced a potentially traumatic event. Collegial first response constitutes such a form of acute care: colleagues of those involved in the accident come straight to the scene, where it is their job to look after the employees concerned. How this is viewed by the people involved has been unclear until now. The objective, therefore, was to gather initial findings about the experience of collegial first response within the context of a potentially traumatic event. Methods: As part of a prospective cohort study, 22 drivers at a German transport company were asked in guideline-based interviews about their experience of suffering an accident at work and the care provided at the scene of the accident. The material collected was assessed with the help of a structured content analysis based on Mayring and a classification system designed to be deductive/inductive. Findings: The experience of the accident could be broken down into four consecutive periods of time: the moment of the accident, the ensuing interval, the time spent dealing with the damage and the departure from the scene of the accident. During this time the people affected felt helpless and overwhelmed at first. They then looked for something that could give them security and guidance. The arrival of a collegial peer supporter at the scene of the accident came as a great relief to the people concerned. The peer supporter was perceived as someone who could give them a sense of no longer being alone at the scene of the accident, of being cared for and receiving assistance. Conclusions: The experience of an accident cannot be reduced down to the moment in which it suddenly occurs. In fact, for those affected it continues until leaving the scene of the accident and beyond. Their state of health at this time cannot typically be described as stable. Collegial first response plays a vital role in the system of assistance deployed at the scene of the accident from the perspective of the people involved.
CRIS-Team Scopus Importer:2020-05-11
Keywords: Accident; Collegial peer support; Psychological first aid; Research in medical care; Transport; Trauma

Designing and Implementing an IT Architecture for a Digital Multicenter Dementia Registry: DigiDEM Bayern - Reichold, Michael; Dietzel, Nikolas; Chmelirsch, Christina; Kolominsky-Rabas, Peter; Grässel, Elmar; Prokosch, Hans-Ulrich (Applied Clinical Informatics, 2021)
Background Registries are an essential research tool to investigate the long-term course of diseases and their impact on the affected. The project digiDEM Bayern will set up a prospective dementia registry to collect long-term data of people with dementia and their caregivers in Bavaria (Germany) supported by more than 300 research partners. Objective The objective of this article is to outline an information technology (IT) architecture for the integration of a registry and comprehensive participant management in a dementia study. Measures to ensure high data quality, study governance, along with data privacy, and security are to be included in the architecture. Methods The architecture was developed based on an iterative, stakeholder-oriented process. The development was inspired by the Twin Peaks Model that focuses on the codevelopment of requirements and architecture. We gradually moved from a general to a detailed understanding of both the requirements and design through a series of iterations. The experience learned from the pilot phase was integrated into a further iterative process of continuous improvement of the architecture. Results The infrastructure provides a standardized workflow to support the electronic data collection and trace each participant's study process. Therefore, the implementation consists of three systems: (1) electronic data capture system for Web-based or offline app-based data collection; (2) participant management system for the administration of the identity data of participants and research partners as well as of the overall study governance process; and (3) videoconferencing software for conducting interviews online. First experiences in the pilot phase have proven the feasibility of the framework. Conclusion This article outlines an IT architecture to integrate a registry and participant management in a dementia research project. The framework was discussed and developed with the involvement of numerous stakeholders. Due to its adaptability of used software systems, a transfer to other projects should be easily possible.
CRIS-Team Scopus Importer:2021-06-25
Keywords: data collection; dementia; participant management; registries; research planning and conduct; workflow

Design of an interactive web application for teaching uncertainty interpretations of clinical tests - Neher, Sebastian; Kapsner, Lorenz; Prokosch, Hans-Ulrich; Toddenroth, Dennis (Studies in Health Technology and Informatics, 2021)
Background: Assessing the uncertainty of diagnostic findings is essential for advising patients. Previous research has demonstrated the difficulty of computing the expected correctness of positive or negative results, although clinical decision support (CDS) tools promise to facilitate adequate interpretations. Objectives: To teach the potential utility of CDS tools to medical students, we designed an interactive software module that computes and visualizes relevant probabilities from typical inputs. Methods: We reviewed the literature on recommended graphical approaches and decided to support contingency tables, plain table formats, tree diagrams, and icon arrays. Results: We implemented these functions in a single-page web application, which was configured to complement our local learning management system where students also access interpretation tasks. Conclusion: Our technical choices promoted a rapid implementation. We intend to explore the utility of the tool during some upcoming courses. Future developments could also model a more complex clinical reality where the likelihood of alternative diagnoses is estimated from sets of clinical investigations.
CRIS-Team Scopus Importer:2021-10-22
Keywords: Bayes Theorem; Clinical Decision Support; Medical Education

Developing Enabling Technologies for Ambient Assisted Living: Natural Language Interfaces, Automatic Focus Detection and User State Recognition - Hönig, Florian Thomas; Hacker, Christian; Warnke, Volker; Nöth, Elmar; Hornegger, Joachim; Kornhuber, Johannes (Tagungsband zum 1. deutschen AAL-Kongress, 2008)

Development and Application of Automatized Routines for Optical Analysis of Synaptic Activity Evoked by Chemical and Electrical Stimulation. - Fejtová, Anna; Guhathakurta, Debarpan; Akdas, Enes Yagiz; Weiss, Eva-Maria (Frontiers in Bioinformatics, 2022)
The recent development of cellular imaging techniques and the application of genetically encoded sensors of neuronal activity led to significant methodological progress in neurobiological studies. These methods often result in complex and large data sets consisting of image stacks or sets of multichannel fluorescent images. The detection of synapses, visualized by fluorescence labeling, is one major challenge in the analysis of these datasets, due to variations in synapse shape, size, and fluorescence intensity across the images. For their detection, most labs use manual or semi-manual techniques that are time-consuming and error-prone. We developed SynEdgeWs, a MATLAB-based segmentation algorithm that combines the application of an edge filter, morphological operators, and marker-controlled watershed segmentation. SynEdgeWs does not need training data and works with low user intervention. It was superior to methods based on cutoff thresholds and local maximum guided approaches in a realistic set of data. We implemented SynEdgeWs in two automatized routines that allow accurate, direct, and unbiased identification of fluorescently labeled synaptic puncta and their consecutive analysis. SynEval routine enables the analysis of three-channel images, and ImgSegRout routine processes image stacks. We tested the feasibility of ImgSegRout on a realistic live-cell imaging data set from experiments designed to monitor neurotransmitter release using synaptic phluorins. Finally, we applied SynEval to compare synaptic vesicle recycling evoked by electrical field stimulation and chemical depolarization in dissociated cortical cultures. Our data indicate that while the proportion of active synapses does not differ between stimulation modes, significantly more vesicles are mobilized upon chemical depolarization.
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Development and technical validation of an immunoassay for the detection of app669–711 (Aβ−3–40) in biological samples - Klafki, Hans W.; Rieper, Petra; Matzen, Anja; Zampar, Silvia; Wirths, Oliver; Vogelgsang, Jonathan; Osterloh, Dirk; Rohdenburg, Lara; Oberstein, Timo; Jahn, Olaf; Beyer, Isaak; Lachmann, Ingolf; et al. (International Journal of Molecular Sciences, 2020)
The ratio of amyloid precursor protein (APP)669–711 (Aβ−3–40)/Aβ1–42 in blood plasma was reported to represent a novel Alzheimer’s disease biomarker. Here, we describe the characterization of two antibodies against the N-terminus of Aβ−3–x and the development and “fit-for-purpose” technical validation of a sandwich immunoassay for the measurement of Aβ−3–40. Antibody selectivity was assessed by capillary isoelectric focusing immunoassay, Western blot analysis, and immunohistochemistry. The analytical validation addressed assay range, repeatability, specificity, between-run variability, impact of pre-analytical sample handling procedures, assay interference, and analytical spike recoveries. Blood plasma was analyzed after Aβ immunoprecipitation by a two-step immunoassay procedure. Both monoclonal antibodies detected Aβ−3–40 with no appreciable cross reactivity with Aβ1–40 or N-terminally truncated Aβ variants. However, the amyloid precursor protein was also recognized. The immunoassay showed high selectivity for Aβ−3–40 with a quantitative assay range of 22 pg/mL–7.5 ng/mL. Acceptable intermediate imprecision of the complete two-step immunoassay was reached after normalization. In a small clinical sample, the measured Aβ42/Aβ−3–40 and Aβ42/Aβ40 ratios were lower in patients with dementia of the Alzheimer’s type than in other dementias. In summary, the methodological groundwork for further optimization and future studies addressing the Aβ42/Aβ−3–40 ratio as a novel biomarker candidate for Alzheimer’s disease has been set.
CRIS-Team Scopus Importer:2020-09-18
Keywords: Alzheimer’s disease; Amyloid β; Assay development; Assay validation; Biomarker

Development and validation of a food-associated olfactory test (FAOT) - Denzer-Lippmann, Melanie; Beauchamp, Jonathan; Freiherr, Jessica; Thürauf, Norbert; Kornhuber, Johannes; Büttner, Andrea (Chemical Senses, 2017)
Olfactory tests are an important tool in human nutritional research for studying food preferences, yet comprehensive tests dedicated solely to food odors are currently lacking. Therefore, within this study, an innovative food-associated olfactory test (FAOT) system was developed. The FAOT comprises 16 odorant pens that contain representative food odors relating to different macronutrient classes. The test underwent a sensory validation based on identification rate, intensity, hedonic value, and food association scores. The accuracy of the test was further compared to the accuracy of the established Sniffin’ Sticks identification test. The identification rates and intensities of this new FAOT were found to be comparable to the Sniffin’ Sticks olfactory identification test. The odorant pens were also assessed chemo-analytically and were found to be chemically stable for at least 24 weeks. Overall, this new identification test for use in assessing olfaction in a food-associated context is valid both in terms of its use in sensory perception studies and its chemical stability. The FOAT is particularly suited to examinations of the sense of smell regarding food odor
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Keywords: food odorants; identification test; olfactory test; olfaction; PT-MS; smell

Development and validation of a questionnaire for measuring team cohesion: the Erlangen Team Cohesion at Work Scale (ETC) - Lieb, Marietta; Erim, Yesim; Morawa, Eva (BMC Psychology, 2024)
Background: Team cohesion is a crucial factor when it comes to job satisfaction and turnovers. However, in Germany, economic measures for team cohesion are scarce. The aim of this study was to develop and validate an economic self-report questionnaire for measuring team cohesion in a work setting in health care. Methods: The questionnaire was developed in a stepwise procedure. After item analysis, exploratory factor analysis was conducted to assess factor structure. Reliability was tested via internal consistency. To assess convergent and divergent validity, we applied the Copenhagen Psychosocial Questionnaire (COPSOQ), the Perceived Cohesion Scale (PCS), the ENRICHD Social Support Inventory (ESSI), the Effort-Reward Imbalance Scale (ERI) and the Patient Health Questionnaire (PHQ-4), respectively. Results: The pilot version was tested in a sample of n = 126 adult nurses. Item analysis resulted in a total of 13 items for the final version. Exploratory factor analysis indicated a two-factor structure. Internal consistency for the two subscales was good, with α = 0.88 and α = 0.84, respectively. Convergent validity with the subscales of COPSOQ and PCS was moderate to high (r =.26– r =.64). For divergent validity, correlations with the ESSI were low (r =.01– r = -.09). We further found significant correlations with depression symptoms (r=-.22– r=-.37), as well as reward (ERI) (r =.41 -r =.47) and effort (ERI) (r=-.20 - r = -.24). Conclusions: We developed and validated the Erlangen Team Cohesion at Work Scale (ETC), a self-report measure for team cohesion with very good psychometric properties. Due to its economic deployment, it is suitable for measuring team cohesion in work settings, especially in health care.
CRIS-Team Scopus Importer:2024-03-01
Keywords: Questionnaire; Team cohesion; Validation; Work

Development and Validation of a Questionnaire for Patient Competence in Coping with Cancer (PCQ) - Aderhold, Caroline; Morawa, Eva; Paslakis, Georgios; Erim, Yesim (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2018)

Development of a Computerized Diagnostic System for Elderly Drivers: A Feasibility Study - Giese, Katrin; Hönig, Florian Thomas; Erzigkeit, Andreas; Soutschek, Stefan; Hornegger, Joachim; Kornhuber, Johannes (Proceedings of the 5th Russian Bavarian Conference on Bio-Medical Engineering (RBC), 2009)

Development of a Standardized Rating Tool for Drug Alerts to Reduce Information Overload - Pfistermeister, Barbara; Sedlmayr, Brita; Patapovas, Andrius; Suttner, Gerald; Tektas, Ozan; Tarkhov, Aleksey; Kornhuber, Johannes; Fromm, Martin; Buerkle, Thomas; Prokosch, Hans-Ulrich; Maas, Renke (Methods of Information in Medicine, 2016)
A well-known problem in current clinical decision support systems (CDSS) is the high number of alerts, which are often medically incorrect or irrelevant. This may lead to the so-called alert fatigue, an overriding of alerts, including those that are clinically relevant, and underuse of CDSS in general.The aim of our study was to develop and to apply a standardized tool that allows its users to evaluate the quality of system-generated drug alerts. The users' ratings can subsequently be used to derive recommendations for developing a filter function to reduce irrelevant alerts.We developed a rating tool for drug alerts and performed a web-based evaluation study that also included a user review of alerts. In this study the following categories were evaluated: "data linked correctly", "medically correct", "action required", "medication change", "critical alert", "information gained" and "show again". For this purpose, 20 anonymized clinical cases were randomly selected and displayed in our customized CDSS research prototype, which used the summary of product characteristics (SPC) for alert generation. All the alerts that were provided were evaluated by 13 physicians. The users' ratings were used to derive a filtering algorithm to reduce overalerting.In total, our CDSS research prototype generated 399 alerts. In 98 % of all alerts, medication data were rated as linked correctly to drug information; in 93 %, the alerts were assessed as "medically correct"; 19.5 % of all alerts were rated as "show again". The interrater-agreement was, on average, 68.4 %. After the application of our filtering algorithm, the rate of alerts that should be shown again decreased to 14.8 %.The new standardized rating tool supports a standardized feedback of user-perceived clinical relevance of CDSS alerts. Overall, the results indicated that physicians may consider the majority of alerts formally correct but clinically irrelevant and override them. Filtering may help to reduce overalerting and increase the specificity of a CDSS.
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Development of Comorbid Depression after Social Fear Conditioning in Mice and Its Effects on Brain Sphingolipid Metabolism - Zoicas, Iulia; Mühle, Christiane; Schumacher, Fabian; Kleuser, Burkhard; Kornhuber, Johannes (Cells, 2023)
Currently, there are no animal models for studying both specific social fear and social fear with comorbidities. Here, we investigated whether social fear conditioning (SFC), an animal model with face, predictive and construct validity for social anxiety disorder (SAD), leads to the development of comorbidities at a later stage over the course of the disease and how this affects the brain sphingolipid metabolism. SFC altered both the emotional behavior and the brain sphingolipid metabolism in a time-point-dependent manner. While social fear was not accompanied by changes in non-social anxiety-like and depressive-like behavior for at least two to three weeks, a comorbid depressive-like behavior developed five weeks after SFC. These different pathologies were accompanied by different alterations in the brain sphingolipid metabolism. Specific social fear was accompanied by increased activity of ceramidases in the ventral hippocampus and ventral mesencephalon and by small changes in sphingolipid levels in the dorsal hippocampus. Social fear with comorbid depression, however, altered the activity of sphingomyelinases and ceramidases as well as the sphingolipid levels and sphingolipid ratios in most of the investigated brain regions. This suggests that changes in the brain sphingolipid metabolism might be related to the short- and long-term pathophysiology of SAD.
CRIS-Team Scopus Importer:2023-06-09
Keywords: acid ceramidase; acid sphingomyelinase; anxiety-like behavior; ceramide; depressive-like behavior; neutral ceramidase; neutral sphingomyelinase; social anxiety; sphingolipids; sphingomyelin

Diagnostic Accuracy of the Drug Use Disorder Identification Test and Its Short Form, the DUDIT-C, in German Adolescent Psychiatric Patients - Basedow, Lukas A.; Kuitunen-Paul, Soeren; Eichler, Anna; Roessner, Veit; Golub, Yulia (Frontiers in Psychology, 2021)
Background: A common screening instrument for substance use disorders (SUDs) is the Drug Use Disorders Identification Test (DUDIT) which includes a short form regarding only drug consumption (DUDIT-C). We aim to assess if a German version of the DUDIT, adapted for adolescents, is a suitable screening instrument in a sample of adolescent psychiatric patients. Methods: N = 124 (54 female) German adolescent (M = 15.6 + 1.5 years) psychiatric patients completed the DUDIT and received a diagnostic interview (MINI-KID) assessing DSM-5 SUD criteria. A confirmatory factor analysis (CFA), receiver operating characteristic (ROC) curves, the area under the curve (AUC), and Youden’s Index were calculated. Results: A two-factor model of the DUDIT shows the best model fit (CFI = 0.995, SRMR = 0.055, RMSEA = 0.059, WRMR = 0.603). The DUDIT as well as the DUDIT-C show high diagnostic accuracy, with AUC = 0.95 and AUC = 0.88, respectively. For the DUDIT a cut-off value of 8.5 was optimal (sensitivity = 0.93, specificity = 0.91, J = 0.84), while for the DUDIT-C the optimal cut-off value was at 1.5 (sensitivity = 0.86, specificity = 0.84, J = 0.70). Conclusion: This is the first psychometric evaluation of the DUDIT in German, adolescent psychiatric outpatients, using the DSM-5 diagnostic criteria. The DUDIT as well as the DUDIT-C are well suited for use in this population. Since in our sample only few patients presented with a mild or moderate SUD, our results need to be replicated in a sample of adolescents with mild SUD.
CRIS-Team Scopus Importer:2021-07-02
Keywords: adolescence; cut-off; DUDIT; psychoactive drugs; ROC curve; screening; substance use disorder

Did you drink alcohol during pregnancy? Inaccuracy and discontinuity of women's self-reports: On the way to establish meconium ethyl glucuronide (EtG) as a biomarker for alcohol consumption during pregnancy - Eichler, Anna; Grunitz, Juliane; Grimm, Jennifer; Walz, Lisa; Raabe, Eva; Goecke, Tamme W.; Beckmann, Matthias; Kratz, Oliver; Heinrich, Hartmut; Moll, Gunther; Fasching, Peter; Kornhuber, Johannes (Alcohol, 2016)
Consuming alcohol during pregnancy is one of the most verified prenatal risk factors for impaired child development. Information about the amount of alcohol consumed prenatally is needed to anticipate negative effects and to offer timely support. Women's self-reports are not reliable, often influenced by social stigmas and retrospective recall bias, causing biomarkers of intrauterine ethanol exposure to become more and more relevant. The present study compares both women's gestational and retrospective self-reports of prenatal alcohol consumption with levels of ethyl glucuronide (EtG) in meconium. Women (n = 180) gave self-reports of prenatal alcohol consumption both during their 3rd trimester (gestational self-report) and when their children were 6-8 years old (retrospective self-report). Child meconium was collected after birth and analyzed for EtG. No individual feedback of children's EtG level was given to the women. All analyses were run separately for two cut-offs: 10 ng/g (limit of detection) and 120 ng/g (established by Goecke et al., 2014). Mothers of children with EtG values above 10 ng/g (n = 42) tended to report prenatal alcohol consumption more frequently. There was no trend or significance for the EtG cut-off of 120 ng/g (n = 26) or for retrospective self-report. When focusing on women who retrospectively reported alcohol consumption during pregnancy, a claim to five or more consumed glasses per month made an EtG over the 10 ng/g and the 120 ng/g cut-off more probable. Women whose children were over the 10 ng/g EtG cut-off were the most inconsistent in their self-report behavior, whereas the consistency in the above 120 ng/g EtG group was higher than in any other group. The next step to establish EtG as a biomarker for intrauterine alcohol exposure is to correlate EtG values in meconium with child developmental impairments.
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Die Bedeutung mütterlicher präpartaler Depression und Mutter-Kind-Bindung für die Entwicklung der kindlichen Emotionsregulation: Erste Befunde einer Längsschnittstudie - Ziegler, Clara; Zalan, Vera; Eichler, Anna; Heinrich, Hartmut; Moll, Gunther; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Lenz, Bernd; Spangler, Gottfried (50. Jahreskongress der Deutschen Gesellschaft für Psychologie, 2016)

Die „Volksheilige“ Therese Neumann von Konnersreuth und ihre Stigmata - Braun, Birgit; Demling, Joachim; Loew, Thomas H. (Der Nervenarzt, 2020)
BACKGROUND: In present times, we see ourselves confronted by the challenge of engaging increasingly diverse views of the world, god and healing in a constructive dialogue. Consequently, it is important to research into the contrary effects of religiosity on the human psyche. METHODS: Original- and literary medical historian research RESULTS: Gottfried Ewald (1888-1963), a psychiatric expert at the Friedrich-Alexander University of Erlangen, was appointed 90 years ago with the task of examining Therese Neumann (1898-1962), colloquially known as Resl of Konnersreuth. In 1927, Ewald retrospectively confirmed the diagnosis of "most severe hysteria with blindness and partial paralysis". Within the context of regular pastoral care, Resl's "hysterical blindness" disappeared on 24.06.1923. This remission might be ascribed to a positive effect of religiosity on mental health. Besides the beneficial effects of religiosity on healing, pathogenic phenomena of religion can also be seen in the case of Resl. During Lent in 1926, Resl experienced ecstatic states as well as blood-stained tears. On Good Friday in 1926, bleeding of the scalp occurred; since Holy Saturday 1927, she experienced stigmata on her hands and the soles of her feet. Ewald assessed the latter as probably being genuine, although he spoke in favor of a clinical observation in hospital to obtain scientifically substantiated findings. DISCUSSION: The story of Resl of Konnersreuth shows the contrary influences of religiosity on mental health in one and the same individual. CONCLUSION: Detailed psychiatric historical and ethical research on the interaction of the psyche and religiosity can provide information about mechanisms that channel the psychic power of religiosity to promote remission. It is further important to take a religious and spiritual history of the patients.
CRIS-Team Scopus Importer:2020-01-24
Keywords: Ecstasy; Hysteria; Mental health; Religion-pathogen phenomena; Religiosity/spirituality (R/S)

Differences in Intrusive Memory Experiences in Post-traumatic Stress Disorder after Single, Re- and Prolonged Traumatization - Mueller, Helge H.; Möller, Sebastian; Jenderek, Konstanze; Stroebel, Armin; Wiendieck, Kurt; Sperling, Wolfgang (Frontiers in Psychology, 2016)
Intrusive memory experiences (IMEs) are a common symptom of post-traumatic stress disorder (PTSD). Sensory perceptions of IMEs in the PTSD context vary substantially. The present research examined 20 patients with a single trauma, 20 re-traumatized patients and 80 Holocaust-traumatized patients who suffered from PTSD. Our results revealed significant differences in IME frequency based on the types of trauma experience. The findings suggest that patients with prolonged (Holocaust) traumata suffered from visual (65%) and combined visual/acoustic intrusive memories (29%), whereas visual memory experiences were most frequent (90%) among single-trauma patients. The trauma experience and the intrusive memory trigger stimulus were interdependent. The type of trauma critically affects the traumatic experience. Future studies should focus on these findings to improve PTSD therapeutic options.
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Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion - Barschke, Peggy; Öckl, Patrick; Steinacker, Petra; Al Shweiki, M. H.D.Rami; Weishaupt, Jochen H.; Landwehrmeyer, G. Bernhard; Anderl-Straub, Sarah; Weydt, Patrick; Diehl-Schmid, Janine; Danek, Adrian; Kornhuber, Johannes; Schroeter, Matthias L.; et al. (Journal of Neurology Neurosurgery and Psychiatry, 2020)
Objectives: The hexanucleotide repeat expansion in the C9orf72 gene is the most common mutation associated with amyotrophic lateral sclerosis (C9-ALS) and frontotemporal dementia (C9-FTD). Until now, it is unknown which factors define whether C9orf72 mutation carriers develop ALS or FTD. Our aim was to identify protein biomarker candidates in the cerebrospinal fluid (CSF) which differentiate between C9-ALS and C9-FTD and might be indicative for the outcome of the mutation. Methods: We compared the CSF proteome of 16 C9-ALS and 8 C9-FTD patients and 11 asymptomatic C9orf72 mutation carriers (CAR) by isobaric tags for relative and absolute quantitation. Eleven biomarker candidates were selected from the pool of differentially regulated proteins for further validation by multiple reaction monitoring and single-molecule array in a larger cohort (n=156). Results: In total, 2095 CSF proteins were identified and 236 proteins were significantly different in C9-ALS versus C9-FTD including neurofilament medium polypeptide (NEFM) and chitotriosidase-1 (CHIT1). Eight candidates were successfully validated including significantly increased ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) levels in C9-ALS compared with C9-FTD and controls and decreased neuronal pentraxin receptor (NPTXR) levels in C9-FTD versus CAR. Conclusions: This study presents a deep proteomic CSF analysis of C9-ALS versus C9-FTD patients. As a proof of concept, we observed higher NEFM and CHIT1 CSF levels in C9-ALS. In addition, we also show clear upregulation of UCHL1 in C9-ALS and downregulation of NPTXR in C9-FTD. Significant differences in UCHL1 CSF levels may explain diverging ubiquitination and autophagy processes and NPTXR levels might reflect different synapses organisation processes.
CRIS-Team Scopus Importer:2020-03-31

Differential contribution of pyramidal cells and interneurons to activity-dependent gene transcription changes - Salar, Seda; Guhathakurta, Debarpan; Marx Hofmann, Lena (Journal of Neurophysiology, 2019)
The type of neuronal activity determines the outcome of gene expression. Hence, the characterization of underlying mechanisms in transcriptome alterations may serve as a biomarker and provide new intervention methods for the treatment of pathologic conditions. Parrish et al. (Parrish RR, Codadu NK, Racca C, Trevelyan AJ. J Neurophysiol 120: 2358-2367, 2018) show that the changes in interneuronal gene transcription are correlated with the type of the activated neuronal population and that the initiation route of Ras/ERK MAPK pathway determines the polarity of the gene expression.
CRIS-Team Scopus Importer:2019-12-10
Keywords: 0 Mg2+; 4AP; activity-dependent gene expression; Gad1; Pvalb

Differential Diagnoses of Food-Related Gastrointestinal Symptoms in Patients with Anorexia Nervosa and Bulimia Nervosa: A Review of Literature. - Kress, Inge Ulrike; Paslakis, Georgios; Erim, Yesim (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2018)

Differential Release of Exocytosis Marker Dyes Indicates Stimulation-Dependent Regulation of Synaptic Activity - Henkel, Andreas W.; Mouihate, Abdeslam; Welzel, Oliver (Frontiers in Neuroscience, 2019)
There is a general consensus that synaptic vesicular release by a full collapse process is the primary machinery of synaptic transmission. However, competing view suggests that synaptic vesicular release operates via a kiss-and-run mechanism. By monitoring the release dynamics of a synaptic vesicular marker, FM1-43 from individual synapses in hippocampal neurons, we found evidence that the release of synaptic vesicle was delayed by several seconds after the start of field stimulation. This phenomenon was associated with modified opening kinetics of fusion pores. Detailed analysis revealed that some synapses were completely inactive for a few seconds after stimulation, despite immediate calcium influx. This delay in vesicular release was modulated by various stimulation protocols and different frequencies, indicating an activity-dependent regulation mechanism for neurotransmitter exocytosis. Staurosporine, a drug known to induce “kiss-and-run” exocytosis, increased the proportion of delayed synapses as well as the delay duration, while fluoxetine acted contrarily. Besides being a serotonin reuptake inhibitor, it directly enhanced vesicle mobilization and reduced synaptic fatigue. Exocytosis was never delayed, when it was monitored with pH-sensitive probes, synaptopHlourin and αSyt-CypHerE5 antibody, indicating an instantaneous formation of a fusion pore that allowed rapid equilibration of vesicular lumenal pH but prevented FM1-43 release because of its slow dissociation from the inner vesicular membrane. Our observations suggest that synapses operate via a sequential “kiss-and-run” and “full-collapse” exocytosis mechanism. The initially narrow vesicular pore allows the equilibration of intravesicular pH which then progresses toward full fusion, causing FM1-43 release.
CRIS-Team Scopus Importer:2019-10-29
Keywords: exocytosis; FM1-43; fusion pore; hippocampal neurons; kiss-and-run

Differentiating Benign and Malignant Breast Lesions in Diffusion Kurtosis MRI: Does the Averaging Procedure Matter? - Pistel, Mona; Laun, Frederik Bernd; Bickelhaupt, Sebastian; Dada, Anes; Weiland, Elisabeth; Niederdränk, Torsten; Uder, Michael; Janka, Rolf Matthias; Wenkel, Evelyn; Ohlmeyer, Sabine (Journal of Magnetic Resonance Imaging, 2022)
Background: Diffusion kurtosis imaging (DKI) is used to differentiate between benign and malignant breast lesions. DKI fits are performed either on voxel-by-voxel basis or using volume-averaged signal. Purpose: Investigate and compare DKI parameters' diagnostic performance using voxel-by-voxel and volume-averaged signal fit approach. Study type: Retrospective. Study population: A total of 104 patients, aged 24.1–86.4 years. Field Strength/Sequence: A 3 T Spin-echo planar diffusion-weighted sequence with b-values: 50 s/mm2, 750 s/mm2, and 1500 s/mm2. Dynamic contrast enhanced (DCE) sequence. Assessment: Lesions were manually segmented by M.P. under supervision of S.O. (2 and 5 years of experience in breast MRI). DKI fits were performed on voxel-by-voxel basis and with volume-averaged signal. Diagnostic performance of DKI parameters (Formula presented.) (kurtosis corrected diffusion coefficient) and kurtosis (Formula presented.) was compared between both approaches. Statistical Tests: Receiver operating characteristics analysis and area under the curve (AUC) values were computed. Wilcoxon rank sum and Students t-test tested DKI parameters for significant (P <0.05) difference between benign and malignant lesions. DeLong test was used to test the DKI parameter performance for significant fit approach dependency. Correlation between parameters of the two approaches was determined by Pearson correlation coefficient. Results: DKI parameters were significantly different between benign and malignant lesions for both fit approaches. Median benign vs. malignant values for voxel-by-voxel and volume-averaged approach were 2.00 vs. 1.28 ((Formula presented.) in μm2/msec), 2.03 vs. 1.26 ((Formula presented.) in μm2/msec), 0.54 vs. 0.90 ((Formula presented.)), 0.55 vs. 0.99 ((Formula presented.)). AUC for voxel-by-voxel and volume-averaged fit were 0.9494 and 0.9508 ((Formula presented.)); 0.9175 and 0.9298 ((Formula presented.)). For both, AUC did not differ significantly (P = 0.20). Correlation of values between the two approaches was very high (r = 0.99 for (Formula presented.) and r = 0.97 for (Formula presented.)). Data Conclusion: Voxel-by-voxel and volume-averaged signal fit approach are equally well suited for differentiating between benign and malignant breast lesions in DKI. Evidence Level: 3. Technical Efficacy: Stage 3.
CRIS-Team Scopus Importer:2022-03-25
Keywords: breast lesions; diffusion kurtosis fitting; diffusion magnetic resonance imaging

Different methodological approaches for the construction of a therapy sensitive ADL scale for the assessment of Alzheimer patients - Stemmler, Mark; Steinwachs, Klaus; Lehfeld, Hartmut; Jentzsch, Juliane; Tritt, Karin; Hulla, Franz; Erzigkeit, Helmut (New Trends in the Diagnosis and Therapy of Alzheimer’s Disease, 1994)
The purpose of this paper was the presentation of the work of the international ADL project which aims to construct a therapy sensitive ADL scale for cognitively impaired elderly or demented patients. No final scale was presented, rather different ways for generating ADL items were introduced. Different methodological approaches were applied because no existing ADL or I ADL scale meets the various goals of the international ADL project. By surveying existing scales or assessment tools for measuring daily life behaviour it was recognized that no traditional method of scale construction seems appropriate. Instead, different methodological approaches were adapted in order to meet the high demands for a newly to be constructed internationally valid and therapy sensitive ADL scale for mild to moderate dementia. The scale construction is still in progress. A first scale is expected to be tested by the end of 1994. An international validation in European and American research centers (including one center in Russia) is planne

Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase - Oeckl, Patrick; Weydt, Patrick; Steinacker, Petra; Anderl-Straub, Sarah; Nordin, Frida; Volk, Alexander E.; Diehl-Schmid, Janine; Andersen, Peter M.; Kornhuber, Johannes; Danek, Adrian; Fassbender, Klaus; Fliessbach, Klaus; et al. (Journal of Neurology Neurosurgery and Psychiatry, 2019)
Objective To investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers.
CRIS-Team WoS Importer:2019-03-06

Digital Dementia Registry Bavaria - DigiDEM Bayern: Study protocol for a multicentre, prospective, longitudinal register study - Dietzel, Nikolas; Kürten, Lara; Karrer, Linda; Reichold, Michael; Köhler, Laura; Nagel, Andreas; Chmelirsch, Christina; Seebahn, Kathrin; Hladik, Markus; Meuer, Sebastian; Kirchner, Anna; Holm, Kristina; et al. (BMJ Open, 2021)
Introduction Dementia is one of the most relevant widespread diseases, with a prevalence of currently 50 million people with dementia worldwide. The care of people with dementia will be one of the major challenges for healthcare systems worldwide. Digitalisation offers new possibilities to improve both dementia healthcare and health outcomes research as a fundament for national healthcare planning. The a € Digital Dementia Registry Bavaria - digiDEM Bayern' aims to improve the understanding of the complexity and long-term progression of dementia and the current care situation in Bavaria. Moreover, by offering digital services, digiDEM will actively contribute to improving the care situation in Bavaria. Methods and analysis digiDEM will recruit people with dementia and their family caregivers in all administrative regions of Bavaria. All participants will undergo dementia screening prior to study inclusion in order to identify people with mild cognitive impairment and mild-to-moderate dementia. Participants will be followed up over a period of three years. Sociodemographic data, type of dementia, symptoms, diagnosis, cognitive trajectories, activities of daily living, behavioural and psychological symptoms, falls, resource utilisation, caregiver burden, quality of life, needs of people with dementia and their caregivers, mobility, use of media and sources of information will be assessed. The project will implement a digital web-based platform for data collection. Data will be collected by means of standardised online or face-to-face interviews. Ethics and dissemination The study obtained ethical approval from the Ethics Committee of the Medical Faculty of Friedrich-Alexander-University Erlangen-Nürnberg (FAU) (application number: 253_20 B). Findings will be used for evidence-based decision-making for health decision-makers in order to optimise dementia healthcare in the state of Bavaria. Specific analyses will be conducted for the participating research partners. Results of the study will be published in peer-reviewed journals.
CRIS-Team Scopus Importer:2021-02-26
Keywords: dementia; neurology; public health

DIGITALLY ENHANCED TREAT-TO-TARGET AND SHARED DECISION-MAKING APPROACH WITH A DIGITAL HEALTH APPLICATION: INTERIM RESULTS FROM A RANDOMIZED CONTROLLED TRIAL - Knitza, Johannes; Grahammer, M.; Böltz, Sebastian; Lang, Johannes; Detert, M.; Bader, M.; Kleyer, Arnd; Simon, David; Kronke, G.; Schett, Georg; Detert, J. (ANNALS OF THE RHEUMATIC DISEASES, 2022)
CRIS-Team WoS Importer:2022-11-04

Digit ratio (2D:4D) and academic success as measured by achievement in the academic degree "Habilitation" - Tektas, Ozan Yueksel; Kapsner, Lorenz; Lemmer, Miriam; Bouna-Pyrrou, Polyxeni; Lewczuk, Piotr; Lenz, Bernd; Kornhuber, Johannes (PLoS ONE, 2019)
Introduction
CRIS-Team WoS Importer:2019-03-15

Digit ratio (2D:4D) and behavioral symptoms in primary-school aged boys - Eichler, Anna; Heinrich, Hartmut; Moll, Gunther; Beckmann, Matthias; Goecke, Tamme W.; Fasching, Peter; Muschler, Marcel-Rene; Bouna-Pyrrou, Polyxeni; Lenz, Bernd; Kornhuber, Johannes (Early Human Development, 2018)
The second-to-forth digit length ratio (2D:4D) is considered to be a biomarker for intrauterine androgen levels. It is associated with adult and child mental health problems, primarily with behavioral symptoms and predominantly in males. Using a cross-sectional design, we examined whether 2D:4D was associated with conduct disorder (CD) symptoms in 138 primary-school aged children (54% boys, Mage = 7.70 years) and considered child sex as a moderating factor. Children's digit lengths were measured from hand scans and mothers rated the behavioral/emotional symptoms of their child. The regression analyses revealed that 2D:4D ratios were associated with behavioral symptoms in boys (β = -0.260, p = 0.026), but not in girls (β = -0.040, p = 0.762). Child emotional symptoms, analyzed as a control, were not significantly correlated with 2D:4D. In conclusion, prenatal brain hyperandrogenization - operationalized by the 2D:4D biomarker - could result in behavioral symptoms in boys at early school age, reflecting one predictor for early onset CD. Our data support the use of 2D:4D as a marker of prenatal androgen exposure.
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Digit ratio (2D:4D) and transgender identity: new original data and a meta-analysis - Siegmann, Eva-Maria; Müller, Tobias; Dziadeck, Isabelle; Mühle, Christiane; Lenz, Bernd; Kornhuber, Johannes (Scientific Reports, 2020)
Previously reported associations between second-to-fourth digit length ratio (2D:4D), a proxy for prenatal androgen load, and transgender identity have been inconsistent. The objectives of the present study were to provide additional original data and an updated meta-analysis concerning this association. In a study of 464 participants, we compared the 2D:4D of transgender individuals with age- and sex-matched controls. Patients were recruited at a specialized psychiatrist’s medical office, whereas controls were hired via flyers, advertisements, and as convenience sample. A random-effects meta-analysis of the literature (17 samples, n = 3674) also quantifies the overall magnitude of the difference in 2D:4D between transgender individuals and controls. In our study providing new original data, we found a significantly higher (i.e. feminized) left-hand 2D:4D in the male-to-female transgender (MtF) identity [mean age: 32.3 (18; 61)] than in the male control group [mean age: 34.5 (18; 65)] with a Cohen’s d = 0.271. Concordantly, the meta-analytic results suggest a significant difference in 2D:4D among MtF individuals compared to male controls [g = 0.153; 95% CI (0.063; 0.243)], which was even more pronounced when individuals had been diagnosed by a clinician instead of self-identified as transgender [g = 0.193; 95% CI (0.086; 0.300)]. In both studies, no significant results were revealed for female-to-male transgender individuals [mean age: 26.1 (18; 53)] versus female controls [mean age: 27.2 (18; 55)]. This original investigation and the updated meta-analysis clarify the association between transgender identity and 2D:4D indicating the influence of prenatal androgen on the development of gender identity in subjects born as males.
CRIS-Team Scopus Importer:2020-11-20

Digit ratio (2D:4D) in relation to substance and computer use: a meta-analysis - Siegmann, Eva-Maria; Bouna-Pyrrou, Polyxeni; Lenz, Bernd; Kornhuber, Johannes (Journal of Neural Transmission, 2019)
Human studies have reported inconsistent associations between the length ratio of the second finger to the fourth finger (2D:4D), which is a proxy for prenatal androgen load, and substance or computer use in adolescents and adults. This meta-analysis quantifies the magnitude of this relationship and investigates the roles of sex, definition of caseness, different forms of addiction, the hand measured (right hand versus left hand), and other cohort characteristics. Univariate random-effects meta-analyses were performed, and moderators were tested with Bonferroni-corrected meta-regression analyses. The study included 18 independent samples with a total of 175,955 participants (96,316 males and 79,639 females). There was a significant difference in 2D:4D between the substance and computer-using subjects and the controls for the combined sample (Hedge’s g = − 0.178 [− 0.291; − 0.064]) and for males (Hedge’s g = − 0.260 [− 0.399; − 0.122]), but not for females. These effects were amplified when only analyzing studies that compared dependent versus non-dependent subjects (combined sample: g = − 0.325 [− 0.492; − 0.157]; males: g = − 0.427 [− 0.564; − 0.291]), but did not reach significance in the subgroup of studies examining other parameters of substance and computer use. When analyzing different forms of substance and computer use separately, alcohol intake and computer use revealed a significant difference in the standardized mean. Again, the effects were amplified when analyzing the subgroup of males and the subgroup of studies comparing dependent versus non-dependent subjects, with effect sizes showing Hedge’s g values as many as − 0.552 [− 0.785; − 0.319] (alcohol-dependent males). Thus, this meta-analysis confirms that lower 2D:4D is associated with substance and computer dependency. Further studies are encouraged to explore the link between intrauterine hormone environment and addiction risk.
CRIS-Team Scopus Importer:2019-05-14
Keywords: 2D:4D; Alcohol; Androgens; Brain organization; Prenatal androgen exposure; Substance use; Testosterone; Tobacco

Digit Ratio (2D:4D) Is Not Associated with Alzheimer’s Disease in the Elderly - Siegmann, Eva-Maria; Olm, Pauline; Lenz, Bernd; Mühle, Christiane; Oberstein, Timo; Maler, Juan Manuel; Kornhuber, Johannes (Brain Sciences, 2023)
The development of Alzheimer’s disease (AD) is influenced by sex hormones—estrogens and androgens in particular. However, the impact of prenatal sex hormone exposure is less clear; very few investigations have examined the relationship between the second-to-fourth digit length ratio (2D:4D), a putative proxy for the ratio of prenatal estrogens to androgens, and AD, with inconsistent results among the few that have. Therefore, we aimed to investigate this relationship using methodologically robust metrics. In a 2 (sex) × 4 (group) MANOVA incorporating 108 participants (30 AD patients, 19 patients with tauopathy but no amyloidopathy, 31 clinical and 28 healthy age- and education-matched controls), the effects of sex and group on the dependent variables right and left 2D:4D were examined. We also explored the association between 2D:4D and the severity of AD symptoms assessed via neuropsychological examination. We did not find any significant differences in the right- and left-hand 2D:4D between patients with AD and the other groups; no significant associations between 2D:4D and neuropsychological task performances were found in the dementia groups. The 2D:4D of healthy women was significantly lower than that of depressed women without AD, i.e., clinical controls, but not significantly different from depressed female patients with AD. This investigation does not support the role of 2D:4D in the development or severity of AD in general, but suggests a potential role of 2D:4D for depression in women. Future studies are warranted to clarify whether 2D:4D can distinguish between early- and late-onset depression in women.
CRIS-Team Scopus Importer:2023-10-06
Keywords: Alzheimer’s disease; dementia; digit ratio; fetal development; finger length ratio

Disability-Adjusted Life-Years Associated with Intracerebral Hemorrhage and Secondary Injury - Haupenthal, David; Kuramatsu, Joji; Volbers, Bastian; Sembill, Jochen; Mrochen, Anne; Balk, Stefanie; Hölter, Philip; Lücking, Hannes; Engelhorn, Tobias; Dörfler, Arnd; Schwab, Stefan; Huttner, Hagen; et al. (JAMA Network Open, 2021)
Importance: Intracerebral hemorrhage (ICH) contributes significantly to the global burden of disease. Objective: To examine the association of ICH and secondary injury with disability-adjusted life-years (DALYs) for the individual patient. Design, Setting, and Participants: This cohort study was conducted using data from the Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage study. Consecutive patients admitted to a single tertiary care center from January 1, 2006, to December 31, 2015, were included. The sample comprised patients with oral anticoagulation-associated ICH (OAC-ICH) or primary spontaneous ICH (non-OAC-ICH). Statistical analysis was conducted from October 1 to December 31, 2020. Exposures: ICH occurrence and secondary injury. Main Outcomes and Measures: DALYs, years of life lost (YLL), and years lived with disability (YLD) were analyzed by hematoma location, ICH volume, and secondary injury (ie, hematoma expansion [HE], intraventricular hemorrhage [IVH], and perihemorrhagic edema [PHE]). Results: Among 1322 patients with ICH, 615 (46.5%) were women and the mean (SD) age at hospital admission was 71 (13) years; ICH was associated with a mean (SD) of 9.46 (8.08) DALYs, 5.72 (8.29) YLL, and 3.74 (5.95) YLD. There were statistically significant differences in mean (SD) DALYs by extent of hematoma volume (< 10 mL ICH: 7.05 [6.79] DALYs; 10-30 mL ICH: 9.91 [8.35] DALYs; >30 mL ICH: 12.42 [8.47] DALYs; P <.001) and ICH location (deep location: 10.60 [8.35] DALYs; lobar location: 8.18 [7.63] DALYs; cerebellum: 8.14 [6.80] DALYs; brainstem: 12.63 [9.21] DALYs; P <.001). Regarding population-level disease burden of secondary injuries after ICH, there was a statistically significant difference in mean (SD) by injury type, with 0.94 (3.19) DALYs for HE, 2.45 (4.16) DALYs for IVH, and 1.96 (2.66) DALYs for PHE (P <.001) among the entire ICH cohort. Regarding individual-level exposure to secondary injuries after ICH, there were a mean (SD) 7.14 (6.62) DALYs for HE, 4.58 (4.75) DALYs for IVH, and 3.35 (3.28) DALYs for PHE among patients with ICH affected by secondary injuries. Conclusions and Relevance: These findings suggest that there is a high burden of disability associated with ICH and secondary injuries, and the findings may guide public health strategies. The study findings further suggest that IVH and PHE may be relevant for the overall outcome of patients with ICH, that DALYs may represent a viable outcome parameter for studies to evaluate treatment outcomes in ICH research, and that IVH and PHE may represent potential treatment targets..
CRIS-Team Scopus Importer:2021-07-30

Discovery of G Protein-Biased Dopaminergics with a Pyrazolo[1,5-a]pyridine Substructure - Möller, Dorothee; Banerjee, Ashutosh; Uzuneser, Taygun; Skultety, Marika; Huth, Tobias; Plouffe, Bianca; Hübner, Harald; Alzheimer, Christian; Friedland, Kristina; Müller, Christian P.; Bouvier, Michel; Gmeiner, Peter (Journal of Medicinal Chemistry, 2017)
1,4-Disubstituted aromatic piperazines are privileged structural motifs recognized by aminergic G protein-coupled receptors. Connection of a lipophilic moiety to the arylpiperazine core by an appropriate linker represents a promising concept to increase binding affinity and to fine-tune functional properties. In particular, incorporation of a pyrazolo[1,5-a]pyridine heterocyclic appendage led to a series of high-affinity dopamine receptor partial agonists. Comprehensive pharmacological characterization involving BRET biosensors, binding studies, electrophysiology, and complementation-based assays revealed compounds favoring activation of G proteins (preferably G(o)) over beta-arrestin recruitment at dopamine D-2 receptors. The feasibility to design G protein-biased partial agonists as putative novel therapeutics was demonstrated for the representative 2-methoxyphenylpiperazine 16c, which unequivocally displayed antipsychotic activity in vivo. Moreover, combination of the pyrazolo[1,5-a]pyridine appendage with a 5-hydroxy-N-propy1-2-aminotetraline unit led to balanced or G protein-biased dopaminergic ligands depending on the stereochemistry of the headgroup, illustrating the complex structure functional selectivity relationships at dopamine D2 receptors.

Disease concepts of oncological patients in cultural comparison - Morawa, Eva; Erim, Yesim (ONCOLOGY RESEARCH AND TREATMENT, 2021)
CRIS-Team WoS Importer:2022-03-25

Disentangling the relationship of subjective cognitive decline and depressive symptoms in the development of cognitive decline and dementia - Kleineidam, Luca; Wagner, Michael; Guski, Jannis; Wolfsgruber, Steffen; Miebach, Lisa; Bickel, Horst; Koenig, Hans-Helmut; Weyerer, Siegfried; Luehmann, Dagmar; Kaduszkiewicz, Hanna; Luppa, Melanie; Rohr, Susanne; et al. (Alzheimers & Dementia, 2022)
Introduction: Subjective cognitive decline (SCD) and depressive symptoms (DS) frequently co-occur prior to dementia. However, the temporal sequence of their emergence and their combined prognostic value for cognitive decline and dementia is unclear. Methods: Temporal relationships of SCD, DS and memory decline were examined by latent difference score modeling in a high-aged, population-based cohort (N = 3217) and validated using Cox-regression of dementia-conversion. In 334 cognitively unimpaired SCD-patients from memory-clinics, we examined the association of DS with cognitive decline and with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers. Results: In the population-based cohort, SCD preceded DS. High DS were associated with increased risk of dementia conversion in individuals with SCD. In SCD-patients from memory-clinics, high DS were associated with greater cognitive decline. CSF Aß42 predicted increasing DS. Discussion: SCD typically precedes DS in the evolution to dementia. SCD-patients from memory-clinics with DS may constitute a high-risk group for cognitive decline. Highlights: Subjective cognitive decline (SCD) precedes depressive symptoms (DS) as memory declines. Emerging or persistent DS after SCD reports predict dementia. In SCD patients, more amyloid pathology relates to increasing DS. SCD patients with DS are at high risk for symptomatic progression.
CRIS-Team Scopus Importer:2022-10-21
Keywords: Alzheimer's disease; depression; latent difference score model; subjective cognitive decline; temporal sequence

Disrupted-in-Schizophrenia 1 (DISC1) Overexpression and Juvenile Immune Activation Cause Sex-Specific Schizophrenia-Related Psychopathology in Rats - Uzuneser, Taygun; Speidel, Jil; Kogias, Georgios; Wang, An-Li; Silva, Maria A. De Souza; Huston, Joseph P.; Zoicas, Iulia; von Hörsten, Stephan; Kornhuber, Johannes; Korth, Carsten; Müller, Christian P. (Frontiers in Psychiatry, 2019)
Synaptic pruning is a critical refinement step during neurodevelopment, and schizophrenia has been associated with overpruning of cortical dendritic spines. Both human studies and animal models implicate disrupted-in-schizophrenia 1 (DISC1) gene as a strong susceptibility factor for schizophrenia. Accumulating evidence supports the involvement of DISC1 protein in the modulation of synaptic elimination during critical periods of neurodevelopment and of dopamine D2-receptor-mediated signaling during adulthood. In many species, synaptic pruning occurs during juvenile and adolescent periods and is mediated by microglia, which can be over-activated by an immune challenge, giving rise to overpruning. Therefore, we sought to investigate possible interactions between a transgenic DISC1 model (tgDISC1) and juvenile immune activation (JIA) by the bacterial cell wall endotoxin lipopolysaccharide on the induction of schizophrenia-related behavioral and neurochemical disruptions in adult female and male rats. We examined possible behavioral aberrations along three major symptom dimensions of schizophrenia including psychosis, social and emotional disruptions, and cognitive impairments. We detected significant gene environment interactions in the amphetamine-induced locomotion in female animals and in the amphetamine-induced anxiety in male animals. Surprisingly, gene environment interactions improved social memory in both male and female animals. JIA alone disrupted spatial memory and recognition memory, but only in male animals. DISC1 overexpression alone induced an improvement in sensorimotor gating, but only in female animals. Our neurochemical analyses detected sex- and manipulation-dependent changes in the postmortem monoamine content of animals. Taken together, we here report sex-specific effects of environment and genotype as well as their interaction on behavioral phenotypes and neurochemical profiles relevant for schizophrenia.
CRIS-Team WoS Importer:2019-04-18

Distraction effects on chemosensory perception in lean and obese volunteers - Ruda, Iryna; Freiherr, Jessica (CHEMICAL SENSES, 2022)
CRIS-Team WoS Importer:2023-03-10

Distress, Main Burdens, Engagement Motivators and Needs of Fulltime and Volunteer Refugee Aid Workers - Grimm, Theresa; Georgiadou, Ekaterini; Silbermann, Andrea; Junker, Katharina; Nisslbeck, Winfried; Erim, Yesim (Psychotherapie Psychosomatik Medizinische Psychologie, 2017)
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Distributions of A beta 42 and A beta 42/40 in the Cerebrospinal Fluid in View of the Probability Theory - Lewczuk, Piotr; Wiltfang, Jens; Kornhuber, Johannes; Verhasselt, Anneleen (Diagnostics, 2021)
Amyloid beta 42/40 concentration quotient has been empirically shown to improve accuracy of the neurochemical diagnostics of Alzheimer's Disease (AD) compared to the A beta 42 concentration alone, but this improvement in diagnostic performance has not been backed up by a theoretical argumentation so far. In this report we show that better accuracy of A beta 42/40 compared to A beta 1-42 is granted by fundamental laws of probability. In particular, it can be shown that the dispersion of a distribution of a quotient of two random variables (A beta 42/40) is smaller than the dispersion of the random variable in the numerator (A beta 42), provided that the two variables are proportional. Further, this concept predicts and explains presence of outlying observations, i.e., AD patients with falsely negatively high A beta 42/40 ratio, and non-AD subjects with extremely low, falsely positive, A beta 42/40 ratio.
CRIS-Team WoS Importer:2022-01-14

DNA-methylation of the dopamin receptor 2 gene is altered during alcohol withdrawal - Hillemacher, Thomas; Rhein, Mathias; Burkert, Alexandra; Heberlein, Annemarie; Wilhelm, Julia; Glahn, Alexander; Muschler, Marc Andre Nicolas; Kahl, Kai G.; Kornhuber, Johannes; Bleich, Stefan; Frieling, Helge (European Neuropsychopharmacology, 2019)
The dopaminergic neurotransmission is known to be of crucial importance in addictive behavior. Epigenetic regulation like methylation of DNA influences the function of dopaminergic transmission. The present study investigated alterations of DNA methylation in the dopamine D2 receptor (DRD2)-gene in patients suffering from alcohol dependence. The study sample consists of 99 alcohol dependent males admitted for alcohol withdrawal treatment and a control group of 33 healthy participants. Blood samples underwent bisulfite sequencing to determine levels of DNA-methylation of the promoter region of the DRD2 gene. Mixed linear modeling was used to test differences between patients and controls, course of methylation during detoxification. While DRD2-gene methylation did not differ significantly between patients and controls, we found a significant increase of DRD2-gene methylation during alcohol withdrawal/early abstinence. Craving, measured with the Obsessive Compulsive Drinking Scale (OCDS), was significantly associated with DRD2-gene methylation. Furthermore, smoking significantly influenced DRD2-gene methylation in both, patients and controls. As in other types of addictive disorders, DRD2-gene methylation is altered during alcohol withdrawal/early abstinence. The findings regarding an association with alcohol craving and tobacco consumption point towards a crucial role of DRD2-gene methylation in the neurobiology of addictive behavior.
CRIS-Team Scopus Importer:2019-09-24
Keywords: Alcohol; Dopamine; Gene expression; Nicotine

DNA methylation of the LEP gene is associated with craving during alcohol withdrawal - Hillemacher, Thomas; Weinland, Christian; Lenz, Bernd; Kraus, Thomas; Heberlein, Annemarie; Glahn, Alexander; Muschler, Marc A. N.; Bleich, Stefan; Kornhuber, Johannes; Frieling, Helge (Psychoneuroendocrinology, 2015)
Different studies have described evidence for an association between leptin serum levels and craving in alcohol dependent patients. As leptin expression is regulated by DNA methylation we investigated changes of DNA methylation of the LEP gene promoter region in alcohol dependent patients undergoing withdrawal. Results show that low methylation status is associated with increasing serum leptin levels and elevation of craving for alcohol in the referring patients group. These findings point towards a pathophysiological relevance of changes in DNA methylation of the LEP gene promoter region in alcohol dependence.
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Do changes in the BDNF promoter methylation indicate the risk of alcohol relapse? - Heberlein, Annemarie; Blischer, Patricia; Schuster, Rilana; Kleimann, Alexandra; Lichtinghagen, Ralf; Rhein, Mathias; Kornhuber, Johannes; Bleich, Stefan; Frieling, Helge; Hillemacher, Thomas (European Neuropsychopharmacology, 2015)
The neurotrophic growth factor brain derived neurotrophic factor (BDNF) was linked to the risk of alcohol relapse in clinical studies. In this study we investigated alterations in the methylation of the BDNF gene during alcohol withdrawal (day 1, 7 and 14) in 99 male alcohol-dependent patients compared to age matched healthy males (n=33). In particular, we aimed to investigate a possible association between the BDNF promoter methylation and the self-reported duration of alcohol abstinence before relapse. Mean methylation of the BDNF promoter was significantly increased in alcohol-dependent patients compared to the healthy controls (F=10.014, p<0.001) and decreased significantly during alcohol-withdrawal (F=10.014, p<0.001). Moreover, mean methylation was associated with depressive (F=2.014, p<0.001) and anxious symptoms in the alcohol-dependent patients (F=2.228, p<0.001). On day 14 of alcohol-withdrawal we found significantly higher methylation rates in those patients who abstained longer before relapse compared to those patients who abstained shorter (F=9.938, p<0.001). Our results suggest an association between BDNF expression and the symptomatology of alcohol withdrawal and imply that changes in the methylation of the BDNF IV gene may contribute to alcohol consumption.
EVALuna2:23709

Does the separation from marital partners of Syrian refugees with a residence permit in Germany have an impact on their quality of life? - Georgiadou, Ekaterini; Schmitt, Gregor Martin; Erim, Yesim (Journal of psychosomatic research, 2020)
Objective: Around 700,000 Syrian refugees live in Germany, most of them having come alone since 2015 as asylum seekers and waiting in Germany for family reunification. This study focused on separation from marital partner and its impact on quality of life among Syrian refugees with a residence permit. Methods: For the present investigation, we included only married participants of a larger registry-based study. Therefore, we analyzed 119 participants; 93 of them were married, and their partner accompanied them in Germany at the time of the investigation (partner+), while a further 26 were married but separated from their partner (partner-). The respondents were investigated for mental stress, quality of life and protective factors. Results: The partner- group reported significantly lower quality of life in the domains of psychological and social health in comparison to the partner+ group. Higher general quality of life was associated with higher social support, higher sense of coherence and fewer symptoms of depression. Predictors for a higher quality of life were male gender, fewer symptoms of depression, a higher sense of coherence, higher perceived social support and living together with the marital partner. Conclusion: Family separation of Syrian refugees with a residence permit in Germany can have an impact on their quality of life. Longitudinal studies are needed to confirm our results and determine the long-term effects of family separation.
CRIS-Team Scopus Importer:2020-01-31
Keywords: Family separation; Germany; Mental health; Quality of life; Syrian refugees

Does Voluntary Work Contribute to Cognitive Performance? – An International Systematic Review - Keefer, Anne; Steichele, Kathrin; Grässel, Elmar; Prokosch, Hans-Ulrich; Kolominsky-Rabas, Peter L. (Journal of Multidisciplinary Healthcare, 2023)
Introduction: There is a need for knowledge on activities that can reduce cognitive decline and dementia risk. Volunteering is a productive activity that entails social, physical, and cognitive functions. Therefore, volunteering could be a protective factor for cognitive loss. Thus, this review aims to examine the associations between volunteering and volunteers’ cognition and to identify influencing variables. Methods: Six international literature databases were searched for relevant articles published between 2017 and 2021 (ALOIS, CENTRAL, CINAL, Embase, PsycINFO, PubMed). Quantitative studies of all study designs were included. The primary outcome was the volunteers’ cognition measured by objective, internationally established psychometric function tests. Two authors independently assessed the eligibility and quality of the studies. A narrative synthesis was performed using all studies included in this review. The methodology was in line with the PRISMA guidelines. Results: Fourteen studies met the inclusion criteria and were included. Seven of the included studies confirmed that volunteering positively affects the volunteers’ cognitive function. Two other studies identified an association between volunteer activity and volunteers’ cognition using cross-sectional measurements. In particular, women and people with a low level of education benefit from the positive effects and associations. The study quality of the included articles was moderate to weak. Discussion: Our review suggests that volunteering can improve volunteers’ cognition. Unfortunately, little attention is given to specific volunteer activities and the frequency of engagement. Additionally, more attention is needed on various risk factors of cognitive impairment.
CRIS-Team Scopus Importer:2023-05-26
Keywords: cognitive health; dementia prevention; health promotion; social engagement

Donor quality of life up to two years after living donor liver transplantation: a prospective study - Kroencke, Sylvia; Nashan, Björn; Fischer, Lutz; Erim, Yesim; Schulz, Karl-Heinz (Transplantation, 2014)
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Donors' eligibility in the frame of living donor liver transplantation from the psychosomatic perspective - Erim, Yesim; Beckmann, M.; Kroencke, S.; Schulz, K. -H. (Transplant International, 2010)

Don't forget about tau: the effects of ApoE4 genotype on Alzheimer's disease cerebrospinal fluid biomarkers in subjects with mild cognitive impairment-data from the Dementia Competence Network - Benson, Gloria S.; Bauer, Chris; Hausner, Lucrezia; Couturier, Samuel; Lewczuk, Piotr; Peters, Oliver; Huell, Michael; Jahn, Holger; Jessen, Frank; Pantel, Johannes; Teipel, Stefan J.; Wagner, Michael; et al. (Journal of Neural Transmission, 2022)
ApoE4, the strongest genetic risk factor for Alzheimer's disease (AD), has been shown to be associated with both beta-amyloid (A beta) and tau pathology, with the strongest evidence for effects on A beta, while the association between ApoE4 and tau pathology remains inconsistent. This study aimed to investigate the associations between ApoE4 with CSF A beta 42, total tau (t-tau), phospho-tau181 (p-tau), and with the progression of decline in a large cohort of MCI subjects, both progressors to AD and other dementias, as well as non-progressors. We analyzed associations of CSF A beta 42, p-tau and t-tau with ApoE4 allele frequency cross-sectionally and longitudinally over 3 years of follow-up in 195 individuals with a diagnosis of MCI-stable, MCI-AD converters and MCI progressing to other dementias from the German Dementia Competence Network. In the total sample, ApoE4 carriers had lower concentrations of CSF A beta 42, and increased concentrations of t-tau and p-tau compared to non-carriers in a gene dose-dependent manner. Comparisons of these associations stratified by MCI-progression groups showed a significant influence of ApoE4 carriership and diagnostic group on all CSF biomarker levels. The effect of ApoE4 was present in MCI-stable individuals but not in the other groups, with ApoE4 + carriers having decreased CSF A beta 42 levels, and increased concentration of t-tau and p-tau. Longitudinally, individuals with abnormal t-tau and A beta 42 had a more rapid progression of cognitive and clinical decline, independently of ApoE4 genotype. Overall, our results contribute to an emerging framework in which ApoE4 involves mechanisms associated with both CSF amyloid-beta burden and tau aggregation at specific time points in AD pathogenesis.
CRIS-Team WoS Importer:2022-01-28

Do we still need positron emission tomography for early Alzheimer's disease diagnosis? - Lewczuk, Piotr; Kornhuber, Johannes (Brain, 2016)
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DPP4-deficient congenic rats display blunted stress, improved fear extinction and increased central NPY - Canneva, Fabio; Golub, Yulia; Distler, Jörg; Dobner, Julia; Meyer, Sarah Katharina; von Hörsten, Stephan (Psychoneuroendocrinology, 2015)
Inhibitors of dipeptidyl peptidase 4 (DPP4, CD26) are used for the treatment of type 2 diabetic patients and better glucose tolerance has been confirmed in functionally DPP4-deficient congenic rats (DPP4mut), along with immunological alterations and, interestingly, a stress-resilient phenotype. All these findings are in agreement with the "moonlighting" properties of DPP4, whose proteolytic action is responsible for the inactivation of a number of regulatory peptides including, but not limited to, neuropeptide Y (NPY). Among all candidate substrates, DPP4 displays highest affinity for NPY, an endogenous anxiolytic neurotransmitter that is suggested as a candidate biomarker in post-traumatic stress disorder (PTSD) and depression.Central and peripheral NPY levels were measured by ELISA in DPP4mut and DAwt rats revealing a significantly higher concentration of the peptide in the CSF of DPP4mut animals. This finding positively correlated with the blunted stress phenotype measured on an analgesia-meter. Additionally, when a classical fear-conditioning paradigm was investigated, short-term fear extinction was significantly potentiated in DPP4mut rats as compared to wt controls.Our findings indicate a positive correlation between reduced stress-responsiveness and increased central NPY, in DPP4mut rats. Most interestingly, the behavioral phenotype extends to facilitation of fear extinction. These observations raise further interest in DPP4-modulating drugs for the potential effect on NPY metabolism, as a therapeutic tool for psychiatric conditions such as anxiety disorders and PTSD.
EVALuna2:13098

Drug-induced phospholipidosis caused by combinations of common drugs in vitro - Glock, Mareike; Mühlbacher, Markus; Hurtig, Henoch; Tripal, Philipp; Kornhuber, Johannes (Toxicology in Vitro, 2016)
Drug-induced phospholipidosis (DIPLD), characterized by the accumulation of phospholipids within lysosomes, is suspected to impair lysosomal function and considered an adverse side effect of the administered medication. The increasing use of polypharmacy and the resultant elevated risks of adverse drug reactions raise the need to explore the effects of drug combinations with respect to their influence on side effects, such as DIPLD. In this study, we utilized an in vitro assay to investigate DIPLD that was caused by 24 commonly used drugs applied alone and in binary combinations with each other. Moreover, we attempted to predict the extent of DIPLD resulting from the combinations using a simple additive approach based on the increase in phospholipid levels caused by the single drugs. The results suggest that DIPLD, which was caused by combinations of drugs, occurs in an additive manner, depending on total drug concentration. Furthermore, we show that the extent of DIPLD can be predicted from the DIPLD caused by the single drugs. Thus, the simultaneous use of multiple drugs with PLD-inducing properties increases the event risk, as well as the severity of drug-induced phospholipidosis. The findings underline the importance of considering the DIPLD-inducing properties of drugs, especially in the context of polypharmacy.
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Drug instrumentalization - Müller, Christian P. (Behavioural Brain Research, 2020)
Psychoactive drugs with addiction potential are widely used by people of virtually all cultures in a non-addictive way. In order to understand this behaviour, its population penetrance, and its persistence, drug instrumentalization was suggested as a driving force for this consumption. Drug instrumentalization theory holds that psychoactive drugs are consumed in a very systematic way in order to make other, non-drug-related behaviours more efficient. Here, we review the evolutionary origin of this behaviour and its psychological mechanisms and explore the neurobiological and neuropharmacological mechanisms underlying them. Instrumentalization goals are discussed, for which an environmentally selective and mental state-dependent consumption of psychoactive drugs can be learned and maintained in a non-addictive way. A small percentage of people who regularly instrumentalize psychoactive drugs make a transition to addiction, which often starts with qualitative and quantitative changes in the instrumentalization goals. As such, addiction is proposed to develop from previously established long-term drug instrumentalization. Thus, preventing and treating drug addiction in an individualized medicine approach may essentially require understanding and supporting personal instrumentalization goals.
CRIS-Team Scopus Importer:2020-06-02
Keywords: Drug abuse; Drug addiction; Drug instrumentalization; Drug use; Instrumentalization goals

DSC Brain Perfusion Using Advanced Deconvolution Models in the Diagnostic Work-Up of Dementia and Mild Cognitive Impairment: A Semiquantitative Comparison with HMPAO-SPECT-Brain Perfusion - Schmidt, Manuel; Engelhorn, Tobias; Lang, Stefan; Lücking, Hannes; Hölter, Philip; Fröhlich, Kilian; Ritt, Philipp; Maler, Juan Manuel; Kuwert, Torsten; Kornhuber, Johannes; Dörfler, Arnd (Journal of Clinical Medicine, 2020)
Background: SPECT (single-photon emission-computed tomography) is used for the detection of hypoperfusion in cognitive impairment and dementia but is not widely available and related to radiation dose exposure. We compared the performance of DSC (dynamic susceptibility contrast) perfusion using semi- and fully adaptive deconvolution models to HMPAO-SPECT (99mTc-hexamethylpropyleneamine oxime-SPECT). Material and Methods: Twenty-seven patients with dementia of different subtypes including frontotemporal dementia (FTD) and mild cognitive impairment (MCI) received a multimodal diagnostic work-up including DSC perfusion at a clinical 3T high-field scanner and HMPAO-SPECT. Nineteen healthy control individuals received DSC perfusion. For calculation of the hemodynamic parameter maps, oscillation-index standard truncated singular value decomposition (oSVD, semi-adaptive) as well as Bayesian parameter estimation (BAY, fully adaptive) were performed. Results: Patients showed decreased cortical perfusion in the left frontal lobe compared to controls (relative cerebral blood volume corrected, rBVc: 0.37 vs. 0.27,p= 0.048, adjusted for age and sex). Performance of rBVc (corrected for T1 effects) was highest compared to SPECT for detection of frontal hypoperfusion (sensitivity 83%, specificity 80% for oSVD and BAY, area under curve (AUC) = 0.833 respectively,p< 0.05) in FTD and MCI. For nonleakage-corrected rBV and for rBF (relative cerebral blood flow), sensitivity of frontal hypoperfusion was above 80% for oSVD and for BAY (rBV: sensitivity 83%, specificity 75%, AUC = 0.908 for oSVD and 0.917 for BAY,p< 0.05 respectively; rBF: sensitivity 83%, specificity 65%, AUC = 0.825,p< 0.05 for oSVD). Conclusion: Advanced deconvolution DSC can reliably detect pathological perfusion alterations in FTD and MCI. Hence, this widely accessible technique has the potential to improve the diagnosis of dementia and MCI as part of an interdisciplinary multimodal imaging work-up. Advances in knowledge: Advanced DSC perfusion has a high potential in the work-up of suspected dementia and correlates with SPECT brain perfusion results in dementia and MCI.
CRIS-Team WoS Importer:2020-07-31

Duration of lithium treatment and brain lithium concentration in patients with unipolar and schizoaffective disorder: A study with magnetic resonance spectroscopy - Riedl, Ulrich; Barocka, Arnd; Kolem, Heinrich; Demling, Joachim; Kaschka, Wolfgang P.; Schelp, Rainer; Stemmler, Mark; Ebert, Dieter (Biological Psychiatry, 1997)
Twenty psychiatric patients on lithium medication were examined with 7-Li-magnetic resonance spectroscopy of the brain. Patients on long-term lithium treatment (>6 months) were compared with a short-term group who had been taking lithium for between 4 and 8 weeks. Patients met DSM-III-R criteria for either recurrent unipolar depressive disorder (DSM-III-R 296.3x) or schizoaffective disorder, depressive type (DSM-III-R 295.70). The brain:serum lithium ratio was 0.76 ± 0.26; there was no significant difference between short-term and long-term treatment. In the group of long-term treatment patients there was a positive correlation between lithium dose per day and brain lithium concentration (R = .72, p <.01), and between lithium plasma concentration and brain lithium concentration (R = .65, p < .05). In the short-term group, however, there was no significant correlation for these parameters. No differences between unipolar and schizoaffective disorder were found.
Keywords: Lithium; magnetic resonance spectroscopy; unipolar disorder; schizoaffective disorder

Dynamic Angiography and Perfusion Imaging Using Flat Detector CT in the Angiography Suite: A Pilot Study in Patients with Acute Middle Cerebral Artery Occlusions - Struffert, Tobias; Deuerling-Zheng, Y.; Kloska, Stephan; Engelhorn, Tobias; Lang, Sabine; Mennecke, Angelika; Manhart, M.; Strother, C. M.; Schwab, Sibylle; Dörfler, Arnd (American Journal of Neuroradiology, 2015)
Perfusion and angiographic imaging using intravenous contrast application to evaluate stroke patients is now technically feasible by flat detector CT performed by the angiographic system. The aim of this pilot study was to show the feasibility and qualitative comparability of a novel flat detector CT dynamic perfusion and angiographic imaging protocol in comparison with a multimodal stroke MR imaging protocol.In 12 patients with acute stroke, MR imaging and the novel flat detector CT protocol were performed before endovascular treatment. Perfusion parameter maps (MTT, TTP, CBV, CBF) and MIP/volume-rendering technique images obtained by using both modalities (MR imaging and flat detector CT) were compared.Comparison of MIP/volume-rendering technique images demonstrated equivalent visibility of the occlusion site. Qualitative comparison of perfusion parameter maps by using ASPECTS revealed high Pearson correlation coefficients for parameters CBF, MTT, and TTP (0.95-0.98), while for CBV, the coefficient was lower (0.49).We have shown the feasibility of a novel dynamic flat detector CT perfusion and angiographic protocol for the diagnosis and triage of patients with acute ischemic stroke. In a qualitative comparison, the parameter maps and MIP/volume-rendering technique images compared well with MR imaging. In our opinion, this flat detector CT application may substitute for multisection CT imaging in selected patients with acute stroke so that in the future, patients with acute stroke may be directly referred to the angiography suite, thereby avoiding transportation and saving time.
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Dynamic properties of the alkaline vesicle population at hippocampal synapses - Röther, Mareike; Brauner, Jan M.; Ebert, Katrin; Welzel, Oliver; Jung, Jasmin; Bauereiß, Anna; Kornhuber, Johannes; Groemer, Teja W. (PLoS ONE, 2014)
In compensatory endocytosis, scission of vesicles from the plasma membrane to the cytoplasm is a prerequisite for intravesicular reacidification and accumulation of neurotransmitter molecules. Here, we provide time-resolved measurements of the dynamics of the alkaline vesicle population which appears upon endocytic retrieval. Using fast perfusion pH-cycling in live-cell microscopy, synapto-pHluorin expressing rat hippocampal neurons were electrically stimulated. We found that the relative size of the alkaline vesicle population depended significantly on the electrical stimulus size: With increasing number of action potentials the relative size of the alkaline vesicle population expanded. In contrast to that, increasing the stimulus frequency reduced the relative size of the population of alkaline vesicles. Measurement of the time constant for reacification and calculation of the time constant for endocytosis revealed that both time constants were variable with regard to the stimulus condition. Furthermore, we show that the dynamics of the alkaline vesicle population can be predicted by a simple mathematical model. In conclusion, here a novel methodical approach to analyze dynamic properties of alkaline vesicles is presented and validated as a convenient method for the detection of intracellular events. Using this method we show that the population of alkaline vesicles is highly dynamic and depends both on stimulus strength and frequency. Our results implicate that determination of the alkaline vesicle population size may provide new insights into the kinetics of endocytic retrieval.
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Dysfunction of spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia - Perez-Branguli, Francesc; Mishra, Himanshu Kumar; Prots, Iryna; Havlicek, Steven; Kohl, Zacharias; Saul, Domenica; Rummel, Christine; Dorca-Arevalo, Jonatan; Regensburger, Martin; Graef, Daniela; Sock, Elisabeth; Blasi, Juan; et al. (Human Molecular Genetics, 2014)
Hereditary spastic paraplegias are a group of inherited motor neuron diseases characterized by progressive paraparesis and spasticity. Mutations in the spastic paraplegia gene SPG11, encoding spatacsin, cause an autosomal-recessive disease trait; however, the precise knowledge about the role of spatacsin in neurons is very limited. We for the first time analyzed the expression and function of spatacsin in human forebrain neurons derived from human pluripotent stem cells including lines from two SPG11 patients and two controls. SPG11 patients'-derived neurons exhibited downregulation of specific axonal-related genes, decreased neurite complexity and accumulation of membranous bodies within axonal processes. Altogether, these data point towards axonal pathologies in human neurons with SPG11 mutations. To further corroborate spatacsin function, we investigated human pluripotent stem cell-derived neurons and mouse cortical neurons. In these cells, spatacsin was located in axons and dendrites. It colocalized with cytoskeletal and synaptic vesicle (SV) markers and was present in synaptosomes. Knockdown of spatacsin in mouse cortical neurons evidenced that the loss of function of spatacsin leads to axonal instability by downregulation of acetylated tubulin. Finally, time-lapse assays performed in SPG11 patients'-derived neurons and spatacsin-silenced mouse neurons highlighted a reduction in the anterograde vesicle trafficking indicative of impaired axonal transport. By employing SPG11 patient-derived forebrain neurons and mouse cortical neurons, this study provides the first evidence that SPG11 is implicated in axonal maintenance and cargo trafficking. Understanding the cellular functions of spatacsin will allow deciphering mechanisms of motor cortex dysfunction in autosomal-recessive hereditary spastic paraplegia.
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Dysregulated Retinoic Acid Signaling in the Pathogenesis of Pseudoexfoliation Syndrome - Zenkel, Matthias; Hoja, Ursula; Gießl, Andreas; Berner, Daniel; Hohberger, Bettina; Weller, Julia; König, Loretta; Huebner, Lisa; Ostermann, Thomas A.; Gusek-Schneider, Gabriele; Kruse, Friedrich; Pasutto, Francesca; et al. (International Journal of Molecular Sciences, 2022)
Pseudoexfoliation (PEX) syndrome, a stress-induced fibrotic matrix process, is the most common recognizable cause of open-angle glaucoma worldwide. The recent identification of PEX-associated gene variants uncovered the vitamin A metabolic pathway as a factor influencing the risk of disease. In this study, we analyzed the role of the retinoic acid (RA) signaling pathway in the PEX-associated matrix metabolism and evaluated its targeting as a potential candidate for an anti-fibrotic intervention. We provided evidence that decreased expression levels of RA pathway components and diminished RA signaling activity occur in an antagonistic crosstalk with TGF-beta 1/Smad signaling in ocular tissues and cells from PEX patients when compared with age-matched controls. Genetic and pharmacologic modes of RA pathway inhibition induced the expression and production of PEX-associated matrix components by disease-relevant cell culture models in vitro. Conversely, RA signaling pathway activation by natural and synthetic retinoids was able to suppress PEX-associated matrix production and formation of microfibrillar networks via antagonization of Smad-dependent TGF-beta 1 signaling. The findings indicate that deficient RA signaling in conjunction with hyperactivated TGF-beta 1 /Smad signaling is a driver of PEX-associated fibrosis, and that restoration of RA signaling may be a promising strategy for anti-fibrotic intervention in patients with PEX syndrome and glaucoma.
CRIS-Team WoS Importer:2022-06-24
Keywords: pseudoexfoliation syndrome; pseudoexfoliation glaucoma; retinol; retinoic acid; extracellular matrix; fibrosis; TGF-β1

Early Initiation of Anticoagulation with Direct Oral Anticoagulants in Patients after Transient Ischemic Attack or Ischemic Stroke - Macha, Kosmas; Volbers, Bastian; Bobinger, Tobias; Kurka, Natalia; Breuer, Lorenz; Huttner, Hagen; Schwab, Stefan; Köhrmann, Martin (Journal of Stroke and Cerebrovascular Diseases, 2016)
Direct oral anticoagulants (DOACs) are increasingly used for secondary prevention of cardioembolic stroke. While DOACs are associated with a long-term reduced risk of intracranial hemorrhage compared to vitamin K antagonists, pivotal trials avoided the very early period after stroke and few data exist on early initiation of DOAC therapy post stroke.We retrospectively analyzed data from our prospective database of all consecutive transient ischemic attack (TIA) or ischemic stroke patients with atrial fibrillation treated with DOACs during hospital stay. As per our institutional treatment algorithm for patients with cardioembolic ischemia DOACs are started immediately in TIA and minor stroke (group 1), within days 3-5 in patients with infarcts affecting one third or less of the middle cerebral artery, the anterior cerebral artery, or the posterior cerebral artery territories (group 2) as well as in infratentorial stroke (group 3) and after 1-2 weeks in patients with large infarcts (> 1/3 MCA territory, group 4). We investigated baseline characteristics, time to initiation of DOAC therapy after symptom onset, and hemorrhagic complications.In 243 included patients, administration of DOAC was initiated 40.5 hours (interquartile range [IQR] 23.0-65.5) after stroke onset in group 1 (n = 41) and after 76.7 hours (IQR 48.0-134.0), 108.4 hours (IQR 67.3-176.4), and 161.8 hours (IQR 153.9-593.8) in groups 2-4 (n = 170, 28, and 4), respectively. Two cases of asymptomatic intracranial hemorrhage (.8%) and 1 case of symptomatic intracranial hemorrhage (.4%) were observed, both in group 2.No severe safety issues were observed in early initiation of DOACs for secondary prevention after acute stroke in our in-patient cohort.
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Early intervention, treatment and rehabilitation of employees with common mental disorders by using psychotherapeutic consultation at work: study protocol of a randomised controlled multicentre trial (friaa project) - Weber, Jeannette; Angerer, Peter; Brenner, Lorena; Brezinski, Jolanda; Chrysanthou, Sophia; Erim, Yesim; Feisst, Manuel; Hansmann, Marieke; Hondong, Sinja; Kessemeier, Franziska Maria; Kilian, Reinhold; Klose, Christina; et al. (BMC Public Health, 2021)
BackgroundCommon mental disorders are one of the leading causes for sickness absence and early retirement due to reduced health. Furthermore, a treatment gap for common mental disorders has been described worldwide. Within this study, psychotherapeutic consultation at work defined as a tailored, module-based and work-related psychotherapeutic intervention will be applied to improve mental health care.MethodsThis study comprises a randomised controlled multicentre trial with 1:1 allocation to an intervention and control group. In total, 520 employees with common mental disorders shall be recruited from companies being located around five study centres in Germany. Besides care as usual, the intervention group will receive up to 17 sessions of psychotherapy. The first session will include basics diagnostics and medical indication of treatment and the second session will include work-related diagnostics. Then, participants of the intervention group may receive work-related psychotherapeutic consultation for up to ten sessions. Further psychotherapeutic consultation during return to work for up to five sessions will be offered where appropriate. The control group will receive care as usual and the first intervention session of basic diagnostics and medical indication of treatment. After enrolment to the study, participants will be followed up after nine (first follow-up) and fifteen (second follow-up) months. Self-reported days of sickness absence within the last 6 months at the second follow-up will be used as the primary outcome and self-efficacy at the second follow-up as the secondary outcome. Furthermore, a cost-benefit assessment related to costs of common mental disorders for social insurances and companies will be performed.DiscussionPsychotherapeutic consultation at work represents a low threshold care model aiming to overcome treatment gaps for employees with common mental disorders. If successfully implemented and evaluated, it might serve as a role model to the care of employees with common mental disorders and might be adopted in standard care in cooperation with sickness and pension insurances in Germany.Trial registrationThe friaa project was registered at the German Clinical Trial Register (DRKS) at 01.03.2021 (DRKS00023049): https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023049.
CRIS-Team WoS Importer:2021-07-23

Early prediction of delayed cerebral ischemia in subarachnoid hemorrhage based on quantitative EEG: A prospective study in adults - Gollwitzer, S.; Groemer, Teja W.; Rampp, Stefan; Hagge, Mareike; Olmes, D.; Huttner, Hagen; Schwab, Sibylle; Madzar, D.; Hopfengaertner, R.; Hamer, Hajo (Clinical Neurophysiology, 2015)
Delayed cerebral infarction (DCI) has a significant impact on mortality and morbidity of patients with subarachnoid hemorrhage (SAH). The aim of this study was to define quantitative EEG (qEEG) parameters for the early and reliable prediction of DCI and compare the validity and time course of qEEG to standard procedures.12 consecutive unselected SAH patients (8 female, mean age 52 years, Hunt-and-Hess grade I-IV) were prospectively examined. Continuous six channel EEG monitoring was started within 48 h after admission (mean duration 5.2 days; range: 2-12 days). All raw and unselected EEG signal underwent automated artifact rejection, Short Time Fast Fourier Transformation and a detrending procedure in order to analyze regional spectral power changes in different frequency bands. According to clinical standards, transcranial Doppler sonography (TCD) was performed at least on alternate days and repeat cerebral computer tomography (CCT) as needed.6 patients (50%) developed vasospasm/DCI. Decrease of ?40% in power persisting over ?5h in the alpha band and ?6h in the theta band marked the optimal cut-off to detect DCI (sensitivity 89%, specificity 77% for alpha). EEG changes preceded detection of vasospasm/DCI in standard procedures by 2.3d ays. Changes in the beta and delta band as well as in the alpha/delta ratio demonstrated lower correlation with imminent DCI.Focal reduction in alpha power may represent a valid, observer independent, non-invasive and continuous marker for vasospasm/DCI in SAH patients.qEEG indicates imminent ischemia earlier than established diagnostic tools, such as TCD.
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Early Tracheostomy Is Associated With Shorter Ventilation Time and Duration of ICU Stay in Patients With Myasthenic Crisis—A Multicenter Analysis - Angstwurm, Klemens; Vidal, Amelie; Stetefeld, Henning; Dohmen, Christian; Mergenthaler, Philipp; Kohler, Siegfried; Schönenberger, Silvia; Bösel, Julian; Neumann, Ursula; Lee, De Hyung; Gerner, Stefan; Huttner, Hagen; et al. (Journal of Intensive Care Medicine, 2020)
Background: Myasthenic crisis (MC) requiring mechanical ventilation (MV) is a rare and serious complication of myasthenia gravis. Here we analyzed the frequency of performed tracheostomies, risk factors correlating with a tracheostomy, as well as the impact of an early tracheostomy on ventilation time and ICU length of stay (LOS) in MC. Methods: Retrospective chart review on patients treated for MC in 12 German neurological departments between 2006 and 2015 to assess demographic/diagnostic data, rates and timing of tracheostomy and outcome. Results: In 107 out of 215 MC (49.8%), a tracheostomy was performed. Patients without tracheostomy were more likely to have an early-onset myasthenia gravis (27 [25.2%] vs 12 [11.5%], p = 0.01). Patients receiving a tracheostomy, however, were more frequently suffering from multiple comorbidities (20 [18.7%] vs 9 [8.3%], p = 0.03) and also the ventilation time (34.4 days ± 27.7 versus 7.9 ± 7.8, p < 0.0001) and ICU-LOS (34.8 days ± 25.5 versus 12.1 ± 8.0, p < 0.0001) was significantly longer than in non-tracheostomized patients. Demographics and characteristics of the course of the disease up to the crisis were not significantly different between patients with an early (within 10 days) compared to a late tracheostomy. However, an early tracheostomy correlated with a shorter duration of MV at ICU (26.2 days ± 18.1 versus 42.0 ± 33.1, p = 0.006), and ICU-LOS (26.2 days ± 14.6 versus 42.3 ± 33.0, p = 0.003). Conclusion: Half of the ventilated patients with MC required a tracheostomy. Poorer health condition before the crisis and late-onset MG were associated with a tracheostomy. An early tracheostomy (≤ day 10), however, was associated with a shorter duration of MV and ICU-LOS by 2 weeks.
CRIS-Team Scopus Importer:2020-12-04
Keywords: mechanical ventilation; myasthenic crisis; tracheostomy

Editorial: Identifying the isoform-specific roles of RAS paralogs in health and disease - Nakhaei-Rad, Saeideh; Fejtová, Anna (Frontiers in Cell and Developmental Biology, 2023)
CRIS-Team Scopus Importer:2023-05-05
Keywords: cancer; effector; isoform; paralog; RAS; rasopathy

Editorial Perspective: How should child psychologists and psychiatrists interpret FDA device approval? Caveat emptor - Arns, Martijn; Loo, Sandra K.; Sterman, M. Barry; Heinrich, Hartmut; Kuntsi, Jonna; Asherson, Philip; Banaschewski, Tobias; Brandeis, Daniel (The journal of child psychology and psychiatry, 2016)
Recently several new tests have received US Federal Drug Administration (FDA) marketing approval as aids in the diagnostic process for attention deficit hyperactivity disorder (ADHD), including the Neuropsychiatric electroencephalogram (EEG)-Based ADHD Assessment Aid (NEBA) Health test. The NEBA test relies upon an EEG-based measure, called the theta to beta ratio (TBR). Although this measure has yielded large differences between ADHD and non-ADHD groups in studies prior to 2009, recent studies and a meta-analysis could not replicate these findings. In this article, we have used the NEBA device as an exemplar for a discussion that distinguishes between FDA de novo marketing approval for a device and any claims that that device is empirically supported, scientifically validated with replicated findings. It is understood that the aims of each differ; however, for many, including the lay public as well as some mental health professionals, these terms may be confused and treated as though they are synonymous. With regard to the TBR measure, there is no reliable association or replication for its clinical usage in the ADHD diagnostic process. The recommendation for potential consumers of the NEBA Health test (as well as perhaps for other existing FDA-approved diagnostic tests) is caveat emptor (let the buyer beware!).
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EEG spectral analysis of attention in ADHD: implications for neurofeedback training? - Heinrich, Hartmut; Busch, Katrin; Studer, Petra; Erbe, Karlheinz; Moll, Gunther; Kratz, Oliver (Frontiers in Human Neuroscience, 2014)
In children with attention-deficit/hyperactivity disorder (ADHD), an increased theta/beta ratio in the resting EEG typically serves as a rationale to conduct theta/beta neurofeedback (NF) training. However, this finding is increasingly challenged. As NF may rather target an active than a passive state, we studied the EEG in a condition that requires attention.In children with ADHD of the DSM-IV combined type (ADHD-C; N = 15) and of the predominantly inattentive type (ADHD-I; N = 9) and in typically developing children (N = 19), EEG spectral analysis was conducted for segments during the attention network test (ANT) without processing of stimuli and overt behavior. Frontal (F3, Fz, F4), central (C3, Cz, C4) and parietal (P3, Pz, P4) electrodes were included in the statistical analysis. To investigate if EEG spectral parameters are related to performance measures, correlation coefficients were calculated.Particularly in the ADHD-C group, higher theta and alpha activity was found with the most prominent effect in the upper-theta/lower-alpha (5.5-10.5 Hz) range. In the ADHD-I group, a significantly higher theta/beta ratio was observed at single electrodes (F3, Fz) and a tendency for a higher theta/beta ratio when considering all electrodes (large effect size). Higher 5.5-10.5 Hz activity was associated with higher reaction time variability with the effect most prominent in the ADHD-C group. A higher theta/beta ratio was associated with higher reaction times, particularly in the ADHD-I group.(1) In an attention demanding period, children with ADHD are characterized by an underactivated state in the EEG with subtype-specific differences. (2) The functional relevance of related EEG parameters is indicated by associations with performance (reaction time) measures. (3) Findings provide a rationale for applying NF protocols targeting theta (and alpha) activity and the theta/beta ratio in subgroups of children with ADHD.
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Effectiveness of a Multimodal, Day Clinic Group-Based Treatment Program for Trauma-Related Disorders: Differential Therapy Outcome for Complex PTSD vs. Non-Complex Trauma-Related Disorders - Philipps, Anke; Silbermann, Andrea; Morawa, Eva; Stemmler, Mark; Erim, Yesim (Frontiers in Psychiatry, 2019)
Background: The effectiveness of the psychotherapeutic treatment of posttraumatic stress disorder is evidence-based and generally considered proven. However, the effectiveness of multimodal, group-based day clinic treatment programs has rarely been investigated. Moreover, there is no consensus in the literature concerning the question whether psychotherapeutic approaches for trauma-related disorders are also applicable for patients with complex PTSD (cPTSD). The aim of the study was to evaluate our multimodal group-based treatment program regarding a change of psychiatric burden, a change of protective factors, and possible differences in therapy outcome for patients with or without cPTSD. Methods: The group-based treatment for patients with trauma-related disorders was examined in 66 patients who filled out the following questionnaires in the first and in the last week of treatment: Essen Trauma Inventory (ETI), Screening for complex PTSD (SkPTBS), Patient Health Questionnaire—somatization module (PHQ-15), Beck Depression Inventory—Revised (BDI-II), Posttraumatic Growth Inventory (PTGI), and Questionnaire on social support (F-SozU). Results: The treatment was shown to significantly reduce depressive symptoms (p < 0.001, d = -0.536) and increase posttraumatic growth (New Possibilities: p = 0.004, d = 0.405; Personal Strength: p = 0.005, d = 0.414). For patients with cPTSD, depressive (p = 0.010, d = -0.63) as well as cPTSD symptoms (p = 0.020, d = -0.796) were significantly reduced; perceived social support was increased after day clinic treatment (p = 0.003, d = 0.61). Contrary to our expectations, somatoform symptoms were increased after therapy. Conclusions: The present work expands previous research by demonstrating that multimodal group-based, day clinic treatment is effective in the treatment of trauma-related disorders, also in their complex form.
CRIS-Team Scopus Importer:2019-12-03
Keywords: complex PTSD; day clinic treatment; depression; posttraumatic growth; posttraumatic stress disorder; social support; therapy outcome; trauma

Effectiveness of Inpatient Psychotherapy for Patients With and Without Migratory Background: Do They Benefit Equally? - Kobel, Friederike; Morawa, Eva; Erim, Yesim (Frontiers in Psychiatry, 2020)
Background: Research on the effectiveness of inpatient psychotherapy for migrant patients predominantly concludes that they have greater symptom severity at admission and benefit less from psychotherapy. This study aims to compare symptom severity and effects of psychotherapy regarding depression, somatoform disorders, anxiety disorders, and posttraumatic stress disorder (PTSD) in a sample of patients with and without migratory background (MB). Methods: Symptom severity of 263 patients (T0, pretreatment) and 256 patients (T1, posttreatment) was assessed using the Patient Health Questionnaire somatization module (PHQ-15), depression module (PHQ-9), and general anxiety disorder module (GAD-7), and the PTSD Checklist (PCL-5). Calculations were made for a completer sample and an intention-to-treat (ITT) sample. To investigate the effectiveness of psychotherapy, we calculated effect sizes (Cohen's d) and clinically significant changes using the reliable change index (RCI). Results: Patients with MB showed significantly higher symptom burden at admission for somatization (p = 0.025, d = 0.345) and posttraumatic symptoms (p = 0.008, d = 0.424) than patients without MB. At discharge, patients with MB reported significantly higher severity regarding all assessed symptoms (somatization: p = 0.001, d = 0.507; depression: p = 0.045, d = 0.313; anxiety: p = 0.012, d = 0.428; traumatization: p = 0.040, d = 0.329) compared with non-migrant patients. Patients without MB improved significantly regarding all assessed symptoms (somatization: p < 0.001, d = -0.304; depression: p < 0.001, d = -0.692; anxiety: p < 0.001, d = -0.605; posttraumatic symptoms: p < 0.001, d = -0.204). Patients with MB improved significantly concerning depression (p < 0.001, d = -0.649) and anxiety (p = 0.002, d = -0.441). Occurrence of comorbidity was high (87.1% had more than one psychiatric diagnosis). Neurotic, stress-related, and somatoform disorders (F4) and personality disorders (F6) were more frequent among patients with MB. Conclusions: Patients with MB showed higher symptom severity at admission. Our study demonstrated a significant reduction of depressive and anxiety symptoms among patients with MB receiving psychotherapy. Further research is needed to identify interventions that effectively improve somatization and posttraumatic stress for patients with MB, since these symptoms were not significantly reduced.
CRIS-Team Scopus Importer:2020-07-10
Keywords: anxiety disorder; depression; effectiveness; migrants; posttraumatic stress disorder; psychosomatic treatment; psychotherapy; somatoform disorder

Effect of a Multi-Dimensional and Inter-Sectoral Intervention on the Adherence of Psychiatric Patients - Pauly, Anne; Wolf, Carolin; Mayr, Andreas; Lenz, Bernd; Kornhuber, Johannes; Friedland, Kristina (PLoS ONE, 2015)
In psychiatry, hospital stays and transitions to the ambulatory sector are susceptible to major changes in drug therapy that lead to complex medication regimens and common non-adherence among psychiatric patients. A multi-dimensional and inter-sectoral intervention is hypothesized to improve the adherence of psychiatric patients to their pharmacotherapy.269 patients from a German university hospital were included in a prospective, open, clinical trial with consecutive control and intervention groups. Control patients (09/2012-03/2013) received usual care, whereas intervention patients (05/2013-12/2013) underwent a program to enhance adherence during their stay and up to three months after discharge. The program consisted of therapy simplification and individualized patient education (multi-dimensional component) during the stay and at discharge, as well as subsequent phone calls after discharge (inter-sectoral component). Adherence was measured by the "Medication Adherence Report Scale" (MARS) and the "Drug Attitude Inventory" (DAI).The improvement in the MARS score between admission and three months after discharge was 1.33 points (95% CI: 0.73-1.93) higher in the intervention group compared to controls. In addition, the DAI score improved 1.93 points (95% CI: 1.15-2.72) more for intervention patients.These two findings indicate significantly higher medication adherence following the investigated multi-dimensional and inter-sectoral program.German Clinical Trials Register DRKS00006358.
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Effect of Idelalisib on PKC beta/NF-kappa B regulation in stromal cells of chronic lymphocytic leukemia - Lutzny-Geier, Gloria; Handl, Sarah Annika; Von Heydebrand, F.; Wilke, J.; Kremer, Anna-Lena; Mackensen, Andreas; Völkl, Simon (ONCOLOGY RESEARCH AND TREATMENT, 2021)
CRIS-Team WoS Importer:2022-03-25

Effect of Minocycline on Depressive Symptoms in Patients with Treatment-Resistant Depression: A Randomized Clinical Trial - Hellmann-Regen, Julian; Clemens, Vera; Grozinger, Michael; Kornhuber, Johannes; Reif, Andreas; Prvulovic, David; Goya-Maldonado, Roberto; Wiltfang, Jens; Gruber, Oliver; Schule, Cornelius; Padberg, Frank; Ising, Marcus; et al. (JAMA Network Open, 2022)
Importance: Insufficient treatment response and resulting chronicity constitute a major problem in depressive disorders. Remission rates range as low as 15% to 40% and treatment-resistant depression (TRD) is associated with low-grade inflammation, suggesting anti-inflammatory interventions as a rational treatment strategy. Minocycline, which inhibits microglial activation, represents a promising repurposing candidate in the treatment of TRD. Objective: To determine whether 6 weeks of minocycline as add-on to antidepressant treatment as usual can significantly reduce depressive symptoms in patients with TRD. Design, Setting, and Participants: The study was conducted in Germany and designed as a multicenter double-blind randomized clinical trial (RCT) of 200 mg/d minocycline treatment over a course of 6 weeks with a 6-month follow-up. Participants were recruited from January 2016 to August 2020 at 9 university hospitals that served as study sites. Key inclusion criteria were a diagnosis of major depressive disorder (according to Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] criteria), severity of depressive symptoms on the Hamilton Depression Rating Scale (HAMD-17) greater than or equal to 16 points, aged 18 to 75 years, body mass index 18 to 40, Clinical Global Impression Scale (CGI-S) greater than or equal to 4, failure to adequately respond to an initial antidepressant standard medication as per Massachusetts General Hospital Antidepressant Treatment History Questionnaire, and stable medication for at least 2 weeks. A total of 258 patients were screened, of whom 173 were randomized and 168 were included into the intention-to-treat population. Statistical analysis was performed from April to November 2020. Interventions: Participants were randomized (1:1) to receive adjunct minocycline (200 mg/d) or placebo for 6 weeks. Main Outcomes and Measures: Primary outcome measure was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 6 analyzed by intention-to-treat mixed model repeated measures. Secondary outcome measures were response, remission, and various other clinical rating scales. Results: Of 173 eligible and randomized participants (84 randomized to minocycline and 89 randomized to placebo), 168 formed the intention-to-treat sample (79 [47.0%] were women, 89 [53.0%] were men, 159 [94.6%] were White, 9 [6.4%] were of other race and ethnicity, including Asian and unknown ethnicity), with 81 in the minocycline group and 87 in the placebo group. The mean (SD) age was 46.1 (13.1) years, and the mean (SD) MADRS score at baseline was 26.5 (5.0). There was no difference in rates of completion between the minocycline (83.3% [70 of 81]) and the placebo group (83.1% [74 of 87]). Minocycline treatment did not alter the course of depression severity compared with placebo as assessed by a decrease in MADRS scores over 6 weeks of treatment (1.46 [-1.04 to 3.96], P =.25). Minocycline treatment also exhibited no statistically significant effect on secondary outcomes. Conclusions and Relevance: In this large randomized clinical trial with minocycline at a dose of 200 mg/d added to antidepressant treatment as usual for 6 weeks, minocycline was well tolerated but not superior to placebo in reducing depressive symptoms in patients with TRD. The results of this RCT emphasize the unmet need for therapeutic approaches and predictive biomarkers in TRD. Trial Registration: EU Clinical Trials Register Number: EudraCT 2015-001456-29.
CRIS-Team Scopus Importer:2022-09-30

Effect of oral bolus versus sustained release application of nutrient solution on olfaction - Denzer-Lippmann, Melanie; Bachlechner, S.; Wielopolski, Jan; Fischer, M.; Büttner, Andrea; Dörfler, Arnd; Schöfl, Christof; Münch, Gerald; Kornhuber, Johannes; Thürauf, Norbert (2016)
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Effects of activin A on hippocampal network activity - Dahlmanns, Marc; Dahlmanns, Jana; Zheng, Fang; Alzheimer, Christian (ACTA PHYSIOLOGICA, 2019)
CRIS-Team WoS Importer:2019-11-12

Effects of an App-Based Mindfulness Intervention during Pregnancy on the Infant’s Prenatal Androgen Exposure: A Randomized Controlled Pilot Trial - Siegmann, Eva-Maria; Eichler, Anna; Buchholz, Verena Nadine; Gerlach, Jennifer; Pontones, Constanza; Titzmann, Adriana; Arnaud, Nicolas; Consortium, Imac Mind; Mühle, Christiane; Beckmann, Matthias; Fasching, Peter; Kratz, Oliver; et al. (Journal of Clinical Medicine, 2023)
Prenatal androgen exposure modulates the development of the brain, with lasting effects on its function and behavior over the infant’s life span. Environmental factors during pregnancy, in particular maternal stress, have been shown to influence the androgen load of the unborn child. We here addressed the research gap on whether a mindfulness intervention or a pregnancy education administered to pregnant women more affects the androgen exposure of the unborn child (quantified by the proxies of second-to-fourth digit length ratio (2D:4D) and anogenital distance assessed one year after delivery and at delivery, respectively). Moreover, we tested the mindfulness intervention’s effects on maternal perceived stress, anxiety, depressiveness, and mindfulness. Pregnant women (gestation weeks 8–14) were randomized to a 15-week app-based mindfulness-oriented intervention (N = 72) or a pregnancy education intervention (control condition; N = 74). The mindfulness-oriented group did not significantly differ from the pregnancy education group in infants’ 2D:4D or anogenital distance (partial η2 ≤ 0.01) or in maternal stress, anxiety, depressiveness, or mindfulness. However, the descriptive results indicate that across pregnancy, stress and anxiety decreased and mindfulness increased in both groups. Overall, this study did not show that the mindfulness intervention (relative to the pregnancy education) reduced the prenatal androgen exposure of the unborn children or improved the maternal outcomes significantly.
CRIS-Team Scopus Importer:2023-10-20
Keywords: digit ratio; mindfulness; prenatal programming

Effects of blue- and red-enriched light on attention and sleep in typically developing adolescents - Studer, Petra; Brucker, Judith M.; Haag, Cornelia; Van Doren, Jessica; Moll, Gunther; Heinrich, Hartmut; Kratz, Oliver (Physiology & behavior, 2019)
Differential effects of blue- and red-enriched light on attention and sleep have been primarily described in adults. In our cross-over study in typically developing adolescents (11-17 years old), we found attention enhancing effects of blue- compared to red-enriched light in the morning (high intensity of ca. 10001x, short duration: < 1 h) in two of three attention tasks: e.g. better performance in math tests and reduced reaction time variability in a computerized attention test. In our pilot study, actigraphy measures of sleep indicated slight benefits for red- compared to blue-enriched light in the evening: tendencies toward a lower number of phases with movement activity after sleep onset in the complete sample and shorter sleep onset latency in a subgroup with later evening exposure times. These findings point to the relevance of light concepts regarding attention and sleep in typically developing adolescents. Such concepts should be developed and tested further in attention demanding contexts (at school) and for therapeutic purposes in adolescents with impaired attention or impaired circadian rhythms.
CRIS-Team WoS Importer:2019-02-21

Effects of conditioned social fear on ethanol drinking and vice-versa in male mice - Kornhuber, Johannes; Huber, Sabine; Zoicas, Iulia (Psychopharmacology, 2019)
Rationale: Social anxiety disorder (SAD) is highly comorbid with alcohol use disorders, but the complex relationship between social fear and alcohol drinking is poorly understood due to the lack of specific animal models. Objectives: We investigated whether social fear alters ethanol drinking under both stress-free and stress-inducing conditions and whether ethanol alleviates symptoms of social fear. Methods: We used the social fear conditioning (SFC) paradigm, an animal model with face and predictive validity to SAD, to induce specific social fear in male CD1 mice, i.e., without comorbid depression or anxiety-like behavior. Plasma corticosterone (CORT) levels were measured in conditioned (SFC+) and unconditioned (SFC−) mice after exposure to non-social or social stimuli. Ethanol drinking was assessed in the two-bottle free-choice paradigm (1) for 16 days under stress-free conditions and (2) for 6 h after exposure to social stimuli. The effects of ethanol drinking and social fear on anxiety-like behavior and taste preference were tested in the elevated plus-maze and sucrose and quinine preference tests. Results: We show that exposure to social but not non-social stimuli leads to higher plasma CORT levels in SFC+ compared with SFC− mice. We also show that social fear decreases voluntary ethanol consumption under stress-free conditions, but increases ethanol consumption after exposure to social stimuli. Ethanol drinking, on the other hand, reduces social fear without altering anxiety-like behavior, locomotor activity, and taste preference. Conclusions: These results have important clinical connotations as they suggest that voluntary ethanol drinking might specifically reverse symptoms of social fear in a SAD-relevant animal model.
CRIS-Team Scopus Importer:2019-07-19
Keywords: Anxiety; CORT ELISA; Corticosterone; Ethanol drinking; Extinction; Locomotion; Social fear conditioning; Social investigation; Taste preference

Effects of Conventional Uric Acid-Lowering Therapy on Monosodium Urate Crystal Deposits - Ellmann, Hanna; Bayat, Sara; Guilhon de Araujo, Elizabeth; Manger, Bernhard; Kleyer, Arnd; Cavallaro, Alexander; Lell, Michael; Schenker, Hannah; Simon, David; Tascilar, Koray; Baraf, Herbert S. B.; Schett, Georg; et al. (Arthritis and Rheumatology, 2019)
Objective Few studies have systematically and quantitatively addressed the impact of urate-lowering therapy on monosodium urate (MSU) deposits. This study was undertaken to analyze the effect of lifestyle measures and conventional urate-lowering therapy on MSU deposits in patients with gout. Methods In this prospective study, subjects with gout according to the American College of Rheumatology/European League Against Rheumatism classification criteria and presence of MSU deposits seen on dual-energy computed tomography (DECT) scans received either lifestyle intervention or conventional urate-lowering therapy for a mean period of 18 months before a follow-up DECT scan. Detected MSU deposits were quantified by volumetric measurement and validated by semiquantitative scoring, and baseline and follow-up measurements were compared. Results Baseline and follow-up DECT scans were available for all 83 subjects. Six subjects discontinued treatment, and 77 subjects underwent a lifestyle intervention (n = 24) or were treated with allopurinol (n = 29), febuxostat (n = 22), or benzbromarone (n = 2) over the entire observation period. The mean serum uric acid (UA) level decreased from 7.2 to 5.8 mg/dl in the overall population. In patients who discontinued treatment, no change in MSU deposits or serum UA levels was observed. The burden of MSU deposits significantly decreased in patients undergoing lifestyle intervention (MSU volume P = 0.007; MSU score P = 0.001), and in patients treated with allopurinol (MSU volume and score P < 0.001) or febuxostat (MSU volume P < 0.001; MSU score P = 0.001). No significant decline in MSU deposits was noted in patients who discontinued treatment. Conclusion These data show that lifestyle intervention and xanthine oxidase inhibitors significantly decrease the MSU deposit burden. Hence, conventional gout therapy not only lowers serum UA levels, but also reduces pathologic MSU deposits.
CRIS-Team WoS Importer:2019-12-20

Effects of different isocaloric oral nutrient solutions on olfactory functioning, hunger and food craving - Thürauf, Norbert; Denzer-Lippmann, Melanie; Bachlechner, Stephan; Wielopolski, Jan; Fischer, Marie; Büttner, Andrea; Dörfler, Arnd; Schöfl, Christof; Münch, Gerald; Kornhuber, Johannes (2017)
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Effects of family risk on early attachment security: Gender-specific susceptibility and mediation by parenting behavior - Gerlach, Jennifer; Fößel, Judith M.; Vierhaus, Marc; Sann, Alexandra; Eickhorst, Andreas; Zimmermann, Peter; Spangler, Gottfried (Developmental Child Welfare, 2022)
Growing up in high-risk environments is detrimental to children’s development of attachment security. Parenting behavior is hypothesized to be the mechanism through which risks exert their influence. However, risk influences can vary between individuals by gender. Aim of this study was to explore specific pathways of family risk on early attachment security and additionally examine the transmission via parenting behavior. The sample consisted of 197 children and their primary caregivers. Children’s age ranged between 10 and 21 months (M = 15.25, SD = 3.59). Data assessment included 21 distal and proximal family risk factors, children’s attachment security, and parental responsivity and supportive presence. Whereas distal risk factors had an adverse effect only on girls’ attachment security, proximal risks negatively affected only boys’ attachment security. Additionally, patterns of risk factors occurring in our sample were analyzed using an exploratory principal component analysis. Regardless of the child’s gender, a low socio-economic status was negatively related to attachment security of all children. Migration and crowding and a high emotional load of the primary caregiver both negatively predicted girls’ but not boys’ attachment security. However, the attachment security of boys was affected by a negative family climate. Most of the adverse risk effects on attachment security were mediated by parental responsivity and supportive presence so that the transmission of risk occurs through parenting behavior. Results revealed a different susceptibility of family risks for girls and boys. The consideration of a gender-sensitive approach in developmental psychopathology and interventions of developmental child welfare services is recommended.
CRIS-Team Scopus Importer:2022-04-15
Keywords: attachment; gender effects; infancy; risk; sensitivity; toddlerhood

Effects of Hippocampal Sparing Radiotherapy on Brain Microstructure—A Diffusion Tensor Imaging Analysis - Dinkel, Johannes; Lahmer, Godehard; Mennecke, Angelika; Hock, Stefan; Richter-Schmidinger, Tanja; Fietkau, Rainer; Distel, Luitpold; Putz, Florian; Dörfler, Arnd; Schmidt, Manuel (Brain Sciences, 2022)
Hippocampal-sparing radiotherapy (HSR) is a promising approach to alleviate cognitive side effects following cranial radiotherapy. Microstructural brain changes after irradiation have been demonstrated using Diffusion Tensor Imaging (DTI). However, evidence is conflicting for certain parameters and anatomic structures. This study examines the effects of radiation on white matter and hippocampal microstructure using DTI and evaluates whether these may be mitigated using HSR. A total of 35 tumor patients undergoing a prospective randomized controlled trial receiving either conventional or HSR underwent DTI before as well as 6, 12, 18, 24, and 30 (±3) months after radiotherapy. Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD), and Radial Diffusivity (RD) were measured in the hippocampus (CA), temporal, and frontal lobe white matter (TL, FL), and corpus callosum (CC). Longitudinal analysis was performed using linear mixed models. Analysis of the entire patient collective demonstrated an overall FACC decrease and RDCC increase compared to baseline in all follow-ups; ADCC decreased after 6 months, and MDCC increased after 12 months (p ≤ 0.001, 0.001, 0.007, 0.018). ADTL decreased after 24 and 30 months (p ≤ 0.004, 0.009). Hippocampal FA increased after 6 and 12 months, driven by a distinct increase in ADCA and MDCA, with RDCA not increasing until 30 months after radiotherapy (p ≤ 0.011, 0.039, 0.005, 0.040, 0.019). Mean radiation dose correlated positively with hippocampal FA (p < 0.001). These findings may indicate complex pathophysiological changes in cerebral microstructures after radiation, insufficiently explained by conventional DTI models. Hippocampal microstructure differed between patients undergoing HSR and conventional cranial radiotherapy after 6 months with a higher ADCA in the HSR subgroup (p ≤ 0.034).
CRIS-Team Scopus Importer:2022-07-22
Keywords: cognitive impairment; cranial radiotherapy; diffusion tensor imaging; fractional anisotropy; hippocampal sparing radiotherapy; hippocampus

Effects of In utero environment and maternal behavior on neuroendocrine and behavioral alterations in a mouse model of prenatal trauma - Golub, Yulia; Canneva, F.; Funke, R.; Frey, Silke; Distler, Jörg; von Hörsten, Stephan; Freitag, C. M.; Kratz, Oliver; Moll, Gunther; Solati, Jalal (Developmental Neurobiology, 2016)
Maternal posttraumatic stress disorder (PTSD) following trauma exposure during pregnancy is associated with an increased risk of affective disorders in children. To investigate the mechanisms by which prenatal trauma and/or maternal PTSD affect brain development and behavior we established a mouse model of prenatal traumatic (PT) experience based on the application of an electric foot shock to C57Bl/6N female mice on the gestational day 12 during their pregnancy. The model is based on a previously validated animal model of PTSD. We found high anxiety levels and poor maternal care along with reduced serum prolactin and increased corticosterone levels in dams following maternal trauma (MT). PT-pups were born smaller and stayed smaller throughout their life. We show increased time and frequency of ultrasonic calls in PT-pups when separated from the mothers on the postnatal day (PND) 9. Cross-fostering experiments reveal lower anxiety levels in PT pups raised by healthy mothers as compared to trauma-naive pups raised by MT-dams. Importantly, the combination of prenatal trauma and being raised by a traumatized mother leads to: (1) the highest corticosterone levels in pups, (2) longest USV-call time and (3) highest anxiety levels in comparison to other experimental groups. Our data indicates a distinct change in maternal care following MT which is possibly associated with trauma-induced decrease in prolactin levels. Furthermore, we show that maternal behavior is crucial for the development of the offspring anxiety and specific aspects in maternal care overwrite to a significant extend the effects of in utero and postnatal environment. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1254-1265, 2016.
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Effects of neurofeedback on the dysregulation profile in children with ADHD: SCP NF meets SDQ-DP - A retrospective analysis - Heinrich, Hartmut; Gevensleben, Holger; Becker, Andreas; Rothenberger, Aribert (Psychological medicine, 2019)
BackgroundAs children with attention-deficit/hyperactivity disorder (ADHD) usually show psychopathological signs beyond their core symptoms (e.g. elevated scores of the dysregulation profile (DP) in 30-40%), treatments with a broader approach to self-regulation skills may be supportive. Neurofeedback (NF) may reflect such an option. Aim of the present analysis was to compare the effects of slow cortical potential (SCP) NF and /β NF on the DP using data from a previous trial.MethodsThirty children with ADHD (aged 8-12 years) and a DP score in the Strengths and Difficulties Questionnaire (SDQ-DP) 3/4 3 were included. NF treatment consisted of one block of SCP NF and one block of /β NF (18 units per block) allowing an intraindividual comparison. Effects of the NF protocols were also contrasted to a control group (n = 18) that completed an attention skills training (between-group analysis).ResultsRegarding the SDQ-DP, SCP NF was superior to /β NF and the control condition. Effects of SCP NF and /β NF on ADHD symptom severity were not significantly different. The SDQ-DP score did not correlate with EEG-related measures previously found to be predictors for SCP NF on ADHD symptoms.ConclusionsSCP NF may reflect a more general approach to improve cognitive, emotional and behavioral self-regulation skills. If confirmed in a larger sample, the SDQ-DP score could be used as an indication criterion and contribute to the individualization of NF in ADHD. Overall, the differential effect provides further evidence for the specificity of NF effects.
CRIS-Team Scopus Importer:2019-12-13
Keywords: Attention-deficit/hyperactivity disorder (ADHD); dysregulation profile; neurofeedback; slow cortical potentials (SCPs); Strengths and Difficulties Questionnaire (SDQ)

Effects of neurofeedback on the dysregulation profile in children with ADHD: SCP NF meets SDQ-DP - a retrospective analysis - Heinrich, Hartmut; Gevensleben, Holger; Becker, Andreas; Rothenberger, Aribert (Psychological Medicine, 2020)
BACKGROUND: As children with attention-deficit/hyperactivity disorder (ADHD) usually show psychopathological signs beyond their core symptoms (e.g. elevated scores of the dysregulation profile (DP) in 30-40%), treatments with a broader approach to self-regulation skills may be supportive. Neurofeedback (NF) may reflect such an option. Aim of the present analysis was to compare the effects of slow cortical potential (SCP) NF and θ/β NF on the DP using data from a previous trial. METHODS: Thirty children with ADHD (aged 8-12 years) and a DP score in the Strengths and Difficulties Questionnaire (SDQ-DP) ⩾ 3 were included. NF treatment consisted of one block of SCP NF and one block of θ/β NF (18 units per block) allowing an intraindividual comparison. Effects of the NF protocols were also contrasted to a control group (n = 18) that completed an attention skills training (between-group analysis). RESULTS: Regarding the SDQ-DP, SCP NF was superior to θ/β NF and the control condition. Effects of SCP NF and θ/β NF on ADHD symptom severity were not significantly different. The SDQ-DP score did not correlate with EEG-related measures previously found to be predictors for SCP NF on ADHD symptoms. CONCLUSIONS: SCP NF may reflect a more general approach to improve cognitive, emotional and behavioral self-regulation skills. If confirmed in a larger sample, the SDQ-DP score could be used as an indication criterion and contribute to the individualization of NF in ADHD. Overall, the differential effect provides further evidence for the specificity of NF effects.
EVALuna2:211386

Effects of olanzapine and clozapine upon pulse rate variability - Mück-Weymann, Michael; Rechlin, Thomas; Ehrengut, Franz; Rauh, Robert; Acker, Jens; Dittmann, Ralf W.; Czekalla, Jörg; Joraschky, Peter; Musselman, Dominique (Depression and Anxiety, 2002)
Based upon their in vitro receptor binding profiles, the atypical antipsychotics clozapine and olanzapine exhibit cholinergic receptor binding of similar potency. Data comparing the in vivo anticholinergic effects, however, of these neuroleptics upon neurocardiac control are sparse. The goal of this study was to compare the in vivo effects of clozapine and olanzapine upon neurocardiac control by assessment of the pulse rate variability (PRV) in schizophrenic patients and healthy controls. Twenty patients with schizophrenia (according to DSM-III-R criteria) treated with either clozapine (100-600 mg/day) or olanzapine (10-20 mg/day), and ten healthy controls, were recruited into the study. PRV was assessed by continuously recording the skin blood volume in the fingertip of the second digit under resting conditions and PRV parameters were calculated. When significant differences in PRV parameters between the patients and controls were detected by Kruskal-Wallis tests, Mann-Whitney tests were used to test for group differences between the olanzapine- and clozapine-treated patients. In comparison to the healthy controls, the PRV parameters of the clozapine- and olanzapine-treated schizophrenic patients were significantly reduced. Indeed the reduction of PRV was significantly greater in the clozapine-treated group compared to the olanzapine-treated group (P<0.05). Compared to the controls, only the clozapine-treated patients showed a significantly diminished low-frequency (LF)/high frequency (HF)-ratio, a PRV parameter reflecting sympatho-vagal balance. The significantly greater reductions in PRV parameters of the clozapine-treated compared to olanzapine-treated patients may be caused by clozapine's higher affinity for α1-adrenergic receptors in vivo compared with olanzapine. The similar LF/HF ratios of the healthy controls and olanzapine-treated patients suggests that the sympathetic-parasympathetic modulation of PRV remains relatively unchanged even during olanzapine treatment. © 2002 Wiley-Liss, Inc.
Created from Fastlane, Scopus look-up
Keywords: Atypical antipsychotics; Autonomic neuropathy; Clozapine; Heart rate variability; Neurocardiac control; Olanzapine; Pulse rate variability

Effects of prenatal alcohol consumption on cognitive development and ADHD-related behaviour in primary-school age: a multilevel study based on meconium ethyl glucuronide - Eichler, Anna; Hudler, Linda; Grunitz, Juliane; Grimm, Jennifer; Raabe, Eva; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kratz, Oliver; Moll, Gunther; Kornhuber, Johannes; Heinrich, Hartmut (The journal of child psychology and psychiatry, 2018)
BACKGROUND: Alcohol intake during pregnancy is considered to be a risk factor for child development. Child biomarkers of intrauterine alcohol exposure have been rarely studied. We investigated whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with cognitive development, ADHD-related behaviour and neurophysiological markers of attention and executive control of children at primary-school age. METHODS: Mothers provided self-report on prenatal alcohol consumption during their 3rd trimester. Meconium samples were collected at birth. A total of 44 children with a meconium EtG above the detection limit (≥10 ng/g) and 44 nonexposed matched controls were compared. A second threshold (≥154 ng/g) was applied to study the dose effects. When children reached primary-school age, mothers rated ADHD-related behaviour, child cognitive development was measured using an IQ test battery, and event-related potentials were recorded during a cued go/nogo task. RESULTS: Children in both EtG-positive groups allocated fewer attentional resources than controls to the go/nogo task (reduced P3 component in go-trials). Children with a meconium EtG above 154 ng/g were also found to have an IQ that was six points lower than the other groups. Within the EtG ≥ 154 ng/g group, there was a positive correlation between EtG value and ADHD-related behaviour. These significant effects were not observed in relation to the maternal self-report data. CONCLUSIONS: Associations between EtG and cognitive deficits, attentional resource capacity and ADHD-related behaviour could be documented with effects that were partially dose-dependent. In addition to maternal self-reports, this biomarker of intrauterine alcohol exposure may be considered as a predictor of child development.
EVALuna2:33526

Effects of prenatal alcohol exposition on cognitive outcomes in childhood and youth: a longitudinal analysis based on meconium ethyl glucuronide. - Roetner, Jakob; Van Doren, Jessica; Maschke, Janina; Kulke, Louisa; Pontones, Constanza; Fasching, Peter A.; Beckmann, Matthias W.; Lenz, Bernd; Kratz, Oliver; Moll, Gunther; Kornhuber, Johannes; Eichler, Anna (European archives of psychiatry and clinical neuroscience, 2024)
BACKGROUND: Prenatal alcohol exposure (PAE) has been linked to severe, adverse child outcomes. However, little is known regarding subclinical outcomes of low/moderate PAE and its longitudinal consequences, especially regarding neurophysiological and neurocognitive development. A newborn biomarker of PAE, meconium ethyl glucuronide (EtG), has been shown to predict cognitive impairments in primary-school-aged children. The current study investigated the ongoing effects of subclinical PAE in adolescence. METHODS: A sample of n = 96 mother-child dyads of the FRAMES/FRANCES cohort were classified into PAE/no PAE using EtG with a 10 ng/g cutoff. Mothers were recruited during pregnancy and children were assessed during primary-school age (M = 7.57, SD = 0.65, range: 6.00-9.92 years) and adolescence (M = 13.26, SD = 0.31, range: 12.79-14.20 years) on three levels: clinical (ADHD rating), neuropsychological (IQ score and performance in a go/nogo task), and neurophysiological (analysis of P3 event-related potentials (ERP) during said go/nogo task). Developmental outcomes and courses following PAE were assessed using rmANCOVAs, controlling for relevant confounders (socioeconomic status (SES), birth weight, and maternal psychopathology). RESULTS: Neurophysiological impairments emerged for exposed children in the form of diminished attentional resource recruiting in childhood and adolescence (reduced go-P3 amplitudes) with no differences in performance. Neuropsychological testing showed a reduced IQ score for both time points with dose-dependent effects in childhood. Clinical ADHD symptoms were not significantly affected. CONCLUSION: Subclinical PAE, as determined by meconium EtG, has negative developmental consequences on cognitive function that persist from childhood to adolescence. These findings suggest that there is no safe limit for alcohol consumption during pregnancy and that more thorough screening of alcohol consumption during pregnancy is necessary for early identification and treatment of at-risk children.
EVALuna2:538816

Effects of the COVID-19 Restrictions on Eating Behaviour and Eating Disorder Symptomology in Female Adolescents - Muth, Lois; Leven, Karl-Heinz; Moll, Gunther; Kratz, Oliver; Horndasch, Stefanie (International Journal of Environmental Research and Public Health, 2022)
Confinement due to the COVID-19 pandemic imposes a burden on adolescents worldwide and may seriously impact patients with an eating disorder (ED). The current FRanconian Anorexia Nervosa during COVID-19 (FRANCO) study explored (1) perceived change of depressive and ED symptomology during lockdown, (2) the role of social media, and (3) coping strategies of anorexia nervosa (AN) patients and clinical as well as healthy comparison groups. From June 2021 to September 2021, 222 female adolescents (19 with AN, 20 with depression, 45 with a self-reported psychiatric disorder (SRPD), and 138 controls) aged 11.2 to 18.9 years completed a one-time anonymous survey retrospectively reporting back on ED and depressive symptomology before and during the pandemic, the impact of social media, and coping strategies. A reduced quality of life (QoL) due to confinement was observed in almost half of female adolescents. All groups reported a significant perceived increase of disordered eating, overeating, anxiety, and depressive symptoms and emotion-regulation problems. In AN patients, significantly higher percentual deterioration of disordered eating and anxiety and depressive symptoms was found. For controls, a younger age and higher susceptibility of the sociocultural body image significantly correlated with increased disordered eating. Large-scale media literacy interventions are recommended.
CRIS-Team Scopus Importer:2022-08-12
Keywords: adolescents; anorexia nervosa; COVID-19 pandemic; depression

Efficacy and long-term tuning parameters of vagus nerve stimulation in long-term treated depressive patients - Mueller, Helge H. O.; Luecke, Caroline; Moeller, Sebastian; Philipsen, Alexandra; Sperling, Wolfgang (Journal of Clinical Neuroscience, 2017)
Vagus nerve stimulation (VNS) is a promising neurostimulation tool for the treatment of treatment-resistant depression. Here, we report the effects of positive remission rates and tuning parameters in a group of 18 (6 female, 12 male, mean age 54) long-term treated patients. Treatment varied between 3 and 200months (mean 104.9months). Mean stimulation intensity was 1.46mA, ranging from 0.5 to 2.0mA and high-frequency stimulation of 20-25Hz (mean 23.61Hz). The remission rates in our study population clearly indicate ongoing positive effects of VNS and highlight stimulation tunings between 0.5 and 2.0mA and 20-25Hz as best dosage for achieving remittance in long-term treatment of VNS.
EVALuna2:33574

Efficacy and safety of combined intraventricular fibrinolysis with lumbar drainage for prevention of permanent shunt dependency after intracerebral hemorrhage with severe ventricular involvement: A randomized trial and individual patient data meta-analysi - Staykov, Dimitre; Kuramatsu, Joji; Bardutzky, Juergen; Volbers, Bastian; Gerner, Stefan; Kloska, Stephan; Dörfler, Arnd; Schwab, Stefan; Huttner, Hagen (Annals of Neurology, 2017)
Intraventricular hemorrhage (IVH) is a negative prognostic factor in intracerebral hemorrhage (ICH) and is associated with permanent shunt dependency in a substantial proportion of patients post-ICH. IVH treatment by intraventricular fibrinolysis (IVF) was recently linked to reduced mortality rates in the CLEAR III study and IVF represents a safe and effective strategy to hasten clot resolution that may reduce shunt rates. Additionally, promising results from observational studies reported reductions in shunt dependency for a combined treatment approach of IVF plus lumbar drains (LDs). The present randomized, controlled trial investigated efficacy and safety of a combined strategy-IVF plus LD versus IVF alone-on shunt dependency in patients with ICH and severe IVH.This randomized, open-label, parallel-group study included patients aged 18 to 85 years, prehospital modified Rankin Scale <=3, ICH volume < 60ml, Glasgow Coma Scale of <9, and severe IVH with tamponade of the third and fourth ventricles requiring placement of external ventricular drainage (EVD). Over a 3-year recruitment period, patients were allocated to either standard treatment (control group receiving IVF consisting of 1mg of recombinant human tissue plasminogen activator every 8 hours until clot clearance of third and fourth ventricles) or a combined treatment approach of IVF and-upon clot clearance of third and fourth ventricles-subsequent placement of an LD for drainage of cerebrospinal fluid (CSF; intervention group). The primary endpoint consisted of permanent shunt placement indicated after a total of three unsuccessful EVD clamping attempts or need for CSF drainage longer than 14 days in both groups. Secondary endpoints included IVF- and LD-related safety, such as bleeding or infections, and functional outcome at 90 and 180 days. Conducted endpoint analyses used individual patient data meta-analyses. The study was registered at clinicaltrials.gov (NCT01041950).The trial was stopped upon predefined interim analysis after 30 patients because of significant efficacy of tested intervention. The primary endpoint was analyzed without dropouts and was reached in 43% (7 of 16) of the control group versus 0% (0 of 14) of the intervention group (p = 0.007). Meta-analyses were based on overall 97 patients, 45 patients receiving IVF plus LD versus 42 with IVF only. Meta-analyses on shunt dependency showed an absolute risk reduction of 24% for the intervention (LD, 2.2% [1 of 45] vs no-LD, 26.2% [11 of 42]; odds ratio [OR] = 0.062; confidence interval [CI], 0.011-0.361; p = 0.002). Secondary endpoints did not show significant differences for CSF infections (OR = 0.869;CI, 0.445-1.695; p = 0.680) and functional outcome at 90 days (OR = 0.478; CI, 0.190-1.201; p = 0.116), yet bleeding complications were significantly reduced in favor of the intervention (OR = 0.401; CI, 0.302-0.532; p < 0.001).The present trial and individual patient data meta-analyses provide evidence that, in patients with severe IVH, as compared to IVF alone, a combined approach of IVF plus LD treatment is feasible and safe and significantly reduces rates of permanent shunt dependency for aresorptive hydrocephalus post-ICH. ANN NEUROL 2017;81:93-103.
EVALuna2:22478

Efficacy, safety, and immunosuppressant adherence in stable liver transplant patients converted from a twice-daily tacrolimus-based regimen to once-daily tacrolimus extended-release formulation - Beckebaum, Susanne; Iacob, Speranta; Sweid, Dani; Sotiropoulos, Georgios C.; Saner, F. H.; Kaiser, Gernot; Radtke, Arnold; Klein, Christian-Georg; Erim, Yesim; de Geest, Sabine; Paul, Andreas; Gerken, Guido; et al. (Transplant International, 2011)
Keywords: adherence; efficacy; extended-release tacrolimus; immunosuppression; safety

EFhd2/Swiprosin-1 is a common genetic determinator for sensation-seeking/low anxiety and alcohol addiction - Mielenz, Dirk; Reichel, Martin; Jia, T.; Quinlan, E. B.; Stöckl, Thomas; Mettang, M.; Zilske, Daniel; Kirmizi Alsan, Elif; Schoenberger, P.; Praetner, M.; Huber, Sabine; Amato, Davide; et al. (Molecular Psychiatry, 2017)
In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show a high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in the control of alcohol addiction-associated behaviours. EFhd2 knockout (KO) mice drink more alcohol than controls and spontaneously escalate their consumption. This coincided with a sensation-seeking and low-anxiety phenotype. A reversal of the behavioural phenotype with β-carboline, an anxiogenic inverse benzodiazepine receptor agonist, normalized alcohol preference in EFhd2 KO mice, demonstrating an EFhd2-driven relationship between personality traits and alcohol preference. These findings were confirmed in a human sample where we observed a positive association of the EFhd2 single-nucleotide polymorphism rs112146896 with lifetime drinking and a negative association with anxiety in healthy adolescents. The lack of EFhd2 reduced extracellular dopamine levels in the brain, but enhanced responses to alcohol. In confirmation, gene expression analysis revealed reduced tyrosine hydroxylase expression and the regulation of genes involved in cortex development, Eomes and Pax6, in EFhd2 KO cortices. These findings were corroborated in Xenopus tadpoles by EFhd2 knockdown. Magnetic resonance imaging (MRI) in mice showed that a lack of EFhd2 reduces cortical volume in adults. Moreover, human MRI confirmed the negative association between lifetime alcohol drinking and superior frontal gyrus volume. We propose that EFhd2 is a conserved resilience factor against alcohol consumption and its escalation, working through Pax6/Eomes. Reduced EFhd2 function induces high-risk personality traits of sensation-seeking/low anxiety associated with enhanced alcohol consumption, which may be related to cortex function.
EVALuna2:4036

EFHD2/SWIPROSIN-1 IS A CONSERVED RESILIENCE FACTOR AGAINST ALCOHOL DRINKING ESCALATION - Müller, Christian P.; Reichel, Martin; Jia, T.; Quinlan, E. B.; Schambony, Alexandra; Bäuerle, Tobias; Eulenburg, Volker; Lourdusamy, A.; Schumann, G.; Mielenz, Dirk (2018)
EVALuna2:35243

[egePan-VOICE study on the psychosocial burden of the Covid-19 pandemic among - medical technical assistants]. - Beschoner, Petra; Jarczok, Marc N.; Kempf, Maximilian; Weimer, Katja; Geiser, Franziska; Hiebel, Nina; Erim, Yesim; Morawa, Eva; Steudte-Schmiedgen, Susann; Albus, Christian; Jerg-Bretzke, Lucia (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2022)
egePan-VOICE study on the psychosocial burden of the Covid-19 pandemic among - medical technical assistants Objectives: The Covid-19 pandemic is associated with increased demands on healthcare workers. A previously neglected occupational group is medical technical assistants (MTA). The aim is therefore to identify stress factors among MTA in Germany during the pandemic. Methods: A cross-sectional online survey of medical staff was conducted in spring 2020 (N = 8088). Results: N = 1483 records of MTA were analyzed. Retrospectively, the stress increased under the pandemic, and 60.1 % of MTA suffered from work stress (ERI). Staff shortages and extra work were associated with an increase in work stress. Problems of work-life balance and contact with contaminated material/infected persons favored stressful experiences. Conclusions: Some working conditions in the pandemic pose a potential health risk to MTA. It seems necessary to create improvements in the general conditions that enable healthily and effective work.
EVALuna2:500289

Einflussfaktoren auf die Pflegebelastung der Angehörigen von Menschen mit Demenz: der Bayerische Demenz Survey (BayDem) - Dietzel, Nikolas; Karrer, Linda; Wolff, Franziska; Kratzer, André; Hess, Manuela; Grässel, Elmar; Kolominsky-Rabas, Peter (Gesundheitswesen, 2020)
Background Dementia is an age-specific disease with increasing care needs over the course of the disease. Care is predominantly conducted by caregivers. Caregiver burden is a core criterion for the evaluation of the care situation. The aims of this examination are to identify predictors of caregiver burden and to analyze the course of the caregiver burden over a 12 months period. Methods The Bavarian Dementia Survey (BayDem) is a supra-regional, longitudinal study carried out at 3 different sites in Bavaria, Germany. Participants were people with dementia (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 statistical analysis, a multiple regression as well as a mixed ANOVA (Analysis of Variance) and repeated measures ANOVAs were used. Results In this analysis, 295 pwd and 276 caregivers were studied. Key factors influencing caregiver burden were gender of the pwd, behavioral and psychological symptoms and a decline of everyday functioning of the pwd as well as gender of the informal caregivers, their relation to the pwd and if they live at the same household as the pwd. Analysis showed a significant main effect of time over the course of the caregiver burden. Conclusion A permanent high caregiver burden can cause health problems for the caregivers. However, caregivers can be supported according to the specific factors of the caregiver burden. One approach in order to support caregivers could be a combination of pharmacological and non-pharmacological interventions for the treatment of disease-specific symptoms and an empowerment as well as the provision of support services for the caregivers. Furthermore, tailored services for specific target groups can be meaningful.
CRIS-Team Scopus Importer:2020-02-04
Keywords: Burden Scale for Family Caregivers (BSFC-s); caregiver burden; course; dementia; informal caregivers; predictors