von Mojtaba Oraki Kohshour ; Eva C. Schulte ; Urs Heilbronner ; Monika Budde ; Janos L. Kalman ; Fanny Senner ; Maria Heilbronner ; Daniela Reich-Erkelenz ; Sabrina K. Schaupp ; Thomas Vogl ; Kristina Adorjan ; Ion-George Anghelescu ; Volker Arolt ; Bernhardt T. Baune ; Udo Dannlowski ; Detlef Dietrich ; Andreas Fallgatter ; Christian Figge ; Markus Jäger ; Fabian U. Lang ; Georg Juckel ; Carsten Konrad ; Jens Reimer ; Eva Z. Reininghaus ; Max Schmauß ; Carsten Spitzer ; Martin von Hagen ; Jens Wiltfang ; Jörg Zimmermann ; Till F. M. Andlauer ; Markus Maria Nöthen ; Franziska Degenhardt ; Andreas J. Forstner ; Marcella Rietschel ; Stephanie Witt ; Andre Fischer ; Peter Falkai ; Sergi Papiol ; Thomas G. Schulze
Background - Mitochondria generate energy through oxidative phosphorylation (OXPHOS). The function of key OXPHOS proteins can be altered by variation in mitochondria-related genes, which may increase the risk of mental illness. We investigated the association of mitochondria-related genes and their genetic risk burden with cognitive performance. - Methods - We leveraged cross-sectional data from 1320 individuals with a severe psychiatric disorder and 466 neurotypical individuals from the PsyCourse Study. The cognitive tests analyzed were the Trail-Making Test, Verbal Digit Span Test, Digit-Symbol Test, and Multiple Choice Vocabulary Intelligence Test. Association analyses between the cognitive tests, and single-nucleotide polymorphisms (SNPs) mapped to mitochondria-related genes, and their polygenic risk score (PRS) for schizophrenia (SCZ) were performed with PLINK 1.9 and R program. - Results - We found a significant association (FDR-adjusted p < 0.05) in the Cytochrome C Oxidase Assembly Factor 8 (COA8) gene locus of the OXPHOS pathway with the Verbal Digit Span (forward) test. Mitochondrial PRS was not significantly associated with any of the cognitive tests. - Limitations - Moderate statistical power due to relatively small sample size. - Conclusions - COA8 encodes a poorly characterized mitochondrial protein involved in apoptosis. Here, this gene was associated with the Verbal Digit Span (forward) test, which evaluates short-term memory. Our results warrant replication and may lead to better understanding of cognitive impairment in mental disorders.
Journal of affective disorders Amsterdam [u.a.] : Elsevier Science, 1979 325(2023) vom: Jan., Seite 1-6 Online-Ressource
Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium’s possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response — defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10−12, R2 = 1.9%) and continuous (P = 6.4 × 10−9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10−4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
Molecular psychiatry London : Macmillan, 1997 (2023), Seite 1-11 Online-Ressource
GMS Medizinische Informatik, Biometrie und Epidemiologie [Köln] : Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS), 2005 18(2022), 2, Artikel-ID Doc06, Seite 1-17 Online-Ressource
von Fatime Hawchar ; Dana Tomescu ; Karl Träger ; Dominik Jóskowiak ; Klaus Kogelmann ; Jens Soukup ; Sigrun Friesecke ; David Jacob ; Jan Gummert ; Andreas Faltlhauser ; Filippo Aucella ; Martijn van Tellingen ; Manu Malbrain ; Ralph Bogdanski ; Günter Weiss ; Andreas Herbrich ; Stefan Utzolino ; Axel Nierhaus ; Andreas Baumann ; Andreas Hartjes ; Dietrich Henzler ; Evgeny Grigoryev ; Harald Georg Fritz ; Friedhelm Bach ; Stefan Schröder ; Andreas Weyland ; Udo Gottschaldt ; Matthias Menzel ; Olivier Zachariae ; Radovan Novak ; Jernej Berden ; Hendrik Haake ; Michael Quintel ; Stephan Fritz Klösel ; Andreas Kortgen ; Stephanie-Susanne Stecher ; Patricia Torti ; Frieder Nestler ; Markus Nitsch ; Detlef Olboeter ; Philip Martin Muck ; Michael Findeisen ; Diane Inge Bitzinger ; Jens Kraßler ; Martin Benad ; Martin Schott ; Ulrike Schumacher ; Zsolt Molnar ; Frank Martin Brunkhorst
von Klaus Edgar Roth ; Gerrit Steffen Maier ; Irene Maria Schmidtmann ; Ulrich Eigner ; Wolf Dietrich Hübner ; Fabian Peters ; Philipp Drees ; Uwe Martin Maus
European Photovoltaic Solar Energy Conference and Exhibition (27 : 2012 : Frankfurt am Main) Proceedings München : WIP Renewable Energies, 2012 (2012), Seite 2166-2177 1 DVD-ROM
Festschrift für Dietrich Ritschl zum 80. Geburtstag
Theologie; a Christian union; a Christianity and other religions; Aufsatzsammlung; FestschriftÖkumeneInterkonfessionelles GesprächChristentumInterreligiöser DialogInterreligiositätReligionKircheChristChristinÖkumenische BewegungReligionsgesprächKirchengemeinschaft
