Background Employment and relationship are crucial for social integration. However, individuals with major psychiatric disorders often face challenges in these domains. Aims We investigated employment and relationship status changes among patients across the affective and psychotic spectrum – in comparison with healthy controls, examining whether diagnostic groups or functional levels influence these transitions. Method The sample from the longitudinal multicentric PsyCourse Study comprised 1260 patients with affective and psychotic spectrum disorders and 441 controls (mean age ± s.d., 39.91 ± 12.65 years; 48.9% female). Multistate models (Markov) were used to analyse transitions in employment and relationship status, focusing on transition intensities. Analyses contained multiple multistate models adjusted for age, gender, job or partner, diagnostic group and Global Assessment of Functioning (GAF) in different combinations to analyse the impact of the covariates on the hazard ratio of changing employment or relationship status. Results The clinical group had a higher hazard ratio of losing partner (hazard ratio 1.46, P < 0.001) and job (hazard ratio 4.18, P < 0.001) than the control group (corrected for age/gender). Compared with controls, clinical groups had a higher hazard of losing partner (affective group, hazard ratio 2.69, P = 0.003; psychotic group, hazard ratio 3.06, P = 0.001) and job (affective group, hazard ratio 3.43, P < 0.001; psychotic group, hazard ratio 4.11, P < 0.001). Adjusting for GAF, the hazard ratio of losing partner and job decreased in both clinical groups compared with controls. Conclusion Patients face an increased hazard of job loss and relationship dissolution compared with healthy controls, and this is partially conditioned by the diagnosis and functional level. These findings underscore a high demand for destigmatisation and support for individuals in managing their functional limitations.
BJPsych Open Cambridge : Cambridge University Press, 2015 11(2024), 1, Artikel-ID e11, Seite 1-10 Online-Ressource
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.
von Stefanie Enriquez Geppert ; René J. Huster ; Robert Scharfenort ; Zacharais Njam Mokom ; Johannes Voßkuhl ; Christian Figge ; Jörg Zimmermann ; Christoph S. Herrmann
