Influence of Sex and Diagnosis on Clinical Variables and Neurocognitive Performance in Severe Mental Illness. Results From the PsyCourse Study.

Introduction: Bipolar disorder (BD) and schizophrenia (SZ) are serious mental illnesses (SMI) with overlapping symptoms but distinct differences in onset and course. Sex differences are an area of growing interest in SMI. This study aims to examine potential interactions between sex and diagnosis across a broad range of variables, to compare males and females within SZ and BD, and to investigate sex-specific group differences.

Pathway-Specific Polygenic Scores for Predicting Clinical Lithium Treatment Response in Patients With Bipolar Disorder.

Background: Polygenic scores (PGSs) hold the potential to identify patients who respond favorably to specific psychiatric treatments. However, their biological interpretation remains unclear. In this study, we developed pathway-specific PGSs (PS) for lithium response and assessed their association with clinical lithium response in patients with bipolar disorder.

Disease severity across psychiatric disorders is linked to pro-inflammatory cytokines.

Importance: Numerous studies indicate that the traditional categorical classification of severe mental disorders (SMD), such as schizophrenia, bipolar disorders, and major depressive disorders, does not align with the underlying biology of those disorders as they frequently overlap in terms of symptoms and risk factors.

Objective: This study aimed to identify transdiagnostic patient clusters based on disease severity and explore the underlying biological mechanisms independently of the traditional categorical classification.

Design: We utilized data from 443 participants diagnosed with SMD of the PsyCourse Study, a longitudinal study with deep phenotyping across up to four visits.

How childhood adversities shape minds and lives: An analysis across the affective-to-psychotic spectrum.

Adverse childhood experiences (ACE) contribute significantly to mental disorders. While existing research has primarily focused on specific diagnostic categories, a comprehensive understanding of how childhood trauma interacts with biological factors, symptom severity and functioning requires a broader perspective. Therefore, this study adopted a cross-diagnostic approach to examine the impact of ACE on quality of life (QoL), psychosocial functioning, and symptom burden by analyzing data from the PsyCourse Study, a longitudinal, multicenter research project conducted in Germany and Austria.

Integrative analysis of miRNA expression profiles reveals distinct and common molecular mechanisms underlying broad diagnostic groups of severe mental disorders.

Micro RNAs (miRNAs) play a crucial role as regulators of various biological processes and have been implicated in the pathogenesis of mental disorders such as schizophrenia and bipolar disorders. In this study, we investigate the expression patterns of miRNAs in the PsyCourse Study (n = 1786), contrasting three broad diagnostic groups: Psychotic (Schizophrenia-spectrum disorders), Affective (Bipolar Disorder I, II and recurrent Depression), and neurotypic healthy individuals. Through comprehensive analyses, including differential miRNA expression, miRNA transcriptome-wide association study (TWAS), and predictive modelling, we identified multiple miRNAs unique to Psychotic and Affective groups as well as shared by both.

How variants in inflammatory mediator genes influence symptom severity of psychiatric disorders: Findings from the PsyCourse study.

Alterations in glial cell function and cytokine levels in the central nervous system may be influenced by neuroinflammatory processes, which have a pathogenic role in psychiatric disorders. Variability in genes that encode inflammatory mediators is associated with risk of developing mental disorders. Therefore, by analyzing data from the transdiagnostic PsyCourse Study, we aimed to investigate whether variations in inflammatory mediator genes are associated with current symptom severity.

Pathway-Specific Polygenic Scores for Lithium Response for Predicting Clinical Lithium Treatment Response in Patients with Bipolar Disorder.

Background: Polygenic scores (PGSs) hold the potential to identify patients who respond favourably to specific psychiatric treatments. However, their biological interpretations remain unclear. In this study, we developed pathway-specific PGSs (PS ) for lithium response and assessed their association with clinical lithium response in patients with bipolar disorder (BD).

Investigating the association of the plasma lipidomic profile with cognitive performance and genetic risk in the PsyCourse study.

Although lipid biology may play a key role in the pathophysiology of mental health disorders such as schizophrenia (SCZ) and bipolar disorder (BD), the nature of this interplay and how it could shape phenotypic presentation, including cognitive performance is still incompletely understood. To address this question, we analyzed the association of plasma level of different lipid species with cognitive performance in the transdiagnostic PsyCourse Study. Plasma lipidomic profiles of 623 individuals (188 SCZ, 243 BD, 192 healthy controls) belonging to the PsyCourse Study were assessed using liquid chromatography and untargeted mass spectrometry.

Aggregating single nucleotide polymorphisms improves filtering for false-positive associations postimputation.

Imputation causes bias in P-values in downstream genome-wide association studies. Imputation quality measures such as IMPUTE info are used to discriminate between false and true associations. However, implementing a high threshold often discards true associations, while a low threshold preserves false associations.

Lost and found: dynamics of relationship and employment status over time in people with affective and psychotic spectrum disorders.

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.

Contrasting genetic burden for bipolar disorder: Early onset versus late onset in an older adult bipolar disorder sample.

Older Adults with Bipolar Disorder (OABD) represent a heterogeneous group, including those with early and late onset of the disorder. Recent evidence shows both groups have distinct clinical, cognitive, and medical features, tied to different neurobiological profiles. This study explored the link between polygenic risk scores (PRS) for bipolar disorder (PRS-BD), schizophrenia (PRS-SCZ), and major depressive disorder (PRS-MDD) with age of onset in OABD.

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

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.

Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental 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.

Lipid Alteration Signature in the Blood Plasma of Individuals With Schizophrenia, Depression, and Bipolar Disorder.

Importance: No clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers.

Objective: To define a reproducible profile of lipid alterations in the blood plasma of patients with schizophrenia (SCZ) independent of demographic and environmental variables and to investigate its specificity in association with other psychiatric disorders, ie, major depressive disorder (MDD) and bipolar disorder (BPD).

Association between mitochondria-related genes and cognitive performance in the PsyCourse Study.

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.

Kalpra: A kernel approach for longitudinal pathway regression analysis integrating network information with an application to the longitudinal PsyCourse Study.

A popular approach to reduce the high dimensionality resulting from genome-wide association studies is to analyze a whole pathway in a single test for association with a phenotype. Kernel machine regression (KMR) is a highly flexible pathway analysis approach. Initially, KMR was developed to analyze a simple phenotype with just one measurement per individual.

Interplay between the genetics of personality traits, severe psychiatric disorders and COVID-19 host genetics in the susceptibility to SARS-CoV-2 infection.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with its impact on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behaviour and, therefore, the risk of contracting the virus.

Genetic risk for psychiatric illness is associated with the number of hospitalizations of bipolar disorder patients.

Objectives: Bipolar disorder (BD) has a highly heterogeneous clinical course that is characterized by relapses and increased health care utilization in a significant fraction of patients. A thorough understanding of factors influencing illness course is essential for predicting disorder severity and developing targeted therapies.

Methods: We performed polygenic score analyses in four cohorts (N = 954) to test whether the genetic risk for BD, schizophrenia, or major depression is associated with a severe course of BD.