A recent observational study has uncovered genetic factors that influence the outcomes of bipolar disorder (BD), a mental health condition known for its intricate clinical characteristics. This research aims to create a detailed model of BD psychopathology by integrating premorbid psychosocial deficits and long-term outcomes, including reduced inter-episode remission and chronicity.
The study involved 4,992 participants and utilized Inverse Probability Weighting (IPW) to minimize bias. Researchers employed Exploratory Factor Analysis (EFA) on 77 OPCRIT items, which revealed four distinct symptom dimensions: mania, psychosis, depression, and a new dimension focused on psychosocial functioning. Confirmatory Factor Analysis (CFA) validated this four-factor model using 20 items.
To assess the genetic contributions to these symptom dimensions, researchers calculated Polygenic Risk Scores (PRSs) for five psychiatric disorders: schizophrenia (SCZ), major depression (MDD), attention-deficit and hyperactivity disorder (ADHD), anxiety (ANX), and bipolar disorder itself. Structural Equation Modelling (SEM) was then applied to analyze these genetic influences.
The CFA confirmed that the four-factor model fit well, with specific findings indicating that the PRS for bipolar disorder primarily predicted symptoms of mania, while the PRS for schizophrenia was linked to psychosis and the PRS for major depression correlated with depressive symptoms. Importantly, the psychosocial functioning dimension, which included premorbid psychosocial deficits and poorer outcomes, showed positive associations with PRSs for ADHD and anxiety, but an inverse correlation with the PRS for bipolar disorder.
This study highlights the genetic factors related to psychosocial functioning in bipolar disorder and suggests that ADHD and anxiety may contribute to poorer outcomes in individuals with BD. These findings underline the importance of early identification of psychosocial deficits and genetic burdens, which could lead to targeted interventions for those at risk of experiencing more severe illness trajectories.
The research was partially funded by the Stanley Center for Psychiatric Research at the Broad Institute, with additional support from the UCLH NIHR BRC and the National Institutes of Health Graduate Partnership Program. Ethical guidelines were strictly followed throughout the study, with approvals obtained from the NHS Metropolitan Multi-centre Research Ethics Committee.
All data from the study are available upon reasonable request to the authors, reinforcing the commitment to transparency in mental health research.
Ukrainian 
English 
French 
German 
Russian 
Spanish 
Belarusian