Unravelling the Link Between Body Mass Index and Cognitive Performance in Individuals With Bipolar Disorder and Exploration of PRS Moderation Effect: Findings From the PsyCourse Study

Introduction: Bipolar disorder (BD) is a severe mental disorder characterized by extreme mood swings, often accompanied by metabolic comorbidities, such as cardiovascular disease, which increase mortality and reduce quality of life. Both metabolic dysfunctions and BD are associated with cognitive dysfunction. Body mass index (BMI) is closely linked to metabolic health and cognitive performance. This study examined the link between BMI and cognitive function in individuals with BD and how genetic factors, namely polygenic risk scores (PRS) for BD and BMI, might influence this link. Methods: Genetic (PRS scores) and phenotypic data (sociodemographic factors, clinical symptoms and cognitive function) of 341 adult patients with BD diagnosis from the PsyCourse Study, a large, multi-site, and naturalistic longitudinal study, were utilized for this study. First, we performed univariate and multivariate regression analyses to investigate associations between BMI and cognitive performance. Second, moderation analyses were conducted to examine the potential moderator effects of BD-PRS or BMI-PRS in the relationship between BMI and different cognitive outcomes. Results: BMI was associated with processing speed (TMT-A) and executive function (TMT-B), with individuals with higher BMI showing poorer performance. Moderation analyses revealed that the effect of BMI on cognition was moderated by BD-PRS only regarding the processing speed. BMI-PRS did not moderate the association between BMI and cognitive variables. Conclusions: Our findings indicate that the relationship between BMI and cognitive impairment in BD is partially moderated by BD genetic liability but not by BMI genetic load.