Obesity and frontal-striatal brain structures in offspring of individuals with bipolar disorder: Results from the global mood and brain science initiative

OBJECTIVES: To compare frontal-striatal brain volumes between offspring of individuals with bipolar disorder (BD) and healthy controls; to investigate the associations of body mass index (BMI) and age with brain volumes; and to assess the moderating effects of BMI and age on the relationship between risk status and structural brain differences. METHODS: We cross-sectionally assessed structural regional and global brain volumes using magnetic resonance imaging and BMI among 53 BD offspring subjects, stratified by risk status, and 23 non-BD offspring controls (aged 8-28 years). Analyses of variance and covariance and linear regression analyses were conducted to investigate the associations between BMI and measures of brain volume, as well as the interaction effects between age, BMI, and risk status on brain volumes. RESULTS: After adjusting for age, sex, and intracranial volume, higher BD risk status was associated with lower bilateral cerebellar cortical and right pars orbitalis volumes. Higher BMI was significantly associated with greater brain volumes in frontal and subcortical structures. A significant interaction effect between BMI and risk status was observed in right middle frontal volume. The moderating effect of BMI on brain volume was most robustly observed among subjects aged 14-19 years and less robustly observed among those aged 20-28 years; BMI and brain volumes were negatively correlated among subjects aged 8-13 years. CONCLUSIONS: Alterations in brain structures in individuals at risk for BD may be moderated by BMI. Obesity among individuals with a family history of BD may confer additional risk, particularly in mid-adolescence.