The Link Between Weight Gain and Hippocampal Atrophy in Bipolar Disorder: A Longitudinal Investigation in 934 Participants

Background Obesity, which is common in bipolar disorders (BD), is associated with smaller hippocampal volumes. We do not know whether obesity precedes or results from brain changes or how body mass index (BMI)/weight gain and BD interact in their longitudinal brain effects. Methods In collaboration with the ENIGMA-BD Working Group, we obtained longitudinal T1-weighted MRI and clinical data from 233 participants with BD and 701 healthy controls (CN) scanned twice on average 2.84±1.63 years apart. We estimated subcortical volumes using FreeSurfer longitudinal image processing stream and used linear mixed models to assess the bidirectional relationship between baseline BMI or BMI change and hippocampal volume or volume change. While the hippocampus was our a priori region of interest we repeated these analyses in other subcortical regions. Results Baseline BMI predicted future hippocampal atrophy, but baseline brain structure did not predict future weight changes. BMI increased significantly over time (F(1,1085)=15.98, p