Impact of Weight Gain on Hippocampal Volume Over Time in Individuals with Bipolar Disorders and Healthy Controls

Abstract

Individuals with Bipolar Disorder (BD) are at increased risk for obesity and often exhibit smaller hippocampal volumes, though the relationship between these factors is unclear. This study explored the effects of weight gain on the brain in BD individuals and controls through a multi-site longitudinal study in collaboration with the ENIGMA consortium. T1-weighted MRI scans were collected longitudinally for 233 BD participants and 701 controls over an average of 2.84 years. Hippocampal volumes were analyzed using FreeSurfer, with linear mixed modeling assessing the association between BMI and hippocampal volume changes. BMI increased significantly in all participants, with greater hippocampal volume loss associated with lower baseline BMI (t (904) =3.84, p<0.001) and increased BMI over time (t (895) =-3.81, p<0.001). Weight gain leads to hippocampal atrophy, regardless of BD diagnosis, emphasizing the importance of weight control, particularly in those with low to normal BMI.