Longitudinal structural brain changes in bipolar disorder: A multicenter neuroimaging study of 1232 individuals by the ENIGMA Bipolar Disorder Working Group.

Abstract

Background Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD. Methods Longitudinal structural MRI and clinical data from the ENIGMA-BD Working Group, including 307 BD patients and 925 healthy controls (HC), were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at two time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between BD and HC. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables. Results Compared with HC, BD patients showed faster enlargement of ventricular volumes and slower thinning of fusiform and parahippocampal cortex (0.18<d<0.22). More (hypo)manic episodes were associated with faster cortical thinning, primarily in the prefrontal cortex. Conclusion In the hitherto largest longitudinal MRI study on BD, we did not detect accelerated cortical thinning but noted faster ventricular enlargements in BD. Abnormal fronto-cortical thinning was however observed in association with frequent manic episodes. Our study yields insights into disease progression in BD, and highlights the importance of mania prevention in BD treatment.