Gray and white matter trajectories in patients with bipolar disorder

Objectives: Findings on brain structural abnormalities in patients with bipolar disorder (BP) are inconsistent and little is known about their changes over time. We employed a cross-sectional case-control study to compare structural age-related brain trajectories in patients with BP and healthy control subjects (HC) over a time period of about 50 years. The primary aim was to understand whether white (WM) and gray matter (GM) changes are present form the beginning of the illness and how they change over time. Methods: Seventy-eight patients with BP and 78 HC matched one by one for age, gender and educational level underwent a high-resolution structural magnetic resonance imaging scan protocol. A voxel-based-morphometry (VBM) analysis was used to capture GM and WM differences in BP patients and HC. Factorial analysis of covariance (ANCOVA) was used to compare brain volume alterations at different ages between groups. Results: We found an age-related atrophy in GM and WM volumes both in patients and HC. A main effect of diagnosis emerged in the posterior cingulate cortex bilaterally, in the right thalamus, in the cerebellum bilaterally and in left posterior limb of the internal capsule. No interaction between diagnosis and age emerged, indicating that the volumes of these areas were permanently reduced in BP patients along the entire age range investigated. Conclusions: Brain alterations in BP patients are present from the beginning of the illness and remain stable over time. All the affected areas are involved in mood and psychomotor control process. This suggests a possible neurodevelopmental involvement in the mechanism of BP.