Body Mass Index-Related Regional Gray and White Matter Volume Reductions in First-Episode Mania Patients

Background: We previously reported that overweight/obese first-episode mania patients had reduced white matter (WM) and temporal lobe volumes compared with normal-weight patients. WM reductions are characteristic of early-stage bipolar disorder (BD), whereas temporal lobe reductions are frequently reported later in the illness. These findings thus suggested a testable hypothesis: that the neuropathology of BD is exacerbated with elevated body mass index (BMI). Methods: We used voxel-based morphometry to examine the relationship between BMI and regional gray matter (GM) and WM volumes in our sample of 57 euthymic first-episode mania patients and 55 healthy subjects. We hypothesized that elevated BMI in patients, but not healthy subjects, would be associated with volume reductions in frontal, temporal, and subcortical limbic brain regions implicated in the pathophysiology of BD. Results: At recovery from their first manic episode, patients with higher BMI had GM and WM reductions in the predicted emotion-generating and -regulating regions. In contrast, healthy subjects with higher BMI had reduced occipital lobe GM only. Factorial analyses confirmed significant BMI x diagnosis interactions for the WM reductions. Approximately three-quarters of patients with elevated BMI were overweight rather than obese; thus, weight-related volume reductions were detectable in patients with modestly elevated BMI. Conclusions: This is the first hypothesis-driven test of, and supporting evidence for, our theory that elevated BMI is associated with unique brain changes in BD that have a negative impact on regions believed to be vulnerable in the illness. Our results suggest a neurobiological mechanism to explain the well-validated link between obesity and illness severity in BD.