Elsevier

Biological Psychiatry

Volume 76, Issue 2, 15 July 2014, Pages 138-145
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2013.08.030Get rights and content

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 × 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.

Section snippets

Participants and Assessments

Patients and healthy subjects were enrolled in the University of British Columbia (UBC) Systematic Treatment Optimization Program for Early Mania (STOP-EM), a comprehensive study of clinical outcomes, cognition, brain morphology, and neurochemistry in recently remitted first-episode mania patients with BD. The UBC Clinical Research Ethics Board approved STOP-EM and the procedures outlined here. Written informed consent was obtained from participants before any study activities took place.

Participants

Fifty-seven of the 71 patients enrolled in STOP-EM, and all 30 of the healthy subjects, had baseline data for BMI and brain volumes and were included here. Twenty-five of the 33 healthy subjects enrolled in the first-episode psychosis study were also included; three were excluded for being outside the age range for STOP-EM and five for histories of serious head injuries. Thus, our sample comprised 57 patients and 55 healthy subjects. Their sociodemographic and clinical characteristics are

Discussion

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. At recovery from their first manic episode, patients with elevated BMI had GM and WM reductions in frontal, temporal, and subcortical limbic areas implicated in the pathophysiology of BD. In contrast, age- and gender-matched healthy subjects had weight-related volume

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