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.
Bibliographical noteFunding Information:
Dr. Bond has received speaking fees or sat on advisory boards for the Canadian Network for Mood and Anxiety Treatments ( CANMAT ) and the Canadian Psychiatric Association, Pfizer, Sunovion, BMS, Otsuka, Astra-Zeneca, and Janssen-Ortho. He has received research support from the Canadian Institutes of Health Research ( CIHR), the UBC Institute of Mental Health/Coast Capital Depression Research Fund, and Pfizer. Dr. Ha, Dr. Lang, Mr. Su, and Dr. Torres report no biomedical financial interests or potential conflicts of interest. Dr. Honer has received consulting fees or sat on paid advisory boards for MDH Consulting, In Silico, Novartis, Lundbeck, and Roche; received Honoraria from Rush University, the Korean Society for Schizophrenia Research, the Centre for Addiction and Mental Health ( Toronto, Canada), the British Columbia Schizophrenia Society, the Fraser Providence, and Vancouver Coastal Health Authorities, and the Canadian Agency for Drugs and Technology in Health. He has received grants from CIHR. Dr. Lam is on speaker/advisory boards for, or has received research grants from, AstraZeneca, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Psychiatric Association, Canadian Psychiatric Association Foundation, CANMAT, Eli Lilly, Litebook Company Ltd., Lundbeck, Lundbeck Institute, Merck, Mochida, Pfizer, Servier, St. Jude Medical, UBC Institute of Mental Health/Coast Capital Savings, Takeda, and Wyeth. Dr. Yatham is on speaker/advisory boards for, or has received research grants from, AstraZeneca, Bristol Myers Squibb, CIHR, CANMAT, Eli Lilly, GlaxoSmithKline, Janssen, the Michael Smith Foundation for Health Research, Pfizer, Servier, and the Stanley Foundation.
The data for this study were generated from the Systematic Treatment Optimization Program for Early Mania, which was supported by an unrestricted grant from AstraZeneca Canada. The sponsor had no involvement in designing the study, collecting, analyzing, or interpreting the data, writing the report, or the decision to publish the report.
- Bipolar disorder
- body mass index
- brain volumes
- first-episode mania
- voxel-based morphometry