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Neurobiological correlates of overweight and obesity in people with bipolar disorder Bond, David Joseph


Up to 75% of people with bipolar disorder (BD) are overweight or obese, and these patients suffer more severe psychiatric symptoms than normal-weight patients, including more frequent depressions, more suicide attempts, lower response rates to pharmacotherapy, and greater cognitive impairment. Obesity is a chronic inflammatory condition that damages numerous body organs and is causally linked to the development of diabetes, heart disease, and cancer. BD is fundamentally a brain illness, and this, along with converging evidence from human and animal studies suggesting that the brain is a target organ for obesity-related damage, compelled me to investigate obesity-related neurobiological changes early in BD. I found that at recovery from their first manic episode, there was no difference between BD patients and age- and gender-matched healthy subjects in mean body mass index (BMI) or rates of overweight or obesity. Nonetheless, magnetic resonance imaging (MRI) demonstrated that overweight/obese patients had reduced white matter and temporal lobe volumes compared to normal-weight patients. WM reductions are characteristic of early-stage BD, while 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 BMI. Subsequent investigations supported this hypothesis. A voxel-based analysis of regional brain volumes revealed that BMI-related volume reductions primarily affected frontal, temporal, and subcortical emotion-generating and –regulating brain areas implicated in BD. Moreover, MR spectroscopy showed that overweight/obese patients had reduced hippocampal N-acetylaspartate concentrations compared to normal-weight patients. Similar findings were not detected in overweight/obese healthy subjects, who had reduced occipital lobe grey matter volume and no neurochemical alterations. These are the first data to establish a relationship between elevated BMI and neurobiological alterations in BD, or any psychiatric illness. They demonstrate that elevated BMI is associated with unique brain changes early in BD that negatively impact regions believed to be vulnerable in the illness. This immediately suggests an explanation for the more severe illness course experienced by obese BD patients, and creates a compelling argument for examining the neurobiological impact of obesity in other mental illnesses with high obesity rates, such as major depressive disorder and schizophrenia.

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