Overweight Linked to Deficit in Brain Areas Implicated in Bipolar Disorder

Previous research has suggested that individuals who have bipolar disorder and who are also obese are especially vulnerable to unfavorable outcomes. For example, such individuals have been found to experience more frequent depressive episodes, lower response rates to pharmacotherapy, more frequent suicide attempts, and greater cognitive impairment than individuals who have bipolar disorder and who are not obese.

A possible neurobiological explanation for obesity’s exacerbation of bipolar disorder may have been found by a team of Canadian and Korean researchers. It looks as if obesity might reduce the volume of certain brain areas that are known to contribute to bipolar disorder.

The senior researcher was Lakshmi Yatham, M.D., a professor of psychiatry at the University of British Columbia. The results were published online October 11 in Biological Psychiatry.

The study included 112 subjects between the ages of 14 and 35 years. Fifty-seven were bipolar patients who had recovered from their first mania episode; 55 were age- and gender-matched healthy controls. Out of the 57 bipolar subjects, 20 were overweight or obese—that is, had a body mass index (BMI) of 25 or more; the remaining 37 were of normal weight. Out of the 55 healthy controls, 17 were overweight or obese; the remaining 38 were of normal weight.

The researchers used MRI imaging to measure gray matter and white matter in various areas of the brains of the subjects. The researchers then looked to see whether having an elevated BMI (of 25 or more) could be significantly linked with specific brain volumes found in the subjects.

Bipolar subjects with an elevated BMI had gray matter and white matter reductions in frontal, temporal, and subcortical limbic areas that are known to be implicated in the pathophysiology of bipolar disorder. In contrast, healthy controls with an elevated BMI had gray matter volume reductions in the occipital lobes only.

The results thus suggest that “elevated BMI is associated with unique brain changes in bipolar disorder that have a negative impact on regions believed to be vulnerable in the illness,” the researchers wrote. “Our results suggest a neurobiological mechanism to explain the link between obesity and poor psychiatric outcomes in bipolar disorder.”

To explain their findings, the researchers proposed that an “elevated BMI might create a generalized brain vulnerability that allows bipolar disorder-specific brain changes to progress more rapidly.” Or it might worsen specific pathophysiological processes implicated in bipolar disorder such as systemic inflammation and neuroinflammation.

“This is an intriguing small study,” Sylvia Karasu, M.D., told Psychiatric News. In addition to being a clinical associate professor of psychiatry at Weill Cornell Medical College, Karasu is an obesity expert. However, the study does have certain weaknesses, she said.

“No information was given regarding the medical health, that is, comorbidities, of the overweight or obese ‘healthy’—that is, without bipolar disorder—subjects, nor, for that matter, the medical health of the bipolar patients—for example, hypertension, diabetes, abnormal blood lipids, and so on.”

“There were also many uncontrolled variables in this study. For example, patients were not all on the same medications. They could receive either one or a combination of lithium, divalproex, risperidone, olanzapine, and quetiapine, all of which can affect weight.”

Further, “the sample was not large enough. Only 57 patients were compared to 55 healthy controls. Though the patients and healthy controls had similar BMI distributions, only one-fourth were overweight, and less than 10 percent (fewer than five patients) were obese in each group.”

The researchers agreed that the study sample could have been larger and included more obese subjects. However, since brain volume reductions were detectable even in bipolar subjects who were only modestly overweight, being even a little overweight might have a noxious impact on the bipolar illness process, they indicated in their paper.

The study was funded by an unrestricted grant from AstraZeneca Canada. ■