Association between body mass index and subcortical brain volumes in bipolar disorders–ENIGMA study in 2735 individuals

Abstract

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.

Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness—ENIGMA study in 2436 individuals

“…Aside from the standardization of methods, we also addressed any differences between scanners statistically by using mixed models and including site as a random factor in all analyses. While there are other approaches, this is still by far the most utilized and accepted method for dealing with site effects 27,51 . Information about medications was limited to current usage at the time of scan.…”

Subcortical Brain Volumes Relate to Neurocognition in First-Episode Schizophrenia, Bipolar Disorder, Major Depression Disorder, and Healthy Controls

“…Meanwhile, previous scientific research has confirmed that subcortical structural abnormalities co-occur with widespread cortical volume reduction even in large-scale studies from the ENIGMA working groups for Sch, BD, and MDD ( 10 – 12 ). The most consistent findings are enlarged lateral ventricles and reduced hippocampal and amygdala volumes in these disorders.…”

Cross disorder comparisons of brain structure in schizophrenia, bipolar disorder, major depressive disorder, and 22q11.2 deletion syndrome: A review of ENIGMA findings

“…McWhinney and colleagues investigated the effects of obesity on subcortical volumes from 1134 individuals with BD and 1601 healthy controls from 13 countries worldwide. 57 They found that 18.4% of the total association between BD and ventricular volume was explained by a higher body mass index (BMI) in BD. Other subcortical regions, including the hippocampus, caudate and thalamus, were robustly associated with BD even after controlling BMI, and there was no interaction between BD and BMI in predicting subcortical brain volumes.…”

“…McWhinney and colleagues investigated the effects of obesity on subcortical volumes from 1134 individuals with BD and 1601 healthy controls from 13 countries worldwide 57 . They found that 18.4% of the total association between BD and ventricular volume was explained by a higher body mass index (BMI) in BD.…”