Higher BMI Associates With Lower Cortical Thickness in Bipolar Disorder

Cortical thickness was found to be smaller in individuals with bipolar disorder and a higher BMI.

Individuals with bipolar disorder (BD) with a higher BMI were found to have a smaller cortical thickness in the cerebral mantle, according to results of a study published in Psychological Medicine.

Data for this study were sourced from the ENIGMA-BD Working Group. A total of 17 samples from 13 countries on 6 continents were evaluated for associations between brain structural changes observed by magnetic resonance imaging (MRI) and BMI among patients with BD (n=1231) and healthy controls (n=1601).

The BD and control cohorts comprised individuals aged mean 42.12 (SD, 12.71) and 35.47 (SD, 12.63) years (P <.001), 60.4% and 57.21% were women, and they had BMIs of 26.78 (SD, 5.23) and 24.43 (SD, 4.12) kg/m2 (P <.001), respectively.

Among the BD cohort, 73.4% were diagnosed with BD-I, 52.5% had a history of psychosis, disease onset at 25.68 (SD, 10.94) years of age, 58.5% were euthymic, 35.7% were depressed, 4.2% were manic, and 17.7% were receiving no treatment, 46.7% lithium, 22.9% antiepileptics, 19.9% antidepressants, 14.9% second-generation antipsychotics, and 1.4% first-generation antipsychotics.

[W]e confirmed consistent associations between higher BMI and lower cortical thickness across the cerebral mantle, in regions which were also associated with BD.

In the 34 cortical regions, thicknesses differed significantly on the basis of diagnosis in all regions (all P ≤.048) except for the entorhinal and temporal pole regions.

Significant effects for BMI were observed in the caudal anterior cingulate, caudal middle frontal, entorhinal, fusiform, inferior temporal, paracentral, precentral, rostral anterior cingulate, superior frontal, and transverse temporal regions (r range, -0.094 to -0.051; all P ≤.039).

A group-by-BMI interaction was observed in the lateral occipital cortical thickness, in which BMI affected the cortical thickness among controls (t[2391], -3.03; P =.002) but not patients with BD (t[2391], 0.31; P =.757).

Among the BD group, patients with a higher BMI tended to use more classes of anticonvulsants, antipsychotics, and/or antidepressants (t[1100], 4.89; P <.001) but not lithium (t[736], -0.42; P =.676). In turn, the number of medication classes associated with smaller cortical thickness in 64.7% of the brain regions and a significant interaction between lithium use and BMI was observed in 38.2% of brain regions.

A mediation analysis between BMI and the number of medications was performed for the cortical thickness in the fusiform gyrus. The investigators observed a significant negative indirect effect (34.6%) of the number of medication classes on thickness through BMI (estimate, -0.015; P <.001).

The major limitation of this study was the cross-sectional design which did not allow for causal inferences to be made.

Study authors concluded, “[W]e confirmed consistent associations between higher BMI and lower cortical thickness across the cerebral mantle, in regions which were also associated with BD. […] In most regions number of medications remained associated with lower cortical thickness regardless of BMI, but there were also instances of mediation and moderation of associations between number of medication classes and cortical thickness by BMI.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


McWhinney SR, Abé C, Alda M, et al. Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants. Psychol Med. 2023;1-11. doi:10.1017/S0033291723000223