Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants

Abstract

Background: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. Methods: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. Results: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. Conclusions: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders—ENIGMA study in people with bipolar disorders and obesity

“…The ENIGMA‐BD working group brings together researchers with brain imaging and clinical data from people with BD (Hibar et al, 2016 , 2018 ; McWhinney, Abé, et al, 2021 ; McWhinney et al, 2023 ). Nineteen site members of this group from 13 countries on six continents contributed individual subject structural MRI data, medication information, and body mass index (BMI) values for a total of 2770 participants.…”

“…These open‐source protocols are standardized across the ENIGMA consortium, and available online to foster open science, replication, and better reproducibility. They were applied in prior publications by our group (Hibar et al, 2018 ; McWhinney et al, 2023 ), and more broadly in large‐scale ENIGMA studies of major depression, schizophrenia, ADHD, OCD, PTSD, epilepsy, and autism (Thompson et al, 2020 ).…”

“…Large‐scale, multisite brain imaging datasets are becoming more common through initiatives such as ENIGMA (McWhinney et al, 2023 ), ADNI (Cruciani et al, 2024 ), ABCD (Dahl et al, 2024 ), the human connectome project (Cohen et al, 2023 ), and others. Large datasets allow us to apply multivariate techniques of analyses, which model interplay between regions (Woo et al, 2017 ), but require larger, more ecologically valid samples to provide more replicable results (Marek et al, 2022 ).…”

Neuroanatomical profile of BMI implicates impulsive delay discounting and general cognitive ability

“…Similar findings have been observed in other large cohort studies using data from UK Biobank, which showed that BMI has negative correlations with CT of the bilateral entorhinal, orbitofrontal, and cingulate cortices but shows positive correlations with CT of frontal and parietal cortex ( N = 17,813) [11], and higher BMI was also related to lower GMV of various subcortical regions ( N = 9652) [12]. Furthermore, large cohort studies using data from enhancing neuroimaging genetics through meta analysis study have found that higher BMI in people with bipolar disorders indicated more pronounced CT alterations ( N = 2831) [13], and that both BMI and schizophrenia were primarily associated with changes in CT, with fewer correlates in cortical surface area (CSA; N = 3021) [14]. Moreover, obesity was significantly associated with cortical and subcortical abnormalities in major depressive disorder ( N = 6420) [15].…”

Cohort Profile: The St. Göran Bipolar Project

“…We have found structural brain differences between individuals with bipolar disorder and controls[69]. Further, data from the St. Göran bipolar project has been included in the Enhancing Neuro Imaging Genetics through Meta Analysis (ENIGMA) consortium, thereby contributing to large-scale collaborative brain imaging studies[70][71][72][73][74][75][76][77]}. In addition, associations between brain structure, executive function [78], and psychomotor function have been demonstrated[79, 80].…”