Association between body mass index and subcortical brain volumes in bipolar disorders–ENIGMA study in 2735 individuals
Authors: McWhinney Sean R. , Abé Christoph , Alda Martin , Benedetti Francesco , Bøen Erlend , del Mar Bonnin Caterina , Borgers Tiana , Brosch Katharina , Canales-Rodríguez Erick J. , Cannon Dara M. , Dannlowski Udo , Díaz-Zuluaga Ana M. , Elvsåshagen Torbjørn , Eyler Lisa T. , Fullerton Janice M. , Goikolea Jose M. , Goltermann Janik , Grotegerd Dominik , Haarman Bartholomeus C. M. , Hahn Tim , Howells Fleur M. , Ingvar Martin , Kircher Tilo T. J. , Krug Axel , Kuplicki Rayus T. , Landén Mikael , Lemke Hannah , Liberg Benny , Lopez-Jaramillo Carlos , Malt Ulrik F. , Martyn Fiona M. , Mazza Elena , McDonald Colm , McPhilemy Genevieve , Meier Sandra , Meinert Susanne , Meller Tina , Melloni Elisa M. T. , Mitchell Philip B. , Nabulsi Leila , Nenadic Igor , Opel Nils , Ophoff Roel A. , Overs Bronwyn J. , Pfarr Julia-Katharina , Pineda-Zapata Julian A. , Pomarol-Clotet Edith , Raduà Joaquim , Repple Jonathan , Richter Maike , Ringwald Kai G. , Roberts Gloria , Salvador Raymond , Savitz Jonathan , Schmitt Simon , Schofield Peter R. , Sim Kang , Stein Dan J. , Stein Frederike , Temmingh Henk S. , Thiel Katharina , van Haren Neeltje E. M. , Gestel Holly Van , Vargas Cristian , Vieta Eduard , Vreeker Annabel , Waltemate Lena , Yatham Lakshmi N. , Ching Christopher R. K. , Andreassen Ole , Thompson Paul M. , Hajek Tomas ,   for the ENIGMA Bipolar Disorders Working Group
Published: April 2021

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.