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