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

Sean R. Mcwhinney, Christoph Abé, Martin Alda, Francesco Benedetti, Erlend Boen, Caterina Del Mar Bonnin, Tiana Borgers, Katharina Brosch, Erick J. Canales-Rodríguez, Dara M. Cannon, Udo Dannlowski, Ana M. Diaz-Zuluaga, Lorielle M.F. Dietze, Torbjorn Elvsåshagen, Lisa T. Eyler, Janice M. Fullerton, Jose M. Goikolea, Janik Goltermann, Dominik Grotegerd, Bartholomeus C.M. HaarmanTim Hahn, Fleur M. Howells, Martin Ingvar, Neda Jahanshad, Tilo T.J. Kircher, Axel Krug, Rayus T. Kuplicki, Mikael Landén, Hannah Lemke, Benny Liberg, Carlos Lopez-Jaramillo, Ulrik F. Malt, Fiona M. Martyn, Elena Mazza, Colm Mcdonald, Genevieve Mcphilemy, Sandra Meier, Susanne Meinert, Tina Meller, Elisa M.T. Melloni, Philip B. Mitchell, Leila Nabulsi, Igor Nenadic, 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, Alex Ross, Raymond Salvador, Jonathan Savitz, Simon Schmitt, Peter R. Schofield, Kang Sim, Dan J. Stein, Frederike Stein, Henk S. Temmingh, Katharina Thiel, Sophia I. Thomopoulos, Neeltje E.M. Van Haren, Cristian Vargas, Eduard Vieta, Annabel Vreeker, Lena Waltemate, Lakshmi N. Yatham, Christopher R.K. Ching, Ole A. Andreassen, Paul M. Thompson, Tomas Hajek*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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. 


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. 


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. 


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.

Original languageEnglish
Pages (from-to)6743-6753
Number of pages11
JournalPsychological Medicine
Issue number14
Publication statusPublished - 27 Feb 2023

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© The Author(s), 2023.


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