Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders: Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group

Nils Opel*, Anbupalam Thalamuthu, Yuri Milaneschi, Dominik Grotegerd, Claas Flint, Ramona Leenings, Janik Goltermann, Maike Richter, Tim Hahn, Georg Woditsch, Klaus Berger, Marco Hermesdorf, Andrew McIntosh, Heather C. Whalley, Mathew A. Harris, Frank P. MacMaster, Henrik Walter, Ilya M. Veer, Thomas Frodl, Angela CarballedoAxel Krug, Igor Nenadic, Tilo Kircher, Andre Aleman, Nynke A. Groenewold, Dan J. Stein, Jair C. Soares, Giovana B. Zunta-Soares, Benson Mwangi, Mon Ju Wu, Martin Walter, Meng Li, Ben J. Harrison, Christopher G. Davey, Kathryn R. Cullen, Bonnie Klimes-Dougan, Bryon A. Mueller, Philipp G. Sämann, Brenda Penninx, Laura Nawijn, Dick J. Veltman, Lyubomir Aftanas, Ivan V. Brak, Elena A. Filimonova, Evgeniy A. Osipov, Liesbeth Reneman, Anouk Schrantee, Hans J. Grabe, Sandra Van der Auwera, Katharina Wittfeld, Norbert Hosten, Henry Völzke, Kang Sim, Ian H. Gotlib, Matthew D. Sacchet, Jim Lagopoulos, Sean N. Hatton, Ian Hickie, Elena Pozzi, Paul M. Thompson, Neda Jahanshad, Lianne Schmaal, Bernhard T. Baune, Udo Dannlowski

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = −0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.

Original languageEnglish
Pages (from-to)4839-4852
Number of pages14
JournalMolecular Psychiatry
Issue number9
Publication statusPublished - Sep 2021

Cite this