Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders
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 M. McIntosh, Heather C. Whalley, Mathew A. Harris, Frank P. MacMaster, Henrik Walter, Ilya M. Veer, Thomas Frodl, Angela Carballedo, Axel Krug, Igor Nenadić, Tilo Kircher, André Alemán, Nynke A. Groenewold, Dan J. Stein, Jair C. Soares, Giovana 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 W.J.H. Penninx, Laura Nawijn, Dick J. Veltman, Lyubomir I. Aftanas, И. В. Брак, Elena 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 B. Hickie, Elena Pozzi, Paul M. Thompson, Neda Jahanshad, Lianne Schmaal, Bernhard T. Baune, Udo Dannlowski
Abstract
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.