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

Opel N, Thalamuthu A, Milaneschi Y, Grotegerd D, Flint C, Leenings R, Goltermann J, Richter M, Hahn T, Woditsch G, Berger K, Hermesdorf M, McIntosh A, Whalley HC, Harris MA, MacMaster FP, Walter H, Veer IM, Frodl T, Carballedo A, Krug A, Nenadic I, Kircher T, Aleman A, Groenewold NA, Stein DJ, Soares JC, Zunta-Soares GB, Mwangi B, Wu MJ, Walter M, Li M, Harrison BJ, Davey CG, Cullen KR, Klimes-Dougan B, Mueller BA, Sämann PG, Penninx B, Nawijn L, Veltman DJ, Aftanas L, Brak IV, Filimonova EA, Osipov EA, Reneman L, Schrantee A, Grabe HJ, Van der Auwera S, Wittfeld K, Hosten N, Völzke H, Sim K, Gotlib IH, Sacchet MD, Lagopoulos J, Hatton SN, Hickie I, Pozzi E, Thompson PM, Jahanshad N, Schmaal L, Baune BT, Dannlowski U

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.