Schizophrenia is frequently associated with obesity, which is linked with neurostructural alterations. Yet, we do not understand how the brain correlates of obesity map onto the brain changes in schizophrenia. We obtained MRI-derived brain cortical and subcortical measures and body mass index (BMI) from 1260 individuals with schizophrenia and 1761 controls from 12 independent research sites within the ENIGMA-Schizophrenia Working Group. We jointly modeled the statistical effects of schizophrenia and BMI using mixed effects. BMI was additively associated with structure of many of the same brain regions as schizophrenia, but the cortical and subcortical alterations in schizophrenia were more widespread and pronounced. Both BMI and schizophrenia were primarily associated with changes in cortical thickness, with fewer correlates in surface area. While, BMI was negatively associated with cortical thickness, the significant associations between BMI and surface area or subcortical volumes were positive. Lastly, the brain correlates of obesity were replicated among large studies and closely resembled neurostructural changes in major depressive disorders. We confirmed widespread associations between BMI and brain structure in individuals with schizophrenia. People with both obesity and schizophrenia showed more pronounced brain alterations than people with only one of these conditions. Obesity appears to be a relevant factor which could account for heterogeneity of brain imaging findings and for differences in brain imaging outcomes among people with schizophrenia.
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NAC et al. were supported by the Agencia Nacional de Investigación y Desarrollo, Chile, through its grants PIA ACT1414, ANID-PIA-ACT 192064, and FONDECYT regular 1200601. This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 to UD; SFB-TRR58, Projects C09 and Z02 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD). The NUDZ and IKEM sites were supported by funding from the Ministry of Health of the Czech Republic (16-32791A, NU20-04-00393) and conceptual development of research organization (Institute for Clinical and Experimental Medicine – IKEM, IN 00023001). This work was also funded by the German Research Foundation (DFG grant FOR2107, KI588/14-1 and FOR2107, KI588/14-2 to TTJK, Marburg, Germany), as well as, the Alexander von Humboldt Foundation, EU and Deutsche Forschungsgemeinschaft (DFG), grants NE2254/1-2, NE2254/3-1, NE2254/4-1. Additional support provided by research grants from the National Healthcare Group, Singapore (SIG/05004; SIG/05028), and the Singapore Bioimaging Consortium (RP C009/2006) research grants awarded to KS. EW was supported by the European Union’s Horizon 2020 research and innovation programme (Early Cause, grant n° 848158). Funding for TWW was provided by the National Health and Medical Research Council Australia Project Grant 568807; New South Wales Health, University of New South Wales, Neuroscience Research Australia and the Schizophrenia Research Institute. GD’s research was funded by the European Research Council 677467 and Science Foundation Ireland 16/ERCS/3787. VDC was supported by NIH R01MH118695. PMT was supported by NIMH grant R01MH116147. Lastly, TH was supported by funding from the Canadian Institutes of Health Research (103703, 106469 and 142255), Nova Scotia Health Research Foundation, Dalhousie Clinical Research Scholarship to TH, Brain & Behavior Research Foundation (formerly NARSAD); 2007 Young Investigator and 2015 Independent Investigator Awards to TH.
NAC has received personal fees from Janssen, outside the submitted work. All other authors declare no competing interests.
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McWhinney, S.R., Brosch, K., Calhoun, V.D. et al. Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01616-5