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.

Center for the Neurobiology of Learning and Memory University of California Irvine Irvine CA USA

Centre for Addiction and Mental Health Department of Psychiatry University of Toronto Toronto ON Canada

Centre for Neuroimaging and Cognitive Genomics Clinical Neuroimaging Laboratory NCBES Galway Neuroscience Centre College of Medicine Nursing and Health Sciences National University of Ireland Galway Galway Ireland

Centro de Investigación Biomédica en Red de Salud Mental Madrid Spain

Charles University 3rd Faculty of Medicine Prague Czech Republic

Computación Avanzada y Ciencia Instituto de Física de Cantabria CSIC Santander Spain

Department of Diagnostic and Interventional Radiology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Medicine and Psychiatry School of Medicine University of Cantabria Santander Spain

Department of Neurology and Psychiatry Faculty of Medicine Clínica Alemana Universidad del Desarrollo Santiago Chile

Department of Neuroscience and Physiology SUNY Upstate Medical University Syracuse NY USA

Department of Pscyhiatry and Psychotherapy University of Lübeck Lübeck Germany

Department of Psychiatry and Behavioral Sciences Boston Children's Hospital Boston MA USA

Department of Psychiatry and Psychotherapy Philipps University Marburg Marburg Germany

Department of Psychiatry Dalhousie University Halifax NS Canada

Department of Psychiatry Faculty of Medicine and Health Sciences Stellenbosch University Cape Town South Africa

Department of Psychiatry Harvard Medical School Boston MA USA

Department of Psychiatry Jena University Hospital Friedrich Schiller University Jena Jena Germany

Department of Psychiatry Marqués de Valdecilla University Hospital Valdecilla Biomedical Research Institute IDIVAL Santander Spain

Department of Psychiatry School of Medicina Pontificia Universidad Católica de Chile Santiago Chile

Department of Psychiatry School of Medicine University of Sevilla Sevilla Spain

Department of Psychology Georgia State University Atlanta GA USA

Department of Psychology University of Bath Bath UK

Department of Psychosis Studies King's College London London UK

Department of Radiology Marqués de Valdecilla University Hospital Valdecilla Biomedical Research Institute IDIVAL Santander Spain

Early Intervention in Psychosis Program Instituto Psiquiátrico 'Dr José Horwitz B ' Santiago Chile

IBiS University Hospital Virgen del Rocio Sevilla Spain

Imaging Genetics Center Mark and Mary Stevens Neuroimaging and Informatics Institute Keck School of Medicine University of Southern California Marina del Rey CA USA

Institute for Translational Psychiatry University of Münster Münster Germany

Lee Kong Chian School of Medicine Nanyang Technological University Singapore Singapore

National Institute of Mental Health Klecany Czech Republic

Neuroscience Research Australia Randwick NSW Australia

Olin Neuropsychiatry Research Center Institute of Living Hartford CT USA

Psychiatry and Human Behavior University of California Irvine Irvine CA USA

SAMRC Genomics of Brain Disorders Unit Cape Town South Africa

School of Medicine Universidad Finis Terrae Santiago Chile

School of Psychiatry University of New South Wales Sydney NSW Australia

Translational Developmental Neuroscience Section Division of Psychological and Social Medicine and Developmental Neurosciences Faculty of Medicine TU Dresden Dresden Germany

Tri institutional Center for Translational Research in Neuroimaging and Data Science Georgia State Georgia Tech Emory University Atlanta GA USA

West Region Institute of Mental Health Singapore Singapore

Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore

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Mol Psychiatry. 2022 Sep;27(9):3738. doi: 10.1038/s41380-022-01696-3. PubMed

Erratum v

Mol Psychiatry. 2024 Jan;29(1):56. doi: 10.1038/s41380-023-02055-6. PubMed

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