AIMS: Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry. METHODS: We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14 sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles. RESULTS: We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex. CONCLUSIONS: We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.

Center for Mind Brain and Behavior University of Marburg and Justus Liebig University Giessen Marburg Germany

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

Department of Child and Adolescent Psychiatry and Psychology Erasmus University Medical Center Rotterdam The Netherlands

Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden

Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden

Department of Neurology Institute of Clinical Medicine University of Oslo Oslo Norway

Department of Neuroscience and Physiology Sahlgrenska Academy at Gothenburg University Gothenburg Sweden

Department of Psychiatry and Mental Health University of Cape Town Cape Town South Africa

Department of Psychiatry and Psychotherapy Philipps University Marburg Marburg Germany

Department of Psychiatry and Psychotherapy University of Bonn Bonn Germany

Department of Psychiatry Dalhousie University Halifax Nova Scotia Canada

Department of Psychiatry Erasmus University Medical Center Rotterdam The Netherlands

Department of Psychiatry Social Psychiatry and Psychotherapy Hannover Medical School Hannover Germany

Department of Psychiatry University Medical Center Groningen University of Groningen Groningen The Netherlands

Department of Psychiatry University Medical Center Utrecht Brain Center University Medical Center Utrecht Utrecht University Utrecht The Netherlands

Department of Psychiatry University of California San Diego La Jolla California USA

Department of Psychiatry University of Münster Münster Germany

Desert Pacific MIRECC VA San Diego Healthcare San Diego California USA

Division of Clinical Neuroscience Department of Neurology Oslo University Hospital Oslo Norway

FIDMAG Germanes Hospitalàries Research Foundation Centro de Investigación Biomédica en Red de Salud Mental Barcelona Spain

Hospital Clinic University of Barcelona Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona Spain

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

Institute of Clinical Medicine University of Oslo Oslo Norway

Institute of Psychiartry King's College London London UK

Laureate Institute for Brain Research Tulsa Oklahoma USA

National Institute of Mental Health Klecany Czech Republic

Neuroscience Institute University of Cape Town Cape Town South Africa

Neuroscience Research Australia Randwick New South Wales Australia

Norwegian Centre for Mental Disorders Research Institute of Clinical Medicine University of Oslo Oslo Norway

Oxley College of Health Sciences The University of Tulsa Tulsa Oklahoma USA

Psychiatry and Psychobiology Unit Division of Neuroscience IRCCS San Raffaele Scientific Institute Milan Italy

Research Group in Psychiatry GIPSI Department of Psychiatry Faculty of Medicine Universidad de Antioquia Medellín Colombia

Research Group Instituto de Alta Tecnología Médica Ayudas Diagnósticas SURA Medellin Colombia

School of Medical Sciences University of New South Wales Sydney New South Wales Australia

School of Psychiatry University of New South Wales Sydney New South Wales Australia

South African MRC Unit on Risk and Resilience in Mental Disorders University of Cape Town Cape Town South Africa

UCLA Center for Neurobehavioral Genetics Los Angeles California USA

Unit for Psychosomatics CL Outpatient Clinic for Adults Division of Mental Health and Addiction Oslo University Hospital Oslo Norway

University of British Columbia Vancouver British Columbia Canada

Vita Salute San Raffaele University Milan Italy

West Region Institute of Mental Health Singapore Singapore

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

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