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Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals.

ABSTRACT: 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.

SUBMITTER: McWhinney SR

PROVIDER: S-EPMC9902274 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals.

McWhinney Sean R SR Brosch Katharina K Calhoun Vince D VD Crespo-Facorro Benedicto B Crossley Nicolas A NA Dannlowski Udo U Dickie Erin E Dietze Lorielle M F LMF Donohoe Gary G Du Plessis Stefan S Ehrlich Stefan S Emsley Robin R Furstova Petra P Glahn David C DC Gonzalez-Valderrama Alfonso A Grotegerd Dominik D Holleran Laurena L Kircher Tilo T J TTJ Knytl Pavel P Kolenic Marian M Lencer Rebekka R Nenadić Igor I Opel Nils N Pfarr Julia-Katharina JK Rodrigue Amanda L AL Rootes-Murdy Kelly K Ross Alex J AJ Sim Kang K Škoch Antonín A Spaniel Filip F Stein Frederike F Švancer Patrik P Tordesillas-Gutiérrez Diana D Undurraga Juan J Vázquez-Bourgon Javier J Voineskos Aristotle A Walton Esther E Weickert Thomas W TW Weickert Cynthia Shannon CS Thompson Paul M PM van Erp Theo G M TGM Turner Jessica A JA Hajek Tomas T

Molecular psychiatry 20220614 9

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 ...[more]

PMID: 35739320

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Project description:CONTEXT The single-nucleotide polymorphism rs1344706 in the gene ZNF804a has been associated with schizophrenia and with quantitative phenotypic features, including brain structure volume and the core symptoms of schizophrenia. OBJECTIVE To evaluate associations of rs1344706 with brain structure and the core symptoms of schizophrenia. DESIGN Case-control analysis of covariance. SETTING University-based research hospital. PARTICIPANTS Volunteer sample of 335 individuals with schizophrenia spectrum disorders (306 with core schizophrenia) and 198 healthy volunteers. MAIN OUTCOME MEASURES Cerebral cortical gray matter and white matter (WM) volumes (total and frontal, parietal, temporal, and occipital lobes), lateral ventricular cerebrospinal fluid volume, and symptom severity from the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms divided into 3 domains: psychotic, negative, and disorganized. RESULTS The rs1344706 genotype produced significant main effects on total, frontal, and parietal lobe WM volumes (F = 3.98, P = .02; F = 4.95, P = .007; and F = 3.08, P = .05, respectively). In the schizophrenia group, rs1344706 produced significant simple effects on total (F = 3.93, P = .02) and frontal WM volumes (F = 7.16, P < .001) and on psychotic symptom severity (F = 6.07, P = .003); the pattern of effects was concordant with risk allele carriers having larger volumes and more severe symptoms of disease than nonrisk homozygotes. In the healthy volunteer group, risk allele homozygotes had increased total WM volume compared with nonrisk allele carriers (F = 4.61, P = .03), replicating a previously reported association. CONCLUSIONS A growing body of evidence suggests that the risk allele of rs1347706 is associated with a distinctive set of phenotypic features in healthy volunteers and individuals with schizophrenia. Our study supports this assertion by finding that specific genotypes of the polymorphism are associated with brain structure volumes in individuals with schizophrenia and healthy volunteers and with symptom severity in schizophrenia.

Dataset Information

Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals.

Publications

Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals.

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