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
Open accessAbstract
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.
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Obesity is coupled to structural and functional brain changes that are remarkably similar to those observed in depressive disorders, such as region-specific increases in cell density and compromised neural connectivity and excitability.
“Obesity is coupled to various structural and functional changes in the brain that are remarkably similar to those observed in depressive disorders, such as regionspecific increases in cell density and compromised neural connectivity and excitability [5,6].”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [6]
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- Authors
- 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, H. C., Harris, M. A., MacMaster, F. P., Walter, H., Veer, I. M., Frodl, T., Carballedo, A., Krug, A., Nenadic, I., Kircher, T., Aleman, A., Groenewold, N. A., Stein, D. J., Soares, J. C., Zunta-Soares, G. B., Mwangi, B., Wu, M.-J., Walter, M., Li, M., Harrison, B. J., Davey, C. G., Cullen, K. R., Klimes-Dougan, B., Mueller, B. A., Sämann, P. G., Penninx, B., Nawijn, L., Veltman, D. J., Aftanas, L., Brak, I. V., Filimonova, E. A., Osipov, E. A., Reneman, L., Schrantee, A., Grabe, H. J., Van der Auwera, S., Wittfeld, K., Hosten, N., Völzke, H., Sim, K., Gotlib, I. H., Sacchet, M. D., Lagopoulos, J., Hatton, S. N., Hickie, I., Pozzi, E., Thompson, P. M., Jahanshad, N., Schmaal, L., Baune, B. T., & Dannlowski, U.
- Affiliations
- University of Münster (DE)
- UNSW Sydney (AU)
- Amsterdam University Medical Centers (NL)
- University of Edinburgh (GB)
- University of Calgary (CA)
- Humboldt-Universität zu Berlin (DE)
- Trinity College Dublin (IE)
- Philipps University of Marburg (DE)
- University Medical Center Groningen (NL)
- University of Cape Town (ZA)
- The University of Texas Health Science Center at Houston (US)
- Jena University Hospital (DE)
- The University of Melbourne (AU)
- University of Minnesota (US)
- Max Planck Institute of Psychiatry (DE)
- Institute of Physiology and Basic Medicine (RU)
- Novosibirsk State University (RU)
- Amsterdam UMC Location University of Amsterdam (NL)
- Universitätsmedizin Greifswald (DE)
- National University of Singapore (SG)
- Stanford University (US)
- Harvard University (US)
- University of the Sunshine Coast (AU)
- The University of Sydney (AU)
- University of Southern California (US)
- Corresponding author
- Opel, Nils
- ORCID
- Opel, Nils
- Thalamuthu, Anbupalam
- Milaneschi, Yuri
- Grotegerd, Dominik
- Flint, Claas
- Leenings, Ramona
- Goltermann, Janik
- Richter, Maike
- Hahn, Tim
- Woditsch, Georg
- Berger, Klaus
- Hermesdorf, Marco
- McIntosh, Andrew
- Whalley, Heather C.
- Harris, Mathew A.
- MacMaster, Frank P.
- Walter, Henrik
- Veer, Ilya M.
- Frodl, Thomas
- Krug, Axel
- Kircher, Tilo
- Groenewold, Nynke A.
- Stein, Dan J.
- Soares, Jair C.
- Mwangi, Benson
- Wu, Mon-Ju
- Walter, Martin
- Li, Meng
- Harrison, Ben J.
- Davey, Christopher G.
- Cullen, Kathryn R.
- Mueller, Bryon A.
- Sämann, Philipp G.
- Penninx, Brenda
- Nawijn, Laura
- Veltman, Dick J.
- Aftanas, Lyubomir
- Brak, Ivan V.
- Filimonova, Elena A.
- Osipov, Evgeniy A.
- Reneman, Liesbeth
- Schrantee, Anouk
- Grabe, Hans J.
- Wittfeld, Katharina
- Hosten, Norbert
- Völzke, Henry
- Sim, Kang
- Gotlib, Ian H.
- Sacchet, Matthew D.
- Lagopoulos, Jim
- Hatton, Sean N.
- Hickie, Ian
- Pozzi, Elena
- Thompson, Paul M.
- Jahanshad, Neda
- Schmaal, Lianne
- Baune, Bernhard T.
- Dannlowski, Udo
- Venue
- Molecular Psychiatry
- Published
- 2020-05-28
- Volume
- 26
- Issue
- 9
- Pages
- 4839-4852
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC8589644
- OpenAlex
- W3030929194
- Cited by
- 148
- References
- 79
- Citations by year
- 2026: 15 · 2025: 25 · 2024: 25 · 2023: 36 · 2022: 23 · 2021: 20 · 2020: 4
- FWCI
- 11.15
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-06-22)
- Open access
- hybrid
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- UWA Profiles and Research Repository (UWA) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- UvA-DARE (University of Amsterdam) (acceptedVersion, cc-by)
- National University of Singapore (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- DZNE Pub (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Common Library Network (Der Gemeinsame Bibliotheksverbund) (submittedVersion, cc-by)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- RWTH Publications (RWTH Aachen)
- Funders
- National Science Foundation (0801700, 1147470)
- Foundation for the National Institutes of Health (1RC2 MH089995, U54EB020403, R01MH117601, EB020403, R01 MH116147)
- John S. Dunn Foundation
- University of Minnesota
- Wellcome Trust (U54 EB020403, 104036/Z/14/Z, 104036)
- Children's Hospital Foundation
- EU Joint Programme – Neurodegenerative Disease Research (01ED1615, FKZ:01ED1615)
- European Commission (01ED1615, U54 EB020403, 01ZZ0103, 1RC2 MH089995, 01ZZ0403, 01ZZ9603)
- Science Foundation Ireland (15012, U54 EB020403)
- Deutsche Forschungsgemeinschaft (HA 7070/2-2; HA7070/3; HA7070/4, Dan3/012/17, WI3439/3–2, KI 588/14-2, grant FOR2107, 1204/3-1, KI588/17-1, FOR 2107/ DA1151/5-1, RI908/11–2, DA 1151/5-2 to UD), KR 3822/7–2, HA 7070/2–2, DA1151/5-2, JA 1890/7‐2, TRR‐58, U54 EB020403, RE 737/20-2, 01ZZ0403, JA 1890/7-1, R01MH116147, MU1315/8-2, DE 1614/3-2, KI588/14–1, 01ZZ9603, SFB 779, 559/14-1, SCHW 559/14-1, NE2254/1-2, 1890/7-1, HA7070/3, /14-2, DA1151/5-1, KR 3822/7-1, FOR 2107, 588/14-1, JA1890/7-1, JA1890/7-2, DA1151, /14-1, KI 588/14-1, KI 588/14-2, 01ZZ0103, HA7070/4, SFB TRR 58)
- Universiteit Leiden (10‐000‐1002)
- Vrije Universiteit Amsterdam
- Bundesministerium für Bildung und Forschung (01GS0481, 01ZZ9603, 01ZZ0103, and 01ZZ0403, 01ED1615, DA1151/5-2, 01ER0816, 01ER1506, FOR2107 DA1151/5-1, U54 EB020403, 01ER0816, 01ZZ0403, and 01ZZ0403, R01MH116147, FKZ 01GS0481, 01ER1506, 01ER1205, 01ZZ0103, 01ZZ9603)
- Alberta Children's Hospital Foundation
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (10-000-1002, 01ZZ9603, 01ZZ0403, 15012, 1RC2 MH089995, 01ZZ0103)
- Max-Planck-Gesellschaft
- Westfälische Wilhelms-Universität Münster (DA1151/5-2, FOR2107 DA1151/5-1)
- Leids Universitair Medisch Centrum
- Universitair Medisch Centrum Groningen
- Russian Science Foundation (16-15-00128)
- Siemens Healthineers (01ZZ0103, 01ZZ0403, 01ZZ9603)
- H. Lundbeck A/S
- Universität Greifswald
- Branch Out Neurological Foundation
- Ministry of Cultural Affairs
- National Institutes of Health (JA 1890/7-1, R01D0042157-01A, 104036/Z/14/Z, DA1151/5-1, JA 1890/7-2, R01D0042157, DA1151/5-2, SFB-TRR58, FOR2107, 1147470, 1r01mh081802-01, EB020403)
- Medical Research Council (104036/Z/14/Z, U54 EB020403)
- National Health and Medical Research Council (1024570, 464914, 1140764, 566529, 402864, 1064643)
- National Institute of Mental Health (R01MH116147, MH-081802, SFB-TRR58, RC2MH089995, MH089951, DA 1151/5-1, K23MH090421, FOR2107, DA 1151/5-2, R01 085667, JA 1890/7-2, JA 1890/7-1, RC2MH089951, R01 MH081802, R01MH117601, MH089995)
- National Institute on Drug Abuse (R01DA042157)
- National Institute of Biomedical Imaging and Bioengineering (U54EB020403)
- Division of Graduate Education (1147470, DGE-1147470)
- National Center for Research Resources (P41RR008079)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- obesity, structural brain abnormalities, cortical thickness, subcortical structures, major depressive disorder, polygenic risk score, fusiform gyrus, mental illness, neuroimaging genetics
- MeSH terms
- Aged, Brain, Cerebral Cortex, Depressive Disorder, Major, Major Depressive Disorder, Humans, Magnetic Resonance Imaging, Obesity, Risk Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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