Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness: ENIGMA study in 2436 individuals

Sean R. McWhinney, Christoph Abé, the ENIGMA Bipolar Disorders Working Group, Martin Alda, Francesco Benedetti, Erlend Bøen, Caterina del Mar Bonnin, Tiana Borgers, Katharina Brosch, Erick J. Canales-Rodríguez, Dara M. Cannon, Udo Dannlowski, Ana M. Diaz-Zuluaga, Lorielle Dietze, Torbjørn Elvsåshagen, Lisa T. Eyler, Janice M. Fullerton, Jose M. Goikolea, Janik Goltermann, Dominik GrotegerdBartholomeus C.M. Haarman, Tim Hahn, Fleur M. Howells, Martin Ingvar, Tilo T.J. Kircher, Axel Krug, Rayus T. Kuplicki, Mikael Landén, Hannah Lemke, Benny Liberg, Carlos Lopez-Jaramillo, Ulrik F. Malt, Fiona M. Martyn, Elena Mazza, Colm McDonald, Genevieve McPhilemy, Sandra Meier, Susanne Meinert, Tina Meller, Elisa M.T. Melloni, Philip B. Mitchell, Leila Nabulsi, Igor Nenadic, Nils Opel, Roel A. Ophoff, Bronwyn J. Overs, Julia Katharina Pfarr, Julian A. Pineda-Zapata, Edith Pomarol-Clotet, Neeltje E.M. van Haren, Annabel Vreeker, Paul Thompson, Tomas Hajek

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)509-520
Number of pages12
JournalBipolar Disorders
Issue number5
Early online date11 Dec 2021
Publication statusPublished - Aug 2022

Bibliographical note

Funding Information:
We gratefully acknowledge the following contributions and research funding sources that made this study possible: PT and CRKC of the Marina del Rey studies were supported by NIH grant U54 EB020403 from the Big Data to Knowledge (BD2K) Program; CRKC also acknowledges, NIA T32AG058507, and partial research support from Biogen, Inc. (Boston, USA) for work unrelated to the topic of this manuscript. The St. Göran study was supported by grants from the Swedish Research Council (2018‐02653), the Swedish Foundation for Strategic Research (KF10‐0039), the Swedish Brain Foundation, and the Swedish Federal Government under the LUA/ALF agreement (ALF 20170019, ALFGBG‐716801). This work is also part of the German multicenter consortium “Neurobiology of Affective Disorders. A translational perspective on brain structure and function”, funded by the German Research Foundation (Deutsche Forschungsgemeinschaft DFG; Forschungsgruppe/Research Unit FOR2107). Principal investigators (PIs) with respective areas of responsibility in the FOR2107 consortium are: Work Package WP1, FOR2107 cohort and brain imaging: TK (speaker FOR2107; DFG grant numbers KI 588/14‐1, KI 588/14‐2), UD (co‐speaker FOR2107; DA 1151/5‐1, DA 1151/5‐2), AK (KR 3822/5‐1, KR 3822/7‐2), IN (NE 2254/1‐1 and NE 2254/2‐1), CK (KO 4291/3‐1). Further support from the German sites were provided by MNC and FOR2107‐Muenster: This work was funded by the German Research Foundation (SFB‐TRR58, Project C09 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD and grant SEED11/18 to NO); FOR2107‐Muenster: This work was supported by grants from the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant MzH 3/020/20 to TH) and the German Research Foundation (DFG grants HA7070/2‐2, HA7070/3, HA7070/4 to TH). The NUIG sample was supported by the Health Research Board (HRA_POR/2011/100). The Medellin studies (GIPSI) were supported by the PRISMA UNION TEMPORAL (UNIVERSIDAD DE ANTIOQUIA/HOSPITAL SAN VICENTE FUNDACIÓN), Colciencias‐INVITACIÓN 990 de 3 de agosto de 2017, Codigo 99059634. The San Raffaele site was supported by the Italian Ministry of Health RF‐2011‐02350980 project. This research was also supported by the Irish Research Council (IRC) Postgraduate Scholarship, Ireland awarded to LN and to GM, and by the Health Research Board (HRA‐POR‐324) awarded to DMC. We thank the participants and the support of the Welcome‐Trust HRB Clinical Research Facility and the Centre for Advanced Medical Imaging, St. James Hospital, Dublin, Ireland. The NUIG sample was supported by the Health Research Board (HRA_POR/2011/100). JS and RTK received support from the William K. Warren Foundation National Institute of Mental Health (R21MH113871); JS also acknowledges the National Institute of General Medical Sciences (P20GM121312). This study was also funded by EU‐FP7‐HEALTH‐222963 “MOODIN‐FLAME” and EU‐FP7‐PEOPLE‐286334 “PSYCHAID.” The Barcelona group would like to thank CIBERSAM (EPC) and the Instituto de Salud Carlos III (PI18/00877, and PI19/00394) for their support. This work was supported by the Singapore Bioimaging Consortium (RP C009/2006) research grant awarded to KS. The CIAM group (FMH—PI) was supported by the University Research Committee, University of Cape Town and South African funding bodies National Research Foundation and Medical Research Council; DJS from CIAM was supported by the SAMRC. The Sydney studies were supported by the Australian National Health and Medical Research Council (NHMRC) Program Grant 1037196, Project Grants 1063960 and 1066177, the Lansdowne Foundation, Good Talk and Keith Pettigrew Family; as well as the Janette Mary O’Neil Research Fellowship to JMF. The study was also supported by NIMH grant number: R01 MH090553 (to RAO). Funding for the Oslo‐Malt cohort was provided by the South Eastern Norway Regional Health Authority (2015‐078), the Ebbe Frøland foundation, and a research grant from Mrs. Throne‐Holst. EV acknowledges the support of the Spanish Ministry of Science and Innovation (PI15/00283, PI18/00805) integrated into the Plan Nacional de I+D+I and co‐financed by the ISCIII‐Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357. Lastly, this study was supported by the Canadian Institutes of Health Research (103703, 106469, and 142255), Nova Scotia Health Research Foundation, Dalhousie Clinical Research Scholarship to TH, Brain and Behavior Research Foundation (formerly NARSAD); 2007 Young Investigator and 2015 Independent Investigator Awards to TH. PMT and CRKC received a grant from Biogen, Inc., for research unrelated to this manuscript. DJS has received research grants and/or consultancy honoraria from Lundbeck and Sun. LNY has received speaking/consulting fees and/or research grants from Abbvie, Alkermes, Allergan, AstraZeneca, CANMAT, CIHR, Dainippon Sumitomo Pharma, Janssen, Lundbeck, Otsuka, Sunovion, and Teva. TE received speaker’s honoraria from Lundbeck and Janssen Cilag. EV has received grants and served as consultant, advisor, or CME speaker for the following entities (unrelated to the present work): AB‐Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi‐Aventis, and Takeda.

Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


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