Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals

Molecular Psychiatry volume 30, pages 1770–1779 (2025)Cite this article

Subjects

Abstract

Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group. In a mega-analysis, we investigated the associations between BMI, diagnosis or medication and FA. Lower FA was associated with both BD and BMI in six white matter tracts, including the corpus callosum and thalamic radiation. Higher BMI or BD were uniquely associated with lower FA in three and six white matter tracts, respectively. People not receiving lithium treatment had a greater negative association between FA and BMI than people treated with lithium in the posterior thalamic radiation and sagittal stratum. In three tracts BMI accounted for 10.5 to 17% of the negative association between the number of medication classes other than lithium and FA. Both overweight/obesity and BD demonstrated lower FA in some of the same regions. People prescribed lithium had a weaker association between BMI and FA than people not on lithium. In contrast, greater weight contributed to the negative associations between medications and FA. Obesity may add to brain alterations in BD and may play a role in effects of medications on the brain.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Results of the mega-analysis of the association between BD and obesity with FA.
Fig. 2: Statistical effect of BMI on FA and BMI distribution.
Fig. 3: The effect of medication classes and BMI on fractional anisotropy.
Fig. 4: Interaction between BMI and prescription of lithium at the time of scanning in white matter tracts.

Similar content being viewed by others

Data availability

Data are available upon request, but are not made public due to ethics board approval.

Code availability

All analyses were conducted in R version 4.1.1. Code is available upon request.

References

  1. World Health Organization. Obesity and Overweight. 2021. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.

  2. Flegal KM, Carroll D, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA. 2012;307:491–7.

    PubMed  Google Scholar 

  3. Ogden CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology of obesity. Gastroenterology. 2007;132:2087–102.

    PubMed  Google Scholar 

  4. World Obesity Foundation. Policy Makers | World Obesity Day. 2022. https://www.worldobesityday.org/policy-makers. Accessed 9 October 2023.

  5. Afzal M, Siddiqi N, Ahmad B, Afsheen N, Aslam F, Ali A, et al. Prevalence of overweight and obesity in people with severe mental illness: systematic review and meta-analysis. Front Endocrinol. 2021;12:769309.

    Google Scholar 

  6. Nguyen JCD, Killcross AS, Jenkins TA. Obesity and cognitive decline: role of inflammation and vascular changes. Front Neurosci. 2014;8:375.

    PubMed  PubMed Central  Google Scholar 

  7. Beydoun MA, Beydoun HA, Wang Y. Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis. Obes Rev. 2008;9:204–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Xu WL, Atti AR, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Midlife overweight and obesity increase late-life dementia risk. Neurology. 2011;76:1568–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. McWhinney SR, Abé C, Alda M, Benedetti F, Bøen E, del Mar Bonnin C, et al. Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness—ENIGMA study in 2436 individuals. Bipolar Disord. 2021. https://doi.org/10.1111/BDI.13172.

  10. McWhinney SR, Abé C, Alda M, Benedetti F, Bøen E, del Mar Bonnin C, et al. Association between body mass index and subcortical brain volumes in bipolar disorders–ENIGMA study in 2735 individuals. Mol Psychiatry. 2021;26:6806–6819.

  11. McWhinney SR, Abé C, Alda M, Benedetti F, Bøen E, Del Mar Bonnin C, et al. Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants. Psychol Med. 2023;53:1–11.

    Google Scholar 

  12. Beaulieu C, Allen PS. Water diffusion in the giant axon of the squid: implications for diffusion-weighted MRI of the nervous system. Magn Reson Med. 1994;32:579–83.

    CAS  PubMed  Google Scholar 

  13. Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007;4:316–29.

    PubMed  PubMed Central  Google Scholar 

  14. Mon A, Abé C, Durazzo TC, Meyerhoff DJ. Potential effects of fat on magnetic resonance signal intensity and derived brain tissue volumes. Obes Res Clin Pract. 2016;10:211.

    PubMed  Google Scholar 

  15. Dietze LMF, McWhinney SR, Radua J, Hajek T. Extended and replicated white matter changes in obesity: Voxel-based and region of interest meta-analyses of diffusion tensor imaging studies. Front Nutr. 2023;10:233.

    Google Scholar 

  16. Kullmann S, Schweizer F, Veit R, Fritsche A, Preissl H. Compromised white matter integrity in obesity. Obes Rev. 2015;16:273–81.

    CAS  PubMed  Google Scholar 

  17. Favre P, Pauling M, Stout J, Hozer F, Sarrazin S, Abé C, et al. Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals. Neuropsychopharmacology. 2019;44:2285–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Kuswanto CN, Sum MY, Yang GL, Nowinski WL, McIntyre RS, Sim K. Increased body mass index makes an impact on brain white-matter integrity in adults with remitted first-episode mania. Psychol Med. 2014;44:533–41.

    CAS  PubMed  Google Scholar 

  19. Mazza E, Poletti S, Bollettini I, Locatelli C, Falini A, Colombo C, et al. Body mass index associates with white matter microstructure in bipolar depression. Bipolar Disord. 2017;19:116–27.

    CAS  PubMed  Google Scholar 

  20. Reckziegel R, Rabelo-da-Ponte FD, Feiten JG, Bosini Remus I, Goi PD, Vianna-Sulzbach MF, et al. Bipolar disorder: an association between body mass index and cingulate gyrus fractional anisotropy not mediated by systemic inflammation. Trends Psychiatry Psychother. 2022;44:e20200132.

    PubMed  PubMed Central  Google Scholar 

  21. Thompson PM, Jahanshad N, Ching CRK, Salminen LE, Thomopoulos SI, Bright J, et al. ENIGMA and global neuroscience: a decade of large-scale studies of the brain in health and disease across more than 40 countries. Transl Psychiatry. 2020;10:100.

    PubMed  PubMed Central  Google Scholar 

  22. Mori S, Oishi K, Jiang H, Jiang L, Li X, Akhter K, et al. Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template. Neuroimage. 2008;40:570–82.

    PubMed  Google Scholar 

  23. Hibar DP, Westlye LT, Doan NT, Jahanshad N, Cheung JW, Ching CRK, et al. Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group. Mol Psychiatry. 2018;23:932–42.

    CAS  PubMed  Google Scholar 

  24. McWhinney SR, Brosch K, Calhoun VD, Crespo-Facorro B, Crossley NA, Dannlowski U, et al. Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals. Mol Psychiatry. 2022;27:3731–7.

    PubMed  PubMed Central  Google Scholar 

  25. Gildengers AG, Butters MA, Aizenstein HJ, Marron MM, Emanuel J, Anderson SJ, et al. Longer lithium exposure is associated with better white matter integrity in older adults with bipolar disorder. Bipolar Disord. 2015;17:248.

    PubMed  Google Scholar 

  26. Kafantaris V, Spritzer L, Doshi V, Saito E, Szeszko PR. Changes in white matter microstructure predict lithium response in adolescents with bipolar disorder. Bipolar Disord. 2017;19:587–94.

    CAS  PubMed  Google Scholar 

  27. Hayes AF Beyond Baron and Kenny: Statistical Mediation Analysis in the New Millennium; 2009;76:408–20. https://doi.org/10.1080/03637750903310360.

  28. Canales-Rodríguez EJ, Verdolini N, Alonso-Lana S, Torres ML, Panicalli F, Argila-Plaza I, et al. Widespread intra-axonal signal fraction abnormalities in bipolar disorder from multicompartment diffusion MRI: Sensitivity to diagnosis, association with clinical features and pharmacologic treatment. Hum Brain Mapp. 2023;44:4605–22.

    PubMed  PubMed Central  Google Scholar 

  29. Repple J, Opel N, Meinert S, Redlich R, Hahn T, Winter NR, et al. Elevated body-mass index is associated with reduced white matter integrity in two large independent cohorts. Psychoneuroendocrinology. 2018;91:179–85.

    PubMed  Google Scholar 

  30. Zhang R, Beyer F, Lampe L, Luck T, Riedel-Heller SG, Loeffler M, et al. White matter microstructural variability mediates the relation between obesity and cognition in healthy adults. Neuroimage. 2018;172:239–49.

    PubMed  Google Scholar 

  31. Freeze WM, Zanon Zotin MC, Scherlek AA, Perosa V, Auger CA, Warren AD, et al. Corpus callosum lesions are associated with worse cognitive performance in cerebral amyloid angiopathy. Brain Commun. 2022;4:fcac105.

    PubMed  PubMed Central  Google Scholar 

  32. Huang X, Du X, Song H, Zhang Q, Jia J, Xiao T, et al. Cognitive impairments associated with corpus callosum infarction: a ten cases study. Int J Clin Exp Med. 2015;8:21991.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Ubukata S, Ueda K, Sugihara G, Yassin W, Aso T, Fukuyama H, et al. Corpus callosum pathology as a potential surrogate marker of cognitive impairment in diffuse axonal injury. J Neuropsychiatry Clin Neurosci. 2016;28:97–103.

    PubMed  Google Scholar 

  34. Hinkley LBN, Marco EJ, Findlay AM, Honma S, Jeremy RJ, Strominger Z, et al. The role of corpus callosum development in functional connectivity and cognitive processing. PLoS ONE. 2012;7:e39804.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Paul LK, Erickson RL, Hartman JA, Brown WS. Learning and memory in individuals with agenesis of the corpus callosum. Neuropsychologia. 2016;86:183–92.

    PubMed  Google Scholar 

  36. Oouchi H, Yamada K, Sakai K, Kizu O, Kubota T, Ito H, et al. Diffusion anisotropy measurement of brain white matter is affected by voxel size: underestimation occurs in areas with crossing fibers. AJNR. Am J Neuroradiol. 2007;28:1102–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Todd KL, Brighton T, Norton ES, Schick S, Elkins W, Pletnikova O, et al. Ventricular and periventricular anomalies in the aging and cognitively impaired brain. Front Aging Neurosci. 2017;9:445.

    PubMed  Google Scholar 

  38. Dalton CM, Brex PA, Jenkins R, Fox NC, Miszkiel KA, Crum WR, et al. Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2002;73:141–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Narr KL, Thompson PM, Sharma T, Moussai J, Blanton R, Anvar B, et al. Three-dimensional mapping of temporo-limbic regions and the lateral ventricles in schizophrenia: gender effects. Biol Psychiatry. 2001;50:84–97.

    CAS  PubMed  Google Scholar 

  40. Pearlson GD, Garbacz DJ, Breakey WR, Ahn HS, DePaulo JR. Lateral ventricular enlargement associated with persistent unemployment and negative symptoms in both schizophrenia and bipolar disorder. Psychiatry Res. 1984;12:1–9.

    CAS  PubMed  Google Scholar 

  41. Silbert LC, Quinn JF, Moore MM, Corbridge E, Ball MJ, Murdoch G, et al. Changes in premorbid brain volume predict Alzheimer’s disease pathology. Neurology. 2003;61:487–92.

    CAS  PubMed  Google Scholar 

  42. Stȩpień M, Stȩpień A, Wlazeł RN, Paradowski M, Banach M, Rysz J. Obesity indices and inflammatory markers in obese non-diabetic normo- and hypertensive patients: a comparative pilot study. Lipids Health Dis. 2014;13:29.

    PubMed  PubMed Central  Google Scholar 

  43. De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL, Boschero AC, et al. Consumption of a Fat-Rich Diet Activates a Proinflammatory Response and Induces Insulin Resistance in the Hypothalamus. Endocrinology. 2005;146:4192–9.

    PubMed  Google Scholar 

  44. Baufeld C, Osterloh A, Prokop S, Miller KR, Heppner FL. High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia. Acta Neuropathol. 2016;132:361–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Ottino-González J, Jurado MA, García-García I, Segura B, Marqués-Iturria I, Sender-Palacios MJ, et al. Allostatic load and disordered white matter microstructure in overweight adults. Sci Rep. 2018;8:15898.

    PubMed  PubMed Central  Google Scholar 

  46. Cox SR, Lyall DM, Ritchie SJ, Bastin ME, Harris MA, Buchanan CR, et al. Associations between vascular risk factors and brain MRI indices in UK Biobank. Eur Heart J. 2019;40:2290–2300.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Goldstein BI, Baune BT, Bond DJ, Chen PH, Eyler L, Fagiolini A, et al. Call to action regarding the vascular-bipolar link: a report from the vascular task force of the international society for bipolar disorders. Bipolar Disord. 2020;22:440–60.

    PubMed  PubMed Central  Google Scholar 

  48. Hajek T, Calkin C, Blagdon R, Slaney C, Uher R, Alda M. Insulin resistance, diabetes mellitus, and brain structure in bipolar disorders. Neuropsychopharmacology. 2014;39:2910–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Parimisetty A, Dorsemans AC, Awada R, Ravanan P, Diotel N, Lefebvre d’Hellencourt C. Secret talk between adipose tissue and central nervous system via secreted factors—an emerging frontier in the neurodegenerative research. J Neuroinflammation. 2016;13:1–13.

    Google Scholar 

  50. Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nat. 2006;444:875–80.

    Google Scholar 

  51. Wisse BE. The inflammatory syndrome: The role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol. 2004;15:2792–2800.

    CAS  PubMed  Google Scholar 

  52. Williams OA, An Y, Beason-Held L, Huo Y, Ferrucci L, Landman BA, et al. Vascular burden and APOE ε4 are associated with white matter microstructural decline in cognitively normal older adults. Neuroimage. 2019;188:572–83.

    CAS  PubMed  Google Scholar 

  53. Smith E, Hay P, Campbell L, Trollor JN. A review of the association between obesity and cognitive function across the lifespan: implications for novel approaches to prevention and treatment. Obes Rev. 2011;12:740–55.

    CAS  PubMed  Google Scholar 

  54. Serdar CC, Cihan M, Yücel D, Serdar MA. Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies. Biochem Med. 2021;31:1–27.

    Google Scholar 

  55. Dekkers IA, Jansen PR, Lamb HJ. Obesity, brain volume, and white matter microstructure at MRI: a cross-sectional UK biobank study. Radiology. 2019;291:763–71.

    PubMed  Google Scholar 

  56. Daoust J, Schaffer J, Zeighami Y, Dagher A, García-García I, Michaud A. White matter integrity differences in obesity: A meta-analysis of diffusion tensor imaging studies. Neurosci Biobehav Rev. 2021;129:133–41.

    PubMed  Google Scholar 

  57. McLaren L. Socioeconomic status and obesity. Epidemiol Rev. 2007;29:29–48.

    PubMed  Google Scholar 

  58. Nuttall FQ. Body mass index: Obesity, BMI, and health: a critical review. Nutr Today. 2015;50:117–28.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the following contributions and research funding sources that made this study possible: PT, CRKC, and NJ were supported by Baszucki Brain Research Fund and the Milken Institute’s Center for Strategic Philanthropy grant; R01 MH129742–01; Consortium grant (U54 EB020403) from the NIH Institutes contributing to the Big Data to Knowledge (BD2K) Initiative; The ENIGMA World Aging Center (R56 AG058854); The ENIGMA Sex Differences Initiative (R01 MH116147); The ENIGMA Bipolar Initiative (R01 MH129742-01). OA was supported by the NIMH Award 1R01MH129742 – 01, Research Council of Norway (#223273, #324252, #324499) EU’s H2020 RIA grant # 847776 CoMorMent. This work is also part of the German multicenter consortium “FOR 2107: 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: For FOR2107-Marburg to TK (speaker FOR2107; DFG grant numbers KI588/14-1, and KI588/14-2, and KI588/20-1, KI588/22-1), AK (KR 3822/5-1, KR 3822/7-2), IN (NE2254/1-2, NE2254/2-1, NE2254/3-1, NE2254/4-1), and CK (KO 4291/3-1). Biosamples and corresponding data were sampled, processed, and stored in the Marburg Biobank CBBMR. 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). Funding FOR2107-Muenster: This work was funded by the German Research Foundation (DFG), UD (co-speaker FOR2107, DA 1151/5-1, DA 1151/5-2, grant DA1151/9-1, DA1151/10-1 and DA1151/11-1) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/022/22 to UD). The San Raffaele site was supported by the European Union H2020 EU.3.1.1 grant 754740 MOODSTRATIFICATION. The St. Göran study was supported by grants from the Swedish Research Council (2022-01643), the Swedish foundation for Strategic Research (KF10-0039), the Swedish Brain foundation (FO2022-0217), and the Swedish Federal Government under the LUA/ALF agreement (ALF 20200036, ALFGBG-965444). The UNSW cohort was supported by Australian NHMRC Investigator Grant (1177991); Australian NHMRC Partnership Project Grant (1195643); Australian NHMRC Center of Research Excellence (2015747); Lansdowne Foundation; Good Talk charity. The Singapore study was supported by research grant from the Singapore Bioimaging Consortium (RP C009/06) research grant awarded to K.S. COGSBD cohort - TVR was supported by an NHMRC Early Career Fellowship 1088785, a Dame Kate Campbell Fellowship, and an Al and Val Rosenstrauss Fellowship from the Rebecca L Cooper Medical Research Foundation. SR was supported by an NHMRC Senior Research Fellowship 1154651. MB is supported by a NHMRC Senior Principal Research Fellowship and Leadership 3 Investigator grant (1156072 and 2017131). JK was supported by an Australian Postgraduate Award. LF was supported by the Australian Rotary Health/Brunslea Park Estate/ Ian Parker Bipolar Research Fund. The authors would also like to acknowledge project specific financial support of the Henry Freeman Trust, Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation and the Society of Mental Health Research. The authors acknowledge the facilities and scientific and technical assistance of the National Imaging Facility, a National Collaborative Research Infrastructure Strategy (NCRIS) capability, at the Swinburne Neuroimaging (SNI) Facility, Swinburne University of Technology. Finally, the authors would like to thank the participants in this study for their time and contribution. 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 University of Galway research was 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 and (HRA_POR/2011/100) awarded to CMcD. We thank the participants and the support of the Welcome-Trust HRB Clinical Research Facility and the Center for Advanced Medical Imaging, St. James Hospital, Dublin, Ireland. The University of Toronto CYBD study was funded by the Canadian Institutes of Health Research (Grant number: MOP 136947) and Sunnybrook Health Sciences Center Brenda Smith Fund. BG also acknowledges the CAMH Discovery Fund and his position as RBC Investments Chair in Children’s Mental Health and Developmental Psychopathology at CAMH, a joint Hospital-University Chair between the University of Toronto, CAMH, and the CAMH Foundation. The funding sources were not involved in study design and the conduct of the research. The Geneva sample was supported by the Swiss National Science Foundation: grant number 32003B-156914. The authors would like to thank the University of Geneva’s Brain and Behavior Laboratory (BBL) for their help in acquiring the data. The IDIBAPS(Clinic) and Barcelona (FIGMAG/Clinic) studies MRI acquisition was supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (PI15/00283, PI19/00394 and PI22/00261), integrated into the Plan Nacional de I + D + I and co-financed by ERDF Funds from the European Commission (“A Way of Making Europe”), CIBERSAM, and the CERCA Program / Generalitat de Catalunya and Secretaria d’Universitats i Recerca del Departament d’Economia I Coneixement and Departament de Salut (SLT002/16/00331, SLT006/17/00357, 2017SGR1365, 2021 SGR 01128). 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. The Groningen study was funded by EU-FP7-HEALTH-222963 ‘MOODIN- FLAME’ and EU-FP7-PEOPLE-286334 ‘PSYCHAID’. TE was supported by the South-Eastern Norway Regional Health Authority (#2015-078, #2022043). This work was partially supported by NIMH (1R01MH085667-01A1), John S. Dunn Foundation (Houston, Texas), and Pat Rutherford Chair in Psychiatry (UTHealth Houston). Grenoble MRI facility IRMaGe is partly funded by the French program Investissement d’avenir run by the Agence Nationale de la Recherche: grant Infrastructure d’avenir en Biologie Santé ANR-11-INBS-0006. AM & HW acknowledge the University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. Is e buidheann carthannais a th’ ann an Oilthigh Dhùn Èideann, clàraichte an Alba, àireamh clàraidh SC005336. The Health Foundation & IMAGEMEND, which received funding from the European Community’s Seventh Framework Program (FP7/2007-2013) [grant number 602450]. MP acknowledges grant funding relevant to the study: R37MH1000401, The Pittsburgh Foundation, The Baszucki Brain Research Fund. The Paris site was funded by the French Agence Nationale Pour la Recherche (Labex BioPsy and ANR-DFG FUNDO projects) and by Fondation pour la Recherche Biomédicale (Bioinformatique pour la biologie). Lastly, this study was supported by the Canadian Institutes of Health Research (grants #142255, 180449, 186254), Nova Scotia Health Research Foundation, Dalhousie Clinical Research Scholarship to TH, Brain & Behavior Research Foundation (formerly NARSAD); 2007 Young Investigator and 2015 Independent Investigator Awards to TH.

Author information

Authors and Affiliations

  1. Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada

    Lorielle M. F. Dietze

  2. Department of Psychiatry, Dalhousie University, Halifax, NS, Canada

    Lorielle M. F. Dietze, Sean R. McWhinney, Emily L. V. Corkum, Alex J. Ross & Tomas Hajek

  3. Neurospin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France

    Pauline Favre & Josselin Houenou

  4. INSERM Unit U955, Team Translational Neuropsychiatry, Créteil, France

    Pauline Favre & Josselin Houenou

  5. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Christoph Abé

  6. Quantify Research Stockholm Sweden, Stockholm, Sweden

    Christoph Abé

  7. Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg, Marburg, Germany

    Nina Alexander, Katharina Brosch, Hamidreza Jamalabadi, Andreas Jansen, Tilo T. J. Kircher, Igor Nenadić, Frederike Stein, Benjamin Straube, Lea Teutenberg, Florian Thomas-Odenthal & Paula Usemann

  8. Institute for Translational Psychiatry, University of Münster, Münster, Germany

    Carlotta Barkhau, Udo Dannlowski, Katharina Dohm, Kira Flinkenflügel, Dominik Grotegerd, Marius Gruber, Anna Kraus, Hannah Meinert, Susanne Meinert & Nils Opel

  9. Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milano, Italy

    Francesco Benedetti, Elena Mazza & Elisa M. T. Melloni

  10. University Vita-Salute San Raffaele, Milano, Italy

    Francesco Benedetti, Elena Mazza & Elisa M. T. Melloni

  11. Institute for Mental and Physical Health and Clinical Translation School of Medicine, Deakin University, Geelong, VIC, Australia

    Michael Berk & Chao Suo

  12. Unit for Psychosomatics and C-L psychiatry for adults, Oslo University Hospital, Oslo, Norway

    Erlend Bøen & Birgitte Boye

  13. Department of Behavioural Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

    Birgitte Boye & Torbjørn Elvsåshagen

  14. FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain

    Erick J. Canales-Rodríguez, Edith Pomarol-Clotet, Raymond Salvador & Edith Pomarol-Clotet

  15. Mental Health Research Networking Center (CIBERSAM), ISC III, Barcelona, Spain

    Erick J. Canales-Rodríguez, Edith Pomarol-Clotet, Joaquim Radua, Raymond Salvador, Eduard Vieta, Enric Vilajosana & Edith Pomarol-Clotet

  16. Centre for Neuroimaging and Cognitive Genomics, Clinical Neuroimaging Laboratory, Galway Neuroscience Centre, College of Medicine, Nursing, and Health Sciences, University of Galway, Galway, Ireland

    Dara M. Cannon & Colm McDonald

  17. Centre for Mental Health and Brain Sciences, School of Health Sciences, Swinburne University, Melbourne, VIC, Australia

    Sean P. Carruthers, Susan L. Rossell, Tamsyn E. Van Rheenen & Tamsyn E. Van Rheenen

  18. Research Group in Psychiatry GIPSI, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellin, Colombia

    Ana M. Díaz-Zuluaga & Carlos López-Jaramillo

  19. Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Torbjørn Elvsåshagen

  20. Department of Neurology, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway

    Torbjørn Elvsåshagen

  21. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

    Lydia Fortea, Joaquim Radua, Eduard Vieta & Enric Vilajosana

  22. Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia

    Lisa S. Furlong, James A. Karantonis, Tamsyn E. Van Rheenen & Tamsyn E. Van Rheenen

  23. Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Benjamin I. Goldstein, Kody G. Kennedy & Bradley J. MacIntosh

  24. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Goethe, Germany

    Marius Gruber

  25. Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Bartholomeus C. M. Haarman

  26. Neuroscience Institute, University of Cape Town, Cape Town, South Africa

    Fleur M. Howells

  27. Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa

    Fleur M. Howells

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

    Neda Jahanshad, Sophia I. Thomopoulos, Christopher R. K. Ching & Paul M. Thompson

  29. Core-Facility Brainimaging, Faculty of Medicine, University of Marburg, Marburg, Germany

    Andreas Jansen

  30. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden

    Anna Luisa Klahn & Mikael Landén

  31. Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA

    Peter Kochunov, Jair C. Soares, Giovana B. Zunta-Soares, Benson Mwangi & Mon-Ju Wu

  32. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Mikael Landén

  33. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    Bradley J. MacIntosh

  34. Center for Brain Resilience & Recovery, Hurvitz Brain Sciences Program, Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada

    Bradley J. MacIntosh

  35. Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, UK

    Andrew M. McIntosh & Heather C. Whalley

  36. Generation Scotland, Institute for Genetics and Cancer, University of Edinburgh, Edinburgh, UK

    Andrew M. McIntosh & Heather C. Whalley

  37. Institute for Translational Neuroscience, University of Münster, Münster, Germany

    Susanne Meinert

  38. Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia

    Philip B. Mitchell, Gloria Roberts & Wei Wen

  39. Black Dog Institute, Sydney, Sydney, NSW, Australia

    Philip B. Mitchell

  40. Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany

    Nils Opel

  41. German Center for Mental Health (DZPG), Jena, Germany

    Nils Opel

  42. University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Mary Phillips & Amelia Versace

  43. Synapsy Center, Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Camille Piguet

  44. Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble, France

    Mircea Polosan & Arnaud Pouchon

  45. Department of Psychiatry, St. Vincent’s Hospital, Melbourne, Australia

    Susan L. Rossell

  46. West Region, Institute of Mental Health, Singapore, Singapore

    Kang Sim

  47. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Kang Sim

  48. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

    Kang Sim

  49. Bipolar Disorders Unit, Clinical Institute of Neurosciences, Hospital Clínic, Barcelona, Spain

    Eduard Vieta

  50. Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway

    Ole A. Andreassen

  51. NORMENT Centre, University of Oslo, Oslo, Norway

    Ole A. Andreassen

  52. Assistance Publique-Hôpitaux de Paris (AP-HP), CHU Mondor, Psychiatry Department, Créteil, France

    Josselin Houenou

  53. Faculté de Médecine, Université Paris Est Créteil, Créteil, France

    Josselin Houenou

  54. National Institute of Mental Health, Klecany, Czech Republic

    Tomas Hajek

Authors
  1. Lorielle M. F. Dietze
    View author publications

    Search author on:PubMed Google Scholar

  2. Sean R. McWhinney
    View author publications

    Search author on:PubMed Google Scholar

  3. Pauline Favre
    View author publications

    Search author on:PubMed Google Scholar

  4. Christoph Abé
    View author publications

    Search author on:PubMed Google Scholar

  5. Nina Alexander
    View author publications

    Search author on:PubMed Google Scholar

  6. Carlotta Barkhau
    View author publications

    Search author on:PubMed Google Scholar

  7. Francesco Benedetti
    View author publications

    Search author on:PubMed Google Scholar

  8. Michael Berk
    View author publications

    Search author on:PubMed Google Scholar

  9. Erlend Bøen
    View author publications

    Search author on:PubMed Google Scholar

  10. Birgitte Boye
    View author publications

    Search author on:PubMed Google Scholar

  11. Katharina Brosch
    View author publications

    Search author on:PubMed Google Scholar

  12. Erick J. Canales-Rodríguez
    View author publications

    Search author on:PubMed Google Scholar

  13. Dara M. Cannon
    View author publications

    Search author on:PubMed Google Scholar

  14. Sean P. Carruthers
    View author publications

    Search author on:PubMed Google Scholar

  15. Emily L. V. Corkum
    View author publications

    Search author on:PubMed Google Scholar

  16. Udo Dannlowski
    View author publications

    Search author on:PubMed Google Scholar

  17. Ana M. Díaz-Zuluaga
    View author publications

    Search author on:PubMed Google Scholar

  18. Katharina Dohm
    View author publications

    Search author on:PubMed Google Scholar

  19. Torbjørn Elvsåshagen
    View author publications

    Search author on:PubMed Google Scholar

  20. Kira Flinkenflügel
    View author publications

    Search author on:PubMed Google Scholar

  21. Lydia Fortea
    View author publications

    Search author on:PubMed Google Scholar

  22. Lisa S. Furlong
    View author publications

    Search author on:PubMed Google Scholar

  23. Benjamin I. Goldstein
    View author publications

    Search author on:PubMed Google Scholar

  24. Dominik Grotegerd
    View author publications

    Search author on:PubMed Google Scholar

  25. Marius Gruber
    View author publications

    Search author on:PubMed Google Scholar

  26. Bartholomeus C. M. Haarman
    View author publications

    Search author on:PubMed Google Scholar

  27. Fleur M. Howells
    View author publications

    Search author on:PubMed Google Scholar

  28. Neda Jahanshad
    View author publications

    Search author on:PubMed Google Scholar

  29. Hamidreza Jamalabadi
    View author publications

    Search author on:PubMed Google Scholar

  30. Andreas Jansen
    View author publications

    Search author on:PubMed Google Scholar

  31. James A. Karantonis
    View author publications

    Search author on:PubMed Google Scholar

  32. Kody G. Kennedy
    View author publications

    Search author on:PubMed Google Scholar

  33. Tilo T. J. Kircher
    View author publications

    Search author on:PubMed Google Scholar

  34. Anna Luisa Klahn
    View author publications

    Search author on:PubMed Google Scholar

  35. Peter Kochunov
    View author publications

    Search author on:PubMed Google Scholar

  36. Anna Kraus
    View author publications

    Search author on:PubMed Google Scholar

  37. Mikael Landén
    View author publications

    Search author on:PubMed Google Scholar

  38. Carlos López-Jaramillo
    View author publications

    Search author on:PubMed Google Scholar

  39. Bradley J. MacIntosh
    View author publications

    Search author on:PubMed Google Scholar

  40. Elena Mazza
    View author publications

    Search author on:PubMed Google Scholar

  41. Colm McDonald
    View author publications

    Search author on:PubMed Google Scholar

  42. Andrew M. McIntosh
    View author publications

    Search author on:PubMed Google Scholar

  43. Hannah Meinert
    View author publications

    Search author on:PubMed Google Scholar

  44. Susanne Meinert
    View author publications

    Search author on:PubMed Google Scholar

  45. Elisa M. T. Melloni
    View author publications

    Search author on:PubMed Google Scholar

  46. Philip B. Mitchell
    View author publications

    Search author on:PubMed Google Scholar

  47. Igor Nenadić
    View author publications

    Search author on:PubMed Google Scholar

  48. Nils Opel
    View author publications

    Search author on:PubMed Google Scholar

  49. Mary Phillips
    View author publications

    Search author on:PubMed Google Scholar

  50. Camille Piguet
    View author publications

    Search author on:PubMed Google Scholar

  51. Mircea Polosan
    View author publications

    Search author on:PubMed Google Scholar

  52. Edith Pomarol-Clotet
    View author publications

    Search author on:PubMed Google Scholar

  53. Arnaud Pouchon
    View author publications

    Search author on:PubMed Google Scholar

  54. Joaquim Radua
    View author publications

    Search author on:PubMed Google Scholar

  55. Gloria Roberts
    View author publications

    Search author on:PubMed Google Scholar

  56. Alex J. Ross
    View author publications

    Search author on:PubMed Google Scholar

  57. Susan L. Rossell
    View author publications

    Search author on:PubMed Google Scholar

  58. Raymond Salvador
    View author publications

    Search author on:PubMed Google Scholar

  59. Kang Sim
    View author publications

    Search author on:PubMed Google Scholar

  60. Jair C. Soares
    View author publications

    Search author on:PubMed Google Scholar

  61. Giovana B. Zunta-Soares
    View author publications

    Search author on:PubMed Google Scholar

  62. Frederike Stein
    View author publications

    Search author on:PubMed Google Scholar

  63. Benjamin Straube
    View author publications

    Search author on:PubMed Google Scholar

  64. Chao Suo
    View author publications

    Search author on:PubMed Google Scholar

  65. Lea Teutenberg
    View author publications

    Search author on:PubMed Google Scholar

  66. Florian Thomas-Odenthal
    View author publications

    Search author on:PubMed Google Scholar

  67. Sophia I. Thomopoulos
    View author publications

    Search author on:PubMed Google Scholar

  68. Paula Usemann
    View author publications

    Search author on:PubMed Google Scholar

  69. Tamsyn E. Van Rheenen
    View author publications

    Search author on:PubMed Google Scholar

  70. Amelia Versace
    View author publications

    Search author on:PubMed Google Scholar

  71. Eduard Vieta
    View author publications

    Search author on:PubMed Google Scholar

  72. Enric Vilajosana
    View author publications

    Search author on:PubMed Google Scholar

  73. Benson Mwangi
    View author publications

    Search author on:PubMed Google Scholar

  74. Wei Wen
    View author publications

    Search author on:PubMed Google Scholar

  75. Heather C. Whalley
    View author publications

    Search author on:PubMed Google Scholar

  76. Mon-Ju Wu
    View author publications

    Search author on:PubMed Google Scholar

  77. Ole A. Andreassen
    View author publications

    Search author on:PubMed Google Scholar

  78. Christopher R. K. Ching
    View author publications

    Search author on:PubMed Google Scholar

  79. Paul M. Thompson
    View author publications

    Search author on:PubMed Google Scholar

  80. Josselin Houenou
    View author publications

    Search author on:PubMed Google Scholar

  81. Tomas Hajek
    View author publications

    Search author on:PubMed Google Scholar

Consortia

for the ENIGMA Bipolar Disorder Working Group

  • Francesco Benedetti
  • , Michael Berk
  • , Dara M. Cannon
  • , Udo Dannlowski
  • , Torbjørn Elvsåshagen
  • , Benjamin I. Goldstein
  • , Bartholomeus C. M. Haarman
  • , Fleur M. Howells
  • , Neda Jahanshad
  • , Tilo T. J. Kircher
  • , Mikael Landén
  • , Carlos López-Jaramillo
  • , Colm McDonald
  • , Andrew M. McIntosh
  • , Philip B. Mitchell
  • , Mary Phillips
  • , Camille Piguet
  • , Mircea Polosan
  • , Edith Pomarol-Clotet
  • , Joaquim Radua
  • , Kang Sim
  • , Jair C. Soares
  • , Tamsyn E. Van Rheenen
  • , Eduard Vieta
  • , Heather C. Whalley
  • , Ole A. Andreassen
  • , Christopher R. K. Ching
  • , Paul M. Thompson
  • , Josselin Houenou
  •  & Tomas Hajek

for the ENIGMA BMI-X Working Group

  • Benjamin I. Goldstein
  • , Andrew M. McIntosh
  • , Nils Opel
  • , Heather C. Whalley
  • , Christopher R. K. Ching
  • , Paul M. Thompson
  •  & Tomas Hajek

Contributions

The following authors contributed substantially to the conception, design, analyses and interpretation of the data (LMFD, TH, SRM, PMT, PF, JH). All authors contributed to data collection/processing, revised the paper critically for important intellectual content and gave final approval of the version to be published.

Corresponding author

Correspondence to Tomas Hajek.

Ethics declarations

Competing interests

PMT, CRKC and NJ received past research support from Biogen Inc. for work unrelated to this manuscript. TE is a consultant to Sumitomo Pharma and Cumulus and received speaker’s honoraria from Lundbeck and Janssen Cilag. Texas cohort (JS) has received speaking/consulting and/or research grants from: ALKERMES (Advisory Board), BOEHRINGER Ingelheim (Consultant), COMPASS Pathways (Research Grant), JOHNSON & JOHNSON (Consultant), LIVANOVA (Consultant), RELMADA (Research Grant), SUNOVION (Research Grant), Mind Med (Research Grant).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dietze, L.M.F., McWhinney, S.R., Favre, P. et al. White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals. Mol Psychiatry 30, 1770–1779 (2025). https://doi.org/10.1038/s41380-024-02784-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-024-02784-2

Search

Advanced search

Quick links