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Genetics and neurobiology of eating disorders

Nature Neuroscience volume 25, pages 543–554 (2022)Cite this article

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Abstract

Eating disorders (anorexia nervosa, bulimia nervosa and binge-eating disorder) are a heterogeneous class of complex illnesses marked by weight and appetite dysregulation coupled with distinctive behavioral and psychological features. Our understanding of their genetics and neurobiology is evolving thanks to global cooperation on genome-wide association studies, neuroimaging, and animal models. Until now, however, these approaches have advanced the field in parallel, with inadequate cross-talk. This review covers overlapping advances in these key domains and encourages greater integration of hypotheses and findings to create a more unified science of eating disorders. We highlight ongoing and future work designed to identify implicated biological pathways that will inform staging models based on biology as well as targeted prevention and tailored intervention, and will galvanize interest in the development of pharmacologic agents that target the core biology of the illnesses, for which we currently have few effective pharmacotherapeutics.

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Fig. 1: Genetic correlations between anorexia nervosa and selected top traits.
Fig. 2: Human neuroimaging circuitry involved in eating disorders.
Fig. 3: Forward and backward translation of eating disorder-relevant traits at different levels of biological hierarchy.
Fig. 4: Mesocorticolimbic reward dysfunction in activity-based anorexia.
Fig. 5: Mesolimbic-centered neural circuits that modulate binge-like eating.

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Acknowledgements

C.M.B. is supported by the National Institute of Mental Health (R01MH120170, R01MH124871, R01MH119084, R01MH118278 and R01MH124871), a Brain and Behavior Research Foundation Distinguished Investigator grant, the Swedish Research Council (Vetenskapsrådet, award no. 538-2013-8864), and the Lundbeck Foundation (grant no. R276-2018-4581). J.R.I.C. and G.B. acknowledge that the paper represents independent research part funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. J.A.H. is supported by K01DK115902. C.D.B. is supported by U01DA050243 and U01DA055299. L.B. is supported by T32MH112485, a Harvard Medical School Livingston Fellowship and the International OCD Foundation. G.B. is also supported by the UK Medical Research Council (MR/V012878/1, MR/V03605X/1 and MR/R024804/1) and Charlotte’s Helix.

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Authors and Affiliations

  1. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Cynthia M. Bulik & Hunna J. Watson

  2. Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Cynthia M. Bulik

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

    Cynthia M. Bulik

  4. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Jonathan R. I. Coleman & Gerome Breen

  5. National Institute of Health Research Maudsley Biomedical Research Centre, South London and Maudsley National Health Service Trust, London, UK

    Jonathan R. I. Coleman & Gerome Breen

  6. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA

    J. Andrew Hardaway

  7. Department of Psychiatry, Harvard Medical School, Boston, MA, USA

    Lauren Breithaupt

  8. Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA

    Lauren Breithaupt

  9. School of Psychology, Curtin University, Perth, Western Australia, Australia

    Hunna J. Watson

  10. Division of Paediatrics, School of Medicine, The University of Western Australia, Perth, Western Australia, Australia

    Hunna J. Watson

  11. Department of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA

    Camron D. Bryant

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Contributions

C.M.B., J.R.I.C., J.A.H., L.B., C.D.B., H.W. and G.B. all substantially contributed to the writing of the manuscript, approved the submitted version, are personally accountable for their own contribution, and ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.

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Correspondence to Cynthia M. Bulik.

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Competing interests

C.M.B. reports the following competing interests: Shire (grant recipient, Scientific Advisory Board member); Idorsia (consultant); Pearson (author, royalty recipient); Equip Health (Clinical Advisory Board Member). G.B. reports the following competing interests: Otsuka Pharma (advisory board); Illumina (grant recipient, conference sponsorship). The other authors declare no competing interests.

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Bulik, C.M., Coleman, J.R.I., Hardaway, J.A. et al. Genetics and neurobiology of eating disorders. Nat Neurosci 25, 543–554 (2022). https://doi.org/10.1038/s41593-022-01071-z

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