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Major depressive disorder

Nature Reviews Disease Primers volume 9, Article number: 44 (2023) Cite this article

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Abstract

Major depressive disorder (MDD) is characterized by persistent depressed mood, loss of interest or pleasure in previously enjoyable activities, recurrent thoughts of death, and physical and cognitive symptoms. People with MDD can have reduced quality of life owing to the disorder itself as well as related medical comorbidities, social factors, and impaired functional outcomes. MDD is a complex disorder that cannot be fully explained by any one single established biological or environmental pathway. Instead, MDD seems to be caused by a combination of genetic, environmental, psychological and biological factors. Treatment for MDD commonly involves pharmacological therapy with antidepressant medications, psychotherapy or a combination of both. In people with severe and/or treatment-resistant MDD, other biological therapies, such as electroconvulsive therapy, may also be offered.

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Fig. 1: Prevalence of MDD across global regions over time.
Fig. 2: Prevalence of MDD by country.
Fig. 3: Biological mechanisms of action implicated in the pathogenesis of MDD.
Fig. 4: Total score distribution of the PHQ-9 in the general population.
Fig. 5: Efficacy of different antidepressant medications compared to placebo in MDD.

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Acknowledgements

M.B. is supported by an NHMRC Senior Principal Research Fellowship and Leadership 3 Investigator grant (1156072 and 2017131). W.M. is currently funded by an NHMRC Investigator Grant (#2008971). J.F. is supported by UK Research and Innovation Future Leaders Fellowship (MR/T021780/1).

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Authors and Affiliations

  1. Deakin University, IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Victoria, Australia

    Wolfgang Marx, Andre F. Carvalho & Michael Berk

  2. Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands

    Brenda W. J. H. Penninx

  3. Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada

    Marco Solmi

  4. On Track: The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada

    Marco Solmi

  5. Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany

    Marco Solmi

  6. Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan

    Toshi A. Furukawa

  7. Division of Psychology and Mental Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

    Joseph Firth

  8. Greater Manchester Mental Health NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK

    Joseph Firth

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Contributions

Introduction (W.M. and M.B.); Epidemiology (W.M., J.F. and M.B.); Mechanisms/pathophysiology (W.M., B.W.J.H.P. and M.B.); Diagnosis, screening and prevention (W.M., T.A.F. and M.B.); Management (W.M., M.S. and M.B.); Quality of life (W.M., A.F.C. and M.B.); Outlook (W.M. and M.B.); Overview of Primer (W.M. and M.B.).

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Correspondence to Wolfgang Marx.

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Competing interests

M.S. has received honoraria from and has been a consultant for AbbVie, Angelini, Lundbeck and Otsuka. M.B. has received grant and research support from the National Health and Medical Research Council, Wellcome Trust, Medical Research Future Fund, Victorian Medical Research Acceleration Fund, Centre for Research Excellence CRE, Victorian Government Department of Jobs, Precincts and Regions and Victorian COVID-19 Research Fund. He received honoraria from Springer, Oxford University Press, Cambridge University Press, Allen and Unwin, Lundbeck, Controversias Barcelona, Servier, Medisquire, HealthEd, ANZJP, EPA, Janssen, Medplan, Milken Institute, RANZCP, Abbott India, ASCP, Headspace and Sandoz (last 3 years). W.M. has received funding and/or has attended events funded by Cobram Estate Pty. Ltd and Bega Dairy and Drinks Pty Ltd. W.M. has received consultancy funding from Nutrition Research Australia and ParachuteBH. B.W.J.H.P. has received research grants from Boehringer-Ingelheim and Jansen and received consultancy funding from Angelini and Ekademeia Psychiatry. T.A.F. reports personal fees from Boehringer-Ingelheim, DT Axis, Kyoto University Original, Shionogi and SONY, and a grant from Shionogi, outside the submitted work. In addition, T.A.F. has patents 2020-548587 and 2022-082495 pending, and intellectual properties for Kokoro-app licensed to Mitsubishi-Tanabe. J.F. has received honoraria or consultancy fees from Atheneum, Informa, Gillian Kenny Associates, Big Health, Wood For Trees, Nutritional Medicine Institute, Angelini, ParachuteBH, Richmond Foundation and Nirakara, independent of this work.

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Marx, W., Penninx, B.W.J.H., Solmi, M. et al. Major depressive disorder. Nat Rev Dis Primers 9, 44 (2023). https://doi.org/10.1038/s41572-023-00454-1

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