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Diet and depression: exploring the biological mechanisms of action

Molecular Psychiatry volume 26, pages 134–150 (2021)Cite this article

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Abstract

The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression onset and symptom management. To guide future clinical trials and targeted dietary therapies, this review provides an overview of what is currently known regarding underlying mechanisms of action by which diet may influence mental and brain health. The mechanisms of action associating diet with health outcomes are complex, multifaceted, interacting, and not restricted to any one biological pathway. Numerous pathways were identified through which diet could plausibly affect mental health. These include modulation of pathways involved in inflammation, oxidative stress, epigenetics, mitochondrial dysfunction, the gut microbiota, tryptophan–kynurenine metabolism, the HPA axis, neurogenesis and BDNF, epigenetics, and obesity. However, the nascent nature of the nutritional psychiatry field to date means that the existing literature identified in this review is largely comprised of preclinical animal studies. To fully identify and elucidate complex mechanisms of action, intervention studies that assess markers related to these pathways within clinically diagnosed human populations are needed.

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Fig. 1: Overview of the role of diet quality on implicated mechanisms of depression.
Fig. 2: Proposed interplay between dietary quality and implicated mechanisms in alleviating depression.

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Authors and Affiliations

  1. Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, Geelong, VIC, Australia

    Wolfgang Marx, Melissa Lane, Meghan Hockey, Hajara Aslam, Michael Berk, Heidi M. Staudacher, Adrienne O’Neil & Felice N. Jacka

  2. Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health, Melbourne, VIC, Australia

    Michael Berk

  3. Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia

    Michael Berk

  4. Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Metabolic Research Unit, Geelong, VIC, Australia

    Ken Walder

  5. Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Alessandra Borsini & Carmine M. Pariante

  6. Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

    Joseph Firth

  7. NICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia

    Joseph Firth

  8. APC Microbiome Ireland, University College Cork, Cork, Ireland

    Kirsten Berding, John F. Cryan & Gerard Clarke

  9. Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland

    John F. Cryan

  10. Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland

    Gerard Clarke

  11. INFANT Research Centre, University College Cork, Cork, Ireland

    Gerard Clarke

  12. Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Geelong, VIC, Australia

    Jeffrey M. Craig

  13. Departments of Psychiatry and Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan

    Kuan-Pin Su

  14. An-Nan Hospital, China Medical University, Tainan, Taiwan

    Kuan-Pin Su

  15. College of Medicine, China Medical University, Taichung, Taiwan

    Kuan-Pin Su

  16. Department of Psychiatry, Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA

    David Mischoulon

  17. Harvard Medical School, Boston, MA, USA

    David Mischoulon

  18. Departments of Neurosurgery and Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA

    Fernando Gomez-Pinilla

  19. Department of Psychiatry & Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada

    Jane A. Foster

  20. UCLouvain, Université catholique de Louvain, WELBIO—Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Brussels, Belgium

    Patrice D. Cani

  21. Basic and Clinical Neuroscience Department, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, UK

    Sandrine Thuret & Toby Segasby

  22. Nutrition Research Group, Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Gran Canaria, Spain

    Almudena Sánchez-Villegas

  23. Biomedical Research Center Network on Obesity and Nutrition (CIBERobn) Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain

    Almudena Sánchez-Villegas

  24. Université Paris-Saclay, UVSQ, Inserm, CESP, “DevPsy”, 94807, Villejuif, France

    Husnain Arshad & Tasnime Akbaraly

  25. Department of Epidemiology and Public Health, University College London, London, UK

    Tasnime Akbaraly

  26. Centre for Adolescent Health, Murdoch Children’s Research Institute, Melbourne, VIC, Australia

    Felice N. Jacka

  27. Black Dog Institute, Randwick, NSW, Australia

    Felice N. Jacka

  28. James Cook University, Townsville, QLD, Australia

    Felice N. Jacka

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  1. Wolfgang Marx
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  2. Melissa Lane
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  3. Meghan Hockey
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  16. Fernando Gomez-Pinilla
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Correspondence to Wolfgang Marx.

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Conflict of interest

WM is currently funded by an Alfred Deakin Postdoctoral Research Fellowship and a Multiple Sclerosis Research Australia early-career fellowship. WM has previously received funding from the Cancer Council Queensland and university grants/fellowships from La Trobe University, Deakin University, University of Queensland, and Bond University. WM has received industry funding and has attended events funded by Cobram Estate Pty Ltd. WM has received travel funding from Nutrition Society of Australia. WM has received consultancy funding from Nutrition Research Australia. WM has received speakers honoraria from The Cancer Council Queensland and the Princess Alexandra Research Foundation. ML is funded by a Deakin University Ph.D. Scholarship and has received research support from Be Fit Foods. MH is supported by an Australian Rotary Health Ph.D. Scholarship and has received research support from The A2 Milk Company. HA is supported by a Deakin University Postgraduate Industry Research Scholarship. MB is supported by a NHMRC Senior Principal Research Fellowship (1059660 and 1156072) and has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Lundbeck, Merck, Pfizer, and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Lundbeck Merck, Pfizer and Servier. KW has previously received funding from Australian Research Council, National Health and Medical Research Council, and ChemGenex Pharmaceuticals. AB and CMP have received research funding from Johnson & Johnson for research on depression and inflammation which included cellular work (2012–2018); moreover, CMP is funded by a Wellcome Trust strategy award to the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium (104025), which is also funded by Janssen, GlaxoSmithKline, Lundbeck and Pfizer. The work presented in this paper is unrelated to this funding. AB and CMP are funded by the UK Medical Research Council (grants MR/L014815/1, MR/J002739/1 and MR/N029488/1), the European Commission Horizon 2020 (grant SC1-BHC-01-2019) and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. CMP is a NIHR Senior Investigator (2017–2025). KB is funded by an Irish Research Council postdoctoral fellowship. JFC is supported by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273-P2), Joint Programming Initiative JPI-HDHL-NutriCog project ‘AMBROSIAC’ (15/JPHDHL/3270); Joint Programming Initiative HEALTHMARK: Metabolic HEALTH through nutrition,microbiota and tryptophan bioMARKers, 16/ERAHDHL/3362. (EU Horizon 2020 funding—DISCOvERIE (Development, dIagnosis and prevention of gender-related Somatic and mental COmorbiditiEs in iRrItable bowel syndrome in Europe), Swiss National Foundation Sinergia grant GUT–BRAIN; Irish Research Council; European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 797592 and 754535.; Irish Research Council Postgraduate Scholarship GOIPG/2019/3198; GOIPG/2018/2560. Health Research Board (HRB) Grant number ILP-POR-2017-013; Institute for Scientific Information on Coffee, and the Saks Kavanaugh Foundation. JFC received research support from Mead Johnson, Cremo, 4D Pharma, Pharmavite, and Nutricia. He has been a consultant for Alkermes and Nestle and has spoken at meetings sponsored by Mead Johnson, Abbott Nutrition, Roche, Ordesa and Neuraxpharm. GC is a principal investigator in APC Microbiome Ireland, a research centre funded by Science Foundation Ireland (SFI) (grant no. 12/RC/2273-P2). His research is currently supported by the Irish Health Research Board (HRB) (Grant number ILP-POR-2017-013). He has spoken at meetings sponsored by food (Probi) and pharmaceutical companies (Janssen) and is also in receipt of research funding from Pharmavite. JF is supported by a University of Manchester Presidential Fellowship (P123958) and a UK Research and Innovation Future Leaders Fellowship (MR/T021780/1) and has received support from a NICM-Blackmores Institute Fellowship. JMC is currently funded by the Australian Research Council (DP190103081); the National Health and Medical Research Council (APP114333; APP1079102); the Waterloo Foundation; DNA Genotek; and Trajan Scientific and Medical. KPS has received the following research grants related to this work: MOST 106-2314-B-039-027-MY3, 108-2320-B-039-048, 108-2813-C-039-133-B and 108-2314-B-039-016 from the Ministry of Science and Technology, Taiwan; NHRI-EX108-10528NI from the National Health Research Institutes, Taiwan; MYRG2018-00242-ICMS from University of Macau, China; CMRC-CMA-3 from Higher Education Sprout Project by the Ministry of Education (MOE), Taiwan; CMU108-SR-106 from the China Medical University, Taichung, Taiwan; and CRS-108-048, DMR-108-216 and DMR-109-102 from the China Medical University Hospital, Taichung, Taiwan. KPS has been a speaker and/or consultant for Johnson & Johnson, Astra Zeneca, Lundbeck, Eli Lilly, Merck, Pfizer, Servier, Otsuka, Excelsior Biopharma, Chen Hua Biotech, Nutrarex Biotech, and Hoan Pharmaceuticals—all unrelated to this work. DM has received research support from Nordic Naturals and heckel medizintechnik GmbH. He has provided unpaid consulting for Pharmavite LLC and Gnosis USA, Inc. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy, Blackmores, Harvard Blog, and PeerPoint Medical Education Institute, LLC. He has received royalties from Lippincott Williams and Wilkins for published book “Natural medications for Psychiatric Disorders: considering the Alternatives. He also works with the MGH Clinical Trials Network and Institute (CTNI), which has received research funding from multiple pharmaceutical companies and NIMH. FGP is currently funded by research awards from the NINDS of National Institute of Health. He serves as a consultant and member of the Scientific Advisory Board of Nutrient Foods, LLC. JF received research funding from the National Sciences and Engineering Research Council of Canada (NSERC) and the Ontario Brain Institute, which is an independent non-profit corporation, funded partially by the Ontario Government. Jane Foster has received consultancy fees from Novozymes A/S and Rothmans, Benson & Hedges Inc. PDC is a senior research associate at FRS-FNRS (Fonds de la Recherche Scientifique), Belgium. He is supported by the Fonds Baillet Latour (Grant for Medical Research 2015), the Fonds de la Recherche Scientifique (FNRS, FRFS-WELBIO: WELBIO-CR-2019C-02R) and ERC Starting Grant 2013 (336452-ENIGMO). PDC is co-founder of A-Mansia biotech SA and inventors on patent applications about the therapeutic use of Akkermansia muciniphila and its components. ST: Diet and mental health research in the Thuret lab is funded by grants awarded by the Medical Research Council UK (MR/N030087/1 and MR/S00484X/1, the European Union’s H2020 Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’ and the Network of Centres of Excellence in Neurodegeneration (COEN). HS has previously received non-financial and financial support from CD investments VSL pharmaceuticals and is currently funded by an Alfred Deakin Postdoctoral Research Fellowship. HA declares no funding declarations. TA is supported by the Centre of Excellence for Neurodegenerative disorders (COEN—Hospital Centre of Montpellier). AON is supported by a Future Leader Fellowship (#101160) from the Heart Foundation Australia and Wilson Foundation. She has received research funding from the National Health & Medical Research Council, Australian Research Council, University of Melbourne, Deakin University, Sanofi, Meat and Livestock Australia and Woolworths Limited and Honoraria from Novartis. The Food & Mood Centre has received funding from the Fernwood Foundation, the A2 Milk Company and Be Fit Foods. HS has previously received non-financial and financial support from CD investments VSL pharmaceuticals and is currently funded by an Alfred Deakin Postdoctoral Research Fellowship. TS has no funding declarations. FNJ has received Grant/Research support from the Brain and Behaviour Research Institute, the National Health and Medical Research Council (NHMRC), Australian Rotary Health, the Geelong Medical Research Foundation, the Ian Potter Foundation, Eli Lilly, Meat and Livestock Australia, Woolworths Limited, Fernwood Foundation, Wilson Foundation, The A2 Milk Company, Be Fit Foods, and The University of Melbourne and has received speakers honoraria from Sanofi-Synthelabo, Janssen Cilag, Servier, Pfizer, Health Ed, Network Nutrition, Angelini Farmaceutica, Eli Lilly and Metagenics. Felice Jacka has written two books for commercial publication and has a personal belief that good diet quality is important for mental and brain health.

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Marx, W., Lane, M., Hockey, M. et al. Diet and depression: exploring the biological mechanisms of action. Mol Psychiatry 26, 134–150 (2021). https://doi.org/10.1038/s41380-020-00925-x

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