Diet and depression: exploring the biological mechanisms of action

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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.

References

  1. 1.

    Marx W, Moseley G, Berk M, Jacka F. Nutritional psychiatry: the present state of the evidence. Proc Nutr Soc. 2017;76:427–36.

    PubMed  Google Scholar 

  2. 2.

    Jacka FN, O’Neil A, Opie R, Itsiopoulos C, Cotton S, Mohebbi M, et al. A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Med. 2017;15:23.

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Lassale C, Batty GD, Baghdadli A, Jacka F, Sanchez-Villegas A, Kivimaki M, et al. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry. 2019;24:965–86.

    PubMed  Google Scholar 

  4. 4.

    Firth J, Marx W, Dash S, Carney R, Teasdale SB, Solmi M, Stubbs B, Schuch FB, Carvalho AF, Jacka F, Sarris J. The effects of dietary improvement on symptoms of depression and anxiety: a meta-analysis of randomized controlled trials. Psychosomatic medicine. 2019;81:265.

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Jacka FN, Pasco JA, Mykletun A, Williams LJ, Hodge AM, O’Reilly SL, et al. Association of western and traditional diets with depression and anxiety in women. Am J Psychiatry. 2010;167:305–11.

    PubMed  Google Scholar 

  6. 6.

    Jacka FN, Pasco JA, Mykletun A, Williams LJ, Nicholson GC, Kotowicz MA, et al. Diet quality in bipolar disorder in a population-based sample of women. J Affect Disord. 2011;129:332–7.

    PubMed  Google Scholar 

  7. 7.

    Khalid S, Williams CM, Reynolds SA. Is there an association between diet and depression in children and adolescents? A systematic review. Br J Nutr. 2016;116:2097–108.

    CAS  PubMed  Google Scholar 

  8. 8.

    Borge TC, Aase H, Brantsæter AL, Biele G. The importance of maternal diet quality during pregnancy on cognitive and behavioural outcomes in children: a systematic review and meta-analysis. BMJ Open. 2017;7:e016777.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Parletta N, Zarnowiecki D, Cho J, Wilson A, Bogomolova S, Villani A, Itsiopoulos C, Niyonsenga T, Blunden S, Meyer B, Segal L. A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutritional neuroscience. 2019;22:474–87.

    CAS  PubMed  Google Scholar 

  10. 10.

    Francis HM, Stevenson RJ, Chambers JR, Gupta D, Newey B, Lim CK. A brief diet intervention can reduce symptoms of depression in young adults–A randomised controlled trial. PloS one. 2019;14:e0222768.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Ma J, Rosas LG, Lv N, Xiao L, Snowden MB, Venditti EM, et al. Effect of integrated behavioral weight loss treatment and problem-solving therapy on body mass index and depressive symptoms among patients with obesity and depression: the RAINBOW randomized clinical trial. Jama. 2019;321:869–79.

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Bot M, Brouwer IA, Roca M, Kohls E, Penninx B, Watkins E, et al. Effect of multinutrient supplementation and food-related behavioral activation therapy on prevention of major depressive disorder among overweight or obese adults with subsyndromal depressive symptoms: the MooDFOOD randomized clinical trial. Jama. 2019;321:858–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Sanchez-Villegas A, Martinez-Gonzalez M, Estruch R, Salas-Salvado J, Corella D, Covas M, et al. Mediterranean dietary pattern and depression: the PREDIMED randomized trial. BMC Med. 2013;11:208.

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Berk M, Williams LJ, Jacka FN, O’Neil A, Pasco JA, Moylan S, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013;11:200.

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Cryan JF, O’Riordan KJ, Cowan CS, Sandhu KV, Bastiaanssen TF, Boehme M, et al. The microbiota-gut-brain axis. Physiol Rev. 2019;99:1877–2013.

    CAS  PubMed  Google Scholar 

  16. 16.

    Maes M, Galecki P, Chang YS, Berk M. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:676–92.

    CAS  PubMed  Google Scholar 

  17. 17.

    Pariante CM, Lightman SL. The HPA axis in major depression: classical theories and new developments. Trends Neurosci. 2008;31:464–8.

    CAS  PubMed  Google Scholar 

  18. 18.

    Carvalho AF, Solmi M, Sanches M, Machado MO, Stubbs B, Ajnakina O, et al. Evidence-based umbrella review of 162 peripheral biomarkers for major mental disorders. Transl Psychiatry. 2020;10:1–13.

    Google Scholar 

  19. 19.

    Bauer ME, Teixeira AL. Inflammation in psychiatric disorders: what comes first? Ann N Y Acad Sci. 2019;1437:57–67.

    CAS  PubMed  Google Scholar 

  20. 20.

    Osimo EF, Cardinal RN, Jones PB, Khandaker GM. Prevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: An electronic health record-based study. Psychoneuroendocrinology. 2018;91:226–34.

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16:22–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Capuron L, Miller AH. Cytokines and psychopathology: lessons from interferon-alpha. Biol Psychiatry. 2004;56:819–24.

    CAS  PubMed  Google Scholar 

  23. 23.

    Pollak Y, Yirmiya R. Cytokine-induced changes in mood and behaviour: implications for ‘depression due to a general medical condition’, immunotherapy and antidepressive treatment. Int J Neuropsychopharmacol. 2002;5:389–99.

    CAS  PubMed  Google Scholar 

  24. 24.

    Hepgul N, Pariante CM, Baraldi S, Borsini A, Bufalino C, Russell A, et al. Depression and anxiety in patients receiving interferon-alpha: the role of illness perceptions. J Health Psychol. 2018;23:1405–14.

    PubMed  Google Scholar 

  25. 25.

    Köhler‐Forsberg O, Lydholm CN, Hjorthøj C, Nordentoft M, Mors O, Benros ME. Efficacy of anti‐inflammatory treatment on major depressive disorder or depressive symptoms: meta‐analysis of clinical trials. Acta Psychiatr Scand. 2019;139:404–19.

    PubMed  Google Scholar 

  26. 26.

    Kastorini C-M, Milionis HJ, Esposito K, Giugliano D, Goudevenos JA, Panagiotakos DB. The effect of Mediterranean diet on metabolic syndrome and its components: a meta-analysis of 50 studies and 534,906 individuals. J Am Coll Cardiol. 2011;57:1299–313.

    CAS  PubMed  Google Scholar 

  27. 27.

    Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. Jama. 2004;292:1440–6.

    CAS  PubMed  Google Scholar 

  28. 28.

    Giugliano D, Ceriello A, Esposito K. The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol. 2006;48:677–85.

    CAS  PubMed  Google Scholar 

  29. 29.

    Firth J, Stubbs B, Teasdale SB, Ward PB, Veronese N, Shivappa N, et al. Diet as a hot topic in psychiatry: a population‐scale study of nutritional intake and inflammatory potential in severe mental illness. World Psychiatry. 2018;17:365–7.

    PubMed  PubMed Central  Google Scholar 

  30. 30.

    Yahfoufi N, Alsadi N, Jambi M, Matar C. The immunomodulatory and anti-inflammatory role of polyphenols. Nutrients. 2018;10:11.

    Google Scholar 

  31. 31.

    Liao Y, Xie B, Zhang H, He Q, Guo L, Subramaniapillai M, et al. Efficacy of omega-3 PUFAs in depression: a meta-analysis. Transl Psychiatry. 2019;9:190.

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Su KP, Lai HC, Yang HT, Su WP, Peng CY, Chang JP, et al. Omega-3 fatty acids in the prevention of interferon-alpha-induced depression: results from a randomized, controlled trial. Biol psychiatry. 2014;76:559–66.

    CAS  PubMed  Google Scholar 

  33. 33.

    Rapaport MH, Nierenberg AA, Schettler PJ, Kinkead B, Cardoos A, Walker R, et al. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof of concept study. Mol Psychiatry. 2016;21:71–9.

    CAS  PubMed  Google Scholar 

  34. 34.

    Borsini A, Alboni S, Horowitz MA, Tojo LM, Cannazza G, Su KP, et al. Rescue of IL-1beta-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants. Brain Behav Immun. 2017;65:230–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Moylan S, Berk M, Dean OM, Samuni Y, Williams LJ, O’Neil A, et al. Oxidative & nitrosative stress in depression: why so much stress? Neurosci Biobehav Rev. 2014;45:46–62.

    CAS  PubMed  Google Scholar 

  36. 36.

    Liu T, Zhong S, Liao X, Chen J, He T, Lai S, et al. A meta-analysis of oxidative stress markers in depression. PLOS ONE. 2015;10:e0138904.

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Che Y, Wang J-F, Shao L, Young LT. Oxidative damage to RNA but not DNA in the hippocampus of patients with major mental illness. J Psychiatry Neurosci. 2010;35:296.

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Gao S-F, Qi X-R, Zhao J, Balesar R, Bao A-M, Swaab DF. Decreased NOS1 expression in the anterior cingulate cortex in depression. Cereb Cortex. 2013;23:2956–64.

    PubMed  Google Scholar 

  39. 39.

    Morrison CD, Pistell PJ, Ingram DK, Johnson WD, Liu Y, Fernandez‐Kim SO, et al. High fat diet increases hippocampal oxidative stress and cognitive impairment in aged mice: implications for decreased Nrf2 signaling. J Neurochem. 2010;114:1581–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Studzinski CM, Li F, Bruce‐Keller AJ, Fernandez‐Kim SO, Zhang L, Weidner AM, et al. Effects of short‐term Western diet on cerebral oxidative stress and diabetes related factors in APP× PS1 knock‐in mice. J Neurochem. 2009;108:860–6.

    CAS  PubMed  Google Scholar 

  41. 41.

    Cocate PG, Natali AJ, de Oliveira A, Longo GZ, Rita de Cássia GA, Maria, et al. Fruit and vegetable intake and related nutrients are associated with oxidative stress markers in middle-aged men. Nutrition. 2014;30:660–5.

    CAS  PubMed  Google Scholar 

  42. 42.

    Dai J, Jones DP, Goldberg J, Ziegler TR, Bostick RM, Wilson PW, et al. Association between adherence to the Mediterranean diet and oxidative stress. Am J Clin Nutr. 2008;88:1364–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Meyer KA, Sijtsma FP, Nettleton JA, Steffen LM, Van Horn L, Shikany JM, et al. Dietary patterns are associated with plasma F2-isoprostanes in an observational cohort study of adults. Free Radic Biol Med. 2013;57:201–9.

    CAS  PubMed  Google Scholar 

  44. 44.

    Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med. 2011;51:1000–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Fernandes BS, Dean OM, Dodd S, Malhi GS, Berk M. N-acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. The Journal of clinical psychiatry. 2016;77:457–66.

    Google Scholar 

  46. 46.

    Zhang H, Tsao R. Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Curr Opin Food Sci. 2016;8:33–42.

    Google Scholar 

  47. 47.

    Cryan JF, O’Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, et al. The microbiota-gut-brain axis. Physiol Rev. 2019;99:1877–2013.

    CAS  PubMed  Google Scholar 

  48. 48.

    Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336:1268–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Ogbonnaya ES, Clarke G, Shanahan F, Dinan TG, Cryan JF, O’Leary OF. Adult hippocampal neurogenesis is regulated by the microbiome. Biol Psychiatry. 2015;78:e7–9.

    PubMed  Google Scholar 

  50. 50.

    Gheorghe CE, Martin JA, Manriquez FV, Dinan TG, Cryan JF, Clarke G. Focus on the essentials: tryptophan metabolism and the microbiome-gut-brain axis. Curr Opin Pharmacol. 2019;48:137–45.

    CAS  PubMed  Google Scholar 

  51. 51.

    van de Wouw M, Walsh AM, Crispie F, van Leuven L, Lyte JM, Boehme M, et al. Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse. Microbiome. 2020;8:1–20.

    Google Scholar 

  52. 52.

    Shi H, Wang Q, Zheng M, Hao S, Lum JS, Chen X, et al. Supplement of microbiota-accessible carbohydrates prevents neuroinflammation and cognitive decline by improving the gut microbiota-brain axis in diet-induced obese mice. J Neuroinflammation. 2020;17:1–21.

    Google Scholar 

  53. 53.

    Dinan TG, Stanton C, Long-Smith C, Kennedy P, Cryan JF, Cowan CSM, et al. Feeding melancholic microbes: MyNewGut recommendations on diet and mood. Clin Nutr. 2019;38:1995–2001.

    PubMed  Google Scholar 

  54. 54.

    Ohland CL, Kish L, Bell H, Thiesen A, Hotte N, Pankiv E, et al. Effects of Lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome. Psychoneuroendocrinology. 2013;38:1738–47.

    CAS  PubMed  Google Scholar 

  55. 55.

    Pyndt Jorgensen B, Winther G, Kihl P, Nielsen DS, Wegener G, Hansen AK, et al. Dietary magnesium deficiency affects gut microbiota and anxiety-like behaviour in C57BL/6N mice. Acta Neuropsychiatr. 2015;27:307–11.

    PubMed  Google Scholar 

  56. 56.

    Magnusson KR, Hauck L, Jeffrey BM, Elias V, Humphrey A, Nath R, et al. Relationships between diet-related changes in the gut microbiome and cognitive flexibility. Neuroscience. 2015;300:128–40.

    CAS  PubMed  Google Scholar 

  57. 57.

    Reichelt AC, Loughman A, Bernard A, Raipuria M, Abbott KN, Dachtler J, Van TT, Moore RJ. An intermittent hypercaloric diet alters gut microbiota, prefrontal cortical gene expression and social behaviours in rats. Nutritional neuroscience. 2020;23:613–27.

    CAS  PubMed  Google Scholar 

  58. 58.

    Burokas A, Arboleya S, Moloney RD, Peterson VL, Murphy K, Clarke G, et al. Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry. 2017;82:472–87.

    CAS  PubMed  Google Scholar 

  59. 59.

    Cryan JF, O’Riordan KJ, Sandhu K, Peterson V, Dinan TG. The gut microbiome in neurological disorders. Lancet Neurol. 2020;19:179–94.

    CAS  PubMed  Google Scholar 

  60. 60.

    Valles-Colomer M, Falony G, Darzi Y, Tigchelaar EF, Wang J, Tito RY, et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. 2019;4:623–32.

    CAS  PubMed  Google Scholar 

  61. 61.

    David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–63.

    CAS  PubMed  Google Scholar 

  62. 62.

    Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334:105–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Bruce-Keller AJ, Salbaum JM, Luo M, Blanchard Et, Taylor CM, Welsh DA, et al. Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiatry. 2015;77:607–15.

  64. 64.

    Hiel S, Bindels LB, Pachikian BD, Kalala G, Broers V, Zamariola G, et al. Effects of a diet based on inulin-rich vegetables on gut health and nutritional behavior in healthy humans. Am J Clin Nutr. 2019;109:1683–95.

    PubMed  PubMed Central  Google Scholar 

  65. 65.

    Ghosh TS, Rampelli S, Jeffery IB, Santoro A, Neto M, Capri M, Giampieri E, Jennings A, Candela M, Turroni S, Zoetendal EG. Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut. 2020;69:1218–1228.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Robertson RC, Seira Oriach C, Murphy K, Moloney GM, Cryan JF, Dinan TG, et al. Omega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood. Brain Behav Immun. 2017;59:21–37.

    CAS  PubMed  Google Scholar 

  67. 67.

    Pasinetti GM, Singh R, Westfall S, Herman F, Faith J, Ho L. The role of the gut microbiota in the metabolism of polyphenols as characterized by gnotobiotic mice. J Alzheimers Dis. 2018;63:409–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Ozdal T, Sela DA, Xiao J, Boyacioglu D, Chen F, Capanoglu E. The reciprocal interactions between polyphenols and gut microbiota and effects on bioaccessibility. Nutrients. 2016;8:78.

    PubMed  PubMed Central  Google Scholar 

  69. 69.

    Long-Smith C, O'Riordan KJ, Clarke G, Stanton C, Dinan TG, Cryan JF. Microbiota-gut-brain axis: new therapeutic opportunities. Annual review of pharmacology and toxicology. 2020;60(Jan):477–502.

    CAS  PubMed  Google Scholar 

  70. 70.

    Liu RT, Walsh RF, Sheehan AE. Prebiotics and probiotics for depression and anxiety: a systematic review and meta-analysis of controlled clinical trials. Neuroscience & Biobehavioral Reviews. 2019;102(Jul):13–23.

    CAS  Google Scholar 

  71. 71.

    Aslam H, Green J, Jacka FN, Collier F, Berk M, Pasco J, Dawson SL. Fermented foods, the gut and mental health: a mechanistic overview with implications for depression and anxiety. Nutritional neuroscience. 2020;23(Sep):659–71.

    CAS  PubMed  Google Scholar 

  72. 72.

    Bambury A, Sandhu K, Cryan JF, Dinan TG. Finding the needle in the haystack: systematic identification of psychobiotics. Br J Pharmacol. 2018;175:4430–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Suez J, Zmora N, Segal E, Elinav E. The pros, cons, and many unknowns of probiotics. Nat Med. 2019;25:716–29.

    CAS  PubMed  Google Scholar 

  74. 74.

    Hidese S, Nogawa S, Saito K, Kunugi H. Food allergy is associated with depression and psychological distress: a web-based study in 11,876 Japanese. J Affect Disord. 2019;245:213–8.

    PubMed  Google Scholar 

  75. 75.

    Portsmouth Uo. Literature searches and reviews related to the prevalence of food allergy in Europe. EFSA Support Publ. 2013;10:506E.

    Google Scholar 

  76. 76.

    Jarvinen KM, Konstantinou GN, Pilapil M, Arrieta MC, Noone S, Sampson HA, et al. Intestinal permeability in children with food allergy on specific elimination diets. Pediatr Allergy Immunol. 2013;24:589–95.

    PubMed  PubMed Central  Google Scholar 

  77. 77.

    Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008;29:117–24.

    PubMed  Google Scholar 

  78. 78.

    Lerner BA, Green PH, Lebwohl B. Going against the grains: gluten-free diets in patients without celiac disease—worthwhile or not? Dig Dis Sci. 2019;64:1740–7.

    PubMed  Google Scholar 

  79. 79.

    Haq MRU, Kapila R, Sharma R, Saliganti V, Kapila S. Comparative evaluation of cow β-casein variants (A1/A2) consumption on Th 2-mediated inflammatory response in mouse gut. Eur J Nutr. 2014;53:1039–49.

    Google Scholar 

  80. 80.

    Naughton M, Dinan TG, Scott LV. Corticotropin-releasing hormone and the hypothalamic–pituitary–adrenal axis in psychiatric disease. Handb Clin Neurol. 2014;124:69–91.

    PubMed  Google Scholar 

  81. 81.

    Brody S, Preut R, Schommer K, Schürmeyer TH. A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress. Psychopharmacology. 2002;159:319–24.

    CAS  PubMed  Google Scholar 

  82. 82.

    Barbadoro P, Annino I, Ponzio E, Romanelli RM, D’Errico MM, Prospero E, et al. Fish oil supplementation reduces cortisol basal levels and perceived stress: a randomized, placebo‐controlled trial in abstinent alcoholics. Mol Nutr Food Res. 2013;57:1110–4.

    CAS  PubMed  Google Scholar 

  83. 83.

    Delarue J, Matzinger O, Binnert C, Schneiter P, Chiolero R, Tappy L. Fish oil prevents the adrenal activation elicited by mental stress in healthy men. Diabetes Metab. 2003;29:289–95.

    CAS  PubMed  Google Scholar 

  84. 84.

    Tsang C, Hodgson L, Bussu A, Farhat G, Al-Dujaili E. Effect of polyphenol-rich dark chocolate on salivary cortisol and mood in adults. Antioxidants. 2019;8:149.

    CAS  PubMed Central  Google Scholar 

  85. 85.

    Tsang C, Smail NF, Almoosawi S, Davidson I, Al-Dujaili EA. Intake of polyphenol-rich pomegranate pure juice influences urinary glucocorticoids, blood pressure and homeostasis model assessment of insulin resistance in human volunteers. J Nutr Sci. 2012;1:e9.

    PubMed  PubMed Central  Google Scholar 

  86. 86.

    Dhabhar FS. Stress‐induced enhancement of cell‐mediated immunity. Ann N Y Acad Sci. 1998;840:359–72.

    CAS  PubMed  Google Scholar 

  87. 87.

    Al-Dujaili EA, Ashmore S, Tsang C. A short study exploring the effect of the glycaemic index of the diet on energy intake and salivary steroid hormones. Nutrients. 2019;11:260.

    CAS  PubMed Central  Google Scholar 

  88. 88.

    Gareau MG, Jury J, MacQueen G, Sherman PM, Perdue MH. Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut. 2007;56:1522–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011;105:755–64.

    CAS  PubMed  Google Scholar 

  90. 90.

    Rudzki L, Ostrowska L, Pawlak D, Małus A, Pawlak K, Waszkiewicz N, et al. Probiotic lactobacillus plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: a double-blind, randomized, placebo controlled study. Psychoneuroendocrinology. 2019;100:213–22.

    CAS  PubMed  Google Scholar 

  91. 91.

    Fanselow MS, Dong HW. Are the dorsal and ventral hippocampus functionally distinct structures? Neuron. 2010;65:7–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Anacker C, Hen R. Adult hippocampal neurogenesis and cognitive flexibility—linking memory and mood. Nature Reviews Neuroscience. 2017;18(Jun):335–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Toda T, Parylak SL, Linker SB, Gage FH. The role of adult hippocampal neurogenesis in brain health and disease. Mol Psychiatry. 2019;24:67–87.

    CAS  PubMed  Google Scholar 

  94. 94.

    Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res. 2002;109:143–8.

    CAS  PubMed  Google Scholar 

  95. 95.

    Filus JF, Rybakowski J. [Neurotrophic factors and their role in the pathogenesis of affective disorders]. Psychiatr Pol. 2005;39:883–97.

    PubMed  Google Scholar 

  96. 96.

    Caviedes A, Lafourcade C, Soto C, Wyneken U. BDNF/NF-kappaB signaling in the neurobiology of depression. Curr Pharm Des. 2017;23:3154–63.

    CAS  PubMed  Google Scholar 

  97. 97.

    Zainuddin MS, Thuret S. Nutrition, adult hippocampal neurogenesis and mental health. Br Med Bull. 2012;103:89–114.

    PubMed  Google Scholar 

  98. 98.

    Kanoski SE, Davidson TL. Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiol Behav. 2011;103:59–68.

    CAS  PubMed  Google Scholar 

  99. 99.

    Savignac HM, Corona G, Mills H, Chen L, Spencer JP, Tzortzis G, et al. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine. Neurochemistry Int. 2013;63:756–64.

    CAS  Google Scholar 

  100. 100.

    Balanza-Martinez V, Fries GR, Colpo GD, Silveira PP, Portella AK, Tabares-Seisdedos R, et al. Therapeutic use of omega-3 fatty acids in bipolar disorder. Expert Rev Neurother. 2011;11:1029–47.

    PubMed  Google Scholar 

  101. 101.

    Dias GP, Cavegn N, Nix A, do Nascimento Bevilaqua MC, Stangl D, Zainuddin MS, et al. The role of dietary polyphenols on adult hippocampal neurogenesis: molecular mechanisms and behavioural effects on depression and anxiety. Oxid Med Cell Longev. 2012;2012:541971.

    PubMed  PubMed Central  Google Scholar 

  102. 102.

    Zainuddin MSA, Thuret S. Nutrition, adult hippocampal neurogenesis and mental health. Br Med Bull. 2012;103:89–114.

    PubMed  Google Scholar 

  103. 103.

    Jacka FN, Cherbuin N, Anstey KJ, Sachdev P, Butterworth P. Western diet is associated with a smaller hippocampus: a longitudinal investigation. BMC medicine. 2015;13:1–8.

    Google Scholar 

  104. 104.

    Akbaraly T, Sexton C, Zsoldos E, Mahmood A, Filippini N, Kerleau C, et al. Association of long-term diet quality with hippocampal volume: longitudinal cohort study. Am J Med. 2018;131:1372–81.e4.

    PubMed  PubMed Central  Google Scholar 

  105. 105.

    Croll PH, Voortman T, Ikram MA, Franco OH, Schoufour JD, Bos D, et al. Better diet quality relates to larger brain tissue volumes: the Rotterdam study. Neurology. 2018;90:e2166–73.

    PubMed  Google Scholar 

  106. 106.

    Sánchez-Villegas A, Galbete C, Martinez-González MÁ, Martinez JA, Razquin C, Salas-Salvadó J, et al. The effect of the Mediterranean diet on plasma brain-derived neurotrophic factor (BDNF) levels: the PREDIMED-NAVARRA randomized trial. Nutr Neurosci. 2011;14:195–201.

    PubMed  Google Scholar 

  107. 107.

    Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ. Transport of brain-derived neurotrophic factor across the blood–brain barrier. Neuropharmacology. 1998;37:1553–61.

    CAS  PubMed  Google Scholar 

  108. 108.

    Gejl AK, Enevold C, Bugge A, Andersen MS, Nielsen CH, Andersen LB. Associations between serum and plasma brain-derived neurotrophic factor and influence of storage time and centrifugation strategy. Sci Rep. 2019;9:1–9.

    CAS  Google Scholar 

  109. 109.

    Mattson MP, Duan W, Guo Z. Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms. J Neurochem. 2003;84:417–31.

    CAS  PubMed  Google Scholar 

  110. 110.

    Stevenson RJ, Francis HM, Attuquayefio T, Gupta D, Yeomans MR, Oaten MJ, et al. Hippocampal-dependent appetitive control is impaired by experimental exposure to a Western-style diet. R Soc Open Sci. 2020;7:191338.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. 111.

    Attuquayefio T, Stevenson RJ, Oaten MJ, Francis HM. A four-day Western-style dietary intervention causes reductions in hippocampal-dependent learning and memory and interoceptive sensitivity. PLoS ONE. 2017;12:e0172645.

    PubMed  PubMed Central  Google Scholar 

  112. 112.

    Fernstrom JD. A perspective on the safety of supplemental tryptophan based on its metabolic fates. J Nutr. 2016;146:2601S–8S.

    CAS  PubMed  Google Scholar 

  113. 113.

    Russo S, Kema IP, Bosker F, Haavik J, Korf J. Tryptophan as an evolutionarily conserved signal to brain serotonin: molecular evidence and psychiatric implications. World J Biol Psychiatry. 2009;10:258–68.

    PubMed  Google Scholar 

  114. 114.

    Cervenka I, Agudelo LZ, Ruas JL. Kynurenines: tryptophan’s metabolites in exercise, inflammation, and mental health. Science. 2017;357:6349.

    Google Scholar 

  115. 115.

    Pu J, Liu Y, Zhang H, Tian L, Gui S, Yu Y, Chen X, Chen Y, Yang L, Ran Y, Zhong X. An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder. Molecular Psychiatry. 2020:1-2.

  116. 116.

    Lovelace MD, Varney B, Sundaram G, Lennon MJ, Lim CK, Jacobs K, et al. Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases. Neuropharmacology. 2017;112:373–88.

    CAS  PubMed  Google Scholar 

  117. 117.

    O’Farrell K, Harkin A. Stress-related regulation of the kynurenine pathway: Relevance to neuropsychiatric and degenerative disorders. Neuropharmacology. 2017;112:307–23.

    PubMed  Google Scholar 

  118. 118.

    Strasser B, Becker K, Fuchs D, Gostner JM. Kynurenine pathway metabolism and immune activation: Peripheral measurements in psychiatric and co-morbid conditions. Neuropharmacology. 2017;112:286–96.

    CAS  PubMed  Google Scholar 

  119. 119.

    Agus A, Planchais J, Sokol H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe. 2018;23:716–24.

    CAS  PubMed  Google Scholar 

  120. 120.

    Roager HM, Licht TR. Microbial tryptophan catabolites in health and disease. Nat Commun. 2018;9:3294.

    PubMed  PubMed Central  Google Scholar 

  121. 121.

    Lukic I, Getselter D, Koren O, Elliott E. Role of tryptophan in microbiota-induced depressive-like behavior: evidence from tryptophan depletion study. Front Behav Neurosci. 2019;13:123.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. 122.

    Badawy AA. Tryptophan availability for kynurenine pathway metabolism across the life span: Control mechanisms and focus on aging, exercise, diet and nutritional supplements. Neuropharmacology. 2017;112:248–63.

    CAS  PubMed  Google Scholar 

  123. 123.

    Fernstrom JD. Effects and side effects associated with the non-nutritional use of tryptophan by humans. J Nutr. 2012;142:2236S–44S.

    CAS  PubMed  Google Scholar 

  124. 124.

    Wirleitner B, Schroecksnadel K, Winkler C, Schennach H, Fuchs D. Resveratrol suppresses interferon-γ-induced biochemical pathways in human peripheral blood mononuclear cells in vitro. Immunol Lett. 2005;100:159–63.

    CAS  PubMed  Google Scholar 

  125. 125.

    Dolpady J, Sorini C, Di Pietro C, Cosorich I, Ferrarese R, Saita D, et al. Oral probiotic VSL# 3 prevents autoimmune diabetes by modulating microbiota and promoting indoleamine 2, 3-dioxygenase-enriched tolerogenic intestinal environment. J Diabetes Res. 2016;2016:7569431.

    PubMed  Google Scholar 

  126. 126.

    Jeong YI, Kim SW, Jung ID, Lee JS, Chang JH, Lee CM, et al. Curcumin suppresses the induction of indoleamine 2, 3-dioxygenase by blocking the Janus-activated kinase-protein kinase Cδ-STAT1 signaling pathway in interferon-γ-stimulated murine dendritic cells. J Biol Chem. 2009;284:3700–8.

    CAS  PubMed  Google Scholar 

  127. 127.

    Min SY, Yan M, Kim SB, Ravikumar S, Kwon SR, Vanarsa K, et al. Green tea epigallocatechin-3-gallate suppresses autoimmune arthritis through indoleamine-2, 3-dioxygenase expressing dendritic cells and the nuclear factor, erythroid 2-like 2 antioxidant pathway. J Inflamm. 2015;12:1–15.

    Google Scholar 

  128. 128.

    Heischmann S, Gano LB, Quinn K, Liang LP, Klepacki J, Christians U, et al. Regulation of kynurenine metabolism by a ketogenic diet. J Lipid Res. 2018;59:958–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. 129.

    Lemieux GA, Cunningham KA, Lin L, Mayer F, Werb Z, Ashrafi K. Kynurenic acid is a nutritional cue that enables behavioral plasticity. Cell. 2015;160:119–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  130. 130.

    Strasser B, Berger K, Fuchs D. Effects of a caloric restriction weight loss diet on tryptophan metabolism and inflammatory biomarkers in overweight adults. Eur J Nutr. 2015;54:101–7.

    CAS  PubMed  Google Scholar 

  131. 131.

    Gostner JM, Becker K, Croft KD, Woodman RJ, Puddey IB, Fuchs D, et al. Regular consumption of black tea increases circulating kynurenine concentrations: a randomized controlled trial. BBA Clin. 2015;3:31–5.

    CAS  PubMed  Google Scholar 

  132. 132.

    Gualdoni GA, Fuchs D, Zlabinger GJ, Gostner JM. Resveratrol intake enhances indoleamine-2, 3-dioxygenase activity in humans. Pharmacol Rep. 2016;68:1065–8.

    CAS  PubMed  Google Scholar 

  133. 133.

    Rezin GT, Amboni G, Zugno AI, Quevedo J, Streck EL. Mitochondrial dysfunction and psychiatric disorders. Neurochem Res. 2009;34:1021.

    CAS  PubMed  Google Scholar 

  134. 134.

    Filler K, Lyon D, Bennett J, McCain N, Elswick R, Lukkahatai N, et al. Association of mitochondrial dysfunction and fatigue: a review of the literature. BBA Clin. 2014;1:12–23.

    PubMed  PubMed Central  Google Scholar 

  135. 135.

    Wang Y, Ni J, Gao C, Xie L, Zhai L, Cui G, et al. Mitochondrial transplantation attenuates lipopolysaccharide-induced depression-like behaviors. Prog Neuro-Psychopharmacol Biol Psychiatry. 2019;93:240–9.

    CAS  Google Scholar 

  136. 136.

    Sergi D, Naumovski NN, Heilbronn LHK, Abeywardena M, O’Callaghan N, Lionetti L, et al. Mitochondrial (dys) function and insulin resistance: from pathophysiological molecular mechanisms to the impact of diet. Front Physiol. 2019;10:532.

    PubMed  PubMed Central  Google Scholar 

  137. 137.

    Kuipers EN, Held NM, in het Panhuis W, Modder M, Ruppert PM, Kersten S, et al. A single day of high-fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice. Am J Physiol Endocrinol Metab. 2019;317:E820–30.

    CAS  PubMed  Google Scholar 

  138. 138.

    Marín-Royo G, Rodríguez C, Le Pape A, Jurado-López R, Luaces M, Antequera A, et al. The role of mitochondrial oxidative stress in the metabolic alterations in diet-induced obesity in rats. FASEB J. 2019;33:12060–72.

    PubMed  PubMed Central  Google Scholar 

  139. 139.

    Yang X-X, Wang X, Shi T-T, Dong J-C, Li F-J, Zeng L-X, et al. Mitochondrial dysfunction in high-fat diet-induced nonalcoholic fatty liver disease: the alleviating effect and its mechanism of Polygonatum kingianum. Biomed Pharmacother. 2019;117:109083.

    CAS  PubMed  Google Scholar 

  140. 140.

    Sihali-Beloui O, Aroune D, Benazouz F, Hadji A, El-Aoufi S, Marco S. A hypercaloric diet induces hepatic oxidative stress, infiltration of lymphocytes, and mitochondrial reshuffle in Psammomys obesus, a murine model of insulin resistance. C R Biol. 2019;342:209–19.

    PubMed  Google Scholar 

  141. 141.

    Woodman AG, Mah R, Keddie DL, Noble RM, Holody CD, Panahi S, et al. Perinatal iron deficiency and a high salt diet cause long-term kidney mitochondrial dysfunction and oxidative stress. Cardiovasc Res. 2020;116:183–92.

    CAS  PubMed  Google Scholar 

  142. 142.

    Ferey JL, Boudoures AL, Reid M, Drury A, Scheaffer S, Modi Z, et al. A maternal high-fat, high-sucrose diet induces transgenerational cardiac mitochondrial dysfunction independently of maternal mitochondrial inheritance. Am J Physiol Heart Circ Physiol. 2019;316:H1202–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  143. 143.

    Menshikova EV, Ritov VB, Dube JJ, Amati F, Stefanovic-Racic M, Toledo FG, et al. Calorie restriction-induced weight loss and exercise have differential effects on skeletal muscle mitochondria despite similar effects on insulin sensitivity. J Gerontol Ser A. 2018;73:81–7.

    CAS  Google Scholar 

  144. 144.

    Hancock CR, Han D-H, Higashida K, Kim SH, Holloszy JO. Does calorie restriction induce mitochondrial biogenesis? A reevaluation. FASEB J. 2011;25:785–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  145. 145.

    Brietzke E, Mansur RB, Subramaniapillai M, Balanzá-Martínez V, Vinberg M, González-Pinto A, et al. Ketogenic diet as a metabolic therapy for mood disorders: evidence and developments. Neurosci Biobehav Rev. 2018;94:11–6.

    CAS  PubMed  Google Scholar 

  146. 146.

    Sullivan PG, Rippy NA, Dorenbos K, Concepcion RC, Agarwal AK, Rho JM. The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann Neurol. 2004;55:576–80.

    CAS  PubMed  Google Scholar 

  147. 147.

    Cocco T, Sgobbo P, Clemente M, Lopriore B, Grattagliano I, Di Paola M, et al. Tissue-specific changes of mitochondrial functions in aged rats: effect of a long-term dietary treatment with N-acetylcysteine. Free Radic Biol Med. 2005;38:796–805.

    CAS  PubMed  Google Scholar 

  148. 148.

    Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011;14:612–22.

    CAS  PubMed  Google Scholar 

  149. 149.

    Cavalli G, Heard E. Advances in epigenetics link genetics to the environment and disease. Nature. 2019;571:489–99.

    CAS  PubMed  Google Scholar 

  150. 150.

    Li M, D’Arcy C, Li X, Zhang T, Joober R, Meng X. What do DNA methylation studies tell us about depression? A systematic review. Transl psychiatry. 2019;9:1–14.

    Google Scholar 

  151. 151.

    Bressler J, Marioni RE, Walker RM, Xia R, Gottesman RF, Windham BG, Grove ML, Guan W, Pankow JS, Evans KL, Mcintosh AM. Epigenetic age acceleration and cognitive function in African American adults in midlife: the atherosclerosis risk in communities study. The Journals of Gerontology: Series A. 2020;75(Feb):473–80.

    Google Scholar 

  152. 152.

    Rosen AD, Robertson KD, Hlady RA, Muench C, Lee J, Philibert R, et al. DNA methylation age is accelerated in alcohol dependence. Transl Psychiatry. 2018;8:182.

    PubMed  PubMed Central  Google Scholar 

  153. 153.

    Fries GR, Bauer IE, Scaini G, Valvassori SS, Walss‐Bass C, Soares JC, Quevedo J. Accelerated hippocampal biological aging in bipolar disorder. Bipolar disorders. 2020;22(Aug):498–507.

    CAS  PubMed  Google Scholar 

  154. 154.

    Davis EG, Humphreys KL, McEwen LM, Sacchet MD, Camacho MC, MacIsaac JL, et al. Accelerated DNA methylation age in adolescent girls: associations with elevated diurnal cortisol and reduced hippocampal volume. Transl Psychiatry. 2017;7:e1223.

    CAS  PubMed  PubMed Central  Google Scholar 

  155. 155.

    Voisey J, Lawford BR, Morris CP, Wockner LF, Noble EP, Young RM, et al. Epigenetic analysis confirms no accelerated brain aging in schizophrenia. NPJ Schizophr. 2017;3:26.

    PubMed  PubMed Central  Google Scholar 

  156. 156.

    Chen L, Dong Y, Bhagatwala J, Raed A, Huang Y, Zhu H. Effects of vitamin D3 supplementation on epigenetic aging in overweight and obese African Americans with suboptimal vitamin D status: a randomized clinical trial. J Gerontol A Biol Sci Med Sci. 2019;74:91–8.

    CAS  PubMed  Google Scholar 

  157. 157.

    Stubbs TM, Bonder MJ, Stark AK, Krueger F, Team BIAC, von Meyenn F, et al. Multi-tissue DNA methylation age predictor in mouse. Genome Biol. 2017;18:68.

  158. 158.

    Sae-Lee C, Corsi S, Barrow TM, Kuhnle GGC, Bollati V, Mathers JC, et al. Dietary intervention modifies DNA methylation age assessed by the epigenetic clock. Mol Nutr Food Res. 2018;62:e1800092.

    PubMed  Google Scholar 

  159. 159.

    O’Neil A, Itsiopoulos C, Skouteris H, Opie RS, McPhie S, Hill B, et al. Preventing mental health problems in offspring by targeting dietary intake of pregnant women. BMC Med. 2014;12:208.

    PubMed  PubMed Central  Google Scholar 

  160. 160.

    Mill J, Heijmans BT. From promises to practical strategies in epigenetic epidemiology. Nat Rev Genet. 2013;14:585–94.

    CAS  PubMed  Google Scholar 

  161. 161.

    Bianco-Miotto T, Craig JM, Gasser YP, van Dijk SJ, Ozanne SE. Epigenetics and DOHaD: from basics to birth and beyond. J Dev Orig Health Dis. 2017;8:513–9.

    CAS  PubMed  Google Scholar 

  162. 162.

    Choi SW, Friso S. Epigenetics: a new bridge between nutrition and health. Adv Nutr. 2010;1:8–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  163. 163.

    Remely M, Stefanska B, Lovrecic L, Magnet U, Haslberger AG. Nutriepigenomics: the role of nutrition in epigenetic control of human diseases. Curr Opin Clin Nutr Metab Care. 2015;18:328–33.

    CAS  PubMed  Google Scholar 

  164. 164.

    Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA. 2008;105:17046–9.

    CAS  PubMed  Google Scholar 

  165. 165.

    Barker ED, Walton E, Cecil CAM. Annual research review: DNA methylation as a mediator in the association between risk exposure and child and adolescent psychopathology. J Child Psychol Psychiatry. 2018;59:303–22.

    PubMed  Google Scholar 

  166. 166.

    Peter CJ, Fischer LK, Kundakovic M, Garg P, Jakovcevski M, Dincer A, et al. DNA methylation signatures of early childhood malnutrition associated with impairments in attention and cognition. Biol Psychiatry. 2016;80:765–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  167. 167.

    McGowan PO, Meaney MJ, Szyf M. Diet and the epigenetic (re)programming of phenotypic differences in behavior. Brain Res. 2008;1237:12–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  168. 168.

    Burdge GC, Lillycrop KA. Nutrition, epigenetics, and developmental plasticity: implications for understanding human disease. Annu Rev Nutr. 2010;30:315–39.

    CAS  PubMed  Google Scholar 

  169. 169.

    Gomez-Pinilla F, Yang X. System biology approach intersecting diet and cell metabolism with pathogenesis of brain disorders. Prog Neurobiol. 2018;169:76–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  170. 170.

    Remely M, Lovrecic L, de la Garza AL, Migliore L, Peterlin B, Milagro FI, et al. Therapeutic perspectives of epigenetically active nutrients. Br J Pharmacol. 2015;172:2756–68.

    CAS  PubMed  Google Scholar 

  171. 171.

    Gonzalez-Becerra K, Ramos-Lopez O, Barron-Cabrera E, Riezu-Boj JI, Milagro FI, Martinez-Lopez E, et al. Fatty acids, epigenetic mechanisms and chronic diseases: a systematic review. Lipids Health Dis. 2019;18:178.

    CAS  PubMed  PubMed Central  Google Scholar 

  172. 172.

    Qin Y, Wade PA. Crosstalk between the microbiome and epigenome: messages from bugs. J Biochem. 2018;163:105–12.

    CAS  PubMed  Google Scholar 

  173. 173.

    Agustí A, García-Pardo MP, López-Almela I, Campillo I, Maes M, Romaní-Pérez M, et al. Interplay between the gut-brain axis, obesity and cognitive function. Front Neurosci. 2018;12:155.

    PubMed  PubMed Central  Google Scholar 

  174. 174.

    Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, et al. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010;67:220–9.

    PubMed  Google Scholar 

  175. 175.

    Mansur RB, Brietzke E, McIntyre RS. Is there a “metabolic-mood syndrome”? A review of the relationship between obesity and mood disorders. Neurosci Biobehav Rev. 2015;52:89–104.

    PubMed  Google Scholar 

  176. 176.

    Dallman MF, Pecoraro N, Akana SF, La Fleur SE, Gomez F, Houshyar H, et al. Chronic stress and obesity: a new view of “comfort food”. Proc Natl Acad Sci USA. 2003;100:11696–701.

    CAS  PubMed  Google Scholar 

  177. 177.

    Bornstein SR, Schuppenies A, Wong ML, Licinio J. Approaching the shared biology of obesity and depression: the stress axis as the locus of gene–environment interactions. Mol Psychiatry. 2006;11:892–902.

    CAS  PubMed  Google Scholar 

  178. 178.

    Schachter J, Martel J, Lin CS, Chang CJ, Wu TR, Lu CC, et al. Effects of obesity on depression: a role for inflammation and the gut microbiota. Brain Behav Immun. 2018;69:1–8.

    CAS  PubMed  Google Scholar 

  179. 179.

    Miller GE, Freedland KE, Carney RM, Stetler CA, Banks WA. Pathways linking depression, adiposity, and inflammatory markers in healthy young adults. Brain Behav Immun. 2003;17:276–85.

    CAS  PubMed  Google Scholar 

  180. 180.

    Manu P, Khan S, Radhakrishnan R, Russ MJ, Kane JM, Correll CU. Body mass index identified as an independent predictor of psychiatric readmission. J Clin Psychiatry. 2014;75:e573–7.

    PubMed  Google Scholar 

  181. 181.

    Bellavia A, Centorrino F, Jackson JW, Fitzmaurice G, Valeri L. The role of weight gain in explaining the effects of antipsychotic drugs on positive and negative symptoms: an analysis of the CATIE schizophrenia trial. Schizophr Res. 2019;206:96–102.

    PubMed  Google Scholar 

  182. 182.

    Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci USA. 2004;101:6659–63.

    CAS  PubMed  Google Scholar 

  183. 183.

    Rizza W, Veronese N, Fontana L. What are the roles of calorie restriction and diet quality in promoting healthy longevity? Ageing Res Rev. 2014;13:38–45.

    PubMed  Google Scholar 

  184. 184.

    Jebeile H, Gow ML, Baur LA, Garnett SP, Paxton SJ, Lister NB. Association of pediatric obesity treatment, including a dietary component, with change in depression and anxiety: a systematic review and meta-analysis. JAMA Pediatr. 2019;173:e192841.

    PubMed Central  Google Scholar 

  185. 185.

    Jacka FN, Mykletun A, Berk M, Bjelland I, Tell GS. The association between habitual diet quality and the common mental disorders in community-dwelling adults: the Hordaland Health study. Psychosom Med. 2011;73:483–90.

    PubMed  Google Scholar 

  186. 186.

    Mezuk B, Eaton WW, Albrecht S, Golden SH. Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care. 2008;31:2383–90.

    PubMed  PubMed Central  Google Scholar 

  187. 187.

    Huffman JC, Celano CM, Beach SR, Motiwala SR, Januzzi JL. Depression and cardiac disease: epidemiology, mechanisms, and diagnosis. Cardiovasc Psychiatry Neurol. 2013;2013:695925.

    PubMed  PubMed Central  Google Scholar 

  188. 188.

    Jung SJ, Woo HT, Cho S, et al. Association between body size, weight change and depression: systematic review and meta-analysis. Br J Psychiatry. 2017;211:14–21.

    PubMed  Google Scholar 

  189. 189.

    Power ML, Schulkin J. Sex differences in fat storage, fat metabolism, and the health risks from obesity: possible evolutionary origins. Br J Nutr. 2008;99:931–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  190. 190.

    Kiefer I, Rathmanner T, Kunze M. Eating and dieting differences in men and women. J Men’s Health Gend. 2005;2:194–201.

    Google Scholar 

  191. 191.

    Buening-Fesel M, Rueckert-John J. Why do men eat how they eat?: considerations from a nutritional-and gender-sociological perspective. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2016;59:950–6.

    Google Scholar 

  192. 192.

    Wardle J, Haase AM, Steptoe A, Nillapun M, Jonwutiwes K, Bellisie F. Gender differences in food choice: the contribution of health beliefs and dieting. Ann Behav Med. 2004;27:107–16.

    PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Wolfgang Marx.

Ethics declarations

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.

Additional information

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

Further reading

Search

Quick links