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Nutritional psychiatry: the present state of the evidence

  • Wolfgang Marx (a1), Genevieve Moseley (a2), Michael Berk (a2) (a3) (a4) (a5) and Felice Jacka (a2) (a3) (a6) (a7)

Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy; however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness. This review provides an overview of the nutritional psychiatry field. It includes a discussion of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research. Potential biological pathways related to mental disorders include inflammation, oxidative stress, the gut microbiome, epigenetic modifications and neuroplasticity. Consistent epidemiological evidence, particularly for depression, suggests an association between measures of diet quality and mental health, across multiple populations and age groups; these do not appear to be explained by other demographic, lifestyle factors or reverse causality. Our recently published intervention trial provides preliminary clinical evidence that dietary interventions in clinically diagnosed populations are feasible and can provide significant clinical benefit. Furthermore, nutraceuticals including n-3 fatty acids, folate, S-adenosylmethionine, N-acetyl cysteine and probiotics, among others, are promising avenues for future research. Continued research is now required to investigate the efficacy of intervention studies in large cohorts and within clinically relevant populations, particularly in patients with schizophrenia, bipolar and anxiety disorders.

Corresponding author
* Corresponding author: F. Jacka, email
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1. Whiteford, HA, Ferrari, AJ, Degenhardt, L et al. (2015) The global burden of mental, neurological and substance use disorders: an analysis from the global burden of disease study 2010. PLoS ONE 10, e0116820.
2. Chisholm, D, Sweeny, K, Sheehan, P et al. (2016) Scaling-up treatment of depression and anxiety: a global return on investment analysis. Lancet Psychiatry 3, 415424.
3. Olfson, M, Druss, BG & Marcus, SC (2015) Trends in mental health care among children and adolescents. N Engl J Med 372, 20292038.
4. Casacalenda, N, Perry, JC & Looper, K (2002) Remission in major depressive disorder: a comparison of pharmacotherapy, psychotherapy, and control conditions. Am J Psychiatry 159, 13541360.
5. Jorm, AF, Patten, SB, Brugha, TS et al. (2017) Has increased provision of treatment reduced the prevalence of common mental disorders? Review of the evidence from four countries. World Psychiatry 16, 9099.
6. Lai, JS, Hiles, S, Bisquera, A et al. (2014) A systematic review and meta-analysis of dietary patterns and depression in community-dwelling adults. Am J Clin Nutr 99, 181197.
7. Psaltopoulou, T, Sergentanis, TN, Panagiotakos, DB et al. (2013) Mediterranean diet, stroke, cognitive impairment, and depression: a meta-analysis. Ann Neurol 74, 580591.
8. Opie, RS, O'Neil, A, Itsiopoulos, C et al. (2015) The impact of whole-of-diet interventions on depression and anxiety: a systematic review of randomised controlled trials. Public Health Nutr 18, 20472093.
9. O'Neil, A, Quirk, SE, Housden, S et al. (2014) Relationship between diet and mental health in children and adolescents: a systematic review. Am J Public Health 104, e31e42.
10. Jacka, FN, Ystrom, E, Brantsaeter, AL et al. (2013) Maternal and early postnatal nutrition and mental health of offspring by age 5 years: a prospective cohort study. J Am Acad Child Adolesc Psychiatry 52, 10381047.
11. Pina-Camacho, L, Jensen, SK, Gaysina, D et al. (2015) Maternal depression symptoms, unhealthy diet and child emotional-behavioural dysregulation. Psychol Med 45, 18511860.
12. Steenweg-de Graaff, J, Tiemeier, H, Steegers-Theunissen, RP et al. (2014) Maternal dietary patterns during pregnancy and child internalising and externalising problems. Gener R Study Clin Nutr 33, 115121.
13. Berk, M, Williams, LJ, Jacka, FN et al. (2013) So depression is an inflammatory disease, but where does the inflammation come from? BMC Med 11, 200.
14. Moylan, S, Berk, M, Dean, OM et al. (2014) Oxidative & nitrosative stress in depression: why so much stress? Neurosci Biobehav Rev 45, 4662.
15. Jacka, FN, Cherbuin, N, Anstey, KJ et al. (2015) Western diet is associated with a smaller hippocampus: a longitudinal investigation. BMC Med 13, 215.
16. Slyepchenko, A, Maes, M, Jacka, FN et al. (2017) Gut microbiota, bacterial translocation, and interactions with diet: pathophysiological links between major depressive disorder and non-communicable medical comorbidities. Psychother Psychosom 86, 3146.
17. Sarris, J, Murphy, J, Mischoulon, D et al. (2016) Adjunctive nutraceuticals for depression: a systematic review and meta-analyses. Am J Psychiatry 173, 575587.
18. Sarris, J, Schoendorfer, N & Kavanagh, DJ (2009) Major depressive disorder and nutritional medicine: a review of monotherapies and adjuvant treatments. Nutr Rev 67, 125131.
19. Berk, M, Malhi, GS, Gray, LJ et al. (2013) The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci 34, 167177.
20. Jacka, FN, O'Neil, A, Opie, R et al. (2017) A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Med 15, 23.
21. Zainuddin, MS & Thuret, S (2012) Nutrition, adult hippocampal neurogenesis and mental health. Br Med Bull 103, 89114.
22. Fernandes, BS, Steiner, J, Molendijk, ML et al. (2016) C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry 3, 11471156.
23. Fernandes, BS, Steiner, J, Bernstein, HG et al. (2016) C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications. Mol Psychiatry 21, 554564.
24. Estruch, R (2010) Anti-inflammatory effects of the Mediterranean diet: the experience of the PREDIMED study. Proc Nutr Soc 69, 333340.
25. Watzl, B, Kulling, SE, Moseneder, J et al. (2005) A 4-wk intervention with high intake of carotenoid-rich vegetables and fruit reduces plasma C-reactive protein in healthy, nonsmoking men. Am J Clin Nutr 82, 10521058.
26. Schwingshackl, L & Hoffmann, G (2014) Mediterranean dietary pattern, inflammation and endothelial function: a systematic review and meta-analysis of intervention trials. Nutr Metab Cardiovasc Dis 24, 929939.
27. Dean, OM, van den Buuse, M, Bush, AI et al. (2009) A role for glutathione in the pathophysiology of bipolar disorder and schizophrenia? Animal models and relevance to clinical practice. Curr Med Chem 16, 29652976.
28. Liu, T, Zhong, S, Liao, X et al. (2015) A meta-analysis of oxidative stress markers in depression. PLoS ONE 10, e0138904.
29. Fernandes, BS, Berk, M, Turck, CW et al. (2014) Decreased peripheral brain-derived neurotrophic factor levels are a biomarker of disease activity in major psychiatric disorders: a comparative meta-analysis. Mol Psychiatry 19, 750751.
30. Fernandes, BS, Molendijk, ML, Kohler, CA et al. (2015) Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies. BMC Med 13, 289.
31. Guimaraes, LR, Jacka, FN, Gama, CS et al. (2008) Serum levels of brain-derived neurotrophic factor in schizophrenia on a hypocaloric diet. Prog Neuropsychopharmacol Biol Psychiatry 32, 15951598.
32. Kawakita, E, Hashimoto, M & Shido, O (2006) Docosahexaenoic acid promotes neurogenesis in vitro and in vivo. Neuroscience 139, 991997.
33. Williams, CM, El Mohsen, MA, Vauzour, D et al. (2008) Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels. Free Radic Biol Med 45, 295305.
34. Wakabayashi, C, Numakawa, T, Ninomiya, M et al. (2012) Behavioral and molecular evidence for psychotropic effects in L-theanine. Psychopharmacology (Berl) 219, 10991109.
35. Cecchini, T, Ciaroni, S, Ferri, P et al. (2003) Alpha-tocopherol, an exogenous factor of adult hippocampal neurogenesis regulation. J Neurosci Res 73, 447455.
36. Molteni, R, Barnard, RJ, Ying, Z et al. (2002) A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 112, 803814.
37. Martire, SI, Maniam, J, South, T et al. (2014) Extended exposure to a palatable cafeteria diet alters gene expression in brain regions implicated in reward, and withdrawal from this diet alters gene expression in brain regions associated with stress. Behav Brain Res 265, 132141.
38. Fung, TC, Olson, CA & Hsiao, EY (2017) Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci 20, 145155.
39. Sudo, N, Chida, Y, Aiba, Y et al. (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 558(Pt 1), 263275.
40. O'Mahony, SM, Clarke, G, Borre, YE et al. (2015) Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res 277, 3248.
41. Hooper, LV, Littman, DR & Macpherson, AJ (2012) Interactions between the microbiota and the immune system. Science (New York, NY) 336, 12681273.
42. Dinan, TG & Cryan, JF (2012) Regulation of the stress response by the gut microbiota: implications for psychoneuroendocrinology. Psychoneuroendocrinology 37, 13691378.
43. Clarke, G, Grenham, S, Scully, P et al. (2013) The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18, 666673.
44. O'Mahony, SM, Marchesi, JR, Scully, P et al. (2009) Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 65, 263267.
45. Kelly, JR, Borre, Y, O'Brien, C et al. (2016) Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res 82, 109118.
46. Zheng, P, Zeng, B, Zhou, C et al. (2016) Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Mol Psychiatry 21, 786796.
47. Bravo, JA, Forsythe, P, Chew, MV et al. (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA 108, 1605016055.
48. Amar, J, Chabo, C, Waget, A et al. (2011) Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol Med 3, 559572.
49. Dantzer, R, O'Connor, JC, Freund, GG et al. (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9, 4656.
50. Maes, M, Kubera, M, Leunis, JC et al. (2013) In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS-damaged neoepitopes. Acta Psychiatr Scand 127, 344354.
51. Morris, G, Walder, K, McGee, SL et al. (2017) A model of the mitochondrial basis of bipolar disorder. Neurosci Biobehav Rev 74(Pt A), 120.
52. Morris, G & Berk, M (2015) The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med 13, 68.
53. Wright, DJ, Renoir, T, Smith, ZM et al. (2015) N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington's disease. Transl Psychiatry 5, e492.
54. Maes, M, Fisar, Z, Medina, M et al. (2012) New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates – Nrf2 activators and GSK-3 inhibitors. Inflammopharmacology 20, 127150.
55. Dean, OM, Turner, A, Malhi, GS et al. (2015) Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression. Rev Bras Psiquiatr 37, 312.
56. Jacka, FN, Kremer, PJ, Berk, M et al. (2011) A prospective study of diet quality and mental health in adolescents. PLoS ONE 6, e24805.
57. Munoz, MA, Fito, M, Marrugat, J et al. (2009) Adherence to the Mediterranean diet is associated with better mental and physical health. Br J Nutr 101, 18211827.
58. Oellingrath, IM, Svendsen, MV & Hestetun, I (2014) Eating patterns and mental health problems in early adolescence – a cross-sectional study of 12–13-year-old Norwegian schoolchildren. Public Health Nutr 17, 25542562.
59. Jacka, FN, Cherbuin, N, Anstey, KJ et al. (2014) Dietary patterns and depressive symptoms over time: examining the relationships with socioeconomic position, health behaviours and cardiovascular risk. PLoS ONE 9, e87657.
60. Jacka, FN, Cherbuin, N, Anstey, KJ et al. (2015) Does reverse causality explain the relationship between diet and depression? J Affect Disord 175, 248250.
61. Sanchez-Villegas, A, Delgado-Rodriguez, M, Alonso, A et al. (2009) Association of the Mediterranean dietary pattern with the incidence of depression: the Seguimiento Universidad de Navarra/University of Navarra follow-up (SUN) cohort. Arch Gen Psychiatry 66, 10901098.
62. Quirk, SE, Williams, LJ, O'Neil, A et al. (2013) The association between diet quality, dietary patterns and depression in adults: a systematic review. BMC Psychiatry 13, 175.
63. Rahe, C, Unrath, M & Berger, K (2014) Dietary patterns and the risk of depression in adults: a systematic review of observational studies. Eur J Nutr 53, 9971013.
64. Li, Y, Lv, MR, Wei, YJ et al. (2017) Dietary patterns and depression risk: a meta-analysis. Psychiatry Res 253, 373382.
65. Muhlig, Y, Antel, J, Focker, M et al. (2016) Are bidirectional associations of obesity and depression already apparent in childhood and adolescence as based on high-quality studies? A systematic review. Obes Rev 17, 235249.
66. Sparling, TM, Henschke, N, Nesbitt, RC et al. (2017) The role of diet and nutritional supplementation in perinatal depression: a systematic review. Matern Child Nutr 13, e12235.
67. Baskin, R, Hill, B, Jacka, FN et al. (2015) The association between diet quality and mental health during the perinatal period. A systematic review. Appetite 91, 4147.
68. Martinez-Gonzalez, MA & Sanchez-Villegas, A (2016) Food patterns and the prevention of depression. Proc Nutr Soc 75, 139146.
69. Jacka, FN, Pasco, JA, Mykletun, A et al. (2010) Association of Western and traditional diets with depression and anxiety in women. Am J Psychiatry 167, 305311.
70. Nanri, A, Kimura, Y, Matsushita, Y et al. (2010) Dietary patterns and depressive symptoms among Japanese men and women. Eur J Clin Nutr 64, 832839.
71. Jacka, FN, Mykletun, A, Berk, M et al. (2011) The association between habitual diet quality and the common mental disorders in community-dwelling adults: the Hordaland Health Study. Psychosom Med 73, 483490.
72. Jacka, FN (2017) Nutritional psychiatry: where to next? EBio Med 17, 2429.
73. Murakami, K & Sasaki, S (2010) Dietary intake and depressive symptoms: a systematic review of observational studies. Mol Nutr Food Res 54, 471488.
74. Delgado-Lista, J, Perez-Martinez, P, Garcia-Rios, A et al. (2016) CORonary diet intervention with olive oil and cardiovascular PREVention study (the CORDIOPREV study): rationale, methods, and baseline characteristics. Am Heart J 177, 4250.
75. Li, Z, Li, B, Song, X et al. (2017) Dietary zinc and iron intake and risk of depression: a meta-analysis. Psychiatry Res 251, 4147.
76. Li, F, Liu, X & Zhang, D (2016) Fish consumption and risk of depression: a meta-analysis. J Epidemiol Commun Health 70, 299304.
77. Sanchez-Villegas, A, Martinez-Gonzalez, MA, Estruch, R et al. (2013) Mediterranean dietary pattern and depression: the PREDIMED randomized trial. BMC Med 11, 208.
78. Forsyth, A, Deane, FP & Williams, P (2015) A lifestyle intervention for primary care patients with depression and anxiety: a randomised controlled trial. Psychiatry Res 230, 537544.
79. Wu, A, Ying, Z & Gomez-Pinilla, F (2004) Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma 21, 14571467.
80. Wu, A, Ying, Z & Gomez-Pinilla, F (2004) The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition. Eur J Neurosci 19, 16991707.
81. Lim, SY, Kim, EJ, Kim, A et al. (2016) Nutritional factors affecting mental health. Clin Nutr Res 5, 143152.
82. Cui, Y-h & Zheng, Y (2016) A meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults. Neuropsychiatr Dis Treat 12, 17151723.
83. Appleton, KM, Sallis, HM, Perry, R et al. (2016) ω-3 Fatty acids for major depressive disorder in adults: an abridged Cochrane review. BMJ Open 6, e010172.
84. Sublette, ME, Ellis, SP, Geant, AL et al. (2011) Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry 72, 15771584.
85. Sanders, KM, Stuart, AL, Williamson, EJ et al. (2011) Annual high-dose vitamin D3 and mental well-being: randomised controlled trial. Br J Psychiatry 198, 357364.
86. Sarris, J, Mischoulon, D & Schweitzer, I (2011) Adjunctive nutraceuticals with standard pharmacotherapies in bipolar disorder: a systematic review of clinical trials. Bipolar Disord 13, 454465.
87. Almeida, OP, Ford, AH & Flicker, L (2015) Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. Int Psychogeriatr 27, 727737.
88. Gowda, U, Mutowo, MP, Smith, BJ et al. (2015) Vitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trials. Nutrition 31, 421429.
89. Sarris, J, Mischoulon, D & Schweitzer, I (2012) Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression. J Clin Psychiatry 73, 8186.
90. Grosso, G, Pajak, A, Marventano, S et al. (2014) Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS ONE 9, e96905.
91. Fernandes, BS, Dean, OM, Dodd, S et al. (2016) N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. J Clin Psychiatry 77, e457e466.
92. Rucklidge, JJ & Kaplan, BJ (2013) Broad-spectrum micronutrient formulas for the treatment of psychiatric symptoms: a systematic review. Expert Rev Neurother 13, 4973.
93. Firth, J, Stubbs, B, Sarris, J et al. (2017) The effects of vitamin and mineral supplementation on symptoms of schizophrenia: a systematic review and meta-analysis. Psychol Med 47, 15151527.
94. Salagre, E, Vizuete, AF, Leite, M et al. (2017) Homocysteine as a peripheral biomarker in bipolar disorder: a meta-analysis. Eur Psychiatry 43, 8191.
95. Deng, W, Cheung, ST, Tsao, SW et al. (2016) Telomerase activity and its association with psychological stress, mental disorders, lifestyle factors and interventions: a systematic review. Psychoneuroendocrinology 64, 150163.
96. Januar, V, Saffery, R & Ryan, J (2015) Epigenetics and depressive disorders: a review of current progress and future directions. Int J Epidemiol 44, 13641387.
97. Cerimele, JM & Katon, WJ (2013) Associations between health risk behaviors and symptoms of schizophrenia and bipolar disorder: a systematic review. Gen Hosp Psychiatry 35, 1622.
98. Anderson, G, Berk, M, Dodd, S et al. (2013) Immuno-inflammatory, oxidative and nitrosative stress, and neuroprogressive pathways in the etiology, course and treatment of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 42, 14.
99. Nemani, K, Hosseini Ghomi, R, McCormick, B et al. (2015) Schizophrenia and the gut-brain axis. Prog Neuropsychopharmacol Biol Psychiatry 56, 155160.
100. Huang, R, Wang, K & Hu, J (2016) Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients 8, e483.
101. Wallace, CJK & Milev, R (2017) The effects of probiotics on depressive symptoms in humans: a systematic review. Ann Gen Psychiatry 16, 14.
102. Romijn, AR & Rucklidge, JJ (2015) Systematic review of evidence to support the theory of psychobiotics. Nutr Rev 73, 675693.
103. Asevedo, E, Mendes, AC, Berk, M et al. (2014) Systematic review of N-acetylcysteine in the treatment of addictions. Rev Bras Psiquiatr 36, 168175.
104. Deepmala, D, Slattery, J, Kumar, N et al. (2015) Clinical trials of N-acetylcysteine in psychiatry and neurology: a systematic review. Neurosci Biobehav Rev 55, 294321.
105. Dash, SR, O'Neil, A & Jacka, FN (2016) Diet and common mental disorders: the imperative to translate evidence into action. Frontiers in Public Health 4, 81.
106. Lakhan, SE & Vieira, KF (2010) Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutr J 9, 42.
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