1932

Abstract

Mood disorders such as depression are among the most prevalent psychiatric disorders in the United States, but they are inadequately treated in a substantial proportion of patients. Accordingly, neuropsychiatric research has pivoted from investigation of monoaminergic mechanisms to exploration of novel mediators, including the role of inflammatory processes. Subsets of mood disorder patients exhibit immune-related abnormalities, including elevated levels of proinflammatory cytokines, monocytes, and neutrophils in the peripheral circulation; dysregulation of neuroglia and blood-brain barrier function; and disruption of gut microbiota. The field of psychoneuroimmunology is one of great therapeutic opportunity, yielding experimental therapeutics for mood disorders, such as peripheral cytokine targeting antibodies, microglia and astrocyte targeting therapies, and probiotic treatments for gut dysbiosis, and producing findings that identify therapeutic targets for future development.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-010617-052823
2018-01-06
2024-06-20
Loading full text...

Full text loading...

/deliver/fulltext/pharmtox/58/1/annurev-pharmtox-010617-052823.html?itemId=/content/journals/10.1146/annurev-pharmtox-010617-052823&mimeType=html&fmt=ahah

Literature Cited

  1. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. 1.  2005. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62:593–602 [Google Scholar]
  2. Krishnan V, Nestler EJ. 2.  2008. The molecular neurobiology of depression. Nature 455:894–902 [Google Scholar]
  3. Hodes GE, Kana V, Ménard C, Merad M, Russo SJ. 3.  2015. Neuroimmune mechanisms of depression. Nat. Neurosci. 18:1386–93 [Google Scholar]
  4. Lopez AD, Murray CC. 4.  1998. The global burden of disease, 1990–2020. Nat. Med. 4:1241–43 [Google Scholar]
  5. Ménard C, Pfau ML, Hodes GE, Russo SJ. 5.  2017. Immune and neuroendocrine mechanisms of stress vulnerability and resilience. Neuropsychopharmacology 42:62–80 [Google Scholar]
  6. Renault PF, Hoofnagle JH, Park Y, Mullen KD, Peters M. 6.  et al. 1987. Psychiatric complications of long-term interferon alfa therapy. Arch. Intern. Med. 147:1577–80 [Google Scholar]
  7. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L. 7.  et al. 2010. A meta-analysis of cytokines in major depression. Biol. Psychiatry 67:446–57 [Google Scholar]
  8. Maes M, Van der Planken M, Stevens WJ, Peeters D, DeClerck LS. 8.  et al. 1992. Leukocytosis, monocytosis and neutrophilia: hallmarks of severe depression. J. Psychiatr. Res. 26:125–34 [Google Scholar]
  9. Miller AH, Raison CL. 9.  2016. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat. Rev. Immunol. 16:22–34 [Google Scholar]
  10. Barnes J, Mondelli V, Pariante CM. 10.  2017. Genetic contributions of inflammation to depression. Neuropsychopharmacology 42:81–98 [Google Scholar]
  11. Kulmatycki KM, Jamali F. 11.  2001. Therapeutic relevance of altered cytokine expression. Cytokine 14:1–10 [Google Scholar]
  12. Vogelzangs N, Duivis HE, Beekman ATF, Kluft C, Neuteboom J. 12.  et al. 2012. Association of depressive disorders, depression characteristics and antidepressant medication with inflammation. Transl. Psychiatry 2:e79 [Google Scholar]
  13. Russo SJ, Nestler EJ. 13.  2013. The brain reward circuitry in mood disorders. Nat. Rev. Neurosci. 14:609–25 [Google Scholar]
  14. Felger JC, Li Z, Haroon E, Woolwine BJ, Jung MY. 14.  et al. 2016. Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression. Mol. Psychiatry 21:1358–65 [Google Scholar]
  15. Rosenblat JD, Cha DS, Mansur RB, McIntyre RS. 15.  2014. Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry 53:23–34 [Google Scholar]
  16. Shi C, Pamer EG. 16.  2011. Monocyte recruitment during infection and inflammation. Nat. Rev. Immunol. 11:762–74 [Google Scholar]
  17. Mueller SN, Mackay LK. 17.  2016. Tissue-resident memory T cells: local specialists in immune defence. Nat. Rev. Immunol. 16:79–89 [Google Scholar]
  18. Lewitus GM, Schwartz M. 18.  2009. Behavioral immunization: immunity to self-antigens contributes to psychological stress resilience. Mol. Psychiatry 14:532–36 [Google Scholar]
  19. Miller AH. 19.  2010. Depression and immunity: a role for T cells?. Brain Behav. Immun. 24:1–8 [Google Scholar]
  20. Lewitus GM, Wilf-Yarkoni A, Ziv Y, Shabat-Simon M, Gersner R. 20.  et al. 2009. Vaccination as a novel approach for treating depressive behavior. Biol. Psychiatry 65:283–88 [Google Scholar]
  21. Cohen H, Ziv Y, Cardon M, Kaplan Z, Matar MA. 21.  et al. 2006. Maladaptation to mental stress mitigated by the adaptive immune system via depletion of naturally occurring regulatory CD4+CD25+ cells. J. Neurobiol. 66:552–63 [Google Scholar]
  22. Brachman RA, Lehmann ML, Maric D, Herkenham M. 22.  2015. Lymphocytes from chronically stressed mice confer antidepressant-like effects to naive mice. J. Neurosci. 35:1530–38 [Google Scholar]
  23. Toben C, Baune BT. 23.  2015. An act of balance between adaptive and maladaptive immunity in depression: a role for T lymphocytes. J. Neuroimmune Pharmacol. 10:595–609 [Google Scholar]
  24. Frick LR, Rapanelli M, Cremaschi GA, Genaro AM. 24.  2009. Fluoxetine directly counteracts the adverse effects of chronic stress on T cell immunity by compensatory and specific mechanisms. Brain Behav. Immun. 23:36–40 [Google Scholar]
  25. Curzytek K, Kubera M, Majewska-Szczepanik M, Szczepanik M, Ptak W. 25.  et al. 2015. Inhibitory effect of antidepressant drugs on contact hypersensitivity reaction is connected with their suppressive effect on NKT and CD8+ T cells but not on TCR delta T cells. Int. Immunopharmacol. 28:1091–96 [Google Scholar]
  26. Himmerich H, Milenović S, Fulda S, Plümäkers B, Sheldrick AJ. 26.  et al. 2010. Regulatory T cells increased while IL-1β decreased during antidepressant therapy. J. Psychiatr. Res. 44:1052–57 [Google Scholar]
  27. Eyre HA, Lavretsky H, Kartika J, Qassim A, Baune BT. 27.  2016. Modulatory effects of antidepressant classes on the innate and adaptive immune system in depression. Pharmacopsychiatry 49:85–96 [Google Scholar]
  28. Wohleb ES, McKim DB, Sheridan JF, Godbout JP. 28.  2014. Monocyte trafficking to the brain with stress and inflammation: a novel axis of immune-to-brain communication that influences mood and behavior. Front. Neurosci. 8:447 [Google Scholar]
  29. Powell ND, Sloan EK, Bailey MT, Arevalo JMG, Miller GE. 29.  et al. 2013. Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. PNAS 110:16574–79 [Google Scholar]
  30. Heidt T, Sager HB, Courties G, Dutta P, Iwamoto Y. 30.  et al. 2014. Chronic variable stress activates hematopoietic stem cells. Nat. Med. 20:754–58 [Google Scholar]
  31. Avitsur R, Kavelaars A, Heijnen C, Sheridan JF. 31.  2005. Social stress and the regulation of tumor necrosis factor-α secretion. Brain Behav. Immun. 19:311–17 [Google Scholar]
  32. Avitsur R, Stark JL, Sheridan JF. 32.  2001. Social stress induces glucocorticoid resistance in subordinate animals. Horm. Behav. 39:247–57 [Google Scholar]
  33. Stark JL, Avitsur R, Padgett DA, Campbell KA, Beck FM, Sheridan JF. 33.  2001. Social stress induces glucocorticoid resistance in macrophages. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280:R1799–805 [Google Scholar]
  34. Ramirez K, Sheridan JF. 34.  2016. Antidepressant imipramine diminishes stress-induced inflammation in the periphery and central nervous system and related anxiety- and depressive- like behaviors. Brain Behav. Immun. 57:293–303 [Google Scholar]
  35. Hodes GE, Pfau ML, Leboeuf M, Golden SA, Christoffel DJ. 35.  et al. 2014. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. PNAS 111:16136–41 [Google Scholar]
  36. Modabbernia A, Taslimi S, Brietzke E, Ashrafi M. 36.  2013. Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies. Biol. Psychiatry 74:15–25 [Google Scholar]
  37. Kappelmann N, Lewis G, Dantzer R, Jones PB, Khandaker GM. 37.  2016. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol. Psychiatry. In press. https://doi.org/10.1038/mp.2016.167 [Crossref] [Google Scholar]
  38. Brietzke E, Scheinberg M, Lafer B. 38.  2011. Therapeutic potential of interleukin-6 antagonism in bipolar disorder. Med. Hypotheses 76:21–23 [Google Scholar]
  39. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P. 39.  et al. 2013. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70:31–41 [Google Scholar]
  40. Kohler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL. 40.  et al. 2014. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 71:1381–91 [Google Scholar]
  41. Warner-Schmidt JL, Vanover KE, Chen EY, Marshall JJ, Greengard P. 41.  2011. Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. PNAS 108:9262–67 [Google Scholar]
  42. Setiawan E, Wilson AA, Mizrahi R, Rusjan PM, Miler L. 42.  et al. 2015. Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry 72:268–75 [Google Scholar]
  43. Steiner J, Walter M, Gos T, Guillemin GJ, Bernstein HG. 43.  et al. 2011. Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: evidence for an immune-modulated glutamatergic neurotransmission?. J. Neuroinflamm. 8:94 [Google Scholar]
  44. Cotter D, Mackay D, Landau S, Kerwin R, Everall I. 44.  2001. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch. Gen. Psychiatry 58:545–53 [Google Scholar]
  45. Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD. 45.  et al. 1999. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol. Psychiatry 45:1085–98 [Google Scholar]
  46. Ongur D, Drevets WC, Price JL. 46.  1998. Glial reduction in the subgenual prefrontal cortex in mood disorders. PNAS 95:13290–95 [Google Scholar]
  47. Bowley MP, Drevets WC, Ongur D, Price JL. 47.  2002. Low glial numbers in the amygdala in major depressive disorder. Biol. Psychiatry 52:404–12 [Google Scholar]
  48. Si X, Miguel-Hidalgo JJ, O'Dwyer G, Stockmeier CA, Rajkowska G. 48.  2004. Age-dependent reductions in the level of glial fibrillary acidic protein in the prefrontal cortex in major depression. Neuropsychopharmacology 29:2088–96 [Google Scholar]
  49. Rajkowska G, Stockmeier CA. 49.  2013. Astrocyte pathology in major depressive disorder: insights from human postmortem brain tissue. Curr. Drug Targets 14:1225–36 [Google Scholar]
  50. Torres-Platas SG, Hercher C, Davoli MA, Maussion G, Labonte B. 50.  et al. 2011. Astrocytic hypertrophy in anterior cingulate white matter of depressed suicides. Neuropsychopharmacology 36:2650–58 [Google Scholar]
  51. Rajkowska G, Hughes J, Stockmeier CA, Javier Miguel-Hidalgo J, Maciag D. 51.  2013. Coverage of blood vessels by astrocytic endfeet is reduced in major depressive disorder. Biol. Psychiatry 73:613–21 [Google Scholar]
  52. Najjar S, Pearlman DM, Devinsky O, Najjar A, Zagzag D. 52.  2013. Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence. J. Neuroinflamm. 10:142 [Google Scholar]
  53. Valkanova V, Ebmeier KP. 53.  2013. Vascular risk factors and depression in later life: a systematic review and meta-analysis. Biol. Psychiatry 73:406–13 [Google Scholar]
  54. Politi P, Brondino N, Emanuele E. 54.  2008. Increased proapoptotic serum activity in patients with chronic mood disorders. Arch. Med. Res. 39:242–45 [Google Scholar]
  55. Ménard C, Pfau ML, Hodes GE, Russo SJ. 55.  2016. Immune and neuroendocrine mechanisms of stress vulnerability and resilience. Neuropsychopharmacology 42:62–80 [Google Scholar]
  56. Wohleb ES. 56.  2016. Neuron–microglia interactions in mental health disorders: “for better, and for worse.”. Front. Immunol. 7:544 [Google Scholar]
  57. Wohleb ES, Hanke ML, Corona AW, Powell ND, Stiner LM. 57.  et al. 2011. β-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat. J. Neurosci. 31:6277–88 [Google Scholar]
  58. Johnson JD, Campisi J, Sharkey CM, Kennedy SL, Nickerson M. 58.  et al. 2005. Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines. Neuroscience 135:1295–307 [Google Scholar]
  59. Blandino P Jr., Barnum CJ, Deak T. 59.  2006. The involvement of norepinephrine and microglia in hypothalamic and splenic IL-1β responses to stress. J. Neuroimmunol. 173:87–95 [Google Scholar]
  60. Frank MG, Thompson BM, Watkins LR, Maier SF. 60.  2012. Glucocorticoids mediate stress-induced priming of microglial pro-inflammatory responses. Brain Behav. Immun. 26:337–45 [Google Scholar]
  61. Alcocer-Gómez E, Ulecia-Morón C, Marín-Aguilar F, Rybkina T, Casas-Barquero N. 61.  et al. 2016. Stress-induced depressive behaviors require a functional NLRP3 inflammasome. Mol. Neurobiol. 53:4874–82 [Google Scholar]
  62. Iwata M, Ota KT, Li XY, Sakaue F, Li N. 62.  et al. 2016. Psychological stress activates the inflammasome via release of adenosine triphosphate and stimulation of the purinergic type 2X7 receptor. Biol. Psychiatry 80:12–22 [Google Scholar]
  63. Meeuwsen S, Persoon-Deen C, Bsibsi M, Ravid R, van Noort JM. 63.  2003. Cytokine, chemokine and growth factor gene profiling of cultured human astrocytes after exposure to proinflammatory stimuli. Glia 43:243–53 [Google Scholar]
  64. Santha P, Veszelka S, Hoyk Z, Meszaros M, Walter FR. 64.  et al. 2015. Restraint stress-induced morphological changes at the blood-brain barrier in adult rats. Front. Mol. Neurosci. 8:88 [Google Scholar]
  65. Wohleb ES, Patterson JM, Sharma V, Quan N, Godbout JP, Sheridan JF. 65.  2014. Knockdown of interleukin-1 receptor type-1 on endothelial cells attenuated stress-induced neuroinflammation and prevented anxiety-like behavior. J. Neurosci. 34:2583–91 [Google Scholar]
  66. Hellwig S, Heinrich A, Biber K. 66.  2013. The brain's best friend: microglial neurotoxicity revisited. Front. Cell. Neurosci. 7:71 [Google Scholar]
  67. McKim DB, Niraula A, Tarr AJ, Wohleb ES, Sheridan JF, Godbout JP. 67.  2016. Neuroinflammatory dynamics underlie memory impairments after repeated social defeat. J. Neurosci. 36:2590–604 [Google Scholar]
  68. Zhang Y, Liu L, Liu YZ, Shen XL, Wu TY. 68.  et al. 2015. NLRP3 inflammasome mediates chronic mild stress-induced depression in mice via neuroinflammation. Int. J. Neuropsychopharmacol. 18:pyv006 [Google Scholar]
  69. Wohleb ES, Powell ND, Godbout JP, Sheridan JF. 69.  2013. Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior. J. Neurosci. 33:13820–33 [Google Scholar]
  70. Hellwig S, Brioschi S, Dieni S, Frings L, Masuch A. 70.  et al. 2016. Altered microglia morphology and higher resilience to stress-induced depression-like behavior in CX3CR1-deficient mice. Brain Behav. Immun. 55:126–37 [Google Scholar]
  71. Ernst C, Nagy C, Kim S, Yang JP, Deng X. 71.  et al. 2011. Dysfunction of astrocyte connexins 30 and 43 in dorsal lateral prefrontal cortex of suicide completers. Biol. Psychiatry 70:312–19 [Google Scholar]
  72. Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS. 72.  et al. 2010. Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Mol. Psychiatry 15:501–11 [Google Scholar]
  73. Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M. 73.  et al. 2012. Minocycline as adjunctive therapy for patients with unipolar psychotic depression: an open-label study. Prog. Neuropsychopharmacol. Biol. Psychiatry 37:222–26 [Google Scholar]
  74. Emadi-Kouchak H, Mohammadinejad P, Asadollahi-Amin A, Rasoulinejad M, Zeinoddini A. 74.  et al. 2016. Therapeutic effects of minocycline on mild-to-moderate depression in HIV patients: a double-blind, placebo-controlled, randomized trial. Int. Clin. Psychopharmacol. 31:20–26 [Google Scholar]
  75. Nakasujja N, Miyahara S, Evans S, Lee A, Musisi S. 75.  et al. 2013. Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment. Neurology 80:196–202 [Google Scholar]
  76. Husain MI, Chaudhry IB, Rahman RR, Hamirani MM, Qurashi I. 76.  et al. 2015. Minocycline as an adjunct for treatment-resistant depressive symptoms: study protocol for a pilot randomised controlled trial. Trials 16:410 [Google Scholar]
  77. Dean OM, Maes M, Ashton M, Berk L, Kanchanatawan B. 77.  et al. 2014. Protocol and rationale - the efficacy of minocycline as an adjunctive treatment for major depressive disorder: a double blind, randomised, placebo controlled trial. Clin. Psychopharmacol. Neurosci. 12:180–88 [Google Scholar]
  78. Husain MI, Chaudhry IB, Hamirani MM, Minhas FA, Kazmi A. 78.  et al. 2017. Minocycline and celecoxib as adjunctive treatments for bipolar depression: a study protocol for a multicenter factorial design randomized controlled trial. Neuropsychiatr. Dis. Treat. 13:1–8 [Google Scholar]
  79. Zarate CA Jr., Payne JL, Quiroz J, Sporn J, Denicoff KK. 79.  et al. 2004. An open-label trial of riluzole in patients with treatment-resistant major depression. Am. J. Psychiatry 161:171–74 [Google Scholar]
  80. Sanacora G, Kendell SF, Fenton L, Coric V, Krystal JH. 80.  2004. Riluzole augmentation for treatment-resistant depression. Am. J. Psychiatry 161:2132 [Google Scholar]
  81. Sanacora G, Kendell SF, Levin Y, Simen AA, Fenton LR. 81.  et al. 2007. Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. Biol. Psychiatry 61:822–25 [Google Scholar]
  82. Mathew SJ, Amiel JM, Coplan JD, Fitterling HA, Sackeim HA, Gorman JM. 82.  2005. Open-label trial of riluzole in generalized anxiety disorder. Am. J. Psychiatry 162:2379–81 [Google Scholar]
  83. Salardini E, Zeinoddini A, Mohammadinejad P, Khodaie-Ardakani MR, Zahraei N. 83.  et al. 2016. Riluzole combination therapy for moderate-to-severe major depressive disorder: a randomized, double-blind, placebo-controlled trial. J. Psychiatr. Res. 75:24–30 [Google Scholar]
  84. Alcocer-Gómez E, de Miguel M, Casas-Barquero N, Núñez-Vasco J, Sánchez-Alcazar JA. 84.  et al. 2014. NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder. Brain Behav. Immun. 36:111–17 [Google Scholar]
  85. Iwata M, Ota KT, Duman RS. 85.  2013. The inflammasome: pathways linking psychological stress, depression, and systemic illnesses. Brain Behav. Immun. 31:105–14 [Google Scholar]
  86. Lamkanfi M, Mueller JL, Vitari AC, Misaghi S, Fedorova A. 86.  et al. 2009. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J. Cell Biol. 187:61–70 [Google Scholar]
  87. 87. Mayo Clinic. 2017. Glyburide (Oral Route) http://www.mayoclinic.org/drugs-supplements/glyburide-oral-route/side-effects/drg-20072094 [Google Scholar]
  88. Dinan TG, Cryan JF. 88.  2017. Microbes, immunity, and behavior: Psychoneuroimmunology meets the microbiome. Neuropsychopharmacology 42:178–92 [Google Scholar]
  89. Aizawa E, Tsuji H, Asahara T, Takahashi T, Teraishi T. 89.  et al. 2016. Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. J. Affect. Disord. 202:254–57 [Google Scholar]
  90. Fung TC, Olson CA, Hsiao EY. 90.  2017. Interactions between the microbiota, immune and nervous systems in health and disease. Nat. Neurosci. 20:145–55 [Google Scholar]
  91. Zheng P, Zeng B, Zhou C, Liu M, Fang Z. 91.  et al. 2016. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Mol. Psychiatry 21:786–96 [Google Scholar]
  92. Kelly JR, Borre Y, O'Brien C, Patterson E, El Aidy S. 92.  et al. 2016. Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. J. Psychiatr. Res. 82:109–18 [Google Scholar]
  93. Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. 93.  2015. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front. Cell. Neurosci. 9:392 [Google Scholar]
  94. Vanuytsel T, van Wanrooy S, Vanheel H, Vanormelingen C, Verschueren S. 94.  et al. 2014. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut 63:1293–99 [Google Scholar]
  95. Alonso C, Guilarte M, Vicario M, Ramos L, Rezzi S. 95.  et al. 2012. Acute experimental stress evokes a differential gender-determined increase in human intestinal macromolecular permeability. Neurogastroenterol. Motil. 24:740–46 [Google Scholar]
  96. Grenham S, Clarke G, Cryan JF, Dinan TG. 96.  2011. Brain–gut–microbe communication in health and disease. Front. Physiol. 2:94 [Google Scholar]
  97. O'Mahony SM, Hyland NP, Dinan TG, Cryan JF. 97.  2011. Maternal separation as a model of brain-gut axis dysfunction. Psychopharmacology 214:71–88 [Google Scholar]
  98. Torow N, Hornef MW. 98.  2017. The neonatal window of opportunity: setting the stage for life-long host-microbial interaction and immune homeostasis. J. Immunol. 198:557–63 [Google Scholar]
  99. Heijtz RD, Wang S, Anuar F, Qian Y, Bjorkholm B. 99.  et al. 2011. Normal gut microbiota modulates brain development and behavior. PNAS 108:3047–52 [Google Scholar]
  100. Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD. 100.  et al. 2013. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol. Psychiatry 18:666–73 [Google Scholar]
  101. Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N. 101.  et al. 2004. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol. 558:263–75 [Google Scholar]
  102. Reber SO, Siebler PH, Donner NC, Morton JT, Smith DG. 102.  et al. 2016. Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice. PNAS 113:E3130–39 [Google Scholar]
  103. Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan TG. 103.  2010. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 170:1179–88 [Google Scholar]
  104. Savignac HM, Kiely B, Dinan TG, Cryan JF. 104.  2014. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol. Motil. 26:1615–27 [Google Scholar]
  105. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM. 105.  et al. 2011. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. PNAS 108:16050–55 [Google Scholar]
  106. Bharwani A, Mian MF, Surette MG, Bienenstock J, Forsythe P. 106.  2017. Oral treatment with Lactobacillus rhamnosus attenuates behavioural deficits and immune changes in chronic social stress. BMC Med 15:7 [Google Scholar]
  107. Arseneault-Breárd J, Rondeau I, Gilbert K, Girard SA, Tompkins TA. 107.  et al. 2012. Combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces post-myocardial infarction depression symptoms and restores intestinal permeability in a rat model. Br. J. Nutr. 107:1793–99 [Google Scholar]
  108. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. 108.  2008. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J. Psychiatr. Res. 43:164–74 [Google Scholar]
  109. Lavasani S, Dzhambazov B, Nouri M, Fak F, Buske S. 109.  et al. 2010. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLOS ONE 5:e9009 [Google Scholar]
  110. Akkasheh G, Kashani-Poor Z, Tajabadi-Ebrahimi M, Jafari P, Akbari H. 110.  et al. 2016. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial. Nutrition 32:315–20 [Google Scholar]
  111. Mohammadi AA, Jazayeri S, Khosravi-Darani K, Solati Z, Mohammadpour N. 111.  et al. 2016. The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: a randomized, double-blind, placebo-controlled trial in petrochemical workers. Nutr. Neurosci. 19:387–95 [Google Scholar]
  112. Rao AV, Bested AC, Beaulne TM, Katzman MA, Iorio C. 112.  et al. 2009. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog 1:6 [Google Scholar]
  113. Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D. 113.  et al. 2011. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br. J. Nutr. 105:755–64 [Google Scholar]
  114. Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. 114.  2015. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav. Immun. 48:258–64 [Google Scholar]
  115. Vindigni SM, Surawicz CM. 115.  2017. Fecal microbiota transplantation. Gastroenterol. Clin. N. Am. 46:171–85 [Google Scholar]
  116. Kang DW, Adams JB, Gregory AC, Borody T, Chittick L. 116.  et al. 2017. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 5:10 [Google Scholar]
  117. Benros ME, Waltoft BL, Nordentoft M, Ostergaard SD, Eaton WW. 117.  et al. 2013. Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. JAMA Psychiatry 70:812–20 [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-010617-052823
Loading
/content/journals/10.1146/annurev-pharmtox-010617-052823
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error