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Inflammation: a mechanism of depression?

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Abstract

In recent decades, major depression has become more prevalent and research has shown that immune activation and cytokine production may be involved. This review is mainly focused on the contribution of inflammation to depression. We first briefly introduce the inflammatory biomarkers of depression, then discuss the sources of cytokines in the brain, and finally describe the neuroimmunological mechanisms underlying the association between inflammation and depression.

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References

  1. Compton WM, Conway KP, Stinson FS, Grant BF. Changes in the prevalence of major depression and comorbid substance use disorders in the United States between 1991–1992 and 2001–2002. Am J Psychiatry 2006, 163: 2141–2147.

    PubMed  Google Scholar 

  2. Kessler RC, McGonagle KA, Swartz M, Blazer DG, Nelson CB. Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence, chronicity and recurrence. J Affect Disord 1993, 29: 85–96.

    CAS  PubMed  Google Scholar 

  3. Sharpley CF, Agnew LL. Cytokines and depression: findings, issues, and treatment implications. Rev Neurosci 2011, 22: 295–302.

    CAS  PubMed  Google Scholar 

  4. Dunn AJ, Swiergiel AH, de Beaurepaire R. Cytokines as mediators of depression: what can we learn from animal studies? Neurosci Biobehav Rev 2005, 29: 891–909.

    CAS  PubMed  Google Scholar 

  5. Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 2009, 71: 171–186.

    CAS  PubMed  Google Scholar 

  6. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996, 87: 2095–2147.

    CAS  PubMed  Google Scholar 

  7. Plata-Salaman CR, Ilyin SE. Interleukin-1beta (IL-1beta)-induced modulation of the hypothalamic IL-1beta system, tumor necrosis factor-alpha, and transforming growth factorbeta1 mRNAs in obese (fa/fa) and lean (Fa/Fa) Zucker rats: implications to IL-1beta feedback systems and cytokine-cytokine interactions. J Neurosci Res 1997, 49: 541–550.

    CAS  PubMed  Google Scholar 

  8. Kronfol Z, Remick DG. Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry 2000, 157: 683–694.

    CAS  PubMed  Google Scholar 

  9. Macaluso M, Drevets WC, Preskorn SH. How biomarkers will change psychiatry. Part II: Biomarker selection and potential inflammatory markers of depression. J Psychiatr Pract 2012, 18: 281–286.

    PubMed  Google Scholar 

  10. Schmidt HD, Shelton RC, Duman RS. Functional biomarkers of depression: diagnosis, treatment, and pathophysiology. Neuropsychopharmacology 2011, 36: 2375–2394.

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Taler M, Gil-Ad I, Lomnitski L, Korov I, Baharav E, Bar M, et al. Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur Neuropsychopharmacol 2007, 17: 774–780.

    CAS  PubMed  Google Scholar 

  12. Sutcigil L, Oktenli C, Musabak U, Bozkurt A, Cansever A, Uzun O, et al. Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy. Clin Dev Immunol 2007, 2007: 76396.

    PubMed Central  PubMed  Google Scholar 

  13. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010, 67: 446–457.

    CAS  PubMed  Google Scholar 

  14. Kahl KG, Bens S, Ziegler K, Rudolf S, Dibbelt L, Kordon A, et al. Cortisol, the cortisol-dehydroepiandrosterone ratio, and pro-inflammatory cytokines in patients with current major depressive disorder comorbid with borderline personality disorder. Biol Psychiatry 2006, 59: 667–671.

    CAS  PubMed  Google Scholar 

  15. Steptoe A, Hamer M, Chida Y. The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun 2007, 21: 901–912.

    CAS  PubMed  Google Scholar 

  16. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006, 27: 24–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Diniz BS, Teixeira AL, Talib L, Gattaz WF, Forlenza OV. Interleukin-1beta serum levels is increased in antidepressant-free elderly depressed patients. Am J Geriatr Psychiatry 2010, 18: 172–176.

    PubMed  Google Scholar 

  18. Yoshimura R, Hori H, Ikenouchi-Sugita A, Umene-Nakano W, Ueda N, Nakamura J. Higher plasma interleukin-6 (IL-6) level is associated with SSRI- or SNRI-refractory depression. Prog Neuropsychopharmacol Biol Psychiatry 2009, 33: 722–726.

    CAS  PubMed  Google Scholar 

  19. Himmerich H, Milenovic S, Fulda S, Plumakers B, Sheldrick AJ, Michel TM, et al. Regulatory T cells increased while IL-1beta decreased during antidepressant therapy. J Psychiatr Res 2010, 44: 1052–1057.

    PubMed  Google Scholar 

  20. Tuglu C, Kara SH, Caliyurt O, Vardar E, Abay E. Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacology (Berl) 2003, 170: 429–433.

    CAS  Google Scholar 

  21. Jazayeri S, Keshavarz SA, Tehrani-Doost M, Djalali M, Hosseini M, Amini H, et al. Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder. Psychiatry Res 2010, 178: 112–115.

    CAS  PubMed  Google Scholar 

  22. Shelton RC, Miller AH. Inflammation in depression: is adiposity a cause? Dialogues Clin Neurosci 2011, 13: 41–53.

    PubMed  Google Scholar 

  23. Wu XP, Wang D, Song ZJ, Sun CZ, Xiao XL, He YD, et al. [Impact of anxiety-depression symptoms on clinical recovery and serum TNF-alpha and IL-6 of patients with burns]. Sichuan Da Xue Xue Bao Yi Xue Ban 2008, 39: 105–107.

    PubMed  Google Scholar 

  24. Jehn CF, Kuhnhardt D, Bartholomae A, Pfeiffer S, Schmid P, Possinger K, et al. Association of IL-6, hypothalamus-pituitary-adrenal axis function, and depression in patients with cancer. Integr Cancer Ther 2010, 9: 270–275.

    CAS  PubMed  Google Scholar 

  25. Liu Y, Ho RC, Mak A. The role of interleukin (IL)-17 in anxiety and depression of patients with rheumatoid arthritis. Int J Rheum Dis 2012, 15: 183–187.

    CAS  PubMed  Google Scholar 

  26. Cheng J, Zhang J, Lu C, Wang L. Using optogenetics to translate the “inflammatory dialogue” between heart and brain in the context of stress. Neurosci Bull 2012, 28: 435–448.

    CAS  PubMed  Google Scholar 

  27. Quan N, Banks WA. Br ain-immune communication pathways. Brain Behav Immun 2007, 21: 727–735.

    CAS  PubMed  Google Scholar 

  28. Krishnadas R, Cavanagh J. Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry 2012, 83: 495–502.

    PubMed  Google Scholar 

  29. Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther 2011, 130: 226–238.

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008, 9: 46–56.

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Freidin M, Bennett MV, Kessler JA. Cultured sympathetic neurons synthesize and release the cytokine interleukin 1 beta. Proc Natl Acad Sci U S A 1992, 89: 10440–10443.

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Breder CD, Tsujimoto M, Terano Y, Scott DW, Saper CB. Distribution and characterization of tumor necrosis factor-alpha-like immunoreactivity in the murine central nervous system. J Comp Neurol 1993, 337: 543–567.

    CAS  PubMed  Google Scholar 

  33. Bethea JR, Chung IY, Sparacio SM, Gillespie GY, Benveniste EN. Interleukin-1 beta induction of tumor necrosis factor-alpha gene expression in human astroglioma cells. J Neuroimmunol 1992, 36: 179–191.

    CAS  PubMed  Google Scholar 

  34. Juul SE, Anderson DK, Li Y, Christensen RD. Erythropoietin and erythropoietin receptor in the developing human central nervous system. Pediatr Res 1998, 43: 40–49.

    CAS  PubMed  Google Scholar 

  35. Tweardy DJ, Mott PL, Glazer EW. Monokine modulation of human astroglial cell production of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. I. Effects of IL-1 alpha and IL-beta. J Immunol 1990, 144: 2233–2241.

    CAS  PubMed  Google Scholar 

  36. Breder CD, Dinarello CA, Saper CB. Interleukin-1 immunoreactive innervation of the human hypothalamus. Science 1988, 240: 321–324.

    CAS  PubMed  Google Scholar 

  37. Rothwell NJ, Luheshi G. Pharma cology of interleukin-1 actions in the brain. Adv Pharmacol 1994, 25: 1–20.

    CAS  PubMed  Google Scholar 

  38. Hanisch UK, Quirion R. Interleu kin-2 as a neuroregulatory cytokine. Brain Res Brain Res Rev 1995, 21: 246–284.

    CAS  PubMed  Google Scholar 

  39. Konishi Y, Chui DH, Kunishita T, Yamamura T, Higashi Y, Tabira T. Demonstration of interleukin-3 receptor-associated antigen in the central nervous system. J Neurosci Res 1995, 41: 572–582.

    CAS  PubMed  Google Scholar 

  40. Racke MK, Burnett D, Pak SH, Albert PS, Cannella B, Raine CS, et al. Retinoid treatment of experimental allergic encephalomyelitis. IL-4 production correlates with improved disease course. J Immunol 1995, 154: 450–458.

    CAS  PubMed  Google Scholar 

  41. Benveniste EN, Sparacio SM, Norris JG, Grenett HE, Fuller GM. Induction and regulation of interleukin-6 gene expression in rat astrocytes. J Neuroimmunol 1990, 30: 201–212.

    CAS  PubMed  Google Scholar 

  42. Ehrlich LC, Hu S, Sheng WS, Sutton RL, Rockswold GL, Peterson PK, et al. Cytokine regulation of human microglial cell IL-8 production. J Immunol 1998, 160: 1944–1948.

    CAS  PubMed  Google Scholar 

  43. Wong ML, Bongiorno PB, Rettori V, McCann SM, Licinio J. Interleukin (IL) 1beta, IL-1 receptor antagonist, IL-10, and IL-13 gene expression in the central nervous system and anterior pituitary during systemic inflammation: pathophysiological implications. Proc Natl Acad Sci U S A 1997, 94: 227–232.

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Stalder AK, Pagenstecher A, Yu NC, Kincaid C, Chiang CS, Hobbs MV, et al. Lipopolysaccharide-induced IL-12 expression in the central nervous system and cultured astrocytes and microglia. J Immunol 1997, 159: 1344–1351.

    CAS  PubMed  Google Scholar 

  45. Bethea JR, Gillespie GY, Benveniste EN. Interleukin-1 beta induction of TNF-alpha gene expression: involvement of protein kinase C. J Cell Physiol 1992, 152: 264–273.

    CAS  PubMed  Google Scholar 

  46. Tilders FJ, DeRijk RH, Van Dam AM, Vincent VA, Schotanus K, Persoons JH. Activation of the hypothalamus-pituitary-adrenal axis by bacterial endotoxins: routes and intermediate signals. Psychoneuroendocrinology 1994, 19: 209–232.

    CAS  PubMed  Google Scholar 

  47. Monje FJ, Cabatic M, Divisch I, Kim EJ, Herkner KR, Binder BR, et al. Constant darkness induces IL-6-dependent depression-like behavior through the NF-kappaB signaling pathway. J Neurosci 2011, 31: 9075–9083.

    CAS  PubMed  Google Scholar 

  48. Marini H, Altavilla D, Bellomo M, Adamo E B, Marini R, Laureanti F, et al. Modulation of IL-1 beta gene expression by lipid peroxidation inhibition after kainic acid-induced rat brain injury. Exp Neurol 2004, 188: 178–186.

    CAS  PubMed  Google Scholar 

  49. Kumagai N, Chiba Y, Hosono M, Fujii M, Kawamura N, Keino H, et al. Involvement of pro-inflammatory cytokines and microglia in an age-associated neurodegeneration model, the SAMP10 mouse. Brain Res 2007, 1185: 75–85.

    CAS  PubMed  Google Scholar 

  50. Feuerstein GZ, Wang X, Barone FC. Inflammat ory gene expression in cerebral ischemia and trauma. Potential new therapeutic targets. Ann N Y Acad Sci 1997, 825: 179–193.

    CAS  PubMed  Google Scholar 

  51. Minami M, Kuraishi Y, Satoh M. Effects of ka inic acid on messenger RNA levels of IL-1 beta, IL-6, TNF alpha and LIF in the rat brain. Biochem Biophys Res Commun 1991, 176: 593–598.

    CAS  PubMed  Google Scholar 

  52. Siren AL, Heldman E, Doron D, Lysko PG, Yue T L, Liu Y, et al. Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Stroke 1992, 23: 1643–1650; discussion 1650–1641.

    CAS  PubMed  Google Scholar 

  53. Alvarez XA, Franco A, Fernandez-Novoa L, Cacabelos R. Effects of neurotoxic lesions in histaminergic neurons on brain tumor necrosis factor levels. Agents Actions 1994, 41 Spec No: C70–72.

    Google Scholar 

  54. Shohami E, Novikov M, Bass R, Yamin A, Gallily R. Closed head injury triggers early production of TNF alpha and IL-6 by brain tissue. J Cereb Blood Flow Metab 1994, 14: 615–619.

    CAS  PubMed  Google Scholar 

  55. Taupin V, Toulmond S, Serrano A, Benavides J, Zavala F. Increase in IL-6, IL-1 and TNF levels in rat brain following traumatic lesion. Influence of pre- and post-traumatic treatment with Ro5 4864, a peripheral-type (p site) benzodiazepine ligand. J Neuroimmunol 1993, 42: 177–185.

    CAS  PubMed  Google Scholar 

  56. van der Werf-Eldering MJ, Riemersma-van der Lek R F, Burger H, Holthausen EA, Aleman A, Nolen WA. Can variation in hypothalamic-pituitary-adrenal (HPA)-axis activity explain the relationship between depression and cognition in bipolar patients? PLoS One 2012, 7: e37119.

    PubMed Central  PubMed  Google Scholar 

  57. Mastorakos G, Chrousos GP, Weber JS. Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. J Clin Endocrinol Metab 1993, 77: 1690–1694.

    CAS  PubMed  Google Scholar 

  58. Himmerich H, Binder EB, Kunzel HE, Schuld A, Lucae S, Uhr M, et al. Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis. Biol Psychiatry 2006, 60: 882–888.

    CAS  PubMed  Google Scholar 

  59. O’Keane V, Frodl T, Dinan TG. A review of Atypical depression in relation to the course of depression and changes in HPA axis organization. Psychoneuroendocrinology 2012, 37: 1589–1599.

    PubMed  Google Scholar 

  60. Frost P, Bornstein S, Ehrhart-Bornstein M, O’Kirwan F, Hutson C, Heber D, et al. The prototypic antidepressant drug, imipramine, but not Hypericum perforatum (St. John’s Wort), reduces HPA-axis function in the rat. Horm Metab Res 2003, 35: 602–606.

    CAS  PubMed  Google Scholar 

  61. Myint AM, Kim YK. Cytokine-serotonin interaction thro ugh IDO: a neurodegeneration hypothesis of depression. Med Hypotheses 2003, 61: 519–525.

    CAS  PubMed  Google Scholar 

  62. Catena-Dell’Osso M, Rotella F, Dell’Osso A, Fagiolini A, Marazziti D. Inflammation, serotonin and major depression. Curr Drug Targets 2013, 14: 571–577.

    PubMed  Google Scholar 

  63. Pemberton LA, Kerr SJ, Smythe G, Brew BJ. Quinolinic ac id production by macrophages stimulated with IFN-gamma, TNF-alpha, and IFN-alpha. J Interferon Cytokine Res 1997, 17: 589–595.

    CAS  PubMed  Google Scholar 

  64. Fujigaki S, Saito K, Sekikawa K, Tone S, Takikawa O, Fujii H, et al. Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-gamma-independent mechanism. Eur J Immunol 2001, 31: 2313–2318.

    CAS  PubMed  Google Scholar 

  65. Wichers MC, Maes M. The role of indoleamine 2,3-dioxy gena se (IDO) in the pathophysiology of interferon-alpha-induced depression. J Psychiatry Neurosci 2004, 29: 11–17.

    PubMed Central  PubMed  Google Scholar 

  66. Heyes MP, Saito K, Crowley JS, Davis LE, Demitrack MA, Der M, et al. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain 1992, 115(Pt 5): 1249–1273.

    PubMed  Google Scholar 

  67. Wichers M, Maes M. The psychoneuroimmuno-patho physiology of cytokine-induced depression in humans. Int J Neuropsychopharmacol 2002, 5: 375–388.

    CAS  PubMed  Google Scholar 

  68. Dantzer R. Cytokine, sickness behavior, and depression. Immu nol Allergy Clin North Am 2009, 29: 247–264.

    Google Scholar 

  69. Sublette ME, Postolache TT. Neuroinflammation and depression: the role of indoleamine 2,3-dioxygenase (IDO) as a molecular pathway. Psychosom Med 2012, 74: 668–672.

    PubMed  Google Scholar 

  70. Prendergast GC, Chang MY, Mandik-Nayak L, Metz R, Muller AJ. I ndoleamine 2,3-dioxygenase as a modifier of pathogenic inflammation in cancer and other inflammation-associated diseases. Curr Med Chem 2011, 18: 2257–2262.

    CAS  PubMed  Google Scholar 

  71. Lesch KP, Mossner R. Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental, and neurodegenerative disorders? Biol Psychiatry 1998, 44: 179–192.

    CAS  PubMed  Google Scholar 

  72. Staley JK, Malison RT, Innis RB. Imaging of the serotonergic sys tem: interactions of neuroanatomical and functional abnormalities of depression. Biol Psychiatry 1998, 44: 534–549.

    CAS  PubMed  Google Scholar 

  73. Tsao CW, Lin YS, Chen CC, Bai CH, Wu SR. Cytokines and serotonin transporter in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 2006, 30: 899–905.

    CAS  PubMed  Google Scholar 

  74. Morikawa O, Sakai N, Obara H, Saito N. Effects of interferon-alpha, interferon-gamma and cAMP on the transcriptional regulation of the serotonin transporter. Eur J Pharmacol 1998, 349: 317–324.

    CAS  PubMed  Google Scholar 

  75. Mossner R, Heils A, Stober G, Okladnova O, Daniel S, Lesch KP. Enha ncement of serotonin transporter function by tumor necrosis factor alpha but not by interleukin-6. Neurochem Int 1998, 33: 251–254.

    CAS  PubMed  Google Scholar 

  76. Abe S, Hori T, Suzuki T, Baba A, Shiraishi H, Yamamoto T. Effects of chronic administration of interferon alpha A/D on serotonergic receptors in rat brain. Neurochem Res 1999, 24: 359–363.

    CAS  PubMed  Google Scholar 

  77. Kugaya A, Kagaya A, Uchitomi Y, Yokota N, Yamawaki S. Effect of inter feron-alpha on DOI-induced wet-dog shakes in rats. J Neural Transm 1996, 103: 947–955.

    CAS  PubMed  Google Scholar 

  78. Zalcman S, Green-Johnson JM, Murray L, Nance DM, Dyck D, Anisman H, et al. Cytokine-specific central monoamine alterations induced by interleukin-1, -2 and -6. Brain Res 1994, 643: 40–49.

    CAS  PubMed  Google Scholar 

  79. Hurst SM, Collins SM. Mechanism underlying tumor necrosis factor-alpha suppression of norepinephrine release from rat myenteric plexus. Am J Physiol 1994, 266: G1123–1129.

    CAS  PubMed  Google Scholar 

  80. Ando T, Dunn AJ. Mouse tumor necrosis factor-alpha increases brain trypt ophan concentrations and norepinephrine metabolism while activating the HPA axis in mice. Neuroimmunomodulation 1999, 6: 319–329.

    CAS  PubMed  Google Scholar 

  81. Moron JA, Zakharova I, Ferrer JV, Merrill GA, Hope B, Lafer EM, et al. Mi togen-activated protein kinase regulates dopamine transporter surface expression and dopamine transport capacity. J Neurosci 2003, 23: 8480–8488.

    CAS  PubMed  Google Scholar 

  82. Wu HQ, Rassoulpour A, Schwarcz R. Kynurenic acid leads, dopamine follows: a new case of volume transmission in the brain? J Neural Transm 2007, 114: 33–41.

    PubMed  Google Scholar 

  83. Shuto H, Kataoka Y, Horikawa T, Fujihara N, Oishi R. Repeated interferon-al pha administration inhibits dopaminergic neural activity in the mouse brain. Brain Res 1997, 747: 348–351.

    CAS  PubMed  Google Scholar 

  84. Felger JC, Alagbe O, Hu F, Mook D, Freeman AA, Sanchez MM, et al. Effects of interferon-alpha on rhesus monkeys: a nonhuman primate model of cytokine-induced depression. Biol Psychiatry 2007, 62: 1324–1333.

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Kitagami T, Yamada K, Miura H, Hashimoto R, Nabeshima T, Ohta T. Mechanism of systemically injected interferon-alpha impeding monoamine biosynthesis in rats: role of nitric oxide as a signal crossing the blood-brain barrier. Brain Res 2003, 978: 104–114.

    CAS  PubMed  Google Scholar 

  86. McNally L, Bhagwagar Z, Hannestad J. Inflammation, glutamate, and glia in depr ession: a literature review. CNS Spectr 2008, 13: 501–510.

    PubMed  Google Scholar 

  87. Viviani B, Bartesaghi S, Gardoni F, Vezzani A, Behrens MM, Bartfai T, et al. In terleukin-1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci 2003, 23: 8692–8700.

    CAS  PubMed  Google Scholar 

  88. Hu S, Sheng WS, Ehrlich LC, Peterson PK, Chao CC. Cytokine effects on glutamate uptake by human astrocytes. Neuroimmunomodulation 2000, 7: 153–159.

    CAS  PubMed  Google Scholar 

  89. Dowben JS, Grant JS, Keltner NL. Ketamine as an alternative treatment for treatme nt-resistant depression. Perspect Psychiatr Care 2013, 49: 2–4.

    PubMed  Google Scholar 

  90. Mathews DC, Zarate CA, Jr. Current status of ketamine and related compounds for de pression. J Clin Psychiatry 2013, 74: 516–517.

    PubMed Central  PubMed  Google Scholar 

  91. Katalinic N, Lai R, Somogyi A, Mitchell PB, Glue P, Loo CK. Ketamine as a new treat ment for depression: a review of its efficacy and adverse effects. Aust N Z J Psychiatry 2013, 47: 710–727.

    PubMed  Google Scholar 

  92. Howland RH. Ketamine for the treatment of depression. J Psychosoc Nurs Ment Health S erv 2013, 51: 11–14.

    Google Scholar 

  93. Hayley S, Poulter MO, Merali Z, Anisman H. The pathogenesis of clinical depression: s tressor- and cytokine-induced alterations of neuroplasticity. Neuroscience 2005, 135: 659–678.

    CAS  PubMed  Google Scholar 

  94. Fuchs E, Czeh B, Kole MH, Michaelis T, Lucassen PJ. Alterations of neuroplasticity in depression: the hippocampus and beyond. Eur Neuropsychopharmacol 2004, 14 Suppl 5: S481–490.

    Google Scholar 

  95. Carlson PJ, Singh JB, Zarate CA, Jr., Drevets WC, Manji HK. Neural circuitry and neurop lasticity in mood disorders: insights for novel therapeutic targets. NeuroRx 2006, 3: 22–41.

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Sapolsky RM. The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry 2000, 48: 755–765.

    CAS  PubMed  Google Scholar 

  97. Manji HK, Quiroz JA, Sporn J, Payne JL, Denicoff K, N AG, et al. Enhancing neuronal plast icity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry 2003, 53: 707–742.

    CAS  PubMed  Google Scholar 

  98. Kaneko N, Kudo K, Mabuchi T, Takemoto K, Fujimaki K, Wati H, et al. Suppression of cell pr oliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus. Neuropsychopharmacology 2006, 31: 2619–2626.

    CAS  PubMed  Google Scholar 

  99. Alboni S, Gibellini L, Montanari C, Benatti C, Benatti S, Tascedda F, et al. N-acetyl-cyste ine prevents toxic oxidative effects induced by IFN-alpha in human neurons. Int J Neuropsychopharmacol 2013, 16: 1849–1865.

    CAS  PubMed  Google Scholar 

  100. Sapolsky RM, Krey LC, McEwen BS. Prolonged glucocorticoid exposure reduces hippocampal neur on number: implications for aging. J Neurosci 1985, 5: 1222–1227.

    CAS  PubMed  Google Scholar 

  101. McEwen BS. Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Ann N Y Acad Sci 2001, 933: 265–277.

    CAS  PubMed  Google Scholar 

  102. Poo MM. Neurotrophins as synaptic modulators. Nat Rev Neurosci 2001, 2: 24–32.

    CAS  PubMed  Google Scholar 

  103. Patapoutian A, Reichardt LF. Trk receptors: mediators of neurotrophin action. Curr Opin Neurob iol 2001, 11: 272–280.

    CAS  Google Scholar 

  104. Mattson MP, Maudsley S, Martin B. BDNF and 5-HT: a dynamic duo in age-related neuronal plastici ty and neurodegenerative disorders. Trends Neurosci 2004, 27: 589–594.

    CAS  PubMed  Google Scholar 

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  1. Department of Integrative Medicine and Neurobiology, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Qiu-Qin Han & Jin Yu

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Han, QQ., Yu, J. Inflammation: a mechanism of depression?. Neurosci. Bull. 30, 515–523 (2014). https://doi.org/10.1007/s12264-013-1439-3

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