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Mood Disorders and Immunity

  • Adam K. Walker
  • Robert Dantzer
  • Keith W. Kelley
Chapter

Abstract

Depression is a common comorbid condition in substance abuse disorders. In particular, comorbidity between alcoholism and depression occurs with extremely high prevalence in the general population. Early studies investigating this dual diagnosis issue reported alcohol abuse to occur in almost a quarter of patients with affective disorders [1, 2]. Prevalence rises as high as 32 % if other substance abuse disorders are included [2]. These findings made it clear that enormous challenges lie ahead in tracing the individual etiology of substance abuse and depression, let alone their interaction. Clearly, this dilemma was to produce further difficulties in providing adequate and appropriate treatment for sufferers.

Keywords

Glucocorticoid Receptor Quinolinic Acid Kynurenine Pathway Sickness Behavior Neurotoxic Metabolite 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by National Institutes of Health grant RO1 AG029573 to Keith W. Kelley.

References

  1. 1.
    Hasin DS, Endicott J, Lewis C (1985) Alcohol and drug abuse in patients with affective syndromes. Compr Psychiatry 26:283–295PubMedGoogle Scholar
  2. 2.
    Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, Goodwin FK (1990) Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiological Catchment Area (ECA) Study. JAMA 264:2511–2518PubMedGoogle Scholar
  3. 3.
    Boschloo L, Vogelzangs N, Smit JH, van den Brink W, Veltman DJ, Beekman ATF, Penninx BWJH (2011) Comorbidity and risk indicators for alcohol use disorders among ­persons with anxiety and/or depressive disorders: findings from the Netherlands Study of Depression and Anxiety (NESDA). J Affect Disord 131:233–242PubMedGoogle Scholar
  4. 4.
    Buysse DJ, Angst J, Gamma A, Ajdacic V, Eich D, Rössler W (2008) Prevalence, course, and comorbidity of insomnia and depression in young adults. Sleep 31:473–480PubMedGoogle Scholar
  5. 5.
    Jim HSL, Small B, Faul LA, Franzen J, Apte S, Jacobsen PB (2011) Fatigue, depression, sleep, and activity during chemotherapy: daily and intraday variation and relationships among symptom changes. Ann Behav Med 42:321–333. doi: 10.1007/s12160-011-9294-9 PubMedGoogle Scholar
  6. 6.
    Rodin J, McAvay G, Timko C (1988) A longitudinal study of depressed mood and sleep disturbances in elderly adults. J Gerontol 43:P45–P53PubMedGoogle Scholar
  7. 7.
    Sinha R, Robinson J, Merikangas K, Wilson GT, Rodin J, O’Malley S (1996) Eating pathology among women with alcoholism and/or anxiety disorders. Alcohol Clin Exp Res 20:1184–1191PubMedGoogle Scholar
  8. 8.
    Swendsen JD, Merikangas KR (2000) The comorbidity of depression and substance use disorders. Clin Psychol Rev 20:173–189PubMedGoogle Scholar
  9. 9.
    Boden JM, Fergusson DM (2011) Alcohol and depression. Addiction 106(5):906–914PubMedGoogle Scholar
  10. 10.
    Kessler RC, Price RH (1993) Primary prevention of secondary disorders: a proposal and agenda. Am J Comm Psychol 21:607–633Google Scholar
  11. 11.
    Fergusson DM, Boden JM, Horwood LJ (2009) Tests of causal links between alcohol abuse or dependence and major depression. Arch Gen Psychiatry 66:260–266PubMedGoogle Scholar
  12. 12.
    Paljarvi T, Koskenvuo M, Poikolainen K, Kauhanen J, Sillinmaki L, Makela P (2009) Binge drinking and depressive symptoms: a 5 year population-based cohort study. Addiction 104:1168–1178PubMedGoogle Scholar
  13. 13.
    Nurnberger JI, Foroud T, Flury L, Su J, Meyer ET, Hu K, Crowe R, Edenberg H, Goate A, Bierut L, Reich T, Schuckit M, Reich W (2001) Evidence for a locus on chromosome 1 that influences vulnerability to alcoholism and affective disorder. Am J Psychiatry 158:718–724PubMedGoogle Scholar
  14. 14.
    Fu Q, Heath AC, Bucholz KK, Nelson E, Goldberg J, Lyons MJ, True WR, Jacob T, Tsuang MT, Eisen SA (2002) Shared genetic risk of major depression, alcohol dependence, and marijuana dependence. Arch Gen Psychiatry 59:1125–1132PubMedGoogle Scholar
  15. 15.
    Kuo PH, Neale MC, Walsh D, Patterson DG, Riley B, Prescott CA, Kendler KS (2010) Genome-wide linkage scans for major depression in individuals with alcohol dependence. J Psychiatr Res 44:616–619PubMedGoogle Scholar
  16. 16.
    Kendler KS, Kessler RC, Walters EE, MacLean CJ, Sham PC, Neale MC, Heath AC, Eaves LJ (1995) Stressful life events, genetic liability and onset of an episode of major depression in women. Am J Psychiatry 152:833–842PubMedGoogle Scholar
  17. 17.
    Fava M, Davidson KG (1996) Definition and epidemiology of treatment-resistant depression. Psychiatr Clin North Am 19:179–200PubMedGoogle Scholar
  18. 18.
    Lesch KP (2004) Gene–environment interaction and the genetics of depression. J Psychiatry Neurosci 29:174–184PubMedGoogle Scholar
  19. 19.
    Agrawal A, Scherrer JF, Lynskey MT, Sartor CE, Grant JD, Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, Kavalali ET (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475:91–97Google Scholar
  20. 20.
    Miguel-Hidalgo JJ, Nithuairisg S, Stockmeier C, Rajkowska G (2007) Distribution of ICAM-1 immunoreactivity during aging in the human orbitofrontal cortex. Brain Behav Immun 21:100–111PubMedGoogle Scholar
  21. 21.
    Haddad JJ (2004) Alcoholism and neuro-immune-endocrine interactions: physiochemical aspects. Biochem Biophys Res Commun 323:361–371PubMedGoogle Scholar
  22. 22.
    Crews FT, Zou J, Qin L (2011) Induction of innate immune genes in brain create the neurobiology of addiction. Brain Behav Immun 25:S4–S12PubMedGoogle Scholar
  23. 23.
    Blednov YA, Benavidez JM, Geil C, Perra S, Morikawa H, Harris RA (2011) Activation of inflammatory signaling by lipopolysaccharide produces a prolonged increase of voluntary alcohol intake in mice. Brain Behav Immun 25(Suppl 1):S92–S105PubMedGoogle Scholar
  24. 24.
    Stevenson JR, Schroeder JP, Nixon K, Besheer J, Crews FT, Hodge CW (2009) Abstinence following alcohol drinking produces depression-like behavior and reduced hippocampal ­neurogenesis in mice. Neuropsychopharmacology 34:1209–1222PubMedGoogle Scholar
  25. 25.
    Capuron L, Miller AH (2004) Cytokines and psychopathology: lessons from interferon-alpha. Biol Psychiatry 56:819–824PubMedGoogle Scholar
  26. 26.
    Capuron L, Pagnoni G, Lawson DH, Demetrashvili M, Woolwine BJ, Kilts CD, Bremner JD, Nemeroff CB, Miller AH (2002) Altered fronto-pallidal activity during high-dose interferon-alpha treatment as determined by positron emission tomography. Abstr Soc Neurosci 498:5Google Scholar
  27. 27.
    Haas HS, Schaenstein K (1997) Neuroimmunomodulation via limbic structures: the neuroanatomy of psychoimmunology. Prog Neurobiol 51:195–222PubMedGoogle Scholar
  28. 28.
    Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65:732–741PubMedGoogle Scholar
  29. 29.
    Alfonso-Loeches S, Pascual-Lucas M, Blanco AM, Sanchez-Vera I, Guerri C (2010) Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage. J Neurosci 30:8285–8295PubMedGoogle Scholar
  30. 30.
    Lu YC, Yeh WC, Ohashi PS (2008) LPS/TLR4 signal transduction pathway. Cytokine 42:145–151PubMedGoogle Scholar
  31. 31.
    Irwin MR, Olmstead R, Valladares EM, Crabb Breen E, Ehlers CL (2009) Tumor necrosis factor antagonism normalizes rapid eye movement sleep in alcohol dependence. Biol Psychiatry 66:191–195PubMedGoogle Scholar
  32. 32.
    Ford DE, Kamerow DB (1989) Epidemiologic study of sleep disturbances and psychiatric disorders: an opportunity for prevention? JAMA 262:1479–1484PubMedGoogle Scholar
  33. 33.
    Clark CP, Gillin JC, Golshan S, Demodena A, Smith TL, Danowski S, Irwin M, Schuckit M (1998) Increased REM sleep density at admission predicts relapse by three months in primary alcoholics with a lifetime diagnosis of secondary depression. Biol Psychiatry 43:601–607PubMedGoogle Scholar
  34. 34.
    Opp MR, Toth LA (2003) Neural-immune interactions in the regulation of sleep. Front Biosci 8:d768–d779PubMedGoogle Scholar
  35. 35.
    Dantzer R, Kelley KW (1989) Stress and immunity: an integrated view of relationships between the brain and the immune system. Life Sci 44:1995–2008PubMedGoogle Scholar
  36. 36.
    Bluthé RM, Michaud B, Poli V, Dantzer R (2000) Role of IL-6 in cytokine-induced sickness behavior: a study with IL-6 deficient mice. Physiol Behav 70:367–373PubMedGoogle Scholar
  37. 37.
    Opp MR, Krueger JM (1991) Interleukin 1-receptor antagonist blocks interleukin 1-induced sleep and fever. Am J Physiol 260:R453–R457PubMedGoogle Scholar
  38. 38.
    Palin K, Bluthé RM, McCusker RH, Moos F, Dantzer R, Kelley KW (2007) TNF alpha-induced sickness behavior in mice with functional 55 kD TNF receptors is blocked by central IGF-I. J Neuroimmunol 187:55–60PubMedGoogle Scholar
  39. 39.
    Yirmiya R (1996) Endotoxin produces a depressive-like episode in rats. Brain Res 711:163–174PubMedGoogle Scholar
  40. 40.
    Dantzer R, Kelley KW (2007) Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun 21:153–160PubMedGoogle Scholar
  41. 41.
    O’Connor JC, André C, Wang Y, Lawson MA, Szegedi SS, Lestage J, Castanon N, Kelley KW, Dantzer R (2009) Interferon-γ and tumor necrosis factor-α mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to Bacillus Calmette-Guerin. J Neurosci 29:4200–4209PubMedGoogle Scholar
  42. 42.
    O’Connor JC, Lawson MA, André C, Briley EM, Szegedi SS, Lestage J, Castanon N, Herkenham M, Dantzer R, Kelley KW (2009) Induction of IDO by Bacilli Calmette-Guerin is responsible for development of murine depressive-like behavior. J Immunol 182:3202–3212PubMedGoogle Scholar
  43. 43.
    O’Connor JC, Lawson MA, André C, Moreau M, Lestage J, Castanon N, Kelley KW, Dantzer R (2009) Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry 14:511–522PubMedGoogle Scholar
  44. 44.
    Frenois F, Moreau M, O’Connor J, Lawson M, Micon C, Lestage J, Kelley KW, Dantzer R, Castanon N (2007) Lipopolysaccharide induces delayed Fos B/Delta Fos B immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior. Psychoneuroendocrinology 32:516–531PubMedGoogle Scholar
  45. 45.
    Henry CJ, Huang Y, Wynne A, Hanke M, Himler J, Bailey MT, Sheridan JF, Godbout JP (2008) Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. J Neuroinflammation 5:15PubMedGoogle Scholar
  46. 46.
    Kelley KW, Aubert A, Dantzer R (2011) Inflammation and behavior. In: Demas GE, Nelson RJ (eds) Eco-immunology and behavior. Oxford University Press, OxfordGoogle Scholar
  47. 47.
    Kelley KW, Dantzer R (2011) Alcoholism and inflammation: neuroimmunology of behavioral and mood disorders. Brain Behav Immun 25:S13–S20. doi: 10.1016/j.bbi.2010.12.013 PubMedGoogle Scholar
  48. 48.
    Bluthé RM, Walter V, Parnet P, Layé S, Lestage J, Verrier D, Poole S, Stenning BE, Kelley KW, Dantzer R (1994) Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. C R Acad Sci III 317:499–503PubMedGoogle Scholar
  49. 49.
    Watkins LR, Weirtelak EP, Goehler LE, Smith KP, Martin D, Maier SF (1994) Characterization of cytokine induced hyperalgesia. Brain Res 654:15–26PubMedGoogle Scholar
  50. 50.
    Watkins LR, Maier SF, Goehler LE (1995) Cytokine-to-brain communication: a review and analysis of alternative mechanisms. Life Sci 57:1011–1026PubMedGoogle Scholar
  51. 51.
    Wan W, Janz L, Vriend CY, Sorensen CM, Greenberg AH, Nance DM (1993) Differential induction of c-Fos immunoreactivity in hypothalamus and brain stem nuclei following central and peripheral administration of endotoxin. Brain Res Bull 32:581–587PubMedGoogle Scholar
  52. 52.
    Elmquist JK, Saper CB (1996) Activation of neurons projecting to the paraventricular hypothalamic nucleus by intravenous lipopolysaccharide. J Comp Neurol 374:315–331PubMedGoogle Scholar
  53. 53.
    Blatteis CM, Bealer SL, Hunter WS, Llanos-Q J, Ahokas RA, Mashburn TA Jr (1983) Suppression of fever after lesions of the anteroventral third ventricle in guinea pigs. Brain Res Bull 11:519–526PubMedGoogle Scholar
  54. 54.
    Quan N, Banks WA (2007) Brain-immune communications pathways. Brain Behav Immun 21:727–735PubMedGoogle Scholar
  55. 55.
    Banks WA, Kastin AK (1991) Blood to brain transport of interleukin links the immune and central nervous systems. Life Sci 48:PL117–PL121PubMedGoogle Scholar
  56. 56.
    Gutierrez EG, Banks WA, Kastin AJ (1993) Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J Neuroimmunol 47:169–176PubMedGoogle Scholar
  57. 57.
    Blatteis CM (2000) The afferent signalling of fever. J Physiol 526(Pt 3):470PubMedGoogle Scholar
  58. 58.
    Dantzer R (2004) Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity. Eur J Pharmacol 500:399–411PubMedGoogle Scholar
  59. 59.
    Konsman JP, Parnet P, Dantzer R (2002) Cytokine induced sickness behaviour: mechanisms and implications. Trends Neurosci 25:154–159PubMedGoogle Scholar
  60. 60.
    Tancredi V, D’Antuono M, Café C, Giovedì S, Bué MC, D’Arcangelo G, Onofri F, Benfenati F (2000) The inhibitory effects of interleukin-6 on synaptic plasticity in the rat hippocampus are associated with an inhibition of mitogen-activated protein kinase ERK. J Neurochem 75:634–643PubMedGoogle Scholar
  61. 61.
    Wang X, Wu H, Miller AH (2004) Interleukin 1a (IL-1a) induced activation of p38 mitogen-activated protein kinase inhibits glucocorticoid receptor function. Mol Psychiatry 9:65–75PubMedGoogle Scholar
  62. 62.
    Lynch MA (2004) Long-term potentiation and memory. Physiol Rev 84:87–136PubMedGoogle Scholar
  63. 63.
    Griffin R, Nally R, Nolan Y, McCartney Y, Linden J, Lynch MA (2006) The age-related attenuation in long-term potentiation is associated with microglial activation. J Neurochem 99(4):1263–1272PubMedGoogle Scholar
  64. 64.
    Gemma C, Bickford PC (2007) Interleukin-1beta and caspase-1: players in the regulation of age-related cognitive dysfunction. Rev Neurosci 18(2):137–148PubMedGoogle Scholar
  65. 65.
    Costello DA, Watson MB, Cowley TR, Murphy N, Murphy Royal C, Garlanda C, Lynch MA (2011) Interleukin-1alpha and HMGB1 mediate hippocampal dysfunction in SIGIRR-deficient mice. J Neurosci 31:3871–3879PubMedGoogle Scholar
  66. 66.
    Takeda K, Akira S (2005) Toll-like receptors in innate immunity. Int Immunol 17:1–14PubMedGoogle Scholar
  67. 67.
    Farrar WL, Kilian PL, Ruff MR, Hill JM, Pert CB (1987) Visualization and characterization of interleukin 1 receptors in brain. J Immunol 139:459–463PubMedGoogle Scholar
  68. 68.
    Ericsson A, Liu C, Hart RP, Sawchenko PE (1995) Type 1 interleukin-1 receptor in the rat brain: distribution, regulation, and relationship to sites of IL-1-induced cellular activation. J Comp Neurol 361:681–698PubMedGoogle Scholar
  69. 69.
    de Pablos RM, Villarán RF, Argüelles S, Herrera AJ, Venero JL, Ayala A, Cano J, Machado A (2006) Stress increases vulnerability to inflammation in the rat prefrontal cortex. J Neurosci 26:5709–5719PubMedGoogle Scholar
  70. 70.
    Dantzer R (2001) Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun 15:7–24PubMedGoogle Scholar
  71. 71.
    Besedovsky H, del Rey A, Sorkin E, Dinarello CA (1986) Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science 233:652–654PubMedGoogle Scholar
  72. 72.
    Berkenbosch F, van Oers J, del Rey A, Tilders F, Besedovsky H (1987) Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1. Science 238:524–526PubMedGoogle Scholar
  73. 73.
    Sapolsky R, Rivier C, Yamamoto G, Plotsky P, Vale W (1987) Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science 238:522PubMedGoogle Scholar
  74. 74.
    Dalton SO, Laursen TM, Ross L, Mortensen PB, Johansen C (2009) Risk for hospitalization with depression after a cancer diagnosis: a nationwide, population-based study of cancer patients in Denmark from 1973 to 2003. J Clin Oncol 27:1440–1445PubMedGoogle Scholar
  75. 75.
    Musselman DL, Lawson DH, Gumnick JF, Manatunga AK, Penna S, Goodkin RS, Greiner K, Nemeroff CB, Miller AH (2001) Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med 344:961–966PubMedGoogle Scholar
  76. 76.
    Schäfer A, Scheurlen M, Seufert J, Keicher C, Weiss brich B, Rieger P, Kraus MR (2010) Platelet serotonin (5-HT) levels in interferon-treated patients with hepatitis C and its possible association with interferon-induced depression. J Hepatol 52:10–15PubMedGoogle Scholar
  77. 77.
    Maes M, Lambrechts J, Bosmans E, Jacobs J, Suy E, Vandervorst C (1992) Evidence for a systemic immune activation during depression: results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining. Psychol Med 22:45–53PubMedGoogle Scholar
  78. 78.
    Capuron L (1999) Prediction of the depressive effects of interferon alfa therapy by the patient’s initial affective state. N Engl J Med 340:1370PubMedGoogle Scholar
  79. 79.
    Capuron L, Gumnick JF, Musselman DL, Lawson DH, Reemsnyder A, Nemeroff CB, Miller AH (2002) Neurobehavioral effects of interferon-α in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology 26:643–652PubMedGoogle Scholar
  80. 80.
    Prather AA, Rabinovitz M, Pollock BG, Lotrich FE (2009) Cytokine-induced depression during IFN-alpha treatment: the role of IL-6 and sleep quality. Brain Behav Immun 23:1109–1116PubMedGoogle Scholar
  81. 81.
    Capuron L, Pagnoni G, Demetrashvili M, Woolwine BJ, Nemeroff CB, Berns GS, Miller AH (2005) Anterior cingulate activation and error processing during interferon alpha treatment. Biol Psychiatry 58:190–196PubMedGoogle Scholar
  82. 82.
    Marks DH, Adineh M, Wang B, Gupta S (2007) Use of fMRI to predict psychiatric adverse effects of interferon treatment for Hepatitis C – preliminary report. Neuropsychiatr Dis Treat 3:655–667PubMedGoogle Scholar
  83. 83.
    Goldney RD, Fischer LJ, Phillips PJ, Wilson DH (2004) Diabetes, depression, and quality of life: a population study. Diabetes Care 17:1066–1070Google Scholar
  84. 84.
    Anderson RJ, Clouse RE, Freedland KE, Lustman PJ (2001) The prevalence of comorbid depression in adults with diabetes. Diabetes Care 24:1069–1078PubMedGoogle Scholar
  85. 85.
    Pickup JC, Chusney GD, Thomas SM, Burt D (2000) Plasma interleukin-6, tumour necrosis factor α and blood cytokine production in type 2 diabetes. Life Sci 67:291–300PubMedGoogle Scholar
  86. 86.
    Pasic J, Levy WC, Sullivan MD (2003) Cytokines in depression and heart failure. Psychosom Med 65:181–193PubMedGoogle Scholar
  87. 87.
    Alesci S, Martinez PE, Kelkar S, Ilias I, Ronsaville DS, Listwak SJ, Ayala AR, Licinio J, Gold HK, Kling MA, Chrousos GP, Gold PW (2005) Major depression is associated with significant diurnal elevations in plasma IL-6 levels, a shift of its circadian rhythm, and loss of physiologic complexity in its secretion: clinical implications. J Clin Endocrinol Metab 90:2522–2530PubMedGoogle Scholar
  88. 88.
    Frommberger UH, Bauer J, Haselbauer P, Fraulin A, Riemann D, Berger M (1997) Interleukin-6-(IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission. Eur Arch Psychiatry Clin Neurosci 247:228–233PubMedGoogle Scholar
  89. 89.
    Maes M, Lin A, Delmeire L, Van Gastel A, Kenis G, De Jongh R, Bosmons E (1999) Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events. Biol Psychiatry 45:833–839PubMedGoogle Scholar
  90. 90.
    Schlatter J, Ortuño F, Cervera-Enguix S (2004) Monocytic parameters in patients with dysthymia versus major depression. J Affect Disord 78:243–247PubMedGoogle Scholar
  91. 91.
    Zorrilla EP, Luborsky L, McKay JR, Rosenthal R, Houldin A, Tax A, McCorkle R, Seligman DA, Schmidt K (2001) The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun 15(3):199–226PubMedGoogle Scholar
  92. 92.
    Sluzewska A, Rybakowski JK, Laciak M, Mackiewicz A, Sobieska M, Wiktorowicv K (1995) Interleukin-6 serum levels in depressed patients before and after treatment with fluoxetine. Ann N Y Acad Sci 762:474–476PubMedGoogle Scholar
  93. 93.
    Basterzi AD, Aydemir C, Kisa C, Aksaray C, Tuzer V, Yazici K, Goka E (2005) IL-6 levels decrease with SSRI treatment in patients with major depression. Hum Psychopharmacol 20:473–476PubMedGoogle Scholar
  94. 94.
    O’Brien SM, Scott LV, Dinan TG (2006) Antidepressant therapy and C-reactive protein levels. Br J Psychiatry 188:449–452PubMedGoogle Scholar
  95. 95.
    O’Brien SM, Scully P, Fitzgerald P, Scott LV, Dinan TG (2007) Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatr Res 41:326–331PubMedGoogle Scholar
  96. 96.
    Hannestad J, DellaGioia N, Bloch M (2011) The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology 36:2452–2459. doi: 10.1038/npp.2011.132 PubMedGoogle Scholar
  97. 97.
    Penninx BWJH, Kritchevsky SB, Yaffe K, Newman AB, Simonsick EM, Rubin S, Ferrucci L, Harris T, Pahor M (2003) Inflammatory markers and depressed mood in older persons: results from the Health, Aging and Body Composition Study. Biol Psychiatry 54:566–572PubMedGoogle Scholar
  98. 98.
    Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD (2009) Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry 66:407–414PubMedGoogle Scholar
  99. 99.
    Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, Pollmächer T (2001) Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry 58:445–452PubMedGoogle Scholar
  100. 100.
    Strike PC, Wardle J, Steptoe A (2004) Mild acute inflammatory stimulation induces transient negative mood. J Psychosom Res 57:189–194PubMedGoogle Scholar
  101. 101.
    Wright CE, Strike PC, Brydon L, Steptoe A (2005) Acute inflammation and negative mood: mediation by cytokine activation. Brain Behav Immun 19:345–350PubMedGoogle Scholar
  102. 102.
    Stewart JC, Rand KL, Muldoon MF, Kamarck TW (2009) A prospective evaluation of the directionality of the depression-inflammation relationship. Brain Behav Immun 23:936–944PubMedGoogle Scholar
  103. 103.
    Copeland WE, Shanahan L, Worthman C, Angold A, Costello EJ (2012) Cumulative depression episodes predict later C-reactive protein levels: a prospective analysis. Biol Psychiatry 71:15–21PubMedGoogle Scholar
  104. 104.
    Loftis JM, Wall JM, Pagel RL, Hauser P (2006) Administration of pegylated interferon-α-2a or -2b does not induce sickness behavior in Lewis rats. Psychoneuroendocrinology 31:1289–1294PubMedGoogle Scholar
  105. 105.
    Hori T, Nakashima T, Take S, Kaizuka Y, Mori T, Katafuchi T (1991) Immune cytokines and regulation of body temperature, food intake and cellular immunity. Brain Res Bull 27:309–313PubMedGoogle Scholar
  106. 106.
    Thompson CM, Proctor DM, Suh M, Haws LC, Hebert CD, Mann JF, Shertzer HG, Hixon JG, Harris MA (2012) Comparison of the effects of hexavalent chromium in the alimentary canal of F344 and B6C3F1 mice following exposure in drinking water: implications for carcinogenic models of action. Toxicol Sci 125:79–90PubMedGoogle Scholar
  107. 107.
    Suzuki M, Fujii E, Kato C, Yamazaki M, Adachi K, Sugimoto T, Doi K (2008) Differences in bone responses to recombinant human granulocyte colony-stimulating factor between mice and rats. J Toxicol Sci 33:245–249PubMedGoogle Scholar
  108. 108.
    Sammut S, Goodall G, Muscat R (2001) Acute interferon-α administration modulates sucrose consumption in the rat. Psychoneuroendocrinology 26:261–272PubMedGoogle Scholar
  109. 109.
    Dunn AJ, Swiergel AH (2005) Effects of interleukin-1 and endotoxin in the forced swim and tail suspension tests in mice. Pharmacol Biochem Behav 81:688–693PubMedGoogle Scholar
  110. 110.
    Connor TJ, Song C, Leonard BE, Merali Z, Anisman H (1998) An assessment of the effects of central interleukin-1β, -2, -6, and tumor necrosis factor-α administration on some behavioural, neurochemical, endocrine and immune parameters in the rat. Neuroscience 84:923–933PubMedGoogle Scholar
  111. 111.
    Huang Y, Henry CJ, Dantzer R, Johnson RW, Godbout JP (2008) Exaggerated sickness behavior and brain proinflammatory cytokine expression in aged mice in response to intracerebroventricular lipopolysaccharide. Neurobiol Aging 29:1744–1753PubMedGoogle Scholar
  112. 112.
    Palin K, McCusker RH, Strle K, Moos F, Dantzer R, Kelley KW (2008) Tumor necrosis factor-α-induced sickness behavior is impaired by central administration of an inhibitor of c-jun N-terminal kinase. Psychopharmacology 197:629–635PubMedGoogle Scholar
  113. 113.
    Kent S, Bluthé RM, Kellet KW, Dantzer R (1992) Sickness behavior as a new target for drug development. Trends Pharmacol Sci 13:24–28PubMedGoogle Scholar
  114. 114.
    Kent S, Bluthé RM, Dantzer R, Hardwick AJ, Kelley KW, Rothwell NJ, Vannice JL (1992) Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin-1. Proc Natl Acad Sci USA 89:9117–9120PubMedGoogle Scholar
  115. 115.
    Kent S, Kelley KW, Dantzer R (1992) Effects of lipopolysaccharide on food-motivated behavior in the rat are not blocked by an interleukin-1 receptor antagonist. Neurosci Lett 145:83–86PubMedGoogle Scholar
  116. 116.
    Burgess W, Gheusi G, Yao J, Johnson RW, Dantzer R, Kelley KW (1998) Interleukin-1β-converting enzyme-deficient mice resist central but not systemic endotoxin-induced anorexia. Am J Physiol 274:R1829–R1833PubMedGoogle Scholar
  117. 117.
    Chourbaji S, Urani A, Inta I, Sanchis-Segura C, Brandwein C, Zink M, Schwaninger M, Gass P (2006) IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors. Neurobiol Dis 23:587–594PubMedGoogle Scholar
  118. 118.
    Swiergiel AH, Dunn AJ (2006) Feeding, exploratory, anxiety- and depression-related behaviors are not altered in interleukin-6-deficient male mice. Behav Brain Res 171(1):94–108PubMedGoogle Scholar
  119. 119.
    von Meyenburg B, Hrupka H, Arsenijevic D, Schwartz GJ, Landmann R, Langhans W (2004) Role for CD14, TLR2, and TLR4 in bacterial product-induced anorexia. Am J Physiol Regul Integr Comp Physiol 287:R298–R305Google Scholar
  120. 120.
    Palin K, Bluthe RM, McCusker RH, Levade T, Moos F, Dantzer R, Kelley KW (2009) The type 1 TNF receptor and its associated adapter protein, FAN, are required for TNF alpha-induced sickness behavior. Psychopharmacology 201:549–556PubMedGoogle Scholar
  121. 121.
    Mathew SJ, Charney DS (2009) Publication bias and the efficacy of antidepressants. Am J Psychiatry 166:140–145PubMedGoogle Scholar
  122. 122.
    Lacasse JR, Leo J (2005) Serotonin and depression: a disconnect between the advertisements and the scientific literature. PLoS Med 2:e392PubMedGoogle Scholar
  123. 123.
    Hindmarch I (2001) Expanding the horizons of depression: beyond the monoamine hypothesis. Hum Psychopharmacol 16:203–218PubMedGoogle Scholar
  124. 124.
    Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M (2003) Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 54:70–75PubMedGoogle Scholar
  125. 125.
    Hensler JG, Ladenheim EE, Lyons WE (2003) Ethanol consumption and serotonin-1A (5-HT1A) receptor function in heterozygous BDNF(+/−) mice. J Neurochem 85:1139–1147PubMedGoogle Scholar
  126. 126.
    Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, Kavalali ET, Monteggia LM (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 15:91–95Google Scholar
  127. 127.
    Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351–354PubMedGoogle Scholar
  128. 128.
    Maj J, Rogoz Z, Skuza G, Sowinska H (1992) Effects of MK-801 and antidepressant drugs in the forced swimming test in rats. Eur Neuropsychopharmacol 2:37–41PubMedGoogle Scholar
  129. 129.
    Salomon RM, Miller HL, Krystal JH, Heninger GR, Charney DS (1997) Lack of behavioral effects of monoamine depletion in healthy subjects. Biol Psychiatry 41:58–64PubMedGoogle Scholar
  130. 130.
    Heninger G, Delgado P, Charney D (1996) The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans. Pharmacopsychiatry 29:2–11PubMedGoogle Scholar
  131. 131.
    Delgado PL, Miller HL, Salomon RM, Licinio J, Krystal JH, Moreno FA, Heninger GR, Charney DS (1999) Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action. Biol Psychiatry 46:212–220PubMedGoogle Scholar
  132. 132.
    Berman RM, Sanacora G, Anand A, Roach LM, Fasula MK, Finkelstein CO, Wachen RM, Oren DA, Heninger GR, Charney DS (2002) Monoamine depletion in unmedicated depressed subjects. Biol Psychiatry 51:469–473PubMedGoogle Scholar
  133. 133.
    Nestler EJ (1998) Antidepressant treatments in the 21st Century. Biol Psychiatry 44:526–533PubMedGoogle Scholar
  134. 134.
    Den Boer JA, Bosker FJ, Slaap BR (2000) Serotonergic drugs in the treatment of depressive and anxiety disorders. Hum Psychopharmacol 15:315–336Google Scholar
  135. 135.
    Raison CL, Lin JMS, Reeves WC (2009) Association of peripheral inflammatory markers with chronic fatigue in a population-based sample. Brain Behav Immun 23:327–337PubMedGoogle Scholar
  136. 136.
    Bonaccorso S, Marino V, Biondi M, Grimaldi F, Ippoliti F, Maes M (2002) Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. J Affect Disord 72:237–241PubMedGoogle Scholar
  137. 137.
    Blackburn-Munro G, Blackburn-Munro RE (2001) Chronic pain, chronic stress and depression: coincidence or consequence? J Neuroendocrinol 13:1009–1023PubMedGoogle Scholar
  138. 138.
    Jarskog FL, Xiao H, Wilkie MB, Lauder JM, Gilmore JH (1997) Cytokine regulation of embryonic rat dopamine and serotonin neuronal survival in vitro. Int J Dev Neurosci 15:711–716PubMedGoogle Scholar
  139. 139.
    Zhu CB, Blakely RD, Hewlett WA (2006) The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Neuropsychopharmacology 31:2121–2131PubMedGoogle Scholar
  140. 140.
    Zalcman S, Green-Johnson JM, Murray L, Nance DM, Dyck D, Anismanc H, Greenberg AH (1994) Cytokine-specific central monoamine alterations induced by interleukin-1, -2 and -6. Brain Res 643:40–49PubMedGoogle Scholar
  141. 141.
    Pae CU, Marks DM, Han C, Patkar AA (2008) Does minocycline have antidepressant effect? Biomed Pharmacother 62:308–311PubMedGoogle Scholar
  142. 142.
    Fuchs D, Weiss G, Wachter H (1993) Neopterin, biochemistry and clinical use as a marker of cellular immune reaction. Int Arch Allergy Immunol 101:1–6PubMedGoogle Scholar
  143. 143.
    Maes M, Meltzer HY, Scharpe S, Bosmans E, Suy E, De Meester I, Calabrese J, Cosyns P (1993) Relationships between lower plasma L-tryptophan level and immune-inflammatory variables in depression. Psychiatry Res 49:151–165PubMedGoogle Scholar
  144. 144.
    Maes M, Meltzer HY, Bosmans E, Bergmans R, Vandoolaeghe E, Ranjan R, Desnyder R (1995) Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord 34:301–309PubMedGoogle Scholar
  145. 145.
    Häusler KG, Prinz M, Nolte C, Weber JR, Schumann RR, Kettenmann H, Hanisch UK (2002) Interferon-γ differentially modulates the release of cytokines and chemokines in lipopolysaccharide- and pneumococcal cell wall-stimulated mouse microglia and macrophages. Eur J Neurosci 16:2113–2122PubMedGoogle Scholar
  146. 146.
    Arkins S, Rebeiz N, Brunke-Reese DL, Biragyn A, Kelley KW (1995) Interferon-gamma inhibits macrophage insulin-like growth factor-I synthesis at the transcriptional level. Mol Endocrinol 9:350–360PubMedGoogle Scholar
  147. 147.
    Dunn AJ (2000) Cytokine activation of the HPA axis. Ann N Y Acad Sci 917:608–617PubMedGoogle Scholar
  148. 148.
    Silverman MN, Miller AH, Biron CA, Pearce BD (2004) Characterization of an interleukin-6 and adrenocorticotropin-dependent, immune-to-adrenal pathway during viral infection. Endocrinology 145:3580–3589PubMedGoogle Scholar
  149. 149.
    Sullivan GM, Canfield SM, Lederman S, Xiao E, Ferin M, Wardlaw SL (1997) Intracerebroventricular injection of interleukin-1 suppresses peripheral lymphocyte function in the primate. Neuroimmunomodulation 4:12–18PubMedGoogle Scholar
  150. 150.
    Watanabe T, Morimoto A, Murakami N (1991) ACTH response in rats during biphasic fever induced by interleukin-1. Am J Physiol 261:R11014–R11108Google Scholar
  151. 151.
    Krishnan V, Nestler EJ (2010) Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry 167:1305–1320PubMedGoogle Scholar
  152. 152.
    Chesnokova V, Melmed S (2002) Minireview: neuro-immuno-endocrine modulation of the hypothalamic-pituitary-adrenal (HPA) axis by gp130 signaling molecules. Endocrinology 143:1571–1574PubMedGoogle Scholar
  153. 153.
    Guan Z, Fang J (2006) Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats. Brain Behav Immun 20:64–71PubMedGoogle Scholar
  154. 154.
    Kelley KW, Weigent DA, Kooijman R (2007) Protein hormones and immunity. Brain Behav Immun 21:384–392PubMedGoogle Scholar
  155. 155.
    Park SE, Lawson M, Dantzer R, Kelley KW, McCusker RH (2011) Insulin-like growth factor-I peptides act centrally to decrease depression-like behavior of mice treated intraperitoneally with lipopolysaccharide. J Neuroinflammation 21:179Google Scholar
  156. 156.
    Park SE, Dantzer R, Kelley KW, McCusker RH (2011) Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice. J Neuroinflammation 9:8–12Google Scholar
  157. 157.
    Kaneko N, Kudo K, Mabuchi T, Takemoto K, Fujimaki K, Wati H, Iguchi H, Tezuka H, Kanba S (2006) Suppression of cell proliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus. Neuropsychopharmacology 31:2619–2626PubMedGoogle Scholar
  158. 158.
    Monje ML, Toda H, Palmer TD (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302:1760–1765PubMedGoogle Scholar
  159. 159.
    Vallières L, Campbell IL, Gage FH, Sawchenko PE (2002) Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci 22:486–492PubMedGoogle Scholar
  160. 160.
    Seguin JA, Brennan J, Mangano E, Hayley S (2009) Proinflammatory cytokines differentially influence adult hippocampal cell proliferation depending upon the route and chronicity of administration. Neuropsychiatr Dis Treat 5:5–14PubMedGoogle Scholar
  161. 161.
    Tolosa L, Caraballo-Miralles V, Olmos G, Llado J (2011) TNF-α potentiates glutamate-induced spinal cord motoneuron death via NF-ΚB. Mol Cell Neurosci 46:176–186PubMedGoogle Scholar
  162. 162.
    Villani GR, Gargiulo N, Faraonio R, Castaldo S, Gonzalez Y, Reyero E, Di Natale P (2007) Cytokines, neurotrophins, and oxidative stress in brain disease from mucopolysaccharidosis IIIB. J Neurosci Res 85:612–622PubMedGoogle Scholar
  163. 163.
    Zhu W, Zheng H, Shao X, Wang W, Yao Q, Li Z (2010) Excitotoxicity of TNF alpha derived from KA activated microglia on hippocampal neurons in vitro and in vivo. J Neurochem 23:386–396Google Scholar
  164. 164.
    Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71:171–186PubMedGoogle Scholar
  165. 165.
    Liukkonen T, Silvennoinen-Kassinen S, Jokelainen J, Räsänend P, Leinoneng M, Meyer-Rochowe VB, Timonen M (2006) The association between C-reactive protein levels and depression: results from the Northern Finland 1966 birth cohort study. Biol Psychiatry 60:825–830PubMedGoogle Scholar
  166. 166.
    Heinrich PC, Castell JV, Andus T (1990) Interleukin-6 and the acute phase response. Biochem J 265:621–636PubMedGoogle Scholar
  167. 167.
    Anisman H, Merali Z, Poulter MO, Hayley S (2005) Cytokines as a precipitant of depressive illness: animal and human studies. Curr Pharm Des 11:963–972PubMedGoogle Scholar
  168. 168.
    Pace TWW, Mletzko TC, Alagbe O, Musselman DL, Nemeroff CB, Miller AH, Heim CM (2006) Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. Am J Psychiatry 163:1630–1633PubMedGoogle Scholar
  169. 169.
    Goshen I, Yirmiya R, Iverfeldt K, Weidenfeld J (2003) The role of endogenous interleukin-1 in stress-induced adrenal activation and adrenalectomy induced adrenocorticotropic hormone hypersecretion. Endocrinology 144:4453–4458PubMedGoogle Scholar
  170. 170.
    Goshen I, Yirmiya R (2007) The role of pro-inflammatory cytokines in memory processes and neural plasticity. In: Ader R (ed) Psychoneuroimmunology, 4th edn. Academic, Amsterdam, pp 337–377Google Scholar
  171. 171.
    Kendler KS, Karkowski LM, Prescott CA (1999) Causal relationships between stressful life events and the onset of major depression. Am J Psychiatry 156:837–841PubMedGoogle Scholar
  172. 172.
    Luby JL, Heffelfinger A, Mrakotsky C, Brown K, Hessler M, Spitznagel E (2003) Alterations in stress cortisol reactivity in depressed preschoolers relative to psychiatric and no-disorder comparison groups. Arch Gen Psychiatry 60:1248–1255PubMedGoogle Scholar
  173. 173.
    Tennes K, Downey K, Vernadakis A (1977) Urinary cortisol excretion rates and anxiety in normal one year old infants. Psychosom Med 39:178–187PubMedGoogle Scholar
  174. 174.
    Guerry JD, Hastings PD (2011) In search of HPA axis dysregulation in child and adolescent depression. Clin Child Fam Psychol Rev 14:135–160PubMedGoogle Scholar
  175. 175.
    Bhagwagar Z, Hafizi S, Cowen PJ (2003) Increase in concentration of waking salivary cortisol in recovered patients with depression. Am J Psychiatry 160:1890–1891PubMedGoogle Scholar
  176. 176.
    Pariante CM, Lightman SL (2008) The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31:464–468PubMedGoogle Scholar
  177. 177.
    Koolschijn PCMP, van Haren NEM, Lensvelt-Mulders GJLM, Hulshoff Pol HE, Kahn RS (2009) Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp 30:3719–3735PubMedGoogle Scholar
  178. 178.
    den Heijer T, Tiemeier H, Luijendijk HJ, van der Lijn F, Koudstaal PJ, Hofman A, Breteler MMB (2011) A study of the bidirectional association between hippocampal volume on magnetic resonance imaging and depression in the elderly. Biol Psychiatry 70:191–197Google Scholar
  179. 179.
    Heim C, Nemeroff CB (1999) The impact of early adverse experiences on brain systems involved in the pathophysiology of anxiety and affective disorders. Biol Psychiatry 46:1509–1522PubMedGoogle Scholar
  180. 180.
    Humphreys D, Schlesinger L, Lopez M, Araya AV (2006) Interleukin-6 production and deregulation of the hypothalamic-pituitary-adrenal axis in patients with major depressive disorders. Endocrine 30:371–376PubMedGoogle Scholar
  181. 181.
    Webster JC, Oakley RH, Jewell CM, Cidlowski JA (2001) Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative β isoform: a mechanism for the generation of glucocorticoid resistance. Proc Natl Acad Sci USA 98:6865–6870PubMedGoogle Scholar
  182. 182.
    Fitzgerald P, O’Brien SM, Scully P, Rijkers K, Scott LV, Dinan TG (2006) Cutaneous glucocorticoid receptor sensitivity and pro-inflammatory cytokine levels in antidepressant-resistant depression. Psychol Med 36:37–43PubMedGoogle Scholar
  183. 183.
    Jehn CF, Kuehnhardt D, Bartholomae A, Pfeiffer S, Krebs M, Regierer AC, Schmid P, Possinger K, Rath BC (2006) Biomarkers of depression in cancer patients. Cancer 107:2723–2729PubMedGoogle Scholar
  184. 184.
    Shanks N, Larocque S, Meaney MJ (1995) Neonatal endotoxin exposure alters the development of the hypothalamic-pituitary-adrenal axis: early illness and later responsivity to stress. J Neurosci 15:376–384PubMedGoogle Scholar
  185. 185.
    Walker AK, Nakamura T, Byrne R, Naicker S, Tynan RJ, Hodgson DM (2009) Neonatal lipopolysaccharide and adult stress exposure predisposes rats to anxiety-like behavior and blunted corticosterone responses: implications for the double-hit hypothesis. Psychoneuroendocrinology 34:1515–1525PubMedGoogle Scholar
  186. 186.
    Walker AK, Nakamura T, Hodgson DM (2010) Neonatal lipopolysaccharide exposure alters central cytokine responses to stress in adulthood in Wistar rats. Stress 13(6):506–515PubMedGoogle Scholar
  187. 187.
    Hajszan T, Dow A, Warner-Schmidt JL, Szigeti-Buck K, Sallam NL, Parducz A, Leranth A, Duman RS (2009) Remodeling of hippocampal spine synapses in the rat learned helplessness model of depression. Biol Psychiatry 65:392–400PubMedGoogle Scholar
  188. 188.
    Pittenger C, Duman RS (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33:88–109PubMedGoogle Scholar
  189. 189.
    Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110PubMedGoogle Scholar
  190. 190.
    Frodl T, Jäger M, Smajstrlova I, Born C, Bottlender R, Palladino T, Reiser M, Möller HJ, Meisenzahl EM (2008) Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study. J Psychiatry Neurosci 33:423–430PubMedGoogle Scholar
  191. 191.
    Jehn CF, Kühnhardt D, Bartholomae A, Pfeiffer S, Schmid P, Possibger K, Flath BC, Lüftner D (2010) Association of IL-6, hypothalamus–pituitary–adrenal axis function, and depression in patients with cancer. Integr Cancer Ther 9:270–275PubMedGoogle Scholar
  192. 192.
    Pace T, Hu F, Miller AH (2007) Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun 21:9–19PubMedGoogle Scholar
  193. 193.
    Pace TW, Miller AH (2009) Cytokines and glucocorticoid receptor signaling. Relevance to major depression. Ann N Y Acad Sci 1179:86–105PubMedGoogle Scholar
  194. 194.
    Hu F, Wang X, Pace TWW, Wu H, Miller AH (2005) Inhibition of COX-2 by celecoxib enhances glucocorticoid receptor function. Mol Psychiatry 10:426–433PubMedGoogle Scholar
  195. 195.
    Klinesmith J, Kasser T, McAndrew FT (2006) Guns, testosterone, and aggression: an experimental test of a mediational hypothesis. Psychol Sci 17:568PubMedGoogle Scholar
  196. 196.
    Newman ML, Josephs RA (2009) Testosterone as a personality variable. J Res Pers 43:258–259Google Scholar
  197. 197.
    Schweiger U, Deuschle M, Weber B, Korner A, Lammers CH, Schmeider J, Gotthardt U, Heuser I (1999) Testosterone, gonadotropin, and cortisol secretion in male patients with major depression. Psychosom Med 61:292–296PubMedGoogle Scholar
  198. 198.
    Perry PJ, Yates WR, Williams RD, Anderson AE, MacIndoe JH, Lund BC, Holman TL (2002) Testosterone therapy in late-life major depression in males. J Clin Psychiatry 63:1096–1101PubMedGoogle Scholar
  199. 199.
    Yoo MJ, Nishihara M, Takahashi M (1997) Tumor necrosis factor a mediates endotoxin induced suppression of gonadotropin-releasing hormone pulse generator activity in the rat. Endocr J 44:141–148PubMedGoogle Scholar
  200. 200.
    Ebisui O, Fukata J, Tominaga T, Murakami N, Kobayashi H, Segawa H, Muro S, Naito Y, Nakai Y, Maui Y, Nishida T, Imura H (1992) Roles of interleukin-1a and 21b in endotoxin-induced suppression of plasma gonadotropin levels in rats. Endocrinology 130:3307–3313PubMedGoogle Scholar
  201. 201.
    Rivest S, Rivier C (1993) Interleukin-1b inhibits the endogenous expression of the early gene c-fos located within the nucleus of LH-RH neurons and interferes with hypothalamic LH-RH release during proestrus in the rat. Brain Res 613:132–142PubMedGoogle Scholar
  202. 202.
    Avitsur R, Cohen E, Yirmiya R (1998) Effects of interleukin-1 on sexual attractivity in a model of sickness behavior. Physiol Behav 63:25–30Google Scholar
  203. 203.
    Avitsur R, Yirmiya R (1999) Cytokines inhibit sexual behavior in female rats: I. Synergistic effects of tumor necrosis factor α and interleukin-1. Brain Behav Immun 13:14–32PubMedGoogle Scholar
  204. 204.
    Avitsur R, Wiedenfeld J, Yirmiya R (1999) Cytokines inhibit sexual behavior in female rats: II. Prostaglandins mediate the suppressive effects of interleukin-1β. Brain Behav Immun 13:33–45PubMedGoogle Scholar
  205. 205.
    Imura H, Fukata JI, Mori T (1991) Cytokines and endocrine function: an interaction between the immune and neuroendocrine systems. Clin Endocrinol 35:107–115Google Scholar
  206. 206.
    Li XF, Bowe JE, Lightman SL, O’Byrne KT (2005) Role of corticotropin-releasing factor receptor-2 in stress-induced suppression of pulsatile luteinizing hormone secretion in the rat. Endocrinology 146:318–322PubMedGoogle Scholar
  207. 207.
    Matsuwaki T, Suzuki M, Yamanouchi K, Nishihara M (2004) Glucocorticoid counteracts the suppressive effect of tumor necrosis factor-alpha on the surge of luteinizing hormone secretion in rats. J Endocrinol 181:509–513PubMedGoogle Scholar
  208. 208.
    Li XF, Kinsey-Jones JS, Knox AM, Wu XQ, Tahsinsoy D, Brain SD, Lightman SL, O’Byrne KT (2007) Neonatal lipopolysaccharide exposure exacerbates stress-induced suppression of luteinizing hormone pulse frequency in adulthood. Endocrinology 148:5984–5990PubMedGoogle Scholar
  209. 209.
    Knox AM, Li XF, Kinsey-Jones JS, Wilkinson ES, Wu XQ, Cheng YS, Milligan SR, Lightman SL, O’Byrne KT (2009) Neonatal lipopolysaccharide exposure delays puberty and alters hypothalamic Kiss1 and Kiss1r mRNA expression in the female rat. J Neuroendocrinol 21:683–689PubMedGoogle Scholar
  210. 210.
    Walker AK, Hiles SA, Sominsky L, Mclaughlin EA, Hodgson DM (2011) Neonatal lipopolysaccharide exposure impairs sexual development and reproductive success in the Wistar rat. Brain Behav Immun 25:674–684PubMedGoogle Scholar
  211. 211.
    Weissman MN, Bland R, Joyce PR, Newman S, Wells JE, Wittchen HU (1993) Sex differences in rates of depression: cross-national perspectives. J Affect Disord 29:77–84PubMedGoogle Scholar
  212. 212.
    Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 51:8–19PubMedGoogle Scholar
  213. 213.
    Cowen PJ, Parry-Billings M, Newsholme EA (1989) Decreased plasma tryptophan levels in major depression. J Affect Disord 16:27–31PubMedGoogle Scholar
  214. 214.
    Maes M, Minner B, Suy E (1991) The relationships between the availability of l-tryptophan to the brain, the spontaneous HPA-axis activity, and the HPA-axis responses to dexamethasone in depressed patients. J Amino Acids 1:57–65Google Scholar
  215. 215.
    Maes M, Schotte C, D’Hondt P, Claes M, Vandewoude M, Scharpe S, Cosyns P (1991) Biological heterogeneity of melancholia: results of pattern recognition methods. J Psychiatr Res 25:95–108PubMedGoogle Scholar
  216. 216.
    Quintana J (1992) Platelet serotonin and plasma tryptophan decreases in endogenous depression. Clinical, therapeutic, and biological correlations. J Affect Disord 24:55–62PubMedGoogle Scholar
  217. 217.
    Song C, Lin A, Bonaccorse S, Heide C, Verkerk R, Kenis G, Bosmans E, Scharpé S, Whelan A, Cosyns P, de Jongh R, Maes M (1998) The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression. J Affect Disord 49:211–219PubMedGoogle Scholar
  218. 218.
    Guilleman GJ, Smythe G, Takikawa O, Brew BJ (2005) Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes and neurons. Glia 49:15–23Google Scholar
  219. 219.
    Kwidzinski E, Bechmann I (2007) IDO expression in the brain: a double-edged sword. J Mol Med 85:1351–1359PubMedGoogle Scholar
  220. 220.
    Heyes MP, Achim CL, Wiley CA, Major EO, Saito K, Markey SP (1996) Human microglia convert l-tryptophan into the neurotoxin quinolinic acid. Biochem J 320:595–597PubMedGoogle Scholar
  221. 221.
    Myint AM, Kim YK, Verkerk R, Scharpé S, Syeinbusch H, Leonard B (2007) Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord 98:143–151PubMedGoogle Scholar
  222. 222.
    Myint AM, Schwarz MJ, Verkerk R, Mueller HH, Zach J, Scharpé S, Steinbusch HWM, Leonard BE, Kim YK (2011) Reversal of imbalance between kynurenic acid and 3-hydroxykynurenine by antipsychotics in medication-naïve and medication-free schizophrenic patients. Brain Behav Immun 25:1576–1581. doi: 10.1016/j.bbi.2011.05.005 PubMedGoogle Scholar
  223. 223.
    Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C, Mellor AL (1998) Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281:1191–1193PubMedGoogle Scholar
  224. 224.
    Mellor AL, Munn DH (2000) Immunology at the maternal–fetal interface: lessons for T cell tolerance and suppression. Annu Rev Immunol 18:367–391PubMedGoogle Scholar
  225. 225.
    Mellor AL, Sivakumar J, Chandler P, Smith K, Molina H, Mao D, Munn DH (2001) Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol 2:64–68PubMedGoogle Scholar
  226. 226.
    Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, Miller AH (2003) Interferon-alpha-induced changes in tryptophan metabolism: relationship to depression and paroxetine treatment. Biol Psychiatry 54:906–914PubMedGoogle Scholar
  227. 227.
    Capuron L, Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R (2002) Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry 7:468–473PubMedGoogle Scholar
  228. 228.
    Wichers MC, Koek GH, Robays G, Verkerk R, Scharpé S, Maes M (2005) IDO and interferon-α-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. Mol Psychiatry 10:538–544PubMedGoogle Scholar
  229. 229.
    Raison CL, Dantzer R, Kelley KW, Lawson MA, Wool Wine BJ, Vogt G, Spivey JR, Saito K, Miller AH (2010) CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-α: relationship to CNS immune responses and depression. Mol Psychiatry 15:393–403PubMedGoogle Scholar
  230. 230.
    Sublette ME, Galfalvy HC, Fuchs D, Lapidus M, Grunebaum MF, Oquendo MA, Mann JJ, Postolache TT (2011) Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder. Brain Behav Immun 25:1272–1278PubMedGoogle Scholar
  231. 231.
    Moreau M, Lestage J, Verrier D, Mormede C, Kelley KW, Dantzer R, Castanon N (2005) Bacille calmette-guerin inoculation induces chronic activation of peripheral and brain indoleamine 2,3-dioxygenase in mice. J Infect Dis 192:537–544PubMedGoogle Scholar
  232. 232.
    Godbout JP, Moreau M, Lestage J, Chen J, Sparkman NL, O’Connor J, Castanon N, Kelley KW, Dantzer R, Johnson RW (2008) Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system. Neuropsychopharmacology 33:2341–2351PubMedGoogle Scholar
  233. 233.
    Yadav MC, Burudi EM, Alirezaei M, Flynn CC, Watry DD, Lanigan CM, Fox HS (2007) IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4. Glia 55:1385–1396PubMedGoogle Scholar
  234. 234.
    Müller N, Schwarz MJ (2007) The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression. Mol Psychiatry 12:988–1000PubMedGoogle Scholar
  235. 235.
    Funakoshi H, Kanai M, Nakamura T (2011) Modulation of tryptophan metabolism, promotion of neurogenesis and alteration of anxiety-related behavior in tryptophan 2,3-dioxygenase-deficient mice. Int J Tryptophan Res 4:7–18Google Scholar
  236. 236.
    Metz R, Du Hadaway JB, Kamasani U, Laury-Kleintop L, Muller AJ, Prendergast JC (2007) Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res 67:7082–7087PubMedGoogle Scholar
  237. 237.
    Branchey L, Lieber CS (1982) Activation of tryptophan pyrrolase after chronic alcohol administration. Subst Alcohol Actions Misuse 3:225–229PubMedGoogle Scholar
  238. 238.
    Badawy AA-B, Dougherty DM, Marsh-Richard DM, Steptoe A (2009) Activation of liver tryptophan pyrrolase mediates the decrease in tryptophan availability to the brain after acute alcohol consumption in normal subjects. Alcohol Alcohol 44:267–271PubMedGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Adam K. Walker
    • 1
  • Robert Dantzer
    • 1
    • 2
  • Keith W. Kelley
    • 1
    • 2
  1. 1.Integrative Immunology and Behavior Program, Department of Animal SciencesUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Department of Medical PathologyUniversity of Illinois at Urbana-ChampaignUrbanaUSA

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