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Stress
The International Journal on the Biology of Stress
Volume 11, 2008 - Issue 3
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Original

A link between stress and depression: Shifts in the balance between the kynurenine and serotonin pathways of tryptophan metabolism and the etiology and pathophysiology of depression

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Pages 198-209 | Received 26 May 2007, Accepted 16 Oct 2007, Published online: 07 Jul 2009

References

  • 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
  • Banks WA, Kastin AJ, Broadwell RD. Passage of cytokines across the blood–brain barrier. Neuroimmunomodulation 1995; 2: 241–248
  • Bhagwagar Z, Hafizi S, Cowen PJ. Cortisol modulation of 5-HT-mediated growth hormone release in recovered depressed patients. J Affect Disord 2002; 72: 249–255
  • Black PH. Immune system–central nervous system interactions: Effect and immunomodulatory consequences of immune system mediators on the brain. Antimicrob Agents Chemother 1994; 38: 7–12
  • Bonaccorso S, Meltzer H, Maes M. Psychological and behavioural effects of interferons. Curr Opin Psychiatry 2000; 13: 673–677
  • Bonaccorso S, Marino V, Puzella A, Pasquini M, Biondi M, Artini M, Almerighi C, Verkerk R, Meltzer H, Maes M. Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system. J Clin Psychopharmacol 2002; 22: 86–90
  • Broderick PA. Interleukin 1alpha alters hippocampal serotonin and norepinephrine release during open-field behavior in Sprague–Dawley animals: Differences from the Fawn-Hooded animal model of depression. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 1355–1372
  • Capuron L, Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R. Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry 2002; 7: 468–473
  • Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, Miller AH. Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment. Biol Psychiatry 2003; 54: 906–914
  • Castanon N, Leonard BE, Neveu PJ, Yirmiya R. Effects of antidepressants on cytokine production and actions. Brain Behav Immun 2002; 16: 569–574
  • Chaouloff F. Effects of acute physical exercise on central serotonergic systems. Med Sci Sports Exerc 1997; 29: 58–62
  • Cowen PJ, Charig EM. Neuroendocrine responses to intravenous tryptophan in major depression. Arch Gen Psychiatry 1987; 44: 958–966
  • Curzon G, Joseph MH, Knott PJ. Effects of immobilization and food deprivation on rat brain tryptophan metabolism. J Neurochem 1972; 19: 1967–1974
  • Curzon G, Friedel J, Knott PJ. The effect of fatty acids on the binding of tryptophan to plasma protein. Nature 1973; 242: 198–200
  • Dantzer R, Wollman E, Vitkovic L, Yirmiya R. Cytokines and depression: Fortuitous or causative association?. Mol Psychiatry 1999; 4: 328–332
  • De La Garza R, II, Anis GM. The non-steroidal anti-inflammatory drug diclofenac sodium attenuates IFN-alpha induced alterations to monoamine turnover in prefrontal cortex and hippocampus. Brain Res 2003; 977: 70–79
  • De La Garza R, II, Asnis GM, Pedrosa E, Stearns C, Migdal AL, Reinus JF, Paladugu R, Vemulapalli S. Recombinant human interferon-alpha does not alter reward behavior, or neuroimmune and neuroendocrine activation in rats. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 781–792
  • Delgado PL. How antidepressants help depression: Mechanisms of action and clinical response. J Clin Psychiatry 2004; 65(Suppl 4)25–30
  • Dunn AJ. Systemic interleukin-1 administration stimulates hypothalamic norepinephrine metabolism parallelling the increased plasma corticosterone. Life Sci 1988a; 43: 429–435
  • Dunn AJ. Stress-related changes in cerebral catecholamine and indoleamine metabolism: Lack of effect of adrenalectomy and corticosterone. J Neurochem 1988b; 51: 406–412
  • Dunn AJ, Welch J. Stress- and endotoxin-induced increases in brain tryptophan and serotonin metabolism depend on sympathetic nervous system activity. J Neurochem 1991; 57: 1615–1622
  • Fernstrom JD, Wurtman RJ. Brain serotonin content: Physiological regulation by plasma neutral amino acids. Science 1972; 178: 414–416
  • Frank MG, Baratta MV, Sprunger DB, Watkins LR, Maier SF. Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses. Brain Behav Immun 2007; 21: 47–59
  • Guillemin GJ, Smythe G, Takikawa O, Brew BJ. Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons. Glia 2004; 49: 15–23
  • Haack M, Hinze-Selch D, Fenzel T, Kraus T, Kuhn M, Schuld A, Pollmacher T. Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: Effects of confounding factors and diagnosis. J Psychiatr Res 1999; 33: 407–418
  • Hayaishi O, Rothberg S, Mehler AH, Saito Y. Studies on oxygenases; enzymatic formation of kynurenine from tryptophan. J Biol Chem 1957; 229: 889–896
  • Heyes MP, Mefford IN, Quearry BJ, Dedhia M, Lackner A. Increased ratio of quinolinic acid to kynurenic acid in cerebrospinal fluid of D retrovirus-infected rhesus macaques: Relationship to clinical and viral status. Ann Neurol 1990; 27: 666–675
  • Heyes MP, Achim CL, Wiley CA, Major EO, Saito K, Markey SP. Human microglia convert l-tryptophan into the neurotoxin quinolinic acid. Biochem J 1996; 320(Pt 2)595–597
  • Hirata F, Hayaishi O, Tokuyama T, Senoh S. In vitro and in vivo formation of two new metabolites of melatonin. J Biol Chem 1974; 249: 1311–1313
  • Hirota T, Hirota K, Sanno Y, Tanaka T. A new glucocorticoid receptor species: Relation to induction of tryptophan dioxygenase by glucocorticoids. Endocrinology 1985; 117: 1788–1795
  • Hoes MJ, Sijben N. The clinical significance of disordered renal excretion of xanthurenic acid in depressive patients. Psychopharmacology (Berl) 1981; 75: 346–349
  • Ichiyama A, Nakamura S, Nishizuka Y, Hayaishi O. Enzymic studies on the biosynthesis of serotonin in mammalian brain. J Biol Chem 1970; 245: 1699–1709
  • Johnson JD, O'Connor KA, Deak T, Stark M, Watkins LR, Maier SF. Prior stressor exposure sensitizes LPS-induced cytokine production. Brain Behav Immun 2002; 16: 461–476
  • Kabiersch A, del Rey A, Honegger CG, Besedovsky HO. Interleukin-1 induces changes in norepinephrine metabolism in the rat brain. Brain Behav Immun 1988; 2: 267–274
  • Kendler KS, Kessler RC, Neale MC, Heath AC, Eaves LJ. The prediction of major depression in women: Toward an integrated etiologic model. Am J Psychiatry 1993; 150: 1139–1148
  • Kohl C, Walch T, Huber R, Kemmler G, Neurauter G, Fuchs D, Solder E, Schrocksnadel H, Sperner-Unterweger B. Measurement of tryptophan, kynurenine and neopterin in women with and without postpartum blues. J Affect Disord 2005; 86: 135–142
  • Konsman JP, Parnet P, Dantzer R. Cytokine-induced sickness behaviour: Mechanisms and implications. Trends Neurosci 2002; 25: 154–159
  • Kubera M, Kenis G, Bosmans E, Scharpe S, Maes M. Effects of serotonin and serotonergic agonists and antagonists on the production of interferon-gamma and interleukin-10. Neuropsychopharmacology 2000; 23: 89–98
  • LeMay LG, Vander AJ, Kluger MJ. The effects of psychological stress on plasma interleukin-6 activity in rats. Physiol Behav 1990; 47: 957–961
  • Leipnitz G, Schumacher C, Scussiato K, Dalcin KB, Wannmacher CM, Wyse AT, Dutra-Filho CS, Wajner M, Latini A. Quinolinic acid reduces the antioxidant defenses in cerebral cortex of young rats. Int J Dev Neurosci 2005; 23: 695–701
  • Leonard BE. Changes in the immune system in depression and dementia: Causal or co-incidental effects?. Int J Dev Neurosci. 2001; 19: 305–312
  • Leonard BE. The HPA and immune axes in stress: The involvement of the serotonergic system. Eur Psychiatry 2005; 20(Suppl 3)S302–S306
  • Maes M, De Ruyter M, Hobin P, Suy E. Relationship between the dexamethasone suppression test and the l-tryptophan/competing amino acids ratio in depression. Psychiatry Res 1987; 21: 323–335
  • Maes M, Jacobs MP, Suy E, Minner B, Leclercq C, Christiaens F, Raus J. Suppressant effects of dexamethasone on the availability of plasma l-tryptophan and tyrosine in healthy controls and in depressed patients. Acta Psychiatr Scand 1990a; 81: 19–23
  • Maes M, Schotte C, Scharpe S, Martin M, Blockx P. The effects of glucocorticoids on the availability of l-tryptophan and tyrosine in the plasma of depressed patients. J Affect Disord 1990b; 18: 121–127
  • Maes M, Vandewoude M, Schotte C, Maes L, Martin M, Scharpe S, Blockx P. The relationships between the cortisol responses to dexamethasone and to l-5-HTP, and the availability of l-tryptophan in depressed females. Biol Psychiatry 1990c; 27: 601–608
  • Maes M, Meltzer HY, Scharpe S, Bosmans E, Suy E, De Meester I, Calabrese J, Cosyns P. Relationships between lower plasma l-tryptophan levels and immune-inflammatory variables in depression. Psychiatry Res 1993; 49: 151–165
  • Maes M, Smith R, Scharpe S. The monocyte-T-lymphocyte hypothesis of major depression. Psychoneuroendocrinology 1995; 20: 111–116
  • Maes M, Wauters A, Verkerk R, Demedts P, Neels H, Van Gastel A, Cosyns P, Scharpe S, Desnyder R. Lower serum l-tryptophan availability in depression as a marker of a more generalized disorder in protein metabolism. Neuropsychopharmacology 1996; 15: 243–251
  • Maes M, Song C, Lin A, De Jongh R, Van Gastel A, Kenis G, Bosmans E, De Meester I, Benoy I, Neels H, Demedts P, Janca A, Scharpe S, Smith RS. The effects of psychological stress on humans: Increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine 1998; 10: 313–318
  • Maes M. The immunoregulatory effects of antidepressants. Hum Psychopharmacol 2001; 16: 95–103
  • Maes M, Verkerk R, Bonaccorso S, Ombelet W, Bosmans E, Scharpe S. Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation. Life Sci 2002; 71: 1837–1848
  • Maier SF. Bi-directional immune–brain communication: Implications for understanding stress, pain, and cognition. Brain Behav Immun 2003; 17: 69–85
  • McEwen BS. Protection and damage from acute and chronic stress: Allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Ann NY Acad Sci 2004; 1032: 1–7
  • McMenamy RH. Binding of indole analogues to human serum albumin. Effects of fatty acids. J Biol Chem 1965; 240: 4235–4243
  • Minami M, Kuraishi Y, Yamaguchi T, Nakai S, Hirai Y, Satoh M. Immobilization stress induces interleukin-1 beta mRNA in the rat hypothalamus. Neurosci Lett 1991; 123: 254–256
  • Miura H, Ozaki N, Shirokawa T, Isobe K. Changes in brain tryptophan metabolism elicited by age, social environment, and psychological stress in mice. Stress 2007, in press
  • Moffett JR, Namboodiri MA. Tryptophan and the immune response. Immunol Cell Biol 2003; 81: 247–265
  • Mössner R, Heils A, Stöber G, Okladnova O, Daniel S, Lesch KP. Enhancement of serotonin transporter function by tumor necrosis factor alpha but not by interleukin-6. Neurochem Int 1998; 33: 251–254
  • Myint AM, Kim YK. Cytokine–serotonin interaction through IDO: A neurodegeneration hypothesis of depression. Med Hypotheses 2003; 61: 519–525
  • Myint AM, Kim YK, Verkerk R, Scharpe S, Steinbusch H, Leonard B. Kynurenine pathway in major depression: Evidence of impaired neuroprotection. J Affect Disord 2007; 98: 143–151
  • Nguyen KT, Deak T, Owens SM, Kohno T, Fleshner M, Watkins LR, Maier SF. Exposure to acute stress induces brain interleukin-1beta protein in the rat. J Neurosci 1998; 18: 2239–2246
  • O'Connor KA, Johnson JD, Hansen MK, Wieseler Frank JL, Maksimova E, Watkins LR, Maier SF. Peripheral and central proinflammatory cytokine response to a severe acute stressor. Brain Res 2003; 991: 123–132
  • Okuda S, Nishiyama N, Saito H, Katsuki H. Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine. Proc Natl Acad Sci USA 1996; 93: 12553–12558
  • Owens MJ. Selectivity of antidepressants: From the monoamine hypothesis of depression to the SSRI revolution and beyond. J Clin Psychiatry 2004; 65(Suppl 4)5–10
  • Pardridge WM. Blood–brain barrier carrier-mediated transport and brain metabolism of amino acids. Neurochem Res 1998; 23: 635–644
  • Pawlak D, Takada Y, Urano T, Takada A. Serotonergic and kynurenic pathways in rats exposed to foot shock. Brain Res Bull 2000; 52: 197–205
  • Paykel ES. Life events, social support and depression. Acta Psychiatr Scand Suppl 1994; 377: 50–58
  • Porter RJ, McAllister-Williams RH, Jones S, Young AH. Effects of dexamethasone on neuroendocrine and psychological responses to l-tryptophan infusion. Psychopharmacology (Berl) 1999; 143: 64–71
  • Porter RJ, Gallagher P, Watson S, Young AH. Corticosteroid-serotonin interactions in depression: A review of the human evidence. Psychopharmacology (Berl) 2004; 173: 1–17
  • Price LH, Charney DS, Delgado PL, Heninger GR. Serotonin function and depression: Neuroendocrine and mood responses to intravenous l-tryptophan in depressed patients and healthy comparison subjects. Am J Psychiatry 1991; 148: 1518–1525
  • Ramamoorthy S, Ramamoorthy JD, Prasad PD, Bhat GK, Mahesh VB, Leibach FH, Ganapathy V. Regulation of the human serotonin transporter by interleukin-1 beta. Biochem Biophys Res Commun 1995; 216: 560–567
  • Roy EJ, Takikawa O, Kranz DM, Brown AR, Thomas DL. Neuronal localization of indoleamine 2,3-dioxygenase in mice. Neurosci Lett 2005; 387: 95–99
  • Saito K, Crowley JS, Markey SP, Heyes MP. A mechanism for increased quinolinic acid formation following acute systemic immune stimulation. J Biol Chem 1993; 268: 15496–15503
  • Sato T, Suzuki E, Yokoyama M, Semba J, Watanabe S, Miyaoka H. Chronic intraperitoneal injection of interferon-alpha reduces serotonin levels in various regions of rat brain, but does not change levels of serotonin transporter mRNA, nitrite or nitrate. Psychiatry Clin Neurosci 2006; 60: 499–506
  • Schäfer M, Mousa SA, Stein C. Corticotropin-releasing factor in antinociception and inflammation. Eur J Pharmacol 1997; 323: 1–10
  • Schiepers OJ, Wichers MC, Maes M. Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 201–217
  • Schule C. Neuroendocrinological mechanisms of actions of antidepressant drugs. J Neuroendocrinol 2007; 19: 213–226
  • Schulte HM, Bamberger CM, Elsen H, Herrmann G, Bamberger AM, Barth J. Systemic interleukin-1 alpha and interleukin-2 secretion in response to acute stress and to corticotropin-releasing hormone in humans. Eur J Clin Invest 1994; 24: 773–777
  • Shintani F, Nakaki T, Kanba S, Sato K, Yagi G, Shiozawa M, Aiso S, Kato R, Asai M. Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat. J Neurosci 1995; 15: 1961–1970
  • Shuto H, Kataoka Y, Horikawa T, Fujihara N, Oishi R. Repeated interferon-alpha administration inhibits dopaminergic neural activity in the mouse brain. Brain Res 1997; 747: 348–351
  • Smith RS. The macrophage theory of depression. Med Hypotheses 1991; 35: 298–306
  • Song C. The interaction between cytokines and neurotransmitters in depression and stress: Possible mechanism of antidepressant treatments. Hum Psychopharmacol 2000; 15: 199–211
  • Stone TW, Darlington LG. Endogenous kynurenines as targets for drug discovery and development. Nat Rev Drug Discov 2002; 1: 609–620
  • Strüder HK, Hollmann W, Platen P, Wostmann R, Weicker H, Molderings GJ. Effect of acute and chronic exercise on plasma amino acids and prolactin concentrations and on [3H]ketanserin binding to serotonin2A receptors on human platelets. Eur J Appl Physiol Occup Physiol 1999; 79: 318–324
  • Tu H, Rady PL, Juelich T, Smith EM, Tyring SK, Hughes TK. Cytokine regulation of tryptophan metabolism in the hypothalamic-pituitary-adrenal (HPA) axis: Implications for protective and toxic consequences in neuroendocrine regulation. Cell Mol Neurobiol 2005; 25: 673–680
  • Van der Does AJ. The effects of tryptophan depletion on mood and psychiatric symptoms. J Affect Disord 2001; 64: 107–119
  • Watkins LR, Maier SF, Goehler LE. Cytokine-to-brain communication: A review & analysis of alternative mechanisms. Life Sci 1995; 57: 1011–1026
  • Wichers MC, Maes M. The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-alpha-induced depression. J Psychiatry Neurosci 2004; 29: 11–17
  • Wichers MC, Koek GH, Robaeys G, Verkerk R, Scharpe S, Maes M. IDO and interferon-alpha-induced depressive symptoms: A shift in hypothesis from tryptophan depletion to neurotoxicity. Mol Psychiatry 2005; 10: 538–544
  • Widner B, Laich A, Sperner-Unterweger B, Ledochowski M, Fuchs D. Neopterin production, tryptophan degradation, and mental depression—what is the link?. Brain Behav Immun 2002; 16: 590–595
  • Xia Z, DePierre JW, Nassberger L. Tricyclic antidepressants inhibit IL-6, IL-1 beta and TNF-alpha release in human blood monocytes and IL-2 and interferon-gamma in T cells. Immunopharmacology 1996; 34: 27–37
  • Zalcman S, Green-Johnson JM, Murray L, Nance DM, Dyck D, Anisman H, Greenberg AH. Cytokine-specific central monoamine alterations induced by interleukin − 1, − 2 and − 6. Brain Res 1994; 643: 40–49

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