Hostname: page-component-77c89778f8-vsgnj Total loading time: 0 Render date: 2024-07-18T13:11:26.094Z Has data issue: false hasContentIssue false
  • English
  • Français

Antidepressant treatment of cytokine-induced mood disorders

Published online by Cambridge University Press:  24 June 2014

Charles L Raison ,
Michael Marcin  and
Andrew H Miller
Charles L Raison
Affiliation:
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
Michael Marcin
Affiliation:
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
Andrew H Miller*
Affiliation:
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
*
Andrew H. Miller, M.D., Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Dr, Suite 4000, Atlanta, GA 30322, USA. Tel: + 404-727-8260; Fax: + 404-727-3233; E-mail: amill02@emory.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Significant evidence suggests that the immune system is capable of profoundly affecting central nervous system (CNS) functioning in ways that may contribute to the development and expression of neuropsychiatric disorders, including disorders of mood. This paper reviews evidence that the production of proinflammatory cytokines, whether in the context of therapeutic administration (e.g. interferon-α-2b for hepatitis C infection) or medical illness, induces a state of sickness behavior that closely resembles major depression. Antidepressants have been shown to abolish or attenuate cytokine-induced sickness behavior in laboratory animals and to protect against the development of major depression in the context of therapeutic cytokine administration in humans. Potential mechanisms by which antidepressants ameliorate depressive and/or sickness symptoms in the context of immune activation include direct effects on immune cell functioning, as well as modulatory effects on monoamine neurotransmitters, intracellular second messenger pathways and the neuroendocrine system, in particular the hypothalamic–pituitary–adrenal axis.

Keywords

antidepressantmood disorderscytokinesimmune
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 14 , Issue 6 , December 2002 , pp. 336 - 343
Copyright
Copyright © Acta Neuropsychiatrica 2002

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Quan, N, Stern, E L, Whiteside, MB, Herkenham, M. Induction of pro-inflammatory cytokine mRNAs in the brain after peripheral injection of subseptic doses of lipopolysaccharide in the rat. J Neuroimmunol 1999;93: 72–80.CrossRefGoogle ScholarPubMed
Watkins, LR, Goehler, LE, Relton, JKet al. Blockade of interleukin-1 induced hyperthermia by subdiaphragmatic vagotomy: evidence for vagal mediation of immune-brain communication. Neurosci Lett 1995;183: 27–31.CrossRefGoogle ScholarPubMed
Maier, SF, Watkins, LR. Cytokines for psychologists. implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychol Rev 1998;105: 83–107.CrossRefGoogle Scholar
Yirmiya, R, Pollak, Y, Barak, Oet al. Effects of antidepressant drugs on the behavioral and physiological responses to lipopolysaccharide (LPS) in rodents. Neuropsychopharmacology 2001;24: 531–544.CrossRefGoogle Scholar
Musselman, DL, Lawson, DH, Gumnick, JFet al. Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med 2001;344: 961–966.CrossRefGoogle ScholarPubMed
Yirmiya, R, Weidenfeld, J, Pollak, Yet al. Cytokines, ‘depression due to a general medical condition’, and antidepressant drugs. Adv Exp Med Biol 1999;461: 283–316.CrossRefGoogle Scholar
Greden, JF. The burden of recurrent depression: causes, consequences, and future prospects. J Clin Psychiatry 2001;62(Suppl. 22):5–9.Google ScholarPubMed
Frasure-Smith, N, Lesperance, F, Talajic, M. Depression following myocardial infarction. Impact on 6-month survival. JAMA 1993;270: 1819–1825.CrossRefGoogle Scholar
von Ammon Cavanaugh, S, Furlanetto, LM, Creech, SD, Powell, LH. Medical illness, past depression, and present depression: a predictive triad for in-hospital mortality. Am J Psychiatry 2001;158: 43–48.CrossRefGoogle ScholarPubMed
Koenig, HG, George, LK, Larson, DB, McCullough, ME, Branch, PS, Kuchibhatla, M. Depressive symptoms and nine-year survival of 1,001 male veterans hospitalized with medical illness. Am J Geriatr Psychiatry 1999;7: 124–131.CrossRefGoogle ScholarPubMed
Kent, S, Bluthe, RM, Kelley, KW, Dantzer, R. Sickness behavior as a new target for drug development. Trends Pharmacol Sci 1992;13: 24–28.CrossRefGoogle ScholarPubMed
Dantzer, R. Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun 2001;15: 7–24.CrossRefGoogle ScholarPubMed
Bluthe, RM, Crestani, F, Kelley, KW, Dantzer, R. Mechanisms of the behavioral effects of interleukin 1. Role of prostaglandins and CRF. Ann NY Acad Sci 1992;650: 268–275.CrossRefGoogle ScholarPubMed
Capuron, L, Ravaud, A, Dantzer, R. Timing and specificity of the cognitive changes induced by interleukin-2 and interferon-alpha treatments in cancer patients. Psychosom Med 2001;63: 376–386.CrossRefGoogle Scholar
Capuron, L, Gumnick, JF, Musselman, DLet al. Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology 2002;26: 643–652.CrossRefGoogle ScholarPubMed
Maier, SF, Watkins, LR. Intracerebroventricular interleukin-1 receptor antagonist blocks the enhancement of fear conditioning and interference with escape produced by inescapable shock. Brain Res 1995;695: 279–282.CrossRefGoogle ScholarPubMed
Pugh, CR, Nguyen, KT, Gonyea, JLet al. Role of interleukin-1 beta in impairment of contextual fear conditioning caused by social isolation. Behav Brain Res 1999;106: 109–118.CrossRefGoogle Scholar
Sapolsky, R, Rivier, C, Yamamoto, G, Plotsky, P, Vale, W. Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science 1987;238: 522–524.CrossRefGoogle ScholarPubMed
Owens, MJ, Nemeroff, CB. The role of corticotropin-releasing factor in the pathophysiology of affective and anxiety disorders: laboratory and clinical studies. Ciba Found Symp 1993;172: 296–308.Google ScholarPubMed
Dunn, AJ, Wang, J, Ando, T. Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Adv Exp Med Biol 1999;461: 117–1127.CrossRefGoogle ScholarPubMed
Musselman, DL, Debatista, C, Nathan, KI, Kilts, CD, Schatzberg, AF, Nemeroff, CB. Biology of mood disorders. In: Textbook of Psychopharmacology, 2nd edn. (eds Schatzberg, AF, Nemeroff, CB). Washington, DC. American Psychiatric Press, 1998: pp. 549–588.Google Scholar
Hu, B, Hissong, BD, Carlin, JM. Interleukin-1 enhances indoleamine 2,3-dioxygenase activity by increasing specific mRNA expression in human mononuclear phagocytes. J Interferon Cytokine Res 1995;15: 617–624.CrossRefGoogle ScholarPubMed
Delgado, PL, Price, LH, Miller, HLet al. Rapid serotonin depletion as a provocative challenge test for patients with major depression. relevance to antidepressant action and the neurobiology of depression. Psychopharmacol Bull 1991;27: 321–330.Google Scholar
Papanicolaou, DA. Euthyroid Sick Syndrome and the role of cytokines. Rev Endocr Metabol Disord 2000;1: 43–48. CrossRefGoogle ScholarPubMed
Haggerty, JJ Jr, Prange, AJ Jr.Borderline hypothyroidism and depression. Ann Rev Med 1995;46: 37–46.CrossRefGoogle ScholarPubMed
Miller, AH, Pariante, CM, Pearce, BD. Effects of cytokines on glucocorticoid receptor expression and function. Glucocorticoid resistance and relevance to depression. Adv Exp Med Biol 1999;461: 107–116.CrossRefGoogle Scholar
Evans, DL, Staab, J, Ward, Het al. Depression in the medically ill: management considerations. Depression Anxiety 1996;4: 199–208. 3.0.CO;2-A>CrossRefGoogle Scholar
Evans, DL, Staab, JP, Petitto, JMet al. Depression in the medical setting: biopsychological interactions and treatment considerations. J Clin Psychiatry 1999;60 (Suppl. 4):40–55.Google ScholarPubMed
Sutor, B, Rummans, TA, Jowsey, SGet al. Major depression in medically ill patients. Mayo Clin Proc 1998;73: 329–337.CrossRefGoogle ScholarPubMed
Blazer, DG, Kessler, RC, McGonagle, KA, Swartz, MS. The prevalence and distribution of major depression in a national community sample: the National Comorbidity Survey. Am J Psychiatry 1994;151: 979–986.Google Scholar
Maes, M. Major depression and activation of the inflammatory response system. Adv Exp Med Biol 1999;461: 25–46.CrossRefGoogle ScholarPubMed
Musselman, DL. Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am J Psychiatry 2001;158: 1252–1257.CrossRefGoogle Scholar
Maes, M. A review on the acute phase response in major depression. Rev Neurosci 1993;4: 407–416.CrossRefGoogle ScholarPubMed
Maes, M, Smith, R, Christophe, A, Cosyns, P, Desnyder, R, Meltzer, H. Fatty acid composition in major depression. decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20: 5 omega 3 ratio in cholesteryl esters and phospholipids. J Affect Disord 1996;38: 35–46.CrossRefGoogle Scholar
Irwin, M. Immune correlates of depression. Adv Exp Med Biol 1999;461: 1–24.CrossRefGoogle Scholar
Zorilla, E, Luborsky, L, McKay, J, Roesnthal, Ret al. The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun 2001;15: 199–226.CrossRefGoogle Scholar
Maes, M, Scharpe, S, Meltzer, HY, Bosmans, E, Suy, E, Calabrese, J, Cosyns, P. Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic-pituitary-adrenal axis in severe depression. Psychiatry Res 1993;49: 11–27.CrossRefGoogle Scholar
Pariante, CM, Miller, AH. Glucocorticoid receptors in major depression. relevance to pathophysiology and treatment. Biol Psychiatry 2001;49: 391–404.CrossRefGoogle ScholarPubMed
Castanon, N, Bluthe, RM, Dantzer, R. Chronic treatment with the atypical antidepressant tianeptine attenuates sickness behavior induced by peripheral but not central lipopolysaccharide and interleukin-1beta in the rat. Psychopharmacology (Berl) 2001;154: 50–60.CrossRefGoogle Scholar
Shen, Y, Connor, TJ, Nolan, Y, Kelly, JP, Leonard, BE. Differential effect of chronic antidepressant treatments on lipopolysaccharide-induced depressive-like behavioural symptoms in the rat. Life Sci 1999;65: 1773–1786.CrossRefGoogle ScholarPubMed
Mohr, DC, Goodkin, DE, Likosky, W, Gatto, N, Baumann, KA, Rudick, RA. Treatment of depression improves adherence to interferon beta-1b therapy for multiple sclerosis. Arch Neurol 1997;54: 531–533.CrossRefGoogle Scholar
Schramm, TM, Lawford, BR, Macdonald, GA, Cooksley, WG. Sertraline treatment of interferon-alfa-induced depressive disorder. Med J Aust 2000;173: 359–361.Google Scholar
Gleason, OC, Yates, WR. Five cases of interferon-alpha-induced depression treated with antidepressant therapy. Psychosomatics 1999;40: 510–512.CrossRefGoogle Scholar
Levenson, JL, Fallon, HJ. Fluoxetine treatment of depression caused by interferon-alpha. [see comments.] Am J Gastroenterol 1993;88: 760–761.Google Scholar
Miller, AH, Asnis, GM, Van Praag, HM, Norin, AJ. Influence of desmethylimipramine on natural killer cell activity. Psychiatry Res 1986;19: 9–15.CrossRefGoogle ScholarPubMed
Frank, MG, Hendricks, SE, Johnson, DR, Wieseler, JL, Burke, WJ. Antidepressants augment natural killer cell activity. in vivo and in vitro. Neuropsychobiology 1999;39: 18–24.CrossRefGoogle ScholarPubMed
Maes, M, Song, C, Lin, AH, Bonaccorso, Set al. Negative immunoregulatory effects of antidepressants: inhibition of interferon-gamma and stimulation of interleukin-10 secretion. Neuropsychopharmacology 1999;20: 370–379.CrossRefGoogle ScholarPubMed
Brambilla, F, Maggioni, M. Blood levels of cytokines in elderly patients with major depressive disorder. Acta Psychiatr Scand 1998;97: 309–313.CrossRefGoogle ScholarPubMed
Maes, M, Meltzer, HY, Bosmans, Eet al. Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord 1995;34: 301–309.CrossRefGoogle ScholarPubMed
Landmann, R, Schaub, B, Link, S, Wacker, HR. Unaltered monocyte function in patients with major depression before and after three months of antidepressive therapy. Biol Psychiatry 1997;41: 675–681.CrossRefGoogle ScholarPubMed
Pariante, CM, Miller, AH. Natural killer cell activity in major depression. a prospective study of the in vivo effects of desmethylimipramine treatment. Eur Neuropsychopharmacol 1995;5 (Suppl. ):83–88.CrossRefGoogle Scholar
Ravindran, AV, Griffiths, J, Merali, Z, Anisman, H. Circulating lymphocyte subsets in major depression and dysthymia with typical or atypical features. Psychosom Med 1998;60: 283–289.CrossRefGoogle ScholarPubMed
Weizman, R, Laor, N, Podliszewski, E, Notti, I, Djaldetti, M, Bessler, H. Cytokine production in major depressed patients before and after clomipramine treatment. [see comments.] Biol Psychiatry 1994;35: 42–47.CrossRefGoogle Scholar
Ignatowski, TA, Spengler, RN. Tumor necrosis factor-alpha: presynaptic sensitivity is modified after antidepressant drug administration. Brain Res 1994;665: 293–299.CrossRefGoogle ScholarPubMed
McKay, LI, Cidlowski, JA. Molecular control of immune/inflammatory responses: interactions between nuclear factor-kappa B and steroid receptor-signaling pathways. Endocr Rev 1999;20: 435–459.Google ScholarPubMed
Pariante, CM, Pearce, BD, Pisell, TL, Owens, MJ, Miller, AH. Steroid-independent translocation of the glucocorticoid receptor by the antidepressant desipramine. Mol Pharmacol 1997;52: 571–581.Google ScholarPubMed
Holsboer, F. The corticosteroid hypothesis of depression. Neuropsychopharmacology 2000;23: 477–501.CrossRefGoogle Scholar
Stout, SC, Owens, MJ, Nemeroff, CB. Regulation of corticotropin-releasing factor neuronal systems and hypothalamic-pituitary-adrenal axis activity by stress and chronic antidepressant treatment. J Pharmacol Exp Therap 2002;300: 1085–1092. CrossRefGoogle ScholarPubMed
Miller, AH, Spencer, RL, Trestman, RL, Kim, C, McEwen, BS, Stein, M. Adrenal steroid receptor activation in vivo and immune function. Am J Physiol 1991;261 (1 Part 1):E126–E131.Google Scholar
Duman, RS, Heninger, GR, Nestler, EJ. A molecular and cellular theory of depression. [see comments.] Arch Gen Psychiatry 1997;54: 597–606.CrossRefGoogle Scholar
Chen, J, Rasenick, MM. Chronic antidepressant treatment facilitates G protein activation of adenylyl cyclase without altering G protein content. J Pharmacol Exp Therapeut 1995;275: 509–517. Google ScholarPubMed
Snijdewint, FG, Kalinski, P, Wierenga, EA, Bos, JD, Kapsenberg, ML. Prostaglandin E2 differentially modulates cytokine secretion profiles of human T helper lymphocytes. J Immunol 1993;150: 5321–5329.Google ScholarPubMed
Irie, K, Fujii, E, Ishida, Het al. Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)-induced microvascular permeability change in mouse skin. Br J Pharmacol 2001;133: 237–242.CrossRefGoogle ScholarPubMed
Benbernou, N, Esnault, S, Shin, HC, Fekkar, H, Guenounou, M. Differential regulation of IFN-gamma, IL-10 and inducible nitric oxide synthase in human T cells by cyclic AMP-dependent signal transduction pathway. Immunology 1997;91: 361–368.CrossRefGoogle Scholar