Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-669899f699-7tmb6 Total loading time: 0 Render date: 2025-05-03T04:48:54.580Z Has data issue: false hasContentIssue false

Chapter 14 - Depression and the Adaptive Immune System

Published online by Cambridge University Press:  02 September 2021

By
Robert Dantzer
Edited by
Golam Khandaker ,
Neil Harrison ,
Edward Bullmore  and
Robert Dantzer
Golam Khandaker
Affiliation:
University of Cambridge
Neil Harrison
Affiliation:
Cardiff University Brain Research Imaging Centre (CUBRIC)
Edward Bullmore
Affiliation:
University of Cambridge
Robert Dantzer
Affiliation:
University of Texas, MD Anderson Cancer Center
Get access

Summary

In the context of immunopsychiatry it is important to know whether the association between psychiatric disorders and the immune system that is reported in more and more scientific publications is a real one or just another manifestation of the many comorbid physical conditions that are affecting psychiatric patients. In the case this association is real, the next question is whether the reported alterations in immunity are causal to the psychiatric disorder or just one of its consequences, in the form for instance of the impact of unhealthy lifestyles on the microbiota. Causality, when it exists, provides a unique opportunity to identify new mechanistic targets for drug development. The observation of consistent immune alterations in psychiatric patients also leads to the important interrogation of their functional outcome on the organism resistance to infection or the progression of somatic diseases such as cancer and autoimmunity.

Type
Chapter
Information
Textbook of Immunopsychiatry , pp. 292 - 308
Publisher: Cambridge University Press
Print publication year: 2021

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.)

Book purchase

Temporarily unavailable

References

Raison, CL, Miller, AH. Role of inflammation in depression: implications for phenomenology, pathophysiology and treatment. Mod Trends Pharmacopsychiatry. 2013;28:33–48.CrossRefGoogle Scholar
Miller, AH, Raison, CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16(1):22–34.Google Scholar
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(1):46–56.CrossRefGoogle ScholarPubMed
Dantzer, R, O’Connor, JC, Lawson, MA, Kelley, KW. Inflammation-associated depression: from serotonin to kynurenine. Psychoneuroendocrinology. 2011;36(3):426–36.CrossRefGoogle ScholarPubMed
Dantzer, R, Capuron, L. Inflammation-Associated Depression: Evidence, Mechanisms, and Implicaiton. Geyer, MA, Ellenbroek, BA, Marsden, CA, Barnes, TRE, eds. Springer. Switzerland; 2017.CrossRefGoogle Scholar
Kappelmann, N, Lewis, G, Dantzer, R, Jones, PB, Khandaker, GM. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol Psychiatry. 2018 Feb;23(2):335–43. doi:10.1038/mp.2016.167. Epub 2016 Oct 18.Google Scholar
Raison, CL, Rutherford, RE, Woolwine, BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013;70(1):31–41.CrossRefGoogle ScholarPubMed
Leday, GGR, Vertes, PE, Richardson, S, et al. Replicable and coupled changes in innate and adaptive immune gene expression in two case-control studies of blood microarrays in major depressive disorder. Biol Psychiatry. 2018 Jan;83(1):70–80. doi:10.1016/j.biopsych.2017.01.021. Epub 2017 Jul 6.Google Scholar
Haapakoski, R, Mathieu, J, Ebmeier, KP, Alenius, H, Kivimaki, M. Cumulative meta-analysis of interleukins 6 and 1beta, tumour necrosis factor alpha and C-reactive protein in patients with major depressive disorder. Brain Behav Immun. 2015;49:206–15.CrossRefGoogle ScholarPubMed
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(2):171–86.Google Scholar
Kohler, CA, Freitas, TH, Stubbs, B, et al. Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol Neurobiol. 2018 May;55(5):4195–206. doi:10.1007/s12035-017-0632-1. Epub 2017 Jun 13.Google Scholar
Valkanova, V, Ebmeier, KP, Allan, CL. CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J Affect Disord. 2013;150(3):736–44.CrossRefGoogle ScholarPubMed
Grosse, L, Hoogenboezem, T, Ambree, O, et al. Deficiencies of the T and natural killer cell system in major depressive disorder: T regulatory cell defects are associated with inflammatory monocyte activation. Brain Behav Immun. 2016;54:38–44.CrossRefGoogle Scholar
Snijders, G, Schiweck, C, Mesman, E, et al. A dynamic course of T cell defects in individuals at risk for mood disorders. Brain Behav Immun. 2016;58:11–7.Google Scholar
Darko, DF, Rose, J, Gillin, JC, Golshan, S, Baird, SM. Neutrophilia and lymphopenia in major mood disorders. Psychiatry Res. 1988;25(3):243–51.Google Scholar
Caldwell, CL, Irwin, M, Lohr, J. Reduced natural killer cell cytotoxicity in depression but not in schizophrenia. Biol Psychiatry. 1991;30(11):1131–8.Google Scholar
Andersson, NW, Goodwin, RD, Okkels, N, et al. Depression and the risk of severe infections: prospective analyses on a nationwide representative sample. Int J Epidemiol. 2016;45(1):131–9.CrossRefGoogle ScholarPubMed
Benton, T, Staab, J, Evans, DL. Medical co-morbidity in depressive disorders. Ann Clin Psychiatry. 2007;19(4):289–303.CrossRefGoogle ScholarPubMed
Enache, D, Pariante, CM, Mondelli, V. Markers of central inflammation in major depressive disorder: A systematic review and meta-analysis of studies examining cerebrospinal fluid, positron emission tomography and post-mortem brain tissue. Brain Behav Immun. 2019;81:24–40.CrossRefGoogle ScholarPubMed
Schleifer, SJ, Keller, SE, Camerino, M, Thornton, JC, Stein, M. Suppression of lymphocyte stimulation following bereavement. JAMA. 1983;250(3):374–7.Google Scholar
Kronfol, Z, Silva, J, Jr., Greden, J, et al. Impaired lymphocyte function in depressive illness. Life Sci. 1983;33(3):241–7.Google Scholar
Schleifer, SJ, Keller, SE, Meyerson, AT, et al. Lymphocyte function in major depressive disorder. Arch Gen Psychiatry. 1984;41(5):484–6.Google Scholar
Schleifer, SJ, Keller, SE, Siris, SG, Davis, KL, Stein, M. Depression and immunity. Lymphocyte function in ambulatory depressed patients, hospitalized schizophrenic patients, and patients hospitalized for herniorrhaphy. Arch Gen Psychiatry. 1985;42(2):129–33.CrossRefGoogle ScholarPubMed
Denman, AM. Immunity and depression. Br Med J (Clin Res Ed). 1986;293(6545):464–5.Google Scholar
Levy, EM, Borrelli, DJ, Mirin, SM, et al. Biological measures and cellular immunological function in depressed psychiatric inpatients. Psychiatry Res. 1991;36(2):157–67.Google Scholar
Herbert, TB, Cohen, S. Depression and immunity: a meta-analytic review. Psychol Bull. 1993;113(3):472–86.Google Scholar
Hughes, MM, Connor, TJ, Harkin, A. Stress-related immune markers in depression: implications for treatment. Int J Neuropsychopharmacol. 2016 Jun;19(6):pyw001. doi:10.1093/ijnp/pyw001. Epub 2016 Jan 16.Google Scholar
Maes, M, Stevens, W, DeClerck, L, et al. Immune disorders in depression: higher T helper/T suppressor-cytotoxic cell ratio. Acta Psychiatr Scand. 1992;86(6):423–31.Google Scholar
Maes, M, Bosmans, E, Suy, E, et al. Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology. 1990;24(3):115–20.Google Scholar
Muller, N, Hofschuster, E, Ackenheil, M, Mempel, W, Eckstein, R. Investigations of the cellular immunity during depression and the free interval: evidence for an immune activation in affective psychosis. Prog Neuropsychopharmacol Biol Psychiatry. 1993;17(5):713–30.Google Scholar
Kubera, M, Van Bockstaele, D, Maes, M. Leukocyte subsets in treatment-resistant major depression. Pol J Pharmacol. 1999;51(6):547–9.Google Scholar
Charles, G, Machowski, R, Brohee, D, Wilmotte, J, Kennes, B. Lymphocyte subsets in major depressive patients. Influence of anxiety and corticoadrenal overdrive. Neuropsychobiology. 1992;25(2):94–8.CrossRefGoogle ScholarPubMed
Scanlan, JM, Vitaliano, PP, Ochs, H, Savage, MV, Borson, S. CD4 and CD8 counts are associated with interactions of gender and psychosocial stress. Psychosom Med. 1998;60(5):644–53.Google Scholar
Huang, TL, Leu, HS, Liu, JW. Lymphocyte subsets and viral load in male AIDS patients with major depression: naturalistic study. Psychiatry Clin Neurosci. 2006;60(6):687–92.Google Scholar
Manceaux, P, Zdanowicz, N. Immunity, coping and depression. Psychiatr Danub. 2016;28(Suppl-1):165–9.Google ScholarPubMed
Atanackovic, D, Kroger, H, Serke, S, Deter, HC. Immune parameters in patients with anxiety or depression during psychotherapy. J Affect Disord. 2004;81(3):201–9.Google Scholar
Muller, N, Ackenheil, M, Hofschuster, E, Mempel, W, Eckstein, R. Cellular immunity, HLA-class I antigens, and family history of psychiatric disorder in endogenous psychoses. Psychiatry Res. 1993;48(3):201–17.Google Scholar
Ellul, P, Mariotti-Ferrandiz, E, Leboyer, M, Klatzmann, D. Regulatory T cells as supporters of psychoimmune resilience: toward immunotherapy of major depressive disorder. Front Neurol. 2018;9:167.CrossRefGoogle ScholarPubMed
Kohler, CA, Freitas, TH, Maes, M, et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017;135(5):373–87.Google Scholar
Sowa-Kucma, M, Styczen, K, Siwek, M, et al. Lipid peroxidation and immune biomarkers are associated with major depression and its phenotypes, including treatment-resistant depression and melancholia. Neurotox Res. 2018;33(2):448–60.Google Scholar
Patas, K, Willing, A, Demiralay, C, et al. T cell phenotype and T cell receptor repertoire in patients with major depressive disorder. Front Immunol. 2018;9:291.Google Scholar
Suzuki, H, Savitz, J, Kent Teague, T, et al. Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance. Brain Behav Immun. 2017;66:193–200.Google Scholar
Slyepchenko, A, Maes, M, Kohler, CA, et al. T helper 17 cells may drive neuroprogression in major depressive disorder: proposal of an integrative model. Neurosci Biobehav Rev. 2016;64:83–100.Google Scholar
Waisman, A, Hauptmann, J, Regen, T. The role of IL-17 in CNS diseases. Acta Neuropathol. 2015;129(5):625–37.Google Scholar
Chen, Y, Jiang, T, Chen, P, et al. Emerging tendency towards autoimmune process in major depressive patients: a novel insight from Th17 cells. Psychiatry Res. 2011;188(2):224–30.Google Scholar
Poletti, S, de Wit, H, Mazza, E, et al. Th17 cells correlate positively to the structural and functional integrity of the brain in bipolar depression and healthy controls. Brain Behav Immun. 2017;61:317–25.Google Scholar
Osborne, LM, Brar, A, Klein, SL. The role of Th17 cells in the pathophysiology of pregnancy and perinatal mood and anxiety disorders. Brain Behav Immun. 2019;76:7–16.Google Scholar
Maes, M, Stevens, WJ, DeClerck, LS, et al. A significantly increased number and percentage of B cells in depressed subjects: results of flow cytometric measurements. J Affect Disord. 1992;24(3):127–34.Google Scholar
Andreoli, AV, Keller, SE, Rabaeus, M, et al. Depression and immunity: age, severity, and clinical course. Brain Behav Immun. 1993;7(4):279–92.Google 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(3):283–9.CrossRefGoogle ScholarPubMed
Ahmetspahic, D, Schwarte, K, Ambree, O, et al. Altered B cell homeostasis in patients with major depressive disorder and normalization of CD5 surface expression on regulatory B cells in treatment responders. J Neuroimmune Pharmacol. 2018;13(1):90–9.Google Scholar
Shopsin, B, Sathananthan, GL, Chan, TL, Kravitz, H, Gershon, S. Antinuclear factor in psychiatric patients. Biol Psychiatry. 1973;7(2):81–7.Google Scholar
Johnstone, EC, Whaley, K. Antinuclear antibodies in psychiatric illness: their relationship to diagnosis and drug treatment. Br Med J. 1975;2(5973):724–5.Google Scholar
Deberdt, R, Van Hooren, J, Biesbrouck, M, Amery, W. Antinuclear factor-positive mental depression: a single disease entity? Biol Psychiatry. 1976;11(1):69–74.Google Scholar
Appleby, B. Are anti-nuclear antibodies common in affective disorders? A review of the past 35 years. Psychosomatics. 2007;48(4):286–9.Google Scholar
Iseme, RA, McEvoy, M, Kelly, B, et al. Autoantibodies and depression: evidence for a causal link? Neurosci Biobehav Rev. 2014;40:62–79.Google Scholar
Iseme, RA, McEvoy, M, Kelly, B, et al. Autoantibodies are not predictive markers for the development of depressive symptoms in a population-based cohort of older adults. Eur Psychiatry. 2015;30(6):694–700.Google Scholar
Fjaellegaard, K, Kvetny, J, Allerup, PN, Bech, P, Ellervik, C. Well-being and depression in individuals with subclinical hypothyroidism and thyroid autoimmunity – a general population study. Nord J Psychiatry. 2015;69(1):73–8.Google Scholar
Pearlman, DM, Najjar, S. Meta-analysis of the association between N-methyl-d-aspartate receptor antibodies and schizophrenia, schizoaffective disorder, bipolar disorder, and major depressive disorder. Schizophr Res. 2014;157(1–3):249–58.Google Scholar
Maes, M, Galecki, P, Chang, YS, Berk, M. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(3):676–92.Google Scholar
Maes, M, Kubera, M, Mihaylova, I, et al. Increased autoimmune responses against auto-epitopes modified by oxidative and nitrosative damage in depression: implications for the pathways to chronic depression and neuroprogression. J Affect Disord. 2013;149(1–3):23–9.Google Scholar
Morris, G, Berk, M, Klein, H, et al. Nitrosative stress, hypernitrosylation, and autoimmune responses to nitrosylated proteins: new pathways in neuroprogressive disorders including depression and chronic fatigue syndrome. Mol Neurobiol. 2017;54(6):4271–91.Google Scholar
White, J, Kivimaki, M, Jokela, M, Batty, GD. Association of inflammation with specific symptoms of depression in a general population of older people: the English Longitudinal Study of Ageing. Brain Behav Immun. 2017;61:27–30.Google Scholar
Jokela, M, Virtanen, M, Batty, GD, Kivimaki, M. Inflammation and specific symptoms of depression. JAMA Psychiatry. 2016;73(1):87–8.Google Scholar
Schleifer, SJ, Keller, SE, Bartlett, JA. Depression and immunity: clinical factors and therapeutic course. Psychiatry Res. 1999;85(1):63–9.Google Scholar
Jha, MK, Miller, AH, Minhajuddin, A, Trivedi, MH. Association of T and non-T cell cytokines with anhedonia: role of gender differences. Psychoneuroendocrinology. 2018;95:1–7.CrossRefGoogle ScholarPubMed
Irwin, M, Costlow, C, Williams, H, et al. Cellular immunity to varicella-zoster virus in patients with major depression. J Infect Dis. 1998;178(Suppl 1):S104–8.Google Scholar
Irwin, MR, Levin, MJ, Carrillo, C, et al. Major depressive disorder and immunity to varicella-zoster virus in the elderly. Brain Behav Immun. 2011;25(4):759–66.Google Scholar
Irwin, MR, Levin, MJ, Laudenslager, ML, et al. Varicella zoster virus-specific immune responses to a herpes zoster vaccine in elderly recipients with major depression and the impact of antidepressant medications. Clin Infect Dis. 2013;56(8):1085–93.Google Scholar
Laursen, TM, Musliner, KL, Benros, ME, Vestergaard, M, Munk-Olsen, T. Mortality and life expectancy in persons with severe unipolar depression. J Affect Disord. 2016;193:203–7.Google Scholar
Eyre, HA, Lavretsky, H, Kartika, J, Qassim, A, Baune, BT. Modulatory Effects of Antidepressant Classes on the Innate and Adaptive Immune System in Depression. Pharmacopsychiatry. 2016;49(3):85–96.Google Scholar
Grosse, L, Carvalho, LA, Birkenhager, TK, et al. Circulating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy. Psychopharmacology (Berl). 2016;233(9):1679–88.Google Scholar
Jha, MK, Minhajuddin, A, Gadad, BS, et al. Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: novel T cell biomarker for antidepressant medication selection. Brain Behav Immun. 2017;66:103–10.Google Scholar
Irwin, MR, Cole, SW. Reciprocal regulation of the neural and innate immune systems. Nat Rev Immunol. 2011;11(9):625–32.CrossRefGoogle ScholarPubMed
Miller, AH. Depression and immunity: a role for T cells? Brain Behav Immun. 2010;24(1):1–8.Google Scholar
Wei, J, Zhang, M, Zhou, J. Myeloid-derived suppressor cells in major depression patients suppress T-cell responses through the production of reactive oxygen species. Psychiatry Res. 2015;228(3):695–701.Google Scholar
Lewitus, GM, Wilf-Yarkoni, A, Ziv, Y, et al. Vaccination as a novel approach for treating depressive behavior. Biol Psychiatry. 2009;65(4):283–8.Google Scholar
Sakic, B, Szechtman, H, Denburg, JA. Neurobehavioral alterations in autoimmune mice. Neurosci Biobehav Rev. 1997;21(3):327–40.Google Scholar
Sakic, B, Lacosta, S, Denburg, JA, Szechtman, H. Altered neurotransmission in brains of autoimmune mice: pharmacological and neurochemical evidence. J Neuroimmunol. 2002;129(1–2):84–96.Google Scholar
Stock, AD, Wen, J, Doerner, J, et al. Neuropsychiatric systemic lupus erythematosus persists despite attenuation of systemic disease in MRL/lpr mice. J Neuroinflammation. 2015;12:205.CrossRefGoogle ScholarPubMed
Cathomas, F, Fuertig, R, Sigrist, H, et al. CD40-TNF activation in mice induces extended sickness behavior syndrome co-incident with but not dependent on activation of the kynurenine pathway. Brain Behav Immun. 2015;50:125–40.Google Scholar
Beurel, E, Harrington, LE, Jope, RS. Inflammatory T helper 17 cells promote depression-like behavior in mice. Biol Psychiatry. 2013;73(7):622–30.CrossRefGoogle ScholarPubMed
Beurel, E, Lowell, JA. Th17 cells in depression. Brain Behav Immun. 2018;69:28–34.Google Scholar
Cheng, Y, Desse, S, Martinez, A, et al. TNFalpha disrupts blood brain barrier integrity to maintain prolonged depressive-like behavior in mice. Brain Behav Immun. 2018;69:556–67.CrossRefGoogle ScholarPubMed
Brachman, RA, Lehmann, ML, Maric, D, Herkenham, M. Lymphocytes from chronically stressed mice confer antidepressant-like effects to naive mice. J Neurosci. 2015;35(4):1530–8.CrossRefGoogle ScholarPubMed
Scheinert, RB, Haeri, MH, Lehmann, ML, Herkenham, M. Therapeutic effects of stress-programmed lymphocytes transferred to chronically stressed mice. Prog Neuropsychopharmacol Biol Psychiatry. 2016;70:1–7.Google Scholar
Laumet, G, Edralin, JD, Chiang, AC, et al. Resolution of inflammation-induced depression requires T lymphocytes and endogenous brain interleukin-10 signaling. Neuropsychopharmacology. 2018;43(13):2597–605.Google Scholar
Kohler, CA, Freitas, TH, Stubbs, B, et al. Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol Neurobiol. 2018;55(5):4195–206.Google Scholar
Lago, SG, Tomasik, J, van Rees, GF, et al. Exploring the neuropsychiatric spectrum using high-content functional analysis of single-cell signaling networks. Mol Psychiatry. 2020 Oct;25(10):2355–72. doi:10.1038/s41380-018-0123-4. Epub 2018 Jul 23.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×