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The immune system and schizophrenia: an update for clinicians

  • Rachel Upthegrove and Nicholas M. Barnes
Summary

It has long been recognised that the pathology of schizophrenia may involve the immune system, yet this has been a relatively neglected area of research. Recent advances in our understanding of the complexities and functioning of the immune system have allowed new investigation into this area from many angles, including cellular and genetic avenues. A number of prominent theories have been developed. This article gives an overview of our understanding of the immune system and highlights recent advances pertaining to schizophrenia.

LEARNING OBJECTIVES

  1. To refresh and update understanding of the innate and adaptive immune system, presented clearly to the non-expert audience.
  2. To understand key advances in immunological theories of schizophrenia.
  3. To engender clinicians' enthusiasm for further reading and interest in this topic.

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Copyright
Corresponding author
Dr R. Upthegrove, The Barberry National Centre for Mental Health, 25 Vincent Drive, Edgbaston, Birmingham B15 2FG, UK. Email: r.upthegrove@bham.ac.uk
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Declaration of Interest

N.B. is a major shareholder in Celentyx Ltd.

Footnotes
References
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Aberg, KA, Liu, Y, Bukszár, J et al (2013) A comprehensive family-based replication study of schizophrenia genes. JAMA Psychiatry, 70: 573–81.
Aghajanian, GK, Marek, GJ (2000) Serotonin model of schizophrenia: emerging role of glutamate mechanisms. Brain Research Reviews, 31: 302–12.
Akhondzadeh, S, Tabatabaee, M, Amini, H et al (2007) Celecoxib as adjunctive therapy in schizophrenia: a double-blind, randomized and placebo-controlled trial. Schizophrenia Research, 90: 179–85.
Benros, ME, Nielsen, PR, Nordentoft, M et al (2011) Autoimmune diseases and severe infections as risk factors for schizophrenia: a 30-year population-based register study. American Journal of Psychiatry, 168: 1303–10.
Bradbury, TN, Miller, GA (1985) Season of birth in schizophrenia: a review of evidence, methodology, and etiology. Psychological Bulletin, 98: 569–94.
Cazzullo, CL, Sacchetti, E, Galluzzo, A et al (2001) Cytokine profiles in drug-naive schizophrenic patients. Schizophrenia Research, 47: 293–8.
Chaudhry, IB, Hallak, J, Husain, N et al (2012) Minocycline benefits negative symptoms in early schizophrenia; a randomised double-blind placebo-controlled clinical trial in patients on standard treatment. Journal of Psychopharmacology, 26: 1185–93.
Collip, D, Myin-Germeys, I, Wichers, M et al (2013) FKBP5 as a possible moderator of the psychosis-inducing effects of childhood trauma. British Journal of Psychiatry, 202: 261–8.
Corsellis, JA, Goldberg, GJ, Norton, AR (1968) ‘Limbic encephalitis’ and its association with carcinoma. Brain, 91: 481–96.
Coyle, JT (2006) Glutamate and schizophrenia: beyond the dopamine hypothesis. Cellular and Molecular Neurobiology, 26: 363–82.
Craddock, N, Owen, MJ (2010) The Kraepelinian dichotomy – going, going… but still not gone. British Journal of Psychiatry, 196: 92–5.
Craddock, N, Sklar, P (2013) Genetics of bipolar disorder. Lancet, 381: 1654–62.
Dalmau, J, Gleichman, AJ, Hughes, EG et al (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurology, 7: 1091–8.
Dameshek, W (1930) White blood cells in dementia praecox and dementia paralytica. Archives of Neurological Psychiatry, 24: 855.
Falkai, P, Möller, H-J (2012) Neurobiology of schizophrenia: from outcome to pathophysiological insights. European Archives of Psychiatry and Clinical Neuroscience, 262: 93–4.
Fineberg, AM, Ellman, LM (2013) Inflammatory cytokines and neurological and neurocognitive alterations in the course of schizophrenia. Biological Psychiatry, 73: 951–66.
Frangou, S, Murray, RM (2000) Schizophrenia (2nd edn). Martin Dunitz.
Gardiner, EJ, Cairns, MJ, Liu, B et al (2013) Gene expression analysis reveals schizophrenia-associated dysregulation of immune pathways in peripheral blood mononuclear cells. Journal of Psychiatric Research, 47: 425–37.
Gordon, J, Barnes, NM (2003) Lymphocytes transport serotonin and dopamine: agony or ecstasy? Trends in Immunology, 24: 438–43.
Howes, OD, Kapur, S (2009) The dopamine hypothesis of schizophrenia. Version III: The final common pathway. Schizophrenia Bulletin, 35: 549–62.
Irani, S, Vincent, A (2011) Autoimmune encephalitis: new awareness, challenging questions. Discovery Medicine, 11: 449–58.
Kinney, DK, Hintz, K, Shearer, EM et al (2010) A unifying hypothesis of schizophrenia: abnormal immune system development may help explain roles of prenatal hazards, post-pubertal onset, stress, genes, climate, infections, and brain dysfunction. Medical Hypotheses, 74: 555–63.
Kluge, M, Schuld, A, Schacht, A et al (2009) Effects of clozapine and olanzapine on cytokine systems are closely linked to weight gain and drug-induced fever. Psychoneuroendocrinology, 34: 118–28.
Lennox, BR, Coles, AJ, Vincent, A (2012) Antibody-mediated encephalitis: a treatable cause of schizophrenia. British Journal of Psychiatry, 200: 92–4.
Maes, M, Bosmans, E, Kenis, G et al (1997) In vivo immunomodulatory effects of clozapine in schizophrenia. Schizophrenia Research, 26: 221–5.
Miller, BJ, Buckley, P, Seabolt, W et al (2011) Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biological Psychiatry, 70: 663–71.
Miller, BJ, Gassama, B, Sebastian, D et al (2013) Meta-analysis of lymphocytes in schizophrenia: clinical status and antipsychotic effects. Biological Psychiatry, 73: 993–9.
Miyaoka, T, Yasukawa, R, Yasuda, H et al (2007) Possible antipsychotic effects of minocycline in patients with schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 31: 304–7.
Monji, A, Kato, T, Kanba, S (2009) Cytokines and schizophrenia: microglia hypothesis of schizophrenia. Psychiatry and Clinical Neurosciences, 63: 257–65.
Mortensen, PB, Pedersen, CB, Westergaard, T et al (1999) Effects of family history and place and season of birth on the risk of schizophrenia. New England Journal of Medicine, 340: 603–8.
Müller, N, Schwarz, MJ (2010a) Immune system and schizophrenia. Current Immunology Reviews, 6: 213–20.
Müller, N, Krause, D, Dehning, S et al (2010b) Celecoxib treatment in an early stage of schizophrenia: results of a randomized, double-blind, placebo-controlled trial of celecoxib augmentation of amisulpride treatment. Schizophrenia Research, 121: 118–24.
Müller, N (2011) Inflammation and schizophrenia: pathophysiological and therapeutic aspects. Minerva Psichiatrica, 52: 205–18.
Müller, N, Myint, AM, Krause, D et al (2013) Anti-inflammatory treatment in schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 42: 146–53.
Myin, GI, Peeters, F, Havermans, R et al (2003) Emotional reactivity to daily life stress in psychosis and affective disorder: an experience sampling study. Acta Psychiatrica Scandinavica, 107: 124–31.
Oh, G, Petronis, A (2008) Environmental studies of schizophrenia through the prism of epigenetics. Schizophrenia Bulletin, 34: 1122–9.
Pedrini, M, Massuda, R, Fries, GR et al (2012) Similarities in serum oxidative stress markers and inflammatory cytokines in patients with overt schizophrenia at early and late stages of chronicity. Journal of Psychiatric Research, 46: 819–24.
Potvin, S, Stip, E, Sepehry, AA et al (2008) Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biological Psychiatry, 63: 801–8.
Raison, CL, Miller, AH (2013) Malaise, melancholia and madness: the evolutionary legacy of an inflammatory bias. Brain, Behavior, and Immunity, 31: 18.
Reichenberg, A, Yirmiya, R, Schuld, A et al (2001) Cytokine-associated emotional and cognitive disturbances in humans. Archives of General Psychiatry, 58: 445–52.
Rickards, HE, Jacob, S, Lennox, B et al (2014) Autoimmune encephalitis: a potentially treatable cause of mental disorder. Advances in Psychiatric Treatment, 20: 92100.
Sainz, J, Mata, I, Barrera, J et al (2012) Inflammatory and immune response genes have significantly altered expression in schizophrenia. Molecular Psychiatry, 18: 1056–7.
Saunders, JC, Muchmore, E (1964) Phenothiazine effect on human antibody synthesis. British Journal of Psychiatry, 110: 84–9.
Schwarz, MJ (2007) The immunological basis of glutamatergic disturbance in schizophrenia: towards an integrated view. In Neuropsychiatric Disorders: An Integrative Approach (eds Gerlach, M, Deckert, J, Double, K et al): 269–80. Springer.
Sham, PC, O'Callaghan, E, Takei, N et al (1992) Schizophrenia following prenatal exposure to influenza epidemics between 1939 and 1960. British Journal of Psychiatry, 160: 461–6.
Silveira, C, Marques-Teixeira, J, De Bastos-Leite, AJ (2012) More than one century of schizophrenia: an evolving perspective. Journal of Nervous and Mental Disease, 200: 1054–7.
Smith, RS, Maes, M (1995) The macrophage-T-lymphocyte theory of schizophrenia: additional evidence. Medical Hypotheses, 45: 135–41.
Stefansson, H, Rujescu, D, Cichon, S et al (2008) Large recurrent microdeletions associated with schizophrenia. Nature, 455: 232–6.
Stefansson, H, Ophoff, RA, Steinberg, S et al (2009) Common variants conferring risk of schizophrenia. Nature, 460: 744–7.
Titulaer, MJ, McCracken, L, Gabilondo, I et al (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurology, 12: 157–65.
Tsutsui, K, Kanbayashi, T, Tanaka, K et al (2012) Anti-NMDA-receptor antibody detected in encephalitis, schizophrenia, and narcolepsy with psychotic features. BMC Psychiatry, 12: 37.
Upthegrove, R (2009) Depression in schizophrenia and early psychosis: implications for assessment and treatment. Advances in Psychiatric Treatment, 15: 372–9.
Upthegrove, R, Atulomah, O, Brunet, K et al (2012) Cultural and social influences of negative illness appraisals in first-episode psychosis. Early Intervention in Psychiatry, 7: 399406.
van de Riet, EHCW, Schieveld, JNM (2013) First-onset psychosis, anti-NMDAR encephalitis, schizophrenia and consultation-liaison psychiatry. General Hospital Psychiatry, 35: 442–3.
van Venrooij, JA, Fluitman, SB, Lijmer, JG et al (2012) Impaired neuroendocrine and immune response to acute stress in medication-naive patients with a first episode of psychosis. Schizophrenia Bulletin, 38: 272–9.
Wekking, E, Nossent, J, van Dam, A et al (2010) Cognitive and emotional disturbances in systemic lupus erythematosus. Psychotherapy and Psychosomatics, 55: 126–31.
Wright, P, Takei, N, Rifkin, L et al (1995) Maternal influenza, obstetric complications, and schizophrenia. American Journal of Psychiatry, 152: 1714–20.
Xiu, MH, Chen, DC, Wang, D et al (2012) Elevated interleukin-18 serum levels in chronic schizophrenia: association with psychopathology. Journal of Psychiatric Research, 46: 1093–8.
Zandi, M, Irani, S, Lang, B et al (2011) Disease-relevant autoantibodies in first episode schizophrenia. Journal of Neurology, 258: 686–8.
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BJPsych Advances
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The immune system and schizophrenia: an update for clinicians

  • Rachel Upthegrove and Nicholas M. Barnes
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