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Immune Dysfunction in Obsessive-Compulsive Disorder: From Risk Factors to Multisystem Involvement

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Immuno-Psychiatry

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Abstract

Immune dysfunction has been proposed as an important component of the pathophysiology of obsessive-compulsive disorder (OCD), motivating innovative research hypotheses with potential clinical interest. In this chapter, we will review published evidence supporting a model for immune dysfunction in OCD as multifactorial, constitutive, and environmental, contributing to illness development, clinical presentation, and multisystem impact. The fact that OCD patients present comorbidity with several systemic illnesses, including auto-immune disorders, and that the majority of recognized risk factors, such as perinatal complications, traumatic life events or childhood infections, induce inflammation, motivated the development of studies trying to achieve a deeper comprehension regarding the association between inflammation and OCD. While case-control studies demonstrated an increase in different inflammatory and oxidative markers, studies evaluating genetic determinants suggested that immunogenetic risk may also be a source of vulnerability for OCD. Lastly, animal models have been contributing to a deeper understanding of the biological mechanisms underlying immune changes in OCD, focusing on the role of microglia and central nervous system (CNS) infections. Thus, similarly to other psychiatric illnesses, systemic dysregulation of the immune system is an important mechanism in OCD pathophysiology, reflecting genetic variability, environmental insults, or the behavioral and socioeconomic impact of the disorder. A better comprehension of immune dysfunction in OCD may ultimately promote the development of novel prevention, diagnosis, and treatment techniques, potentially leading to improved care and quality of life for these patients.

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References

  1. Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry. 2010;15(1):53–63.

    Article  CAS  PubMed  Google Scholar 

  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-V). 5th ed; 2013.

    Book  Google Scholar 

  3. Brady CF. Obsessive-compulsive disorder and common comorbidities. J Clin Psychiatry. 2014;75(1):e02.

    Article  PubMed  Google Scholar 

  4. Albert U, Aguglia A, Chiarle A, Bogetto F, Maina G. Metabolic syndrome and obsessive-compulsive disorder: a naturalistic Italian study. Gen Hosp Psychiatry. 2013;35(2):154–9.

    Article  PubMed  Google Scholar 

  5. Lochner C, Fineberg NA, Zohar J, van Ameringen M, Juven-Wetzler A, Altamura AC, et al. Comorbidity in obsessive-compulsive disorder (OCD): a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS). Compr Psychiatry. 2014;55(7):1513–9.

    Article  PubMed  Google Scholar 

  6. Leckman JF, Denys D, Simpson HB, Mataix-Cols D, Hollander E, Saxena S, et al. Obsessive-compulsive disorder: a review of the diagnostic criteria and possible subtypes and dimensional specifiers for DSM-V. Depress Anxiety. 2010;27(6):507–27.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kugler BB, Lewin AB, Phares V, Geffken GR, Murphy TK, Storch EA. Quality of life in obsessive-compulsive disorder: the role of mediating variables. Psychiatry Res. 2013;206(1):43–9.

    Article  PubMed  Google Scholar 

  8. Erzegovesi S, Cavallini MC, Cavedini P, Diaferia G, Locatelli M, Bellodi L. Clinical predictors of drug response in obsessive-compulsive disorder. J Clin Psychopharmacol. 2001;21(5):488–92.

    Article  CAS  PubMed  Google Scholar 

  9. Mancebo MC, Eisen JL, Sibrava N, Dyck IR, Rasmussen SA. Patient utilization of cognitive-behavioral therapy for OCD. Behav Ther. 2011;42(3):399–412.

    Article  PubMed  Google Scholar 

  10. Hollander E, Stein DJ, Kwon JH, Rowland C, Wong CM, Broatch J, et al. Psychosocial function and economic costs of obsessive-compulsive disorder. CNS Spectr. 1997;2(10):16–25.

    Article  Google Scholar 

  11. Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014;15(6):410–24.

    Article  CAS  PubMed  Google Scholar 

  12. Rotge JY, Aouizerate B, Tignol J, Bioulac B, Burbaud P, Guehl D. The glutamate-based genetic immune hypothesis in obsessive-compulsive disorder. An integrative approach from genes to symptoms. Neuroscience. 2010;165(2):408–17.

    Article  CAS  PubMed  Google Scholar 

  13. Nakao T, Okada K, Kanba S. Neurobiological model of obsessive-compulsive disorder: evidence from recent neuropsychological and neuroimaging findings. Psychiatry Clin Neurosci. 2014;68(8):587–605.

    Article  PubMed  Google Scholar 

  14. Zohar J, Greenberg B, Denys D. Obsessive-compulsive disorder. Handb Clin Neurol. 2012;106:375–90.

    Article  CAS  PubMed  Google Scholar 

  15. Gerentes M, Pelissolo A, Rajagopal K, Tamouza R, Hamdani N. Obsessive-compulsive disorder: autoimmunity and neuroinflammation. Curr Psychiatry Rep. 2019;21(8):78.

    Article  PubMed  Google Scholar 

  16. Lamothe H, Baleyte J-M, Smith P, Pelissolo A, Mallet L. Individualized immunological data for precise classification of OCD patients. Brain Sci. 2018;8(8)

    Google Scholar 

  17. Leboyer M, Oliveira J, Tamouza R, Groc L. Is it time for immunopsychiatry in psychotic disorders? Psychopharmacology. 2016;233(9):1651–60.

    Article  CAS  PubMed  Google Scholar 

  18. Dinn WM, Harris CL, McGonigal KM, Raynard RC. Obsessive-compulsive disorder and immunocompetence. Int J Psychiatry Med. 2001;31(3):311–20.

    Article  CAS  PubMed  Google Scholar 

  19. Marazziti D, Mucci F, Fontenelle LF. Immune system and obsessive-compulsive disorder. Psychoneuroendocrinology. 2018;93:39–44.

    Article  CAS  PubMed  Google Scholar 

  20. Pérez-Vigil A, Fernández de la Cruz L, Brander G, Isomura K, Gromark C, Mataix-Cols D. The link between autoimmune diseases and obsessive-compulsive and tic disorders: a systematic review. Neurosci Biobehav Rev. 2016;71:542–62.

    Article  PubMed  CAS  Google Scholar 

  21. Mataix-Cols D, Frans E, Pérez-Vigil A, Kuja-Halkola R, Gromark C, Isomura K, et al. A total-population multigenerational family clustering study of autoimmune diseases in obsessive-compulsive disorder and Tourette’s/chronic tic disorders. Mol Psychiatry. 2018;23(7):1652–8.

    Article  CAS  PubMed  Google Scholar 

  22. Witthauer CT, Gloster A, Meyer AH, Lieb R. Physical diseases among persons with obsessive compulsive symptoms and disorder: a general population study. Soc Psychiatry Psychiatr Epidemiol. 2014;49(12):2013–22.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Isomura K, Brander G, Chang Z, Kuja-Halkola R, Rück C, Hellner C, et al. Metabolic and cardiovascular complications in obsessive-compulsive disorder: a total population, sibling comparison study with long-term follow-up. Biol Psychiatry. 2018;84(5):324–31.

    Article  PubMed  Google Scholar 

  24. Meier SM, Mattheisen M, Mors O, Schendel DE, Mortensen PB, Plessen KJ. Mortality among persons with obsessive-compulsive disorder in Denmark. JAMA Psychiat. 2016;73(3):268–74.

    Article  Google Scholar 

  25. Zammit S, Owen MJ, Lewis G. Misconceptions about gene-environment interactions in psychiatry. Evid Based Ment Health. 2010;13(3):65–8.

    Article  PubMed  Google Scholar 

  26. Murphy TK, Sajid MW, Goodman WK. Immunology of obsessive-compulsive disorder. Psychiatr Clin North Am. 2006;29(2):445–69.

    Article  PubMed  Google Scholar 

  27. Brander G, Pérez-Vigil A, Larsson H, Mataix-Cols D. Systematic review of environmental risk factors for obsessive-compulsive disorder: a proposed roadmap from association to causation. Neurosci Biobehav Rev. 2016;65:36–62.

    Article  PubMed  Google Scholar 

  28. Baumeister D, Akhtar R, Ciufolini S, Pariante CM, Mondelli V. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Mol Psychiatry. 2016;21(5):642–9.

    Article  CAS  PubMed  Google Scholar 

  29. Depino AM. Perinatal inflammation and adult psychopathology: from preclinical models to humans. Semin Cell Dev Biol. 2018;77:104–14.

    Article  CAS  PubMed  Google Scholar 

  30. Muscatell KA, Brosso SN, Humphreys KL. Socioeconomic status and inflammation: a meta-analysis. Mol Psychiatry. 2018;1

    Google Scholar 

  31. Glaus J, Vandeleur CL, von Känel R, Lasserre AM, Strippoli M-PF, Gholam-Rezaee M, et al. Associations between mood, anxiety or substance use disorders and inflammatory markers after adjustment for multiple covariates in a population-based study. J Psychiatr Res. 2014;58:36–45.

    Article  PubMed  Google Scholar 

  32. Corps KN, Roth TL, McGavern DB. Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol. 2015;72(3):355–62.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Calton EK, Keane KN, Newsholme P, Soares MJ. The impact of vitamin D levels on inflammatory status: a systematic review of immune cell studies. PLoS One. 2015;10(11)

    Google Scholar 

  34. Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998;155(2):264–71.

    Article  CAS  PubMed  Google Scholar 

  35. Orlovska S, Vestergaard CH, Bech BH, Nordentoft M, Vestergaard M, Benros ME. Association of streptococcal throat infection with mental disorders: testing key aspects of the PANDAS hypothesis in a nationwide study. JAMA Psychiat. 2017;74(7):740–6.

    Article  Google Scholar 

  36. Miman O, Mutlu EA, Ozcan O, Atambay M, Karlidag R, Unal S. Is there any role of toxoplasma gondii in the etiology of obsessive-compulsive disorder? Psychiatry Res. 2010;177(1–2):263–5.

    Article  PubMed  Google Scholar 

  37. Akaltun İ, Kara SS, Kara T. The relationship between toxoplasma gondii IgG antibodies and generalized anxiety disorder and obsessive-compulsive disorder in children and adolescents: a new approach. Nord J Psychiatry. 2018;72(1):57–62.

    Article  PubMed  Google Scholar 

  38. Flegr J, Horáček J. Toxoplasma-infected subjects report an obsessive-compulsive disorder diagnosis more often and score higher in obsessive-compulsive inventory. Eur Psychiatry. 2017;40:82–7.

    Article  CAS  PubMed  Google Scholar 

  39. Strittmatter C, Lang W, Wiestler OD, Kleihues P. The changing pattern of human immunodeficiency virus-associated cerebral toxoplasmosis: a study of 46 postmortem cases. Acta Neuropathol (Berl). 1992;83(5):475–81.

    Article  CAS  Google Scholar 

  40. Johnco C, Kugler BB, Murphy TK, Storch EA. Obsessive-compulsive symptoms in adults with Lyme disease. Gen Hosp Psychiatry. 2018;51:85–9.

    Article  PubMed  Google Scholar 

  41. Ercan TE, Ercan G, Severge B, Arpaozu M, Karasu G. Mycoplasma pneumoniae infection and obsessive-compulsive disease: a case report. J Child Neurol. 2008;23(3):338–40.

    Article  PubMed  Google Scholar 

  42. Johnson J, Lucey PA. Encephalitis lethargica, a contemporary cause of catatonic stupor. A report of two cases. Br J Psychiatry. 1987;151:550–2.

    Article  CAS  PubMed  Google Scholar 

  43. Laplane D, Levasseur M, Pillon B, Dubois B, Baulac M, Mazoyer B, et al. Obsessive-compulsive and other behavioural changes with bilateral basal ganglia lesions. A neuropsychological, magnetic resonance imaging and positron tomography study. Brain. 1989;112(3):699–725.

    Article  PubMed  Google Scholar 

  44. Khanna S, Ravi V, Shenoy PK, Chandramukhi A, Channabasavanna SM. Viral antibodies in blood in obsessive compulsive disorder. Indian J Psychiatry. 1997;39(3):190–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Khanna S, Ravi V, Shenoy PK, Chandramukhi A, Channabasavanna SM. Cerebrospinal fluid viral antibodies in obsessive-compulsive disorder in an Indian population. Biol Psychiatry. 1997;41(8):883–90.

    Article  CAS  PubMed  Google Scholar 

  46. Dietrich DE, Zhang Y, Bode L, Münte TF, Hauser U, Schmorl P, et al. Brain potential amplitude varies as a function of Borna disease virus-specific immune complexes in obsessive–compulsive disorder. Mol Psychiatry. 2005;10(6):515.

    Article  CAS  PubMed  Google Scholar 

  47. Pauls DL. The genetics of obsessive-compulsive disorder: a review. Dialogues Clin Neurosci. 2010;12(2):149–63.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Lougee L, Perlmutter SJ, Nicolson R, Garvey MA, Swedo SE. Psychiatric disorders in first-degree relatives of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). J Am Acad Child Adolesc Psychiatry. 2000;39(9):1120–6.

    Article  CAS  PubMed  Google Scholar 

  49. Seixas AAA, Hounie AG, Fossaluza V, Curi M, Alvarenga PG, De Mathis MA, et al. Anxiety disorders and rheumatic fever: is there an association? CNS Spectr. 2008;13(12):1039–46.

    Article  PubMed  Google Scholar 

  50. Hounie AG, Pauls DL, do Rosario-Campos MC, Mercadante MT, Diniz JB, De Mathis MA, et al. Obsessive-compulsive spectrum disorders and rheumatic fever: a family study. Biol Psychiatry. 2007;61(3):266–72.

    Article  PubMed  Google Scholar 

  51. Engel ME, Stander R, Vogel J, Adeyemo AA, Mayosi BM. Genetic susceptibility to acute rheumatic fever: a systematic review and meta-analysis of twin studies. PLoS One. 2011;6(9):e25326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Cappi C, Brentani H, Lima L, Sanders SJ, Zai G, Diniz BJ, et al. Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways. Transl Psychiatry. 2016;6(3):e764.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Komuro A, Imamura T, Saitoh M, Yoshida Y, Yamori T, Miyazono K, et al. Negative regulation of transforming growth factor-beta (TGF-beta) signaling by WW domain-containing protein 1 (WWP1). Oncogene. 2004;23(41):6914–23.

    Article  CAS  PubMed  Google Scholar 

  54. ten Dijke P, Hill CS. New insights into TGF-beta-Smad signalling. Trends Biochem Sci. 2004;29(5):265–73.

    Article  PubMed  CAS  Google Scholar 

  55. Noris M, Remuzzi G. Overview of complement activation and regulation. Semin Nephrol. 2013;33(6):479–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mosaad YM. Clinical role of human leukocyte antigen in health and disease. Scand J Immunol. 2015;82(4):283–306.

    Article  CAS  PubMed  Google Scholar 

  57. Choo SY, The HLA. System: genetics, immunology, clinical testing, and clinical implications. Yonsei Med J. 2007;48(1):11–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Needleman LA, McAllister AK. The major histocompatibility complex and autism spectrum disorder. Dev Neurobiol. 2012;72(10):1288–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Mokhtari R, Lachman HM. The major histocompatibility complex (MHC) in schizophrenia: a review. J Clin Cell Immunol. 2016;7(6)

    Google Scholar 

  60. Thomson G, Valdes AM, Noble JA, Kockum I, Grote MN, Najman J, et al. Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis. Tissue Antigens. 2007;70(2):110–27.

    Article  CAS  PubMed  Google Scholar 

  61. Fogdell-Hahn A, Ligers A, Grønning M, Hillert J, Olerup O. Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease. Tissue Antigens. 2000;55(2):140–8.

    Article  CAS  PubMed  Google Scholar 

  62. Kampstra ASB, Toes REM. HLA class II and rheumatoid arthritis: the bumpy road of revelation. Immunogenetics. 2017;69(8–9):597–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Miyadera H, Tokunaga K. Associations of human leukocyte antigens with autoimmune diseases: challenges in identifying the mechanism. J Hum Genet. 2015;60(11):697–702.

    Article  CAS  PubMed  Google Scholar 

  64. Tamouza R, Oliveira J, Etain B, Bengoufa D, Hamdani N, Manier C, et al. HLA genetics in bipolar disorder. Acta Psychiatr Scand. 2018;138(5):464–71.

    Article  CAS  PubMed  Google Scholar 

  65. Rodriguez N, Morer A, González-Navarro EA, Gassó P, Boloc D, Serra-Pagès C, et al. Human-leukocyte antigen class II genes in early-onset obsessive-compulsive disorder. World J Biol Psychiatry. 2017:1–7.

    Google Scholar 

  66. Johns TG, Bernard CC. The structure and function of myelin oligodendrocyte glycoprotein. J Neurochem. 1999;72(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  67. Peschl P, Bradl M, Höftberger R, Berger T, Reindl M. Myelin oligodendrocyte glycoprotein: deciphering a target in inflammatory demyelinating diseases. Front Immunol. 2017;8

    Google Scholar 

  68. Zai G, Bezchlibnyk YB, Richter MA, Arnold P, Burroughs E, Barr CL, et al. Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder. Am J Med Genet Part B Neuropsychiatr Genet. 2004;129B(1):64–8.

    Article  Google Scholar 

  69. Wu F, Kong L, Zhu Y, Zhou Q, Jiang X, Chang M, et al. The influence of myelin oligodendrocyte glycoprotein on white matter abnormalities in different onset age of drug-Naïve depression. Front Psych. 2018;9

    Google Scholar 

  70. Parameswaran N, Patial S. Tumor necrosis factor-α signaling in macrophages. Crit Rev Eukaryot Gene Expr. 2010;20(2):87–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hounie AG, Cappi C, Cordeiro Q, Sampaio AS, Moraes I, Rosário MC, do Rosario MC, et al. TNF-alpha polymorphisms are associated with obsessive-compulsive disorder. Neurosci Lett. 2008;442(2):86–90.

    Article  CAS  PubMed  Google Scholar 

  72. Cappi C, Muniz RK, Sampaio AS, Cordeiro Q, Brentani H, Palácios SA, et al. Association study between functional polymorphisms in the TNF-alpha gene and obsessive-compulsive disorder. Arq Neuropsiquiatr. 2012;70(2):87–90.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Lüleyap H, Onatoğlu D, Tahiroğlu A, Alptekin D, Yılmaz M, Cetiner S, et al. Association between obsessive compulsive disorder and tumor necrosis factor-α gene −308 (G>a) and −850 (C>T) polymorphisms in Turkish children. Balk J Med Genet. 2012;15(2):61–6.

    Article  Google Scholar 

  74. Jiang C, Ma X, Qi S, Han G, Li Y, Liu Y, et al. Association between TNF-α-238G/A gene polymorphism and OCD susceptibility. Medicine (Baltimore). 2018;97(5)

    Google Scholar 

  75. Zhag X, Yin W, Liu S, Ma X. A case-control association study between obsessive-compulsive disorder (OCD) and the MCP-1 -2518G/a polymorphism in a Chinese sample. Braz J Psychiatry. 2012;34(4):451–3.

    Article  Google Scholar 

  76. Liu S, Liu Y, Yin Y, Zhang X, Ma X. A case-control study of interleukin-12 1188A/C polymorphism in obsessive-compulsive disorder in Chinese population. Acta Neuropsychiatr. 2012;24(3):172–5.

    Article  PubMed  Google Scholar 

  77. Cordeiro Q, Cappi C, Sampaio AS, Palácios SA, Pereira CA, de B, Shavitt RG, et al. Association study between the -62A/T NFKBIL1 polymorphism and obsessive-compulsive disorder. Braz J Psychiatry. 2009;31(2):131–5.

    Article  PubMed  Google Scholar 

  78. Murphy TK, Goodman WK, Fudge MW, Williams RC, Ayoub EM, Dalal M, et al. B lymphocyte antigen D8/17: a peripheral marker for childhood-onset obsessive-compulsive disorder and Tourette’s syndrome? Am J Psychiatry. 1997;154(3):402–7.

    Article  CAS  PubMed  Google Scholar 

  79. Swedo SE, Leonard HL, Mittleman BB, Allen AJ, Rapoport JL, Dow SP, et al. Identification of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections by a marker associated with rheumatic fever. Am J Psychiatry. 1997;154(1):110–2.

    Article  CAS  PubMed  Google Scholar 

  80. Luo F, Leckman JF, Katsovich L, Findley D, Grantz H, Tucker DM, et al. Prospective longitudinal study of children with tic disorders and/or obsessive-compulsive disorder: relationship of symptom exacerbations to newly acquired streptococcal infections. Pediatrics. 2004;113(6):e578–85.

    Article  PubMed  Google Scholar 

  81. Kiessling LS, Marcotte AC, Culpepper L. Antineuronal antibodies: tics and obsessive-compulsive symptoms. J Dev Behav Pediatr. 1994;15(6):421–5.

    Article  CAS  PubMed  Google Scholar 

  82. Peterson BS, Leckman JF, Tucker D, Scahill L, Staib L, Zhang H, et al. Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders. Arch Gen Psychiatry. 2000;57(4):364–72.

    Article  CAS  PubMed  Google Scholar 

  83. Pavone P, Bianchini R, Parano E, Incorpora G, Rizzo R, Mazzone L, et al. Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection. Pediatr Neurol. 2004;30(2):107–10.

    Article  PubMed  Google Scholar 

  84. Dale RC, Heyman I, Giovannoni G, Church AJ. Incidence of anti-brain antibodies in children with obsessive–compulsive disorder. Br J Psychiatry. 2005;187(4):314–9.

    Article  PubMed  Google Scholar 

  85. Barber Y, Toren P, Achiron A, Noy S, Wolmer L, Weizman R, et al. T cell subsets in obsessive-compulsive disorder. Neuropsychobiology. 1996;34(2):63–6.

    Article  CAS  PubMed  Google Scholar 

  86. Marazziti D, Presta S, Pfanner C, Gemignani A, Rossi A, Sbrana S, et al. Immunological alterations in adult obsessive-compulsive disorder. Biol Psychiatry. 1999;46(6):810–4.

    Article  CAS  PubMed  Google Scholar 

  87. Ravindran AV, Griffiths J, Merali Z, Anisman H. Circulating lymphocyte subsets in obsessive compulsive disorder, major depression and normal controls. J Affect Disord. 1999;52(1–3):1–10.

    Article  CAS  PubMed  Google Scholar 

  88. Weizman R, Laor N, Barber Y, Hermesh H, Notti I, Djaldetti M, et al. Cytokine production in obsessive-compulsive disorder. Biol Psychiatry. 1996;40(9):908–12.

    Article  CAS  PubMed  Google Scholar 

  89. Brambilla F, Perna G, Bellodi L, Arancio C, Bertani A, Perini G, et al. Plasma interleukin-1 beta and tumor necrosis factor concentrations in obsessive-compulsive disorders. Biol Psychiatry. 1997;42(11):976–81.

    Article  CAS  PubMed  Google Scholar 

  90. Maes M, Meltzer HY, Bosmans E. Psychoimmune investigation in obsessive-compulsive disorder: assays of plasma transferrin, IL-2 and IL-6 receptor, and IL-1 beta and IL-6 concentrations. Neuropsychobiology. 1994;30(2–3):57–60.

    Article  CAS  PubMed  Google Scholar 

  91. Monteleone P, Catapano F, Fabrazzo M, Tortorella A, Maj M. Decreased blood levels of tumor necrosis factor-alpha in patients with obsessive-compulsive disorder. Neuropsychobiology. 1998;37(4):182–5.

    Article  CAS  PubMed  Google Scholar 

  92. Carpenter LL, Heninger GR, McDougle CJ, Tyrka AR, Epperson CN, Price LH. Cerebrospinal fluid interleukin-6 in obsessive-compulsive disorder and trichotillomania. Psychiatry Res. 2002;112(3):257–62.

    Article  CAS  PubMed  Google Scholar 

  93. Denys D, Fluitman S, Kavelaars A, Heijnen C, Westenberg H. Decreased TNF-alpha and NK activity in obsessive-compulsive disorder. Psychoneuroendocrinology. 2004;29(7):945–52.

    Article  CAS  PubMed  Google Scholar 

  94. Konuk N, Tekin IO, Ozturk U, Atik L, Atasoy N, Bektas S, et al. Plasma levels of tumor necrosis factor-alpha and interleukin-6 in obsessive compulsive disorder. Mediat Inflamm. 2007;65704

    Google Scholar 

  95. Ekinci A, Ekinci O. The relationships between low grade inflammation, demographic and clinical characteristics in patients with obsessive compulsive disorder. Anatolian J Psychiatry. 2017;18(5):438–45.

    Google Scholar 

  96. da Rocha F, Correa H, Lucio TA. Obsessive-compulsive disorder and immunology: a review. Prog Neuro-Psychopharmacol Biol Psychiatry. 2008;32(5):1139–46.

    Article  CAS  Google Scholar 

  97. Gray SM, Bloch MH. Systematic review of proinflammatory cytokines in obsessive-compulsive disorder. Curr Psychiatry Rep. 14(3):220–8.

    Google Scholar 

  98. Denys D, Fluitman S, Kavelaars A, Heijnen C, Westenberg HGM. Effects of paroxetine and venlafaxine on immune parameters in patients with obsessive compulsive disorder. Psychoneuroendocrinology. 31(3):355–60.

    Google Scholar 

  99. Murphy T, Goodman W. Genetics of childhood disorders: XXXIV. Autoimmune disorders, part 7: D8/17 reactivity as an immunological marker of susceptibility to neuropsychiatric disorders. J Am Acad Child Adolesc Psychiatry. 2002;41(1):98–100.

    Article  PubMed  Google Scholar 

  100. Church AJ, Cardoso F, Dale RC, Lees AJ, Thompson EJ, Giovannoni G. Anti-basal ganglia antibodies in acute and persistent Sydenham’s chorea. Neurology. 2002;59(2):227–31.

    Article  CAS  PubMed  Google Scholar 

  101. Cosco TD, Pillinger T, Emam H, Solmi M, Budhdeo S, Matthew Prina A, et al. Immune aberrations in obsessive-compulsive disorder: a systematic review and meta-analysis. Mol Neurobiol. 2019;56(7):4751–9.

    Article  CAS  PubMed  Google Scholar 

  102. Pearlman DM, Vora HS, Marquis BG, Najjar S, Dudley LA. Anti-basal ganglia antibodies in primary obsessive-compulsive disorder: systematic review and meta-analysis. Br J Psychiatry. 2014;205(1):8–16.

    Article  PubMed  Google Scholar 

  103. Bhattacharyya S, Khanna S, Chakrabarty K, Mahadevan A, Christopher R, Shankar SK. Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive disorder. Neuropsychopharmacology. 2009;34(12):2489–96.

    Article  CAS  PubMed  Google Scholar 

  104. Rodríguez N, Morer A, González-Navarro EA, Serra-Pages C, Boloc D, Torres T, et al. Altered frequencies of Th17 and Treg cells in children and adolescents with obsessive-compulsive disorder. Brain Behav Immun. 2019 Oct;81:608–16.

    Article  PubMed  CAS  Google Scholar 

  105. Attwells S, Setiawan E, Wilson AA, Rusjan PM, Mizrahi R, Miler L, et al. Inflammation in the neurocircuitry of obsessive-compulsive disorder. JAMA Psychiat. 2017;74(8):833–40.

    Article  Google Scholar 

  106. Lai AY, Todd KG. Hypoxia-activated microglial mediators of neuronal survival are differentially regulated by tetracyclines. Glia. 2006;53(8):809–16.

    Article  PubMed  Google Scholar 

  107. Esalatmanesh S, Abrishami Z, Zeinoddini A, Rahiminejad F, Sadeghi M, Najarzadegan M-R, et al. Minocycline combination therapy with fluvoxamine in moderate-to-severe obsessive-compulsive disorder: a placebo-controlled, double-blind, randomized trial. Psychiatry Clin Neurosci. 2016;70(11):517–26.

    Article  CAS  PubMed  Google Scholar 

  108. Rodriguez CI, Bender J, Marcus SM, Snape M, Rynn M, Simpson HB. Minocycline augmentation of pharmacotherapy in obsessive-compulsive disorder: an open-label trial. J Clin Psychiatry. 2010;71(9):1247.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012;5(1):9–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem. 2015;97:55–74.

    Article  CAS  PubMed  Google Scholar 

  111. Hassan W, Noreen H, Castro-Gomes V, Mohammadzai I, da Rocha JBT, Landeira-Fernandez J. Association of oxidative stress with psychiatric disorders. Curr Pharm Des. 2016;22(20):2960–74.

    Article  CAS  PubMed  Google Scholar 

  112. Brown NC, Andreazza AC, Young LT. An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Res. 2014;218(1–2):61–8.

    Article  CAS  PubMed  Google Scholar 

  113. Flatow J, Buckley P, Miller BJ. Meta-analysis of oxidative stress in schizophrenia. Biol Psychiatry. 2013;74(6):400–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Jiménez-Fernández S, Gurpegui M, Díaz-Atienza F, Pérez-Costillas L, Gerstenberg M, Correll CU. Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis. J Clin Psychiatry. 2015;76(12):1658–67.

    Article  PubMed  Google Scholar 

  115. Black CN, Bot M, Scheffer PG, Cuijpers P, Penninx BWJH. Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology. 2015;51:164–75.

    Article  CAS  PubMed  Google Scholar 

  116. Liu T, Zhong S, Liao X, Chen J, He T, Lai S, et al. A meta-analysis of oxidative stress markers in depression. PLoS One. 2015;10(10):e0138904.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Andreazza AC, Kauer-Sant’anna M, Frey BN, Bond DJ, Kapczinski F, Young LT, et al. Oxidative stress markers in bipolar disorder: a meta-analysis. J Affect Disord. 2008;111(2–3):135–44.

    Article  CAS  PubMed  Google Scholar 

  118. Maia A, Oliveira J, Lajnef M, Mallet L, Tamouza R, Leboyer M, et al. Oxidative and nitrosative stress markers in obsessive-compulsive disorder: a systematic review and meta-analysis. Acta Psychiatr Scand. 2019;139(5):420–33.

    Article  CAS  PubMed  Google Scholar 

  119. Knight JA. Review: free radicals, antioxidants, and the immune system. Ann Clin Lab Sci. 2000;30(2):145–58.

    CAS  PubMed  Google Scholar 

  120. Meydani SN, Wu D, Santos MS, Hayek MG. Antioxidants and immune response in aged persons: overview of present evidence. Am J Clin Nutr. 1995;62(6 Suppl):1462S–76S.

    Article  CAS  PubMed  Google Scholar 

  121. Oliver G, Dean O, Camfield D, Blair-West S, Ng C, Berk M, et al. N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review. Clin Psychopharmacol Neurosci. 2015;13(1):12–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Smith L, Tracy DK, Giaroli G. What future role might N-acetyl-cysteine have in the treatment of obsessive compulsive and grooming disorders?: a systematic review. J Clin Psychopharmacol. 2016;36(1):57–62.

    Article  CAS  PubMed  Google Scholar 

  123. Berk M, Malhi GS, Gray LJ, Dean OM. The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci. 2013;34(3):167–77.

    Article  CAS  PubMed  Google Scholar 

  124. Afshar H, Roohafza H, Mohammad-Beigi H, Haghighi M, Jahangard L, Shokouh P, et al. N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2012;32(6):797–803.

    Article  CAS  PubMed  Google Scholar 

  125. Gehrmann J, Matsumoto Y, Kreutzberg GW. Microglia: intrinsic immuneffector cell of the brain. Brain Res Brain Res Rev. 1995;20(3):269–87.

    Article  CAS  PubMed  Google Scholar 

  126. Sierra A, Encinas JM, Deudero JJP, Chancey JH, Enikolopov G, Overstreet-Wadiche LS, et al. Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell. 2010;7(4):483–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012;74(4):691–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, et al. Synaptic pruning by microglia is necessary for normal brain development. Science. 2011;333(6048):1456–8.

    Article  CAS  PubMed  Google Scholar 

  129. Tay TL, Savage JC, Hui CW, Bisht K, Tremblay M. Microglia across the lifespan: from origin to function in brain development, plasticity and cognition. J Physiol. 2017;595(6):1929–45.

    Article  CAS  PubMed  Google Scholar 

  130. Greer JM, Capecchi MR. Hoxb8 is required for normal grooming behavior in mice. Neuron. 2002;33(1):23–34.

    Article  CAS  PubMed  Google Scholar 

  131. Holstege JC, de Graaff W, Hossaini M, Cardona Cano S, Jaarsma D, van den Akker E, et al. Loss of Hoxb8 alters spinal dorsal laminae and sensory responses in mice. Proc Natl Acad Sci U S A. 2008;105(17):6338–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Chen S-K, Tvrdik P, Peden E, Cho S, Wu S, Spangrude G, et al. Hematopoietic origin of pathological grooming in Hoxb8 mutant mice. Cell. 2010;141(5):775–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Nagarajan N, Jones BW, West PJ, Marc RE, Capecchi MR. Corticostriatal circuit defects in Hoxb8 mutant mice. Mol Psychiatry. 2018;23(9):1.

    Article  CAS  Google Scholar 

  134. Chen SK, He X, Hu D, Jensen P, Capecchi M. Autoimmunity developed in Hoxb8 knock-out mice (P4082). J Immunol. 2013;190(1 Supplement):51.7.

    Article  Google Scholar 

  135. Toh H, Chitramuthu BP, Bennett HPJ, Bateman A. Structure, function, and mechanism of progranulin; the brain and beyond. J Mol Neurosci. 2011;45(3):538–48.

    Article  CAS  PubMed  Google Scholar 

  136. Sleegers K, Brouwers N, Van Damme P, Engelborghs S, Gijselinck I, van der Zee J, et al. Serum biomarker for progranulin-associated frontotemporal lobar degeneration. Ann Neurol. 2009;65(5):603–9.

    Article  CAS  PubMed  Google Scholar 

  137. Finch N, Baker M, Crook R, Swanson K, Kuntz K, Surtees R, et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain. 2009;132(3):583–91.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Lui H, Zhang J, Makinson SR, Cahill MK, Kelley KW, Huang H-Y, et al. Progranulin deficiency promotes circuit-specific synaptic pruning by microglia via complement activation. Cell. 2016;165(4):921–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Zhan Y, Paolicelli RC, Sforazzini F, Weinhard L, Bolasco G, Pagani F, et al. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat Neurosci. 2014;17(3):400–6.

    Article  CAS  PubMed  Google Scholar 

  140. Park H-S, Francis KP, Yu J, Cleary PP. Membranous cells in nasal-associated lymphoid tissue: a portal of entry for the respiratory mucosal pathogen group A streptococcus. J Immunol. 2003;171(5):2532–7.

    Article  CAS  PubMed  Google Scholar 

  141. Wang B, Dileepan T, Briscoe S, Hyland KA, Kang J, Khoruts A, et al. Induction of TGF-beta1 and TGF-beta1-dependent predominant Th17 differentiation by group A streptococcal infection. Proc Natl Acad Sci U S A. 2010;107(13):5937–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Dileepan T, Smith ED, Knowland D, Hsu M, Platt M, Bittner-Eddy P, et al. Group A Streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific Th17 cells. J Clin Invest. 2016;126(1):303–17.

    Article  PubMed  Google Scholar 

  143. Yaddanapudi K, Hornig M, Serge R, De Miranda J, Baghban A, Villar G, et al. Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Mol Psychiatry. 2010;15(7):712–26.

    Article  CAS  PubMed  Google Scholar 

  144. Oliveira J, Tabouy L, Leboyer M. Immune dysfunction: a common feature of major psychiatric disorders? In: Teixeira AL, Bauer ME, editors. Immunopsychiatry a Clinician’s introduction to the immune basis of mental disorders. Oxford: Oxford University Press; 2018. p. 141–64.

    Chapter  Google Scholar 

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Authors and Affiliations

  1. Champalimaud Research and Clinical Centre, Champalimaud Centre for the Unknown, Lisbon, Portugal

    Ana Maia, Bernardo Barahona-Corrêa, Albino J. Oliveira-Maia & José Oliveira

  2. Department of Psychiatry and Mental Health, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal

    Ana Maia, Bernardo Barahona-Corrêa & Albino J. Oliveira-Maia

  3. NOVA Medical School | Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal

    Ana Maia, Bernardo Barahona-Corrêa, Albino J. Oliveira-Maia & José Oliveira

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  1. Ana Maia
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  2. Bernardo Barahona-Corrêa
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  3. Albino J. Oliveira-Maia
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  4. José Oliveira
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Correspondence to José Oliveira .

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Editors and Affiliations

  1. Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, VIC, Australia

    Michael Berk

  2. University Paris Est Créteil (UPEC), Inserm, IMRB (Translational NeuroPsychiatry lab), AP-HP, DMU IMPACT, AP-HP, Fondation FondaMental, Créteil, France

    Marion Leboyer

  3. UMC Groningen, Groningen, The Netherlands

    Iris E. Sommer

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Maia, A., Barahona-Corrêa, B., Oliveira-Maia, A.J., Oliveira, J. (2021). Immune Dysfunction in Obsessive-Compulsive Disorder: From Risk Factors to Multisystem Involvement. In: Berk, M., Leboyer, M., Sommer, I.E. (eds) Immuno-Psychiatry. Springer, Cham. https://doi.org/10.1007/978-3-030-71229-7_17

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