Obsessive-Compulsive Disorder: Autoimmunity and Neuroinflammation


Purpose of Review

Here, we propose to review the immuno-inflammatory hypothesis in OCD given the concurrent incidence of autoimmune comorbidities, infectious stigma, and raised levels of inflammatory markers in a significant subset of patients. A better understanding of the immune dysfunction in OCD may allow stratifying the patients in order to design personalized pharmaco/psychotherapeutic strategies.

Recent Findings

A persistent low-grade inflammation involving both innate and adaptive immune system with coexisting autoimmune morbidities and stigma of infectious events has been prominently observed in OCD. Hence, specific treatments targeting inflammation/infection are a feasible alternative in OCD.


This review highlights that OCD is associated with low-grade inflammation, neural antibodies, and neuro-inflammatory and auto-immune disorders. In some subset of OCD patients, autoimmunity is likely triggered by specific bacterial, viral, or parasitic agents with overlapping surface epitopes in CNS. Hence, subset-profiling in OCD is warranted to benefit from distinct immune-targeted treatment modalities.

This is a preview of subscription content, access via your institution.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    • Gray SM, Bloch MH. Systematic review of proinflammatory cytokines in obsessive-compulsive disorder. Curr Psychiatry Rep. 2012;14(3):220–8. An inaugural important review of immuno-inflammatory markers involved in OCD.

    PubMed  PubMed Central  Google Scholar 

  2. 2.

    Fontenelle LF, Barbosa IG, Luna JV, de Sousa LP, Abreu MNS, Teixeira AL. A cytokine study of adult patients with obsessive-compulsive disorder. Compr Psychiatry. 2012;53(6):797–804.

    PubMed  Google Scholar 

  3. 3.

    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.

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Rodríguez N, Morer A, González-Navarro EA, Serra-Pages C, Boloc D, Torres T, et al. Inflammatory dysregulation of monocytes in pediatric patients with obsessive-compulsive disorder. J Neuroinflammation. 2017;14(1):261.

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Şimşek Ş, Yüksel T, Çim A, Kaya S. Serum cytokine profiles of children with obsessive-compulsive disorder shows the evidence of autoimmunity. Int J Neuropsychopharmacol. 2016;19(8):pyw027.

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    • Rao NP, Venkatasubramanian G, Ravi V, Kalmady S, Cherian A, Yc JR. Plasma cytokine abnormalities in drug-naïve, comorbidity-free obsessive-compulsive disorder. Psychiatry Res. 2015;229(3):949–52. This study showed significantly greater plasma levels of IL-2, IL-4, IL-6, IL-10 and TNF-α levels in patients with OCD.

    CAS  PubMed  Google Scholar 

  7. 7.

    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.

    CAS  PubMed  Google Scholar 

  8. 8.

    Singer HS, Mascaro-Blanco A, Alvarez K, Morris-Berry C, Kawikova I, Ben-Pazi H, et al. Neuronal antibody biomarkers for Sydenham’s chorea identify a new group of children with chronic recurrent episodic acute exacerbations of tic and obsessive compulsive symptoms following a streptococcal infection. PLoS One. 2015;10(3):e0120499.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Cox CJ, Zuccolo AJ, Edwards EV, Mascaro-Blanco A, Alvarez K, Stoner J, et al. Antineuronal antibodies in a heterogeneous group of youth and young adults with tics and obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2015;25(1):76–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

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

    PubMed  Google Scholar 

  11. 11.

    Morer A, Lázaro L, Sabater L, Massana J, Castro J, Graus F. Antineuronal antibodies in a group of children with obsessive-compulsive disorder and Tourette syndrome. J Psychiatr Res. 2008;42(1):64–8.

    PubMed  Google Scholar 

  12. 12.

    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.

    CAS  PubMed  Google Scholar 

  13. 13.

    Maina G, Albert U, Bogetto F, Borghese C, Berro AC, Mutani R, et al. Anti-brain antibodies in adult patients with obsessive-compulsive disorder. J Affect Disord. 2009;116(3):192–200.

    CAS  PubMed  Google Scholar 

  14. 14.

    Gause C, Morris C, Vernekar S, Pardo-Villamizar C, Grados MA, Singer HS. Antineuronal antibodies in OCD: comparisons in children with OCD-only, OCD+chronic tics and OCD+PANDAS. J Neuroimmunol. 2009;214(1–2):118–24.

    CAS  PubMed  Google Scholar 

  15. 15.

    • 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. A meta-analysis involving anti-basal ganglia antibodies in OCD with a strong but non specific association.

    PubMed  Google Scholar 

  16. 16.

    Kirvan CA, Swedo SE, Heuser JS, Cunningham MW. Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med. 2003;9(7):914–20.

    CAS  PubMed  Google Scholar 

  17. 17.

    Kirvan CA, Swedo SE, Snider LA, Cunningham MW. Antibody-mediated neuronal cell signaling in behavior and movement disorders. J Neuroimmunol. 2006;179(1–2):173–9.

    CAS  PubMed  Google Scholar 

  18. 18.

    Kirvan CA, Cox CJ, Swedo SE, Cunningham MW. Tubulin is a neuronal target of autoantibodies in Sydenham’s chorea. J Immunol. 2007;178(11):7412–21.

    CAS  PubMed  Google Scholar 

  19. 19.

    Chiaie RD, Caronti B, Macrì F, Campi S, Marino M, Corrado A, et al. Anti-purkinje cell and natural autoantibodies in a group of psychiatric patients. Evidences for a correlation with the psychopathological status. Clin Pract Epidemiol Ment Health. 2012;8:81–90.

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Mollace V, Muscoli C, Masini E, Cuzzocrea S, Salvemini D. Modulation of prostaglandin biosynthesis by nitric oxide and nitric oxide donors. Pharmacol Rev. 2005;57(2):217–52.

    CAS  PubMed  Google Scholar 

  21. 21.

    Hamdani N, Doukhan R, Kurtlucan O, Tamouza R, Leboyer M. Immunity, inflammation, and bipolar disorder: diagnostic and therapeutic implications. Curr Psychiatry Rep. 2013;15(9):387.

    PubMed  Google Scholar 

  22. 22.

    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.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, et al. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci. 2006;9(2):268–75.

    CAS  PubMed  Google Scholar 

  24. 24.

    Ueno M, Fujita Y, Tanaka T, Nakamura Y, Kikuta J, Ishii M, et al. Layer V cortical neurons require microglial support for survival during postnatal development. Nat Neurosci. 2013;16(5):543–51.

    CAS  PubMed  Google Scholar 

  25. 25.

    Frick L, Pittenger C. Microglial dysregulation in OCD, Tourette syndrome, and PANDAS. J Immunol Res. 2016;8606057:1–8. https://doi.org/10.1155/2016/8606057.

    Google Scholar 

  26. 26.

    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.

    CAS  PubMed  Google Scholar 

  27. 27.

    •• Attwells S, Setiawan E, Wilson AA, Rusjan PM, Mizrahi R, Miler L, et al. Inflammation in the Neurocircuitry of obsessive-compulsive disorder. JAMA Psychiatry. 2017;74(8):833–40. An original study demonstrating inflammation within the neurocircuitry of OCD (beyond the basal ganglia to include the cortico-striato-thalamo-cortical circuit).

    PubMed  PubMed Central  Google Scholar 

  28. 28.

    Frick LR, Williams K, Pittenger C. Microglial dysregulation in psychiatric disease. Clin Dev Immunol. 2013;2013:608654.

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Adam Y, Meinlschmidt G, Gloster AT, Lieb R. Obsessive-compulsive disorder in the community: 12-month prevalence, comorbidity and impairment. Soc Psychiatry Psychiatr Epidemiol. 2012;47(3):339–49.

    PubMed  Google Scholar 

  30. 30.

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

    Google Scholar 

  31. 31.

    Fullana MA, Vilagut G, Rojas-Farreras S, Mataix-Cols D, de Graaf R, Demyttenaere K, et al. Obsessive-compulsive symptom dimensions in the general population: results from an epidemiological study in six European countries. J Affect Disord. 2010;124(3):291–9.

    CAS  PubMed  Google Scholar 

  32. 32.

    Härter MC, Conway KP, Merikangas KR. Associations between anxiety disorders and physical illness. Eur Arch Psychiatry Clin Neurosci. 2003;253(6):313–20.

    PubMed  Google Scholar 

  33. 33.

    Sareen J, Jacobi F, Cox BJ, Belik S-L, Clara I, Stein MB. Disability and poor quality of life associated with comorbid anxiety disorders and physical conditions. Arch Intern Med. 2006;166(19):2109–16.

    PubMed  Google Scholar 

  34. 34.

    Roy-Byrne PP, Davidson KW, Kessler RC, Asmundson GJG, Goodwin RD, Kubzansky L, et al. Anxiety disorders and comorbid medical illness. Gen Hosp Psychiatry. 2008;30(3):208–25.

    PubMed  Google Scholar 

  35. 35.

    •• 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. A recent study that showed a dramatic association between OCD and metabolic or cardiovascular complications.

    PubMed  Google Scholar 

  36. 36.

    •• 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 Jul;23(7):1652–8. This study suggests a familial link between autoimmune diseases in general, not limited to Streptococcus-related conditions, and OCD.

  37. 37.

    Murphy TK, Storch EA, Turner A, Reid JM, Tan J, Lewin AB. Maternal history of autoimmune disease in children presenting with tics and/or obsessive-compulsive disorder. J Neuroimmunol. 2010;229(1–2):243–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Giedd JN, Rapoport JL, Kruesi MJ, Parker C, Schapiro MB, Allen AJ, et al. Sydenham’s chorea: magnetic resonance imaging of the basal ganglia. Neurology. 1995;45(12):2199–202.

    CAS  PubMed  Google Scholar 

  39. 39.

    • Sigra S, Hesselmark E, Bejerot S. Treatment of PANDAS and PANS: a systematic review. Neurosci Biobehav Rev mars. 2018;86:51–65. A comprehensive review which describes a large panel of treatments for patients suffering from PANDAS and PANS.

    Google Scholar 

  40. 40.

    Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (pediatric acute-onset neuropsychiatric syndrome). Pediatrics & Therapeutics. 2012;2(2):1–8.

    Google Scholar 

  41. 41.

    Cox CJ, Sharma M, Leckman JF, Zuccolo J, Zuccolo A, Kovoor A, et al. Brain human monoclonal autoantibody from sydenham chorea targets dopaminergic neurons in transgenic mice and signals dopamine D2 receptor: implications in human disease. J Immunol. 2013;191(11):5524–41.

    CAS  PubMed  Google Scholar 

  42. 42.

    Brimberg L, Benhar I, Mascaro-Blanco A, Alvarez K, Lotan D, Winter C, et al. Behavioral, pharmacological, and immunological abnormalities after streptococcal exposure: a novel rat model of Sydenham chorea and related neuropsychiatric disorders. Neuropsychopharmacology. 2012;37(9):2076–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Ben-Pazi H, Stoner JA, Cunningham MW. Dopamine receptor autoantibodies correlate with symptoms in Sydenham’s chorea. PLoS One. 2013;8(9):e73516.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Orefici G, Cardona F, Cox CJ, Cunningham MW. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). In: Ferretti JJ, Stevens DL, Fischetti VA, eds. Streptococcus pyogenes : Basic Biology to Clinical Manifestations [Internet]. Oklahoma City (OK): University of Oklahoma Health Sciences Center; 2016.

  45. 45.

    Perlmutter SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL, et al. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet. 1999;354(9185):1153–8.

    CAS  PubMed  Google Scholar 

  46. 46.

    Cunningham MW. Streptococcus and rheumatic fever. Curr Opin Rheumatol. 2012;24(4):408–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Cunningham MW, Cox CJ. Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond. Acta Physiol. 2016;216(1):90–100.

    CAS  Google Scholar 

  48. 48.

    Lin H, Williams KA, Katsovich L, Findley DB, Grantz H, Lombroso PJ, et al. Streptococcal upper respiratory tract infections and psychosocial stress predict future tic and obsessive-compulsive symptom severity in children and adolescents with Tourette syndrome and obsessive-compulsive disorder. Biol Psychiatry. 2010;67(7):684–91.

    PubMed  Google Scholar 

  49. 49.

    Murphy TK, Storch EA, Lewin AB, Edge PJ, Goodman WK. Clinical factors associated with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. J Pediatr. f2012;160(2):314–319.

    PubMed  Google Scholar 

  50. 50.

    Cardona F, Orefici G. Group a streptococcal infections and tic disorders in an Italian pediatric population. J Pediatr. 2001;138(1):71–5.

    CAS  PubMed  Google Scholar 

  51. 51.

    Leslie DL, Kozma L, Martin A, Landeros A, Katsovich L, King RA, et al. Neuropsychiatric disorders associated with streptococcal infection: a case-control study among privately insured children. J Am Acad Child Adolesc Psychiatry. 2008;47(10):1166–72.

    PubMed  PubMed Central  Google Scholar 

  52. 52.

    Mell LK, Davis RL, Owens D. Association between streptococcal infection and obsessive-compulsive disorder, Tourette’s syndrome, and tic disorder. Pediatrics. 2005;116(1):56–60.

    PubMed  Google Scholar 

  53. 53.

    Murphy ML, Pichichero ME. Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection (PANDAS). Arch Pediatr Adolesc Med. 2002;156(4):356–61.

    PubMed  Google Scholar 

  54. 54.

    Macerollo A, Martino D. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an evolving concept. Tremor other Hyperkinet Mov. N Y. 2013:3.

  55. 55.

    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.

    PubMed  Google Scholar 

  56. 56.

    Kurlan R, Johnson D, Kaplan EL. Tourette syndrome study group. Streptococcal infection and exacerbations of childhood tics and obsessive-compulsive symptoms: a prospective blinded cohort study. Pediatrics. 2008;121(6):1188–97.

    PubMed  Google Scholar 

  57. 57.

    Leckman JF, King RA, Gilbert DL, Coffey BJ, Singer HS, Dure LS, et al. Streptococcal upper respiratory tract infections and exacerbations of tic and obsessive-compulsive symptoms: a prospective longitudinal study. J Am Acad Child Adolesc Psychiatry. 2011;50(2):108–118.e3.

    PubMed  Google Scholar 

  58. 58.

    Murphy TK, Sajid M, Soto O, Shapira N, Edge P, Yang M, et al. Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics. Biol Psychiatry. 2004;55(1):61–8.

    PubMed  Google Scholar 

  59. 59.

    Schrag A, Gilbert R, Giovannoni G, Robertson MM, Metcalfe C, Ben-Shlomo Y. Streptococcal infection, Tourette syndrome, and OCD: is there a connection? Neurology. 2009;73(16):1256–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    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.

    PubMed  Google Scholar 

  61. 61.

    Yaramiş A, Hergüner S, Kara B, Tatli B, Tüzün U, Ozmen M. Cerebral vasculitis and obsessive-compulsive disorder following varicella infection in childhood. Turk J Pediatr. 2009;51(1):72–5.

    PubMed  Google Scholar 

  62. 62.

    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, 519–20.

    CAS  PubMed  Google Scholar 

  63. 63.

    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.

    PubMed  Google Scholar 

  64. 64.

    Cong W, Dong W, Bai L, Wang X-Y, Ni X-T, Qian A-D, et al. Seroprevalence and associated risk factors of toxoplasma gondii infection in psychiatric patients: a case-control study in eastern China. Epidemiol Infect. 2015;143(14):3103–9.

    CAS  PubMed  Google Scholar 

  65. 65.

    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.

    PubMed  Google Scholar 

  66. 66.

    • 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. An original study associating OCD with T. gondii.

    CAS  PubMed  Google Scholar 

  67. 67.

    Garvey MA, Perlmutter SJ, Allen AJ, Hamburger S, Lougee L, Leonard HL, et al. A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biol Psychiatry. 1999;45(12):1564–71.

    CAS  PubMed  Google Scholar 

  68. 68.

    Snider LA, Lougee L, Slattery M, Grant P, Swedo SE. Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol Psychiatry. 2005;57(7):788–92.

    CAS  PubMed  Google Scholar 

  69. 69.

    Murphy TK, Brennan EM, Johnco C, Parker-Athill EC, Miladinovic B, Storch EA, et al. A double-blind randomized placebo-controlled pilot study of azithromycin in youth with acute-onset obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2017;27(7):640–51.

    CAS  PubMed  Google Scholar 

  70. 70.

    Murphy TK, Parker-Athill EC, Lewin AB, Storch EA, Mutch PJ. Cefdinir for recent-onset pediatric neuropsychiatric disorders: a pilot randomized trial. Journal of Child and Adolescent Psychopharmacology. 2014;25(1):57–64.

    PubMed  Google Scholar 

  71. 71.

    Calaprice D, Tona J, Murphy TK. Treatment of pediatric acute-onset neuropsychiatric disorder in a large survey population. J Child Adolesc Psychopharmacol. 2018;28(2):92–103.

    PubMed  PubMed Central  Google Scholar 

  72. 72.

    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.

    CAS  PubMed  Google Scholar 

  73. 73.

    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):1247–9.

    PubMed  PubMed Central  Google Scholar 

  74. 74.

    Stryjer R, Budnik D, Ebert T, Green T, Polak L, Weizman S, et al. Amantadine augmentation therapy for obsessive compulsive patients resistant to SSRIs-an open-label study. Clin Neuropharmacol. 2014;37(3):79–81.

    CAS  PubMed  Google Scholar 

  75. 75.

    Huber TJ, Dietrich DE, Emrich HM. Possible use of amantadine in depression. Pharmacopsychiatry. 1999;32(2):47–55.

    CAS  PubMed  Google Scholar 

  76. 76.

    Brynska A, Tomaszewicz-Libudzic E, Wolanczyk T. Obsessive-compulsive disorder and acquired toxoplasmosis in two children. Eur Child Adolesc Psychiatry. 2001;10(3):200–4.

    CAS  PubMed  Google Scholar 

  77. 77.

    Spartz EJ, Freeman GM, Brown K, Farhadian B, Thienemann M, Frankovich J. Course of neuropsychiatric symptoms after introduction and removal of nonsteroidal anti-inflammatory drugs: a pediatric observational study. J Child Adolesc Psychopharmacol. 2017;27(7):652–9.

    CAS  PubMed  Google Scholar 

  78. 78.

    Brown KD, Farmer C, Freeman GM, Spartz EJ, Farhadian B, Thienemann M, et al. Effect of early and prophylactic nonsteroidal anti-inflammatory drugs on flare duration in pediatric acute-onset neuropsychiatric syndrome: an observational study of patients followed by an academic community-based pediatric acute-onset neuropsychiatric syndrome clinic. J Child Adolesc Psychopharmacol. 2017;27(7):619–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Paydary K, Akamaloo A, Ahmadipour A, Pishgar F, Emamzadehfard S, Akhondzadeh S. N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder: randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther. 2016;41(2):214–9.

    CAS  PubMed  Google Scholar 

  80. 80.

    Latimer ME, L’Etoile N, Seidlitz J, Swedo SE. Therapeutic plasma apheresis as a treatment for 35 severely ill children and adolescents with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Journal of Child and Adolescent Psychopharmacology. 2015;25(1):70–5.

    PubMed  PubMed Central  Google Scholar 

  81. 81.

    Elia J, Dell ML, Friedman DF, Zimmerman RA, Balamuth N, Ahmed AA, et al. PANDAS with catatonia: a case report. Therapeutic response to lorazepam and plasmapheresis. J Am Acad Child Adolesc Psychiatry. 2005;44(11):1145–50.

    PubMed  Google Scholar 

  82. 82.

    Frankovich J, Thienemann M, Rana S, Chang K. Five youth with pediatric acute-onset neuropsychiatric syndrome of differing etiologies. Journal of Child and Adolescent Psychopharmacology. 2015;25(1):31–7.

    PubMed  PubMed Central  Google Scholar 

  83. 83.

    Allen AJ, Leonard HL, Swedo SE. Case study: a new infection-triggered, autoimmune subtype of pediatric OCD and Tourette’s syndrome. J Am Acad Child Adolesc Psychiatry. 1995;34(3):307–11.

    CAS  PubMed  Google Scholar 

  84. 84.

    Kovacevic M, Grant P, Swedo SE. Use of intravenous immunoglobulin in the treatment of twelve youths with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. J Child Adolesc Psychopharmacol. 2015;25(1):65–9.

    PubMed  PubMed Central  Google Scholar 

  85. 85.

    Williams KA, Swedo SE, Farmer CA, Grantz H, Grant PJ, D’Souza P, et al. Randomized, controlled trial of intravenous immunoglobulin for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. J Am Acad Child Adolesc Psychiatry. 2016;55(10):860–867.e2.

    PubMed  Google Scholar 

  86. 86.

    Murphy TK, Lewin AB, Parker-Athill EC, Storch EA, Mutch PJ. Tonsillectomies and adenoidectomies do not prevent the onset of pediatric autoimmune neuropsychiatric disorder associated with group a streptococcus. Pediatr Infect Dis J. 2013;32(8):834–8.

    PubMed  PubMed Central  Google Scholar 

  87. 87.

    Demesh D, Virbalas JM, Bent JP. The role of tonsillectomy in the treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). JAMA Otolaryngol Head Neck Surg. 2015;141(3):272–5.

    PubMed  Google Scholar 

  88. 88.

    Pavone P, Rapisarda V, Serra A, Nicita F, Spalice A, Parano E, et al. Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment. Int J Immunopathol Pharmacol. 2014;27(3):371–8.

    CAS  PubMed  Google Scholar 

  89. 89.

    Lamothe H, Baleyte JM, Smith P, Pelissolo A, Mallet L. Individualized immunological data for precise classification of OCD patients. Brain Sci. 2018;9(8):8.

    Google Scholar 

Download references


The editors would like to thank Dr. Leonardo Fontenelle for taking the time to review this manuscript.

Author information



Corresponding author

Correspondence to Nora Hamdani.

Ethics declarations

Conflict of Interest

Mona Gerentes, Krishnamoorthy Rajagopal, Ryad Tamouza, and Nora Hamdani each declare no potential conflicts of interest.

Antoine Pelissolo is a section editor for Current Psychiatry Reports.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Anxiety Disorders

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gerentes, M., Pelissolo, A., Rajagopal, K. et al. Obsessive-Compulsive Disorder: Autoimmunity and Neuroinflammation. Curr Psychiatry Rep 21, 78 (2019). https://doi.org/10.1007/s11920-019-1062-8

Download citation


  • Autoimmunity
  • Infections
  • Inflammation
  • OCD