Obsessive–compulsive disorder

Abstract

Obsessive–compulsive disorder (OCD) is a highly prevalent and chronic condition that is associated with substantial global disability. OCD is the key example of the ‘obsessive–compulsive and related disorders’, a group of conditions which are now classified together in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the International Classification of Diseases, 11th Revision, and which are often underdiagnosed and undertreated. In addition, OCD is an important example of a neuropsychiatric disorder in which rigorous research on phenomenology, psychobiology, pharmacotherapy and psychotherapy has contributed to better recognition, assessment and outcomes. Although OCD is a relatively homogenous disorder with similar symptom dimensions globally, individualized assessment of symptoms, the degree of insight, and the extent of comorbidity is needed. Several neurobiological mechanisms underlying OCD have been identified, including specific brain circuits that underpin OCD. In addition, laboratory models have demonstrated how cellular and molecular dysfunction underpins repetitive stereotyped behaviours, and the genetic architecture of OCD is increasingly understood. Effective treatments for OCD include serotonin reuptake inhibitors and cognitive–behavioural therapy, and neurosurgery for those with intractable symptoms. Integration of global mental health and translational neuroscience approaches could further advance knowledge on OCD and improve clinical outcomes.

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Fig. 1: Obsessive–compulsive and related disorders.
Fig. 2: OCD symptom dimensions.
Fig. 3: Comorbidities of OCD.
Fig. 4: Circuits involved in OCD.
Fig. 5: Lifespan changes related to disease stage — brain changes as a cause and consequence of OCD.
Fig. 6: OCD treatment algorithm.
Fig. 7: Targets for treatment.

References

  1. 1.

    Robbins, T. W., Vaghi, M. M. & Banca, P. Obsessive-compulsive disorder: puzzles and prospects. Neuron 102, 27–47 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  2. 2.

    Mataix-Cols, D., do Rosario-Campos, M. C. & Leckman, J. F. A. Multidimensional model of obsessive-compulsive disorder. Am. J. Psychiatry 162, 228–238 (2005).

    PubMed  Article  PubMed Central  Google Scholar 

  3. 3.

    Bloch, M. H., Landeros-Weisenberger, A., Rosario, M. C., Pittenger, C. & Leckman, J. F. Meta-analysis of the symptom structure of obsessive-compulsive disorder. Am. J. Psychiatry 165, 1532–1542 (2008).

    PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Taylor, S. et al. Musical obsessions: a comprehensive review of neglected clinical phenomena. J. Anxiety Disord. 28, 580–589 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  5. 5.

    Stein, D. J., Hollander, E. & Josephson, S. C. Serotonin reuptake blockers for the treatment of obsessional jealousy. J. Clin. Psychiatry 55, 30–33 (1994).

  6. 6.

    Greenberg, D. & Huppert, J. D. Scrupulosity: a unique subtype of obsessive-compulsive disorder. Curr. Psychiatry Rep. 12, 282–289 (2010).

    PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    Phillips, K. A. et al. Should an obsessive-compulsive spectrum grouping of disorders be included in DSM-V? Depress. Anxiety 27, 528–555 (2010). This review provides the rationale for the DSM-5 decision to include a new chapter on OCRDs.

    PubMed  PubMed Central  Article  Google Scholar 

  8. 8.

    Stein, D. J. et al. The classification of obsessive–compulsive and related disorders in the ICD-11. J. Affect. Disord. 190, 663–674 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    Bienvenu, O. J. et al. The relationship of obsessive–compulsive disorder to possible spectrum disorders: results from a family study. Biol. Psychiatry 48, 287–293 (2000).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  10. 10.

    Monzani, B., Rijsdijk, F., Harris, J. & Mataix-Cols, D. The structure of genetic and environmental risk factors for dimensional representations of DSM-5 obsessive-compulsive spectrum disorders. JAMA Psychiatry 71, 182–189 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  11. 11.

    Karno, M. The epidemiology of obsessive-compulsive disorder in five US communities. Arch. Gen. Psychiatry 45, 1094 (1988).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  12. 12.

    Baxter, A. J., Vos, T., Scott, K. M., Ferrari, A. J. & Whiteford, H. A. The global burden of anxiety disorders in 2010. Psychol. Med. 44, 2363–2374 (2014). This systematic review provides the foundation for estimations of the global burden of anxiety and related disorders.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

    Fontenelle, L. F., Mendlowicz, M. V. & Versiani, M. The descriptive epidemiology of obsessive–compulsive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 30, 327–337 (2006).

    PubMed  Article  PubMed Central  Google Scholar 

  14. 14.

    Ruscio, A. M., Stein, D. J., Chiu, W. T. & Kessler, R. C. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol. Psychiatry 15, 53–63 (2008). This community survey provides data on the prevalence and comorbidity of OCD in the general population.

    PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Fontenelle, L. F. & Hasler, G. The analytical epidemiology of obsessive–compulsive disorder: risk factors and correlates. Prog. Neuropsychopharmacol. Biol. Psychiatry 32, 1–15 (2008).

    PubMed  Article  PubMed Central  Google Scholar 

  16. 16.

    Russell, E. J., Fawcett, J. M. & Mazmanian, D. Risk of obsessive-compulsive disorder in pregnant and postpartum women. J. Clin. Psychiatry 74, 377–385 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  17. 17.

    Sharma, E., Thennarasu, K. & Reddy, Y. C. J. Long-term outcome of obsessive-compulsive disorder in adults. J. Clin. Psychiatry 75, 1019–1027 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  18. 18.

    Lewis-Fernández, R. et al. Culture and the anxiety disorders: recommendations for DSM-V. Depress. Anxiety 27, 212–229 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Isomura, K. et al. Metabolic and cardiovascular complications in obsessive-compulsive disorder: a total population, sibling comparison study with long-term follow-up. Biol. Psychiatry 84, 324–331 (2018).

    PubMed  Article  Google Scholar 

  20. 20.

    Meier, S. M. et al. Mortality among persons with obsessive-compulsive disorder in Denmark. JAMA Psychiatry 73, 268–274 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Nelson, E. & Rice, J. Stability of diagnosis of obsessive-compulsive disorder in the Epidemiologic Catchment Area study. Am. J. Psychiatry 154, 826–831 (1997).

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    Weissman, M. M. et al. The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. J. Clin. Psychiatry 55, 5–10 (1994).

    PubMed  Google Scholar 

  23. 23.

    Stein, D. J., Scott, K. M., de Jonge, P. & Kessler, R. C. Epidemiology of anxiety disorders: from surveys to nosology and back. Dialogues Clin. Neurosci. 19, 127–136 (2017).

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Taylor, S. Etiology of obsessions and compulsions: a meta-analysis and narrative review of twin studies. Clin. Psychol. Rev. 31, 1361–1372 (2011).

    PubMed  Article  Google Scholar 

  25. 25.

    Leckman, J. F. et al. Obsessive-compulsive disorder: a review of the diagnostic criteria and possible subtypes and dimensional specifiers for DSM-V. Depress. Anxiety 27, 507–527 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

    Taylor, S. Molecular genetics of obsessive–compulsive disorder: a comprehensive meta-analysis of genetic association studies. Mol. Psychiatry 18, 799–805 (2012).

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Taylor, S. Disorder-specific genetic factors in obsessive-compulsive disorder: a comprehensive meta-analysis. Am. J. Med. Genet. B Neuropsychiatr. Genet. 171, 325–332 (2015).

    Article  CAS  Google Scholar 

  28. 28.

    International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) & OCD Collaborative Genetics Association Studies (OCGAS). Revealing the complex genetic architecture of obsessive–compulsive disorder using meta-analysis. Mol. Psychiatry 23, 1181–1188 (2017). This paper comprises the largest analysis of genome-wide association studies in OCD.

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    McGrath, L. M. et al. Copy number variation in obsessive-compulsive disorder and Tourette syndrome: a cross-disorder study. J. Am. Acad. Child Adolesc. Psychiatry 53, 910–919 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    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. 65, 36–62 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  31. 31.

    Dykshoorn, K. L. Trauma-related obsessive–compulsive disorder: a review. Health Psychol. Behav. Med. 2, 517–528 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Miller, M. L. & Brock, R. L. The effect of trauma on the severity of obsessive-compulsive spectrum symptoms: a meta-analysis. J. Anxiety Disord. 47, 29–44 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  33. 33.

    Mufford, M. S. et al. Neuroimaging genomics in psychiatry—a translational approach. Genome Med. 9, 102 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Wolpe, J. The systematic desensitization treatment of neuroses. J. Nerv. Ment. Dis. 132, 189–203 (1961).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    Rachman, S., Hodgson, R. & Marks, I. M. The treatment of chronic obsessive-compulsive neurosis. Behav. Res. Ther. 9, 237–247 (1971).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  36. 36.

    Rachman, S. Obsessional ruminations. Behav. Res. Ther. 9, 229–235 (1971).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  37. 37.

    Salkovskis, P. M. Obsessional-compulsive problems: a cognitive-behavioural analysis. Behav. Res. Ther. 23, 571–583 (1985).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  38. 38.

    Craske, M. G., Treanor, M., Conway, C. C., Zbozinek, T. & Vervliet, B. Maximizing exposure therapy: an inhibitory learning approach. Behav. Res. Ther. 58, 10–23 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    Jacoby, R. J. & Abramowitz, J. S. Inhibitory learning approaches to exposure therapy: a critical review and translation to obsessive-compulsive disorder. Clin. Psychol. Rev. 49, 28–40 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Obsessive Compulsive Cognitions Working Group. Cognitive assessment of obsessive-compulsive disorder. Behav. Res. Ther. 35, 667–681 (1997).

    Article  Google Scholar 

  41. 41.

    Stein, D. J., Goodman, W. K. & Rauch, S. L. The cognitive-affective neuroscience of obsessive-compulsive disorder. Curr. Psychiatry Rep. 2, 341–346 (2000).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  42. 42.

    Benzina, N., Mallet, L., Burguière, E., N’Diaye, K. & Pelissolo, A. Cognitive dysfunction in obsessive-compulsive disorder. Curr. Psychiatry Rep. 18, 80 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  43. 43.

    Wood, J. & Ahmari, S. E. A. Framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors. Front. Syst. Neurosci. 9, 171 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  44. 44.

    Burguière, E., Monteiro, P., Mallet, L., Feng, G. & Graybiel, A. M. Striatal circuits, habits, and implications for obsessive–compulsive disorder. Curr. Opin. Neurobiol. 30, 59–65 (2015).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  45. 45.

    Kalueff, A. V. et al. Neurobiology of rodent self-grooming and its value for translational neuroscience. Nat. Rev. Neurosci. 17, 45–59 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  46. 46.

    Baxter, L. R. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch. Gen. Psychiatry 49, 681 (1992).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  47. 47.

    Kwon, J. S., Jang, J. H., Choi, J.-S. & Kang, D.-H. Neuroimaging in obsessive–compulsive disorder. Expert Rev. Neurother. 9, 255–269 (2009).

    PubMed  Article  PubMed Central  Google Scholar 

  48. 48.

    van den Heuvel, O. A. et al. Brain circuitry of compulsivity. Eur. Neuropsychopharmacol. 26, 810–827 (2016).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  49. 49.

    van Velzen, L. S., Vriend, C., de Wit, S. J. & van den Heuvel, O. A. Response inhibition and interference control in obsessive-compulsive spectrum disorders. Front. Hum. Neurosci. 8, 419 (2014).

    PubMed  PubMed Central  Google Scholar 

  50. 50.

    Rotge, J.-Y. et al. Provocation of obsessive-compulsive symptoms: a quantitative voxel-based meta-analysis of functional neuroimaging studies. J. Psychiatry Neurosci. 33, 405–412 (2008).

    PubMed  PubMed Central  Google Scholar 

  51. 51.

    Thorsen, A. L. et al. Emotional processing in obsessive-compulsive disorder: a systematic review and meta-analysis of 25 functional neuroimaging studies. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 3, 563–571 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    Del Casale, A. et al. Executive functions in obsessive–compulsive disorder: an activation likelihood estimate meta-analysis of fMRI studies. World J. Biol. Psychiatry 17, 378–393 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  53. 53.

    Eng, G. K., Sim, K. & Chen, S.-H. A. Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: an integrative review. Neurosci. Biobehav. Rev. 52, 233–257 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  54. 54.

    Gillan, C. M., Robbins, T. W., Sahakian, B. J., van den Heuvel, O. A. & van Wingen, G. The role of habit in compulsivity. Eur. Neuropsychopharmacol. 26, 828–840 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Rasgon, A. et al. Neural correlates of affective and non-affective cognition in obsessive compulsive disorder: a meta-analysis of functional imaging studies. Eur. Psychiatry 46, 25–32 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  56. 56.

    Williams, L. M. Precision psychiatry: a neural circuit taxonomy for depression and anxiety. Lancet Psychiatry 3, 472–480 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Sprooten, E. et al. Addressing reverse inference in psychiatric neuroimaging: meta-analyses of task-related brain activation in common mental disorders. Hum. Brain Mapp. 38, 1846–1864 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  58. 58.

    Fineberg, N. A. et al. Mapping compulsivity in the DSM-5 obsessive compulsive and related disorders: cognitive domains, neural circuitry, and treatment. Int. J. Neuropsychopharmacol. 21, 42–58 (2017).

    PubMed Central  Article  CAS  Google Scholar 

  59. 59.

    Carlisi, C. O. et al. Shared and disorder-specific neurocomputational mechanisms of decision-making in autism spectrum disorder and obsessive-compulsive disorder. Cereb. Cortex 27, 5804–5816 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  60. 60.

    Norman, L. J. et al. Neural dysfunction during temporal discounting in paediatric attention-deficit/hyperactivity disorder and obsessive-compulsive disorder. Psychiatry Res. Neuroimaging 269, 97–105 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  61. 61.

    Fan, S. et al. Trans-diagnostic comparison of response inhibition in Tourette’s disorder and obsessive-compulsive disorder. World J. Biol. Psychiatry 19, 527–537 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  62. 62.

    Norman, L. J. et al. Structural and functional brain abnormalities in attention-deficit/hyperactivity disorder and obsessive-compulsive disorder. JAMA Psychiatry 73, 815 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  63. 63.

    Pujol, J. et al. Mapping structural brain alterations in obsessive-compulsive disorder. Arch. Gen. Psychiatry 61, 720 (2004).

    PubMed  Article  PubMed Central  Google Scholar 

  64. 64.

    van den Heuvel, O. A. et al. The major symptom dimensions of obsessive-compulsive disorder are mediated by partially distinct neural systems. Brain 132, 853–868 (2008).

    PubMed  Article  PubMed Central  Google Scholar 

  65. 65.

    Radua, J. & Mataix-Cols, D. Voxel-wise meta-analysis of grey matter changes in obsessive–compulsive disorder. Br. J. Psychiatry 195, 393–402 (2009).

    PubMed  Article  PubMed Central  Google Scholar 

  66. 66.

    Radua, J., van den Heuvel, O. A., Surguladze, S. & Mataix-Cols, D. Meta-analytical comparison of voxel-based morphometry studies in obsessive-compulsive disorder versus other anxiety disorders. Arch. Gen. Psychiatry 67, 701–711 (2010).

    PubMed  Article  PubMed Central  Google Scholar 

  67. 67.

    de Wit, S. J. et al. Multicenter voxel-based morphometry mega-analysis of structural brain scans in obsessive-compulsive disorder. Am. J. Psychiatry 171, 340–349 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  68. 68.

    Fouche, J.-P. et al. Cortical thickness in obsessive–compulsive disorder: multisite mega-analysis of 780 brain scans from six centres. Br. J. Psychiatry 210, 67–74 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  69. 69.

    Subirà, M. et al. Structural covariance of neostriatal and limbic regions in patients with obsessive–compulsive disorder. J. Psychiatry Neurosci. 41, 115–123 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  70. 70.

    Thompson, P. M. et al. ENIGMA and the individual: predicting factors that affect the brain in 35 countries worldwide. NeuroImage 145, 389–408 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  71. 71.

    Boedhoe, P. S. W. et al. Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis. Am. J. Psychiatry 174, 60–69 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  72. 72.

    Goodkind, M. et al. Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry 72, 305–315 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  73. 73.

    Boedhoe, P. S. W. et al. Cortical abnormalities associated with pediatric and adult obsessive-compulsive disorder: findings from the ENIGMA Obsessive-Compulsive Disorder Working Group. Am. J. Psychiatry 175, 453–462 (2018). Together with Boedhoe et al. (2017), this paper comprises the largest brain imaging study of OCD.

    PubMed  Article  PubMed Central  Google Scholar 

  74. 74.

    Radua, J. et al. Multimodal voxel-based meta-analysis of white matter abnormalities in obsessive–compulsive disorder. Neuropsychopharmacology 39, 1547–1557 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  75. 75.

    Jenkins, L. M. et al. Shared white matter alterations across emotional disorders: a voxel-based meta-analysis of fractional anisotropy. Neuroimage Clin. 12, 1022–1034 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  76. 76.

    Bandelow, B. et al. Biological markers for anxiety disorders, OCD and PTSD: a consensus statement. Part II: neurochemistry, neurophysiology and neurocognition. World J. Biol. Psychiatry 18, 162–214 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  77. 77.

    Kim, E. et al. Altered serotonin transporter binding potential in patients with obsessive-compulsive disorder under escitalopram treatment: [11C]DASB PET study. Psychol. Med. 46, 357–366 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  78. 78.

    Nikolaus, S., Antke, C., Beu, M. & Müller, H.-W. Cortical GABA, striatal dopamine and midbrain serotonin as the key players in compulsive and anxiety disorders — results from in vivo imaging studies. Rev. Neurosci. 21, 119–139 (2010).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  79. 79.

    Goodman, W. K. et al. Beyond the serotonin hypothesis: a role for dopamine in some forms of obsessive compulsive disorder? J. Clin. Psychiatry 51, 36–43 (1990).

    PubMed  PubMed Central  Google Scholar 

  80. 80.

    Olver, J. S. et al. Dopamine D1 receptor binding in the anterior cingulate cortex of patients with obsessive–compulsive disorder. Psychiatry Res. 183, 85–88 (2010).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  81. 81.

    Ducasse, D. et al. D2 and D3 dopamine receptor affinity predicts effectiveness of antipsychotic drugs in obsessive-compulsive disorders: a metaregression analysis. Psychopharmacology 231, 3765–3770 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  82. 82.

    Brennan, B. P., Rauch, S. L., Jensen, J. E. & Pope, H. G. A. Critical review of magnetic resonance spectroscopy studies of obsessive-compulsive disorder. Biol. Psychiatry 73, 24–31 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  83. 83.

    Bhattacharyya, S. et al. Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive–compulsive disorder. Neuropsychopharmacology 34, 2489–2496 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  84. 84.

    Stewart, S. E. et al. Meta-analysis of association between obsessive-compulsive disorder and the 3ʹ region of neuronal glutamate transporter gene SLC1A1. Am. J. Med. Genet. B Neuropsychiatr. Genet. 162, 367–379 (2013).

    CAS  Article  Google Scholar 

  85. 85.

    Burguiere, E., Monteiro, P., Feng, G. & Graybiel, A. M. Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive behaviors. Science 340, 1243–1246 (2013). This paper demonstrates the value of basic neuroscience research in shedding light on OCD.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  86. 86.

    Kariuki-Nyuthe, C., Gomez-Mancilla, B. & Stein, D. J. Obsessive compulsive disorder and the glutamatergic system. Curr. Opin. Psychiatry 27, 32–37 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  87. 87.

    Turna, J., Grosman Kaplan, K., Anglin, R. & Van Ameringen, M. “What’s bugging the gut in OCD?” A review of the gut microbiome in obsessive-compulsive disorder. Depress. Anxiety 33, 171–178 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  88. 88.

    Renna, M. E., O’Toole, M. S., Spaeth, P. E., Lekander, M. & Mennin, D. S. The association between anxiety, traumatic stress, and obsessive-compulsive disorders and chronic inflammation: a systematic review and meta-analysis. Depress. Anxiety 35, 1081–1094 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  89. 89.

    Fineberg, N. A. et al. Probing compulsive and impulsive behaviors, from animal models to endophenotypes: a narrative review. Neuropsychopharmacology 35, 591–604 (2009).

    PubMed  PubMed Central  Article  Google Scholar 

  90. 90.

    Mataix-Cols, D. et al. Symptom stability in adult obsessive-compulsive disorder: data from a naturalistic two-year follow-up study. Am. J. Psychiatry 159, 263–268 (2002).

    PubMed  Article  PubMed Central  Google Scholar 

  91. 91.

    Lochner, C. et al. Gender in obsessive–compulsive disorder: clinical and genetic findings. Eur. Neuropsychopharmacol. 14, 105–113 (2004).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  92. 92.

    Torresan, R. C. et al. Symptom dimensions, clinical course and comorbidity in men and women with obsessive-compulsive disorder. Psychiatry Res. 209, 186–195 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  93. 93.

    Rapp, A. M., Bergman, R. L., Piacentini, J. & Mcguire, J. F. Evidence-based assessment of obsessive–compulsive disorder. J. Cent. Nerv. Syst. Dis. 8, 13–29 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  94. 94.

    du Toit, P. L., van Kradenburg, J., Niehaus, D. & Stein, D. J. Comparison of obsessive-compulsive disorder patients with and without comorbid putative obsessive-compulsive spectrum disorders using a structured clinical interview. Compr. Psychiatry 42, 291–300 (2001).

    PubMed  Article  PubMed Central  Google Scholar 

  95. 95.

    Goodman, W. K. et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch. Gen. Psychiatry 46, 1006–1011 (1989). The Y-BOCS remains the gold standard measure for assessing symptom severity in OCD.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  96. 96.

    Rosario-Campos, M. C. et al. The Dimensional Yale–Brown Obsessive–Compulsive Scale (DY-BOCS): an instrument for assessing obsessive–compulsive symptom dimensions. Mol. Psychiatry 11, 495–504 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  97. 97.

    Storch, E. A. et al. Florida obsessive-compulsive inventory: development, reliability, and validity. J. Clin. Psychol. 63, 851–859 (2007).

    PubMed  Article  PubMed Central  Google Scholar 

  98. 98.

    Rosario, M. C. et al. Validation of the University of São Paulo Sensory Phenomena Scale: initial psychometric properties. CNS Spectr. 14, 315–323 (2009).

    PubMed  Article  PubMed Central  Google Scholar 

  99. 99.

    Eisen, J. L. et al. The Brown Assessment of Beliefs Scale: reliability and validity. Am. J. Psychiatry 155, 102–108 (1998).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  100. 100.

    Albert, U., Baffa, A. & Maina, G. Family accommodation in adult obsessive–compulsive disorder: clinical perspectives. Psychol. Res. Behav. Manag. 10, 293–304 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  101. 101.

    Brakoulias, V., Perkes, I. E. & Tsalamanios, E. A call for prevention and early intervention in obsessive-compulsive disorder. Early Interv. Psychiatry 12, 572–577 (2017).

    PubMed  Article  Google Scholar 

  102. 102.

    Fineberg, N. A. et al. Early intervention for obsessive compulsive disorder: an expert consensus statement. Eur. Neuropsychopharmacol. 29, 549–565 (2019).

    CAS  PubMed  Article  Google Scholar 

  103. 103.

    Sarris, J., Camfield, D. & Berk, M. Complementary medicine, self-help, and lifestyle interventions for obsessive compulsive disorder (OCD) and the OCD spectrum: a systematic review. J. Affect. Disord. 138, 213–221 (2012).

    PubMed  Article  Google Scholar 

  104. 104.

    Amerio, A., Odone, A., Marchesi, C. & Ghaemi, S. N. Treatment of comorbid bipolar disorder and obsessive–compulsive disorder: a systematic review. J. Affect. Disord. 166, 258–263 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  105. 105.

    McGuire, J. F. et al. A meta-analysis of cognitive behavior therapy and medication for child obsessive-compulsive disorder: moderators of treatment efficacy, response, and remission. Depress. Anxiety 32, 580–593 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  106. 106.

    Dell’Osso, B. et al. Obsessive-compulsive disorder in the elderly: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS). Eur. Psychiatry 45, 36–40 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  107. 107.

    Skapinakis, P. et al. A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive–compulsive disorder in children/adolescents and adults. Health Technol. Assess. 20, 1–392 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  108. 108.

    Meyer, E. et al. Adding motivational interviewing and thought mapping to cognitive-behavioral group therapy: results from a randomized clinical trial. Braz. J. Psychiatry 32, 20–29 (2010).

    PubMed  Article  PubMed Central  Google Scholar 

  109. 109.

    Simpson, H. B. et al. Challenges using motivational interviewing as an adjunct to exposure therapy for obsessive-compulsive disorder. Behav. Res. Ther. 48, 941–948 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  110. 110.

    Öst, L.-G., Havnen, A., Hansen, B. & Kvale, G. Cognitive behavioral treatments of obsessive-compulsive disorder. A systematic review and meta-analysis of studies published 1993–2014. Clin. Psychol. Rev. 40, 156–169 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  111. 111.

    Öst, L.-G., Riise, E. N., Wergeland, G. J., Hansen, B. & Kvale, G. Cognitive behavioral and pharmacological treatments of OCD in children: a systematic review and meta-analysis. J. Anxiety Disord. 43, 58–69 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  112. 112.

    Huppert, J. D. & Franklin, M. E. Cognitive behavioral therapy for obsessive-compulsive disorder: an update. Curr. Psychiatry Rep. 7, 268–273 (2005).

    PubMed  Article  PubMed Central  Google Scholar 

  113. 113.

    Hirschtritt, M. E., Bloch, M. H. & Mathews, C. A. Obsessive-compulsive disorder. JAMA 317, 1358 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  114. 114.

    Wootton, B. M. Remote cognitive–behavior therapy for obsessive–compulsive symptoms: a meta-analysis. Clin. Psychol. Rev. 43, 103–113 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  115. 115.

    Rogers, M. A., Lemmen, K., Kramer, R., Mann, J. & Chopra, V. Internet-delivered health interventions that work: systematic review of meta-analyses and evaluation of website availability. J. Med. Internet Res. 19, e90 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  116. 116.

    Wheaton, M. G. et al. Patient adherence and treatment outcome with exposure and response prevention for OCD: which components of adherence matter and who becomes well? Behav. Res. Ther. 85, 6–12 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  117. 117.

    Pinto, A., Liebowitz, M. R., Foa, E. B. & Simpson, H. B. Obsessive compulsive personality disorder as a predictor of exposure and ritual prevention outcome for obsessive compulsive disorder. Behav. Res. Ther. 49, 453–458 (2011).

    PubMed  PubMed Central  Article  Google Scholar 

  118. 118.

    Skapinakis, P. et al. Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis. Lancet Psychiatry 3, 730–739 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  119. 119.

    Kvale, G. et al. Successfully treating 90 patients with obsessive compulsive disorder in eight days: the Bergen 4-day treatment. BMC Psychiatry 18, 323 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  120. 120.

    Soomro, G. M., Altman, D. G., Rajagopal, S. & Oakley Browne, M. Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD). Cochrane Database Syst. Rev. 1, CD001765 (2008).

    Google Scholar 

  121. 121.

    Bloch, M. H., McGuire, J., Landeros-Weisenberger, A., Leckman, J. F. & Pittenger, C. Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder. Mol. Psychiatry 15, 850–855 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  122. 122.

    Stein, D. J., Wreford Andersen, E., Tonnoir, B. & Fineberg, N. Escitalopram in obsessive–compulsive disorder: a randomized, placebo-controlled, paroxetine-referenced, fixed-dose, 24-week study. Curr. Med. Res. Opin. 23, 701–711 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  123. 123.

    Koran, L. M. et al. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am. J. Psychiatry 164, 5–53 (2007).

    PubMed  PubMed Central  Google Scholar 

  124. 124.

    Murphy, D. L. et al. Obsessive—compulsive disorder as a 5-HT subsystem-related behavioural disorder. Br. J. Psychiatry 155, 15–24 (1989).

    Article  Google Scholar 

  125. 125.

    Karabanow, O. Double-blind controlled study in phobias and obsessions. J. Int. Med. Res. 5 (Suppl. 5), 42–48 (1977).

    PubMed  PubMed Central  Google Scholar 

  126. 126.

    López-Ibor, J. J. et al. Double-blind comparison of fluoxetine versus clomipramine in the treatment of obsessive compulsive disorder. Eur. Neuropsychopharmacol. 6, 111–118 (1996).

    PubMed  Article  PubMed Central  Google Scholar 

  127. 127.

    Zohar, J. & Judge, R. Paroxetine versus clomipramine in the treatment of obsessive–compulsive disorder. Br. J. Psychiatry 169, 468–474 (1996).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  128. 128.

    Bisserbe, J., Lane, R. & Flament, M. A double-blind comparison of sertraline and clomipramine in outpatients with obsessive-compulsive disorder. Eur. Psychiatry 12, 82–93 (1997).

    CAS  PubMed  Article  Google Scholar 

  129. 129.

    Bandelow, B. et al. Guidelines for the pharmacological treatment of anxiety disorders, obsessive–compulsive disorder and posttraumatic stress disorder in primary care. Int. J. Psychiatry Clin. Pract. 16, 77–84 (2012).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  130. 130.

    Issari, Y., Jakubovski, E., Bartley, C. A., Pittenger, C. & Bloch, M. H. Early onset of response with selective serotonin reuptake inhibitors in obsessive-compulsive disorder. J. Clin. Psychiatry 77, e605–e611 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  131. 131.

    Varigonda, A. L., Jakubovski, E. & Bloch, M. H. Systematic review and meta-analysis: early treatment responses of selective serotonin reuptake inhibitors and clomipramine in pediatric obsessive-compulsive disorder. J. Am. Acad. Child Adolesc. Psychiatry 55, 851–859 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  132. 132.

    da Conceição Costa, D. L. et al. Can early improvement be an indicator of treatment response in obsessive-compulsive disorder? Implications for early-treatment decision-making. J. Psychiatr. Res. 47, 1700–1707 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  133. 133.

    Greist, J. H. et al. WCA recommendations for the long-term treatment of obsessive-compulsive disorder in adults. CNS Spectr. 8, 7–16 (2003).

    PubMed  Article  PubMed Central  Google Scholar 

  134. 134.

    Batelaan, N. M. et al. Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials. BMJ 358, j3927 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  135. 135.

    Erzegovesi, S. et al. Clinical predictors of drug response in obsessive-compulsive disorder. J. Clin. Psychopharmacol. 21, 488–492 (2001).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  136. 136.

    Ravizza, L., Barzega, G., Bellino, S., Bogetto, F. & Maina, G. Predictors of drug treatment response in obsessive-compulsive disorder. J. Clin. Psychiatry 56, 368–373 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. 137.

    Belotto-Silva, C. et al. Group cognitive-behavioral therapy versus selective serotonin reuptake inhibitors for obsessive-compulsive disorder: a practical clinical trial. J. Anxiety Disord. 26, 25–31 (2012).

    PubMed  Article  PubMed Central  Google Scholar 

  138. 138.

    Simpson, H. B. et al. Cognitive-behavioral therapy versus risperidone for augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder: a randomized clinical trial. JAMA Psychiatry 70, 1190–1199 (2013). This randomized controlled trial informs current approaches to the management of treatment-resistant OCD.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  139. 139.

    Cavanagh, K. Geographic inequity in the availability of cognitive behavioural therapy in England and Wales: a 10-year update. Behav. Cogn. Psychother. 42, 497–501 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  140. 140.

    Zhou, D.-D. et al. Augmentation agents to serotonin reuptake inhibitors for treatment-resistant obsessive-compulsive disorder: a network meta-analysis. Prog. Neuropsychopharmacol. Biol. Psychiatry 90, 277–287 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  141. 141.

    Dougherty, D. D. et al. Open-label study of high (30 mg) and moderate (20 mg) dose escitalopram for the treatment of obsessive–compulsive disorder. Int. Clin. Psychopharmacol. 24, 306–311 (2009).

    PubMed  Article  PubMed Central  Google Scholar 

  142. 142.

    Ninan, P. T. et al. High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder. J. Clin. Psychiatry 67, 15–22 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  143. 143.

    Pampaloni, I. et al. High-dose selective serotonin reuptake inhibitors in OCD: a systematic retrospective case notes survey. J. Psychopharmacol. 24, 1439–1445 (2009).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  144. 144.

    Albert, U., Aguglia, E., Maina, G. & Bogetto, F. Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder. J. Clin. Psychiatry 63, 1004–1009 (2002).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  145. 145.

    Denys, D., van Megen, H. J. G. M., van der Wee, N. & Westenberg, H. G. M. A. Double-blind switch study of paroxetine and venlafaxine in obsessive-compulsive disorder. J. Clin. Psychiatry 65, 37–43 (2004).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  146. 146.

    Yeh, Y.-W. et al. High-dose duloxetine for treatment-resistant obsessive-compulsive disorder. Clin. Neuropharmacol. 32, 174–176 (2009).

    PubMed  Article  PubMed Central  Google Scholar 

  147. 147.

    Dougherty, D. D. et al. Open-label study of duloxetine for the treatment of obsessive-compulsive disorder. Int. J. Neuropsychopharmacol. 18, pyu062 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  148. 148.

    Bandelow, B. et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders – first revision. World J. Biol. Psychiatry 9, 248–312 (2008).

    PubMed  Article  PubMed Central  Google Scholar 

  149. 149.

    Bloch, M. H. et al. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol. Psychiatry 11, 622–632 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  150. 150.

    Albert, U. et al. Role and clinical implications of atypical antipsychotics in anxiety disorders, obsessive-compulsive disorder, trauma-related, and somatic symptom disorders. Int. Clin. Psychopharmacol. 31, 249–258 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  151. 151.

    Dold, M., Aigner, M., Lanzenberger, R. & Kasper, S. Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: an update meta-analysis of double-blind, randomized, placebo-controlled trials. Int. J. Neuropsychopharmacol. 18, pyv047 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  152. 152.

    Diniz, J. B. et al. A double-blind, randomized, controlled trial of fluoxetine plus quetiapine or clomipramine versus fluoxetine plus placebo for obsessive-compulsive disorder. J. Clin. Psychopharmacol. 31, 763–768 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  153. 153.

    Pittenger, C. Glutamatergic agents for OCD and related disorders. Curr. Treat. Options Psychiatry 2, 271–283 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  154. 154.

    Popli, A. P. Interactions of serotonin reuptake inhibitors with tricyclic antidepressants. Arch. Gen. Psychiatry 51, 666 (1994).

    CAS  PubMed  Article  Google Scholar 

  155. 155.

    Matsunaga, H. et al. A long-term trial of the effectiveness and safety of atypical antipsychotic agents in augmenting SSRI-refractory obsessive-compulsive disorder. J. Clin. Psychiatry 70, 863–868 (2009).

    CAS  PubMed  Article  Google Scholar 

  156. 156.

    Fineberg, N. A. et al. Obsessive–compulsive disorder (OCD): practical strategies for pharmacological and somatic treatment in adults. Psychiatry Res. 227, 114–125 (2015).

    CAS  PubMed  Article  Google Scholar 

  157. 157.

    Rodriguez, C. I., Levinson, A., Zwerling, J., Vermes, D. & Simpson, H. B. Open-label trial on the effects of memantine in adults with obsessive-compulsive disorder after a single ketamine infusion. J. Clin. Psychiatry 77, 688–689 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  158. 158.

    Costa, D. L. C. et al. Randomized, double-blind, placebo-controlled trial of N-acetylcysteine augmentation for treatment-resistant obsessive-compulsive disorder. J. Clin. Psychiatry 78, e766–e773 (2017).

    PubMed  Article  Google Scholar 

  159. 159.

    Afshar, H. et al. N-Acetylcysteine add-on treatment in refractory obsessive-compulsive disorder. J. Clin. Psychopharmacol. 32, 797–803 (2012).

    CAS  PubMed  Article  Google Scholar 

  160. 160.

    Paydary, K. et al. N-Acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder: randomized, double-blind, placebo-controlled trial. J. Clin. Pharm. Ther. 41, 214–219 (2016).

    CAS  PubMed  Article  Google Scholar 

  161. 161.

    Sarris, J. et al. N-Acetylcysteine (NAC) in the treatment of obsessive-compulsive disorder: a 16-week, double-blind, randomised, placebo-controlled study. CNS Drugs 29, 801–809 (2015).

    CAS  PubMed  Article  Google Scholar 

  162. 162.

    Ghanizadeh, A. et al. Efficacy of N-acetylcysteine augmentation on obsessive compulsive disorder: a multicenter randomized double blind placebo controlled clinical trial. Iran J. Psychiatry 12, 134–141 (2017).

    PubMed  PubMed Central  Google Scholar 

  163. 163.

    Kishi, T., Matsuda, Y. & Iwata, N. Combination therapy of serotonin reuptake inhibitors and memantine for obsessive–compulsive disorder: a meta-analysis of double-blind, randomized, placebo-controlled trials. J. Alzheimers Dis. 64, 43–48 (2018).

    CAS  PubMed  Article  Google Scholar 

  164. 164.

    Senço, N. M. et al. Transcranial direct current stimulation in obsessive–compulsive disorder: emerging clinical evidence and considerations for optimal montage of electrodes. Expert Rev. Med. Devices 12, 381–391 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  165. 165.

    Rehn, S., Eslick, G. D. & Brakoulias, V. A. Meta-analysis of the effectiveness of different cortical targets used in repetitive transcranial magnetic stimulation (rTMS) for the treatment of obsessive-compulsive disorder (OCD). Psychiatr. Q. 89, 645–665 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  166. 166.

    Lefaucheur, J.-P. et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin. Neurophysiol. 125, 2150–2206 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  167. 167.

    Berlim, M. T., Neufeld, N. H. & Van den Eynde, F. Repetitive transcranial magnetic stimulation (rTMS) for obsessive–compulsive disorder (OCD): an exploratory meta-analysis of randomized and sham-controlled trials. J. Psychiatr. Res. 47, 999–1006 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  168. 168.

    Zhou, D.-D., Wang, W., Wang, G.-M., Li, D.-Q. & Kuang, L. An updated meta-analysis: short-term therapeutic effects of repeated transcranial magnetic stimulation in treating obsessive-compulsive disorder. J. Affect. Disord. 215, 187–196 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  169. 169.

    Luis Lujan, J. Tracking the mechanisms of deep brain stimulation for neuropsychiatric disorders. Front. Biosci. 13, 5892–5904 (2008).

    PubMed  PubMed Central  Article  Google Scholar 

  170. 170.

    Garnaat, S. L. et al. Who qualifies for deep brain stimulation for OCD? Data from a naturalistic clinical sample. J. Neuropsychiatry Clin. Neurosci. 26, 81–86 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  171. 171.

    Alonso, P. et al. Deep brain stimulation for obsessive-compulsive disorder: a meta-analysis of treatment outcome and predictors of response. PLOS ONE 10, e0133591 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  172. 172.

    Hamani, C. et al. Deep brain stimulation for obsessive-compulsive disorder. Neurosurgery 75, 327–333 (2014).

    PubMed  Article  Google Scholar 

  173. 173.

    Coenen, V. A. et al. The medial forebrain bundle as a target for deep brain stimulation for obsessive-compulsive disorder. CNS Spectr. 22, 282–289 (2016).

    PubMed  Article  Google Scholar 

  174. 174.

    Greenberg, B. D., Rauch, S. L. & Haber, S. N. Invasive circuitry-based neurotherapeutics: stereotactic ablation and deep brain stimulation for OCD. Neuropsychopharmacology 35, 317–336 (2009).

    PubMed Central  Article  Google Scholar 

  175. 175.

    Jung, H. H. et al. Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study. Mol. Psychiatry 20, 1205–1211 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  176. 176.

    Miguel, E. C. et al. Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder. Mol. Psychiatry 24, 218–240 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  177. 177.

    Lopes, A. C. et al. Gamma ventral capsulotomy for obsessive-compulsive disorder: a randomized clinical trial. JAMA Psychiatry 71, 1066–1076 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  178. 178.

    Shannahoff-Khalsa, D. S. et al. Randomized controlled trial of yogic meditation techniques for patients with obsessive-compulsive disorder. CNS Spectr. 4, 34–47 (1999).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  179. 179.

    Key, B. L., Rowa, K., Bieling, P., McCabe, R. & Pawluk, E. J. Mindfulness-based cognitive therapy as an augmentation treatment for obsessive-compulsive disorder. Clin. Psychol. Psychother. 24, 1109–1120 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  180. 180.

    Kumar, A., Sharma, M., Narayanaswamy, J., Kandavel, T. & Janardhan Reddy, Y. Efficacy of mindfulness-integrated cognitive behavior therapy in patients with predominant obsessions. Indian J. Psychiatry 58, 366 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  181. 181.

    Rector, N. A., Richter, M. A., Lerman, B. & Regev, R. A. Pilot test of the additive benefits of physical exercise to CBT for OCD. Cogn. Behav. Ther. 44, 328–340 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  182. 182.

    Abrantes, A. M. et al. A pilot randomized controlled trial of aerobic exercise as an adjunct to OCD treatment. Gen. Hosp. Psychiatry 49, 51–55 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  183. 183.

    Zhang, Z.-J., Wang, X.-Y., Tan, Q.-R., Jin, G.-X. & Yao, S.-M. Electroacupuncture for refractory obsessive-compulsive disorder. J. Nerv. Ment. Dis. 197, 619–622 (2009).

    PubMed  Article  PubMed Central  Google Scholar 

  184. 184.

    Subramaniam, M., Soh, P., Vaingankar, J. A., Picco, L. & Chong, S. A. Quality of life in obsessive-compulsive disorder: impact of the disorder and of treatment. CNS Drugs 27, 367–383 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  185. 185.

    Macy, A. S. et al. Quality of life in obsessive compulsive disorder. CNS Spectr. 18, 21–33 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  186. 186.

    Coluccia, A. et al. Adult obsessive–compulsive disorder and quality of life outcomes: a systematic review and meta-analysis. Asian J. Psychiatry 22, 41–52 (2016).

    Article  Google Scholar 

  187. 187.

    Coluccia, A., Ferretti, F., Fagiolini, A. & Pozza, A. Quality of life in children and adolescents with obsessive–compulsive disorder: a systematic review and meta-analysis. Neuropsychiatr. Dis. Treat. 13, 597–608 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  188. 188.

    Farris, S. G., McLean, C. P., Van Meter, P. E., Simpson, H. B. & Foa, E. B. Treatment response, symptom remission, and wellness in obsessive-compulsive disorder. J. Clin. Psychiatry 74, 685–690 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  189. 189.

    Cicek, E., Cicek, I. E., Kayhan, F., Uguz, F. & Kaya, N. Quality of life, family burden and associated factors in relatives with obsessive–compulsive disorder. Gen. Hosp. Psychiatry 35, 253–258 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  190. 190.

    Grover, S. & Dutt, A. Perceived burden and quality of life of caregivers in obsessive-compulsive disorder. Psychiatry Clin. Neurosci. 65, 416–422 (2011).

    PubMed  Article  PubMed Central  Google Scholar 

  191. 191.

    Hollander, E., Stein, D. J., Fineberg, N. A., Marteau, F. & Legault, M. Quality of life outcomes in patients with obsessive-compulsive disorder. J. Clin. Psychiatry 71, 784–792 (2010).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  192. 192.

    Srivastava, S., Bhatia, M. S., Thawani, R. & Jhanjee, A. Quality of life in patients with obsessive compulsive disorder: a longitudinal study from India. Asian J. Psychiatry 4, 178–182 (2011).

    Article  Google Scholar 

  193. 193.

    Hauschildt, M., Jelinek, L., Randjbar, S., Hottenrott, B. & Moritz, S. Generic and illness-specific quality of life in obsessive-compulsive disorder. Behav. Cogn. Psychother. 38, 417–436 (2010).

    PubMed  Article  PubMed Central  Google Scholar 

  194. 194.

    Van Ameringen, M., Turna, J., Khalesi, Z., Pullia, K. & Patterson, B. There is an app for that! The current state of mobile applications (apps) for DSM-5 obsessive-compulsive disorder, posttraumatic stress disorder, anxiety and mood disorders. Depress. Anxiety 34, 526–539 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  195. 195.

    Thorsen, A. L., van den Heuvel, O. A., Hansen, B. & Kvale, G. Neuroimaging of psychotherapy for obsessive–compulsive disorder: a systematic review. Psychiatry Res. 233, 306–313 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  196. 196.

    Dougherty, D. D. et al. Neuroscientifically informed formulation and treatment planning for patients with obsessive-compulsive disorder. JAMA Psychiatry 75, 1081–1087 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  197. 197.

    Stein, D. J. et al. Global mental health and neuroscience: potential synergies. Lancet Psychiatry 2, 178–185 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  198. 198.

    Stein, D. Obsessive-compulsive disorder and global mental health. Indian J. Psychiatry 61, 4 (2019).

    Article  Google Scholar 

  199. 199.

    Cheyette, S. R. & Cummings, J. L. Encephalitis lethargica: lessons for contemporary neuropsychiatry. J. Neuropsychiatry Clin. Neurosci. 7, 125–134 (1995).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  200. 200.

    Laplane, D. Obsessive-compulsive disorders caused by basal ganglia diseases [French]. Rev. Neurol. 150, 594–598 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  201. 201.

    Khanna, S. Obsessive-compulsive disorder: is there a frontal lobe dysfunction? Biol. Psychiatry 24, 602–613 (1988).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  202. 202.

    Swedo, S. E. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Mol. Psychiatry 7, S24–S25 (2002). This paper introduces the construct of paediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS).

    PubMed  Article  PubMed Central  Google Scholar 

  203. 203.

    Swedo, S. E. et al. High prevalence of obsessive-compulsive symptoms in patients with Sydenham’s chorea. Am. J. Psychiatry 146, 246–249 (1989).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  204. 204.

    Hounie, A. G. et al. Obsessive-compulsive spectrum disorders in rheumatic fever with and without Sydenham’s chorea. J. Clin. Psychiatry 65, 994–999 (2004).

    PubMed  Article  PubMed Central  Google Scholar 

  205. 205.

    Chang, K. et al. Clinical evaluation of youth with pediatric acute-onset neuropsychiatric syndrome (PANS): recommendations from the 2013 PANS Consensus Conference. J. Child Adolesc. Psychopharmacol. 25, 3–13 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  206. 206.

    Thienemann, M. et al. Clinical management of pediatric acute-onset neuropsychiatric syndrome: part I — psychiatric and behavioral interventions. J. Child Adolesc. Psychopharmacol. 27, 566–573 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  207. 207.

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) (American Psychiatric Press, 2013).

  208. 208.

    Prado, H. S. et al. Sensory phenomena in obsessive-compulsive disorder and tic disorders: a review of the literature. CNS Spectr. 13, 425–432 (2008).

    PubMed  Article  PubMed Central  Google Scholar 

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Introduction (D.J.S.); Epidemiology (D.J.S.); Mechanisms/pathophysiology (O.A.v.d.H.); Diagnosis, screening and prevention (C.L.); Management (E.C.M., D.L.C.C., R.G.S.); Quality of life (Y.C.J.R.); Outlook (H.B.S.); Overview of Primer (D.J.S.).

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Correspondence to Dan J. Stein.

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Competing interests

D.J.S. has received research grants and/or consultancy honoraria from Lundbeck and Sun, and is also on the scientific advisory board of the TLC Foundation for Body-Focused Repetitive Behaviours, the Anxiety and Depression Association of America (ADAA), and the South African Depression and Anxiety Support Group. D.L.C.C. has received consultancy honoraria from Pfizer and Libbs, and a scholarship from Fundação de Amparo à Pesquisa do Estado de Sao Paulo (Sao Paulo State Foundation for Research Support). E.C.M. has received a productivity grant from the Brazilian National Council for Scientific and Technological Development. Y.C.J.R. has been involved in a study on bipolar disorder, supported by GlaxoSmithKline, and is also lead author on clinical guidelines on OCD produced by the Indian Psychiatric Society. R.G.S. has received consultancy honoraria from Lundbeck, and she receives a productivity grant from the Brazilian National Council for Scientific and Technological Development. H.B.S. has received research grants from Biohaven Pharmaceuticals and royalties from UpToDate, Inc. and Cambridge University Press. She is also on the Board of Directors and the Scientific Advisory Board of ADAA, and is an Associate Editor at JAMA Psychiatry. All other authors declare no competing interests.

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Nature Reviews Disease Primers thanks D. Marazziti, D. Tolin, J. Piacentini, and the other, anonymous, reviewer(s), for their contribution to the peer review of this work.

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Related links

Astoc St: www.astocst.com.br

International OCD Foundation: https://iocdf.org/

OCD Action: http://www.ocdaction.org.uk

South African Depression and Anxiety Group: www.sadag.org

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Stein, D.J., Costa, D.L.C., Lochner, C. et al. Obsessive–compulsive disorder. Nat Rev Dis Primers 5, 52 (2019). https://doi.org/10.1038/s41572-019-0102-3

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