Skip to main content

Advertisement

SpringerLink
Log in

The cognitive-affective neuroscience of obsessive-compulsive disorder

  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

There is substantial evidence that obsessive-compulsive disorder (OCD) is mediated by specific cortico-striatalthalamic-cortical (CTSC) circuits. Here we discuss very recent publications that address the following questions: How does damage to CSTC circuitry come about?; What are the neurochemical systems involved in mediating this circuitry?; and What are the implications of such damage for understanding the pathogenesis and management of OCD? A cognitive-affective neuroscience perspective is helpful in advancing our understanding of the role of these circuits in OCD and the dysfunctional procedural strategies that appear to characterize this disorder. Furthermore, this model is becoming integrated with a range of data including brain imaging, genetic, immunologic, and neurochemical findings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Cheyette SR, Cummings JL: Encephalitis lethargica: lessons for contemporary neuropsychiatry. J Neuropsychiatry Clin Neurosci 1995, 7:125–134.

    PubMed  CAS  Google Scholar 

  2. SteinDJ: The neurobiology of obsessive-compulsive disorder. Neuroscientist 1996, 2:300–305.

    Article  Google Scholar 

  3. Rauch SL, Baxter LR Jr:Neuroimaging in obsessive-compulsive disorder and related disorders. InObsessive-Compulsive Disorders: Practical Management, edn 3. Edited by JenickeMA, BaerL, MinichielloWE. St. Louis: Mosby; 1998.

    Google Scholar 

  4. Robinson D, Wu H, Munne RA, et al.: Reduced caudate nucleus volume in obsessive-compulsive disorder. Arch Gen Psychiatry 1995, 52:393–398.

    PubMed  CAS  Google Scholar 

  5. Szeszko PR, Robinson D, Alvir JMJ, et al.: Orbital frontal and amygdala volume reductions in obsessive-compulsive disorder. Arch Gen Psychiatry 1999, 56:913–919.

    Article  PubMed  CAS  Google Scholar 

  6. CummingsJL: Frontal-subcortical circuits and human behavior. Arch Neurol 1993, 50:873–880.

    PubMed  CAS  Google Scholar 

  7. Mishkin M, Petri H: Memories and habits: some implications for the analysis of learning and retentions. InNeuropsychology of Memory. Edited bySquireLR,ButtersN. New York: Guildford Press; 1984.

    Google Scholar 

  8. Robbins TW, Brown VJ: The role of the striatum in the mental chronometry of action: a theoretical review. Rev Neurosci 1990, 2:181–213.

    Google Scholar 

  9. Saint-Cyr JA, Taylor AE, Nicholson K: Behavior and the basal ganglia. InBehavioral Neurology of Movement Disorders. Edited byWeinerWJ, LangAE. New York: Raven Press; 1995.

    Google Scholar 

  10. Swedo SE, Rapoport JL, Cheslow DL, et al.: High prevalence of obsessive-compulsive symptoms in patients with Sydenham’s chorea. Am J Psychiatry 1989, 146:246–249.

    PubMed  CAS  Google Scholar 

  11. Swedo SE, Leonard HL, Garvey M, et al.: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 1998, 155:264–271. This report describes 50 cases of patients who had OCD or a tic disorder, prepubertal symptom onset, episodic course of symptom severity, association with group beta-hemolytic streptococcal infection, and association with neurological abnormalities. The authors designate these patients as having PANDAS.

    PubMed  CAS  Google Scholar 

  12. Perlmutter SJ, Leitman SF, Garvey MA, et al.: Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet 1999, 354:1153–1158. Given that PANDAS is presumably mediated by autoimmune mechanisms, the authors hypothesized that immunomodulatory therapies (plasma exchange, intravenous immunoglobulin) would be effective in these patients. Indeed, these agents were found significantly more effective than placebo in decreasing OCD symptoms in PANDAS patients.

    Article  PubMed  CAS  Google Scholar 

  13. Garvey MA, Perlmutter SA, Allen AJ, et al.: A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biol Psychiatry 1999, 45:1564–1571. As penicillin prophylaxis is effective in preventing recurrences of rheumatic fever, it was hypothesized that it would prevent streptococcal-triggered symptom exacerbations in children with PANDAS. Unfortunately, in these patients, penicillin administration proved ineffective in preventing infection, and there was no significant difference in OCD symptoms between the penicillin and the placebo phase.

    Article  PubMed  CAS  Google Scholar 

  14. Swedo SE, Leonard HL, Mittleman BB, 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, 154:110–112.

    PubMed  CAS  Google Scholar 

  15. Murphy TK, Goodman WK, Fudge MW, et al.: B lymphocyte antigen D8/17: A peripheral marker for childhood-onset obsessive-compulsive disorder and Tourette’s syndrome? Am J Psychiatry 1997, 154:402–407.

    PubMed  CAS  Google Scholar 

  16. Chapman F, Visvanathan K, Carreno-Manjarrez R, Zabriskie JB: A flow cytometric assay for D8/17 B cell marker in patients with Tourette’s syndrome and obsessive compulsive disorder. J Immunol Methods 1998, 219:181–186.

    Article  PubMed  CAS  Google Scholar 

  17. Hollander E, Del Guidice-Asch G, Simon L, et al.: B lymphocyte antigen D8/17 and repetitive behaviors autism. Am J Psychiatry 1999, 156:317–320.

    PubMed  CAS  Google Scholar 

  18. Niehaus DJ, Knowles JA, van Kradenberg J, et al.: D8/17 in obsessive-compulsive disorder and trichotillomania. S Afr Med J 1999, 89:755–756.

    PubMed  CAS  Google Scholar 

  19. Singer HS, Giuliano JD, Hansen BH, et al.: Antibodies against human putamen in children with Tourette syndrome. Neurology 1998, 50:1618–1624.

    PubMed  CAS  Google Scholar 

  20. Singer HS, Giuliano JD, Hansen BH, et al.: Antibodies against a neuron-like (HTB-10 neuroblastoma) cell in children with Tourette syndrome. Biol Psychiatry 1999, 46:775–780.

    Article  PubMed  CAS  Google Scholar 

  21. Black JL, Lamke GT, Walikonis JE: Serological survey of adult patients with obsessive-compulsive disorder for neuron-specific and other autoantibodies. Psychiatry Res 1998, 81:371–380.

    Article  PubMed  CAS  Google Scholar 

  22. Rapoport MH, McAllister CG: The genetics of obsessivecompulsive disorder: an immunological perspective. CNS Spectrums 1999, 4(6):71–77.

    Google Scholar 

  23. Mittleman BB, Castellanos FX, Jacobsen LK, et al.: Cerebrospinal fluid cytokines in pediatric in pediatric neuropsychiatric disease. J Immunol 1997, 159:2994–2999.

    PubMed  CAS  Google Scholar 

  24. Ravindran AV, Griffiths J, Merali Z, et al.: Circulating lymphocyte subsets in obsessive compulsive disorder, major depression and normal controls. J Affect Disord 1999, 52:1–10.

    Article  PubMed  CAS  Google Scholar 

  25. Marazziti D, Presta S, Pfanner C, et al.: Immunological alterations in adult obsessive-compulsive disorder. Biol Psychiatry 1999, 46:810–814.

    Article  PubMed  CAS  Google Scholar 

  26. Monteleone P, Catapano F, Fabrazzo M, et al.: Decreased blood levels of tumor necrosis factor-alpha in patients with obsessive-compulsive disorder. Neuropsychobiology 1998, 37:182–185.

    Article  PubMed  CAS  Google Scholar 

  27. Brambilla F, Perna G, Bellodi L, et al.: Plasma interleukin-1 beta and tumor necrosis factor concentrations in obsessivecompulsive disorders. Biol Psychiatry 1997, 42:976–981.

    Article  PubMed  CAS  Google Scholar 

  28. Rauch SL, Dougherty DD, Shin LM, et al.: Neural correlates of factor-analyzed OCD symptom dimensions: a PET study. CNS Spectrums 1998, 3:37–43.

    Google Scholar 

  29. McDougle CJ, Goodman WK, Leckman JF, et al.: Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder: a double-blind placebo-controlled study in patients with and without tics. Arch Gen Psychiatry 1994, 51:302–308.

    PubMed  CAS  Google Scholar 

  30. Leckman JF, Grice DE, Boardman J, et al.: Symptoms of obsessive-compulsive disorder. Am J Psychiatry 1997, 154:911–917.

    PubMed  CAS  Google Scholar 

  31. BaerL: Factor analysis of symptom subtypes of obsessive-compulsive disorder and their relation to personality and tic disorders. J Clin Psychiatry 1994, 55(suppl):18–23.

    PubMed  Google Scholar 

  32. Damecour CL, Charron M: Hoarding: a symptom, not a syndrome. J Clin Psychiatry 1998, 59:267–272.

    PubMed  CAS  Google Scholar 

  33. Zohar J, Insel TR: Obsessive-compulsive disorder: psychobiological approaches to diagnosis, treatment, and pathophysiology. Biol Psychiatry 1987, 22:667–687.

    Article  PubMed  CAS  Google Scholar 

  34. Blier P, de MontignyC: Possible serotonergic mechanisms underlying the antidepressant and anti-obsessive-compulsive disorder responses. Biol Psychiatry 1998, 44:313–323. This is an important review of the authors’ recent work on preclinical models of the psychopharmacology of OCD and depression. Drugs effective in OCD result in desensitization of serotonin terminal autoreceptors (5-HT1D) in orbitofrontal cortex, but only after administration of relatively high doses for relatively long periods of time—paralleling clinical data in OCD.

    Article  PubMed  CAS  Google Scholar 

  35. Delgado PL, Moreno FA: Hallucinogens, serotonin and obsessive-compulsive disorder. J Psychoactive Drugs 1998, 30:359–366.

    PubMed  CAS  Google Scholar 

  36. Stein DJ, van Heerden B, Wessels CJ, et al.: Single photon emission tomography of the brain with Tc-99m HMPAO during sumatriptan challenge in obsessive-compulsive disorder: Investigating the functional role of the serotonin auto-receptor. Prog Neuropsychopharmacol Biol Psychiatry 1999, 23:1079–1099.

    Article  PubMed  CAS  Google Scholar 

  37. Szechtman H, Culver K, Eilam D: Role of dopamine systems in obsessive-compulsive disorder (OCD): Implications from a novel psychostimulant-induced animal model. Pol J Pharmacol 1999, 51:55–61.

    PubMed  CAS  Google Scholar 

  38. Campbell KM, McGrath MJ, Burton FH: Behavioral effects of cocaine on a transgenic mouse model of cortical-limbic compulsion. Brain Res 1999, 833:216–224.

    Article  PubMed  CAS  Google Scholar 

  39. McDougle CJ, Fleischmann RL, Epperson CN, et al.: Risperidone addition in fluvoxamine-refractory obsessive-compulsive disorder: three cases. J Clin Psychiatry 1995, 56:526–528.

    PubMed  CAS  Google Scholar 

  40. Stein DJ, Bouwer C, Hawkridge S, Emsley RA: Risperidone augmentation of serotonin reuptake inhibitors in obsessive-compulsive and related disorders. J Clin Psychiatry 1997, 58:119–122.

    PubMed  CAS  Google Scholar 

  41. McDougle CJ, Barr LC, Goodman WK, Price LH: Possible role of neuropeptides in obsessive compulsive disorder. Psychoneuroendocrinology 1999, 24:1–24.

    Article  PubMed  CAS  Google Scholar 

  42. Altemus M, Jacobson KR, Debellis M, et al.: Normal CSF oxytocin and NPY levels in OCD. Biol Psychiatry 1999, 45:931–933.

    Article  PubMed  CAS  Google Scholar 

  43. Devor EJ, Magee HJ: Multiple childhood behavioral disorders (Tourette syndrome, multiple tics, ADD and OCD) presenting in a family with a balanced chromosome translocation (t1:8)(q21.1; q22.1). Psychiatr Genet 1999, 9:149–151.

    Article  PubMed  CAS  Google Scholar 

  44. De MarchiN, Morris M, Mennella R, et al.: Association of obsessive-compulsive disorder and pathological gambling with Huntington’s disease in an Italian pedigree: possible association with Huntington’s disease mutation. Acta Psychiatr Scan 1998, 97:62–65.

    Google Scholar 

  45. Bolton PF, Pickles A, Murphy M, Rutter M: Autism, affective and other psychiatric disorders: patterns of familial aggregation. Psychol Med 1998, 28:385–395.

    Article  PubMed  CAS  Google Scholar 

  46. Mataix Cols D, Rauch SL, Manzo PA, et al.: Use of factoranalyzed symptom dimensions to predict outcome with serotonin reuptake inhibitors and placebo in the treatment of obsessive-compulsive disorder. Am J Psychiatry 1999, 156:1409–1416.

    PubMed  CAS  Google Scholar 

  47. The Tourette Syndrome Association International Consortium for Genetics: A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. Am J Hum Genet 1999, 65:1428–1436. In this report, the results of the first systematic genome scan in Tourette’s syndrome, using 76 affected-sib-pair families with a total of 110 sib pairs, are summarized. No results reached acceptable statistical significance, but the multipoint maximum-likelihood scores (MLS) for two regions (4q and 8p) were suggestive (MLS=2.0)

    Article  Google Scholar 

  48. McDougle CJ, Epperson CN, Price LH, Gelernter J: Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. Mol Psychiatry 1998, 3:270–273. Studies showing that a polymorphism in the promoter region of the gene (SLC6A4) encoding the serotonin transporter receptor is associated with anxiety and other symptoms led to the hypothesis that the polymorphism may influence risk for OCD. Linkage disequilibrium was between OCD and alleles at this locus was examined. Heterozygous parents were significantly more likely to transmit the ‘1’ SLC6A4 allele than the ‘s’ allele.

    Article  PubMed  CAS  Google Scholar 

  49. Bengel D, Greenberg BD, Cora-Locatelli G, et al.: Association of the serotonin transporter promoter regulatory region polymorphism and obsessive-compulsive disorder. Mol Psychiatry 1999, 4:463–466.

    Article  PubMed  CAS  Google Scholar 

  50. Hanna GL, Himle JA, Curtis GC, et al.: Serotonin transporter and seasonal variation in blood serotonin in families with obsessive-compulsive disorder. Neuropsychopharmacology 1998, 18:102–111.

    Article  PubMed  CAS  Google Scholar 

  51. Marazziti D, Akiskal HS, Rossi A, Cassano GB: Alteration of the platelet serotonin transporter in romantic love. Psychol Med 1999, 29:741–745.

    Article  PubMed  CAS  Google Scholar 

  52. Cruz C, Camarena B, King N, et al.: Increased prevalence of the 7 repeat variant of the dopamine D4 receptor gene in patients with obsessive-compulsive disorder with tics. Neurosci Lett 1997, 231:1–4.

    Article  PubMed  CAS  Google Scholar 

  53. Billett EA, Richter MA, Sam F, et al.: Investigation of dopamine system genes in obsessive-compulsive disorder. Psychiatr Genet 1998, 8:163–169. OCD patients and matched controls were genotyped for four dopamine system loci; a 40-base-pair repeat in the dopamine transporter gene, the TaqIA polymorphism and the serine/cysteine variation in the D2 dopamine receptor gene, an MscI polymorphism in the D3 dopamine receptor gene, and a 48-base-pair repeat in the D4 dopamine receptor gene. Significant differences in allele frequencies were found between patients and controls for the D4 receptor gene.

    Article  PubMed  CAS  Google Scholar 

  54. Nicolini H, Cruz C, Camarena B, et al.: DRD2, DRD3, 5-HT2A receptor gene polymorphisms in obsessive-compulsive disorder. Mol Psychiatry 1996, 1:461–465.

    PubMed  CAS  Google Scholar 

  55. Camarena B, Cruz C, de laFuenteJR, Nicolini H: A higher frequency of a low activity-related allele of the MAO-A gene in females with obsessive-compulsive disorder. Psychiatr Genet 1998, 8:255–257.

    Article  PubMed  CAS  Google Scholar 

  56. Karayiorgou M, Sobin C, Blundell ML, et al.: Family-based association studies support a sexually dimorphic effect of COMT and MAOA on genetic susceptibility to obsessivecompulsive disorder. Biol Psychiatry 1999, 45:1178–1189.

    Article  PubMed  CAS  Google Scholar 

  57. Barr CL, Wigg KG, Sandor P: Catechol-O-methyltransferase and Gilles de la Tourette syndrome. Mol Psychiatry 1999, 4:492–495.

    Article  PubMed  CAS  Google Scholar 

  58. Ohara K, Nagai M, Suzuki Y, et al.: No association between anxiety disorders and catechol-O-methyltransferase polymorphism. Psychiatry Res 1998, 17:145–148.

    Article  Google Scholar 

  59. Rowe DC, Stever C, Gard JM, et al.: The relation of the dopamine transporter gene (DAT1) to symptoms of internalizing disorders in children. Behav Genet 1998, 28:215–225.

    Article  PubMed  CAS  Google Scholar 

  60. Cavallini MC, Di BellaD, Pasquale L, et al.: 5HT2C CYS23/ SER23 polymorphism is not associated with obsessivecompulsive disorder. Psychiatry Res 1998, 77:97–104.

    Article  PubMed  CAS  Google Scholar 

  61. Enoch MA, Kaye WH, Rotondo A, et al.: 5-HT2A promotor polymorphism-1438G/A, anorexia nervosa, and obsessivecompulsive disorder. Lancet 1998, 351:1785–1786.

    Article  PubMed  CAS  Google Scholar 

  62. Han L, Nielsen DA, Rosenthal NE, et al.: No coding variant of the tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive-compulsive disorder, anorexia nervosa, and alcoholism. Biol Psychiatry 1999, 45:615–619.

    Article  PubMed  CAS  Google Scholar 

  63. Novelli E, Nobile M, Diaferia G, et al.: A molecular investigation suggests no relationship between obsessivecompulsive disorder and the dopamine D2 receptor. Neuropsychobiology 1994, 29:61–63.

    Article  PubMed  CAS  Google Scholar 

  64. Thompson M, Comings DE, Feder L, et al.: Mutation screening of the dopamine D1 receptor gene in Tourette’s syndrome and alcohol dependent patients. Am J Med Genet 1998, 81:241–244.

    Article  PubMed  CAS  Google Scholar 

  65. Saxena S, Brody AL, Schwartz JM, et al.: Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder. Br J Psychiatry 1998, 35:26–37.

    Google Scholar 

  66. Savage CR, Baer L, Keuthen NJ, et al.: Organizational strategies mediate nonverbal memory impairment in obsessivecompulsive disorder. Biol Psychiatry 1999, 45:905–916.

    Article  PubMed  CAS  Google Scholar 

  67. O’Sullivan RL, Rauch SL, Breiter HC, et al.: Reduced basal ganglia volumes in trichotillomania measured via morphometric magnetic resonance imaging. Biol Psychiatry 1997, 42:39–45.

    Article  PubMed  CAS  Google Scholar 

  68. Rosenberg DR, Keshavan MS: Toward a neurodevelopmental model of obsessive-compulsive disorder. Biol Psychiatry 1998, 43:623–640. This paper reports on a series of studies testing the hypothesis that neurodevelopmental abnormalities of ventral prefrontal-striatal circuits are involved in obsessive-compulsive disorder. Studies of oculomotor physiology suggested a selective deficit in neurobehavioral response suppression in OCD, and magnetic resonance imaging studies showed that treatment-naive pediatric OCD patients had significant volumetric abnormalities in ventral prefrontal cortical and striatal regions but not in dorsolateral prefrontal cortex.

    Article  PubMed  CAS  Google Scholar 

  69. Rauch SL, Savage CR, Alpert NM, et al.: Probing striatal function in obsessive compulsive disorder: a PET study of implicit sequence learning. J Neuropsychiatry 1997, 9:568–573.

    CAS  Google Scholar 

  70. Ebert D, Speck O, Konig A, et al.: 1H-magnetic resonance spectroscopy in obsessive-compulsive disorder: evidence for neuronal loss in the cingulate gyrus and the right striatum. Psychiatry Res 1997, 74:173–176.

    Article  PubMed  CAS  Google Scholar 

  71. Bartha R, Stein MB, Williamson PC, et al.: A short echo 1H spectroscopy and volumetric MRI study of the corpus striatum in patients with obsessive-compulsive disorder and comparison subjects. Am J Psychiatry 1998, 155:1584–1591.

    PubMed  CAS  Google Scholar 

  72. Rosenberg DR, Chugani DC, Muzik O, et al.: Altered serotonin synthesis in frontostriatal circuitry in pediatric obsessive compulsive disorder. Biol Psychiatry 1998, 43:243.

    Article  Google Scholar 

  73. Fitzgerald KD, Moore GJ, Paulson LA, et al.: Proton spectroscopic imaging of the thalamus in treatment-naive pediatric obsessive-compulsive disorder. Biol Psychiatry 2000, 47:174–182.

    Article  PubMed  CAS  Google Scholar 

  74. Moore GJ, MacMaster FP, Stewart C, Rosenberg DR: Case study: caudate glutamatergic changes with paroxetine therapy for pediatric obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 1998, 37:663–667.

    Article  PubMed  CAS  Google Scholar 

  75. Brody AL, Saxena S, Schwartz JM, et al.: FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder. Psychiatry Res 1998, 84:1–6. 18F-fluorodeoxyglucose photon emission tomography scans of the brain were obtained in subjects with OCD before treatment with either behavior therapy or fluoxetine. Higher normalized metabolism in the left orbitofrontal cortex region was associated with worse outcome in the fluoxetine treated group (consistent with previous studies), but with greater improvement in the behavior therapy treated group. Differing patterns of metabolism may preferentially respond to behavior therapy versus medication.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Research Council Research Unit on Anxiety Disorders, University of Stellenbosch, PO Box 19063, 7505, Tygerberg, South Africa

    Dan J. Stein MB

  2. Department of Psychiatry, University of Florida, 32610, Gainesville, FL, USA

    Dan J. Stein MB & Wayne K. Goodman MD

  3. Department of Psychiatry, Massachusetts General Hospital, Harvard University Medical School, 02114, Boston, MA, USA

    Scott L. Rauch MD

Authors
  1. Dan J. Stein MB
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wayne K. Goodman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Scott L. Rauch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stein, D.J., Goodman, W.K. & Rauch, S.L. The cognitive-affective neuroscience of obsessive-compulsive disorder. Curr Psychiatry Rep 2, 341–346 (2000). https://doi.org/10.1007/s11920-000-0079-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11920-000-0079-2

Keywords

Search

Navigation