Biology of obsessive–compulsive disorder

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The biology of obsessive–compulsive disorder primarily involves[vague] the brain regions of the striatum, the orbitofrontal cortex and the cingulate cortex. People with OCD evince increased grey matter volumes in bilateral lenticular nuclei, extending to the caudate nuclei, while decreased grey matter volumes in bilateral dorsal medial frontal/anterior cingulate gyri.[1][2] These findings contrast with those in people with other anxiety disorders, who evince decreased (rather than increased) grey matter volumes in bilateral lenticular / caudate nuclei, while also decreased grey matter volumes in bilateral dorsal medial frontal/anterior cingulate gyri.[2] OCD involves several different receptors, mostly H2, M4, NK1, NMDA, and non-NMDA glutamate receptors.[3] The receptors 5-HT1D, 5-HT2C, and the μ opioid receptor exert a secondary effect.[clarification needed] The H2, M4, NK1, and non-NMDA glutamate receptors are active in the striatum, whereas the NMDA receptors are active in the cingulate cortex.

The activity of certain receptors is positively correlated to the severity of OCD, whereas the activity of certain other receptors is negatively correlated to the severity of OCD. Activity of the histamine receptor (H2); the Muscarinic acetylcholine receptor(M4); the Tachykinin receptor (NK1); and non-NMDA glutamate receptors are positively correlated with symptom severity in OCD. Associations for which activity is negatively correlated with severity include the NMDA receptor (NMDA); the Mu opioid receptor (μ opioid); and two types of 5-HT receptors (5-HT1D and 5-HT2C). The central dysfunction[clarification needed] of OCD may involve the receptors nk1, non-NMDA glutamate receptors, and NMDA, whereas the other receptors could simply exert secondary modulatory effects.

Pharmaceuticals that may directly counteract the core mechanisms are aprepitant (nk1 antagonist), riluzole (glutamate release inhibitor), and tautomycin (NMDA receptor sensitizer). Also, the anti-Alzheimer's drug memantine is being studied by the International OCD Foundation in its efficacy in reducing OCD symptoms due to it being an NMDA antagonist.[4] One case study published in The American Journal of Psychiatry suggests that "memantine may be an option for treatment-resistant OCD, but controlled studies are needed to substantiate this observation."[5] The drugs that are popularly used to fight OCD may be limited by their inaction upon what are believed to be the core mechanisms. Many trials are currently underway to investigate the efficacy of a variety of agents that affect these 'core' neurotransmitters, particularly glutamatergic agents.[1] Other genes and receptors under investigation for possible links to OCD include GABBR1, SLC1A1, GRIN2B, TPH2, DRD2, DRD3, DRD4, COMT, and MAO-A.

There is an association between brain-derived neurotrophic factor (BDNF) and OCD.[6] Hormonal dysregulation and a delayed sleep phase in patients with OCD point to a possible role of abnormal circadian rhythms in the pathophysiology of the disorder.[7]

Growing evidence indicates that OCD with rapid onset in children and adolescents may be caused by a syndrome connected to Group A streptococcal infections (PANDAS)[8][9][10] or caused by immunologic reactions to other pathogens (PANS).[11]

See also[edit]


  1. ^ Radua, Joaquim; Mataix-Cols, David (November 2009). "Voxel-wise meta-analysis of grey matter changes in obsessive–compulsive disorder". British Journal of Psychiatry 195 (5): 393–402. doi:10.1192/bjp.bp.108.055046. PMID 19880927. 
  2. ^ a b Radua, Joaquim; van den Heuvel, Odile A.; Surguladze, Simon; Mataix-Cols, David (5 July 2010). "Meta-analytical comparison of voxel-based morphometry studies in obsessive-compulsive disorder vs other anxiety disorders". Archives of General Psychiatry 67 (7): 701–711. doi:10.1001/archgenpsychiatry.2010.70. PMID 20603451. 
  3. ^ Paul, Sean (August 2013). "Serotonin System Dysfunction in OCD" 9. p. 1. 
  4. ^ Bloch, M. H., Coric, V., & Pittenger, C. "New Horizons in OCD Research and the Potential Importance of Glutamate: Can We Develop Treatments That Work Better and Faster?". International OCD Foundation. Retrieved 24 January 2012. 
  5. ^ Poyurovsky M, Weizman R, Weizman A, Koran L (2005). "Memantine for treatment-resistant OCD". The American Journal of Psychiatry 162 (11): 2191–2. doi:10.1176/appi.ajp.162.11.2191-a. PMID 16263867. 
  6. ^ Hall, D.; Dhilla, A.; Charalambous, A.; Gogos, A.; Karayiorgou, M. (Aug 2003). "Sequence Variants of the Brain-Derived Neurotrophic Factor (BDNF) Gene Are Strongly Associated with Obsessive-Compulsive Disorder". The American Journal of Human Genetics 73 (2): 370–376. doi:10.1086/377003. ISSN 0002-9297. PMC 1180373. PMID 12836135.  edit
  7. ^ Lange KW, Lange KM, Hauser J, Tucha L, Tucha O (October 2012). "Circadian rhythms in obsessive-compulsive disorder". J Neural Transm 119 (10): 1077–83. doi:10.1007/s00702-012-0805-z. PMID 22543530. 
  8. ^ Moretto, Germana, Pasquini Massimo, et al.: "What every psychiatrist should know about PANDAS: a review". Department of Psychiatric Sciences and Psychological Medicine, "Sapienza" University of Rome. In: Clinical Practice and Epidemiology in Mental Health 2008.
  9. ^ NIMH PANS/PANDAS Information Page:
  10. ^ "PANDAS studies are no longer recruiting patients". Bethesda, MD: National Institute of Mental Health, Pediatrics and Developmental Neuroscience Branch. 24 February 2009. Retrieved 13 December 2009. 
  11. ^ ↑ Swedo SE, Leckman JF, Rose NR: From Research Subgroup to Clinical Syndrome: Modifying the PANDAS Criteria to Describe PANS; Pediatr Therapeut 2012, 2:2; doi:10.4172/2161-0665.1000113