Neurobiological correlates of obsessive-compulsive disorder (OCD): A narrative review

Giulio Perrotta; Anna Sara Liberati

doi:10.1002/ibra.70013

Ibrain ›› 2026, Vol. 12 ›› Issue (1) :86–95 DOI: 10.1002/ibra.70013

REVIEW

Neurobiological correlates of obsessive-compulsive disorder (OCD): A narrative review

Giulio Perrotta ¹
, Anna Sara Liberati ²

Author information +

History +

PDF (2070KB)

Abstract

Obsessive-compulsive disorder (OCD) is a common and disabling, as well as underdiagnosed, neuropsychiatric condition characterized by involuntary and unwanted obsessions and/or compulsions, often accompanied by states of severe anxiety, distress and shame, as well as other comorbid disorders. Despite the extensive literature available to date, only some of the neurobiological mechanisms underlying the symptomatic manifestations of the disorder have been clarified, underlining the need for further research. The brain structures involved are hippocampus, amygdala, striatum, thalamus, dorsolateral prefrontal cortex, anterior cingulate cortex, and orbitofrontal cortex; furthermore, most studies have mainly focused on the expressive modalities and on the individual structural and functional alterations of the brain, generating sometimes conflicting data. The aim of this article is therefore to summarize and bring together the main evidence collected so far on what would appear to be the neuroanatomical correlates and mechanisms underlying the disorder and its manifestations, to provide a sufficiently clear and complete overview.

Keywords

cortico-striato-thalamo-cortical circuit / limbic system / neuroanatomical correlates / obsessive-compulsive disorder / prefrontal cortex

Cite this article

Download citation ▾

Giulio Perrotta, Anna Sara Liberati. Neurobiological correlates of obsessive-compulsive disorder (OCD): A narrative review. Ibrain, 2026, 12 (1) : 86–95 DOI:10.1002/ibra.70013

登录浏览全文

4963

注册一个新账户忘记密码

References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	American Psychiatric Association. Diagnostic and statistical manual of mental disorders, Fifth edition. Washington, D.C. Trad. It.: Manuale diagnostico e statistico dei disturbi mentali, 5a ed. (DSM-V-TR), Raffaello Cortina; 2022.

[2]	Nazeer A, Latif F, Mondal A, Azeem MW, Greydanus DE. Obsessive-compulsive disorder in children and adolescents: epidemiology, diagnosis and management. Transl Pediatr. 2020;9(1):S76-S93.

[3]	Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014;15(6):410-424.

[4]	International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS). Revealing the complex genetic architecture of obsessive–compulsive disorder using meta-analysis. Mol Psychiatry. 2018;23(5):1181-1188.

[5]	Perera MPN, Gotsis ES, Bailey NW, Fitzgibbon BM, Fitzgerald PB. Exploring functional connectivity in large-scale brain networks in obsessive-compulsive disorder: a systematic review of EEG and fMRI studies. Cerebral Cortex. 2024;34(8):bhae327.

[6]	Noh HJ, Tang R, Flannick J, et al. Integrating evolutionary and regulatory information with a multispecies approach implicates genes and pathways in obsessive-compulsive disorder. Nat Commun. 2017;8(1):774.

[7]	Macul Ferreira de Barros P, do Rosário MC, Szejko N, et al. Risk factors for obsessive-compulsive symptoms. Follow-up of a community-based youth cohort. Eur Child Adolesc Psychiatry. 2021;30(1):89-104.

[8]	Marconi D, Limpido L, Bersani I, Giordano A, Bersani G. [PANDAS: a possible model for adult OCD pathogenesis]. Rivista di psichiatria. 2009;44(5):285-298.

[9]	Piras G, Rattazzi L, Paschalidis N, et al. Immuno-moodulin: a new anxiogenic factor produced by Annexin-A1 transgenic autoimmune-prone T cells. Brain Behav Immun. 2020;87: 689-702.

[10]	Janardhan Reddy Y, Sundar A, Narayanaswamy J, Math S. Clinical practice guidelines for obsessive-compulsive disorder. Indian J Psychiatry. 2017;59(1):74.

[11]	Bloch MH, Landeros-Weisenberger A, Rosario MC, Pittenger C, Leckman JF. Meta-analysis of the symptom structure of obsessive-compulsive disorder. Am J Psychiatry. 2008;165(12):1532-1542.

[12]	Hudepohl N, MacLean JV, Osborne LM. Perinatal obsessive-compulsive disorder: epidemiology, phenomenology, etiology, and treatment. Curr Psychiatry Rep. 2022;24(4):229-237.

[13]	de Wit SJ, Alonso P, Schweren L, et al. Multicenter voxel-based morphometry mega-analysis of structural brain scans in obsessive-compulsive disorder. Am J Psychiatry. 2014;171(3):340-349.

[14]	Boedhoe PSW, Schmaal L, Abe Y, et al. Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and Mega-Analysis. Am J Psychiatry. 2017;174(1):60-69.

[15]	Provenza NR, Reddy S, Allam AK, et al. Disruption of neural periodicity predicts clinical response after deep brain stimulation for obsessive-compulsive disorder. Nat Med. 2024;30(10):3004-3014.

[16]	Robbins TW, Everitt BJ. Neurobehavioural mechanisms of reward and motivation. Curr Opin Neurobiol. 1996;6(2):228-236.

[17]	Yang CR, Mogenson GJ. Ventral pallidal neuronal responses to dopamine receptor stimulation in the nucleus accumbens. Brain Res. 1989;489(2):237-246.

[18]	Jog MS, Kubota Y, Connolly CI, Hillegaart V, Graybiel AM. Building neural representations of habits. Science. 1999;286(5445):1745-1749.

[19]	Saxena S, Rauch SL. Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatr Clin North Am. 2000;23(3):563-586.

[20]	Huey ED, Zahn R, Krueger F, et al. A psychological and neuroanatomical model of obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci. 2008;20(4):390-408.

[21]	Ahmari SE, Spellman T, Douglass NL, et al. Repeated cortico-striatal stimulation generates persistent OCD-like behavior. Science. 2013;340(6137):1234-1239.

[22]	Burguière E, Monteiro P, Feng G, Graybiel AM. Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive behaviors. Science. 2013;340(6137):1243-1246.

[23]	Norman LJ, Carlisi C, Lukito S, et al. Structural and functional brain abnormalities in attention-deficit/hyperactivity disorder and obsessive-compulsive disorder: a comparative meta-analysis. JAMA Psychiatry. 2016;73(8):815-825.

[24]	Mathews C. Obsessive-compulsive disorders. Continuum. 2021;27(6):1764-1784.

[25]	Fitzgerald KD, Welsh RC, Stern ER, et al. Developmental alterations of frontal-striatal-thalamic connectivity in obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2011;50(9):938-948.e3.

[26]	Peng Z, Lui SSY, Cheung EFC, et al. Brain structural abnormalities in obsessive-compulsive disorder: converging evidence from white matter and grey matter. Asian J Psychiatry. 2012;5(4):290-296.

[27]	Taylor SF, Stern ER, Gehring WJ. Neural systems for error monitoring: recent findings and theoretical perspectives. Neuroscientist. 2007;13(2):160-172.

[28]	Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci. 2012;16(1):43-51.

[29]	Schlösser RGM, Wagner G, Schachtzabel C, et al. Fronto-cingulate effective connectivity in obsessive compulsive disorder: a study with fMRI and dynamic causal modeling. Hum Brain Mapp. 2010;31(12):1834-1850.

[30]	Dougherty DD, Baer L, Cosgrove GR, et al. Prospective long-term follow-up of 44 patients who received cingulotomy for treatment-refractory obsessive-compulsive disorder. Am J Psychiatry. 2002;159(2):269-275.

[31]	Perani D, Colombo C, Bressi S, et al. 18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic correlation study after treatment. Br J Psychiatry. 1995;166(2):244-250.

[32]	Yan H, Shan X, Li H, Liu F, Guo W. Abnormal spontaneous neural activity in hippocampal-cortical system of patients with obsessive-compulsive disorder and its potential for diagnosis and prediction of early treatment response. Front Cell Neurosci. 2022;16:906534.

[33]	Simon D, Adler N, Kaufmann C, Kathmann N. Amygdala hyperactivation during symptom provocation in obsessive-compulsive disorder and its modulation by distraction. NeuroImage Clin. 2014;4:549-557.

[34]	Atmaca M, Yildirim H, Ozdemir H, et al. Hippocampus and amygdalar volumes in patients with refractory obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1283-1286.

[35]	Cannistraro PA, Wright CI, Wedig MM, et al. Amygdala responses to human faces in obsessive-compulsive disorder. Biol Psychiatry. 2004;56(12):916-920.

[36]	Britton JC, Stewart SE, Killgore WDS, et al. Amygdala activation in response to facial expressions in pediatric obsessive-compulsive disorder. Depress Anxiety. 2010;27(7):643-651.

[37]	Zhang L, Hu X, Lu L, et al. Abnormalities of hippocampal shape and subfield volumes in medication-free patients with obsessive-compulsive disorder. Hum Brain Mapp. 2019;40(14):4105-4113.

[38]	Hong SB, Shin YW, Kim SH, et al. Hippocampal shape deformity analysis in obsessive-compulsive disorder. Eur Arch Psychiatry Clin Neurosci. 2007;257(4):185-190.

[39]	Liberati AS, Perrotta G. Neuroanatomical and functional correlates in post-traumatic stress disorder: a narrative review. Ibrain. 2024;10(1):46-58.

[40]	Reess TJ, Rus OG, Gürsel DA, et al. Association between hippocampus volume and symptom profiles in obsessive-compulsive disorder. NeuroImage Clin. 2018;17:474-480.