Background: Though several SAPAP3 gene knockout studies in mice have implicated its role in compulsivity, human studies have failed to demonstrate its association with obsessive-compulsive disorder (OCD). We examined the association between allelic variants of a single nucleotide polymorphism in the SAPAP3 gene (rs6662980) with specific aspects of the OCD phenotype. Methods: A total of 200 subjects with OCD were genotyped using the TaqMan assay. All subjects were assessed using Mini International Neuropsychiatric Interview, the Yale-Brown Obsessive-Compulsive Scale, and their treatment response was evaluated over naturalistic treatment and follow-up. Results: After correcting for multiple comparisons, G- allele at rs6662980 was found to be associated with contamination/washing symptoms (p=0.003). Logistic regression analysis also showed that presence of G allele predicted poor response to serotonin reuptake inhibitors [odds ratio = 2.473 (95% CI = 1.157 - 5.407), p=0.021]. Interaction between presence of G-allele and contamination factor score predicted SRI resistance (B= 1.197, p = 0.006). Limitations: We did not use a dimensional measure for assessing OCD symptoms. Treatment response was assessed over naturalistic follow-up. Conclusion: Specific phenotypic manifestations of OCD, which include contamination and washing-related symptoms along with resistance to serotonin reuptake inhibitors, may be related to alterations in the SAPAP3 gene.

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