Association of SAPAP3 allelic variants with symptom dimensions and pharmacological treatment response in obsessive-compulsive disorder

Abstract BackgroundThough 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. MethodsA 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. ResultsAfter 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). LimitationsWe did not use a dimensional measure for assessing OCD symptoms. Treatment response was assessed over naturalistic follow-up. ConclusionSpecific 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. Public Significance Statement“This study finds that a specific polymorphism in the SAPAP3 gene, was found to be associated with the contamination/washing symptoms of OCD and was also found to predict resistance to pharmacological treatment” HighlightsSAPAP3 gene is implicated in OCDAssociation of SAPAP3 gene (rs6662980) with OCD phenotypes was examinedPresence of the minor (G) allele predicted contamination & washing symptomsSAPAP3 polymorphism had a significant association with treatment responseInteraction between presence of G-allele and contamination factor score predicted treatment resistance