Summary What is known and objective Obsessive‐compulsive disorder (OCD) is a chronic neuropsychiatric disorder. Selective serotonin reuptake inhibitors (SSRIs) are the first line of medication for OCD treatment; however, 40%‐60% of patients with OCD do not respond to SSRIs adequately. There are growing pieces of evidence which suggest a significant role for the glutamatergic system in the genesis of OCD and its consequent treatment. In the present study, we aimed to assess the association of SLC1A1 polymorphisms (rs301430, rs2228622 and rs3780413) with OCD and its clinical characteristics, as well as the importance of these SNPs in the response of OCD patients to SSRI pharmacotherapy. Methods Sample study consisted of 243 OCD cases and 221 control subjects. Patients were treated 12 weeks with fluvoxamine (daily dose: 150‐300 mg). Based on the reduction in obsessive and compulsive severity scores using Y‐BOCS severity scale, patients were classified as responders, non‐responders and refractory. A total of 239, 228 and 215 patients were genotyped for rs301430, rs2228622 and rs3780413, respectively, by the means of PCR‐RFLP. Results and discussion No association was detected between SLC1A1 SNPs and OCD, except an association between the familial form of the disease in males with rs2228622 (P = 0.033). The results of pharmacogenetic studies revealed the associations of two SLC1A1 SNPs, rs2228622 (P = 0.031) and rs3780413 (P = 0.008), with treatment response. What is new and conclusion Results of the current study suggest a role for the glutamate transporter in OCD treatment response with SSRIs which should encourage researchers to further investigate the importance of glutamate transporter in OCD pharmacogenetics.

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IntroductionObsessive–compulsive disorder (OCD) is a debilitating psychiatric disorder causing intrusive thoughts or repetitive behaviors. Serotonin reuptake inhibitors are used for OCD treatment, but 40%–60% of patients do not respond to them adequately. In this study, the associations of serotonin receptor 2a polymorphisms rs6311 and rs6313 with OCD, its familial form and fluvoxamine treatment response in Iranian population were investigated.Patients and methodsAssociation analyses were conducted in 293 OCD cases fulfilling the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR and 245 controls. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150–300 mg). Treatment response was considered as >25% reduction in Yale–Brown Obsessive Compulsive Scale score. Genotyping was performed by means of PCR-RFLP.ResultsThe results showed no association of rs6311 or rs6313 with OCD, but their haplotypes had different distribution patterns in cases and controls. Moreover, rs6313 was associated with the familial form of OCD in females significantly (P=0.005) under the recessive genetic model. Moreover, rs6311–rs6313 haplotypes were associated with fluvoxamine treatment response in OCD patients with more AC and less AT in responders.ConclusionHTR2A haplotypes are associated with OCD and its treatment response with a fluvoxamine in Iranian patients. Furthermore, the observed association of rs6313 with the familial form of OCD in females suggests different genetic background of OCD familial and non-familial forms, which needs further investigation.