Genetic and pharmacogenetic study of glutamate transporter (SLC1A1) in Iranian patients with obsessive-compulsive...

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.

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.

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.

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.