Association of the serotonin transporter promoter regulatory region polymorphism and obsessive-compulsive disorder

Although modulation of symptoms of obsessive-compulsive disorder (OCD) by s erotonergic agents is well established, it is unclear whether an abnormalit y in the central serotonergic system is involved in its etiology. The serot onin (5-HT) transporter (5-HTT), which is the key modulator of serotonergic neurotransmission, is the target for serotonin reuptake inhibiting drugs ( SRIs) that are uniquely effective in the treatment of OCD. In this prelimin ary study we report an association of a functional polymorphism in the 5HTT 5' regulatory-region and OCD. Seventy-five OCD Caucasian patients and 397 ethnically-matched individuals from a non-patient control group were genoty ped for the 5-HTTLPR. Population-based association analysis revealed that p atients with OCD were more likely to carry two copies of the long allele (I ) as compared to controls (46.7% vs 32.3%: chi(2) = 5.19, P = 0.023). This finding replicates a recent family-based study of this polymorphism in OCD, and thus indicates that the 5-HTTLPR may be associated with susceptibility to OCD.