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

Mol Psychiatry. 1999 Sep;4(5):463-6. doi: 10.1038/


Although modulation of symptoms of obsessive-compulsive disorder (OCD) by serotonergic agents is well established, it is unclear whether an abnormality in the central serotonergic system is involved in its etiology. The serotonin (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 preliminary study we report an association of a functional polymorphism in the 5-HTT 5' regulatory-region and OCD. Seventy-five OCD Caucasian patients and 397 ethnically-matched individuals from a non-patient control group were genotyped for the 5-HTTLPR. Population-based association analysis revealed that patients with OCD were more likely to carry two copies of the long allele (l) as compared to controls (46.7% vs 32.3%: chi2 = 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.

MeSH terms

  • Alleles
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Chi-Square Distribution
  • Female
  • Gene Frequency
  • Genetic Linkage*
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Obsessive-Compulsive Disorder / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics*
  • Serotonin Plasma Membrane Transport Proteins
  • Whites / genetics


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins