Polymorphisms in the glutamate transporter gene SLC1A1 and obsessive-compulsive symptoms induced by second-generation antipsychotic agents

Psychiatr Genet. 2012 Oct;22(5):245-52. doi: 10.1097/YPG.0b013e328353fbee.


Background: A large subgroup of schizophrenic patients develops obsessive-compulsive symptoms (OCS) during treatment with second-generation antipsychotics (SGA). A genetic risk factor for these secondary OCS was recently described in the gene SLC1A1 encoding the neuronal glutamate transporter excitatory amino acid carrier 1. The aim of this study was to replicate these findings in a European sample.

Methods: A total of 103 schizophrenic patients treated with SGAs were included. Three single nucleotide polymorphisms in SLC1A1 (rs2228622, rs3780412 and rs3780413), which had been associated with SGA-induced OCS, were investigated. Single marker and haplotype analyses were tested with logistic regressions using age, sex and medication type as covariates.

Results: Treatment with markedly antiserotonergic SGAs such as clozapine was more prevalent in the subgroup of patients with comorbid OCS (P<0.001). The dosage and duration of clozapine treatment correlated significantly with the severity of OCS. In contrast to the Asian sample, no genetic associations were found with OCS.

Conclusion: Larger samples are necessary to unravel the interplay of pharmacological and genetic risk factors for OCS in schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antipsychotic Agents / adverse effects*
  • Demography
  • Excitatory Amino Acid Transporter 3 / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Haplotypes / genetics
  • Humans
  • Inheritance Patterns / genetics
  • Logistic Models
  • Male
  • Models, Genetic
  • Obsessive-Compulsive Disorder / chemically induced*
  • Obsessive-Compulsive Disorder / genetics*
  • Polymorphism, Single Nucleotide / genetics*


  • Antipsychotic Agents
  • Excitatory Amino Acid Transporter 3
  • SLC1A1 protein, human