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

Frederike Schirmbeck1, Vanessa Nieratschker, Josef Frank

  • 1Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany. frederike.schirmbeck@zi-mannheim.de

Psychiatric Genetics
|April 26, 2012
PubMed
Abstract

Insights

This study investigated genetic factors in schizophrenia patients developing obsessive-compulsive symptoms (OCS) during second-generation antipsychotic (SGA) treatment. No genetic associations were found in the European sample, unlike previous findings.

Area of Science:

  • Psychiatry
  • Pharmacogenomics
  • Neuroscience

Background:

  • Obsessive-compulsive symptoms (OCS) frequently develop in schizophrenia patients treated with second-generation antipsychotics (SGA).
  • The SLC1A1 gene, encoding a glutamate transporter, was previously implicated as a genetic risk factor for SGA-induced OCS.
  • Replication of these genetic findings in a European cohort was investigated.

Purpose of the Study:

  • To replicate the association between SLC1A1 gene polymorphisms and secondary obsessive-compulsive symptoms (OCS) in schizophrenia patients treated with second-generation antipsychotics (SGA).
  • To explore the role of specific single nucleotide polymorphisms (SNPs) and haplotypes within the SLC1A1 gene.

Main Methods:

  • Genotyping of three SLC1A1 single nucleotide polymorphisms (SNPs) (rs2228622, rs3780412, rs3780413) in 103 schizophrenia patients on SGA treatment.
  • Logistic regression analyses were performed for single marker and haplotype associations, controlling for age, sex, and medication type.
  • Prevalence of OCS was compared between patients treated with different types of SGAs, and correlations with clozapine dosage and duration were examined.

Main Results:

  • Patients with comorbid OCS were more likely to be treated with antiserotonergic SGAs, particularly clozapine (P<0.001).
  • Clozapine dosage and treatment duration significantly correlated with OCS severity.
  • In contrast to a previous Asian sample, no significant genetic associations between the studied SLC1A1 SNPs/haplotypes and OCS were identified in this European cohort.

Conclusions:

  • The study did not replicate the association between SLC1A1 gene variants and secondary OCS in schizophrenia patients treated with SGAs in a European sample.
  • Pharmacological factors, specifically treatment with antiserotonergic SGAs like clozapine, appear to play a significant role in the development of OCS.
  • Larger sample sizes are required to elucidate the complex interplay between genetic and pharmacological risk factors for OCS in schizophrenia.

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