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Influence of polymorphisms in genes SLC1A1, GRIN2B, and GRIK2 on clozapine-induced obsessive-compulsive symptoms

Jun Cai1, Wen Zhang, Zhenghui Yi

  • 1Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China.

Psychopharmacology
|May 11, 2013
PubMed
Abstract

Insights

Clozapine may induce obsessive-compulsive symptoms in schizophrenia patients. Genetic variations in SLC1A1 and GRIN2B, and their interaction, appear to increase susceptibility to these symptoms.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Genetics

Background:

  • Atypical antipsychotics like clozapine can induce obsessive-compulsive (OC) symptoms in schizophrenia patients.
  • Altered glutamate neurotransmission is implicated in obsessive-compulsive disorder (OCD) pathophysiology.
  • Genes SLC1A1, GRIN2B, and GRIK2 are involved in regulating glutamate transmission.

Purpose of the Study:

  • To investigate the association between SLC1A1, GRIN2B, and GRIK2 gene polymorphisms and clozapine-induced OC symptoms in schizophrenia.
  • To explore potential gene-gene interactions influencing OC symptom development.

Main Methods:

  • Genotyping of three polymorphisms (SLC1A1 rs2228622, GRIN2B rs890, GRIK2 rs1556995) in 250 schizophrenia patients on clozapine.
  • Assessment of OC symptom severity using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).
  • Categorization of patients into OC and non-OC groups based on Y-BOCS scores.

Main Results:

  • Trends of association were observed for SLC1A1 (rs2228622A) and GRIN2B (rs890T) alleles with OC symptoms.
  • A significant two-locus gene-gene interaction between SLC1A1 and GRIN2B was identified (p=0.0021).
  • Significant interaction between SLC1A1 and GRIN2B on Y-BOCS scores was found (p<0.001), with specific genotypes showing higher scores.

Conclusions:

  • SLC1A1 and GRIN2B genes, and their interaction, may contribute to the susceptibility of developing OC symptoms in schizophrenia patients treated with clozapine.
  • These findings highlight the role of specific genetic factors in clozapine-induced OC symptoms.

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