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Pharmacogenomics J. 2013 Oct;13(5):470-5. doi: 10.1038/tpj.2012.30. Epub 2012 Jul 10.

Interaction of SLC1A1 gene variants and life stress on pharmacological resistance in obsessive-compulsive disorder.

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1] Neuroscience Group-IDIBELL (Institut d'Investigació Biomèdica de Bellvitge), CIBERSAM (Centro de Investigación en Red de Salud Mental-Instituto de Salud Carlos III), L'Hospitalet de Llobregat, Barcelona, Spain [2] OCD Clinical and Research Unit, Department of Psychiatry, Bellvitge Hospital, Feixa Llarga s/n, L'Hospitalet de Llobregat, Barcelona, Spain.


Genetic and environmental factors seem to interact and influence both the onset and the course of obsessive-compulsive disorder (OCD), but the role of glutamate transporter variants (SLC1A1) in pharmacological resistance is not known. We aimed to assess whether genetic variants in SLC1A1 and life stress at onset of the disorder interact and modulate pharmacological resistance in OCD. A single-marker association study of several single-nucleotide polymorphisms in the SLC1A1 genomic region was performed in a sample of 238 OCD patients. For the most strongly associated SNP (rs3087879), one copy of the risk allele increased the probability of higher treatment resistance (odds ratio=2.42; 95% confidence interval=1.39-4.21; P=0.0018), but only in OCD patients without life stress at onset of the disorder. These results suggest a gene-by-environment interaction effect on treatment resistance in OCD and strengthen the existing evidence of the role of the glutamatergic system in the phenomenology of OCD.

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