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

Schirmbeck, Frederike; Nieratschker, Vanessa; Frank, Josef; Englisch, Susanne; Rausch, Franziska; Meyer-Lindenberg, Andreas; Rietschel, Marcella; Zink, Mathias

doi: 10.1097/YPG.0b013e328353fbee
Original Articles

Background A large subgroup of schizophrenic patients develops obsessivecompulsive 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.

Departments of aPsychiatry and Psychotherapy

bGenetic Epidemiology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany

Correspondence to Frederike Schirmbeck, M.Psych, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, PO Box 12 21 20, D-68159 Mannheim, Germany Tel: +49 621 170 32523; fax: +49 621 170 31205; e-mail:

Received September 22, 2011

Accepted January 17, 2012

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.