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The –1019 C/G polymorphism of the 5–HT₁A receptor gene is associated with negative symptom response to risperidone treatment in schizophrenia patients

¹ Bio–X Center, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China and Institute forNutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai200031, China.
² Bio–X Center, Shanghai Jiao Tong University, Shanghai, China, and Institute for Nutritional Science, ShanghaiInstitute of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
³ Bio–X Center, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China and Institutefor Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai200031, China
⁴ Shanghai Institute of Mental Health, 600 South Wan Ping Road, Shanghai 200030, China
⁵ Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, 294Taiyuan Road, Shanghai 200031, China and NHGG, Bio–X Center, Shanghai Jiao Tong University, Shanghai 200030, China.

^* To whom correspondence should be addressed.

	Abstract

The application of pharmacogenetics is currently one of the most promisingdevelopments in anti–psychotic treatment and is attracting more andmore attention. Although risperidone belongs to the first–line atypicalanti–psychotics, there have been relatively few risperidone pharmacogeneticstudies, especially in Asian populations. We investigated the relationshipbetween the C825T polymorphism of GBN3 (rs5443) and the 21019 C/Gpolymorphism of 5–HT1A (rs6295) and response to risperidone treatment.One–hundred and thirty schizophrenia patients were recruited. They weretreated with risperidone monotherapy for eight weeks. Clinical responsewas assessed on the Positive and Negative Syndrome Scale (PANSS) onthe day of admission and was subsequently assessed after eight weeksfollowing the treatment. Patients were genotyped for two functionalpolymorphisms: C825T of GBN3 (rs5443) and 21019 C/G of HT1A(rs6295). Association tests between genotypes and percentage improvement in total PANSS scores, as well as positive symptom scoresand negative symptom scores, were performed using analyses of variance(ANOVA).The 21019 C/G polymorphism of HT1A (rs6295) was associated withnegative symptom response to treatment. Patients with the CC genotypeshowed substantial improvement as regards negative symptom response(F 5 4.177, df 5 2, P 5 0.019), compared with the patients with the CGand GG genotypes. No association was observed between C825T of GBN3(rs5443) and changes in PANSS scores.The results suggest that the 21019 C/G polymorphism (rs6295)in the 5–HT1A gene may be a useful predictor of reduction innegative symptoms in schizophrenic patients treated withrisperidone.

Key Words: 5–HT1A, pharmacogenomics, schizophrenia, risperidone, treatmentresponse

First published on February 28, 2008, doi:10.1177/0269881107081522

Journal of Psychopharmacology 2008;22:904.

A more recent version of this article appeared on November 1, 2008


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