Risperidone response and 5-HT6 receptor gene variance: genetic association analysis with adjustment for nongenetic confounders

Lane, Hsien-Yuan; Lin, Cheng-Chieh; Huang, Chiung-Hsien; Chang, Yue-Cune; Hsu, Shih-Kuan; Chang, Wen-Ho

doi:10.1016/j.schres.2003.08.006

« Previous Next »Schizophrenia Research
Volume 67, Issue 1 , Pages 63-70, 1 March 2004

Risperidone response and 5-HT₆ receptor gene variance: genetic association analysis with adjustment for nongenetic confounders

Hsien-Yuan Lane
- Corresponding author. Department of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan. Tel.: +886-4-22062121; fax: +886-4-22361042.
- Department of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan
- Department of Medical Research, China Medical University Hospital, Institute of Medical Sciences, China Medical University, Taichung, Taiwan
Cheng-Chieh Lin
- Department of Medical Research, China Medical University Hospital, Institute of Medical Sciences, China Medical University, Taichung, Taiwan
Chiung-Hsien Huang
- Department of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan
- Department of Medical Research, China Medical University Hospital, Institute of Medical Sciences, China Medical University, Taichung, Taiwan
Yue-Cune Chang
- Department of Mathematics, Tamkang University, Taipei, Taiwan
Shih-Kuan Hsu
- Department of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan
Wen-Ho Chang
- Department of Psychiatry, Tzu-Chi University, Hualien, Taiwan

Received 15 May 2003; accepted 24 August 2003.

Abstract

Previous genetic-response studies, usually without considering environmental factors, encountered great difficulties in replication of results. Although atypical antipsychotics are becoming the mainstay for schizophrenia treatment which makes an antipsychotic “atypical” remains unclear. Risperidone (a widely used atypical antipsychotic agent) and several other atypicals have high affinities for 5-HT₆ and 5-HT₇ receptors. This study investigated the effects of the T→C 267 polymorphism in the 5HT₆ receptor gene and two rare Pro279Leu and Thr92Lys substitutions in the 5HT₇ receptor gene on risperidone efficacy after rigorous control for nongenetic confounders. We found an association between the T→C 267 polymorphism of the 5HT₆ receptor gene and response to risperidone in 123 acutely ill schizophrenia inpatients after adjustment for confounders. Compared to patients with the T/C 267 genotype, those with T/T 267 showed less severe positive symptoms (p=0.006) and general psychopathology (including anxiety, depression, and cognitive dysfunctions) (p=0.005). The T→C 267 polymorphism had no influences on negative symptoms. The two rare polymorphisms in the 5HT₇ receptor gene were not observed in our sample. In conclusion, the 5HT₆ receptor gene variant can affect risperidone response to positive symptoms and general psychopathology (but not negative symptoms) after control for nongenetic factors.