TY - JOUR
T1 - Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population
AU - Kishi, Taro
AU - Fukuo, Yasuhisa
AU - Okochi, Tomo
AU - Kitajima, Tsuyoshi
AU - Kawashima, Kunihiro
AU - Naitoh, Hiroshi
AU - Ujike, Hiroshi
AU - Inada, Toshiya
AU - Yamada, Mitsuhiko
AU - Uchimura, Naohisa
AU - Sora, Ichiro
AU - Iyo, Masaomi
AU - Ozaki, Norio
AU - Iwata, Nakao
N1 - Funding Information:
This work was supported in part by research grants from the Japan Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labor and Welfare, and the Health Sciences Foundation (Research on Health Sciences focusing on Drug Innovation).
PY - 2011/1/1
Y1 - 2011/1/1
N2 - Background: Altered serotonergic neural transmission is hypothesized to be a susceptibility factor for psychotic disorders such as schizophrenia. The serotonin 6 (5-HT6) receptor is therapeutically targeted by several second generation antipsychotics, such as clozapine and olanzapine, and d-amphetamine-induced hyperactivity in rats is corrected with the use of a selective 5-HT6 receptor antagonist. In addition, the disrupted prepulse inhibition induced by d-amphetamine or phencyclidine was restored by 5-HT6 receptor antagonist in an animal study using rats. These animal models were considered to reflect the positive symptoms of schizophrenia, and the above evidence suggests that altered 5-HT6 receptors are involved in the pathophysiology of psychotic disorders. The symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid type schizophrenia. Therefore, we conducted an analysis of the association of the 5-HT6 gene (HTR6) with METH-induced psychosis. Method: Using five tagging SNPs (rs6693503, rs1805054, rs4912138, rs3790757 and rs9659997), we conducted a genetic association analysis of case-control samples (197 METH-induced psychosis patients and 337 controls) in the Japanese population. The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients. Results: rs6693503 was associated with METH-induced psychosis patients in the allele/genotype-wise analysis. Moreover, this association remained significant after Bonferroni correction. In the haplotype-wise analysis, we detected an association between two markers (rs6693503 and rs1805054) and three markers (rs6693503, rs1805054 and rs4912138) in HTR6 and METH-induced psychosis patients, respectively. Conclusion: HTR6 may play an important role in the pathophysiology of METH-induced psychosis in the Japanese population.
AB - Background: Altered serotonergic neural transmission is hypothesized to be a susceptibility factor for psychotic disorders such as schizophrenia. The serotonin 6 (5-HT6) receptor is therapeutically targeted by several second generation antipsychotics, such as clozapine and olanzapine, and d-amphetamine-induced hyperactivity in rats is corrected with the use of a selective 5-HT6 receptor antagonist. In addition, the disrupted prepulse inhibition induced by d-amphetamine or phencyclidine was restored by 5-HT6 receptor antagonist in an animal study using rats. These animal models were considered to reflect the positive symptoms of schizophrenia, and the above evidence suggests that altered 5-HT6 receptors are involved in the pathophysiology of psychotic disorders. The symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid type schizophrenia. Therefore, we conducted an analysis of the association of the 5-HT6 gene (HTR6) with METH-induced psychosis. Method: Using five tagging SNPs (rs6693503, rs1805054, rs4912138, rs3790757 and rs9659997), we conducted a genetic association analysis of case-control samples (197 METH-induced psychosis patients and 337 controls) in the Japanese population. The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients. Results: rs6693503 was associated with METH-induced psychosis patients in the allele/genotype-wise analysis. Moreover, this association remained significant after Bonferroni correction. In the haplotype-wise analysis, we detected an association between two markers (rs6693503 and rs1805054) and three markers (rs6693503, rs1805054 and rs4912138) in HTR6 and METH-induced psychosis patients, respectively. Conclusion: HTR6 may play an important role in the pathophysiology of METH-induced psychosis in the Japanese population.
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U2 - 10.1016/j.drugalcdep.2010.06.021
DO - 10.1016/j.drugalcdep.2010.06.021
M3 - Article
C2 - 20705401
AN - SCOPUS:78650242766
SN - 0376-8716
VL - 113
SP - 1
EP - 7
JO - Drug and Alcohol Dependence
JF - Drug and Alcohol Dependence
IS - 1
ER -