Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population

Taro Kishi, Yasuhisa Fukuo, Tomo Okochi, Tsuyoshi Kitajima, Kunihiro Kawashima, Hiroshi Naitoh, Hiroshi Ujike, Toshiya Inada, Mitsuhiko Yamada, Naohisa Uchimura, Ichiro Sora, Masaomi Iyo, Norio Ozaki, Nakao Iwata

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Abstract

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.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalDrug and Alcohol Dependence
Volume113
Issue number1
DOIs
Publication statusPublished - 01-01-2011

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Methamphetamine
Psychotic Disorders
Genes
Population
Dextroamphetamine
olanzapine
Rats
Animals
Schizophrenia
Phencyclidine
Paranoid Schizophrenia
Clozapine
serotonin 6 receptor
Antipsychotic Agents
Synaptic Transmission
Serotonin
Haplotypes
Single Nucleotide Polymorphism
Animal Models
Alleles

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Kishi, Taro ; Fukuo, Yasuhisa ; Okochi, Tomo ; Kitajima, Tsuyoshi ; Kawashima, Kunihiro ; Naitoh, Hiroshi ; Ujike, Hiroshi ; Inada, Toshiya ; Yamada, Mitsuhiko ; Uchimura, Naohisa ; Sora, Ichiro ; Iyo, Masaomi ; Ozaki, Norio ; Iwata, Nakao. / Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population. In: Drug and Alcohol Dependence. 2011 ; Vol. 113, No. 1. pp. 1-7.
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title = "Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population",
abstract = "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.",
author = "Taro Kishi and Yasuhisa Fukuo and Tomo Okochi and Tsuyoshi Kitajima and Kunihiro Kawashima and Hiroshi Naitoh and Hiroshi Ujike and Toshiya Inada and Mitsuhiko Yamada and Naohisa Uchimura and Ichiro Sora and Masaomi Iyo and Norio Ozaki and Nakao Iwata",
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Kishi, T, Fukuo, Y, Okochi, T, Kitajima, T, Kawashima, K, Naitoh, H, Ujike, H, Inada, T, Yamada, M, Uchimura, N, Sora, I, Iyo, M, Ozaki, N & Iwata, N 2011, 'Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population', Drug and Alcohol Dependence, vol. 113, no. 1, pp. 1-7. https://doi.org/10.1016/j.drugalcdep.2010.06.021

Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population. / Kishi, Taro; Fukuo, Yasuhisa; Okochi, Tomo; Kitajima, Tsuyoshi; Kawashima, Kunihiro; Naitoh, Hiroshi; Ujike, Hiroshi; Inada, Toshiya; Yamada, Mitsuhiko; Uchimura, Naohisa; Sora, Ichiro; Iyo, Masaomi; Ozaki, Norio; Iwata, Nakao.

In: Drug and Alcohol Dependence, Vol. 113, No. 1, 01.01.2011, p. 1-7.

Research output: Contribution to journalArticle

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

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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