Abstract
Accumulating evidence suggests that genetic factors contribute to the vulnerability to methamphetamine (MAP) abuse and associated psychiatric symptoms. Chronic MAP abuse leads to psychosis, which may be of a transient or a prolonged type. Serotonergic dysfunction has been proposed as one of the contributory factors in the development of MAP psychosis. Our PET studies revealed that the serotonin transporter (5-HTT) density in global brain regions is significantly lower in MAP abusers. In this study, we examined the role of a functional polymorphism in the 5′ flanking region of the 5-HTT gene (5-HTTLPR) in the development of MAP psychosis in a Japanese population. We analyzed DNA samples from 166 MAP patients (95 with transient and 71 with prolonged psychosis) and 197 age-, sex-, and geographic-origin-matched healthy controls. Patients were also subdivided according to the presence (n = 119) or absence (n = 148) of spontaneous relapse. We observed significant genotypic association of the 5-HTTLPR polymorphism with MAP psychosis (P = 0.022), particularly in patients who show prolonged psychosis. The frequency of the S allele in patients with prolonged psychosis was significantly higher than that of the controls (P = 0.045); it was further higher in patients with prolonged psychosis with spontaneous relapse (P = 0.004). 5-HTTLPR has been suggested to regulate the transcriptional activity of 5-HTT, with S alleles showing lesser transcriptional efficiency and also lower 5-HT1A receptor-binding potential. Prolonged MAP use, combined with the high frequency of 5-HTTLPR S-alleles, may lead to reduced 5-HTT levels and 5-HT1A receptor-binding potential in the brain, resulting in the dysfunction of the serotonergic system. Thus, we suggest a possible role for the 5-HTTLPR polymorphism in MAP psychosis.
| Original language | English |
|---|---|
| Title of host publication | Drug Addiction |
| Subtitle of host publication | Research Frontiers and Treatment Advances |
| Publisher | Blackwell Publishing Inc. |
| Pages | 49-56 |
| Number of pages | 8 |
| ISBN (Print) | 9781573317184 |
| DOIs | |
| Publication status | Published - 01-01-2008 |
Publication series
| Name | Annals of the New York Academy of Sciences |
|---|---|
| Volume | 1139 |
| ISSN (Print) | 0077-8923 |
| ISSN (Electronic) | 1749-6632 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science
Cite this
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Short allele of 5-HTTLPR as a risk factor for the development of psychosis in Japanese methamphetamine abusers. / Ezaki, Norikazu; Nakamura, Kazuhiko; Sekine, Yoshimoto; Thanseem, Ismail; Anitha, Ayyappan; Iwata, Yasuhide; Kawai, Masayoshi; Takebayashi, Kiyokazu; Suzuki, Katsuaki; Takei, Nori; Iyo, Masaomi; Inada, Toshiya; Iwata, Nakao; Harano, Mutsuo; Komiyama, Tokutaro; Yamada, Mitsuhiko; Sora, Ichiro; Ujike, Hiroshi; Mori, Norio.
Drug Addiction: Research Frontiers and Treatment Advances. Blackwell Publishing Inc., 2008. p. 49-56 (Annals of the New York Academy of Sciences; Vol. 1139).Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
TY - GEN
T1 - Short allele of 5-HTTLPR as a risk factor for the development of psychosis in Japanese methamphetamine abusers
AU - Ezaki, Norikazu
AU - Nakamura, Kazuhiko
AU - Sekine, Yoshimoto
AU - Thanseem, Ismail
AU - Anitha, Ayyappan
AU - Iwata, Yasuhide
AU - Kawai, Masayoshi
AU - Takebayashi, Kiyokazu
AU - Suzuki, Katsuaki
AU - Takei, Nori
AU - Iyo, Masaomi
AU - Inada, Toshiya
AU - Iwata, Nakao
AU - Harano, Mutsuo
AU - Komiyama, Tokutaro
AU - Yamada, Mitsuhiko
AU - Sora, Ichiro
AU - Ujike, Hiroshi
AU - Mori, Norio
PY - 2008/1/1
Y1 - 2008/1/1
N2 - Accumulating evidence suggests that genetic factors contribute to the vulnerability to methamphetamine (MAP) abuse and associated psychiatric symptoms. Chronic MAP abuse leads to psychosis, which may be of a transient or a prolonged type. Serotonergic dysfunction has been proposed as one of the contributory factors in the development of MAP psychosis. Our PET studies revealed that the serotonin transporter (5-HTT) density in global brain regions is significantly lower in MAP abusers. In this study, we examined the role of a functional polymorphism in the 5′ flanking region of the 5-HTT gene (5-HTTLPR) in the development of MAP psychosis in a Japanese population. We analyzed DNA samples from 166 MAP patients (95 with transient and 71 with prolonged psychosis) and 197 age-, sex-, and geographic-origin-matched healthy controls. Patients were also subdivided according to the presence (n = 119) or absence (n = 148) of spontaneous relapse. We observed significant genotypic association of the 5-HTTLPR polymorphism with MAP psychosis (P = 0.022), particularly in patients who show prolonged psychosis. The frequency of the S allele in patients with prolonged psychosis was significantly higher than that of the controls (P = 0.045); it was further higher in patients with prolonged psychosis with spontaneous relapse (P = 0.004). 5-HTTLPR has been suggested to regulate the transcriptional activity of 5-HTT, with S alleles showing lesser transcriptional efficiency and also lower 5-HT1A receptor-binding potential. Prolonged MAP use, combined with the high frequency of 5-HTTLPR S-alleles, may lead to reduced 5-HTT levels and 5-HT1A receptor-binding potential in the brain, resulting in the dysfunction of the serotonergic system. Thus, we suggest a possible role for the 5-HTTLPR polymorphism in MAP psychosis.
AB - Accumulating evidence suggests that genetic factors contribute to the vulnerability to methamphetamine (MAP) abuse and associated psychiatric symptoms. Chronic MAP abuse leads to psychosis, which may be of a transient or a prolonged type. Serotonergic dysfunction has been proposed as one of the contributory factors in the development of MAP psychosis. Our PET studies revealed that the serotonin transporter (5-HTT) density in global brain regions is significantly lower in MAP abusers. In this study, we examined the role of a functional polymorphism in the 5′ flanking region of the 5-HTT gene (5-HTTLPR) in the development of MAP psychosis in a Japanese population. We analyzed DNA samples from 166 MAP patients (95 with transient and 71 with prolonged psychosis) and 197 age-, sex-, and geographic-origin-matched healthy controls. Patients were also subdivided according to the presence (n = 119) or absence (n = 148) of spontaneous relapse. We observed significant genotypic association of the 5-HTTLPR polymorphism with MAP psychosis (P = 0.022), particularly in patients who show prolonged psychosis. The frequency of the S allele in patients with prolonged psychosis was significantly higher than that of the controls (P = 0.045); it was further higher in patients with prolonged psychosis with spontaneous relapse (P = 0.004). 5-HTTLPR has been suggested to regulate the transcriptional activity of 5-HTT, with S alleles showing lesser transcriptional efficiency and also lower 5-HT1A receptor-binding potential. Prolonged MAP use, combined with the high frequency of 5-HTTLPR S-alleles, may lead to reduced 5-HTT levels and 5-HT1A receptor-binding potential in the brain, resulting in the dysfunction of the serotonergic system. Thus, we suggest a possible role for the 5-HTTLPR polymorphism in MAP psychosis.
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U2 - 10.1196/annals.1432.011
DO - 10.1196/annals.1432.011
M3 - Conference contribution
SN - 9781573317184
T3 - Annals of the New York Academy of Sciences
SP - 49
EP - 56
BT - Drug Addiction
PB - Blackwell Publishing Inc.
ER -