Genetic variants of D2 but not D3 or D4 dopamine receptor gene are associated with rapid onset and poor prognosis of methamphetamine psychosis

Hiroshi Ujike, Takeshi Katsu, Yuko Okahisa, Manabu Takaki, Masafumi Kodama, Toshiya Inada, Naohisa Uchimura, Mitsuhiko Yamada, Nakao Iwata, Ichiro Sora, Masaomi Iyo, Norio Ozaki, Shigetoshi Kuroda

Research output: Contribution to journalArticle

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Abstract

D2-like receptors are key targets for methamphetamine in the CNS, and their activation is an initial and indispensable effect in the induction of dependence and psychosis. It is possible that genetic variants of D2-like receptors may affect individual susceptibility to methamphetamine dependence and psychosis. To test this hypothesis, 6 putatively functional polymorphisms of D2-like receptors, -141C Ins/Del, Ser311Cys and TaqIA of the DRD2 gene, Ser9Gly of the DRD3 gene, and -521C>T and a variable number of tandem repeats in exon 3 of the DRD4 gene, were analyzed in 202 patients with methamphetamine dependence and/or psychosis and 243 healthy controls in a Japanese population. No polymorphism examined showed significant association with methamphetamine dependence, but two polymorphisms of DRD2 were associated with the clinical course and prognosis of methamphetamine psychosis. The A1/A1 homozygote of DRD2 was a negative risk factor for a poorer prognosis of psychosis that continues for more than 1 month after the discontinuance of methamphetamine abuse and the beginning of treatment with neuroleptics (p = 0.04, odds ratio (OR) = 0.42, 95% CI; 0.27-0.65) and the complication of spontaneous relapse of methamphetamine psychosis after remission (p = 0.014, OR = 0.34, 95% CI; 0.22-0.54). The genotype of -141C Del positive (Del/Del and Del/Ins) was at risk for rapid onset of methamphetamine psychosis that develops into a psychotic state within 3 years after initiation of methamphetamine abuse (p = 0.00037, OR = 3.62, 95% CI 2.48-5.28). These findings revealed that genetic variants of DRD2, but not DRD3 or DRD4, confer individual risks for rapid onset, prolonged duration, and spontaneous relapse of methamphetamine psychosis.

Original languageEnglish
Pages (from-to)625-629
Number of pages5
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume33
Issue number4
DOIs
Publication statusPublished - 15-06-2009

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Dopamine D4 Receptors
Dopamine D3 Receptors
Methamphetamine
Psychotic Disorders
Genes
Odds Ratio
Recurrence
Minisatellite Repeats
Homozygote
Antipsychotic Agents
Exons
Genotype

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Biological Psychiatry

Cite this

Ujike, Hiroshi ; Katsu, Takeshi ; Okahisa, Yuko ; Takaki, Manabu ; Kodama, Masafumi ; Inada, Toshiya ; Uchimura, Naohisa ; Yamada, Mitsuhiko ; Iwata, Nakao ; Sora, Ichiro ; Iyo, Masaomi ; Ozaki, Norio ; Kuroda, Shigetoshi. / Genetic variants of D2 but not D3 or D4 dopamine receptor gene are associated with rapid onset and poor prognosis of methamphetamine psychosis. In: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2009 ; Vol. 33, No. 4. pp. 625-629.
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Genetic variants of D2 but not D3 or D4 dopamine receptor gene are associated with rapid onset and poor prognosis of methamphetamine psychosis. / Ujike, Hiroshi; Katsu, Takeshi; Okahisa, Yuko; Takaki, Manabu; Kodama, Masafumi; Inada, Toshiya; Uchimura, Naohisa; Yamada, Mitsuhiko; Iwata, Nakao; Sora, Ichiro; Iyo, Masaomi; Ozaki, Norio; Kuroda, Shigetoshi.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 33, No. 4, 15.06.2009, p. 625-629.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic variants of D2 but not D3 or D4 dopamine receptor gene are associated with rapid onset and poor prognosis of methamphetamine psychosis

AU - Ujike, Hiroshi

AU - Katsu, Takeshi

AU - Okahisa, Yuko

AU - Takaki, Manabu

AU - Kodama, Masafumi

AU - Inada, Toshiya

AU - Uchimura, Naohisa

AU - Yamada, Mitsuhiko

AU - Iwata, Nakao

AU - Sora, Ichiro

AU - Iyo, Masaomi

AU - Ozaki, Norio

AU - Kuroda, Shigetoshi

PY - 2009/6/15

Y1 - 2009/6/15

N2 - D2-like receptors are key targets for methamphetamine in the CNS, and their activation is an initial and indispensable effect in the induction of dependence and psychosis. It is possible that genetic variants of D2-like receptors may affect individual susceptibility to methamphetamine dependence and psychosis. To test this hypothesis, 6 putatively functional polymorphisms of D2-like receptors, -141C Ins/Del, Ser311Cys and TaqIA of the DRD2 gene, Ser9Gly of the DRD3 gene, and -521C>T and a variable number of tandem repeats in exon 3 of the DRD4 gene, were analyzed in 202 patients with methamphetamine dependence and/or psychosis and 243 healthy controls in a Japanese population. No polymorphism examined showed significant association with methamphetamine dependence, but two polymorphisms of DRD2 were associated with the clinical course and prognosis of methamphetamine psychosis. The A1/A1 homozygote of DRD2 was a negative risk factor for a poorer prognosis of psychosis that continues for more than 1 month after the discontinuance of methamphetamine abuse and the beginning of treatment with neuroleptics (p = 0.04, odds ratio (OR) = 0.42, 95% CI; 0.27-0.65) and the complication of spontaneous relapse of methamphetamine psychosis after remission (p = 0.014, OR = 0.34, 95% CI; 0.22-0.54). The genotype of -141C Del positive (Del/Del and Del/Ins) was at risk for rapid onset of methamphetamine psychosis that develops into a psychotic state within 3 years after initiation of methamphetamine abuse (p = 0.00037, OR = 3.62, 95% CI 2.48-5.28). These findings revealed that genetic variants of DRD2, but not DRD3 or DRD4, confer individual risks for rapid onset, prolonged duration, and spontaneous relapse of methamphetamine psychosis.

AB - D2-like receptors are key targets for methamphetamine in the CNS, and their activation is an initial and indispensable effect in the induction of dependence and psychosis. It is possible that genetic variants of D2-like receptors may affect individual susceptibility to methamphetamine dependence and psychosis. To test this hypothesis, 6 putatively functional polymorphisms of D2-like receptors, -141C Ins/Del, Ser311Cys and TaqIA of the DRD2 gene, Ser9Gly of the DRD3 gene, and -521C>T and a variable number of tandem repeats in exon 3 of the DRD4 gene, were analyzed in 202 patients with methamphetamine dependence and/or psychosis and 243 healthy controls in a Japanese population. No polymorphism examined showed significant association with methamphetamine dependence, but two polymorphisms of DRD2 were associated with the clinical course and prognosis of methamphetamine psychosis. The A1/A1 homozygote of DRD2 was a negative risk factor for a poorer prognosis of psychosis that continues for more than 1 month after the discontinuance of methamphetamine abuse and the beginning of treatment with neuroleptics (p = 0.04, odds ratio (OR) = 0.42, 95% CI; 0.27-0.65) and the complication of spontaneous relapse of methamphetamine psychosis after remission (p = 0.014, OR = 0.34, 95% CI; 0.22-0.54). The genotype of -141C Del positive (Del/Del and Del/Ins) was at risk for rapid onset of methamphetamine psychosis that develops into a psychotic state within 3 years after initiation of methamphetamine abuse (p = 0.00037, OR = 3.62, 95% CI 2.48-5.28). These findings revealed that genetic variants of DRD2, but not DRD3 or DRD4, confer individual risks for rapid onset, prolonged duration, and spontaneous relapse of methamphetamine psychosis.

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