Association study of serine racemase gene with methamphetamine psychosis

E. Yokobayashi, H. Ujike, T. Kotaka, Yuko Okahisa, Manabu Takaki, M. Kodama, T. Inada, N. Uchimura, M. Yamada, N. Iwata, M. Iyo, I. Sora, N. Ozaki, S. Kuroda

Research output: Contribution to journalArticle

Abstract

Experimental studies have demonstrated that not only dopaminergic signaling but also glutamatergic/NMDA receptor signaling play indispensable roles in the development of methamphetamine psychosis. Our recent genetic studies provided evidence that genetic variants of glutamate-related genes such as DTNBP1, GLYT1, and G72, which are involved in glutamate release and regulation of co-agonists for NMDA receptors, conferred susceptibility to methamphetamine psychosis. Serine racemase converts l-serine to d-serine, which is an endogenous co-agonist for NMDA receptors. Three single nucleotide polymorphisms (SNPs) in the promoter region of the serine racemase gene (SRR), rs224770, rs3760229, and rs408067, were proven to affect the transcription activity of SRR. Therefore, we examined these SNPs in 225 patients with methamphetamine psychosis and 291 age- and sex-matched controls. There was no significant association between methamphetamine psychosis and any SNP examined or between the disorder and haplotypes comprising the three SNPs. However, rs408067 was significantly associated with the prognosis for methamphetamine psychosis and multi-substance abuse status. The patients with C-positive genotypes (CC or CG) of rs408067 showed better prognosis of sychosis after therapy and less abuse of multiple substances than the patients with GG genotypes. Because the C allele of rs408067 reduces the expression of SRR, a lower d-serine level or reduced NMDA receptor activation may affect the prognosis of methamphetamine psychosis and multiple substance abuse. Our sample size is, however, not large enough to eliminate the possibility of a type I error, our findings must be confirmed by replicate studies with larger samples.

Original languageEnglish
Pages (from-to)169-175
Number of pages7
JournalCurrent Neuropharmacology
Volume9
Issue number1
DOIs
Publication statusPublished - 2011

Fingerprint

Methamphetamine
Psychotic Disorders
N-Methyl-D-Aspartate Receptors
Single Nucleotide Polymorphism
Serine
Genes
Substance-Related Disorders
Glutamic Acid
Genotype
Genetic Promoter Regions
Sample Size
Haplotypes
serine racemase
Alleles

Keywords

  • Glutamate
  • Methamphetamine psychosis
  • NMDA receptors
  • Serine racemase
  • SNP

ASJC Scopus subject areas

  • Clinical Neurology
  • Pharmacology (medical)
  • Pharmacology
  • Neurology
  • Psychiatry and Mental health

Cite this

Association study of serine racemase gene with methamphetamine psychosis. / Yokobayashi, E.; Ujike, H.; Kotaka, T.; Okahisa, Yuko; Takaki, Manabu; Kodama, M.; Inada, T.; Uchimura, N.; Yamada, M.; Iwata, N.; Iyo, M.; Sora, I.; Ozaki, N.; Kuroda, S.

In: Current Neuropharmacology, Vol. 9, No. 1, 2011, p. 169-175.

Research output: Contribution to journalArticle

Yokobayashi, E, Ujike, H, Kotaka, T, Okahisa, Y, Takaki, M, Kodama, M, Inada, T, Uchimura, N, Yamada, M, Iwata, N, Iyo, M, Sora, I, Ozaki, N & Kuroda, S 2011, 'Association study of serine racemase gene with methamphetamine psychosis', Current Neuropharmacology, vol. 9, no. 1, pp. 169-175. https://doi.org/10.2174/157015911795017092
Yokobayashi, E. ; Ujike, H. ; Kotaka, T. ; Okahisa, Yuko ; Takaki, Manabu ; Kodama, M. ; Inada, T. ; Uchimura, N. ; Yamada, M. ; Iwata, N. ; Iyo, M. ; Sora, I. ; Ozaki, N. ; Kuroda, S. / Association study of serine racemase gene with methamphetamine psychosis. In: Current Neuropharmacology. 2011 ; Vol. 9, No. 1. pp. 169-175.
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