Serotonin 1A receptor gene is associated with Japanese methamphetamine-induced psychosis patients

Neuropharmacology. 2010 Feb;58(2):452-6. doi: 10.1016/j.neuropharm.2009.09.006. Epub 2009 Sep 10.


Background: Several investigations have reported associations the serotonin 1A (5-HT1A) receptor to schizophrenia and psychotic disorders, making 5-HT1A receptor gene (HTR1A) an adequate candidate gene for the pathophysiology of schizophrenia and methamphetamine (METH)-induced psychosis. Huang and colleagues reported that rs6295 in HTR1A was associated with schizophrenia. The symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid type schizophrenia. It may indicate that METH-induced psychosis and schizophrenia have common susceptibility genes. In support of this hypothesis, we reported that the V-act murine thymoma viral oncogene homologue 1 (AKT1) gene was associated with METH-induced psychosis and schizophrenia in the Japanese population. Furthermore, we conducted an analysis of the association of HTR1A with METH-induced psychosis.

Method: Using one functional SNP (rs6295) and one tagging SNP (rs878567), 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: Rs878567 was associated with METH-induced psychosis patients in the allele/genotype-wise analysis. Moreover, this significance remained after Bonferroni correction. In addition, we detected an association between rs6295 and rs878567 in HTR1A and METH-induced psychosis patients in the haplotype-wise analysis. Although we detected an association between rs6295 and METH-induced psychosis patients, this significance disappeared after Bonferroni correction.

Conclusion: HTR1A may play an important role in the pathophysiology of METH-induced psychosis in the Japanese population. However, because we did not perform a mutation scan of HTR1A, a replication study using a larger sample may be required for conclusive results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amphetamine-Related Disorders / genetics*
  • Asian Continental Ancestry Group / genetics
  • Case-Control Studies
  • Central Nervous System Stimulants / toxicity*
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Japan
  • Linkage Disequilibrium
  • Male
  • Methamphetamine / toxicity*
  • Polymorphism, Single Nucleotide*
  • Psychoses, Substance-Induced / genetics*
  • Receptor, Serotonin, 5-HT1A / genetics*
  • Sequence Analysis, DNA


  • Central Nervous System Stimulants
  • Receptor, Serotonin, 5-HT1A
  • Methamphetamine