Evidence for shared genetic risk between methamphetamine-induced psychosis and schizophrenia

Masashi Ikeda, Yuko Okahisa, Branko Aleksic, Mujun Won, Naoki Kondo, Nobuya Naruse, Kumi Aoyama-Uehara, Ichiro Sora, Masaomi Iyo, Ryota Hashimoto, Yoshiya Kawamura, Nao Nishida, Taku Miyagawa, Masatoshi Takeda, Tsukasa Sasaki, Katsushi Tokunaga, Norio Ozaki, Hiroshi Ujike, Nakao Iwata

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Methamphetamine (METH) use can provoke psychotic reactions requiring immediate treatment, namely METH-induced psychosis. Although the distinction between METH-induced and primary psychosis is important for understanding their clinical courses, we do not have clear diagnostic procedure by their symptoms. Not only are there similarities between the clinical features of METH-induced psychosis and schizophrenia (SCZ), but there is also epidemiological evidence of a shared genetic risk between 'METH-related' disorders and SCZ, which makes the differentiation of these two conditions difficult. In this study, we conducted a genome-wide association study (GWAS) targeting METH-dependent patients. The METH sample group, used in the METH-dependence GWAS, included 236 METH-dependent patients and 864 healthy controls. We also included a 'within-case' comparison between 194 METH-induced psychosis patients and 42 METH-dependent patients without psychosis in a METH-induced psychosis GWAS. To investigate the shared genetic components between METH dependence, METH-induced psychosis, and SCZ, data from our previous SCZ GWAS (total N=1108) were re-analyzed. In the SNP-based analysis, none of the SNPs showed genome-wide significance in either data set. By performing a polygenic component analysis, however, we found that a large number of 'risk' alleles for METH-induced psychosis are over-represented in individuals with SCZ (P best =0.0090). Conversely, we did not detect enrichment either between METH dependence and METH-induced psychosis or between METH dependence and SCZ. The results support previous epidemiological and neurobiological evidence for a relationship between METH-induced psychosis and SCZ. These also suggest that the overlap between genes scored as positive in these data sets can have higher probability as susceptibility genes for psychosis.

Original languageEnglish
Pages (from-to)1864-1870
Number of pages7
Issue number10
Publication statusPublished - Sept 2013


  • genome-wide association study
  • methamphetamine
  • polygenic component analysis
  • schizophrenia
  • substance use disorder
  • substance-induced psychosis

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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