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

Abstract

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 (Pbest=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.

• Authors: 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
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 38 Issue 10 Pg. 1864-70 (Sep 2013) ISSN: 1740-634X [Electronic] England
• PMID: 23594818 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Methamphetamine

Topics

• Alleles
• Amphetamine-Related Disorders (genetics)
• Asian People (genetics)
• Case-Control Studies
• Female
• Genetic Predisposition to Disease (genetics)
• Genome-Wide Association Study
• Humans
• Male
• Methamphetamine (adverse effects)
• Polymorphism, Single Nucleotide
• Psychoses, Substance-Induced (genetics)
• Schizophrenia (genetics)