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.
Subject(s)
Amphetamine-Related Disorders/genetics , Genetic Predisposition to Disease/genetics , Methamphetamine/adverse effects , Psychoses, Substance-Induced/genetics , Schizophrenia/genetics , Alleles , Asian People/genetics , Case-Control Studies , Female , Genome-Wide Association Study , Humans , Male , Polymorphism, Single NucleotideABSTRACT
In this study, we examined the effect of the s.c. administration of (+/-) 3,4-methylenedioxymethamphetamine (MDMA) or saline on locomotor activity and Fos expression following the bilateral destruction of hippocampal dentate granule cells by colchicine in rats. The lesioned animals, when administered s.c. saline, showed a significantly greater increase in locomotor activity compared to the intact animals, and revealed a marginally significant level of increased locomotor activity compared to the sham-lesioned animals. In addition, when the lesioned animals were given s.c. saline or MDMA, there was a significant increase in Fos expression in the nucleus accumbens core, but not in the medial prefrontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex, piriform cortex, dorsal striatum, or nucleus accumbens shell, compared to the intact and sham-lesioned animals. Overall, these results suggest that the nucleus accumbens core may be involved in the enhancement of locomotor activity induced by the injection of saline alone (stress loading) or MDMA following bilateral destruction of hippocampal dentate granule cells by colchicine.
