No Association Between GRM3 and Japanese Methamphetamine- Induced Psychosis

Abstract

Several investigations have suggested that abnormalities in glutamate neural transmission play a role in the pathophysiology of psychiatric disorders, including schizophrenia. The metabotropic glutamate 3 receptor (mGluR3) gene was reported to be associated with schizophrenia, and paranoid type schizophrenia has symptoms that are similar to those of methamphetamine-induced psychosis. This suggests that mGluR3 gene (GRM3) is a good candidate gene for the pathogenesis of methamphetamine-induced psychosis. To evaluate the association between GRM3 and methamphetamine-induced psychosis, we conducted a case-control study of Japanese samples (181 methamphetamine-induced psychosis and 232 controls). Methods:We selected one functional SNP (rs6465084), reported to be associated with prefrontal brain functioning, for an association analysis. Written informed consent was obtained from each subject. This study was approved by the ethics committees at Fujita Health University, Nagoya University Graduate School of Medicine and each participating member of the Institute of the Japanese Genetics Initiative for Drug Abuse (JGIDA).Results:We did not detect an association between rs6465084 in GRM3 and Japanese methamphetamine-induced psychosis.Conclusion:Our findings suggest that rs6465084 in GRM3 does not play a major role in the pathophysiology of methamphetamine-induced psychosis in the Japanese population. However, because we did not perform an association analysis based on linkage disequilibrium (LD) or a mutation scan of GRM3, a replication study using a larger sample and based on LD may be required for conclusive results.

Sex-specific sensitivity to methamphetamine-induced schizophrenia-relevant behaviours in neuregulin 1 type III overexpressing mice

“…women use METH at an earlier age and appear more dependent on METH, but respond better to treatment) (Dluzen and Liu, 2008), there is limited clinical research into sex-specific effects of METH on psychotic or schizophrenia-relevant symptoms. However, considering some schizophrenia-relevant susceptibility genes are also associated with methamphetamine susceptibility (Kishi et al, 2010, 2011; Tsunoka et al, 2010; but see also Okumura et al, 2011; Tsunoka et al, 2011), and there are differences in the experience of psychotic symptoms between male and female methamphetamine-dependent individuals (Mahoney et al, 2010), investigating the biological basis of sex differences in response to METH in schizophrenia patients is highly relevant. It is possible that oestrogen may also be protective against METH-induced psychotic symptoms in a clinical setting, but this has yet to be assessed.…”