title: Methamphetamine-induced psychosis is associated with DNA hypomethylation and increased expression of AKT1 and key dopaminergic genes.
abstract: Methamphetamine, one of the most frequently used illicit drugs worldwide, can induce psychosis in a large fraction of abusers and it is becoming a major problem for the health care institutions. There is some evidence that genetic and epigenetic factors may play roles in methamphetamine psychosis. In this study, we examined methamphetamine-induced epigenetic and expression changes of several key genes involved in psychosis. RNA and DNA extracted from the saliva samples of patients with methamphetamine dependency with and without psychosis as well as control subjects (each group 25) were analyzed for expression and promoter DNA methylation status of DRD1, DRD2, DRD3, DRD4, MB-COMT, GAD1, and AKT1 using qRT-PCR and q-MSP, respectively. We found statistically significant DNA hypomethylation of the promoter regions of DRD3 (P = 0.032), DRD4 (P = 0.05), MB-COMT (P = 0.009), and AKT1 (P = 0.0008) associated with increased expression of the corresponding genes in patients with methamphetamine psychosis (P = 0.022, P = 0.034, P = 0.035, P = 0.038, respectively), and to a lesser degree in some of the candidate genes in non-psychotic patients versus the control subjects. In general, methamphetamine dependency is associated with reduced DNA methylation and corresponding increase in expression of several key genes involved in the pathogenesis of psychotic disorders. While these epigenetic changes can be useful diagnostic biomarkers for psychosis in methamphetamine abusers, it is also consistent with the use of methyl rich diet for prevention or suppression of psychosis in these patients. However, this needs to be confirmed in future studies. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Mental Health Research Center and Department of Psychiatry, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Nohesara
authors.affiliation: Mental Health Research Center and Department of Psychiatry, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ghadirivasfi
authors.affiliation: Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Barati
authors.affiliation: Mental Health Research Center and Department of Psychiatry, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Ghasemzadeh
authors.affiliation: Mental Health Research Center and Department of Psychiatry, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Samira
authors.initials: S
authors.lastname: Narimani
authors.affiliation: Mental Health Research Center and Department of Psychiatry, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Mousavi-Behbahani
authors.affiliation: Faculty of Medicine, Department of Anatomy and Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammadtaghi
authors.initials: M
authors.lastname: Joghataei
authors.affiliation: Faculty of Medicine, Department of Anatomy and Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Mental Health Research Center and Department of Psychiatry, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mozhgan
authors.initials: M
authors.lastname: Taban
authors.affiliation: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Soraya
authors.initials: S
authors.lastname: Mehrabi
authors.affiliation: Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts.|Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Sam
authors.initials: S
authors.lastname: Thiagalingam
authors.affiliation: Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Hamid Mostafavi
authors.initials: HM
authors.lastname: Abdolmaleky
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000235:genetics; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics; D004298:Dopamine; D057890:Epigenomics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D011618:Psychotic Disorders / Q000235:genetics* / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000235:genetics; D050638:Receptors, Dopamine D4 / Q000235:genetics; D012463:Saliva; D059467:Transcriptome
chemical_list: C493593:DRD3 protein, human; C493599:DRD4 protein, human; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D008694:Methamphetamine; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D004298:Dopamine
keywords: AKT1; DNA methylation; DRD1; DRD2; DRD3; DRD4; GAD1; MB-COMT; gene expression; methamphetamine; saliva