Methamphetamine-induced psychosis is associated with DNA hypomethylation and increased expression of AKT1 and key dopaminergic genes
| Autor: | Mozhgan Taban, Soraya Mehrabi, Mahmood Barati, Mansoureh Soleimani, Shabnam Nohesara, Zohreh Mousavi-Behbahani, Hamid Mostafavi Abdolmaleky, Samira Narimani, Mohammad Taghi Joghataei, Mohammad Ghadirivasfi, Sam Thiagalingam, Mohammad Reza Ghasemzadeh |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Epigenomics Male Candidate gene Psychosis Dopamine Amphetamine-Related Disorders Pharmacology Biology Bioinformatics Catechol O-Methyltransferase Article Methamphetamine 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine medicine Humans Genetic Predisposition to Disease Epigenetics Promoter Regions Genetic Saliva Genetics (clinical) Receptors Dopamine D4 Receptors Dopamine D3 Promoter Methylation DNA Methylation medicine.disease Psychiatry and Mental health 030104 developmental biology Psychotic Disorders Case-Control Studies DNA methylation Female Transcriptome Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery DNA hypomethylation medicine.drug |
| Zdroj: | American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 171(8) |
| ISSN: | 1552-485X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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