Premium
DNA Methylation/Demethylation Network Expression in Psychotic Patients with a History of Alcohol Abuse
Author(s) -
Guidotti Alessandro,
Dong Erbo,
Gavin David P.,
Veldic Marin,
Zhao Weihan,
Bhaumik Dulal K.,
Pandey Subhash C.,
Grayson Dennis R.
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01947.x
Subject(s) - dna methylation , epigenetics , methylation , demethylation , prefrontal cortex , dna demethylation , positive and negative syndrome scale , methyltransferase , microbiology and biotechnology , dna , chemistry , biology , gene expression , psychosis , psychology , gene , genetics , psychiatry , neuroscience , cognition
Background Recent studies suggest that protracted and excessive alcohol use induces an epigenetic dysregulation in human and rodent brains. We recently reported that DNA methylation dynamics are altered in brains of psychotic ( PS ) patients, including schizophrenia and bipolar disorder patients. Because PS patients are often comorbid with chronic alcohol abuse, we examined whether the altered expression of multiple members of the DNA methylation/demethylation network observed in postmortem brains of PS patients was modified in PS patients with a history of chronic alcohol abuse. Methods DNA ‐methyltransferase‐1 ( DNMT 1) m RNA ‐positive neurons were counted in situ in prefrontal cortex samples obtained from the H arvard B rain T issue R esource C enter, B elmont, MA . 10‐11‐translocation ( TET s 1, 2, 3), apolipoprotein B editing complex enzyme ( APOBEC ‐3 C ), growth and DNA ‐damage‐inducible protein 45β ( GADD 45β), and methyl‐binding domain protein‐4 ( MBD 4) m RNA s were measured by quantitative real‐time polymerase chain reaction in inferior parietal cortical lobule samples obtained from the S tanley F oundation N europathology C onsortium, B ethesda, MD . Results We observed an increase in DNMT 1 m RNA ‐positive neurons in PS patients compared with non‐PS subjects. In addition, there was a pronounced decrease in APOBEC ‐3 C and a pronounced increase in GADD 45β and TET 1 m RNA s in PS patients with no history of alcohol abuse. In PS patients with a history of chronic alcohol abuse, the numbers of DNMT 1‐positive neurons were not increased significantly. Furthermore, the decrease in APOBEC‐3C m RNA was less pronounced, while the increase in TET 1 m RNA had a tendency to be potentiated in those PS patients that were chronic alcohol abusers. GADD 45β and MBD 4 m RNA s were not influenced by alcohol abuse. The effect of chronic alcohol abuse on DNA methylation/demethylation network enzymes cannot be attributed to confounding demographic variables or to the type and dose of medication used. Conclusions Based on these results, we hypothesize that PS patients may abuse alcohol as a potential attempt at self‐medication to normalize altered DNA methylation/demethylation network pathways. However, before accepting this conclusion, we need to study alterations in the DNA methylation/demethylation pathways and the DNA methylation dynamics in a substantial number of alcoholic PS and non‐ PS patients. Additional investigation may also be necessary to determine whether the altered DNA methylation dynamics are direct or the consequence of an indirect interaction of alcohol with the neuropathogenetic mechanisms underlying psychosis.