Journal
SCHIZOPHRENIA RESEARCH
Volume 208, Issue -, Pages 221-227Publisher
ELSEVIER
DOI: 10.1016/j.schres.2019.02.015
Keywords
Methamphetamine; DNA methylation; Schizophrenia; Paranoia; Immune, inflammation
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Funding
- National Science and Technology Development Agency (NSTDA), Thailand
- Center for Alcohol Studies, Thailand
- Fogarty International Center of the National Institutes of Health (NIH) [D43TW009087]
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Background: There is evidence that schizophrenia is a neuro-immune disorder. Genes linked to intragenic LINE-1 methylation show a strong association with immune-associated disorders including psychosis. The aim of this study was to examine LINE-1 methylation patterns in paranoid schizophrenia and methamphetamine-induced paranoia, a model for schizophrenia. Methods: This study recruited 31 patients with paranoid schizophrenia, 94 with methamphetamine-induced paranoia (MIP) and 163 normal controls. LINE-1 methylation patterns were assayed in peripheral blood mononuclear cells and a combined bisulphite restriction analysis and COBRA were used to estimate LINE1 methylation (mC) and CpG dinucleotide methylation patterns, namely 2 methylated (mCmC) and 2 unmethylated (uCuC) CpGs and the partially methylated loci mCuC (5'm with 3'u) and uCmC (5'u with 3'm). Results: Patients with paranoid schizophrenia show highly significant changes in LINE-1 partial methylation patterns, namely a higher percentage of mCuC and lower percentage of uCmC as compared with controls and MIP patients, while the latter show a higher percentage of mCuC but lower percentage of uCmC as compared with controls. Higher mCuC significantly predicts paranoid schizophrenia with a sensitivity of 51.6%, specificity of 97.5% and an area under the ROC curve of 0.895. Conclusions: The results indicate that a common dysfunction in LINE-1 partial methylation may underpin both paranoid schizophrenia and MIP and that this methylation pattern is significantly more expressed in paranoid schizophrenia than MIP. Reciprocal links between impairments in LINE-1 methylation and neuro-immune and neuro-oxidative pathways may underpin the pathophysiology of both MIP and paranoid schizophrenia. (C) 2019 Elsevier B.V. All rights reserved.
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