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Paranoid schizophrenia and methamphetamine-induced paranoia are both characterized by a similar LINE-1 partial methylation profile, which is more pronounced in paranoid schizophrenia.

Abstract：

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.

journal_name

Schizophr Res

journal_title

Schizophrenia research

authors

Kalayasiri R,Kraijak K,Mutirangura A,Maes M

doi

10.1016/j.schres.2019.02.015

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

221-227

eissn

0920-9964

issn

1573-2509

pii

S0920-9964(19)30075-1

journal_volume

208

pub_type

杂志文章

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