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 global methylation (mC) and LINE-1 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 % mCuC and lower % uCmC as compared with controls and MIP patients, while the latter show higher % mCuC but lower % 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. 4

Increased lipid peroxidation and lowered antioxidant defenses predict methamphetamine induced psychosis

“…Schizophrenia and MA dependence and MIP share several clinical characteristics, and MIP is frequently considered to be a mechanistic model of schizophrenia (Ikeda, Okahisa et al 2013, Gan, Song et al 2018, Kalayasiri, Kraijak et al 2019, Kalayasiri, Kraijak et al 2019). Dopaminergic signaling in the mesocorticolimbic and nigrostriatal networks has been implicated in schizophrenia and MIP (Hogarth, Manning et al 2021).…”

Role of GABRD Gene Methylation in the Nucleus Accumbens in Heroin-Seeking Behavior in Rats

“…Additionally, methamphetamine administration may alter DNA methylation patterns through regulation of DNMT1 mRNA levels (Numachi et al, 2007). Interestingly, a recent clinical study showed that methamphetamine-induced changes in long interspersed element-1 methylation are associated with methamphetamine-induced paranoia and therefore may partially explain the pathophysiology of this type of psychosis (Kalayasiri et al, 2019). Previous preclinical study reported that κ1 opioid receptor (OPRK1) promoter methylation was significantly correlated with the length and frequency of drug use in Chinese male heroin addicts (Ji et al, 2018).…”