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- Title
Profiling antipsychotic mediated methylation pattern in schizophrenia patients.
- Authors
Polakkattil, B.; Nair, C.; Banerjee, M.
- Abstract
Introduction: Schizophrenia is a chronic neuropsychiatric disease with a lifetime incidence rate of 1.41% in India. Antipsychotics are a major treatment option for alleviating psychotic symptoms. In-vitro studies have shown that antipsychotic drugs can alter the global methylation level. Therefore, we assume that the epigenetic patterns observed in the etiopathogenesis of schizophrenia are marred with antipsychotic drugs. Objectives: In this study, schizophrenic patients under antipsychotic treatment were compared against drug naïve patients to identify the methylation signatures of antipsychotic drug. Methods: We performed whole-genome methylome analysis of DNA from peripheral mononuclear cells using the Infinium Human Methylation EPIC BeadChip array platform (drug naive=8, under-treatment=16). Data analysis was performed using variuos packages in R environment. Results: LIMMA analysis identified a total of 78 differentially methylated probes (adj.p.value<0.01) out of which 12 probes were transcription factor binding sites, 39 belonged to DNase hypersensitivity region, 8 were from Fantom enhancer region, 14 were promoter associated. Top 5 hypermethylated sites were assigned to the following genes RP11-160E2.13, RP11-430C7, Y RNA, LRRN2, RP11-250B2. Most of these genes codes for long noncoding RNAs. DLX6-AS1, TMEM200B, DAGLB, FAM83H, LSM5 were the genes associated with top 5 hypomethylated sites. Pathway analysis by KEGG showed complement and coagulation cascade, supporting the hypothetical role of immune system modulation in schizophrenia and mTor signalling pathway, which is linked to antipsychotic treatment effects. Conclusions: Comparison between drug treated and drug naive schizophrenia patients show enrichment of complement associated signatures that support the probable role of immune system modulation in schizophrenia and immunosuppressive effect of antipsychotic drugs.
- Subjects
INDIA; PEOPLE with schizophrenia; LINCRNA; METHYLATION; ANTIPSYCHOTIC agents; DNA analysis; NEUROLEPTIC malignant syndrome
- Publication
European Psychiatry, 2020, Vol 63, pS251
- ISSN
0924-9338
- Publication type
Article