Neuropsychiatric Disease and Treatment (Jul 2024)

Global DNA and RNA Methylation Signature in Response to Antipsychotic Treatment in First-Episode Schizophrenia Patients

  • Angelin M,
  • Gopinath P,
  • Raghavan V,
  • Thara R,
  • Ahmad F,
  • Munirajan AK,
  • Sudesh R

Journal volume & issue
Vol. Volume 20
pp. 1435 – 1444

Abstract

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Mary Angelin,1 Padmavathi Gopinath,1 Vijaya Raghavan,1,2 Rangaswamy Thara,2 Faraz Ahmad,3 Arasamabattu Kannan Munirajan,1 Ravi Sudesh4 1Department of Genetics, University of Madras, Dr ALM PG Institute of Basic Medical Sciences, Taramani Campus, Chennai, Tamil Nadu, 600 113, India; 2Schizophrenia Research Foundation, Chennai, Tamil Nadu, 600 101, India; 3Department of Biotechnology, School of Bioscience and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India; 4Department of Biomedical Sciences, School of Bioscience and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, IndiaCorrespondence: Ravi Sudesh, Department of Biomedical Sciences, School of Bioscience and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India, Tel +91-9176028134, Email [email protected]; [email protected] Arasamabattu Kannan Munirajan, Department of Genetics, Dr. ALM PG Institute Basic Medical Sciences, University of Madras, Taramani, Chennai, Tamil Nadu, 600 113, India, Tel +91-44-24547064 ; +91-9444460136, Email [email protected]; [email protected]: Schizophrenia is a heterogeneous chronic psychiatric disorder influenced by genetic and environmental factors. Environmental factors can alter epigenetic marks, which regulate gene expression and cause an array of systemic changes. Several studies have demonstrated the association of epigenetic modulations in schizophrenia, which can influence clinical course, symptoms, and even treatment. Based on this, we have examined the global DNA methylation patterns, namely the 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC); and the global RNA modification N6-methyladenosine (m6A) RNA methylation status in peripheral blood cells. First-Episode Psychosis (FEP) patients who were diagnosed with Schizophrenia (SCZ) and undergoing treatment were stratified as Treatment-Responsive (TR) and Treatment-Non-Responsive (TNR). Age- and sex-matched healthy subjects served as controls.Results: The methylation pattern of 5mC and 5hmC showed significant increases in patients in comparison to controls. Further, when patients were classified based on their response to treatment, there was a statistically significant increase in methylation patterns in the treatment non-responder group. 5fC and m6A levels did not show any statistical significance across the groups. Further, gender-based stratification did not yield any significant difference for the markers.Conclusion: The study highlights the increased global methylation pattern in SCZ patients and a significant difference between the TR versus TNR groups. Global 5mC and 5hmC epigenetic marks suggest their potential roles in schizophrenia pathology, and also in the treatment response to antipsychotics. Since not many studies were available on the treatment response, further validation and the use of more sensitive techniques to study methylation status could unravel the potential of these epigenetic modifications as biomarkers for SCZ as well as distinguishing the antipsychotic treatment response in patients.Keywords: schizophrenia, global methylation, treatment response, 5mC, 5hmC, m6A

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