PMID- 38516266
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240323
IS  - 1664-0640 (Print)
IS  - 1664-0640 (Electronic)
IS  - 1664-0640 (Linking)
VI  - 15
DP  - 2024
TI  - Methylome-wide and meQTL analysis helps to distinguish treatment response from 
      non-response and pathogenesis markers in schizophrenia.
PG  - 1297760
LID - 10.3389/fpsyt.2024.1297760 [doi]
LID - 1297760
AB  - Schizophrenia is a complex condition with entwined genetic and epigenetic risk 
      factors, posing a challenge to disentangle the intermixed pathological and 
      therapeutic epigenetic signatures. To resolve this, we performed 850K 
      methylome-wide and 700K genome-wide studies on the same set of schizophrenia 
      patients by stratifying them into responders, non-responders, and drug-naive 
      patients. The key genes that signified the response were followed up using 
      real-time gene expression studies to understand the effect of antipsychotics at 
      the gene transcription level. The study primarily implicates hypermethylation in 
      therapeutic response and hypomethylation in the drug-non-responsive state. 
      Several differentially methylated sites and regions colocalized with the 
      schizophrenia genome-wide association study (GWAS) risk genes and variants, 
      supporting the convoluted gene-environment association. Gene ontology and 
      protein-protein interaction (PPI) network analyses revealed distinct patterns 
      that differentiated the treatment response from drug resistance. The study 
      highlights the strong involvement of several processes related to nervous system 
      development, cell adhesion, and signaling in the antipsychotic response. The 
      ability of antipsychotic medications to alter the pathology by modulating gene 
      expression or methylation patterns is evident from the general increase in the 
      gene expression of response markers and histone modifiers and the decrease in 
      class II human leukocyte antigen (HLA) genes following treatment with varying 
      concentrations of medications like clozapine, olanzapine, risperidone, and 
      haloperidol. The study indicates a directional overlap of methylation markers 
      between pathogenesis and therapeutic response, thereby suggesting a careful 
      distinction of methylation markers of pathogenesis from treatment response. In 
      addition, there is a need to understand the trade-off between genetic and 
      epigenetic observations. It is suggested that methylomic changes brought about by 
      drugs need careful evaluation for their positive effects on pathogenesis, course 
      of disease progression, symptom severity, side effects, and refractoriness.
CI  - Copyright (c) 2024 Polakkattil, Vellichirammal, Nair, Nair and Banerjee.
FAU - Polakkattil, Binithamol K
AU  - Polakkattil BK
AD  - Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, 
      Thiruvananthapuram, Kerala, India.
AD  - Research Center, University of Kerala, Thiruvananthapuram, Kerala, India.
FAU - Vellichirammal, Neetha N
AU  - Vellichirammal NN
AD  - Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, 
      Thiruvananthapuram, Kerala, India.
FAU - Nair, Indu V
AU  - Nair IV
AD  - Mental Health Centre, Thiruvananthapuram, Kerala, India.
FAU - Nair, Chandrasekharan M
AU  - Nair CM
AD  - Nair's Hospital, Maradu, Kerala, India.
FAU - Banerjee, Moinak
AU  - Banerjee M
AD  - Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, 
      Thiruvananthapuram, Kerala, India.
LA  - eng
PT  - Journal Article
DEP - 20240307
PL  - Switzerland
TA  - Front Psychiatry
JT  - Frontiers in psychiatry
JID - 101545006
PMC - PMC10954811
OTO - NOTNLM
OT  - SNP genotyping
OT  - antipsychotics
OT  - epigenetics
OT  - gene expression
OT  - methylation
OT  - schizophrenia
OT  - treatment response
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/03/22 06:45
MHDA- 2024/03/22 06:46
PMCR- 2024/03/07
CRDT- 2024/03/22 04:08
PHST- 2023/09/21 00:00 [received]
PHST- 2024/02/06 00:00 [accepted]
PHST- 2024/03/22 06:46 [medline]
PHST- 2024/03/22 06:45 [pubmed]
PHST- 2024/03/22 04:08 [entrez]
PHST- 2024/03/07 00:00 [pmc-release]
AID - 10.3389/fpsyt.2024.1297760 [doi]
PST - epublish
SO  - Front Psychiatry. 2024 Mar 7;15:1297760. doi: 10.3389/fpsyt.2024.1297760. 
      eCollection 2024.