Publications

Journal Article Ppublish

PubMed: 42744221 DOI: 10.1016/j.neuint.2026.106262

Epigenome-wide placental methylation landscapes in relation to antenatal depressive symptoms.

Neurochem Int 200:106262

Authors: Chinnasamy Thirumoorthy, Sree Sankar Darveekaran Nair, Mohan Deepa, Uma Ram, Ranjit Mohan Anjana, Muthuswamy Balasubramanyam, Viswanathan Mohan, Ponnusamy Saravanan, Kuppan Gokulakrishnan

Affiliations

  • Department of Neurochemistry, National Institute of Mental Health & Neuro Sciences (NIMHANS), Bangalore, India.
  • Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangaluru, India.
  • Madras Diabetes Research Foundation (MDRF), ICMR Collaboration Centre for Diabetes Research, Chennai, India.
  • Seethapathy Clinic & Hospital, Chennai, India.
  • Warwick Academic Health, Warwick Medical School, University of Warwick, Coventry, UK; Department of Diabetes, Endocrinology and Metabolism, George Eliot Hospital, Nuneaton, UK; Centre for Global Health, University of Warwick, Coventry, UK; Centre for Early Life, University of Warwick, Coventry, UK.
  • Department of Neurochemistry, National Institute of Mental Health & Neuro Sciences (NIMHANS), Bangalore, India.

Abstract

Antenatal depressive symptoms (ADS) are common during pregnancy and are linked to adverse maternal and offspring neurodevelopmental outcomes. The placenta plays a central role in maternal-fetal communication and may function as an epigenetic sensor of maternal psychological stress. However, placental epigenetic signatures associated with ADS remain poorly understood. This study investigated epigenome-wide placental DNA methylation patterns associated with ADS in an Indian cohort. Placental samples were collected at delivery from women recruited in early pregnancy into the STRiDE cohort. Depressive symptoms were assessed at 24-28 weeks' gestation using the Patient Health Questionnaire-9 (PHQ-9). Participants were classified as controls (PHQ-9 ≤ 4; n = 53) or ADS (PHQ-9 > 4; n = 54). Genome-wide DNA methylation profiling was performed using the Illumina Infinium MethylationEPIC array. Epigenome-wide association analysis identified no CpG sites that remained statistically significant after Benjamini-Hochberg FDR correction. Top nominal CpGs showed medium-to-large effect sizes for ADS. Exploratory analyses of the top nominally associated CpGs annotated to genes including TAP2, LRCH1, SLITRK2, RASSF1 and IL3 implicated in immune regulation, cellular signalling and neurodevelopment. Gene enrichment analysis suggested the involvement of biological processes and pathways related to synaptic organization, ion transport, Hippo signalling, and thyroid hormone regulation. In conclusion, the study findings provide preliminary evidence of DNA methylation signatures linked to potential candidate genes and biological pathways that may be relevant to ADS, supporting the need for validation in larger independent cohorts and functional experimental studies.

MeSH

Patient Health Questionnaire, Genes, Pregnancy, Genome, Signs And Symptoms, Epigenome, Placenta, Neurodevelopment