SLC6A4 Methylation as an Epigenetic Marker of Life Adversity Exposures in Humans: A Systematic Review of Literature

Neurosci Biobehav Rev. 2016 Dec;71:7-20. doi: 10.1016/j.neubiorev.2016.08.021. Epub 2016 Aug 24.


The application of epigenetics to the study of behavioral and socio-emotional development in humans has revealed that DNA methylation could be a potential marker of adversity exposure and long-lasting programming of health and disease. The serotonin transporter gene (SLC6A4) is a stress-related gene which has well-documented implications for behavioral and socio-emotional development and which has been shown to be susceptible to transcriptional regulation via epigenetic mechanisms. In the present paper, a systematic review of papers assessing the association among adversity exposures, SLC6A4 methylation and developmental outcomes is reported. Nineteen studies were included. Findings revealed that SLC6A4 methylation has been investigated in humans in association with a number of prenatal and postnatal adverse exposures, encompassing maternal depression during pregnancy, perinatal stress exposure, childhood trauma and abuse, and environmental stress. SLC6A4 is confirmed as a relevant biomarker of early adversity exposures, and epigenetic mechanisms occurring at this gene appear to play a critical role for programming. Nonetheless, specific methodological issues still need to be addressed in future human behavioral epigenetic research.

Keywords: Early adversity; Epigenetics; Methylation; SLC6A4; Serotonin transporter; Stress; Systematic review.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • DNA Methylation
  • Depression
  • Epigenesis, Genetic*
  • Epigenomics
  • Genetic Markers
  • Humans
  • Serotonin Plasma Membrane Transport Proteins / genetics*


  • Genetic Markers
  • Serotonin Plasma Membrane Transport Proteins