Methylation Matters: Interaction Between Methylation Density and Serotonin Transporter Genotype Predicts Unresolved Loss or Trauma

Background: Do genetic or epigenetic factors play a role in making some individuals more vulnerable than others to loss of attachment figures or other traumatic experiences? Methods: DNA was obtained from growth phase entrained Epstein-Barr Virus (EBV) transformed lymphoblast cell lines from 143 adopted participants. Genotype of the serotonin transporter linked polymorphic region (5HTTLPR) was determined, and methylation ratios for each of the C-phosphate-G (CpG) residues were assessed using quantitative mass spectroscopy. Unresolved loss or trauma was established using the Berkeley Adult Attachment Interview. Results: Higher levels of methylation of the 5HTT promoter associated CpG island were associated with increased risk of unresolved responses to loss or other trauma in carriers of the usually protective 5HTTLPR // variant. The ss variant of 5HTTLPR predicted more unresolved loss or trauma, but only in case of lower levels of methylation. Higher levels of methylation of the ss variant were associated with less unresolved loss or other trauma. Conclusions: Associations between 5HTTLPR polymorphisms and psychological problems are significantly altered by environmentally induced methylation patterns. Methylation may serve as the interface between adverse environment and the developing organism.