Elsevier

Biological Psychiatry

Volume 68, Issue 5, 1 September 2010, Pages 405-407
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2010.05.008Get rights and content

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 ll 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.

Section snippets

Participants

The Iowa Adoption Studies are a long-standing series of studies on children (domestically) adopted in the first few months after birth into middle-class families. Biodata were collected in the last round of data collection since 2004 (17). Here we use data from predominantly Caucasian (91%) adoptees who completed the AAI and for whom genotyping of the 5HTTLPR locus and methylation measures were available (n = 143; 50% females; mean age 39 years, SD = 7.32). All procedures were approved by the

Results

The results of the analysis of variance of unresolved loss or trauma with gender and 5HTTLPR genotype (ss, sl, ll) as factors and depression and methylation density as covariates are presented in Table 1. No significant main effects were found. The interaction between 5HTTLPR and promoter methylation significantly predicted scores on unresolved loss or trauma, F(2,121) = 4.87, p = .009, partial η2 = .08. Similar results were found when we controlled for age and when we included the

Discussion

In this study on participants with experiences of loss or other traumatic events, the 5HTTLPR genotype association with unresolved state of mind was dependent on methylation density. As expected, the long variant in combination with high methylation levels of the 5HTT promoter associated CpG islands predicted more unresolved loss or trauma. Methylation of alleles carrying the ll 5HTT variant seemed to hamper the expression of the otherwise protective ll variant (17) and to elevate the risk of

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