Serotonin Transporter Gene Methylation Research Articles

Serotonin transporter gene methylation and emotional regulation in preschool children born preterm: A longitudinal evaluation of the role of negative emotionality in infancy.

The aim of the study was to assess the contribution of negative emotionality at 3 months (T1) and serotonin transporter gene (SLC6A4) DNA methylation at 4.5 years of age (T2) to emotion regulation in pre-schoolers born very preterm and full-term. Forty one children (n=21 born very preterm, n=20 born full-term) participated in the study. Fretful behavior was assessed at T1 in response to the Face-to-FaceStill-Face (FFSF) paradigm. At T2, SLC6A4 DNA methylation was analyzed and emotion regulation was assessed using an observational procedure (i.e., the Pre-schooler Regulation of Emotional Stress, PRES). The very preterm group displayed higher emotion dysregulation during the PRES Reactivity phase than the full-term group. Higher levels of fretful behavior at 3 months were associated with greater emotional distress only for very preterm children with higher methylation at T2. No significant associations emerged in the full-term group. Despite current findings cannot be generalized owing to the relatively small sample size, this work provides preliminary longitudinal evidence about the link between negative emotionality during infancy, stress-linked epigenetic status at 4.5 years and emotion dysregulation in preschoolers born preterm.

231. Serotonin Transporter Gene Methylation and Antidepressant Treatment of Major Depressive Disorder

231. Serotonin Transporter Gene Methylation and Antidepressant Treatment of Major Depressive Disorder

Serotonin transporter gene methylation is associated with hippocampal gray matter volume.

The serotonin transporter (5-HTT) and the 5-HTTLPR/rs25531 polymorphisms in its gene (SLC6A4) have been associated with depression, increased stress-response, and brain structural alterations such as reduced hippocampal volumes. Recently, epigenetic processes including SLC6A4 promoter methylation were shown to be affected by stress, trauma, or maltreatment and are regarded to be involved in the etiology of affective disorders. However, neurobiological correlates of SLC6A4 promoter methylation have never been studied or compared to genotype effects by means of human neuroimaging hitherto Healthy subjects were recruited in two independent samples (N = 94, N = 95) to obtain structural gray matter images processed by voxel-based morphometry (VBM8), focusing on hippocampal, amygdala, and anterior cingulate gyrus gray matter structure. SLC6A4 promoter methylation within an AluJb element and 5-HTTLPR/rs25531 genotypes were analyzed in view of a possible impact on local gray matter volume Strong associations of AluJb methylation and hippocampal gray matter volumes emerged within each sample separately, which in the combined sample withstood most conservative alpha-corrections for the entire brain. The amygdala, insula, and caudate nucleus showed similar associations. The 5-HTTLPR/rs25531 showed no main effect on gray matter, and the effect of methylation rates on hippocampal structure was comparable among the genotype groups Methylation within the AluJb appears to have strong effects on hippocampal gray matter volumes, indicating that epigenetic processes can alter brain structures crucially involved in stress-related disorders. Different ways of regulating SLC6A4 expression might involve exonization or transcription factor binding as potentially underlying mechanisms, which, however, is speculative and warrants further investigation.