1 CHU Sainte-Justine Research Centre, Montreal, Canada.
2 Department of Psychiatry, University of Montreal, Montreal, Canada.
3 Department of Psychology, Concordia University, Montreal, Canada.
4 Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
5 School of Psychoeducation, University of Montreal, Montreal, Canada.
6 Department of Psychology, University of Quebec à Montreal, Montreal, Canada.
7 School of Psychology, University of Laval, Quebec, Canada.
8 Institute of Genetic, Neurobiological, and Social Foundations of Child Development, Tomsk State University, Tomsk, Russian Federation.
9 Department of Psychology, University of Montreal, Montreal, Canada.
10 School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin, Ireland.
11 CHU Sainte-Justine Research Centre, Montreal, Canada. linda.booij@concordia.ca.
12 Department of Psychiatry, University of Montreal, Montreal, Canada. linda.booij@concordia.ca.
13 Department of Psychology, Concordia University, Montreal, Canada. linda.booij@concordia.ca.

Serotonin transporter promoter methylation in peripheral cells and neural responses to negative stimuli: A study of adolescent monozygotic twins.

Transl Psychiatry. 2018 08 08;8(1):147

Authors: Ismaylova E, Lévesque ML, Pomares FB, Szyf M, Nemoda Z, Fahim C, Vitaro F, Brendgen M, Dionne G, Boivin M, Tremblay RE, Booij L

Abstract

Several studies have examined associations between peripheral DNA methylation patterns of the serotonin transporter gene (SLC6A4) promoter and symptoms of depression and anxiety. The SLC6A4 promoter methylation has also been associated with frontal-limbic brain responses to negative stimuli. However, it is unclear how much of this association is confounded by DNA sequence variations. We utilized a monozygotic-twin within-pair discordance design, to test whether DNA methylation at specific CpG sites in the SLC6A4 promoter of peripheral cells is associated with greater frontal-limbic brain responses to negative stimuli (sadness and fear), independently of DNA sequence effects. In total 48 pairs of healthy 15-year-old monozygotic twins from the Quebec Newborn Twin Study, followed regularly since birth, underwent functional magnetic resonance imaging while conducting an emotion-processing task. The SLC6A4 promoter methylation level was assessed in saliva samples using pyrosequencing. Relative to the co-twins with lower SLC6A4 promoter methylation levels, twins with higher peripheral SLC6A4 methylation levels showed greater orbitofrontal cortical (OFC) activity and left amygdala-anterior cingulate cortex (ACC) and left amygdala-right OFC connectivity in response to sadness as well as greater ACC-left amygdala and ACC-left insula connectivity in response to fearful stimuli. By utilising a monozygotic-twin design, we provided evidence that associations between peripheral SLC6A4 promoter methylation and frontal-limbic brain responses to negative stimuli are, in part, independent of DNA sequence variations. Although causality cannot be determined here, SLC6A4 promoter methylation may be one of the mechanisms underlying how environmental factors influence the serotonin system, potentially affecting emotional processing through frontal-limbic areas.

PMID: 30089832 [PubMed - indexed for MEDLINE]