Serotonin transporter gene promoter methylation in peripheral cells: neural correlates and tissue specificity

• In Event: 2-122 - From child conception to adulthood: why epigenetic data analysis should be integrated into longitudinal studies

Integrative Statement

Early adversity can influence gene expression via epigenetic mechanisms, including DNA methylation. Peripheral tissues are essential in psychiatric epigenetics, as DNA methylation generally cannot be assessed in the living human brain. Several magnetic resonance imaging (MRI) studies show associations of peripheral serotonin transporter (SLC6A4) gene methylation with function and/or structure of frontal-limbic circuits and brain’s resting-state. Commonly used samples are derived from blood, saliva or buccal cells. However, little is known regarding which peripheral tissue is most strongly associated with human brain processes. The aim of the current study was to compare the extent of the association between peripheral SLC6A4 gene methylation and frontal-limbic function, structure and resting-state in healthy individuals across peripheral tissues. Forty healthy prospectively-followed adults from the Quebec Longitudinal Study of Kindergarten Children underwent anatomical, resting-state and functional MRI. The use of a well-documented longitudinal sample of children followed for more than three decades allowed this study to have prospective measures of their life history and to have careful control over non-confounding factors; a noteworthy asset in the study of developmental psychopathology and DNA methylation correlates. Saliva-, blood- and buccal-derived DNA methylation was assessed by pyrosequencing. Blood derived SLC6A4 gene methylation was positively associated with superior frontal gray matter (GM) volume and with lateral parietal area (LP)-frontal pole regional resting-state functional connectivity (rsFC) (Figure 1). Saliva-derived SLC6A4 gene methylation was positively associated with superior frontal GM volume. Buccal-derived SLC6A4 gene methylation was positively associated with superior frontal and anterior cingulate cortical (ACC) GM volumes, as well as with LP-ACC and frontal pole regional rsFC. Current results confirmed the relevance of peripheral methylation for frontal-limbic processes in humans. Buccal cells may be the most sensitive cell type when studying SLC6A4 gene promoter methylation and its associated risk for neural vulnerability and resilience for psychopathologies in which serotonin is implicated. These data should be further validated in clinical populations.

Authors

• Elmira Ismaylova, University of Montreal
  Presenting Author

• Jessica Di Sante, Concordia University
  Non-Presenting Author

• Frank Vitaro, University of Montreal
  Non-Presenting Author

• Richard Ernest Tremblay, University of Montreal
  Non-Presenting Author

• Linda Booij, Concordia University
  Non-Presenting Author