Pain-related increase in serotonin transporter gene methylation associates with emotional regulation in 4.5-year-old preterm-born children

Aim: The main goal of this study was to assess the association between pain-related increase in serotonin transporter gene (SLC6A4) methylation and emotional dysregulation in 4.5-year-old preterm children compared with full-term matched counterparts. Methods: Preterm (n = 29) and full-term (n = 26) children recruited from two Italian hospitals were followed-up from October 2011 to December 2017. SLC6A4 methylation was assessed from cord blood at birth from both groups and peripheral blood at discharge for preterm ones. At 4.5 years, emotional regulation (ie, anger, fear and sadness) was assessed through an observational standardised procedure. Results: Preterm children (18 females; mean age = 4.5, range = 4.3-4.8) showed greater anger display compared with full-term controls (14 females; mean age = 4.5, range = 4.4-4.9) in response to emotional stress. Controlling for adverse life events occurrence from discharge to 4.5 years and SLC6A4 methylation at birth, CpG-specific SLC6A4 methylation in the neonatal period was predictive of greater anger display in preterm children but not in full-term ones. Conclusion: These findings contribute to highlight how epigenetic regulation of serotonin transporter gene in response to NICU pain exposure contributes to long-lasting programming of anger regulation in preterm children.