Social and Emotional Learning Program MindUP Outcomes Associate with DNA Methylation and Epigenetic Age Acceleration

• In Event: Stopping the Clock: Evidence Suggests Psychosocial Interventions Attenuate Pediatric Biological Age Acceleration

Abstract

BACKGROUND. Social and emotional learning (SEL) programs implemented in classrooms have been shown to improve well-being, achievement, and positive behaviors. However, it is currently unknown if there are molecular changes associated with these beneficial effects of SEL programs. Thus, the goal of this study was to evaluate molecular associations related to an SEL program that includes mindful attention awareness training, MindUP. DNA methylation (DNAm) was investigated as an epigenetic mark resulting from a methyl group covalently bound to cytosine bases in DNA, which is stable yet reversible and has been implicated in the interplay between environment and genetic regulation. Associations with other interventions and positive mental and physical health have been found both at individual sites and within DNAm biomarkers which measure biological aging, termed epigenetic clocks. These epigenetic clocks, such as the Horvath PanTissue clock, can be used to estimate if an individual is biologically aging faster or slower than their chronological age, termed epigenetic age acceleration (EAA), with faster EAA associated with poorer health in adulthood.

OBJECTIVE. To investigate the potential association of differential DNAm and EAA with randomly assigned MindUP classroom participation and outcomes when compared to business-as-usual classrooms.

APPROACH. In this randomized controlled trial, 4 classrooms of 6th-7th grade students (N = 93) were randomly assigned to receive the 15 lesson MindUP program or serve as business-as-usual controls. Participation in MindUP was associated with increased empathy, positive affect, and prosocial behaviors. To assess biological change, saliva samples were taken before and after implementation measuring DNAm at both time points on the Illumina Infinium EPIC array at ~850,000 genomic sites. To control for DNAm associations with potential genetic susceptibility of individuals, we also accounted for ancestry using the Illumina GSA array. Principal component (PC) analysis was run on the DNAm data. MindUP randomization was not associated with any PCs before implementation but was significantly correlated with PC27 (adjusted p ≤ 0.05) after completion. This association with PC27 suggested MindUP participation associated with a cumulative signal across multiple DNAm sites. At the single site level, changes in ill-being, a composite of negative affect, anxiety, and depressive symptoms, were associated with changes in DNAm within neuroplasticity related genes SIRT2 (Figure 1), PLCH2 and CRAMP1L at the FDR <.05. Subsequently, when considering aspects of ill-being, anxiety symptoms in particular saw associations with extrinsic epigenetic age acceleration (EEAA) in the Horvath PanTissue clock (Table 1). Simple slopes revealed for the most anxious children, those who participated in MindUP did not have an association between anxiety and EEAA (t(1, 28) = -0.614, p = 0.540), but those who did not had increased EEAA with greater anxiety symptoms (t(1, 28) = 2.23, p = 0.028). This indicates a potential buffering of biological aging especially within the context of adolescent anxiety.

SIGNIFICANCE. These preliminary findings suggest this program could influence children at not just psychological levels, but the molecular level as well, and may even provide a biological buffering effect. This provides a foundation of evidence for future studies into the potential biological benefits of classroom-based universal SEL programs.

Authors

• Nicole Gladish, Stanford University
  Presenting Author

• Sarah M Merrill, University of British Columbia (UBC)

• M Jennifer Kitil, University of British Columbia (UBC)

• Jenna Whitehead, University of British Columbia

• Julia MacIsaac

• Molly S. Lawlor

• Michael S. Kobor

• Kimberly Schonert-Reichl, University of Illinois at Chicago