Socially stratified DNA-methylation profiles are associated with disparities in child and adolescent mental health

Abstract

Importance: Economic and racial inequality is linked to disparities in children's mental health. Biomarkers that reflect these social disparities are lacking. Objective: We examined the hypothesis that salivary DNA-methylation patterns of higher inflammation and faster pace of biological aging are economically, racially and ethnically stratified and are associated with child mental health. Design: The Texas Twin Project is an on-going, observational, longitudinal study that began in May 2012. Analyses were preregistered on May 7, 2021, and completed on August 23, 2021. Setting: The population-based study identified and recruited participants from public school rosters in the greater Austin area. Participants: Participants in the analytic data set included all participants that agreed to contribute DNA samples and whose samples were assayed by January 2021. Exposures: Family- and neighborhood-level socioeconomic inequality, racial and ethnic identities (White, Latinx, Black, Asian). Main Measure(s): Environmental exposures were analyzed in relation to salivary DNA-methylation profiles of higher inflammation (DNAm-CRP) and faster pace of biological aging (DunedinPoAm). Child internalizing problems, attention problems, aggression, rule-breaking, ADHD, oppositional defiant disorder, and conduct disorder were measured using parent-reports and self-reports on abbreviated versions of the Achenbach Child Behavior Checklist and Conners 3. The hypotheses being tested were formulated after data collection of the present data freeze and were pre-registered prior to analyses being conducted. Results: In a sample of N=1,183 8-to-19-year-olds (609 female, age M=13.38y), children's salivary DNA-methylation profiles and psychiatric symptoms differed by socioeconomic conditions, race and ethnicity. Children with more parent-reported internalizing symptoms had higher DNAm-CRP (r=0.15, 95% CI=0.05 to 0.25, P=0.004) and DunedinPoAm (r=0.15, CI=0.05 to 0.25, P=0.002), and children with more parent-reported aggression problems had higher DNAm-CRP (r=0.17, CI=0.04 to 0.31, P=0.013). DNAm-CRP partially mediated advantage of higher family socioeconomic status (16% of total effect) and White racial identity (12% of total effect) on reduced internalizing symptoms. DunedinPoAm also partially mediated advantage of White racial identity on internalizing (19% of total effect). Conclusions and Relevance: Socioeconomic and racial inequality are visible in children's epigenetic profiles of inflammation and the rate of biological aging in a manner that is tied to social disparities in mental health.

Negative parenting, epigenetic age, and psychological problems: prospective associations from adolescence to young adulthood

“…First, the sample was relatively homogeneous regarding socio‐economic and ethnic background and included mostly Dutch families of middle‐ to higher‐SES. Our results might not replicate or might emerge even stronger in more varied samples including participants from lower SES strata, and/or ethnic minorities (Raffington, Tanksley, Vinnik, et al., 2021). Second, although we used contemporary algorithms for the most commonly used epigenetic clocks, the field is rapidly moving forward and newer adjustments such as clocks trained in specific (younger) populations may be a way to improve in the future (Dammering et al., 2021; McEwen et al., 2020).…”

“…Previous studies have found links between externalizing symptoms and DNAm (Barker, Walton, & Cecil, 2018; Carpentieri et al., 2021; Cicchetti & Handley, 2017). However, the only study we located that examined the links between externalizing symptoms and EA found a positive link with inflammation‐related methylation profiles, but not with epigenetic age (Raffington, Tanksley, Vinnik, et al., 2021). Thus, to the best of our knowledge, this is the first study showing the potential effects of preceding externalizing problems on EA.…”

“…Negative parenting, including threat, exposure to violence (Colich et al., 2020; Jovanovic et al., 2017; Sumner, Colich, Uddin, Armstrong, & McLaughlin, 2019), and harsh parenting (Brody, Yu, Chen, Beach, & Miller, 2016), has been associated with increased EA. Also, psychological problems, including internalizing symptoms (Dammering et al., 2021; Sumner et al., 2019; Tollenaar et al., 2021) and externalizing problems (Raffington et al., 2021), have been associated with increased EA. However, such links have often been based on cross‐sectional or retrospective data and EA has mostly been based on one single assessment of DNA methylation.…”

Trauma context exerts intergenerational effects on child mental health via DNA methylation

“…Further, evidence underscores the concept that DNA methylation functions as a lifelong mechanism for genome adaptation [ 2 ]. Additionally, studies have illuminated that DNA methylation profiles and psychiatric symptoms in children differ based on socioeconomic conditions, race, and ethnicity [ 3–5 ]. A correlation has been observed where increased symptomatology reports are associated with higher salivary DNA methylation profiles indicating greater inflammation and accelerated biological ageing [ 6 ].…”