DNA methylation signatures of childhood trauma predict psychiatric disorders and other adverse outcomes 17 years after exposure

Childhood trauma is robustly linked to a broad range of adverse outcomes with consequences persisting far into adulthood. We conducted a prospective longitudinal study to predict psychiatric disorders and other adverse outcomes from trauma-related methylation changes 16.9 years after trauma exposure in childhood. Methylation was assayed using a sequencing-based approach that provides near-complete coverage of all 28 million sites in the blood methylome. Methylation data involved 673 assays from 489 participants aged 13.6 years (SD = 1.9) with outcomes measures collected at age 30.4 (SD = 2.26). For a subset of 303 participants we also generated methylation data in adulthood. Trauma-related methylation risk scores (MRSs) significantly predicted adult depression, externalizing problems, nicotine dependence, alcohol use disorder, serious medical problems, social problems and poverty. The predictive power of the MRSs was higher than that of reported trauma and could not be explained by the reported trauma, correlations with demographic variables, or a continuity of the predicted health problems from childhood to adulthood. Rather than measuring the occurrence of traumatic events, the MRSs seemed to capture the subject-specific impact of trauma. The majority of predictive sites did not remain associated with the outcomes suggesting the signatures of trauma do not become biologically embedded in the blood methylome. Instead, the long-term effects of trauma therefore seemed more consistent with a developmental mechanism where the initial subject-specific impacts of trauma are magnified over time. The MRSs have the potential to be a novel clinical biomarker for the assessment of trauma-related health risks.