DNA Methylation, Prenatal Maternal Stress and the Broad Autism Phenotype in Adolescence: Project Ice Storm

Background/Objectives. Prenatal maternal stress (PNMS) predicts risk for autism spectrum disorders (ASD) although the mechanisms are unknown. The aim of this study was to determine the extent to which DNA methylation mediates the effects of PNMS from a natural disaster on autistic-like traits in offspring assessed during adolescence. Methods. Five months following the 1998 ice storm in Quebec, Canada we recruited women who had been pregnant during the crisis and assessed their PNMS: objective hardship, subjective distress, and cognitive appraisal. At age 13, their children provided blood samples for DNA. At ages 15, 16 and 19, the youth self-reported their own autistic-like traits using the Broad Autism Phenotype Questionnaire. Results. Results showed that mothers’ disaster-related objective hardship and their negative cognitive appraisal of the disaster predicted DNA methylation at age 13, which then predicted the severity of their children’s Aloof Personality and Pragmatic Language Deficits, but not Rigid Personality, at ages 15, 16 and 19. Mediation was significant particularly through genes within the PI3K/AKT/mTOR pathway which has been implicated in various neurodevelopmental disorders, including ASD. Interestingly, while greater PNMS predicted more severe ASD traits, the epigenetics effects were for less severe traits. Conclusions. These results suggest that DNA methylation, assessed in early adolescence, may protect against ASD traits at later ages, particularly when there is a mismatch between the prenatal environment (disaster) and the postnatal environment (absence of disaster). The interpretation of these results in the context of fetal programming and the predictive adaptive response are discussed.