Does MAOA increase susceptibility to prenatal stress in young children?

- Whether and how MAOA moderates susceptibility to prenatal adversity is unclear.
- Here MAOA moderated susceptibility to prenatal stress and tobacco exposure in boys.
- Preliminary evidence for passive gene-environment correlation was found.
- Girls whose fathers had MAOA-L genotype experienced higher stress at age 5.
- Future research to elucidate developmental variation in mechanisms is recommended.

BackgroundWe previously demonstrated a gene-by-prenatal-environment interaction whereby the monoamine oxidase A gene (MAOA) modified the impact of prenatal tobacco exposure (PTE) on adolescent disruptive behavior (DB), with the MAOA risk genotype varying by sex. We extend this work by examining whether this mechanism is evident with another common adversity, prenatal stress exposure (PSE), and whether sex differences are present earlier in development in closer proximity to exposure.MethodsParticipants were 281 mothers and their 285 children derived from a prenatal cohort with in-depth prospective measures of PSE and PTE. We assessed DB at age 5 via dimensional developmentally-sensitive measurement. Analyses were stratified by sex based on prior evidence for sex differences.ResultsConcurrent stress exposure predicted DB in children (β = 0.310, p = 0.001), while main effects of prenatal exposures were seen only in boys. We found a three-way interaction of MAOA × PSE × sex on DB (β = 0.813, p = 0.022). Boys with MAOA-H had more DB as a function of PSE, controlling for PTE (β = 0.774, p = 0.015), and as a function of PTE, controlling for PSE (β = 0.362, p = 0.037). Boys with MAOA-L did not show this susceptibility. MAOA did not interact with PSE (β = − 0.133, p = 0.561) nor PTE (β = − 0.144; p = 0.505) in predicting DB in girls. Examination of gene-environment correlation (rGE) showed a correlation between paternal MAOA-L and daughters' concurrent stress exposure (r = − 0.240, p = 0.013).DiscussionFindings underscore complex mechanisms linking genetic susceptibility and early adverse exposures. Replication in larger cohorts followed from the pregnancy through adolescence is suggested to elucidate mechanisms that appear to have varying developmental expression.