Early life stress, MAOA, and gene-environment interactions predict behavioral disinhibition in children


Mary-Anne Enoch, MD, NIH/NIAAA/DICBR/LNG, 5625 Fishers Lane, Room 3S32, MSC 9412, Bethesda, MD 20892, USA. E-mail:maenoch@niaaa.nih.gov


Several, but not all, studies have shown that the monoamine oxidase A functional promoter polymorphism (MAOA-LPR) interacts with childhood adversity to predict adolescent and adult antisocial behavior. However, it is not known whether MAOA-LPR interacts with early life (pre-birth–3 years) stressors to influence behavior in prepubertal children.

The Avon Longitudinal Study of Parents and Children, UK, is a community-representative cohort study of children followed from pre-birth onwards. The impact of family adversity from pre-birth to age 3 years and stressful life events from 6 months to 7 years on behavioral disinhibition was determined in 7500 girls and boys. Behavioral disinhibition measures were: mother-reported hyperactivity and conduct disturbances (Strengths and Difficulties Questionnaire) at ages 4 and 7 years.

In both sexes, exposure to family adversity and stressful life events in the first 3 years of life predicted behavioral disinhibition at age 4, persisting until age 7. In girls, MAOA-LPR interacted with stressful life events experienced from 6 months to 3.5 years to influence hyperactivity at ages 4 and 7. In boys, the interaction of MAOA-LPR with stressful life events between 1.5 and 2.5 years predicted hyperactivity at age 7 years. The low activity MAOA-LPR variant was associated with increased hyperactivity in girls and boys exposed to high stress. In contrast, there was no MAOA-LPR interaction with family adversity.

In a general population sample of prepubertal children, exposure to common stressors from pre-birth to 3 years predicted behavioral disinhibition, and MAOA-LPR– stressful life event interactions specifically predicted hyperactivity.