Childhood adversity often pre-dates externalizing behaviors such as antisocial behavior and internalizing behaviors such as depression, both of which are risk factors for problem drinking and alcoholism. We have used data derived from parental self-report questionnaires in a birth cohort of approximately 7000 Caucasian girls and boys from the Avon Longitudinal Study of Parents and Children (ALSPAC), U.K. Mothers were recruited in early pregnancy and data is available on their children up to age 8 years. We have genotyped the children's DNA for functional polymorphisms in three genes: monoamine oxidase A (MAOA-LPR), serotonin transporter (5-HTTLPR) and catechol-O-methyltransferase (COMT Val158Met). ? ? In both sexes, family adversity and stressful life events had significant effects on behavioral disinhibition as early as age 4, persisting until at least age 8. In girls, MAOA-LPR had a significant effect and interacted with stressful life events experienced from 6 months to 3 years to influence hyperactivity at ages 4 and 7. In boys, the interaction of MAOA-LPR with stressful life events experienced between 1 and 2 years had a significant impact on hyperactivity at age 7 years. The low activity MAOA-LPR allele conferred risk (Enoch et al, submitted). Maternal depression and stressful life events increased the odds of high emotionality in children but there was no main or interactive effect of COMT Val158Met (Evans et al, 2008) or 5-HTTLPR (Araya et al, submitted) on behavior. ? ? In the American Indian sample we found that the MAOA-LPR low activity allele was significantly associated with alcoholism, particularly antisocial alcoholism, only in women who had been exposed to childhood sexual abuse. In contrast, there was no relationship between alcoholism/antisocial behavior and MAOA-LPR genotype among non-abused women (Ducci et al, 2008). In the African American men, the severity of childhood trauma was highly correlated with the risk for any addiction and with polysubstance dependence. An interaction between severe childhood trauma and GABRA2 variation influenced addiction vulnerability, particularly to cocaine (Enoch et al, submitted).
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