The experience of maltreatment and cumulative stressful life events prior to puberty and particularly in the first few years of life is associated with early onset of problem drinking in adolescence and alcohol and drug dependence in early adulthood [60,61]. The risk resilience balance for addiction may in part be due to the interaction between genetic variation and environment stressors (G x E) and this has been confirmed by twin studies of inferred genetic risk [62]. G x E interactive effects are likely for stress and anxiety related genes including HPA axis genes, GABAergic pathway genes and genes with a glucocorticoid response element located within their regulatory region such as MAOA, COMT and SLC6A4. Measured genotype studies to detect G x E effects have used a range of alcohol consumption and diagnostic phenotypes and stressors ranging from early life to adulthood past year life events [63]. To date, three studies have reported G x E effects on risk for AUD: CRHR1 variation and childhood sexual abuse in Australian participants [64]; CRHR1 variation and adulthood traumatic stress exposure in U.S. Caucasians [65] and MAOA variation and childhood sexual abuse in Southwestern American Indian women [66].
