Accumulating evidence from preclinical studies has shown that early-life stress at a time of developmental plasticity can result in widespread, enduring alterations in stress circuitry, including the hypothalamic-pituitary-adrenal (HPA) axis, the mesolimbic dopamine reward pathway, and brain morphometry. It is likely that genetic variation combined with stress exposure will increase the likelihood of physical changes that are potential risk factors for addiction. One such example is the interaction between CRHR1 gene variation and childhood maltreatment as a predictor of HPA axis reactivity [36]. Another example is the finding that Met allele carriers of the functional BDNF Val66Met polymorphism were more sensitive than Val/Val homozygotes to the effects of early-life stress on gray matter volume shrinkage [37].
