Neuroendocrine and immune pathways from pre- and perinatal stress to substance abuse

Early life adversity is a documented risk factor for substance abuse and addiction. The pre- and perinatal period (i.e., from implantation, through pregnancy, to 6 months of age) is a critical period marked by high biological plasticity and vulnerability, making perinatal stress a particularly robust form of adversity. The neuroendocrine and immune systems are key mechanisms implicated in the transmission of addiction risk. We review animal and human studies that provide preliminary evidence for links between perinatal stress, neuroendocrine and immune dysregulation, and risk for substance abuse and addiction. A translational neuroscience perspective is employed to elucidate pre- and perinatally-induced biological mechanisms linked to addiction and discuss implications for prevention and intervention efforts. Significant evidence supports associations between pre- and perinatal stress and dysregulation of the hypothalamic-pituitary-adrenal axis and immune systems as well as links between neuroendocrine/immune functioning and addiction risk. More work is needed to explicitly examine the interplay between pre- and perinatal stress and neuroendocrine/immune disruptions that together heighten substance abuse risk. Future work is needed to fully understand how pre- and perinatal stress induces biological alterations to predispose individuals to higher risk for addiction. Such knowledge will strengthen theoretically-driven and empirically-supported prevention efforts for substance abuse and addiction.