Another pathway that also has been implicated in alcohol abuse, and particularly in the transition to alcohol dependence, involves two stress-response systems, the hypothalamic–pituitary–adrenal (HPA) axis and the extra-hypothalamic corticotropin-releasing factor (CRF) stress response system, which mediate the interaction of psychosocial stress and early alcohol use. The gene discussed is CRH; the disease is alcohol abuse.