Gene-environment interactions resulting in risk alcohol drinking behaviour are mediated by CRF and CRF1

Both genetic and environmental influences are known to influence an individuals' vulnerability to the misuse of alcohol. One of the most relevant environmental risk factors for alcoholism is that of stress. This review aims to examine the role of the biological stress systems in the etiology of alcoholism, with a focus on corticotrophin releasing factor (CRF) and its receptor CRF1. CRF is reviewed in the context of the biological stress systems within which it acts such as the HPA-axis, the noradrenergic system and the central and medial amygdale. These systems are examined in more detail by reviewing their genetic and molecular components in both humans and animals. It is concluded from the findings of the studies discussed in this review that CRF has a central role in the modulation of the stress response and that genetic variations in CRF or CRF1 may confer a susceptibility to alcoholism which is, in part, mediated by life stressors. Together these neurobiological, animal and human data suggest a role for CRF when developing treatment modalities for alcoholism alongside a pharmacogenetic approach to identify subtypes of patients which would benefit from these treatments or interventions.