Genetic and environmental determinants of stress responding

Abstract

The risk for alcohol dependence throughout development is determined by both genetic and environmental factors. Genetic factors that are thought to modulate this risk act on neurobiological pathways regulating reward, impulsivity, and stress responses. For example, genetic variations in pathways using the brain signaling molecule (i.e., neurotransmitter) dopamine, which likely mediate alcohol's rewarding effects, and in two hormonal systems involved in the stress response (i.e., the hypothalamic-pituitary-adrenal axis and the corticotropin-releasing factor system) affect alcoholism risk. This liability is modified further by exposure to environmental risk factors, such as environmental stress and alcohol use itself, and the effects of these factors may be enhanced in genetically vulnerable individuals. The transition from alcohol use to dependence is the result of complex interactions of genes, environment, and neurobiology, which fluctuate throughout development. Therefore, the relevant genetic and environmental risk factors may differ during the different stages of alcohol initiation, abuse, and dependence. The complex interaction of these factors is yet to be fully elucidated, and translational studies, ranging from animal studies to research in humans, and well-characterized longitudinal studies are necessary to further understand the development of alcohol dependence.

Figure

Schematic depiction of the typical progression from alcohol use to alcohol dependence. Both genetic and environmental factors influence each stage of disease progression. Early-life experiences, including prenatal environments and early-life stressors, may affect the onset of alcohol use. In adolescence, heightened sensation seeking, resulting from an increase in cortical dopamine neurons, often results in experimentation with alcohol. In adulthood, alcohol use may occur to downregulate brain stress systems in individuals suffering from alcohol dependence. Thus, early alcohol use is motivated by positive reinforcement, whereas later stages are driven by negative reinforcement, when alcohol is consumed to alleviate negative emotional states.