Academic journal article Alcohol Research: Current Reviews

Genetic and Environmental Determinants of Stress Responding

Academic journal article Alcohol Research: Current Reviews

Genetic and Environmental Determinants of Stress Responding

Article excerpt

The development of alcohol dependence is a complex process influenced by both genetic and environmental risk factors (Prescott and Kendler 1999). The relative contributions of genetic and environmental influences fluctuate across development. During adolescence the initiation of alcohol use is strongly influenced by environmental factors (Dick et al. 2007; Heath et al. 1997; Karvonen 1995; Latendresse et al. 2008; McGue et al. 2000), whereas the genetic contribution to alcohol use at this stage is nonspecific and increases the risk for general externalizing behavior (Moffitt 1993; Moffitt et al. 2002). Specific genetic factors increasingly become relevant, however, as patterns of alcohol use are established (Hopfer et al. 2003; Pagan et al. 2006), particularly in mid-adulthood when dependence tends to emerge (Kendler et al. 2010; Schuckit et al. 1995). Gene-environment interactions also play a role because the influence of certain genetic factors seems to increase when a person is exposed to relevant environmental risk factors (Uhart and Wand 2009). Therefore, the development of dependence can be conceptualized within a temporal framework of genes, environment, and behavior.

The purpose of this review is to explore, within this framework, the contribution of some of the neurobiological systems that are important for the development of alcohol dependence. One of these is the mesolimbic dopaminergic system, which is involved in inducing the rewarding effects of alcohol and plays a central role in early alcohol use. 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. Both of these systems exemplify how the effects of genes and environment may be augmented during critical periods of alcohol use and dependence across the lifespan. For example, the dopaminergic system undergoes developmental transformations during adolescence that are associated with increased reward sensitivity and risk taking (Spear 2000), which presents a window of vulnerability for exposure to alcohol and stress. Then, as alcohol use continues through life, chronic exposure to alcohol can enhance the activity of (i.e., upregulate) the HPA and CRF systems. This dysregulation of the stress response systems becomes a pathological feature of alcohol dependence, perpetuating chronic alcohol drinking based on an allostatic shift (1) of the CRF system (Koob 2010). Moreover, the HPA, CRF, and dopaminergic systems can influence early alcohol drinking as a result of gene-environment interactions. This article will summarize the literature that has explored how genetic variation within the dopaminergic and stress response systems can influence the risk of alcohol dependence and how the exposure to relevant environmental risk factors and their interaction with genetic variants may influence alcoholism pathology. The effects of genes and environment on alcohol dependence will be discussed in a developmental framework from early childhood to adolescence as well as in the context of the development of dependence, when drinking behavior shifts from recreational use to dependence.

Role of Dopaminergic and Stress Response Systems in Alcohol Initiation and Early Alcohol Use

Environmental Factors and the Dopaminergic System

Several environmental factors have been shown to influence the initiation of alcohol consumption and its use during adolescence, including the level and quality of parental monitoring, peer-group influences, alcohol availability, and socioregional effects (Dick et al. 2007; Heath et al. 1997; Karvonen 1995; Latendresse et al. 2008; McGue et al. 2000). Thus, maternal and paternal alcohol use has been positively correlated with adolescent alcohol use at ages 14 and 17 (Latendresse et al. …

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