Page last updated: Tuesday, November 18, 2008
Factors influencing the development of alcohol dependence
by Creina Stockley, Australian Wine Research Institute
Until recently, medical science has attempted to apply linear models of cause and effect to diseases whose origins are polygenic or a consequence of complex gene-environment interactions. For example, separate models of alcohol dependence have been developed for the social, psychological, behavioural, genetic and biological aspects of dependence where the variance in predicting who will become an alcoholic has been attributed 50% to behavioural and social factors, and 50% to genetic and biological factors. Indeed, the risk of alcohol dependence varies by gender and culture, where genetics can determine the specific risk and protection factors for an ethnic group and an individual, which are based on variation in alcohol and acetaldehyde dehydrogenase alleles or variants, and the heritable and non-heritable co-morbid psychopathological factors, such as depression, risk-taking and stress.

Heredity studies to determine the genetic liability for alcoholism, including studies of twins, and adoption studies have been undertaken. Results show there appear to be two types of alcoholics: primarily male with a 9-fold genetic risk; and both male and female with a lesser genetic risk, but a greater significant environmental influence leading to an earlier onset of alcoholism. It has been proposed that the difference between the two types is related to the inherited personalities, e.g.: easily stressed individuals are more susceptible to alcoholism, in particular in a heavy drinking culture. It has also been proposed that alcoholism is a polygenetic disorder whereby different genes affect or influence the frequency and quantity of alcohol consumed as well as the development of neuro-adaption or tolerance by an individual.

Indeed, studies in anima l models and humans have identified both genetic and environmental factors contributing to alcohol consumption, such that this complex behavioural trait is influenced by multiple factors: Genetic factors specifically related to the pharmacology of alcohol; Psychological factors and Socio-cultural factors.

There are two primary biological or genetic factors that influence alcohol consumption behaviour and the development of alcoholism: alcohol metabolism and neuro-adaption. In the US population, for example, there is a three-fold variation in the rate of alcohol metabolism and hence elimination of alcohol from the body, which determines the level and duration of exposure of the body organs to alcohol. Of this variation, approximately 4060% is directly attributable to genetics and the remainder to environmental influences (concurrent consumption of food and/or other drugs).

An increased rate of alcohol metabolism confers a lower blood alcohol and/or acetaldehyde concentration and less toxicity to tissues and organs, while a decreased rate confers a higher concentration that can infer systemic cardiovascular and gastrointestinal adverse reactions, such as nausea, headache, tachycardia, low blood pressure and facial flushing. Alcohol is metabolised primarily by the enzyme alcohol dehydrogenase (ADH) to acetaldehyde. Acetaldehyde is further metabolised by the enzyme acetaldehyde de hydrogenase (AlDH) to acetate. There are genetic variants of ADH and AlDH, which are more or less active at metabolising. Less activity results in an inability to metabolise alcohol or acetaldehyde and a high blood alcohol or acetaldehyde concentration results and remains until the secondary metabolic pathway is induced.

Asian populations, (Chinese and Japanese) inherit primarily the active ADH2 variant whereby alcohol is rapidly converted to acetaldehyde, but they also primarily inherit the inactive AlDH22 gene whereby the toxic acetaldehyde is not converted to acetate, so it accumulates in the blood. A systemic adverse reaction ensues that generally discourages excessive consumption and effectively protects these individuals against the development of alcoholism. The protection is relative rather than absolute, as the adverse effects can be overcome with a slowed drinking pattern.

Tolerance to the adverse behaviourally-impairing effects of ethanol on the central nervous system and on motor function develops with chronic or repeated drinking enabling heavier consumption; the adverse effects generally discourage excessive consumption. Continued excessive consumption can be encouraged by a relative insensitivity, also genetically predisposed, to the adverse systemic cardiovascular and gastrointestinal effects of a high blood concentration of alcohol and acetaldehyde, and to those of the central nervous system and motor function.

The psychological factors include an expectancy of pleasurable effects such as social stimulation, that is, positive effects which occur at a low to moderate level of alcohol consumption. Conversely, expectancy of adverse effects (loss of central nervous system and motor skills) are negative reinforcing effects which occur at higher levels of alcohol consumption and which generally discourage excessive consumption.

The socio-cultural factors contributing to consumption behaviour include ethnicity, family, peers and religion. Thus some people drink alcohol but others do not, some people drink more alcohol than others and some people drink alcohol despite negative consequences. These differences in alcohol consumption behaviour reflect the fact that they experience different kinds of environmental conditions as well as different genetic profiles.

Continued excessive alcohol consumption leads to alcoholism. Physical dependence is exemplified by a series of systemic and behavioural symptoms upon withdrawal of alcohol, primarily mediated by autonomic nervous system hyper-activity. Psychological dependence is exemplified by craving or impaired control leading to a loss of control in consumption and a relapse in behaviour.

The rate of alcoholism is 5x higher in families of alcoholics than in the general population, which is currently the best predictor of the development of alcoholism for an individual. If the influence of family environment is removed, the rate of alcoholism is still 3x higher in the adopted children of alcoholics than those of non-alcoholics, whereby a low level of response to alcohol at age 20 years was associated with a four-fold greater likelihood of developing alcoholism.

An unanswerable ethical or moral dilemma often raised now, is that not all individuals with a genetic predisposition will develop alcohol problems and as such, positive identification may result in an unfair restriction of employment opportunities, and that of automobile and health insurance.

Creina Stockley is Health and Regulatory Manager at the Australian Wine Research Institute and a member of The AIM Editorial Board.

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