The genetic epidemiology of alcoholism.

Despite the variability in sampling and methodology, the majority of the family, twin and adoption studies suggest that alcoholism is familial, a significant proportion of which can be attributed to genetic factors. However, the specific components of alcoholism that may be inherited have yet to be identified. To date, there are no biological trait markers for which there is evidence for specificity for alcoholism. The three major levels of enquiry regarding possible mechanisms for the transmission of alcoholism and the involvement of genes and gene products in its development are factors related to exposure, metabolism, or pharmacological effects of ethanol. Exposure to ethanol is an obvious precondition for the development of tolerance and/or dependence. Therefore, identification of factors which enhance (or decrease) exposure are important goals of studies of the pathogenesis of alcoholism. It is likely that demographic, cultural and environmental factors (i.e. sex, age, religious affiliation, social group influences, income, availability of alcohol, etc.) play a crucial role in mediating exposure to alcohol. The key to alcoholism is likely to reside in the effects of alcohol on the brain. In contrast to nicotine, the opioids, and catecholamines, no specific receptor for ethanol has been found. Thus, one major focus of current research on possible central nervous system (CNS) mechanisms for the effect of alcohol includes assessment of the role of alcohol in the stimulation of brain reward or reinforcement systems. Alternately, alcohol may produce dependence by normalizing abnormal baseline states such as irritability, hyperexcitability, dysphoria, impulsiveness, or stress/tension level. The results of animal studies have yielded information on the central effects of alcohol including sensitivity of neuronal membranes, proteins, and ion channels to alcohol, and factors related to the binding and release of neurotransmitters and neuromodulators including dopamine, norepinephrine, gamma aminobutyric acid, pro-opiomelanocortin, glutamate receptors and the endorphin system (Institute of Medicine, 1987). In addition to possible genetic explanations for the strong degree of familial aggregation of alcoholism, alternative explanations need to be further evaluated. These include: modelling of parental behaviour; possible changes in the susceptibility of the foetus to alcohol as a result of in utero maternal ingestion of alcohol; results of negligent rearing manifested in dietary deficiency, exposure to toxic substances, or brain trauma, which so often characterize the homes of alcoholic parents; or damage to paternal germ cells from alcohol.