The Search for Biochemical Markers.

An important focus of alcohol research is the search for biochemical characteristics, or markers, that could distinguish people who are alcoholic or who have a predisposition for alcoholism from people who do not. Because such markers would represent inborn characteristics, or traits, they also are called trait markers. The identification of reliable trait markers could potentially reduce the damage caused by alcoholism. For instance, trait markers could provide the basis of screening tests for use in high-risk populations (e.g., children of alcoholics) to allow early identification of persons who are vulnerable for alcoholism and who would benefit from targeted prevention and intervention strategies. In addition, trait markers might assist clinicians in better diagnosing subpopulations of alcoholics who differ in their treatment needs. Furthermore, these markers could be an important step in research efforts to identify candidate genes (i.e., genes that are suspected to code for proteins that mediate alcohol's actions on the brain and thus contribute to the development of alcoholism). Researchers to date have proposed numerous potential trait markers of alcoholism. Although the validity of some of these markers could not be confirmed in subsequent experiments, other markers appear to be viable biological measures associated with the risk for alcoholism. This article highlights two such biochemical markers--platelet monoamine oxidase (MAO) and adenylyl cyclase (AC) activity levels--and emphasizes clinically relevant ways these trait markers might be used to help identify subgroups of alcoholics and to focus the search for potential candidate genes. WHAT Is A SUITABLE TRAIT MARKER? The ideal trait marker for alcoholism would fulfill several requirements: *It could be easily and reliably measured. *It would be present only in people susceptible to developing the disorder--that is, it would be specific for alcoholism in general or for one of its subtypes. *It would be either the product of a candidate gene or closely linked to one. *It could be detected before the onset of alcoholism or during periods of stable abstinence. *It would not be affected by other conditions, such as the use of other drugs or the presence of coexisting disorders. For a common disease such as alcoholism, which is mediated via complex genetic and environmental interactions, however, it is not likely that one single marker exists. Previous genetic studies have shown that the familial transmission of alcoholism likely involves multiple genes and incomplete penetrance (i.e., not all persons inheriting the gene(s) will develop alcoholism) and that environmental factors also play a major role in its pathogenesis (Pardes et al. 1989). Because of this genetic heterogeneity (i.e., variability), researchers have focused on identifying more homogeneous subtypes of alcoholism and biological factors associated with these subtypes. (For more information on alcoholism subtypes, see sidebar, p. 178) (Sidebar omitted) PLATELET MAO ACTIVITY Background and History One of the most intensely studied proposed biological markers for a predisposition to some alcoholism subtypes is platelet MAO activity. MAO is an enzyme that is important for the breakdown of a variety of monoamine neurotransmitters(1)--a group of small molecules involved in the signal transmission between nerve cells--in the brain as well as in peripheral tissues. Monoamine neurotransmitters include dopamine, norepinephrine, and serotonin, all of which have been implicated in various phenomena related to the risk for developing alcoholism. These phenomena include a preference for consuming alcohol, the susceptibility to alcohol's rewarding effects, the development of tolerance to alcohol's effects, or personality characteristics (e.g., impulsivity) that predispose a person to repeated alcohol-related problems (Tabakoff and Hoffman 1992). …