THE GOAL OF THIS PROJECT IS TO DEVELOP SIMPLE AND RELIABLE BIOCHEMICAL TESTS WHICH CAN BE USED TO IDENTIFY INDIVIDUALS AT RISK FOR ALCOHOLISM, AND/OR TO ACCURATELY INDICATE RECENT ALCOHOL ABUSE.

THE GOAL OF THIS PROJECT IS TO DEVELOP SIMPLE AND RELIABLE BIOCHEMICAL TESTS WHICH CAN BE USED TO IDENTIFY INDIVIDUALS AT RISK FOR ALCOHOLISM, AND/OR TO ACCURATELY INDICATE RECENT ALCOHOL ABUSE. IN PHASE I, THE FEASIBILITY OF USING PLATELET ENZYMES AS SUCH MARKERS WILL BE ASSESSED. OUR PRELIMINARY STUDIES HAVE INDICATED THAT CERTAIN CHARACTERISTICS OF PLATELET MONOAMINE OXIDASE (MAO) ACTIVITY (I.E., SENSITIVITY TO INHIBITION BY ETHANOL) AND ADENYLATE CYCLASE (AC) ACTIVITY ARE ALTERED IN ALCOHOLICS AS COMPARED TO CONTROLS. IN THE PROPOSED STUDIES, WE WILL CONFIRM THE DIFFERENCES IN A LARGER POPULATION AND DEVELOP RELIABLE METHODS FOR PLATELET PREPARATION AND ENZYME ASSAY WHICH WILL ACCENTUATE THESE DIFFERENCES. WE WILL ALSO EXAMINE ENZYME ACTIVITIES IN PLATELETS OBTAINED FROM ALCOHOLICS WHO HAVE ABSTAINED FROM ALCOHOL FOR VARIOUS LENGTHS OF TIME, IN ORDER TO DETERMINE WHETHER OBSERVED CHANGES IN PLATELET ENZYME ACTIVITIES RESULT FROM EXPOSURE TO ETHANOL, OR ARE INDICATIVE OF GENETICALLY-DETERMINED DIFFERENCES BETWEEN ALCOHOLICS AND CONTROL SUBJECTS. IN PHASE II, OUR CHOSEN ASSAY METHODS FOR MAO AND AC ACTIVITY WILL BE STREAMLINED FOR CLINICAL USE. THE REVERSIBILITY OF ENZYME CHANGES WILL BE FURTHER ASSESSED, AND ENZYME ACTIVITIES IN OTHER PSYCHIATRIC POPULATIONS (E.G., SCHIZOPHRENICS, OR PATIENTS WITH AFFECTIVE DISORDERS), AS WELL AS IN FEMALE ALCOHOLICS, WILL BE EXAMINED TO DETERMINE THE SPECIFICITY OF THESE TESTS FOR ALCOHOLISM OR ALCOHOL ABUSE. THE DEVELOPMENT OF SIMPLE AND RELIABLE TESTS FOR DIAGNOSING PAST ALCOHOL ABUSE OR A PREDISPOSITION TO ABUSE ALCOHOL WILL PROVIDE FOR THE PHYSICIAN: 1) A MEANS OF ASCERTAINING AN IMPORTANT CONTRIBUTING FACTOR TO MAJOR PATHOLOGIC CONDITIONS; 2) A MEANS OF ASSESSING PATIENT COMPLIANCE WITH INSTRUCTIONS TO TERMINATE ALCOHOL INTAKE; AND, 3) A POSSIBLE MEANS OF IDENTIFYING INDIVIDUALS AT RISK FOR DEVELOPING PROBLEMS WITH ALCOHOL IN THE FUTURE. EARLY IDENTIFICATION CAN ALLOW FOR EARLIER AND MORE EFFECTIVE INTERVENTION IN THE PATHOLOGY OF ALCOHOLISM.