RISK FACTOR FOR ALCOHOL'S NEUROPATHOLOGICAL EFFECTS

Project Details

Description

Arylsulfatase A (E.C. 3.1.6.1.) (ASA), an enzyme found in both human brain and blood, catalyzes the degradation of sulfatides. Variant forms of this enzyme, identified by discontinuous electrophoresis, have been shown to occur with relatively high frequency in blood of alcoholic patients. The hypothesis of this research proposal is that variant ASA's are inherited risk factors for the neuropathological effects of alcohol. In order to investigate this proposal, blood samples will be obtained from 60 alcoholic, non-schizophrenic patients, 60 schizophrenic, non-alcoholic patients, 10 patients with both alcoholism and schizophrenia, and 60 normal controls. These blood samples will be analyzed by discontinuous electrophoresis for variant ASA's. The variant and normal ASA's will be characterized and compared by kinetic analysis with naturally occurring sulfatides, by isoelectric focusing, and by a study of physical stability under a variety of conditions (e.g., heat denaturation). If in vivo activity of variant ASA's is deficient, an accumulation of sulfatides, the substrate of ASA, would be expected to occur in urine. Therefore, urinary sulfatide levels will be measured in all subjects. To investigate the possibility that variant ASA's may be under genetic control, the electrophoretic properties of the enzyme taken from first and second degree relatives of subjects with variant ASA's will be studied. Selected alcoholic patients will be investigated using intelligence and neuropsychological testing as well as neurophysiological testing. The neurophysiological parameters that will be measured include electromyography, nerve conduction, including F response and H reflex, and cerebral evoked responses (brainstem auditory, pattern reversal visual, and somatosensory cerebral and subcortical evoked responses). Two subgroups of alcoholic patients will be studied, one with variant ASA's and one with normal enzyme who have been matched for age, sex, and chronicity and severity of alcoholism. If the hypothesis regarding variant ASA's and chronic alcohol intake is correct, this would explain the neuropathological course of the disease in some alcoholic patients. Moreover, it would allow identification of normal subjects who would be at risk to the neuropathological effects of alcohol.
StatusFinished
Effective start/end date12/31/8912/31/89

Funding

  • National Institute on Alcohol Abuse and Alcoholism

ASJC

  • Psychiatry and Mental health

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