For the past twenty years our laboratory as well as several others have repeatedly observed a significantly lower amplitude of the P3 component of the Event-related brain potentials (ERP) in both abstinent alcoholics and offspring of alcoholics. It has been demonstrated that this important finding is not the result of excessive alcohol abuse but is highly related to family density of alcoholism. We have recently postulated that this significantly reduced P3 component of the ERP may be indicative of increased central nervous system disinhibition (CNSD). In this grant proposal we hypothesize that beyond the phenomenological/symptomatic level in which presentation may be exceptionally heterogeneous, alcoholic patients may well display unexpected homogeneity along a continuum of Central Nervous System Disinhibition. It is well established that the male offspring of alcoholics are more likely to display undercontrolled behavior, and children with conduct disorders are more likely to have a positive family history of alcoholism. There is no doubt that loss in inhibitory control is an important component of the frontal-lobe. These characteristics are not only prevalent in abstinent alcoholics, but are also present in children of alcoholics. We propose that disinhibitory processes may identify abnormalities in the function of the prefrontal cortex in alcoholic patients. In this application, we propose to assess neurophysiological correlates of inhibition by implementing novel neurophysiologic paradigms in conjunction with the well-known reduced P3 amplitude of the ERP typically observed in abstinent alcoholics. We postulate that CNS disinihibition will be prevalent in individuals with a positive family history of alcoholism, and to a lesser degree in individuals without an obvious family history of alcoholism. We have invariably assumed that the great variability of symptoms in alcohol dependent individuals is strongly indicative of different pathogenesis, without considering a single underlying mechanism. This seemingly overwhelming evidence has compelled us to consider alcoholism as a heterogeneous disorder. However it is conceivable that the result of the proposed studies could alter our current approaches concerning heterogeneity . The electrophysiological results obtained from this application may find that aspects of brain dysfunction (i.e. lack of differential inhibition) may be involved in a predisposition for alcoholism.
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