What is inherited in the predisposition toward alcoholism? A proposed model

Background: The etiological factors associated with the predisposition to develop alcohol dependence remain largely unknown. In recent years, neurophysiological anomalies have been identified in young and adult offspring of alcoholic probands. These neuroelectric features have been replicated in several laboratories across many different countries and are observed in male and female alcoholics and some of their relatives and offspring. Moreover, these electrophysiological abnormalities are heritable and predictive of future alcohol abuse or dependence. Methods: A model is presented which hypothesizes that the genetic predisposition to develop alcoholism involves an initial state of central nervous system (CNS) disinhibition/hyperexcitability. We propose that the event-related brain potential (ERP) anomalies reflect CNS disinhibition. This homeostatic imbalance results in excess levels of CNS excitability which are temporarily alleviated by the ingestion of alcohol. It is hypothesized that this hyperexcitability is heritable, and is critically involved in the predisposition toward alcoholism and the development of dependence. A brief review of the relevant literature is presented. Results: Neurophysiological, neurochemical, and genetic evidence support the proposed model. In addition, strikingly similar observations between animal research and the human condition are identified. Finally, it is asserted that the proposed model is primarily biological in nature, and therefore does not account for the entire clinical variance. Conclusion: A putative CNS homeostatic imbalance is noted as a critical state of hyperexcitability. This hyperexcitability represents a parsimonious model of what is inherited in the predisposition to develop alcoholism. It is our hope that this model will have heuristic value, resulting in the elucidation of etiological factors involved in alcohol dependence.