Invited review The utility of neurophysiological markers in the study of alcoholism Bernice Porjesz * , Madhavi Rangaswamy, Chella Kamarajan, Kevin A. Jones, Ajayan Padmanabhapillai, Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry, SUNY, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA Accepted 17 December 2004 Abstract Objective: This review attempts to differentiate neuroelectric measures (electroencephalogram (EEG), event-related potentials (ERPs) and event-related oscillations (EROs)) related to acute and chronic effects of alcohol on the brain from those that reflect underlying deficits related to the predisposition to develop alcoholism and related disorders. The utility of these neuroelectric measures as endophenotypes for psychiatric genetics is evaluated. Methods: This article reviews the main findings of EEG and ERP abnormalities in alcoholics, offspring of alcoholics at high risk to develop alcoholism and the electrophysiological effects of alcohol on high risk compared to low-risk offspring. It highlights findings using EROs, a fast developing tool in examining brain function and cognition. It also reviews evidence of genetic findings related to these electrophysiological measures and their relationship to clinical diagnosis. Results: Many of these abnormal neuroelectric measures are under genetic control, may precede the development of alcoholism, and may be markers of a predisposition toward the development of a spectrum of disinhibitory conditions including alcoholism. Genetic loci underlying some neuroelectic measures that involve neurotransmitter systems of the brain have been identified. Conclusions: Quantitative neuroelectric measures (EEG, ERPs, EROs) provide valuable endophenotypes in the study of genetic risk to develop alcoholism and related disorders. Significance: Genetic studies of neuroelectric endophenotypes offer a powerful strategy for identifying susceptibility genes for developing psychiatric disorders, and provide novel insights into etiological factors. q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: EEG; P3; Alcoholism; Event-related oscillations (EROs); Endophenotype; Genetic predisposition; Psychiatric genetics 1. Introduction It is widely recognized that alcoholics manifest brain damage/dysfunction, and electrophysiological methods have long been used to elucidate the nature of this brain dysfunction. Recording brain electrical activity using scalp electrodes provides a non-invasive, sensitive measure of brain function in humans. These neuroelectric phenomena may be recorded with the continuous electroencephalogram (EEG) when the subject is at rest and not involved in a task or with the time-specific event-related brain potentials (ERPs) during cognitive tasks. Newer methods of time– frequency domain analysis have uncovered the phenomenon of event-related oscillations (EROs) which are time-locked to the event in much the same way as ERPs. These new measures of dynamic brain processes have exquisite temporal resolution and allow the study of neural networks underlying sensory and cognitive events, thus providing a closer link to the physiology underlying them. Electrophysiological measures are highly sensitive to the acute and chronic effects of alcohol on the brain, including intoxication, tolerance, withdrawal and long-term absti- nence. For many years, it had been assumed that the aberrant electrophysiological characteristics observed in alcoholics were due to the neurotoxic effects of alcohol on the brain. More recently, data suggest that some electro- physiological characteristics in alcoholics are under genetic control and precede the development of alcoholism, and may be markers of a predisposition toward the development 1388-2457/$30.00 q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2004.12.016 Clinical Neurophysiology 116 (2005) 993–1018 www.elsevier.com/locate/clinph * Corresponding author. Tel.: C1 718 270 2024; fax: C1 718 270 4081. E-mail address: bp@cns.hscbklyn.edu (B. Porjesz).