THE PATHOGENESIS OF ALCOHOLISM BIOLOGICAL FACTORS THE BIOLOGY OF ALCOHOLISM Volume 1: Biochemistry Volume 2: Physiology and Behavior Volume 3: Clinical Pathology Volume 4: Social Aspects of Alcoholism Volume 5: Treatment and Rehabilitation of the Chronic Alcoholic Volume 6: The Pathogenesis of Alcoholism Psychosocial Factors Volume 7: The Pathogenesis of Alcoholism Biological Factors THE PATHOGENESIS OF ALCOHOLISM BIOLOGICAL FACTORS Edited by Benjamin Kissin and Henri Begleiter Downstate Medical Center Brooklyn, New York PLENUM PRESS. NEW YORK AND LONDON Library of Congress Cataloging in Publication Data Main entry under title: The Pathogenesis of alcoholism. (The Biology of alcoholism; v. 7) Includes bibliographical references and index. 1. Alcoholism - Physiological aspects. 2. Alcoholism - Genetic as pects. I. Kissin, Benjamin, 1917 - II. Begleiter, Henri. III. Series. [DNLM: 1. Alcoholism. WM 274 K61b] RC565.B52 1971 vol. 7 616.86'ls [616.86'1] 82-22284 ISBN-13: 978-1-4613-3520-7 e-ISBN-13: 978-1-4613-3518-4 DOl: 10.1007/978-1-4613-3518-4 © 1983 Plenum Press, New York Softcover reprint ofthe hardcover 1st edition 1983 A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Contributors Henri Begleiter, State University of New York, Department of Psychiatry, Downstate Medical Center, Brooklyn, New York. Nelson Butters, Boston University School of Medicine, Boston, Massachusetts J. Remi Cadoret, University of Iowa, College of Medicine, Iowa City, Iowa Howard Cappell, Addiction Research Foundation, Toronto, Ontario, Canada Theodore J. Cicero, Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri Richard A. Deitrich, Alcohol Research Center and Department of Phamacology, University of Colorado School of Medicine, Denver, Colorado Carlton K. Erickson, College of Pharmacy, University of Texas, Austin, Texas C. J. Peter Eriksson, Research Laboratories of the State Alcohol Monopoly (Alko), Helsinki, Finland Kennon M. Garrett, Alcohol and Drug Abuse Research Center, Department of Physiology and Biophysics, University of Illinois Medical Center, Chi cago, Illinois William M. Grove, Department of Psychology, University of Minnesota, Min neapolis, Minnesota Paula L. Hoffman, Department of Physiology and Biophysics, University of Illinois Medical Center, Chicago, Illinois, and Westside Veterans Ad ministration Medical Center, Chicago, Illinois A. Eugene LeBlanc, Addiction Research Foundation, Toronto, Ontario, Canada v vi Contributors Joan C. Martin, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington Gerald E. McClearn, Institute for the Study of Human Development, The Pennsylvania State University, University Park, Pennsylvania Nancy K. Mello, Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, Belmont, Massachusetts Bernice Porjesz, State University of New York, Department of Psychiatry, Downstate Medical Center, Brooklyn, New York David H. Ross, Division of Molecular Pharmacology, Departments of Phar macology and Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas Aryeh Routtenberg, Department of Psychology, Northwestern University, Ev anston, Illinois Christopher Ryan, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Ann Pytkowicz Streissguth, Department of Psychiatry and Behavioral Sci ences, University of Washington, Seattle, Washington Boris Tabakoff, Department of Physiology and Biophysics, University of Illinois Medical Center, Chicago, Illinois, and Westside Veterans Administration Medical Center, Chicago, Illinois Gail Winger, Departments of Pharmacology and Psychology, University of Michigan, Ann Arbor, Michigan Roy A. Wise, Center for Research on Drug Dependence, Department of Psy chology, Concordia University, Montreal, Quebec, Canada James H. Woods, Departments of Pharmacology and Psychology, University of Michigan, Ann Arbor, Michigan Alice M. Young, Departments of Pharmacology and Psychology, University of Michigan, Ann Arbor, Michigan Preface The previous volume, The Pathogenesis of Alcoholism: Psychosocial Factors, attempted to describe the interaction of biological, psychological, and social factors that lead to the initiation and perpetuation of alcoholism. The preface to that volume presented our particular view of the bio-. psycho-social interaction as a progressive process in which earlier developments produce new pathogenetic mechanisms, which in turn lead to still other cyclical feedback activities. Although influences from each of the three phenomenologic levels are at work during each stage of the clinical course, it would appear that social factors are most significant in the early phase, psychological factors at the intermediate level, and biological ones toward the end. These differences are only relative, however, for influences of all three types surely are operative during all stages of the syndrome. This appears to be particularly true for the biological parameters of activity. Don Goodwin (1976), who has supplied much of the data that support the role of hereditary factors in alcoholism, is wont to say that all living behavior is biological-by definition. The operational evidence for this is perhaps more evident in alcoholism than in other syndromes. For example, the general social indifference of many Asians to alcohol may reflect the presence of an atypical isoenzyme of alcohol dehydrogenase rather than some independently derived cultural norm. Similarly, the greater tendency of certain individuals to develop psy- vii s 8 edical complication rrhosis, Pancreatitis, Cardiomyo-pathy, etc. M Ci e ve mag ratig 7 ain da cipient Persevedrinkin Br In lcoholism 6 Protracted ab-stinence syndrome Persistent low-grade withdrawal symptoma-tology A tic Course of 5 Development of physical dependence Withdrawal symptoms Tremor e n f e o hog ent e The Pat 4 Developmtoleranc Metabolic TABLE 1. 3 evelopment of psychological dependence ositive reinforcement conditioning paradigm D P s 2 The psycho-pharmaco-logic effectof alcohol Euphoriant Stimulant Sedative al al Predisposing factors Biological Genetic Prenatal Constitution Psychobiologic Psychological ke off me vere WernicKorsaksyndro e S ysiological Ph and psychological cravings Reactivation of physical dependence by drinking s g n nce kin cal Anxiety DepressioSleep disturba uring drin Loss of control fter bstinence ysiologiPh craving D AA oral ogical vi ol ha ysi e h B P al c gig on ycholcravi s P Tranquilizing Antidepressant Intoxicating Addictive Personality Psychosis Neurotic reactions cial Family Cultural Social o S x Preface chological dependence on alcohol may be due to differences in the pharmacological action of alcohol in different individuals, or indeed to differences in the structure and function of the individual's brain reward system. Certainly there must be a biological anlage to all social and psychological activities-by definition-and our understanding of the entire process will inevitably be enriched by our knowledge of biological function. One of us (Kissin, 1979) has outlined the biological stages of alcoholism leading from incipient predisposing vulnerability to final severe organic disease. The eight stages in development of alcoholism, as described at the top of Table 1, are self-explanatory and form a clinical sequence that occurs in the history of most, or perhaps all, alcoholics. The items listed in each column represent the more signifi cant effects and reactivities resulting from the dominant mechanisms that characterize each phase (i.e., the respective headings). Although the social and psychological equivalents of these biological developments are not specifically spelled out, they are easily extrapolated from the biological and behavioral data. At this point, two alternative models of the course of the devel opment of alcoholism seem to have been presented here-the linear sequential model illustrated in Table 1 and the computer feedback-feedforward model described in Chapter 13 of the previous volume (Gohlke et at., 1983). These two models are not at all contra dictory; they are indeed rather complementary. The linear model of Table 1 can readily be translated, with only slight modification, into the feedback loops of the computer model generated by Collike et al. (1983). For example, Ludwig (1983) has postulated that persistent subclinical withdrawal symptoms (Table 1, column 6) produce a secondary psy chosocial dependence on alcohol, feeding back to column three. Simi larly, recent evidence (Ryan and Butters, Chapter 12) suggests that early damage to the frontal lobes (column 7) results in perseverative drinking, another type of feedback to column three, which then follows sequentially into the next three columns. These, then, are the dominant themes of these two volumes: that alcoholism is a multidetermined condition involving biological, psycho logical and social influences; that these influences may themselves be modified by activities at the other levels (social and psychological tendencies may result from biological anlage, biological reactivities may be changed by social and psychological experience); that alcoholism is a progressive syndrome in which different sequential effects are intro duced at different stages; and finally that, because of the progressive nature of alcoholism, intervention should be directed at interrupting
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