M. Ackenheil. B. Bondy. R. Engel. M. Ermann. N. Nedopil (Eds.) Implications of Psychopharmacology to Psychiatry

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1 M. Ackenheil. B. Bondy. R. Engel. M. Ermann. N. Nedopil (Eds.) Implications of Psychopharmacology to Psychiatry

2 Springer Berlin Heidelberg New York Barcelona Budapest Hong Kong London Milan Paris Tokyo

3 M. Ackenheil. B. Bondy. R. Engel. M. Ermann N. Nedopil (Eds.) Implications of Psychopharmacology to Psychiatry Biological, Nosological, and Therapeutical Concepts With 35 Figures and 34 Tables Springer

4 Prof. Dr. M. Ackenheil Priv.-Doz. Dr. B. Bondy Prof. Dr. R. Engel Prof. Dr. M. Ermann Prof. Dr. N. Nedopil Ludwig-Maximilians-Universitiit Munchen Psychiatrische Klinik und Poliklinik NuBbaumstraBe Munchen ISBN -13: e-isbn-13 : DOl: / Die Deutsche Bibliothek - CIP-Einheitsaufnahme Implications of psychopharmalcology to psychiatry: biological, nosological, and therpeutical concepts; with 34 tables 1 M. Ackenheil... (ed.). - Berlin; Heidelberg; New York; Barcelona; Budapest; Hong Kong; London; Milan; Paris; Tokyo: Springer, 1996 ISBN -13: NE: Ackenheil, Manfred [Hrsg.) This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, reproduction on microfilms or in other ways, and storage in date banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its current version, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. Springer Verlag, Berlin Heidelberg 1996 Softcover reprint of the hardcover 1st edition 1996 Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check ist accuracy by consulting other pharmaceutical literature. The use of registered names, trademarkes, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Typesetting: FotoSatz Pfeifer GmbH, Grafelfing SPIN: / Printed on acid-free paper

5 Preface The discovery of chlorpromazine for the specific treatment of schizophrenic symptoms and, later on, of imipramine for the specific treatment of depressive symptoms marked a new milestone in clinical psychiatry and basic neuroscience 40 years ago. The exploration of biochemical mechanisms of action of these psychotropic drugs created new theories on the pathophysiology of psychiatric disorders, such as the dopamine hypothesis of schizophrenia and the catecholamine and serotonin hypotheses of depression. Thus the discovery of these biological treatments had a major impact on natural science-oriented research. Biological psychiatry as we know it today has its origin in these psychopharmacological drugs and influences many disciplines in psychiatry. It was a fortunate coincidence that Hans Hippius, whose 70th birthday we celebrated this year with an international symposium, started his professional career during this time in the 1950S. He was one of the early pioneers in clinical psychopharmacological research and enthusiastic about both the scientific and the therapeutic prospects of the new psychotropic drugs. He has worked in this field for more than three decades and has made many lasting contributions to biological psychiatry. Among the many activities, his contributions in the development of the new atypical antipsychotic drug clozapine should be mentioned. Hanns Hippius has been active in many international societies and the occasion of his birthday brought together leading experts in the field of psychopharmacology, biological psychiatry, and related disciplines. They presented and discussed their views and theories on psychiatric disorders. This Festschrift presents future perspectives in drug development, genetic research in psychiatry, nosological and diagnostic concepts, as well as strategies for a more specific treatment of the different psychiatric disorders. The implications of psychopharmacology to psychiatry are elaborated. The authors, internationally prominent experts, give broad insight into their research and into the clinical perspectives of psychiatry. Many of them are prominent members of the European College of Neuropsychopharmacology, of which Hanns Hippius is a honorary member. We thank the authors of this Festschrift very much for their contributions. M. Ackenheil, B. Bondy Miinchen, September 1995

6 List of Authors Professor Dr. Jules Angst, Psychiatric University Hospital Zurich, Research Department, P.O. Box 68, LenggstraBe 31, CH-8029 Zurich, Switzerland Professor Arvid Carlsson, Depatment of Pharmacology, University of Goteborg, Medicinaregatan 7, S Goteborg, Sweden Dr. Elliot S. Gershon, Chief, Clinical Neurogenetics Branch, National Institute of Mental Health, 10-3N218, Bethesda, Maryland 20892, U.S.A. Dr. Frederik K. Goodwin, The George Washington Unviversity, Medical Center, Department of Psychiatry, 2300 I Street, NW Rm 514, Washington D.C , U.S.A. Prof. Dr. Dr. Heinz Hafner, Zentralinstitut fur Seelische Gesundheit, Postfach , Mannheim Professor John M. Kane, Hillside Hospital, Department of Psychiatry, rd Street, Glen Oaks, N.Y , U.S.A. Professor Otto F. Kernberg, The New York Hospital, Cornell Medical Center, 21 Bloomingdale Road, White Planes, N.Y , U.S.A. Dr. Donald F. Klein, Director of Research, New York State Psychiatric Institute, 722 West 168th Street, New York, N.Y , U.S.A. Professor Malcolm Lader, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, U.K. Professor Julien Mendlewicz, Free University of Brussels, Erasme Hospital, Department of Psychiatry, Route de Lennick 808, B-I070 Belgium Professor H.-J. Moller, Psychiatric Hospital, University of Munich, Nussbaumstr. 7, D Munich Professor Stuart Montgomery, St. Mary's Hospital Medical School, Academic Department of Psychiatry, Praed Street, London W 2 INY, U.K. Dr. Steven Paul, Vice President, Lilly Research Laboratories, Indianapolis, Indiana 46285, U.S.A. Professor Herman van Praag, Academic Hospital Maastricht, Department of Psychiatry, P. Delylaan 25, 6202 AZ Maastricht, The Netherlands

7 Vlll List of Authors Professor Giorgio Racagni, Center of Neuropharmacology, University of Milan, Via Balzaretti 9, Milan, Italy Prof. Dr. M. L. Rao, Psychiatrische Klinik und Poliklinik der Universitat Bonn, Sigmund-Freud-Str. 25, Bonn Sir Martin Roth, Professor Emeritus of Psychiatry, Trinity College, Cambridge CB2 2 TQ, U.K. Sitting, from left to right: A. Carlsson, J. Mendlewicz, J. Angst, B. Bondy, Sir M. Roth, M. Ackenheil Standing, from left to right, first row: G. Kurtz, P. Buchheim, O. Kernberg, H. van Praag, J. Racagni, S. Montgomery, N. Sartorius, D. Klein, H. Hafner, M. Lader, W. Greil, W. Guenther, P. Simon, H. Dilling Standing, second row: J. Martinius, R. Cohen, A. Erfurth, R. Steinberg, P. Berner, E. Riither, H. Helmchen, G. Laakmann, E. Gershon, H. Hippius, R. Engel, U. Heger!, H. Sass, D. van Zerssen

8 Contents Neurotransmitter Interactions Important for Schizophrenia A. CARLSSON.... The Etiology of Affective Illness EK. GOODWIN New Findings in the Genetic of Bipolar Illness E.S. GERSHON Targeting the Action of Antidepressant Drugs on Second-Messenger Systems G. RACAGNI, M. POPOL!, S. MORI, N. BRUNELLO, and J. PEREZ New Concepts of Schizophrenia Derived from Epidemiological Research H. HAFNER The Course of Psychiatric Disorders as a Diagnostic Tool J. ANGST A Psychonanalytic Model for the Classification of Personality Disorders O.E KERNBERG Functional Pathology: An Essential Diagnostic Step in Biological Psychiatric Research H.M. VAN PRAAG The Development of Nosological Concepts in Anxiety Disorders D.E KLEIN Classification of the Affective and Related Disorders SIR MARTIN ROTH and DORGIVAL CAETANO The Ideal Neuroleptic M. LADER

9 x Contents Long-Term Treatment of Schizophrenia J.M. KANE Treatment of Affective Disorders S.A. MONTGOMERY Negative Symptoms of Schizophrenia: Methodological Issues, Biochemical Findings and Efficacy of Neuroleptic Treatment H.-J. MOLLER and M.L. RAO... "..., Interaction of Long-Term Antidepressant Treatment with Psychosocial Factors F. BAUWENS, D. PARDOEN, and J. MENDLEWICZ