Table Of ContentThe Psychopharmacology of Schizophrenia
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The Psychopharmacology
of Schizophrenia
A TITLE IN THE BRITISH ASSOCIATION FOR
PSYCHOPHARMACOLOGY SERIES
Edited by
MICHAEL A REVELEY MD, PhD, FRCPsych
Professor of Psychiatry, Department of Psychiatry, University of Leicester,
Leicester, UK
and
J F WILLIAM DEAKIN PhD, FRCPsych
Professor of Psychiatry and Director of the Neuroscience and Psychiatry Unit,
School of Psychiatry and Behavioural Sciences, The University of Manchester,
Manchester, UK
A member of the Hodder Headline Group
LONDON
Co-published in the United States of America by
Oxford University Press Inc., New York
First published in Great Britain in 2000 by
Arnold, a member of the Hodder Headline Group
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recognized. For these reasons the reader is strongly urged to consult the
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drugs recommended in this book.
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ISBN 0340 75912 7
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Contents
Colour plates appear between pages 150 and 151
Contributors vii
Preface ix
1. Recent advances in schizophrenia research Hassen A Al-Amin and
Daniel R Weinberger 1
2. Is the association between obstetric complications and schizophrenia
mediated by glutamatergic excitotoxic damage in the fetal/neonatal
brain? Paul Fearon, David Cotter and Robin M Murray 21
3. The neuropharmacology of schizophrenia: past, present and future
Robert Kerwin 41
4. Glutamate, GABA and cortical circuitry in schizophrenia
J F William Deakin 56
5. Molecular genetics of schizophrenia Paul R Buckland and
Peter McGuffin 71
6. Structural imaging and treatment response in schizophrenia
Calum G Crosthwaite and Michael A Reveley 89
7. Functional brain imaging of schizophrenia Peter F Liddle 109
8. Neurochemical imaging in schizophrenia Goran C Sedvall, Lars Farde
and Stefan Pauli 131
9. The neuropsychology of schizophrenia Ann M Mortimer 153
10. Movement disorders associated with antipsychotic drugs: clinical
and biological implications Thomas R E Barnes and Sean A Spence 178
11. New strategies with conventional antipsychotics Stephen R Marder,
William C Wirshing and Donna Ames Wirshing 211
12. New antipsychotic drugs: preclinical evaluation and clinical profiles
in the treatment of schizophrenia John L Waddington 225
13. Treatment of schizophrenia in the community Robin G McCreadie 251
Index 263
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Contributors
Hassen A Al-Amin Clinical Brain Disorder Branch, Intramural Research Programs, National
Institute of Mental Health, NIH Neuroscience Centre at St. Elizabeth's, Washington DC
20032, USA
Thomas R E Barnes MD, FRCPsych Professor of Clinical Psychiatry, Division of Neuroscience
and Psychological Medicine, Imperial College School of Medicine, London, UK
Paul R Buckland BSc, PhD Reader, Division of Psychological Medicine, University of Wales
College of Medicine, Heath Park, Cardiff, Wales, UK
David Cotter MRCPsych Department of Psychological Medicine, Department of
Neuropathology, Institute of Psychiatry and King's College School of Medicine, De
Crespigny Park, London, UK
Calum G Crosthwaite BSc (Hons) Research Assistant, Department of Psychiatry, University
of Leicester School of Medicine, Clinical Sciences Building, Leicester Royal Infirmary,
Leicester, UK
J F William Deakin BSc, PhD, FRCPsych Professor of Psychiatry, School of Psychiatry and
Behavioural Sciences, The University of Manchester, Manchester, UK
Lars Farde MD, PhD Department of Clinical Neuroscience, Psychiatry Section, Karolinska
Institute and Hospital, S-171 76, Stockholm, Sweden
Paul Fearon MRCPI, MRCPsych Department of Psychological Medicine, Institute of Psychiatry
& King's College School of Medicine, De Crespigny Park, London, UK
Robert Kervvin MA, PhD, MB Bchir., DSc, FRCPsych Professor of Clinical Neuropharmacology,
Institute of Psychiatry, De Crespigny Park, London, UK
Peter F Liddle Jack Bell Professor and Head, Schizophrenia Division, Department of
Psychiatry, The University of British Columbia, Vancouver, BC, Canada
Stephen R Marder MD Psychiatry Service (116A), West Los Angeles Veterans Affairs
Medical Center, Los Angeles, CA 90073, USA
Peter McGuffin MD, PhD, FRCP, FRCPsych Professor of Psychological Medicine, Institute of
Psychiatry & King's College School of Medicine, De Crespigny Park, London, UK
Robin G McCreadie DSc, MD, FRCPsych Director of Clinical Research and Consultant
Psychiatrist, Crichton Royal Hospital, Dumfries, Scotland, UK
Ann M Mortimer BSc, MB, ChB, MmedSc, FRCPsych Professor, Foundation Chair in Psychiatry,
The School of Medicine, The University of Hull, Willerby, Hull, UK
viii Contributors •
Robin M Murray MD, DSc, FRCP, FRCPsych Institute of Psychiatry & King's College School of
Medicine, De Crespigny Park, London SE5 8AF, UK
Stefan Pauli MD Department of Clinical Neuroscience, Psychiatry Section, Karolinska
Institute and Hospital, S-171 76, Stockholm, Sweden
Michael A Reveley MD, PhD, FRCPsych Professor of Psychiatry, Department of Psychiatry,
University of Leicester School of Medicine, Clinical Sciences Building, Leicester Royal
Infirmary, Leicester, UK
Goran C Sedvall MD, PhD Department of Clinical Neuroscience, Psychiatry Section,
Karolinska Institute and Hospital, S-171 76 Stockholm, Sweden
Sean A Spence Functional Neuroimaging Laboratory, The New York Hospital, Cornell
Medical Center, New York NY 10021, USA
John L Waddington PhD, DSc Professor of Neuroscience, Department of Clinical
Pharmacology, Royal College of Surgeons in Ireland, Dublin, Republic of Ireland
Daniel R Weinberger MD Clinical Brain Disorder Branch, Intramural Research Programs,
National Institute of Mental Health, NIH Neuroscience Center at St. Elizabeths, Washington,
DC 20032, USA
Donna Ames Wirshing Psychiatry Service (116A), West Los Angeles Veterans Affairs
Medical Center, Los Angeles, CA 90073, USA
William C Wirshing MD Psychiatry Service (116A), West Los Angeles Veterans Affairs
Medical Center, Los Angeles, CA 90073, USA
Preface
Schizophrenia is the most severe of the mental illnesses, often causing lifelong dis-
ability for its sufferers and a substantial financial burden to society, both in loss of
productivity and in services to care for disabled people.
A great deal has been learnt over the latter part of this century about the treatment
of schizophrenia. There was a time when the majority of patients with schizophrenia
were in long stay institutions receiving, principally, custodial care, with only mini-
mal hope for discharge from hospital. The discovery of chlorpromazine in the 1950s
and widespread treatment with conventional antipsychotics has led to the discharge
of many patients into the community and has prevented new long-term admissions.
This development has brought its own problems, especially in the management of
patients in the community, but there can be no doubt about the transformation of the
quality of life of the majority of patients with schizophrenia because of the preven-
tion of much of the disability of schizophrenia with effective pharmacological treat-
ment combined with psychosocial support. With new understanding of how
anti-psychotics work it is now possible to develop new psychopharmacological treat-
ments which are targeted towards special symptoms and disabilities in schizophre-
nia, and which have fewer adverse effects.
Over the past decade, the decade of the brain, major advances have been made in
understanding the brain mechanism underlying schizophrenia. It is now widely
accepted that schizophrenia is a brain disorder. At last, the brainlessness of psychia-
try is waning. Thus, the proper understanding of the psychopharmacology of schizo-
phrenia requires not just the clinical understanding of the drugs and their use, but also
an understanding of the basic and clinical sciences relevant to drug treatment. The
aim of this book is to present the pharmacological treatment of schizophrenia in the
context of the basic and clinical sciences underpinning clinical treatment.
The first chapter by Al-Amin and Weinberger reviews the dopamine hypothesis in
the light of new evidence from molecular biology and points to new directions in
understanding the pathophysiology of schizophrenia. Chapter 2 by Fearon, Cotter
and Murray reviews the evidence for the neurodevelopmental theory of schizophre-
nia and presents a review of the mechanisms by which obstetric complications may
interact with glutamate to contribute to the development of schizophrenia in early
adult life. Chapter 3 by Kerwin provides an in-depth exploration of the molecular
biology of dopamine and serotonin receptors and their relevance to the mechanisms
of action of anti-psychotic medication. Chapter 4 by Deakin reviews the new neu-
ropathology in which neurotransmitter circuits are visualized. Much evidence impli-
cates glutamatergic abnormalities and this is leading to completely new treatment
approaches. Chapter 5 by Buckland and McGuffin reviews the molecular genetics of
Description:Schizophrenia is a severe and enduring mental disorder which begins in early adulthood and persists throughout life. This book describes the current thinking in regard to the aetiology and schizophrenia and relates this thinking to the treatment strategies with psychopharmacological agents.
