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1 The neurobiological basis of psychiatric disorder is a rapidly expanding field of study, primarily as a result of recent developments in the basic neurosciences. Neurobiology and Psychiatry will serve as a regular forum for evaluation and dissemination of information in this fundamental field of biological psychiatry. Topics selected for review will illustrate the application of a range of modern neurobiological techniques to all the major psychiatric disorders, providing a comprehensive and up-to-date review of work in this field. The intended readership includes established research workers in the field, postgraduate psychiatrists, psychiatric trainees and other clinical and laboratory workers.

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3 Cambridge Medical Reviews Neurobiology and Psychiatry Volume I

4 Cambridge Medical Reviews set out to provide regular volumes of critically selected review material in a growing range of emerging and established disciplines within clinical medicine. They will concentrate particularly on areas where advances in basic biomedical science have a substantial contribution to make to the understanding and treatment of disease. Rigorous standards of selection and editing ensure a reliable, topical and clinically relevant series of volumes, focused to meet the requirements of clinicians and research workers in each discipline. Neurobiology and Psychiatry Editor Robert Kerwin Institute of Psychiatry, University of London, London, UK Advisory editors David Dawbarn Department of Medicine, Bristol Royal Infirmary, Bristol, UK James McCulloch Wellcome Surgical Institute and Hugh Fraser Neuroscience Laboratories, University of Glasgow, Glasgow, UK Carol Tamminga Inpatient Program, Maryland Psychiatric Research Center, Baltimore, Maryland, USA

5 Cambridge Medical Reviews Neurobiology and Psychiatry Volume I EDITOR ROBERT KERWIN Institute of Psychiatry, University of London, London, UK ADVISORY EDITORS DAVID DAWBARN Department of Medicine, Bristol Royal Infirmary, Bristol, UK JAMES McCULLOCH Wellcome Surgical Institute and Hugh Fraser Neuroscience Laboratories, University of Glasgow, Glasgow, UK CAROL TAMMINGA Inpatient Program, Maryland Psychiatric Research Center, Baltimore, Maryland, USA The right of the University of Cambridge to print and sell all manner ofbooks was granted by Henry Vlll in The University has printed and published continuously since CAMBRIDGE UNIVERSITY PRESS Cambridge New York PortChester' Melbourne. Sydney

6 cambridge university press Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo, Delhi, Tokyo, Mexico City Cambridge University Press The Edinburgh Building, Cambridge CB2 8RU, UK Published in the United States of America by Cambridge University Press, New York Information on this title: / Cambridge University Press 1991 This publication is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published 1991 First paperback edition 2011 A catalogue record for this publication is available from the British Library Library of Congress Cataloguing in Publication data isbn Hardback isbn Paperback Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. Information regarding prices, travel timetables, and other factual information given in this work is correct at the time of first printing but Cambridge University Press does not guarantee the accuracy of such information thereafter.

7 Contents Contributors Editors' preface Post-mortem neurochemistry of schizophrenia M C ROYSTON and M D C SIMPSON page ix Temporal lobe pathology and schizophrenia 15 G W ROBERTS Frontal lobe, structure, function and connectivity in schizophrenia 39 J M GOLD and D R WEINBERGER Neurotransmitter system abnormalities associated with the neuropathology of Alzheimer's disease 61 D DEWAR Molecular neuropathology of Alzheimer's disease 95 M GOEDERT, M C POTIER and M G SPILLANTINI Neurochemical studies of cortical and subcortical dementias 123 A J CROSS Subcortical dementia - defining a clinical syndrome 137 S FLEMINGER Molecular and cell biology of epilepsy 155 B S MELDRUM and A G CHAPMAN New developments in neuroimaging in schizophrenia 167 L S PILOWSKY and R KERWIN Index 181 Xl Vll

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9 Contributors CHAPMAN, A G, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF CROSS, A J, Astra Neuroscience Research Unit, 1 Wakefield Street, London WCIN IPJ DEW AR, D, Wellcome Surgical Institute & Hugh Fraser Neuroscience Laboratories, Garscube Estate, Bearsden Road, Glasgow G61 lqh FLEMINGER, S, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF GOEDERT, M, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH GOLD, J M, Clinical Brain Disorders Branch, National Institute of Mental Health, NIMH Neuroscience Center at St Elizabeth's, 2700 Martin Luther King Avenue, S E Washington DC 20032, USA KERWIN, R W, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF MELDRUM, B S, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF PILOWSKY, L S, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF POTIER, M C, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH ROBERTS, G W, Department of Anatomy and Cell Biology, St Mary's Hospital Medical School, Norfolk Place, London W2 IPG ROYSTON, M C, Department of Physiological Sciences, Medical School, Oxford Road, Manchester M13 9PT SIMPSON, M D C, Department of Physiological Sciences, Medical School, Oxford Road, Manchester M13 9PT SPILLANTINI, M G, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH WEINBERGER, D R, Clinical Brain Disorders Branch, National Institute of Mental Health, NIMH Neuroscience Center at St Elizabeth's, 2700 Martin Luther King Avenue, S E Washington DC 20032, USA IX

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11 Preface Neurobiology and Psychiatry VolI is the first in a series of five volumes within the Cambridge Medical Reviews Series. After several decades of disenchantment with some of the 'biological' aspects of psychiatric research, the past five years have seen tangible progress in the application of basic neurosciences towards understanding the brain mechanisms underlying psychiatric disorders. This is probably because the level of sophistication achieved within the basic sciences is now capable of grappling with the subtle and arcane pathophysiology and biochemistry of human psychiatric disorders. This can now be achieved without resorting to indirect or empirical measures such as animal models or the study of peripheral markers. These volumes will attempt to review, in depth, progress in these areas, concentrating on those conditions and areas where real progress is being made. Volumes I and II will focus primarily on the dementias and schizophrenia, Volume I dealing primarily with neurochemistry, neuropsychology and neuropathology. There still remains much to cover in these areas, and Volume II will also review other fields such as molecular genetics and developmental biology. Topics reviewed in subsequent volumes will depend on areas of future progress, and, in all cases, authors will be chosen from among the most active research workers in biological psychiatry and the neurosciences. I should like to take the opportunity to thank Professor Shepherd of the Institute of Psychiatry who suggested the project and Richard Barling of CUP for helping to ensure its development and continuity. Robert Kerwin Institute of Psychiatry Xl

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