The Maudsley Family Study of Psychosis: A Quest for Intermediate Phenotypes

247 Pages·2008·3.16 MB·English

by  Colm McDonald

THE MAUDSLEY
Maudsley Monographs
MAUDSLEY MONOGRAPHS
HENRYMAUDSLEY,fromwhomtheseriesofmonographstakesitsname,wasthe
founder of The Maudsley Hospital and the most prominent English psychiatrist of
hisgeneration.TheMaudsleyHospitalwasunitedwiththeBethlemRoyalHospital
in 1948 and its medical school, renamed the Institute of Psychiatry at the same
time,becameaconstituentpartoftheBritishPostgraduateMedicalFederation.Itis
nowaschoolof King’sCollege,London, andentrustedwith thedutyofadvancing
psychiatry by teaching and research. The South London & Maudsley NHS Trust,
together with the Institute of Psychiatry, are jointly known as The Maudsley.
The monograph series reports high quality empirical work on a single topic of
relevance to mental health, carried out at the Maudsley. This can be by single or
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problems; others, are in scientific fields of direct or indirect relevance to mental
health and that are cultivated for the furtherance of psychiatry.
Editor
Professor A. S. David MPhil MSc FRCP MRCPsych MD
AssistantEditor
Professor T. Wykes BSc PhD MPhil
PreviousEditors
1955–1962 Professor Sir Aubrey Lewis LLD DSc MD FRCP
and Professor G. W. Harris MA MD DSc FRS
1962–1966 Professor Sir Aubrey Lewis LLD DSc MD FRCP
1966–1970 Professor Sir Denis Hill MB FRCP FRCPsych DPM
and Professor J. T. Eayrs PhD DSc
1970–1979 Professor Sir Denis Hill MB FRCP FRCPsych DPM
and Professor G. S. Brindley
1979–1981 Professor G. S. Brindley MD FRCP FRS
and Professor G. F. M. Russell MD FRCP FRC(ED)
FRCPsych
1981–1983 Professor G. F. M. Russell MD FRCP FRCP(ED) FRCPsych
1983–1989 Professor G. F. M. Russell MD FRCP FRCP(ED) FRCPsych
and Professor E. Marley MA MD DSc FRCP FRCPsych DPM
1989–1993 Professor G. F. M. Russell MD FRCP FRCP(ED) FRCPsych
and Professor B. H. Anderton BSc PhD
1993–1999 ProfessorSirDavidGoldbergMADMMScFRCPFRCPsychDPM
Maudsley Monographs number fifty
The Maudsley Family Study of Psychosis
A Quest for Intermediate Phenotypes
Edited by Colm McDonald
First published 2008
by Psychology Press
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SimultaneouslypublishedintheUSAandCanada
by Psychology Press
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(cid:216) 2008 Psychology Press
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British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library
Library of Congress Cataloging in Publication Data
The Maudsley family study of psychosis : a quest for intermediate
phenotypes / edited by Colm McDonald.
p. ; cm. – (Maudsley monograph, ISSN 0076-5465 ; no. 50)
Includes bibliographical references and index.
ISBN 978-1-84169-734-5 (hardback)
1. Schizophrenia–Genetic aspects. 2. Manic-depressive illness–
Genetic aspects. 3. Phenotype. 4. Genetic markers. I. McDonald,
Colm. II. Series: Maudsley monographs ; no. 50.
[DNLM: 1. Schizophrenia–genetics. 2. Family. 3. Genetic
PredispositiontoDisease–genetics.4.PsychoticDisorders–genetics.
W1 MA997 no.50 2008 / WM 203 M448 2008]
RC514.M375 2008
616.89'8042–dc22
2008001507
ISBN 0-203-88525-2(cid:13)(cid:10) Master e-book ISBN
ISBN:978-1-84169-734-5
ISSN: 0076-5465
Contents
List of contributors ix
List of figures xi
List of colour plates xiii
List of tables xv
Preface xix
1. Exploring intermediate phenotypes of psychosis 1
Colm McDonald, Robin Murray
The contribution of genetic liability to schizophrenia 1
Heritability estimates for schizophrenia 3
Mode of genetic transmission 3
Molecular genetics 4
Overlap in genetic liability for schizophrenia and bipolar disorder 6
Endophenotypes 10
The Maudsley Family Study of Psychosis 12
References 14
2. The Maudsley Family Study of Psychosis – overview of clinical
methodology and characteristics 21
Colm McDonald
Participant recruitment 21
Study phases 22
Inclusion and exclusion criteria 22
Clinical assessments 23
v
vi CONTENTS
Sociodemographic characteristics of the complete sample 25
Clinical characteristics of the sample 27
Genetic liability scale 29
References 38
3. Auditory evoked potentials as genetic trait markers of schizophrenia 41
I. Williams, S. Frangou and E. Bramon
Introduction 41
How severe are neurophysiological deficits in schizophrenia?
Meta-analyses of the published literature 44
The acquisition and analysis of EEG/ERP data in the Maudsley
Family Study of Psychosis 49
Results 51
Discussion 54
Conclusion 63
References 64
4. Are eye movement abnormalities related to susceptibility genes for
schizophrenia? 71
James MacCabe, Jolanta Zanelli
Introduction 71
Methodology 75
Results 78
Discussion 82
Conclusions 88
References 88
5. Neuropsychological impairments in patients with schizophrenia and
their unaffected relatives 93
Timothea Toulopoulou, Francesca Filbey and Eugenia Kravariti
Background 93
Study 1: Episodic memory 94
Study 2: Executive function 105
Study 3: Sustained and selective attention 114
Study 4: Intellectual asymmetry 120
Overall summary of the neuropsychological findings and
conclusions 124
References 126
6. Neurological abnormalities in patients with schizophrenia from singly
and multiply affected families and their relatives 133
Paola Dazzan, Timothy D. Griffiths
Introduction 133
Methods 135
CONTENTS vii
Results 138
Discussion 146
Conclusion 151
Acknowledgements 151
References 151
7. Structural brain deviations in schizophrenia and bipolar disorder – to
what extent are they genetically mediated? 155
Colm McDonald
Introduction 155
Study 1: Region-of-interest analyses of patients with schizophrenia
or bipolar disorder and their unaffected relatives 157
Study 2: Structural brain deviations associated with schizophrenia
and bipolar disorder assessed using computational morphometry 167
Study 3: Structural brain deviations associated with genetic
liability to schizophrenia and bipolar disorder assessed using
computational morphometry 179
Summary 188
References 189
8. Summary and implications 197
Colm McDonald
Summary of key findings 197
Implication of findings 203
The next stages 207
Appendix 1 209
Index 213

List of contributors
Elvira Bramon,
Senior Lecturer,
Division of Psychological Medicine and Psychiatry,
Institute of Psychiatry,
King’s College London,
London
Paola Dazzan,
Senior Lecturer,
Division of Psychological Medicine and Psychiatry,
Institute of Psychiatry,
King’s College London,
London
Francesca Filbey,
Research Scientist, The MIND Research Network,
Adjunct Assistant Professor,
Psychology Department,
University of New Mexico,
Albuquerque, NM 87131
USA
Sophia Frangou,
Reader,
Head, Section of Neurobiology of Psychosis,
Division of Psychological Medicine and Psychiatry,
Institute of Psychiatry,
King’s College London,
London
ix