The Maudsley Family Study of Psychosis: A

Psychotic disorders such as schizophrenia and bipolar disorder are known to be highly heritable. Despite decades of research, however, the genetic variations conferring susceptibility to these illnesses have yet to be identified. Such genetic variations most likely produce abnormalities of brain structure and function from which the clinical features of psychosis emerge. The Maudsley Family Study of Psychosisinvestigates the genetically produced markers of abnormal brain structure and function ('intermediate phenotypes') which underlie the clinical syndrome of schizophrenia, and more recently bipolar disorder. In this book, key findings of this important research program, and their implications for this field, are discussed in detail. Contributors outline research examining brain structure and functioning in patients with schizophrenia and their unaffected first degree relatives, incorporating detailed clinical assessments, magnetic resonance imaging, electrophysiology, eye tracking measures and neuropsychology. This book provides an improved understanding of illness pathways and potential scope for intervention in order to better manage and prevent psychotic disorders and will be of interest to academics and clinicians in the field.

List of contributors	p. ix
List of figures	p. xi
List of colour plates	p. xiii
List of tables	p. xv
Preface	p. xix
Exploring intermediate phenotypes of psychosis	p. 1
The contribution of genetic liability to schizophrenia	p. 1
Heritability estimates for schizophrenia	p. 3
Mode of genetic transmission	p. 3
Molecular genetics	p. 4
Overlap in genetic liability for schizophrenia and bipolar disorder	p. 6
Endophenotypes	p. 10
The Maudsley Family Study of Psychosis	p. 12
References	p. 14
The Maudsley Family Study of Psychosis - overview of clinical methodology and characteristics	p. 21
Participant recruitment	p. 21
Study phases	p. 22
Inclusion and exclusion criteria	p. 22
Clinical assessments	p. 23
Sociodemographic characteristics of the complete sample	p. 25
Clinical characteristics of the sample	p. 27
Genetic liability scale	p. 29
References	p. 38
Auditory evoked potentials as genetic trait markers of schizophrenia	p. 41
Introduction	p. 41
How severe are neurophysiological deficits in schizophrenia? Meta-analyses of the published literature	p. 44
The acquisition and analysis of EEG/ERP data in the Maudsley Family Study of Psychosis	p. 49
Results	p. 51
Discussion	p. 54
Conclusion	p. 63
References	p. 64
Are eye movement abnormalities related to susceptibility genes for schizophrenia?	p. 71
Introduction	p. 71
Methodology	p. 75
Results	p. 78
Discussion	p. 82
Conclusions	p. 88
References	p. 88
Neuropsychological impairments in patients with schizophrenia and their unaffected relatives	p. 93
Background	p. 93
Episodic memory	p. 94
Executive function	p. 105
Sustained and selective attention	p. 114
Intellectual asymmetry	p. 120
Overall summary of the neuropsychological findings and conclusions	p. 124
References	p. 126
Neurological abnormalities in patients with schizophrenia from singly and multiply affected families and their relatives	p. 133
Introduction	p. 133
Methods	p. 135
Results	p. 138
Discussion	p. 146
Conclusion	p. 151
Acknowledgements	p. 151
References	p. 151
Structural brain deviations in schizophrenia and bipolar disorder - to what extent are they genetically mediated?	p. 155
Introduction	p. 155
Region-of-interest analyses of patients with schizophrenia or bipolar disorder and their unaffected relatives	p. 157
Structural brain deviations associated with schizophrenia and bipolar disorder assessed using computational morphometry	p. 167
Structural brain deviations associated with genetic liability to schizophrenia and bipolar disorder assessed using computational morphometry	p. 179
Summary	p. 188
References	p. 189
Summary and implications	p. 197
Summary of key findings	p. 197
Implication of findings	p. 203
The next stages	p. 207
Appendix 1	p. 209
Index	p. 213
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The Maudsley Family Study of Psychosis: A Quest for Intermediate Phenotypes

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