The adverse effects of psychotic illnesses such as schizophrenia can be wide ranging and long-lasting. It is clear that some components of psychosis are heritable, but despite advances in genetic techniques and the accumulation of much data in recent years, we have yet to pin down the genetic basis of the disease. This much is clear: that it is complex, and likely polygenic.
Although psychotic disorders are inherited, the precise nature of the genetic variability and its consequences are yet to be established. In the preface of this book, the authors stress the difficulty of answering this question in patient studies, due to the potential confounds presented by psychotic illness. They argue that one way to avoid this difficulty and examine gene action independently of acute illness is by studying neurobiological abnormalities displayed by the unaffected first-degree relatives of patients.
The Maudsley Family Study of Psychosis was conceived for exactly this purpose. In particular, it seeks to understand which abnormalities are associated with increased genetic risk for schizophrenia, and are therefore potentially useful as endophenotypes for the disease. This book comprises a collection of chapters authored by various members of the study team that together provide a description and summary of key findings, including previously unpublished data.
In chapter 1 the authors describe the background and rationale to the Maudsley Family Study of Psychosis, providing the reader with an analysis of current literature in genetic studies of schizophrenia and bipolar disorder. They proceed to outline the endophenotype concept and its potential utility, providing a sound base for readers who are not familiar with the concept and a reminder for those who are.
Chapter 2 focuses on methodological details common to all arms of the study, detailing recruitment strategies and the sociodemographic and clinical characteristics of the wider sample. The Maudsley Family Study of Psychosis hinges on the investigation of association between genetic liability and neurobiological characteristics and it is in this chapter that the genetic liability scale used is described in detail.
Five domains of investigation are summarized in chapters 3–7: auditory evoked potentials (chapter 3); eye movement abnormalities (chapter 4); neuropsychological abnormalities (chapter 5); primary and integrative neurological abnormalities (chapter 6); and structural brain deviations (chapter 7). This provides a broad base of key topics in endophenotype research, bringing together a wide range of disciplines in what could be a promising move towards the identification of multivariate endophenotypes of psychosis.
Each chapter takes the format of an academic paper with the exception of chapter 3, which provides in addition a useful meta-analysis of the existing literature on auditory evoked potentials, before proceeding to the study description. Background and methodology are clearly explained in each chapter, and should thus be accessible to those with limited prior knowledge of the techniques in question. The results of these studies both support and depart from previous literature. Rationale is provided wherever the latter occurs.
In the closing chapter, editor Colm McDonald summarizes the foregoing chapters, drawing diverse findings together to create a persuasive story of disrupted frontal temporal/subcortical connectivity, the molecular processes underlying which, he argues, provide ‘targets for exploring pathways from genetic variation to neurobiological intermediate phenotypes’. McDonald gives an indication of the work yet to be done with this sample: this book often raises as many questions as it answers and McDonald provides hope that these may be answered in the future.
This book will be equally useful to those looking for a summary of the achievements of this exciting project to date, and to those simply wishing to know more about the investigation of endophenotypes in schizophrenia.
