Brain, Vol. 124, No. 2, 448-449,
February 2001
© 2001 Oxford University Press
Book reviews |
THE NEUROPATHOLOGY OF SCHIZOPHRENIA. PROGRESS AND INTERPRETATION.
Edited by Paul J. Harrison and Gareth W. Roberts 2000. Oxford: Oxford University Press. Price £65. Pp. 374. ISBN 0-19-262907-7.
Neuropathology, Southampton General Hospital, Southampton, UK
After many years of neglect, there is welcome renewed interest in the neuropathology of schizophrenia. At the XIVth International Congress of Neuropathology in Birmingham, UK in September 2000, a large auidience gathered to hear a Keynote Lecture, a Plenary Lecture and Symposium on the neuoropathology of psychoses, which concentrated mainly on schizophrenia. The reason this renewed enthusiasm has come about is outlined in the foreword to The Neuropathology of Schizophrenia by Janice Stevens. She explains the factors that have increased the rate of progress towards resolving the problem of the neuropathology of schizophrenia. CT and MR imaging has allowed in vivo neuropathology to be monitored and the observation of ventricular enlargement in schizophrenic patients to be repeatedly confirmed. A further factor in the renewed interest is the recognition that schizophrenia is a syndrome and, in all probability, has multiple causes. This concept is not new to neuropathology as it is a feature of multiple sclerosis, many forms of dementia and the muscular dystrophies. However, whereas the morphological features in these diseases are very striking, those of schizophrenia are subtle and difficult to characterize. Grouping of patients with schizophrenia into different subtypes may greatly facilitate clarification of the pathological features, as may detailed examination of parts of the central nervous system other than the cerebral cortex, such as the basal ganglia and thalamus. As the brain in patients with schizophrenia usually reaches normal adult size, any developmental abnormalities must be very subtle if they play a role in the development of the syndrome.
This volume, The Neuropathology of Schizophrenia edit by Paul Harrison and Gareth Roberts, is a timely publication and is one of the most comprehensive accounts of the subject so far published. The arguments heard in the lecture hall in Birmingham also rage in this book. One of the most exciting features is that it is not yet possible to point to neuropathological changes that are specific to schizophrenia but this compendium of imaging, anatomical, histological, immunocytochemical, developmental and experimental data makes fascinating reading for those seeking new avenues of research into psychiatric disorders.
Twenty-four authors contribute to the book and they are drawn from a wide range of disciplines. It starts with an overview of structural imaging and macroscopic pathology in schizophrenia by Hopkins and Lewis. They review the evidence that people with schizophrenia have brains that are relatively smaller than normal age-sex matched subjects with enlargement of the ventricles and reduced volumes of certain adjacent subcortical nuclei, particularly the thalamus. In some families, the structural abnormalities are observed in non-psychotic relatives. The authors conclude that the current structural and imaging evidence supports the hypothesis that schizophrenia is a largely genetic, neurodevelopmental disorder of the cerebral cortex. They also emphasize the value of imaging in progressing the study of the structural aspects of the disorder.
The following four chapters concentrate on histological studies to find tissue correlates for the imaging studies. These chapters demonstrate how advances in histological techniques for the identification of neuronal proteins and mRNA can be used to define subtle histological abnormalities. Findings in the hippocampus (Arnold) suggest that neurodevelopmental abnormalities are resposible for schizophrenia far more than a neurodegenerative process. Furthermore, it is highly unlikely that such histopathalogical and molecular abnormalities are exclusive to the hippocampal formation, even though this region plays a pivotal role in the neural systems serving cognition and emotion. The possibility that schizophrenia may involve a subtle and perhaps prolonged process of excitotoxicity (Benes) and that changes in the glutamate system could result either in neuronal death or in a less overt form of injury to distal branches of pyramidal cell dendrites is explored. Furthermore, the suggestion that alterations in neural circuitry may be under the control of an abnormal gene is expressed. The role of altered synaptic connectivity in schizophrenia is also considered in 'The neuropathology of dementias' (Esiri) and in 'Synaptic pathology' (Honer).
Subsequent chapters review the possible role of gliosis in the disease process of schizophrenia and that of cerebral asymmetry which has long been recognized in schizophrenic brains (Hollinger). Advances in functional imaging in the investigation of neural circuitry (Schultz) have provided clear evidence that measurable anatomical differences are present in schizophrenia. Again, this route allows much more intensive study in vivo rather than using the classical neuropathalogical techniques.
One favoured hypothesis for schizophrenia is the neurodevelopmental model and this is reviewed by Akil and its limitations are explored in this chapter by Price and Roberts. Quite apart from concentrating on schizophrenia, there is much general information in this book with regard to neurodevelopment and the organization of cortical circuitry (Lewis). The developmental model suggests that there may be a failure of telencephalic pattern formation.
Other chapters deal with animal models of schizophrenia and there is a very valuable chapter by Chua and McKenna, entitled 'The sceptical view of the neuropathology of schizophrenia'. Methodological issues and the neuropathological consequences of treatments for schizophrenia are the last two chapters in this book. Any disease that relies on long-term treatment may have the added complication of damage through drug administration. It is, therefore, useful to have the chapter 'Neuropathalogical consequence of Schizophrenia treatments' (Harrison) which concentrates largely on the neuropathalogical effects of anti-psychotic drugs.
This book is not one that can be read from cover to cover as it contains a huge amount of information regarding the successful and unsuccessful attempts to define the neuropathology of schizophrenia. However, the summaries to each chapter are very informative and this makes it extremely valuable for the general reader. For the expert and for those involved in research into schizophrenia, this book should be invaluable. It is a mine of information and the starting point for anyone entering the field. With these multiple facets, I would recommend this book to clinicians treating schizophrenia, to neuropathologists who may be soon called upon to enter more seriously into the study of the pathology of schizophrenia and to research scientists investigating the basic neuroscience of schizophrenia. Paul Harrison and Gareth Roberts should be congratulated on their excellent choice of authors, the uniformity of the text and layout and the bright perspective for future research into schizophrenia that the book conveys.
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