Book Review

New Biological Vistas on Schizophrenia

N Engl J Med 1993; 328:1134-1135April 15, 1993

Article

New Biological Vistas on Schizophrenia
(Clinical and Experimental Psychiatry. Monograph No. 6.) Edited by Jean-Pierre Lindenmayer and Stanley R. Kay. 299 pp., illustrated. New York, Brunner/Mazel, 1992. $41.95. ISBN: 0-87630-654-7

Research on schizophrenia is experiencing a growth spurt at the moment. Several areas, such as epidemiology and neuropsychology, are undergoing a radical overhaul. Others, such as structural imaging and neuropathology, continue to produce new findings. As with the rest of neuroscience, molecular biology and neurochemistry are the fastest-growing fields. The dopamine hypothesis of schizophrenia, which has been looking rather shaky for some time now, has effectively been toppled in its classic form, and the search is on for the missing neurochemical link.

This book charts some, although not all, of these developments. Edited by faculty members of the Albert Einstein College of Medicine, it both gains and suffers from the current tidal wave of biologic research: gains, because much of what is reported here is new; suffers, because even more important findings have emerged since the book went to press.

In the opening chapter, the late, much-respected Stanley Kay reviews his own considerable contribution to the knotty problem of the relation between positive and negative symptoms, the focus of much research in the 1980s. This chapter is the only exception to an unashamedly biologic menu. In chapter 2, Lynn DeLisi reviews cytogenetic and molecular-genetic evidence on schizophrenia as it stood at the end of 1989. It is a good review, but it unavoidably omits recent developments -- the emergence of chromosome 11 as everyone's favorite candidate for a genetic association with schizophrenia, for example. Jeffrey Zigun and Daniel Weinberger review the computed-tomographic evidence of structural brain changes, but they miss out on most of the intriguing work in magnetic resonance imaging pointing to reduced volume in medial temporal structures. Again, much of this work has been published in the past two years. Manuel Casanova, Janice Stevens, and Joel Kleinman contribute an excellent and refreshingly skeptical chapter, using evidence from postmortem studies to address the question of whether the reported morphologic and histopathological changes in schizophrenia are better explained by a degenerative or a developmental lesion. Another conceptual dichotomy, that of etiologic homogeneity versus heterogeneity in schizophrenia, is addressed next by Eve Johnstone, who, like Stevens in the preceding chapter, comes down firmly in the heterogeneity camp.

The second half of the book reviews pharmacology and neurochemistry, particularly with regard to the drug that spelled the demise of the dopamine theory: clozapine. The clinical importance of clozapine is surpassed only by its theoretical importance. How does it work? Notions of anatomical specificity to the mesolimbic rather than nigrostriatal dopamine pathway and the likelihood of an important modulator -- perhaps D₁, 5-HT₂, glutamate, or neuropeptides -- are explored in a series of definitive chapters by recognized opinion leaders: Herbert Meltzer, Eliot Gardner, Herman Van Praag, Stephen Zukin and Daniel Javitt, and John Kane. But the latest news is once again missing. The discovery and subsequent cloning of the dopamine D₃, D₄, and D₅ receptor subtypes, which are proving to be of central interest in this debate, arrived too late for even a footnote.

This is a good book, and I recommend it. However, it is dating quickly. It illustrates the paradox that the more a field of research, by virtue of recent advances, warrants a book, the more likely it is that the book will be out of date by the time it is published.

Shon W. Lewis, M.D.
Charing Cross and Westminster Medical School, London W6 8RP, England