The Neuropathology of Schizophrenia: Progress and Interpretation

The Neuropathology of Schizophrenia: Progress and Interpretation. Harrison PJ, Roberts GW, editors. Oxford: Oxford University Press; 2000. 374 pp with index. ISBN 0-19-262907-7 (cloth). CDN$112.

From its earliest conceptualization at the end of the 19th century, schizophrenia was considered to be a disease of the brain. Unfortunately, by the 1970s, schizophrenia had also earned the reputation as being the “graveyard of neuropathologists.” The study of the neuropathology of schizophrenia had ground to a halt after close to a century of inconsistent findings. The introduction of computed tomography (CT) and the subsequent advent of magnetic resonance imaging (MRI) breathed new life into the search for the neuropathologic basis of schizophrenia. This excellent edited volume is devoted to critically reviewing the substantial knowledge that has developed in this field in the last 2 decades and sets the stage for the major advances that are anticipated for the future. The contributors include leading scientists in the field who bring an authoritative tone to this fine book.

Neuroimaging studies form the foundation for recent developments in the neuropathology of schizophrenia. They have been important not only in highlighting the presence of structural brain abnormalities in schizophrenia but also in identifying brain regions and tissues that may be of greatest relevance. In the first chapter, CT and MRI studies are reviewed in a comprehensive and critical manner. The important questions addressed in the literature are laid out and addressed in a logical way: Are there brain abnormalities? What structures and tissues are involved? Are findings regional or global? When are they first apparent? Are they progressive? How specific are the findings to schizophrenia? This chapter is particularly valuable in setting the context for the remainder of the book, which is devoted to describing the neuropathologic approaches that have been used to more fully characterize the brain abnormalities associated with schizophrenia.

It is clear from the past generation of CT and MRI studies that there are differences in brain structure that can be consistently identified in groups of patients (but not all individuals) with schizophrenia. These include enlarged lateral ventricles, as well as smaller cortical grey matter volumes and hippocampal volumes. To go beyond this gross level of observation, we must rely on studies using neuropathologic techniques. We need to know if there are consistent differences in the cellular composition and organization of the brain, whether the number and size of neurons is reduced, or whether it is the packing of the cells in the cortex or their degree of connectivity that is disturbed. Recent neuropathologic studies that address these questions are reviewed in a series of comprehensive chapters devoted to hippocampal pathology, cortical pathology and synaptic pathology.

Advances in our understanding of the neuropathology of schizophrenia will not occur simply as a result of studying more postmortem specimens. The ability to interpret these studies is very much dependent on new insights made possible by recent advances in understanding brain development. Chapters on cortical development and the organization of cortical circuitry provide this background and underscore the vast array of mechanisms that could result in an illness such as schizophrenia. In this regard, it may be particularly helpful to compare the neuropathologic findings in schizophrenia with those of other brain diseases known to be neurodevelopmental, degenerative or associated with schizophrenia-like symptoms. An excellent chapter is devoted to this topic. Recent efforts to develop animal models of the neurodevelopmental mechanisms underlying schizophrenia are also summarized.

This book excels at bringing a balanced and scholarly perspective to a very new and complex field. The 3 final chapters, “A Skeptical View of the Neuropathology of Schizophrenia,” “Methodological Issues” and “Neuropathologic Consequences of Schizophrenia Treatments,” emphasize the importance of proceeding cautiously in this field, both in carrying out and interpreting neuropathologic research in schizophrenia.

After reading this book, one cannot help but be struck by the remarkable body of research that has developed in recent years. At the same time, it is clear that unravelling the neuropathology of schizophrenia remains a challenge of the highest order. This excellent volume brings the reader up to date in this rapidly developing field and provides the foundation for interpreting future work in this area. It should be of great interest to specialists in the area, schizophrenia researchers and their students.