Schizophrenia in a Molecular Age

This interesting book, part of volume 18 in the Review of Psychiatry series edited by John M. Oldham, M.D., and Michelle B. Riba, M.D., reviews recent progress in different types of investigation on the neurobiology of schizophrenia.

The main interest of this book stems from the four chapters focusing on the pathophysiology of schizophrenia. Although these insightful chapters emphasize very different methodologies and/or brain systems, they share a common perspective on the heterogeneity of schizophrenia. Indeed, they posit that schizophrenia is not a unitary disorder but, rather, includes distinct dimensional clinical phenotypes. In addition, these chapters posit that the dimensional phenotypes reflect dynamic dysfunctions on specific neural circuits, as opposed to a narrow-minded “localizationist” perspective. Two of these four chapters may be among the best efforts ever at integrating clinical symptoms and pathophysiology; reading these two chapters may be demanding for nonexperts but is definitely worth the extra effort.

First, O’Donnell and Grace provide a brilliant synthesis of recent knowledge of the functional neuroanatomy and cell biology of dopamine systems and their possible involvement in schizophrenia. The authors make a compelling case for a refined and updated model of the involvement of abnormalities in the dopamine systems in schizophrenia, linking the various symptom dimensions with specific dopamine circuits. Second, Gruzelier authoritatively reviews electrophysiological studies of schizophrenia, using several research methods and paradigms. He then provides an impressive integration of these findings into a comprehensive model of the role of dysfunctions in the thalamocortical circuits in the genesis of symptoms of schizophrenia.

The other two chapters on physiopathology, although less innovative, are also very pertinent. First, Liddle reviews the evidence supporting distinct pathophysiology for each of the three dimensions of symptoms of schizophrenia; this review is based on his pioneering work on the factor structure of symptoms of schizophrenia. Second, Holcomb et al. provide an interesting review of the conceptual and methodological challenges in the emerging field of functional neuroimaging studies of schizophrenia. However, I would have appreciated a stronger attempt at integrating the results that these studies have yielded so far.

A fifth chapter focuses on the affinity of different antipsychotics with various receptors. In comparison with the four chapters focusing on etiology, this chapter is somewhat disappointing because several comparable reviews are already available in the literature. A more useful contribution may have been a review of the important findings linking response to treatment to specific genetic loci (e.g., 5-HT_2A and response to clozapine). Overall, this book is relatively weak in terms of coverage of genetics, which has already started to yield important information on schizophrenia. For example, a chapter reviewing the genetic mechanisms controlling the development of the central nervous system would have been very pertinent given the focus of this book.

Despite its limitations, I recommend this textbook to readers seeking comprehensive and innovative reviews on plausible models of the pathophysiology of schizophrenia.