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Book Forum   |    
Neurobiology of Mental Illness, 3rd ed.
Reviewed by ROBERT FREEDMAN
Am J Psychiatry 2009;166:1072-1073. doi:10.1176/appi.ajp.2009.09060873
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edited by Dennis S. Charney, M.D., and Eric J. Nestler, M.D., Ph.D. New York, Oxford University Press, 2008, 1,504 pp., $225.00.

The first impression upon seeing this book is that it is a very large volume, and the second is that the content is indeed what it purports to be, a detailed account of research into the neurobiology of mental disorders. Two decades ago a book like this would have relied on extrapolations from animal studies or rehashed the possible mechanisms of action of psychotropic drugs. Instead, these 87 chapters overflow with the results of investigations directed toward understanding human mental disorders as neurobiological illnesses. The mass of what is presented here should make us proud of all that psychiatry has accomplished as a research discipline.

The eight sections map a DSM-IV typology onto this research data, with major sections on the psychoses, mood and anxiety disorders, substance use disorders, dementia, childhood-onset disorders, and personality. Two introductory sections develop principles of basic neuroscience and methods of clinical neurobiological research. I found the individual chapters detailed but lucid, as would be expected from their authors, who write with ease and precision as the leading experts in these fields.

Two examples are the chapter on the genetics of schizophrenia by Xiangning Chen, Brien Riley, and Kenneth S. Kendler and the chapter on autism and pervasive developmental disorder by Sarah Spence, Paul Grant, Audrey Thurm, and Susan E. Swedo. The genetics chapter skillfully summarizes a vast and sometimes confusing literature with well-constructed tables that present the results of the numerous genome-wide studies that were available at the time of writing in late 2007. The chapter highlights major findings that arise from the consideration of these data as a whole with a synthesis that does not emerge easily when reading the individual studies. The autism chapter has a similar synthetic theme. It integrates a diverse literature that has interesting but often contradictory findings from phenomenology, imaging, genetics, and psychosocial theories. I particularly liked the authors’ challenge to the reader to understand how the cognitive issues of autistic individuals might lead to their social problems or vice versa. I will return to these chapters several times over the coming year as I try to place new research in each of these areas into context.

Indeed, the book is best considered as a good encyclopedia. Chapters of interest, whether they be in one’s own field or in an area that one has not explored, can be read in less than an hour to learn the history of the field and its current research findings. The book is thus useful for a wide range of readers, from experienced as well as beginning investigators to clinicians to family members who seek a sophisticated overview of what types of neurobiological research are occurring for a specific mental disorder.

The compilation of so much research information into one large volume evokes the need for perspective about the reasons for the successes and challenges of this field. The genetics of schizophrenia and the neurobiology of autism are good examples, because both are areas in which there have been important breakthroughs that subsequently seemed to vanish. In fact, most of the major findings have been replicated many times but not in all studies. Both chapters point out that larger studies have paradoxically not produced more definitive results. The usual explanations of methodological differences and heterogeneity between populations are raised. However, when careful researchers produce findings that can be reproduced in some but not all replication studies, it suggests that the perspective of the entire field may need to be deepened. An example is physics at the beginning of the twentieth century, in which anomalies that developed as experimental precision increased led to the replacement of classical Newtonian laws by quantum mechanics and relativity. Until that major theoretical change occurred, there was no way to make sense of the conflicting experimental data.

Psychiatric research has benefited from several theoretical perspectives. The biopsychosocial model, initially developed for clinical practice, allowed researchers to consider these three aspects of the causation of human behavior simultaneously. For human neurobiology, the emerging conceptualization of endophenotypes, neurobiological mechanisms that underlie the clinical pathology, has been helpful in more directly linking genetic abnormalities to neurobiological pathology. What is now needed is an extension of these concepts into a perspective that encompasses the human life cycle. Most researchers accept that major mental illnesses have a genetic origin or, more precisely, result from a gene-environment interaction. However, this interaction begins in utero, when most of brain development and the highest level of gene expression occur. What is laid down in early brain development then becomes the substrate of biopsychosocial development throughout childhood and may emerge into diagnosed pathology only in early adulthood or even later. With so many factors interacting over time, diagnosis not surprisingly becomes confusing, not only changing dramatically during childhood, but remaining fluid into adulthood as well. The result is tangled comorbidity, such as mood and anxiety disorders with themselves and with substance abuse disorder, or irresolvable distinctions, like schizophrenia and schizoaffective disorder.

A textbook on the neurobiology of psychiatric illness that begins with the confusion of psychiatric diagnoses and attempts to work backwards to their cause thus demonstrates the sorts of anomalies that should lead to a reworking of perspective, just like the physicists of 100 years ago were compelled to do. A new perspective might first identify the basic underlying processes, for example, genetically determined endophenotypes, interacting effects of genes and environment during human brain development, and then biopsychosocial influences during maturation. Mapping each factor onto the phenomenology of adult mental disorders, regardless of diagnosis, might be quite clarifying. The disappearance of diagnostic comorbidities would be one piece of evidence that a greater understanding has been achieved. Cardiologists, for example, map an array of different risk factors from familial history to lifestyle differences onto the emergence of cardiac disease. They can then study and treat each of these risk factors individually. Our task is not as simple, because human brain and behavior present many more complexities than the heart, but a resynthesis of the research in this impressive book to track mental illnesses from early cause to adult behavioral manifestation would be a valuable first step.

+The author reports no competing interests.

+Book review accepted for publication June 2009 (doi: 10.1176/appi.ajp.2009.09060873).

Reprints are not available; however, Book Forum reviews can be downloaded at http://ajp.psychiatryonline.org.

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