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The Madness Within Us: Schizophrenia as a Neuronal Process
Reviewed by Jack D. Barchas, M.D.
Am J Psychiatry 2010;167:607-609. doi:10.1176/appi.ajp.2010.10020270
View Author and Article Information
New York, N.Y.

The author owns equity in Lilly, Elan, and Neurocrine and receives patent royalties.

Accepted March , 2010.

Copyright © American Psychiatric Association

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In this beautifully written, brilliant, comprehensive, and thoughtfully integrated book, Dr. Freedman brings together knowledge of specific behaviors characteristic of schizophrenia with what we now know of their neuronal processes, thereby pointing the way to an evolving psychiatry of the future in which the details of behavior, neuroscience, and treatment are joined. The story reads as an exciting mystery.

The author's broad background has made this integration possible. Dr. Freedman is professor and chair of psychiatry at the University of Colorado; editor-in-chief of the American Journal of Psychiatry; a member of the Institute of Medicine; an exceptionally productive and creative basic, translational, and clinical researcher; an able and respected clinician who works with patients with schizophrenia; and a well-read, natural teacher with intrinsic curiosity. A graduate of Harvard Medical School, he started his research career early, took training in the National Institute of Mental Health intramural program, and was trained in psychiatry at the University of Chicago, where the great Daniel X. Freedman (no relation) was a key mentor. Freedman has expertise, understanding, and the ability to explain multiple scientific areas, and he is fabled as an intelligent, knowledgeable, and fair individual—traits reflected in this volume.

The book starts with history, philosophy, and perspectives from ancient and biblical times dealing with symptoms we associate with the syndrome(s) now termed schizophrenia. The work of Kraeplin, Bleuler, Freud, Sullivan, and others led the way to description of the disorder and its course. The subtitle of the volume was inspired by Sullivan's Schizophrenia as a Human Process. In the core of the book, Freedman discusses attributes of behavior and neuronal processes in schizophrenia. We see the thinking of a scientist as he tries to answer interlocking questions that require different knowledge bases and approaches without being tied to a particular method or discipline.

Among the major behavioral changes in schizophrenia are those in attention and habituation, areas in which Freedman has been a leader. They can be reproducibly studied, their anatomy determined, their neuroregulators (transmitters/modulators) identified, and their neural pathways recognized. Some of the behavioral changes, such as smoking and sensory overload, involve neural circuits utilizing acetylcholine and specific receptors including the alpha-7 nicotinic acetylcholine receptor. The neurobiology of specific neurocircuits is considered, such as areas of the hippocampus. Freedman also describes other behaviors and neuronal processes involving such neuroregulators as glutamate, GABA, cannabinoids, serotonin, norepinephrine, and dopamine (now seen in more complex ways). He discusses many behaviors, including paranoia, delusions, and conversions, as well as genetics and epidemiology.

The neural processes are within all of us; the impacts of genetic alterations, some of which may also be common in persons without illness, are emphasized as part of our common humanity reflected in the book's title. The stage is set for a description of current treatments and their successes, failures, and problems, including side effects.

Freedman lays out much of our current knowledge of schizophrenia. Specific facts as we know them today are less important than the framework of connections. With luck, such tantalizing information will lead to new understanding of subtypes of illness that present with a common form but may be different, new possibilities for prevention, new understanding of stress and resilience as well as communication patterns, and better and more specific biological and psychosocial treatments. There are scores of neuroregulators (including neuropeptides such as endorphins and many others) and developmental processes whose relations to specific behaviors or the development of mental illness have barely been studied (if at all). Many new targets for treatment will become possible, perhaps with approaches based on underlying deficits that connect targets together. The final result should be less stigma and more humane responses for patients.

Essentially, Freedman provides a clear description of a paradigm shift: information from many disciplines will result in new understanding of both behavior and neuronal processes. The potential of such knowledge has never been presented so clearly to a broad audience. Similar shifts are taking place across psychiatry, already involving various forms of depression, bipolar disorder, anxiety disorders, autism and some other child disorders, and, surprisingly, substance abuse, which is advancing at a remarkable pace.

As background, this volume highlights the end of the cultural wars in psychiatry, although they already seem distant. A half century ago, Daniel Freedman, a young psychoanalyst at Yale who was adding the new field of psychopharmacology to his repertoire and just starting his academic career, provided the first evidence that LSD directly impacted brain serotonin, an effort oriented to psychosis and schizophrenia. To a standing-room crowd, which included this reviewer as a rather terrified medical student, the major question he was asked was: "Where is this work justified in the writings of Freud?" I remember Daniel Freedman stating that Freud would have worked in the lab developing knowledge about the brain and worked with patients developing psychodynamics. My own work with Daniel Freedman showed that neuroregulators could be differentially altered by stress, a study undertaken in the hope that the results would be relevant to mental processes and illness. Highlighting the changes in the field, today a psychoanalyst, Otto Kernberg, continues his valuable work in psychodynamics while making important contributions comparing the effectiveness of psychotherapies and leading successful efforts to use brain imaging to understand the neurobiology of behaviors in personality disorders.

Many factors brought an end to the cultural wars—almost everyone was partially right, even as they were impeded by being in separate silos. Most important was the growth of science. A profound change in attitudes was influenced by the landmark 1970 report through the National Academy of Sciences, Psychiatry as a Behavioral Science, under the transforming leadership of David A. Hamburg with a group of major figures in psychiatry. It called for utilization of multiple disciplines and for integration, reflected now in this volume. New areas will be valuable additions to the foundations of psychiatry, including cognitive and social neuroscience, developmental psychobiology and neurobiology, and behavioral neurobiology—how behavior changes neurobiology and how that changes future behavior. We will also better understand the mechanisms of psychosocial treatments.

This volume uses synthetic cases derived from the author's work with patients. One senses his direct abilities as a clinician, guide, mentor, teacher, counselor, adviser, and friend, all with wisdom and humanity—"straightening corners," as a patient once told me. There have always been gifted therapists of many different theoretic formulations who had an ability to listen, understand, and calm those with profound anxieties. Those are critical abilities; yet there are battles ongoing, exemplified by a leader in our field who stated that he would be satisfied if his residents memorized DSM and a textbook of psychopharmacology. Those goals are not sufficient in our program or, I hope, in many others.

With its layered nuance and integration, this volume pre­sents a perspective from which all who are concerned with severe mental illness can be hopeful—the next few decades should be remarkable and this volume helps to prepare us. Mind and brain may be for the first half of this century what the revolution in physics was for the last—transforming. As Freedman notes, as we understand severe disorders, we will also better understand ourselves. There are other excellent books on schizophrenia and the experience of the disorder, but this volume brings us up-to-date on neuronal processes and behavior and does so with clarity. The writing is accurate and interesting for professionals, and it will be helpful to many outside the profession, including some families of patients. Thin, tightly packed, quickly paced, alive, inspiring, and of remarkable intellectual power and depth, Freedman's volume should be widely read—it is one of the most important books dealing with mental illness of the past two decades.

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