I know the editors of this important volume, Alan Brown and Paul Patterson, well enough to have a glimmer of insight into how they came together to lead this book. They are both tenacious iconoclasts who have doggedly championed the hypothesis of maternal infection as a risk factor for schizophrenia while the rest of their peers were chasing dopamine and genes. The answer that they arrived at independently, Alan Brown from his tireless and creative work in epidemiology and Paul Patterson from his creative approaches in animal neurobiology, is quite striking because it was entirely unexpected. It is not the infection per se, but rather the reaction of the mother’s body to it that seems to affect the fetal development of an individual who only much later in life will become ill with schizophrenia as he or she approaches adulthood. This remarkable story, with converging evidence from two different disciplines, is the cornerstone of the book. It sets the stage for understanding a range of influences on the risk for schizophrenia—genetic variants in the major histocompatability loci, obstetrical complications, and maternal psychological and social stress. All these factors can cause the mother to mount an immune response on the baby or at least its part of the placenta. The effects on fetal development, although subtle, can have ominous consequences. The title, The Origins of Schizophrenia, is therefore bold and perhaps off-putting, but the book delivers on its promise.
Furthermore, the book delivers in an exciting and provocative way. Clinical chapters are matched hand in hand with neurobiological models in animals for an astonishing diversity of possible causal factors. As I read each human chapter, I found myself mumbling to the potential animal modeler, “model this!” And yet, there it was: not a promise that there would someday be an animal model, but meaningful research that actually provides the possible if not probable mechanism for an observation in the human population. Of course, Paul Patterson’s own work on maternal immune activation as a model for the effects of maternal infection is a prime example.
The book might have begun with the story of how the two of them came together, I suspect at a meeting somewhere when a translational panel was considered. I began to wonder who the other two speakers might have been, if it was the traditional panel of four; who might have organized or chaired it; and if many people were in the audience, or if the panel was held during the last afternoon of the meeting, reserved for the miscellany while the themes currently in vogue grabbed the limelight on the first day.
Why did they do it, and why did they decide to broaden the book beyond their own area of mutual interest? They allude to the reasons in their own introduction. The message, unspoken except in their brief introduction, is that clinical research has advanced to the point to ask many meaningful questions about the pathological mechanisms that cause schizophrenia, and animal neurobiology has responded with answers. These answers carry with them the possibility of new treatments, including new preventive treatment that should begin as early as conception.
This book is a milestone, but I hope that a book on epidemiology and animal models of the relevant mechanisms can be followed soon by a companion book on treatments developed using these animal models and their application to the treatment and ultimately the prevention of schizophrenia in humans. That would indeed be a worthy conclusion to the pioneering efforts of Alan Brown and Paul Patterson and the distinguished cast of contributors who have authored this important volume.
Robert Freedman, M.D.
University of Colorado School of Medicine
Editor-in-Chief, American Journal of Psychiatry
Denver, Colorado