Biology of Schizophrenia and Affective Disease

Biology of Schizophrenia and Affective Disease

SJ Watson, editor

Washington (DC): American Psychiatric Press; 1996. 540 p

Over the past 30 y and particularly over this last decade — the decade of the brain — there has been marked acceleration of research efforts in the fields of neuroscience, molecular genetics, and biochemistry of mental disorders. Coupled with increasing sophistication in clinical observations, there has been an explosion of information about mechanisms of normal and pathological brain function. Although we are still far away from a clear understanding of the psychopathology behind 2 of the major psychiatric disorders, schizophrenia and affective disorders, substantial information already exists linking subcellular biological activities and the functioning of the neurons. The integration of information from molecular genetics, biochemistry, pharmacology, brain anatomy, and neuroimaging has advanced our knowledge about the impact of mental illness on specific brain neural circuits and their response to treatment. The recent and evolving knowledge about such specific brain circuits has inspired a new strategy of pharmacological targeting in the treatment of mental disorders. In this context, this book has its major strength focusing on the interface between several mental disorders and the genetics, pharmacology, neurochemistry, brain imaging, and postmortem studies reported by the researchers themselves, who are active in these fields.

The book emanates from contributions by a number of well-known and accomplished researchers in neuroscience to the 73rd meeting of the Association for Research in Nervous and Mental Disease, which took place in New York in 1993. One major feature of that meeting was that speakers were asked not only to present an overview of their field and their own work but also to provide their views on future developments. The book includes 17 chapters that deal with topics related to schizophrenia, affective disorders, infantile autism, an introductory chapter by the editor himself, and an overview chapter with discussions at the end. The introductory chapter by Watson presents an overview of mood disorders, autism, and schizophrenia from a clinical perspective and sets the stage for the basic science chapters that follow. The chapter written by Akil, “Biology of Stress from Periphery to the Brain,” explores the concept of “stress” as a trigger for psychiatric illnesses. The contributor documents her extensive work on the regulation of the limbic-hypothalamic pituitary-adrenal access and makes clear the well-known point that “the stressful nature of any given stimulus resides less in its objective characteristics and more in the organism’s ability to cope with it” (p 15).

The 5 chapters that relate to affective disorders include a contribution by Blakely about norepinephrine and serotonin transporters that highlights the progress on the molecular targeting of antidepressant effects. Another chapter, by Owens and others, deals with peptides and affective disorders and concludes with an account of future directions in the area based on the development of such new approaches as the application of ribonuclease (RNASE) protection assay, the expanding knowledge of the peptidergic brain circuits, and the ability to image central nervous system tissue with magnetic resonance imaging and positron emission tomography technology. The chapter about the mechanism of action of antidepressants by Berman and others elegantly reviews information, both basic and clinical, about well-known monoamines that have been explored in terms of their mechanism of action: serotonin, norepinephrine, dopamine, and neuropeptides. The chapter delves beyond the monoamines theory, however, by exploring postreceptors signal transduc-tion and neuroanatomy of antidepressant action and their relevance for the development of novel treatment approaches to depressive disorders. The chapter by Raichle and Drevets maps brain circuits relative to brain function and explores its implication for psychiatric illnesses. Another excellent chapter, by Mann and others, presents an up-to-date review of available information spanning more than 2 decades about postmortem studies of suicide victims.

The book includes 8 chapters related to schizophrenia. The chapter by Benes entitled “Excitotoxicity in the Development of Cortico Limbic Alterations in Schizophrenia” examines both the proposition that schizophrenia is a neurodegenerative disorder and the evidence for glutamatergeric dysfunction in schizophrenia. Goldman-Rakic, in her chapter, “Dissolution of Cerebral Cortical Mechanisms in Schizophrenia,” advances the argument from a neurocognitive perspective about the importance of frontal cortex and the role of working memory in the disordered thinking of patients with schizophrenia. Using postmortem studies, Kleinman and Nawroz provide evidence for the involvement of dorsal lateral prefrontal cortex, the hippocampus, and the entrorhinal cortex in the pathology of schizophrenia. An up-to-date review of the “Epidemiology and Behavioral Genetics of Schizophrenia” is provided by Tsuang and Faraone. Khan and her colleagues, in their excellent chapter, “Revisiting the Dopamine Hypothesis in Schizophrenia,” advance the argument for schizophrenia as both a hyper- and hypodopamine state, thus linking such diverse elements of the broad spectrum of symptomatology as positive and negative symptoms as well as neurocognitive deficits. The contributions of neuroimaging to the understanding of the psychopathology of schizophrenia is well presented in a chapter by Van Horn and colleagues. “Abnormal Frontotemporal Interactions in Patients with Schizophrenia,” by Friston and others, provides results of their extensive work using neuroimaging in examining functional connectivity by studying corticocortical interactions in patients with schizophrenia. The last contribution related to schizophrenia is the excellent chapter by Meltzer and others, “Exploring the Mechanism of Atypical Anti-psychotic Medications,” which provides evidence for Meltzer’s recent argument for a major role for serotonergic mechanics in the improved therapeutic effects of atypical antipsychotics, particularly their tendency to produce significantly fewer extrapyramidal side effects.

The chapter devoted to “Linkage and Molecular Genetics of Infantile Autism” by Ciaranello reports the results of extensive linkage studies of 1 of the least understood disorders: infantile autism. This chapter, coming after the recent sudden and untimely death of its author, serves as a memorial to a distinguished scientist.

Overall, the book is a significant contribution, providing valuable information for understanding the mechanisms of normal and pathological brain function and its relevance to schizophrenia and affective disorders. The book makes a good attempt to integrate information at the level of functional neurocircuits. It should be of interest not only to neuroscientists but also to psychiatrists, neurologists, and psychologists. Although the book is about basic neuroscience, its relevance to clinicians is obvious because it explores the basic biological brain functions in relation to mental

illness. The book reads well, which reflects the skills of its editor, Stanley Watson. The only regret I have is that it took 3 y to publish the proceedings of that 73rd meeting of the Association for Research in Nervous and Mental Disease, which is rather a relatively long time in terms of the rapidly evolving neuroscience research. Nevertheless, the book is a valuable contribution and continues to be equally relevant today.