Neurogenetics of Psychiatric Disorders PDF

Preface

Neurogenetics forms the bridge between biology and neuroscience on one hand and genetics on the other. Clinical applications of neurogenetics are evolving, and it is anticipated that within a few years they will expand well beyond the current genetic testing for the few simple "one gene" forms of illness (such as is the case for Huntington's disease and some forms of Alzheimer's disease).

There is a growing expectation that clinicians will soon be able to exploit and utilize pharmacogenetics in the care of their patients. It is further anticipated that knowledge of genetic subtypes of neuropsychiatric disorders will result in a rethinking of the disease concept as it is currently known in the Diagnostic and Statistical Manual of Mental Disorders IV structure of American (and worldwide) psychiatry. Finally, the National Institutes of Health has made restructuring of the clinical research engine a priority, and it has a stated focus on translating the research from bench to bedside.

The focus of this publication is the translation of bench-based research to the clinical bedside, with the aim of ushering in the enthusiasm and practicality of these results at the clinical level. For the most part, textbooks on psychiatric disorders lack updated information on the biology of disease genes. We believe that these disease genes will become the essential platform upon which neuroscience will build a productive application of science in the clinical setting.

book offers the most current overview of how basic neuroscience contributes to the clinical practice of psychiatry. The book begins with an introduction to the current state of genetics in major mental illnesses, including an overview of the relevant history and findings of genetics from the past century. We use Alzheimer's disease as the prototype for the pathways heading to integration of genetics, biology, and clinical studies in the cognitive and behavioral realm and illustrate the points elaborated above. We follow with a discussion of major mental illnesses, such as schizophrenia, as well as the rare single-gene neuropsychiatric diseases. What we have learned from these disease states will serve as an example for how we can approach the more common psychiatric disorders in both the adult and child.

Next, we focus on the disease models involving candidate genes in model organisms. This section is highly significant since such models will ultimately bridge basic science or genes to their clinical applications. It is the translation of such knowledge that has been absent for the clinician. We begin this section with chapters that organize candidate gene products classified by their functions. In particular, we discuss the gene products either as neurotransmission or neurodevelopment associated in the pathophysiology of schizophrenia. Following these chapters, we provide an overview of genetics-based models, including rodents and lower vertebrates. For the final chapter, we develop and present a unified model that includes concepts of genetic and environmental cross-talks for the disorders. We intend to show that this research will soon become the basis for treatment of these disorders. New drugs will no longer be "me too" drugs developed on the basis of similarities to existing medications, but will be the result of specific inquiry of the biological and genetic mechanisms discovered in the wake of the genome project.

It is imperative for the clinician to appreciate how a gene is causally associated with disease. At the same time, we must pay close attention to the ethics and implications of such work, and a chapter summarizing the current discussions in the field is included.

Finally, we conclude with what is on the horizon for translational research. It is our hope that this publication will serve as a reference source for clinicians, researchers, and other health care professionals seeking answers to the many questions related to the understanding of the neurobiology and the relevant treatment implications of neurogenetics of psychiatric disorders. It is our hope that the clinician, upon reading this book, will be able to "translate" the research and its applicability to their patients.