Psychiatric Genetics and Genomics - Softcover

9780198564867: Psychiatric Genetics and Genomics

Softcover

ISBN 10: 0198564864 ISBN 13: 9780198564867

Publisher: Oxford University Press, 2004

Genetics promises to provide one of the most powerful approaches to understanding the functional pathology of the human brain. This book presents a critical review of the evidence for a genetic contribution to common psychiatric conditions and the rarer single-gene disorders that may have psychiatric presentations
The first section of the book introduces the reader to molecular biology and the techniques of molecular genetics. The coverage then moves on to consider the genetics of normal and abnormal development, followed by a look at the genetics of abnormal behaviour in adults. This section includes, amongst others, consideration of personality disorders, schizophrenia and the dementias. The final section considers the applications of the work and covers issues such as counselling and ethics, closing with a look to the future.
The editors are internationally renowned figures in this field and they have invited a team of equally eminent chapter authors.
This will be essential reading for psychiatrists and geneticists and will be essential reading for psychiatrists and geneticists and will be of interest to neurologists, psychologists and neuroscientists.

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About the Author:

Peter McGuffin is at SGDP Centre, Institute of Psychiatry, Denmark Hill, London, UK. Michael J Owen is in the Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK. Irving Gottesman is at the University of Minnesota.

From The New England Journal of Medicine:

The quantitative analysis of the heritability of mental disorders, together with the demonstration of specific neuronal actions of psychotropic drugs, changed the conception of mental illness from a personal and family disgrace to a disorder of brain biology. The editors of this book are among the pioneers of psychiatric genetics who accomplished this feat. Their book summarizes the methods and results of the population-based family, twin, and adoption studies that first estimated the genetic and environmental influences on schizophrenia, bipolar affective disorder, autism, attention-deficit disorder, the dementias, and sociopathy. Using segregation analyses to compare familial distributions of illness with various models of inheritance derived from Mendel's laws of genetics, they theorized that most mental illnesses result from the additive effects of multiple genetic and environmental factors. On the basis of their analyses, which showed relatively small effects associated with any one gene, the prospects of finding actual DNA polymorphisms that produce heritable pathophysiological effects were uncertain. At the time this book was being written, genetic research had not yet identified such molecular abnormalities, but since then, a number of functional polymorphisms that contribute to brain dysfunction in several mental disorders have been identified. The value of this book lies in its chronicle of the epidemiologic approaches used in the initial demonstrations of genetic influence on mental disorders, even before substantive information about the human genome was available. A model for such investigations is the extensive work on the heritability of normal intelligence and personality traits, which is well summarized in a chapter by Robert Plomin, a prominent investigator of this issue, and his colleagues. They point out that the role of the environment in brain function is particularly complex: because the brain seeks and creates its own environment, its genetically constituted abilities have a profound effect on its experience. This phenomenon is amplified in the cases of conduct disorder and substance abuse, in which the influences of parents and siblings as mediated by a shared genetic predisposition toward substance abuse or criminal behavior may produce an environment that encourages such behavior. Thus, early exposure to tobacco, often thought to be a causative environmental factor in nicotine addiction, is more likely to result from the genetic risk of the addiction. The work on intelligence also sheds light on a mystery associated with several mental illnesses -- that is, their appearance during adolescence. Most illnesses express genetic components early in a person's life and are exacerbated by environmental damage over his or her lifetime. Plomin and colleagues point out that the genetic influences on many mental traits become more evident as people grow older, possibly because their environments and experiences become more self-selected and accentuate the manifestations of underlying differences in genetically determined abilities. Because the book does not include recent findings in molecular genetics, it does not provide a perspective on how these findings help us to understand brain function. For example, despite the high heritability of schizophrenia, there is no gene for schizophrenia. Genes code for the ribonucleic acids that produce the proteins that affect specific neuronal functions. Thus, these neuronal functions, rather than the illnesses themselves, are the biologic phenotypes of specific genetic polymorphisms. The question of how to identify such phenotypes is controversial, and the editors relegate the study of these phenotypes to "biological psychiatrists who are not geneticists." One strategy, advocated by the editors, is to use the methods presented in this book to establish the heritability of potential phenotypes, then to analyze their segregation patterns and, finally, to link them to genes. In other words, they propose that the mountain that they heroically climbed in order to establish the heritability of the illnesses on epidemiologic grounds alone be rescaled for each potential biologic measure. However, this approach ignores the considerable information provided by genetic data, which often predict the probable functional change at the neuronal level. Bivariate analyses have been developed to evaluate the relations between genetically controlled changes in neuronal function and traditional diagnoses of psychopathology. Some flaws make the book difficult to read. The frequency of illness in the siblings of ill persons divided by the population frequency, notated as (lamda)(sub s), is a measure that the authors use frequently, but it is defined only incidentally, in a late chapter on affective illness. The summary chapter refers to "consistent evidence for a substantial genetic influence on age of onset in schizophrenia" presented in an earlier chapter, but these data are not found anywhere in the book. Robert Freedman, M.D.
Copyright � 2003 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.

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