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Genes, Environment, and Psychopathology: Understanding the Causes of Psychiatric and Substance Use Disorders
Reviewed by DEBORAH L. LEVY
Am J Psychiatry 2007;164:1763-1764. doi:10.1176/appi.ajp.2007.07081262
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by Kenneth S. Kendler and Carol A. Prescott. New York, Guilford Press, 2006, 388 pp., $45.00.

This book is a gem. It takes the reader on a behind-the-scenes excursion into the rationale, methodology, and findings of one of the most ambitious and influential genetic-epidemiological studies in recent history. The Virginia Adult Twin Study of Psychiatric and Substance Use Disorders (VATSPUD) is a systematic attempt to explore the roles of genetic and environmental risk factors and their interaction in the etiology of a range of common disorders, including generalized anxiety disorder, major depression, and phobias (grouped as internalizing disorders) and childhood conduct disorder, adult antisocial personality disorder, and substance and illicit drug use (grouped as externalizing disorders). Committed to avoiding the methodological flaws of previous generations of twin and epidemiological studies, the authors ascertained a large population-based sample of same-sex and opposite-sex twins (more than 4,500 pairs) through the Virginia Twin Registry. This sample, which included some parents as well, allowed them to test a wide range of hypotheses relevant to the central themes of the study. Many of the subjects were longitudinally assessed. In addition to reporting prevalence data and heritability estimates for each disorder and for comorbidity, this study is the most rigorous attempt to date to parse the role of specific environmental risk factors, both temporally distant and recent. Among the other topics addressed are whether environmental risk factors are truly causal (as opposed to correlational but noncausal), disorder specificity of, and sex differences in, genetic and environmental risk factors, and changes in the interplay between these factors over the course of development. This abbreviated list gives just a sense of the scope of the scientific questions addressed in this study. Whether or not readers share the “penchant for methodological details” that the authors clearly have, one cannot help but gain an appreciation for the authors’ rigorous efforts to attend to quality control, blindness, repeatability, measurement error, validity of the equal environment assumption, and representativeness of the sample, to name just a few.

Kendler and Prescott clearly aim to make their reasoning and methods accessible, and they succeed. They also go to considerable effort to make the book reader-friendly; a list of abbreviations is presented at the beginning, sidebars provide background detail, and data-rich appendices are included at the end of relevant chapters. A list of more than 150 publications on which this book is based makes it possible for interested readers to consult original sources. Rarely does a reader have such an opportunity to be exposed to the kind of thoughtful, deliberative planning that goes into every aspect of the design and implementation of a study. Equally compelling is the way the reader is guided through how to distinguish between various causal explanations and how specific features of the study design make it possible to answer certain questions. Additionally, sources of potential bias and limitations are addressed. When results are inconclusive, the authors explain why. Most importantly, readers learn how two people immersed in psychiatric genetics grapple with challenging questions about the etiology of psychiatric disorders.

The book presents a dazzling array of findings that both clinicians and researchers will be eager to know. Some may come as a surprise, particularly those that seem inconsistent with widely held beliefs. Following are some examples, which hopefully will whet the reader’s appetite for more:

  • The magnitude of genetic effects on risk for the psychiatric and substance use disorders studied is neither huge nor insignificant.

  • The genetic risk factors that predispose one to internalizing disorders or externalizing disorders are largely independent.

  • Modest and almost entirely overlapping genetic factors account for most of the risk for depressive and anxiety disorders. This finding is particularly significant in light of the high rate of comorbidity for these disorders and their similar response to certain classes of antidepressants.

  • The size of the genetic component in substance use disorders is at least as large as, and often larger than, for internalizing disorders.

  • Genetic factors account for all the variance in familial resemblance in liability for alcohol use problems.

  • Depression does not cause alcohol abuse, even though the two disorders are correlated.

  • Early drinking does not cause later alcohol use problems, even though the two are correlated. As with depression and alcohol abuse, shared genetic liability contributes to each, but one does not cause the other. (Note the policy implications for intervention, which are discussed in the book.)

  • Certain environmental factors (e.g., parenting behavior, parental loss, certain stressful life events, and childhood sexual abuse) are causally related to risk for psychiatric disorders, but these effects are modest and nonspecific.

  • Genetic factors mediate sensitivity to the pathogenic effects of environmental risk factors through control of, sensitivity to, and exposure to the environment.

One cannot read this book without learning much in the process. The story told here might not be complete, as the authors state, but it is so much more than a start.

+Book review accepted for publication August 2007 (doi: 10.1176/appi.ajp.2007.07081262).

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