Handbook of Psychiatric Genetics

Commenting on the social construction of the brain for the American Journal of Psychiatry, Leo Eisenberg welcomed the return of the brain to psychiatry by exclaiming: “The brain is back in fashion and a welcome development that is!”¹ Reflections on the brain have never really left psychiatry. Rather, they were shelved with thought experiments, much as Freud had shelved his great manuscript of the “Project for a Scientific Psychology,” so unsure was he of its postulates. With contemporary neuroscience, of course, all this has changed. From molecules to brain images to mind, we scrutinize the brain with multiple lenses, of which genetics is but one. That genes contribute to the expression of psychiatric disorders is beyond dispute. Despite many setbacks, the renewed vigor of genetic inquiry is seminal, for it poses a question crucial for the field: How much of “who we are” is “what we are”? The flurry of activity in psychiatric genetics has brought this discipline to a point where a retrospective look would be welcomed. Clinicians in practice, residents in training, and graduate students beginning their research could use a skillfully assembled book surveying the field. The Handbook is a judicious attempt, but one marred in certain chapters by a proselytizing tone more suited for a pamphlet. Drs. Blum and Noble, both distinguished investigators in the field, have proposed the TAQ1 allele of the DRD2 receptor to be a major susceptibility marker for alcoholism. They have also proposed the existence of a “reward deficiency syndrome” in carriers of the TAQ1 allele. These hypotheses are discussed with zeal in many chapters throughout the book.

The book is organized in six sections, discussing 1) Analytic Approaches, 2) DNA Analysis, 3) Molecular Biology of Receptors and Associated Proteins, 4) Psychiatric Genetics, 5) Substance Use Disorders, and 6) Genetic Impact on Behavior. The usefulness of these chapters will depend on who among the designated readership actually reads this handbook. Clinicians who want to better understand the import of the many receptor types that pervade the psychopharmacology literature will find section III most helpful. It offers very good overviews of the different transmitter systems, particularly of the dopamine and serotonin systems. Graduate students dedicating themselves to psychiatric genetics will also find section 3 helpful, perhaps along with the more technical chapters in sections 1, 2, and 6. Geneticists themselves may find this broad outline of the field useful, though its value to them will be limited.

Like most handbooks in science, this one has certain characteristic drawbacks. Investigators will not find discussed important recent reports like the one concerning clone 22 on chromosome 18p11.2 in bipolar disorder.² This is excusable, of course, reflecting only the built-in delays of publishing. The proselytizing tone mentioned earlier is less so. Close to 130 pages, or one-third of this 481-page book, is devoted to the editor's primary field of inquiry: association studies pertaining to the TAQ1 allele of the D2 receptor. Much statistical and dialectic effort is expended in answering the critics of this hypothesis. There is nothing inherently wrong with this. In scientific circles, handbooks do at times serve such purposes as answering critics, presenting supporting data that may not have been included in published papers, and allowing investigators to speak their minds without the prior censure of the editor's pen. In this instance, unfortunately, the same evidence about the TAQ1 allele is repeated in so many chapters that it is hard to avoid the impression that the editors could not edit themselves.

Nonetheless, the publication of this handbook emphasizes the current importance of genetics for psychiatry. Thus, careful discussion of the methodology used is timely and pertinent—and on no topic is it more so than association studies. Data from association studies abound in this handbook as well as in current journals. Such studies are favored by investigators for the ease with which they can be carried out and for their sensitivity to small genetic effects. However, the numerous contradictory reports they have produced have called into question their genuine utility. Recent editorials in Molecular Psychiatry³ drew a consensus that, beyond their limitations, association studies remain an important tool of psychiatric genetics. In spite of their many pitfalls, small association studies will likely continue to play a role to the extent that their phenotypes are narrowly defined and that they can provide data for larger meta-analysis. To render these studies more comparable with each other, several authors have proposed uniform methodological principles and standards.³ These would be not unlike standards that are applied in chemistry for the nomenclature of chemical compounds or in molecular biology for the classification of serotonin receptors. A common way and a common language serve a common cause.

Psychiatric genetics is one of the frontiers of psychiatry that is redefining our concepts of psychiatric conditions and their treatment. Genetics as it applies to behavior has suffered from quackery and from malevolence. Our discipline continues to suffer from this ill legacy. Yet the future legitimacy of psychiatry lies in how we will approach, size up, criticize, and mold concepts like those brought forward by psychiatric genetics into a coherent theory of the mind. For pointing out the necessity, complexity, limitations, and promise of this endeavor, the authors of the Handbook of Psychiatric Genetics are to be congratulated.