Genes and behavior: nature–nurture interplay explained.

By Michael Rutter. Oxford, Blackwell, 2006. 272 pp. 24. 95, £14. 99. ISBN: 1-4051-1061-9. What a pleasure to read Sir Michael Rutter's new book; to encounter his mind at work as he lays out the terrain of the interplay of genes and their environments. Taken with his recent review of the subject in the 2006 Annual Review issue of our Journal, we have a nearly up-to-date review of this exciting and rapidly expanding field. I highly recommend his book as required reading for experts as well as trainees in our field. The best part of this volume is his reasoning and his appreciation of the challenging complexity. By joining with Ken Kendler (2005) to call into question the convenient shorthand of ‘a gene’ for autism or schizophrenia or for any of the other psychiatric disorders, Sir Michael invites us to view the ways in which genes and their environments are inextricably interwoven. First, genes do not code for specific behaviors or even dimensional traits. Rather, they set the stage for a series of molecular events that ultimately play a role in individual differences in susceptibility to behaviors of all kinds, normal and abnormal. Indeed, common genetic variations may well influence behaviors, attitudes and environmental experiences that are embedded in a social context. Second, it is clear that ‘allelic variations’ changes in the actual sequence of the gene that have been passed on from one generation to the next can dramatically alter the impact of an environmental pathogen such as stressful life events. The best example of this phenomenon comes from the work of Rutter's colleagues at the Institute of Psychiatry, Avshalom Caspi and Terrie Moffitt, who found in their landmark study that the short allele of the serotonin transporter gene (OMIM: 182138 SLC6A4) alters an individual's vulnerability to depression depending on the occurrence of intervening stressful life events (Caspi et al. , 2003). Third, while many of these variations are due to sequence differences, others are due to the level of expression of a specific gene product (i. e. , RNA, protein) that can be a direct result of earlier environmental differences. For example, we now know of several genes including the glucocorticoid receptor gene and the estrogen receptor alpha gene whose expression is altered in an enduring fashion within crucial brain regions depending upon how the newborn was nurtured (Champagne et al. , 2006; Weaver et al. , 2004) and that these alterations in gene expression likely play a role in a cascade of events that will eventually influence how that individual cares for their offspring when their time comes to be a parent (Francis et al. , 1999). Fourth, even after we have identified key susceptibility genes, there is so much that we do not yet know. It will only be through the development of animal models that we can begin to unravel the basic biological mechanisms that causally influence the course and onset of specific disorders. Yet, as pointed out by Rutter (p. 223), this will only be the next step. A more complete understanding will require an appreciation of how these molecular events influence interacting neural circuits, manifest behaviors and the subjective experience of our patients (Buzsáki & Draguhn, 2004). Next, it is a delight to read Rutter's caveats about the limitations of behavioral genetics. I am sure a few of his conclusions will prove to be a source of controversy, but that is good for our field. We need to think deeply and Sir Michael is refreshingly forthright in his appraisals of our simple-minded nosologies and of the assumptions that underlie some of our most sophisticated statistical analyses. Finally and not surprisingly, this volume is already out of date with regard to the identification of potential susceptibility genes associated with certain forms of psychopathology. Remarkable progress is being made. In the case of schizophrenia a dozen or more genes have been found and replicated (Straub & Weinberger, 2006). Investigators are starting to get at least a glimpse of the potential mechanisms by which these genes influence the risk of disease. Hopes are again on the rise that the nature of much of the genetic variation associated with schizophrenia will be clarified within the next decade and at least some of the cellular mechanisms will be elucidated. Even after Sir Michael's 30 years of effort (Folstein & Rutter, 1977) the field of psychiatric genetics remains in its infancy. Reading this book will enormously help to nurture this field along. The conclusion is also inescapable that the benefits from this effort will be enormous as it reaches maturity.