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Genes, Environment, and PsychopathologyReview - Genes, Environment, and Psychopathology
Understanding the Causes of Psychiatric and Substance Use Disorders
by Kenneth S. Kendler and Carol A. Prescott
Guilford Press, 2006
Review by Andrea Bellelli, M.D.
Jul 31st 2007 (Volume 11, Issue 31)

Genes, Environment and Psychopathology reports on the results of a large study of twins aimed at detecting the causes of several psychiatric disorders nicknamed VATSPSUD. It provides a sound analysis of the results obtained and derives its force from the VATSPSUD being the largest scale survey of its kind. It is however a book for specialists, in spite of the intentions of its authors, and a background in medicine or biology is a helpful guide throughout its contents, since several relevant points are assumed without explanation.

Perhaps what the book lacks most is an introduction about the meaning of a causal explanation in the context of complex, multifactorial diseases. Suppose that you are given a sample of a hundred kids and are asked to state who are at risk for developing a given psychiatric disease whose lifetime prevalence is, say, 10%, so that preventive measures can be taken and, should the necessity arise, diagnosis is rapidly made and treatment is promptly instituted. If you have no hints other than the lifetime prevalence of the disease in question, your best prediction is that ten of these children will be diagnosed at some time in the future. If, on the contrary, you know exactly the cause of the disease, and this acts deterministically, and is present since birth (as it happens in the case of genetic defects), you may be able to recognize it in the affected children much before the appearance of the symptoms and split the group in two: 90 children will never fall ill and 10 will. In the real word we have not the knowledge necessary to a precise preventive diagnosis, and the known causes do not act deterministically: thus the most you can do is to consider known genetic and environmental factors and split your group in two or three with different risk levels: e.g. ten children may have 50% chances of falling ill and the remaining ninety may have only 5.5%. The purpose of studies like the VATSPSUD is that of detecting risk conditions and allowing better predictions to be made. This is much different from classical genetic or microbiological or nutritional medical research that aims at detecting true causes, rather than risk factors.

It can be safely stated that the VATSPSUD was a successful study, that identified several risk factors for major depression, phobias, substance abuse and antisocial behavior, and that ruled out other presumed risk factors as irrelevant. Indeed psychiatry has always been plagued by ideological assumptions that, even though apparently reasonable, proved to be fashionable rather than scientifically sound, and have been difficult to get rid of.

The study is based on the comparison of mono- and di- zygotic twins for concordance in psychiatric diagnosis. Each member of the couple (only a small number of triplets was present in the sample, due the rarity of this condition) was interviewed at least twice to investigate for several possible factors, mainly relating to recent and remote life events. The sample was huge, with over 11,000 individuals selected from the Virginia Twin Registry, and average completion rates (the percentage of individuals that completed the study) between 72 and 93%. An important feature of the study is that the sample is composed by "normal" people, i.e. the participants were not selected on the basis of diagnosis or hospitalization. This choice implies, as acknowledged by the authors, that less common diseases may be scarcely represented even in such a huge sample.

Essentially, two basic categories of risk factors were identified from the concordance rates of mono- and di- zygotic twins: genetic and shared environmental factors. Since these categories do not allow the full prediction of susceptibility to psychiatric diseases, a residual category was added, improperly named individual-specific environmental factors. What distinguishes the three categories is the way their relative weight is evaluated (p.42): the experimental data allow the direct determination of the weight of the former two, whereas that of the third is obtained by subtraction: i.e. the weight of individual-specific environmental factor is the difference between 100% and the sum of the other two. Although the logical procedure is relatively sound (and possible errors are considered in a later chapter), the name of the residual category is unfortunate. Let us consider which factors may be grouped together under the heading of individual-specific environmental: stochastic (i.e. probability based); diagnostic false positives (the authors acknowledge under the name of "errors" these two very different groups); true individual-specific environmental (i.e. everything from traumatic experiences to specific disease of only one member of the pair); and still others.

Genetic factors are recognized as very relevant: they explain, or predict, between 30 and 60% of the observed variability. Shared environmental factors are significant but usually poorly relevant; amongst these are parenting styles (classified, by interview, according to three axes: coldness, protectiveness and authoritarianism). By far the most relevant shared environmental factor identified is parental loss, that may increase the risk for the different psychiatric conditions studied by several-fold. A separate discussion is dedicated to childhood sexual abuse (CSA), that is associated to very significantly increased risk for several of the diseases studied, the more so the graver the abuse. CSA, as the environmental factors occurring in the adult life considered under a different heading, qualifies as individual-specific (unless the abusing adult has had access to both twins).

A very interesting test the authors carried out is that of reliability of the self report of psychiatric disease. This was assessed by asking each twin whether or not his or her co-twin ad suffered of psychiatric diseases and comparing this information with that each subject gave on himself. The use of both self assessment and co-twin assessment on each experimental subject corrected significantly the information obtained by self-assessment alone and increased the importance of the genetic influence on psychiatric diagnosis.

 

© 2007 Andrea Bellelli

Andrea Bellelli has an MD and a degree in psychology, and teaches biochemistry in the Medical School of the University of Rome, Italy.


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