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Twin Studies of Psychiatric Illness:  An Update

Kenneth S. Kendler, MD
Arch Gen Psychiatry. 2001;58(11):1005-1014. doi:10.1001/archpsyc.58.11.1005.
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This overview presents selected recent developments in twin studies of adult psychiatric disorders. Subjects examined include the generalizability of heritability estimates, the impact of sex on patterns of familial transmission, gene-environment interaction, twin studies of anxiety and eating disorders, the so-called family environment, special issues raised by twin studies of drug use and abuse, and gene-environment correlation. The studies reviewed suggest that (1) the heritability of many behavioral traits may be greater in permissive than in restrictive environments and, (2) for psychiatric and drug abuse disorders, genes probably work through both traditional within-the-skin physiological pathways and outside-the-skin behavioral pathways. In the latter, genes affect aspects of the social environment, such as exposure to stressful life events and levels of social support, which in turn feed back on risk of illness. Twin studies remain a vibrant part of the field of psychiatric genetics and an important complement to and context for current efforts to localize individual susceptibility genes.

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Figure 1.

A bivariate twin model for substance initiation and subsequent substance misuse. Observed variables are depicted in boxes and latent variables in circles and ellipses. The model begins with the risk factors for initiation (indicated by the subscript I), which are divided into additive genetic (AI), common environmental (CI), and individual-specific environmental (EI) components. For individuals above the threshold on this dimension, initiation occurs and they become susceptible to misuse. The vulnerability to substance misuse derives from 2 sources: (1) risk factors shared between initiation and misuse, reflected in path b, and (2) risk factors that influence misuse that are independent of the liability to initiation. These are also subdivided into additive genetic (AM), common environmental (CM), and individual-specific environmental (EM) components, where the subscript M indicates that they are specific for misuse. Path coefficients, indicated by lowercase letters (a, c, and e), reflect standardized partial regression coefficients. Therefore, the proportion of variance in the observed dependent variables accounted for by the latent independent variable is equal to the square of the connecting path. Heritability of initiation, for example, equals ai2. The total heritable influences on drug misuse can be subdivided into those that are shared with initiation, which equals ai2 × b2, and those that are specific to misuse, am2.

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Figure 2.

A, The traditional view of genes and environment in which genetic expression takes place solely in a physiological internal milieu (ie, inside the skin), whereas the environment exists outside the skin. Both genes and environment can affect disease susceptibility. In this traditional model, the causal relationship between the organism and the environment flows in only one direction: from environment to organism. B, A revisionist view of genes and environment in which genetic factors, by influencing behavior, affect the external (outside-the-skin) milieu. This process has been termed genotype-environment correlation or genetic control of exposure to the environment. C, A combined model of genes and environment that posits 2 pathways through which genes can affect disease susceptibility: the traditional, physiological, inside-the-skin pathway and revisionist, outside-the-skin pathway by influencing exposure to environmental risk factors.

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