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John M. Hettema, MD, PhD; Carol A. Prescott, PhD; John M. Myers, MS; Michael C. Neale, PhD; Kenneth S. Kendler, MD

Arch Gen Psychiatry. 2005;62:182-189.

Background  The anxiety disorders exhibit high levels of lifetime comorbidity with one another. Understanding the underlying causes of this comorbidity can provide insight into the etiology of the disorders and inform classification and treatment.

Objective  To explain anxiety disorder comorbidity by examining the structure of the underlying genetic and environmental risk factors.

Design  Lifetime diagnoses for 6 anxiety disorders (generalized anxiety disorder, panic disorder, agoraphobia, social phobia, animal phobia, and situational phobia) were obtained during personal interviews from a population-based twin registry. Multivariate structural equation modeling that allowed for sex differences was performed.

Setting  General community sample.

Participants  More than 5000 members of male-male and female-female twin pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders.

Main Outcome Measures  Parameter estimates for best-fitting model.

Results  The full model, which contained 2 common genetic, shared environmental, and unique environmental factors plus disorder-specific factors, could be constrained to equality across male and female study participants. In the best-fitting model, the genetic influences on anxiety were best explained by 2 additive genetic factors common across the disorders. The first loaded most strongly in generalized anxiety disorder, panic disorder, and agoraphobia, whereas the second loaded primarily in the 2 specific phobias. Social phobia was intermediate in that it was influenced by both genetic factors. A small role for shared environmental influences was observed owing to a single common factor that accounted for less than 12% of the total variance for any disorder. Unique environmental influences could be explained by a single common factor plus disorder-specific effects.

Conclusions  The underlying structure of the genetic and environmental risk factors for the anxiety disorders is similar between men and women. Genes predispose to 2 broad groups of disorders dichotomized as panic-generalized-agoraphobic anxiety vs the specific phobias. The remaining associations between the disorders are largely explained by a unique environmental factor shared across the disorders and, to a lesser extent, a common shared environmental factor.

Author Affiliations: Virginia Institute for Psychiatry and Behavioral Genetics and Departments of Psychiatry (Drs Hettema, Prescott, Neale, and Kendler and Mr Myers) and Human Genetics (Drs Neale and Kendler), Virginia Commonwealth University, Richmond.

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