The structure of genetic and environmental risk factors for anxiety disorders in men and women.
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.


METHODS
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.


METHODS
General community sample.


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


METHODS
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.
Hettema
John M
JM
Virginia Institute for Psychiatry and Behavioral Genetics and Department of Psychiatry, Virginia Commonwealth University, Richmond, USA. jhettema@hsc.vcu.edu <jhettema@hsc.vcu.edu>
Prescott
Carol A
CA
Myers
John M
JM
Neale
Michael C
MC
Kendler
Kenneth S
KS
D000328:Adult; D001008:Anxiety Disorders / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D015897:Comorbidity; D004200:Diseases in Twins / Q000209:etiology* / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008957:Models, Genetic; D015233:Models, Statistical; D011569:Psychiatric Status Rating Scales; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D012737:Sex Factors; D012931:Social Environment; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics; D014768:Virginia / Q000453:epidemiology