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For unknown reasons the inhalation of CO(2)-enriched air mixtures evokes acute panic-like symptoms in people with panic disorder and in their unaffected relatives. This study was set to determine whether, and to what extent, CO(2)-induced acute anxiety and panic disorder share the same genetic and environmental determinants. Cholesky structural equation models were used to decompose into genetic and environmental elements the correlation between self-assessed anxiety post-35%CO(2)-65%O(2) inhalation and interview-based DSM-IV lifetime diagnoses of panic disorder in 346 young adult twin pairs of the Norwegian Institute of Health Panel, 12% of whom had been invited to take part into the CO(2) study on the basis of self-reported symptoms of anxiety gathered 4-7 years before the provocation challenge. A full model corrected for the partially selective ascertainment showed that the phenotypic correlation between post-CO(2) anxiety and DSM-IV panic was largely due to additive genetic influences, while shared and unique environmental agents concurred to explain a relatively minor proportion of the correlation between these two traits. According to the best-fitting model the genetic correlation between post-CO(2) anxiety and panic was 0.81 (0.50-0.98); a common genetic factor was sufficient to explain the traits' covariation and a further, specific genetic factor was necessary to account for the residual phenotypic variance. The genetic determinants that lead to overreact to a hypercapnic stimulus coincide at a considerable extent with those that influence liability to naturally occurring panic. Environmental factors provide a modest--or no--contribution to the covariation of CO(2)-provoked anxiety with naturally occurring panic.
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