Familial Aggregation and Phenomenology of 'Early'-Onset (at or Before Age 20 Years)

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Abstract
Background: While early age at onset has been associated with increased familial risk, increased clinical severity, and distinctive patterns of comorbidity in a range of psychiatric disorders, it has received limited attention in panic disorder, both in family studies and with respect to clinical presentation. Methods: A family study of 838 adult first-degree relatives of 152 probands in 3 diagnostic groups (panic disorder with or without major depression, subdivided by age at onset at or before 20 and after 20 years, and screened normal controls) was used to examine familial aggregation of panic disorder by proband age at panic disorder onset. Phenomenology of panic disorder in ill probands and their affected adult first-degree relatives was investigated as a function of proband panic disorder onset at or before 20 vs after 20 years of age. Results: Compared with adult first-degree relatives of normal controls, the risks of panic disorder in adult firstdegree relatives of probands with panic disorder onset at or before 20 and after 20 years of age were increased 17-fold and 6-fold, respectively. These findings were not explained by the numerous potential confounding factors that we tested. Age at panic disorder onset did not appear to be specifically transmitted within families. The clinical presentation of panic disorder differed little in either probands or affected relatives by proband age at onset. Conclusion: The strikingly elevated risk of panic disorder in relatives of probands with panic disorder onset at or before 20 years of age suggests that age at onset may be useful in differentiating familial subtypes of panic disorder and that genetic studies of panic disorder should consider age at onset.