Using family studies to understand comorbidity.

Methods for investigating the nature of comorbidity of two psychiatric disorders, where each disorder is known to be familial, using family studies are described. The methods consist of using a study design which include relatives of four proband groups, namely probands with the pure form of each disorder, probands with the comorbid form of the disorders, and control probands who have neither of the disorders. Disorders in relatives were classified to parallel the disorder categories in probands. Patterns of transmission of these disorders between probands and relatives hypothesized under various models of comorbidity, and statistical methods for formally testing these hypothesis are described. These methods are illustrated, by applying them to data from a recent family study to investigate the relationship and the cause of comorbidity between panic disorder and major depressive disorder.