Abstract

Clinical, familial, and biological differences according to age at onset (AAO) and the correlation observed for AAO in relatives with bipolar affective disorder (BPAD) suggest that AAO is a valid candidate characteristic for genetic studies of BPAD. Although much data is available, none of the various thresholds of AAO used has been validated. A preliminary study of AAO in BPAD showed there to be three subgroups of the disease according to AAO. Replication in independent samples, with different methods is needed. Admixture analysis was used to determine the model that best fitted the observed distribution of AAO. In addition, affected sibs were more likely to belong to the same theoretical subgroup identified by admixture analysis. Both analyses were consistent with the existence of three AAO subgroups in BPAD (mean ± S.D.): 17.4 ± 2.3, 25.1 ± 6.2 and 40.4 ± 11.3 years). The proportion of the population in each subgroup differed between the samples, reflecting heterogeneity in sampling procedure. These data further demonstrate the existence of three AAO subgroups in BPAD. Together with the results of clinical, epidemiological, segregation and genetic studies, these results suggest the existence of specific familial vulnerability factors underlying each of the AAO subgroups and/or vulnerability factors involved in the onset of the disorder. Future biological and genetic studies of BPAD should focus on AAO subgroups.

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