Anticipation in bipolar affective disorder: is age at onset a valid criterion?

Anticipation has been suggested among the genetic mechanisms of bipolar disorder (BD), prompting the search for unstable DNA sequences. Past studies of anticipation in BD have generally relied on observed shift in the age at onset between parental and offspring generations. Such a shift, however, may be caused by a number of other factors difficult to correct for. We investigated age at onset distributions in a sample of 161 related subjects and in a sample of "pseudofamilies" consisting of 320 unrelated subjects selected from a large epidemiological cohort using Monte-Carlo simulation to mimic the family sample. Comparison of age at onset distributions in both samples shows a difference between the generations, but of a similar magnitude in each sample. This suggests that age at onset alone may not be a sufficient criterion of anticipation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:804-807, 2000.