Genetic anticipation and imprinting in bipolar I illness

The study focused on: (1) the existence of genetic anticipation in a randomly selected sample of bipolar I patients using broad and narrow definitions of the affection status in the parental generation; (2) the relationship between anticipation and the age at investigation in probands and in their relatives; (3) the relationship between anticipation and imprinting.

One hundred and fifteen bipolar I patients and their first- to third-degree relatives were diagnosed according to DSM-III-R criteria using the Diagnostic Interview for Genetic Studies and the Family Interview for Genetic Studies.

Age at onset was found to be 6-10 years younger in probands with affected parents or uncles/aunts. Two-thirds of these families showed positive anticipation under both the broad and the narrow definitions of affection status in the parents' generation. The age at investigation was younger in probands showing positive anticipation. Anticipation was found only in probands inheriting the disorder from the paternal side.

In spite of the inevitable association between young current age and young age at onset, which could result in spurious anticipation effects, our findings suggest that this phenomenon is not the sole cause of observed anticipation.