Anticipation in schizophrenia and bipolar disorder controlling for an information bias

Anticipation was investigated in schizophrenia (SZ) and bipolar disorder (B P) while addressing several biases in 18 large families (154 subjects) from Eastern Quebec densely affected by SZ, BP, or both over three generations. In particular, we controlled for an information bias using a measure of qu ality and quantity of clinical information (QOI) concerning the subjects' i llness. Otherwise, spurious anticipation could have arisen because we found that QOI varied with the generations as well as with the severity of illne ss. Although anticipation was investigated separately for SZ and BP, both d isorders were also included in one analysis that tested anticipation under the unitary hypothesis that the SZ and the BP spectrums represent a continu um of severity of the same disease. Age of onset (AOO) and five indices of severity were tested for anticipation. Two statistics were used: the differ ence in the mean AOO or severity between two successive generations, and th e mean difference in parent-offspring pairs (POP). The study led to four ma in findings: 1) the choice of the statistics greatly influenced the results , POP yielding systematically greater biased estimates; 2) for SZ and BP, t he evidence for anticipation with the five severity indices vanished after controlling for QOI; 3) as regards AOO a decrease of 8.6 years, p = 0.0001, and 5.3 years, p = 0.009 in AOO was found for SZ between Generations 1-2, and 2-3, respectively, despite controlling for QOI and addressing all biase s; and 4) conversely for BP, anticipation with AOO may be due to censoring. Findings suggest that future anticipation studies should also control for QOI. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:61-68, 2000. (C) 2000 W iley-Liss, Inc.