EXPANDED CAG CTG REPEATS IN BIPOLAR DISORDER - NO CORRELATION WITH PHENOTYPIC MEASURES OF ILLNESS SEVERITY/

The hypothesis that expanded trinucleotide repeats (TNRs) contribute t o the pathogenesis of bipolar disorder has received strong support fro m recent studies showing that, on average, bipolar patients carry larg er repeat sequences of the TNR motif CAG/CTG than do controls, It has been postulated that intergenerational expansion of a TNR may be respo nsible for the tendency for age of onset to become earlier in younger generations (anticipation) observed in some bipolar pedigrees, and tha t length polymorphism may account for variability in clinical phenotyp e, We have used the method of repeat expansion detection to examine th ese predictions in a sample of 133 Caucasian DSM-III-R bipolar I proba nds from the British Isles, We found no evidence to support the notion that CAG/CTG TNR genes are major determinants of phenotypic severity or age at onset in the population examined and conclude that for most cases of bipolar disorder TNR genes may operate as susceptibility gene s rather than as single genes of major effect. (C) 1997 Society of Bio logical Psychiatry.