Triplet repeats and bipolar disorder.

Abstract

Anticipation, the phenomenon of a disease becoming more severe or having earlier onset as it is transmitted down the generations, was originally described in families with psychiatric illness but was thought due to ascertainment bias and became forgotten. Interest was rekindled when a number of neurodegenerative disorders that show this phenomenon, were found to be due to a novel form of mutation--unstable triplet repeats showing intergenerational expansion. Some recent studies of anticipation are consistent with its occurrence in bipolar disorder but are still associated with methodological problems making interpretation difficult. A number of case-control studies employing the repeat expansion detection (RED) technique have found longer repeats in bipolar probands but other studies have found no such association. Despite a large number of studies examining the role of various repeat containing candidate genes, a pathogenic triplet repeat has yet to be found for bipolar disorder. It is likely that the controversy surrounding anticipation and the existence of triplet repeats will only finally be resolved with the demonstration of such a mutation in the aetiology of bipolar disorder.