Trinucleotide repeat expansions: Do they contribute to bipolar disorder?

It has long been known that bipolar disorder has a true but complex genetic background. Reports on genetic anticipation in bipolar disorder opened the way to a new approach for genetic studies. Indeed, anticipation, a decreas ing age at onset, and/or increasing disease severity in successive generati ons, were recently explained by an expansion of trinucleotide repeats in mo nogenic diseases like Huntington's disease and Fragile X syndrome. The invo lvement of trinucleotide repeat expansions in bipolar disorder received eve n more support when studies reported association of large CAG/CTG repeats w ith bipolar disorder. Even though a large number of studies have been condu cted, this association is still unexplained. Here, we review the studies in vestigating the trinucleotide repeat expansion hypothesis in bipolar disord er. Studies on anticipation, on association of anonymous large CAG/CTG repe ats and on specific trinucleotide repeats are critically analysed and discu ssed, showing a field with precipitate conclusions or inconclusive results. The analysis suggests that there are indications, though disputable, suppo rting the trinucleotide repeat expansion hypothesis in bipolar disorder, bu t no conclusive evidence has been hithereto provided. (C) 2001 Elsevier Sci ence Inc.