Background: Unstable DNA has been implicated in a variety of neuropsychiatric disorders, with increasing severity of disease associated with larger DNA repeats. We examined the unstable DNA hypothesis for bipolar disorder by looking for increased severity of symptoms and earlier age of onset amongst bipolar individuals with large CAG/CTG repeats.
Methods: From a sample of 91 bipolar subjects, eight with large CAG/CTG (> or = 270bp) trinucleotide repeats were matched to eight bipolar individuals with small repeats (< or = 150bp). Medical charts were reviewed for age of onset and a number of severity indicators. Candidate CAG/CTG expansions on chromosomes 17 and 18 were also genotyped.
Results: No obvious differences were noted for the clinical indices, however seven out of eight individuals with large Repeat Expansion Detection (RED) products had expansions at the CTG18.1 locus, while four out of eight had large repeats at ERDA1. Both of these sites are unlikely to be related to disease.
Limitations: Our total sample size is small and less than 9% have large repeats.
Conclusions: The lack of increased severity or earlier age of onset amongst bipolar subjects with large CAG/CTG repeats suggests these repeats are unlikely to have a major etiological role in bipolar disorder.