FREQUENCY-ANALYSIS OF LARGE CAG CTG TRINUCLEOTIDE REPEATS IN SCHIZOPHRENIA AND BIPOLAR AFFECTIVE-DISORDER/

Much interest has recently been focussed on the possibility of the inv olvement of unstable DNA in the etiology of schizophrenia and bipolar affective disorder (BPAD), following several publications that report increases in frequency of large CAG/CTG repeats in affected individual s. Using the Repeat Expansion Detection (RED) technique, we have perfo rmed a matched control pair analysis for both disorders, No significan t differences in CAG/CTG repeat sizes were observed for 52 bipolar aff ecteds and matched controls (P=0.15), and borderline significance was observed for 54 schizophrenia affecteds and matched controls (P=0.05), using a (CTG)(10) oligonucleotide (one-tailed t-tests for paired samp les). Furthermore, using a (CTG)(17) oligonucleotide, no significant d ifferences were observed for 58 bipolar affecteds and 55 schizophrenia affecteds compared to 81 unmatched controls. No significant sex effec t was observed for either group, and no significant differences in rep eat size were found for responders and non-responders to drug treatmen ts, More importantly, there was no significant correlation (either pos itive or negative) between age of onset of disease and size of repeat, We thus cannot conclude that CAG/CTG trinucleotides are involved in p sychotic disorders and that either the differences observed in similar studies may be the result of population stratification, or that the i ncreased frequency of larger repeats amongst affected individuals is a much smaller effect than previously thought.