EXPANDED TRINUCLEOTIDE CAG REPEATS IN FAMILIES WITH BIPOLAR AFFECTIVE-DISORDER

Clinical anticipation has been reported in bipolar affective disorder (BPAD). The hypothesis that expanded trinucleotide repeats are related to anticipation and transmission pattern in families with bipolar aff ective disorder is rested in this study, Eighty-seven two-generation p airs of patients recruited from 29 bipolar families were analyzed. The repeat expansion detection method was used to detect CAG repeat expan sions between successive generations. Significant changes in age at on set and episode frequency in successive generations were observed Mean trinucleotide CAG repeat length between parental and offspring genera tion significantly increased when the phenotype increased in severity i.e., changed from major depression, single episode or unipolar recurr ent depression to BPAD, A parent-of-origin effect was also observed wi th a significant increase in median length CAG between G1 and G2 with maternal inheritance. This increase was observed notably in female off spring, Our findings indicate for the first time that expansion of CAG repeat length could explain the clinical observation of anticipation in families with BPAD, These results provide further support for expan ded trinucleotide repeat sequences as risk factors in major affective disorders. (C) 1997 Society of Biological Psychiatry.