LARGE CAG CTG REPEATS ARE ASSOCIATED WITH CHILDHOOD-ONSET SCHIZOPHRENIA/

Recent studies have shown an association between trinucleotide repeat expansions (TREs) and adult-onset schizophrenia (AOS). Childhood-onset schizophrenia (COS) is a severe variant of schizophrenia with onset o f symptoms before age 12 years. We have used the repeat expansion dete ction (RED) method to investigate the occurrence of repeat expansions in a group of well-characterized COS patients as well as a set of clin ically related childhood-onset psychosis cases labeled 'multidimension ally impaired' (MDI). The difference observed in the CAG/CTG RED produ ct distribution between normal (n = 44) and COS (n = 36) samples was o nly marginally significant (P = 0.036). However, male COS samples.(n = 20) had a significantly different RED product distribution compared t o male controls (n = 25, P = 0.002) with longer RED products in COS. N o such difference was seen in females (n(cont) = 10; n(COS) = 16; P = 0.236). The difference remained significant between male COS (n = 12) and male controls (n = 24) when only Caucasian samples were used (P = 0.003). Similarly, the RED product distribution in male MDI samples (n = 18) was significantly different compared to male controls (P = 0.01 8). Some of the detected TREs in all three populations (COS, NIDI and control) correlated with expanded alleles found at the CTG18.1 locus o n chromosome 18, In conclusion, we have found an association between T REs and COS. This association is specifically significant in the male population. Thus, the occurrence of an expanded trinucleotide repeat m ay contribute to the genetic risk of COS, possibly in combination with other factors.