Anticipation in schizophrenia

In Various genetic disorders it has been observed that the severity of illn ess increases and the age at onset decreases in successive generations. Thi s phenomenon is termed anticipation. We sampled 15 families, totalling 123 individuals with at least one person affected by a disease of the schizophr enia spectrum in the index generation in each family (IG; n=33 affected out of a total of 67 individuals) and in the parental generation (PG; n=16 aff ected out of a total of 56 individuals). The pedigrees had originally been identified for linkage studies in schizophrenia. We found a significant dif ference between IG and PG regarding severity of illness as defined by Kendl er et al's hierarchical model of categories of the schizophrenia spectrum ( p=0.001). Age at onset was significantly earlier in the IG (21.6+/-6.6 year s) than in the PG (40.2+/-9.2 years) (p=0.0001). We excluded a potential bi rth cohort effect by investigating a control sample consisting of two non-o verlapping birth cohorts of patients with schizophrenia. Age at onset betwe en the two groups of the control sample did not differ. Anticipation is an important aspect in the investigation of a possible genetic basis, at least for the familial form of schizophrenia. Active research on a molecular lev el with special emphasis on trinucleotide repeats might be able to shed fur ther light on this phenomenon. (C) 1999 Elsevier Science B.V. All rights re served.