FURTHER EPIDEMIOLOGIC EVIDENCE FOR ANTICIPATION IN SCHIZOPHRENIA

Anticipation describes an inheritance pattern within a pedigree in whi ch disease severity increases, and/or age at onset decreases, in succe ssive generations. This phenomenon has been described in different sam ples of schizophrenic subjects, and could explain many inconsistencies in the inheritability of schizophrenia. Anticipation is. however, sub ject to numerous and significant biases, partially controlled by diffe rent methodologies used in different studies. We analyzed the anticipa tion effect on an original sample of schizophrenic patient (n = 57) wh o had at least one other schizophrenic in their family belonging to an other generation (father/mother. uncle/aunt, son/daughter). We tested the anticipation effect according to previously published methodologie s, such as percentages of parent-child pairs showing negative versus p ositive anticipation, comparison of anticipation limited to parent-chi ld or uncle-nephew pairs, anticipation analysis on the basis of famili es with unilineal origins only, and comparison of the age at onset-sur vival distribution of the two generations. The 31 schizophrenic subjec ts who belonged to the younger generation had a significantly earlier age at onset (24.58 years) than the 26 schizophrenic subjects who belo nged to the older generation (36.46 years). Whatever the method used t o control biases, we significantly found earlier age at onset for schi zophrenic patients from the younger generation. There is strong eviden ce for the existence of the anticipation effect in schizophrenia in ou r sample, as well as in various others, which may elucidate numerous i nconsistencies in clinical and epidemiological data which characterize schizophrenia. Looking for expanded trinucleotide repeats is thus the next step to detect the gene(s) that are potentially involved.