ANTICIPATION IN SCHIZOPHRENIA - NEW LIGHT ON A CONTROVERSIAL PROBLEM

Objective: Anticipation, recently found in several neuropsychiatric di sorders, is an inheritance pattern within a pedigree in which disease severity increases or age at onset decreases in successive generations . Demonstration of genetic anticipation in schizophrenia could be of h euristic value, since unstable trinucleotide repeat DNA is known to be the biological basis of anticipation. However, to overcome one of the major ascertainment biases that might mimic anticipation-namely, the fact that patients in different generations are not interviewed at the same age, resulting in a greater chance of finding a later age at ons et in the older generation-a new method of investigating anticipation was used. Method: The study subjects were 97 systematically ascertaine d schizophrenic patients belonging to 24 families with at least two ge nerations affected who were identified during a 1-year prevalence stud y in a limited geographical area of Reunion Island (Indian Ocean). A m ethod of calculating expected age at onset according to age at intervi ew was used in the analyses. Results: In the younger generation of pat ients, the observed age at onset (21.80 years) was earlier than the ex pected age at onset (24.95 years), demonstrating anticipation, even wh en five additional biases that can mimic this genetic effect-the proba nd effect, the presence of an affected father or mother, the bilineali ty of the illness, the fertility effect, and the cohort effect-were ta ken into account. Conclusions: Evidence for anticipation was demonstra ted in this group of schizophrenic patients. This may help the search for pathological genes implicated in the genesis of schizophrenia.