Anticipation in schizophrenia: new light on a controversial problem [published erratum appears in Am J Psychiatry 1997 Apr;154(4):590]

OBJECTIVE: Anticipation, recently found in several neuropsychiatric disorders, 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 heuristic 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 onset in the older generation--a new method of investigating anticipation was used. METHOD: The study subjects were 97 systematically ascertained schizophrenic patients belonging to 24 families with at least two generations affected who were identified during a 1-year prevalence study in a limited geographical area of Reunion Island (Indian Ocean). A method of calculating expected age at onset according to age at interview was used in the analyses. RESULTS: In the younger generation of patients, the observed age at onset (21.80 years) was earlier than the expected age at onset (24.95 years), demonstrating anticipation, even when five additional biases that can mimic this genetic effect-- the proband effect, the presence of an affected father or mother, the bilineality of the illness, the fertility effect, and the cohort effect- -were taken into account. CONCLUSIONS: Evidence for anticipation was demonstrated in this group of schizophrenic patients. This may help the search for pathological genes implicated in the genesis of schizophrenia.