The age of onset of schizophrenia and the theory of anticipation.

The clinical phenomenon called anticipation is usually defined as a decrease in age at onset and/or an increase in disease severity in successive generations of afflicted families. The purpose of this study was to examine variables that might influence anticipation in schizophrenia. A total of 380 Austrian patients, born between 1935 and 1964, met criteria for schizophrenia with ICD-8 or ICD-9, SADS-L and DSM-III-R criteria. The inclusion criteria also required medical records of patients to contain information about the year of birth, season of birth, age at onset, accidents or meningoencephalitic diseases during childhood, first- and second-degree relatives afflicted with schizophrenia, sibship size, sib order, education of patient, age of parents, occupation of parents, loss of parents, and place of residence. A Cox multiple-regression analysis showed three factors as having a significant influence on the age of disease onset, including year of birth (which had the largest influence), family history (sporadic cases showed an onset 2 years later than familial cases) and residence (urban dwellers showed psychotic symptoms approximately 1 year sooner than rural ones). A Kaplan-Meier Survival Analysis showed that younger cohorts had onset approximately 10 years earlier in sporadic and familial cases. This cohort effect might be a major source of bias in studies of anticipation.