Associations between risk factors for schizophrenia and concordance in four monozygotic twin samples

Concordance for schizophrenia is high in monozygotic twins but the extent to which concordance varies according to the presence of other schizophrenia risk factors is not well established. We aimed to investigate this in systematically ascertained twin samples. DSM-III-R/DSM-IV diagnoses were made from original data or published case histories from four systematically ascertained monozygotic twin samples. Probandwise concordance for schizophrenia was calculated according to the presence of psychotic disorder in first-degree relatives, birth order, gender, and age-at-onset. Logistic regression analysis was also performed to adjust for potential confounders. Psychotic disorder in parents and earlier age-at-onset were significantly associated with higher probandwise concordance for schizophrenia, including after adjustment for potential confounders. For example, when no parents had a psychotic disorder concordance was 34/88 (38.6%) versus 10/16 (62.5%) when one parent was affected; and for age-at-onset <23 years concordance was 25/46 (54.3%), declining to 13/44 (29.5%) for age-at-onset >30 years. These results are consistent with psychotic disorder in parents and age-at-onset being markers of the level of familial liability to schizophrenia and these factors may be useful in genetic counseling of monozygotic twins and in identifying and managing those at particularly high risk, if these findings are further replicated.