Reproductive fitness in familial schizophrenia

Background: Reproductive fitness is an important factor in understanding inheritance in genetic disorders. The purpose of this study was to determine whether fitness is reduced in familial schizophrenia (FS) and if fitness in siblings differs from the norm. Method: The number of offspring in 36 subjects with RDC schizophrenia or schizoaffective disorder (SZ) and their 101 siblings from large FS families was compared with age-adjusted census figures. Results: Fitness in the SZ group was significantly reduced: 23% of expected in males and 51% of expected in females. Fitness of unaffected siblings was within census expectations. However, female siblings with schizophrenia spectrum features had increased fitness over census norms. Reduced fitness was correlated with low marital rates, poor functioning and positive symptoms. Conclusions: These results indicate that reduced fitness is an important genetic force in FS and is likely inherent to the illness. Sex differences are important and would need to be considered when examining maternal and paternal transmission of schizophrenia. The results support a proposed high mutation rate for schizophrenia, consistent with a dynamic mutation mechanism.