Reproductive fitness in familial schizophrenia

Abstract

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.

Schizophrenia and genetics: New insights

“…A mechanism that included a high rate of spontaneous mutations predisposing to schizophrenia would be consistent with the low rate of family history of schizophrenia usually found in individuals with the illness, and apparently "sporadic" schizophrenia [26]. The authors have previously pointed out how a high rate of spontaneous mutations could help explain the maintenance of the illness prevalence despite low reproductive fitness [54]. The possibility of spontaneous mutations reemphasizes the idea, also noted previously, that "genetic" does not equate with "inherited.…”

Schizotypy, creativity and mating success in humans

“…It is substantially heritable (Gottesman 1991;Cardno et al 1999), though what is inherited is best described as a diathesis or vulnerability that may or may not lead to actual illness, and whose progression is affected by environmental factors . Many studies have shown that schizophrenia is associated with impaired physical health (Brown et al 2000), and drastically reduced probability of reproduction (Bassett et al 1996;Avila et al 2001). This naturally raises an evolutionary puzzle.…”

Reproductive Fitness and Genetic Transmission of Tetralogy of Fallot in the Molecular Age

“…20 The relative reproductive fitness associated with TOF was assessed using 2 standard proxies: the mean number of liveborn offspring per proband and the proportion of probands who were childless. 13,21 The comparison group consisted of Canadian adults with neither CHD nor 22q11.2 deletions, used in a previous study of reproductive fitness and representative of men and women in the general population. 13 The TOF group and the comparison group were well matched with respect to age and birth cohort.…”