Genetic epidemiology and schizophrenia: a study of reproductive fitness

Genetic epidemiological studies have demonstrated markedly reduced rates in reproduction among schizophrenic patients. According to evolutionary theory, behavioral and psychological phenotypes are selected based on ecological "fit". Where differential survival or reproductive success exists, genotype frequencies are altered in subsequent generations. In the case of schizophrenia, lower rates of reproduction constitute a negative selection factor that should reduce genes in the population associated with the expression of the disease--ultimately leading to decreases in prevalence. However, studies reveal a stable prevalence of about 1% over time. Attempts to explain the apparent contradiction between negative selection and stable prevalence have taken several forms. One explanation suggests that reproductive rates in relatives of schizophrenic patients are increased--compensating for reproductive loss in affected family members. Family data from schizophrenic patients at the Maryland Psychiatric Research Center were compared with those of healthy volunteers and volunteers with schizophrenia spectrum personality (SSP) disorders. Controlling for important socio-cultural and demographic variables, a multiple regression model revealed a significant increase in the number of siblings associated with schizophrenia. No differences in reproductive fitness were found among normal and SSP volunteers. This observed pattern in reproductive fitness provides one mechanism by which prevalence rates can remain stable despite lower reproductive rates among individuals with schizophrenia. Evidence of increased reproductive fitness in relatives suggests the need to consider the complex interactions of proximate and ultimate (evolutionary) mechanisms in the expression of schizophrenia.