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 theor y, behavioral and psychological phenotypes are selected based on ecological 'fit'. Where differential survival or reproductive success exists, genotyp e frequencies are altered in subsequent generations. In the case of schizop hrenia, lower rates of reproduction constitute a negative selection factor that should reduce genes in the population associated with the expression o f the disease - ultimately leading to decreases in prevalence. However, stu dies 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 re productive loss in affected family members. Family data from schizophrenic patients at the Maryland Psychiatric Research Center were compared with tho se of healthy volunteers and volunteers with schizophrenia spectrum persona lity (SSP) disorders. Controlling for important socio-cultural and demograp hic 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 obser ved pattern in reproductive fitness provides one mechanism by which prevale nce rates can remain stable despite lower reproductive rates among individu als with schizophrenia. Evidence of increased reproductive fitness in relat ives suggests the need to consider the complex interactions of proximate an d ultimate (evolutionary) mechanisms in the expression of schizophrenia. (C ) 2001 Elsevier Science B.V. All rights reserved.