Positive selection in human evolution plays a role in genes associated with schizophrenia, according to a new study in the Sept. 2007 edition of Proceedings of the Royal Society B. It found that genes believed to be linked to schizophrenia are more likely to show evidence of natural selection than those not associated with the disorder.

“Schizophrenia has a huge impact on health and reproduction, yet it persists at a high frequency in the human population. This is something of a paradox from an evolutionary perspective,” said East Carolina University biologist Kyle Summers, who conducted the research with colleagues Bernard Crespi from Simon Fraser University (Canada) and Steven Dorus from the University of Bath (United Kingdom).

For years scientists have believed that positive selection may play a role in the persistence of schizophrenia at a frequency of one per cent in human populations around the world, despite its strong negative effects on reproductive fitness and its high heritability from generation-to-generation.

The findings provide the first genetic evidence consistent with the theory that schizophrenia represents, in part, a maladaptive by-product of adaptive changes during human evolution – possibly to do with aspects of creativity and human cognition.

“The exact nature of the selective forces affecting the evolution of these genes is not yet known. Given the complex genetic nature of schizophrenia, selection may be acting on a diverse array of morphological, physiological and psychological mechanisms during neural development,” Summer said.

The researchers hope that their work will contribute to identifying the causal factors underlying schizophrenia. The work may also help to clarify links between schizophrenia and aspects of human creativity and cognition.

“Schizophrenia has been associated with creativity throughout recorded history, but whether, and to what degree, this link has a genetic basis is not clear and is under active investigation,” Summers said.

The researchers analyzed the molecular evolution of the 76 genes that have the strongest genetic association with schizophrenia.

“This study is one of the first to take a molecular evolutionary approach to enhance our understanding of the factors underlying schizophrenia,” Summers said.

The research was funded in part by East Carolina University, the Natural Sciences and Engineering Research Council of Canada, and the National Institutes of Health in Britain.

- East Carolina University