The role of genetic variation in the causation of mental illness: an evolution-informed framework

This paper is a review of some of the leading hypothesis for why mental disorders are present in high numbers in populations and have not been selected against. Uher focuses specifically on fitness reducing illnesses, such as schizophrenia, autism, anorexia nervosa and biopolar disorder, among others. The persistence of these diseases is a paradox in that fitness reducing genetic variants should be under strong negative selection, however studies have shown that these diseases are highly heritable. Uher concludes that a model of polygenic mutation-selection balance best explains this paradox. Because human mental health and brain function is controlled by a large number of genes and processes, and most mutations that contribute to mental illness are newly arising, environmental factors and the cumulative effects of mildly pleiotropic genes could be responsible. It should be noted that Uher does not entertain any epigenetic contributions to mental disease in this review.