Evolutionary perspective on sex differences in the expression of neurological diseases

Sex-specific brain and cognitive deficits emerge with malnutrition, some infectious and neurodegenerative diseases, and often with prenatal or postnatal toxin exposure. These deficits are described in disparate literatures and are generally not linked to one another. Sexual selection may provide a unifying framework that integrates our understanding of these deficits and provides direction for future studies of sex-specific vulnerabilities. Sexually selected traits are those that have evolved to facilitate competition for reproductive resources or that influence mate choices, and are often larger and more complex than other traits. Critically, malnutrition, disease, chronic social stress, and exposure to man-made toxins compromise the development and expression of sexually selected traits more strongly than that of other traits. The fundamental mechanism underlying vulnerability might be the efficiency of mitochondrial energy capture and control of oxidative stress that in turn links these traits to current advances in neuroenergetics, stress endocrinology, and toxicology. The key idea is that the elaboration of these cognitive abilities, with more underlying gray matter or more extensive inter-modular white matter connections, makes them particularly sensitive to disruptions in mitochondrial functioning and oxidative stress. A framework of human sexually selected cognitive abilities and underlying brain systems is proposed and used to organize what is currently known about sex-specific vulnerabilities.