Sex-biased experiences of social stress and the origin of sex-biased inflammatory diseases and mental disorders

Abstract

Women are more susceptible to a range of detrimental diseases surrounding autoimmunity and inflammation, but the causes of this are largely unknown. Much of the current research investigating these patterns focus on a microscopic view of cellular and/or hormonal processes, but holistic perspectives incorporating sociology, psychology, physiology, and evolution are rarely considered. Through investigating interactions between a history of neglecting women’s research, evolutionary origins of sex differences in the immune system, and the impacts of society’s influences on stress, some sex-biased patterns of disease may emerge. The existing SS-SH-SS theory by Brown et al. (2022) describes the complex environmental, psychological, and biological mechanisms that interact to create a female sensitivity to stress-based inflammatory diseases. Using the foundations of this theory, in this study we used global disease and stress exposure data from the World Bank and Global Health Data Exchange project to investigate how the relationships between exposure to stress and prevalence of diseases differ by sex. Using principal component analysis and generalized linear mixed models, we demonstrated a complex relationship between certain stress factors and inflammatory diseases. Particularly, we found that levels of poverty, alcohol use and drug use had distinct, sex-specific impacts on rates of diseases that we studied. Female rates of disease were particularly sensitive to the changes in substance use and poverty, with an inverse relationship with poverty and a direct relationship with substance use. This study can serve as an example for investigating the correlates of sex-biased diseases and mental disorders, particularly about the role of sex-biased experiences of social stress in the origin of sex-biased mental illnesses.