Origin of Sex-Biased Mental Disorders: Do Males and Females Experience Different Selective Regimes?

Abstract

The origins of sex-biased differences in disease and health are of growing interest to both medical researchers and health professionals. Several major factors have been identified that affect sex differences in incidence of diseases and mental disorders. These are: sex chromosomes, sex hormones and female immunity, sexual selection and antagonistic evolution, and differential susceptibility of sexes to environmental factors. These factors work on different time scales and are not exclusive of each other. Recently, a combined Sexual Selection-Sex Hormones (SS-SH) Theory was presented as an evolutionary mechanism to explain sex-biased differences in diseases and mental disorders (Singh in J Mol Evol 89:195–213, 2021). In that paper disease prevalence trends were investigated, and non-sex-specific diseases were hypothesized to be more common in males than in females in general. They showed signs of exceptions to this trend with inflammatory diseases and stress-related mental disorders that were more common in females. We believe that the SS-SH theory requires the consideration of psycho-social stress (PSS) to explain the predominance of female-biased mental disorders and some other exceptions in their findings. Here we present a theory of sex-differential experience of PSS and provide quantitative support for the combined SS-SH-PSS Theory using age-standardized incidence rates (ASIRs) recording the levels of male- and female-bias in data obtained from different countries. The grand theory provides an evolutionary framework for explaining patterns of sex-biased trends in the prevalence of disease and health. Further exploration of women’s vulnerability to social factors may help to facilitate new treatments for female-biased diseases.

The maternal microbiome modifies adverse effects of protein undernutrition on offspring neurobehavioral impairment in mice

“…These findings highlight the importance of examining both males and females, and including sex as a biological variable 87 . Sex biases have been well-documented in various neurodevelopmental conditions, including a male skew in autism spectrum disorder and attention deficit hyperactivity disorder 88 and a female skew in anxiety and mood disorders 89 . Furthermore, findings from this study support the ability of sex to influence susceptibility to, or presentation of, prenatal programming from environmental stressors or maternal microbial shifts 59 .…”