Chromosomal and environmental contributions to sex differences in the vulnerability to neurological and neuropsychiatric disorders: Implications for therapeutic interventions

Post Written By: Benedetta Romeo

Many neurological and neuropsychiatric disorders have been shown to affect men and women differently. The causes of these differences are unknown, and one significant contributing factor is the historical underrepresentation of women/female animals in clinical trials/basic research.

In this review, “Chromosomal and environmental contributions to sex differences in the vulnerability to neurological and neuropsychiatric disorders: Implications for therapeutic interventions,” we talk about how the sex chromosomes. X chromosome inactivation (XCI), and environmental factors (such as stress, diet, …) can have an impact in the sex differences in various diseases.

Key points summarized in the article are:

  1. In females, one of the two X chromosomes is randomly silenced through XCI. This and the accumulation of brain-specific genes on the X chromosome contribute to sex differences in disease susceptibility.
  2. Studies in mice show that sex chromosomes influence sex-specific traits independently of hormonal effects, including brain structure, behavior, and the development of neurological disorders.
  3. Incomplete XCI can lead to female-biased diseases, as some genes escape inactivation and are overexpressed. Autoimmune disorders are more common in females probably due to X-linked immune-related genes and incomplete XCI in immune cells.
  4. Sex differences in vulnerability to neuropsychiatric diseases may be explained by differences in genetic makeup, hormonal factors, and how males and females respond to environmental exposures.

Check our publication here: Chromosomal and environmental contributions to sex differences in the vulnerability to neurological and neuropsychiatric disorders: Implications for therapeutic interventions – ScienceDirect

Thanks to all the amazing people who contributed to the realization of this scientific review!

Patrick N. Pallier,  Maria Ferrara,  Francesca Romagnolo, Maria Teresa Ferretti, Hermona Soreq, Andrea Cerase