Hyperandrogenism during prenatal and pubertal development alters functional brain networks compromising social cognition in daughters of women with Polycystic Ovary Syndrome: a double hit hypothesis

Polycystic ovary syndrome (PCOS) is a highly prevalent disorder in women of reproductive age, characterized by hyperandrogenism, chronic anovulation and polycystic ovarian morphology associated with insulin resistance and obesity. Daughters of women with PCOS (PCOSd) show many features of the syndrome that appear through development and are exposed to hyperandrogenism in 2 important windows, prenatally and during puberty. One important target for androgens is the central nervous system. In this regard, the prefrontal cortex (PFC) and limbic system are the most affected areas and constitute a processing network that is the basis for a very important brain function named social cognition, where memory (hippocampus), emotion (amygdala), attention (PCF) and cortical reasoning operate together to process information about us and others, allowing the perception and inference of other people ́s emotions and thoughts. A disturbance of this function, through exposure of the PFC and limbic system to androgens during critical windows such as prenatal life and puberty, may lead to uncoupling of the PFC-limbic systems compromising social cognition in PCOSd, decreasing their quality of life and social functioning, and increasing their risk for future development of psychiatric disorders. The present proposal will explore this novel issue using an animal and a human model.

Principal Investigator: Dr. Nicolás Crisosto, Universidad de Chile