Rodent models of mental illness in PCOS: The potential role of HPA dysregulation and lessons for behavioral researchers.

Polycystic ovary syndrome (PCOS) is the most commonly diagnosed endocrine disorder in women of reproductive age, with phenotypes including ovarian and metabolic dysfunctions. Women with PCOS also show increased rates of mental illness, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and altered responsiveness to stressors that may contribute to the higher rates of mental illness, specifically depression and anxiety. Animal models of PCOS have provided insight into the ovarian and metabolic mechanisms that underlie the syndrome, and several models have been used to study the behavioral consequences associated with PCOS in the laboratory. Several studies in rodent models of PCOS demonstrate changes in anxiety-like behavior, but researchers often neglect to report procedural details or behavioral data crucial to interpreting the differences observed in those studies. Additionally, the impact of potential HPA dysregulation in animal models of PCOS may influence behavioral findings, although only three studies to date have examined this. As such, researchers should consider and report stress-associated variables (e.g., time of day, light/dark cycle, light intensity, housing, and procedures to control experimenter and litter effects) that may influence depression- and anxiety-like behaviors in rodents. This review will summarize the behavioral and HPA-related studies in women with PCOS and rodent models of the disease, and provide considerations for future studies. Women with PCOS have increased depression and anxiety, as well as HPA dysregulation, which should be taken into consideration when performing behavior studies in rodent models of PCOS.