Understanding the Role of Gender in Stress-Induced Disorders

Amy Arnsten, Ph.D.,Professor of Neurobiology

Depression and post-traumatic stress disorder (or PTSD) are twice as prevalent in women as in men. Dr. Arnsten’s research focuses on how the biology of the brain affects gender differences in the symptoms of these and related disorders, and the role of stress in this process. The gender differences in the symptoms of depression and PTSD appear to be specifically related to the levels of estrogen circulating within the body, and may relate to an evolutionary connection between the role of estrogen and sensitivity to environmental threats. This study investigated these apparent relationships.

Highlighted Study Findings

Exposure to uncontrollable stress is a major risk factor for depression, and exposure to a traumatic, life-threatening stressor can induce symptoms of PTSD. In this Ethel F. Donaghue Women’s Health Investigator Program-funded investigation, Dr. Arnsten’s demonstrated in animal models that even mild, uncontrollable stress can markedly impair the functioning of the prefrontal cortex which controls executive functioning (allowing complex decisions, planning ahead, organizing and multi-tasking) and mediates emotional regulation. She found that this effect was more pronounced in females than in males. Furthermore, these gender differences appeared related to the levels of estrogen in the body. She hypothesizes that this greater sensitivity to stress, particularly under conditions of high estrogen, may have evolved to protect females, particularly pregnant females, making them more cautious and thus enhancing their rate of survival. However, in contemporary human society where these exact same evolutionary-based protective mechanisms are not required, these chemical actions may render women more vulnerable to the symptoms of stress- induced conditions such as depression and PTSD. Understanding the neurobiological basis of these symptoms has aided in the development of a pharmacological intervention by Dr. Arnsten which is currently in clinical trials.