Mood Disorders

Understanding the Role of Gender in Stress-Induced Disorders

Amy Arnsten, Ph.D.

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.

Deciphering the Molecular Determinants of Post-Partum Mood Disorders

Ronald S. Duman, Ph.D.

Ronald S. Duman, Ph.D., Professor of Psychiatry and Pharmacology


Post-partum depression is experienced by 10 to 20% of women in the United States within six months of delivery. Research on pregnancy-related mood disorders indicates that changes in hormones during pregnancy play a role in the onset of these disorders. Dr. Duman investigated the underlying biological/hormonal mechanisms that contribute to postpartum mood disturbances. The findings have been useful in expanding research approaches to understanding postpartum depression.


Highlighted Study Findings

Recent studies have suggested that mood disorders, such as depression, may result in part from the effects of stress (such as pregnancy and delivery) on the growth and survival of brain cells (neurons). In particular, stress decreases the expression of brain derived neurotrophic factor (BDNF), a major factor sustaining cell life. This project investigated the impact of estrogen on the expression of BDNF. Results demonstrated that estrogen influences the expression of BDNF, suggesting a route by which fluctuations of hormones could contribute to neurobiological dysfunction. Moreover, interactions between fluctuating hormones and stress could further compromise the functioning of neurons. These findings have been used to begin to develop strategies for counteracting the effects of stress and hormone fluctuations on BDNF expression and neuronal functioning. Continued research and progress in this area will eventually lead to a more complete understanding of the cellular basis of the effects of hormones on mood, in pregnant and non-pregnant women.