Improving the Understanding of Hormones from Womb to Tomb

New chair of  psychiatry studies the connection of hormones to human behavior

Interviewed By Mark Couch 

Neill-Epperson-350(October 2018) C. Neill Epperson, MD, an expert in women’s behavioral health, particularly the relationship of hormones and the brain, joined the University of Colorado School of Medicine on the Anschutz Medical Campus, as chair of the Department of Psychiatry, effective September 1.  

Previously, she had been a professor of psychiatry and obstetrics and gynecology at the Perelman School of Medicine at the University of Pennsylvania. She was recruited to Penn from Yale School of Medicine in 2009 to launch and serve as director of the Division of Women’s Behavioral Health. In that capacity, she founded and served as director of two clinical, research, and education programs: the Penn Center for Women’s Behavioral Wellness and Penn PROMOTES Research on Sex and Gender in Health.  

Epperson earned her MD from the University of North Carolina and completed her residency and fellowships at Yale University. Her research has been continuously funded for more than 20 years with grants from the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse, the National Institute on Aging, the National Cancer Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health Office of Research on Women’s Health and private foundations and companies.  

As chair, she succeeds Robert Freedman, MD, professor of psychiatry, who joined the CU faculty in 1978 and served as chair from 2000 until August 2016. “I’ve known Dr. Freedman for many years,” Epperson said. “First by reputation as the esteemed editor of the American Journal of Psychiatry, and finally on a more personal level when I was asked to contribute an editorial for the journal on the topic of the premenstrual dysphoric disorder.  

“Dr. Freedman’s exceptional intellectual breadth and vision with respect to the field of psychiatry are just two of his many talents that made him an outstanding journal editor, in addition to being the highly effective and beloved chair of psychiatry here at the CU School of Medicine. I consider it an exceptional honor to be his successor as the Robert Freedman Endowed Professor and chair of psychiatry.” 

Describe the division you were recruited to Penn to start up.   

Debbie Driscoll, MD, who has been the chair of the Department of OB/GYN at the Perelman School of Medicine at the University of Pennsylvania since my recruitment there, has a very broad vision of women’s health that was and continues to be inclusive of behavioral health. A strong and fluid collaboration between the Departments of Psychiatry and OB/GYN were critical to the success of the  Division of Women’s Behavioral Health as we focused primarily on behavioral health issues that arise in the context of dynamic hormonal shifts such as menarche, menstruation, pregnancy, childbirth, and the menopause.   

While our research would literally focus on topics from “womb to tomb” by spanning the entire female lifespan, our clinical endeavors focused primarily on females from late adolescence through old age. For example, we would evaluate and treat adolescent girls suffering from hormone contraceptive-induced depression, perinatal women with depression and anxiety or exacerbation of their post-traumatic stress disorder and older women with menopause-related depression and cognitive declines. For our oldest patients, the challenge was determining whether the woman’s cognitive complaints were due to a major depressive episode, dementia, or other comorbid medical condition. Many of our female patients were also survivors of childhood adversity and maltreatment. As a result, we also shifted to considering a more trauma-focused approach to our clinical care and research endeavors.  

One of the problems that happens in society today is that most psychiatrists are not really trained to appreciate the endocrine system and how hormones impact behavior. Our patients were just relieved that they were coming to clinicians who understood the symptoms they were experiencing and how hormones or their reproductive status could be contributing to their current behavioral health difficulties.  

It seems like that would be an active area of care need.   

It is and there are still relatively few clinicians who have any formal training in reproductive psychiatry. There are a growing number of psychiatry and psychology departments across the country that are developing curricula in these areas. However, reproductive psychiatry is not considered a true sub-specialty like addiction, forensic, or consult-liaison psychiatry, so there is no mandate that clinical training programs include these topics in psychoneuroendocrinology and reproductive health. What we did at Penn is create specialty clinics for the psychiatry residents, psychology doctoral candidates, and psychiatric and women’s health nurse practitioner students so they could participate in didactics as well as gain hands-on experience with patients suffering from reproduction/hormonal-related psychiatric conditions. The important feature of these training programs is that we helped the students and fellows differentiate when a reproductive or hormonal event was causing or exacerbating the woman’s psychiatric presentation. Just because someone questions a “hormonal contribution” does not mean that one actually exists. This knowledge is critical to developing an appropriate treatment plan for the patient. We also had medical students rotating with us as well. The clinical division obviously was the foundation for the educational division when it came to the training piece.  

The area you’re studying covers the whole lifespan. We’re talking about premenstrual young women to postmenopausal women. 

Our center at Penn included one geriatric psychiatrist who would often evaluate and treat women who were many decades into the postmenopause. Again, considering our work with pregnant women, our interdisciplinary program was really a “womb to tomb” enterprise. In my opinion, this lifespan approach is critical to all psychiatric care, not just specialized care for women.   

How will your work fit in at CU?  

My work has always been inter- and trans-disciplinary. It has a lot of application to internal medicine, pediatrics, OB/GYN, endocrinology, as well as radiology, neurology, oncology and immunology. Given that the University of Colorado already has strong interest in women’s health and great strengths in each of these clinical and research areas, I will have a lot of natural collaborators.  

The same is true with respect to my neuroimaging research.  Several young investigators here are interested in the role of estrogen with respect to the aging brain, while others are interested in the use of gender-affirming hormone therapy on adolescent and young adult brain development.    

Some of the disorders I’ve studied, such as premenstrual dysphoric disorder, occur only in women.  Obviously only women menstruate, get pregnant, and experience menopause, but depression, anxiety, PTSD, and other psychiatric disorders occur in both men and women. Moreover, aging effects cognition in both males and females. Hence, my research focusing on hormones and health has expanded over the years to include the investigation of sex as a biological variable with respect to risk for a number of medical and behavioral conditions.    

How did you become interested in the role of hormones in behavioral health?  

I became interested in hormones about halfway through my residency training in psychiatry at Yale. In medical school, I had been taught about the endocrine system, but never that stress, gonadal, and thyroid hormones can have such profound effects on the brain, and thus, behavior. When it came to estradiol and progesterone, we were taught they’re important for menstrual cycles, getting pregnant, and basically, that was about it. Oxytocin, which we now know is critical for the initiation of maternal behavior in mammals, was just a hormone that was responsible for uterine contractions during labor and milk let-down during lactation.   

How challenging is it to study the effects of hormones on the brain in humans?  

Luckily we have neuroimaging techniques that allow us to study the human brain under different hormonal conditions. We can observe how different regions of the brain function during various cognitive and behavioral tasks. We can also observe how well different regions of the brain communicate with one another when someone has high or low levels of estradiol for example.  However, brain imaging is currently limited in its ability to determine the basic molecular mechanisms by which hormones alter behavior in humans. We can study this in other mammals and many of these findings have been generalized to humans, for better or worse. Although we need preclinical research to determine mechanisms at the cellular level, we can indeed examine behavior in humans under different hormonal conditions.  We can assess the impact of hormones on mood, sleep, cognition, sexual behavior, stress responsiveness, and immune function just to name a few.    

The other benefit of studying hormones on behavior in humans is that most individuals do not feel stigmatized by hormonal shifts. People like to talk about hormones, while they may feel uncomfortable talking about depression, anxiety, or changes in their libido and cognition. I have always believed that helping the layperson understand the importance of hormones in behavior could perhaps, in some small way, diminish the stigma related to behavioral health conditions. I hope I am right as I have dedicated my career to this mission. 

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