Perimenopausal Depression Project: 

"Effects of Estradiol on the Neural Reward System and Depression in the Perimenopause"

This study is currently recruiting participants.  This research study is seeking women with current depression and those who have never experienced depression to participate in the study. The study involves wearing a low-dose estrogen patch for 3 weeks, having 2 fMRI brain scans, and coming to UNC for a total of 6 appointments.  For this research study, participants will receive a total of $500, and participants are responsible for their own transportation costs.

To see if you would be a good fit, please visit or call (919) 966-5243.


PI: Crystal Schiller, PhD

Despite decades of research, affective disorders are prevalent and associated with significant morbidity and mortality. Unraveling the pathophysiology of affective disorders has been uniquely challenging because depressive syndromes are heterogeneous and have diverse etiologies. We propose to address this problem by studying perimenopausal major depressive disorder (MDD), a more homogeneous depression subtype with an established trigger (i.e., estradiol withdrawal). Focusing on perimenopausal MDD will therefore increase the likelihood of identifying meaningful neurobiological markers. One of the most powerful tools for understanding the neurobiological mediators of MDD is brain imaging. Prior research suggests that the frontostriatal reward system is regulated by estradiol and implicated in MDD. However, the neural pathophysiology of perimenopausal MDD has never been studied. We will use functional magnetic resonance imaging (fMRI) at baseline and following estradiol treatment to 1) measure the frontostriatal response to reward in perimenopausal MDD and test the effects of estradiol on neural activation in perimenopausal women; 2) quantify behavioral responses to reward at baseline and following estradiol administration in perimenopausal women with and without MDD; and 3) measure the psychological correlates of the frontostriatal response to reward in women with perimenopausal MDD at baseline and following estradiol administration. This study design will allow us to explore the neural pathophysiology of perimenopausal MDD, the effects of estradiol on the neural reward system, and the degree to which neural reward system dysfunction predicts the antidepressant effects of estradiol. My long-term research objectives are to 1) advance our understanding of the effects of ovarian hormones on the brain and how these effects contribute to the triggering of and susceptibility to reproductive-related mood disorders; and 2) to identify neural and endocrine markers of depression risk, thereby improving our ability to prevent affective illness in women. Future directions for this work will include identifying neural biomarkers that predict reproductive mood disorder susceptibility and response to hormonal interventions, and exploring neuroendocrine etiological pathways that may help to explain the preponderance of depression in women.