Brain Reward Changes in Premenstrual Depression
2025 Award: $50,000
Many women with depression experience a worsening of their depressive symptoms during the week before their menstrual period, adding to the burden of their illness. Although increased symptoms appear related to cycle-based changes in the hormones estradiol and progesterone, the underlying neural mechanisms are not known. In this study, we are looking at how the natural premenstrual decline in estradiol and progesterone affects brain reward function in women with premenstrual worsening of their depressive symptoms.
Need/Problem: Many women with depression experience a worsening of their depressive symptoms during the week before their menstrual period, adding to burden of their illness. However, no evidence-based treatments for premenstrual exacerbations of depression exist.
Grant Summary: Using a safe and validated hormone stabilization protocol that prevents the natural decline in the ovarian hormones estradiol and progesterone during the premenstrual phase of the menstrual cycle, this study will identify how ovarian hormones affect brain reward function in women with premenstrual exacerbations of major depression.
Goals & Projected Outcomes: The primary objective of the study is to identify how premenstrual ovarian hormone withdrawal affects brain reward function in women with premenstrual exacerbations of depression. This will be achieved by comparing neural and behavioral markers of reward processing during premenstrual hormone stabilization versus natural withdrawal. We will also compare reward processing between the premenstrual phase and the follicular phase, when symptoms are lower. Data from this study will support a future NIH career development award incorporating other factors affecting premenstrual reward function, such as stress.
Christopher Sikes-Keilp, MD
Grant Details: Approximately 60% of reproductive-aged women with major depressive disorder experience worsening of their depression during the week before their menstrual period, adding to the disease burden of a disabling and highly prevalent illness. Recent findings suggest that the premenstrual decline in ovarian hormones may alter brain reward networks, contributing to symptomatology and clinical outcomes in women with premenstrual worsening of depression. However, this potential mechanism has yet to be studied in an experimental context. The primary objective of this study is therefore to use an experimental approach to determine the role of estradiol and progesterone in the neural and behavioral features of reward function in the premenstrual exacerbations of depression. Findings from this study will build our understanding of the complex relationship between menstrual cycle-based ovarian hormone fluctuation, reward processing, and depressive symptoms, and represents the first step in identifying therapeutic targets for an understudied clinical phenomenon.
