Characterizing the Hormone Sensitive Phenotype of Postpartum Depression: An Experimental Investigation of Mood and Behavior

Need/Problem: Despite decades of research, little is known about the biological causes of postpartum depression. Our past research showed that changes in pregnancy hormone levels cause depression in some women, but at present, there is no simple way to identify these women.

Grant Summary: This research provides a novel approach to testing risk for postpartum depression.

Goals and Projected Outcomes: The purpose of this project is to test two simple, non-invasive approaches to identifying women at high-risk for postpartum depression. The projected outcome of this project is the ability to distinguish those at high and low risk for postpartum depression using minimally invasive, easy-to-implement protocols, thus potentially enabling the identification of women at risk for postpartum depression prior to its development.

Crystal Edler Schiller, Ph.D.

Grant Details: Postpartum depression (PPD) is common and constitutes a significant burden for women, children, and society. However, despite decades of research, little is known about the biological causes of PPD. We recently demonstrated that depression is the direct result of changing hormone levels in a subgroup of women with a history of PPD. This study, which involved administering the reproductive hormones estradiol and progesterone in the context of an intensive, 5-month-long “hormone challenge” protocol, showed that 10 out of the 15 women with a past episode of PPD were hormone sensitive (i.e., reported at least a 30% increase in depressive symptoms during the hormone challenge). However, the only way to identify hormone sensitive women at present with our intensive, 5-month-long hormone challenge protocol

The purpose of the proposed project is to test two less cumbersome approaches to identifying hormone sensitive women. We propose to re-assess the 30 women (15 with a history of PPD and 15 “controls” without such a history) who completed our earlier study to determine whether hormone sensitivity can be detected following subtler variations in hormones during either the normal menstrual cycle or a much briefer (7-day) hormone challenge. The first goal of the project is to characterize the severity of depressive symptoms that hormone sensitive women experience during the normal menstrual cycle. We will measure symptoms during 3 consecutive menstrual cycles in women with a history of PPD and controls. We expect that hormone sensitive women will show at least a 30% increase in mood symptoms during the late luteal phase, similar to those with premenstrual dysphoric disorder. The second goal of the project is to quantify changes in mood and reward-related behaviors during a 7-day hormone challenge. Women with a history of PPD and controls will receive in random order seven days each of combination estradiol/progesterone and placebo in a double-blind crossover design, starting on their first day of menses. Mood and behavioral effects will be assessed in the lab on day 7 of hormone treatment and compared with data collected on day 7 of placebo treatment. We expect that hormone sensitive women will show at least a 30% increase in depressive symptoms and a 30% decrease in performance on behavioral tasks during the brief hormone challenge, compared with control women.

This research is important because it will 1) advance our understanding of the biological mechanisms underlying both the triggering of and susceptibility to PPD; and 2) potentially permit the identification of those at risk for PPD well before illness expression, which would allow for a personalized medicine approach to prevention and treatment, a goal with obvious implications for public health.