Date of Degree
PhD (Doctor of Philosophy)
Michael W. O'Hara
Alan Kim Johnson
The hormone withdrawal hypothesis of postpartum depression (PPD) attributes the onset of depressive symptoms to the rapid postpartum withdrawal of the ovarian hormones estradiol and progesterone that occurs during the first five days following childbirth. Although a number of human and non-human animal studies have supported the hormone withdrawal hypothesis, several studies have failed to support this hypothesis. The current research was designed to test the hormone withdrawal hypothesis of PPD using a novel translational research design that includes a series of experimental animal studies and a longitudinal human study. It was hypothesized that estradiol and progesterone withdrawal would cause increased behavioral despair, anhedonia, and anxiety in the rodent studies. In the human study, it was hypothesized that 1) decreases in estradiol would be associated with increases in negative affect and decreases in positive affect; 2) decreases in progesterone would be associated with increases in anxiety; and 3) these associations would be stronger in women with a past episode of PPD compared to those without a history of PPD. In the animal studies, rats were ovariectomized and administered ovarian hormones or placebo (i.e., hormone administration), followed by placebo only (i.e., withdrawal). Animals in these experiments were given the forced-swim test to measure behavioral despair; lateral hypothalamic self- stimulation to measure anhedonia; or the elevated plus maze to measure anxiety. In the human study, women made mood ratings and collected saliva samples daily starting in the third trimester and continuing until 10 days postpartum. In the animal studies, withdrawal from estradiol alone was associated with behavioral despair (t=2.26, p=.02) and anhedonia (t=-3.2, p=.007). In the human study, there a significant prospective association between estradiol and negative affect in women who developed PPD (r=-0.34, p<.001). This association, when combined with group status (i.e., history of PPD versus no history of depression), was used to correctly identify 100% of women who developed PPD. The results of this project contribute to evidence of a neurobiological basis for PPD. Estradiol withdrawal represents a promising candidate for further study, particularly with regard to individual differences in sensitivity to hormone withdrawal.
Copyright 2011 Crystal Edler Schiller
Schiller, Crystal Elizabeth Edler. "The hormone withdrawal hypothesis of postpartum depression: a translational approach." dissertation, University of Iowa, 2011.