While many women with postpartum depression (PPD) have had previous episodes of major depression and will go on to have other episodes of depression outside of the postpartum period, many have questioned whether postpartum depression represents a specific subtype of major depressive disorder (MDD), postulating that there may be characteristics which distinguish depression emerging during the postpartum period from depression occurring at other times in a woman’s lifetime.  The most distinctive and defining feature of PPD is the timing of its onset.  The temporal link between PPD and the postpartum period has led to the hypothesis that the hormonal changes which take place after delivery — the dramatic fall in levels of estrogen and progesterone — trigger depressive symptoms in vulnerable women.  However, studies examining hormone levels during the postpartum period have not yielded data supporting this hypothesis.  

To explore this question from a slightly different angle, O’Brien and colleagues examined whether women with a history of PPD have specific differences in brain activation which may be triggered by changes in levels of reproductive hormones.  Specifically they looked at brain activation during the late luteal phase of the menstrual cycle, which resembles the postpartum period in that levels of estrogen and progesterone are declining.  They compared patterns of brain activation in women with histories of PPD to women with histories of non-postpartum MDD and to women with no history of MDD.

The study included 30 women: 10 with a history of PPD, 10 with no a history of non-postpartum MDD, and 10 with no history of depression.  Participants underwent blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) during an emotional faces task.  In this paradigm, participants were presented with positive (happy), negative (angry) and neutral facial expressions, and activation of various regions of the brain was assessed.  

Compared to women with previous (non-postpartum) MDD, women who had experienced postpartum depression had a distinct neural response to positive facial emotion during the late luteal phase of the menstrual cycle, demonstrating a significant reduction in activation of the right amygdala when viewing happy faces and a similar, yet non-significant, reduction in the left amygdala.  There was a trend toward decreased activation in the amygdala when women with PPD were compared to never-depressed individuals.  

The finding of reduced amygdala activity in response to happy faces is consistent with a core information processing bias, where the individual attends less to positive stimuli.  This processing bias has also been reported in individuals at risk of depression and in women with PMDD.  (Women with PMDD also have increased activation of the amygdala in response to angry facial expressions.)

While these findings are preliminary and based on a small sample of women, they are thought-provoking and parallel the research of Miki Bloch in collaboration with Peter Schmidt and David Rubinow. In that study women with and without histories of PPD were treated with supraphysiologic levels of estradiol and progesterone for 8 weeks to mimic a normal pregnancy.  After withdrawing the supplemental hormones (to mimic what happens during the postpartum period), women with histories of PPD experienced depressive symptoms similar to their previous episode of PPD.  In contrast, women with no history of PPD did not experience depressive symptoms in this setting.  Thus, Bloch’s study, like the fMRI study, indicates that the brains of women with histories of PPD respond differently to postpartum hormonal changes than women with histories of MDD.  

The findings of the O’Brien study support the hypothesis that women with vulnerability to postpartum depression represent a distinct subgroup of women with a differential sensitivity to changes in reproductive hormones.  The authors of the article speculate that this may be a potentially useful biomarker for identifying women at risk for postpartum depression.  In addition, understanding the etiology of PPD in the context of a cognitive model of depression may help us to design specific interventions which target these deficits in cognitive processing.  


Ruta Nonacs, MD PhD


Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR.  Effects of gonadal steroids in women with a history of postpartum depression.  Am J Psychiatry. 2000 Jun;157(6):924-30. 

O’ Brien S, Sethi A, Gudbrandsen M, Lennuyeux-Comnene L, Murphy DGM, Craig MC.   Is postnatal depression a distinct subtype of major depressive disorder? An exploratory study.  Arch Womens Ment Health. 2020 Jul 15. 

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