SAT-145 - Lower Progesterone and Higher Allopregnanolone to Progesterone Ratio in Women with A History of Recurrent Depression WHO Develop Postpartum Depression

The progesterone metabolite allopregnanolone (ALLO) has been implicated in the development of postpartum depression (PPD), though reported associations between ALLO and PPD vary across studies. Blunted ALLO has also been implicated in the pathogenesis of major depression (MDD), but studies in the perinatal period have not consistently accounted for pre-pregnancy history of MDD and timing of depression onset (antenatal-onset versus postpartum-onset), which may contribute to varied findings. This preliminary study investigated how levels of ALLO and other neuroactive steroids differed across pregnancy and postpartum in women who were not depressed during pregnancy and either did or did not go on to develop PPD, and who did or did not have a pre-pregnancy history of recurrent MDD.

Participants were 103 pregnant women who were not depressed during pregnancy, were not on psychiatric medications, and completed a structured clinical diagnostic interview to assess current and past psychiatric illness, the Edinburgh Postnatal Depression Scale (EPDS), and blood draws at 2nd trimester (24-28 weeks gestation), 3rd trimester (32-36 weeks), and 6 weeks postpartum study visits. Plasma levels of neuroactive steroids (ALLO, pregnanolone, isoallopregnanolone, epipregnanolone) and progesterone were measured at each visit using gas chromatography mass spectrometry. Mixed effects models assessed differences in steroid levels and ratios to progesterone over time between groups based on a history of recurrent MDD and development of PPD.

Progesterone levels were lower, on average, over time in women with a history of recurrent MDD who developed PPD compared to women with no history of recurrent MDD who did (b=.48, p=.07) or did not (b=.37, p=.08) develop PPD. The ratio of ALLO to progesterone was significantly higher over time in women with a history of recurrent MDD who developed PPD compared to women with no history of recurrent MDD who did (b=-.11, p=.004) or did not (b=-.07, p=.03) develop PPD, and compared to women with a history of recurrent MDD who did not develop PPD (b=-.07, p=.03). There were no significant group by time interactions, and no significant group differences in levels of any other steroid or ratio to progesterone.

These results suggest that it is crucial to carefully characterize psychiatric history and depression onset when investigating the role of ALLO and other neurosteroids in PPD, as neurosteroid-related vulnerabilities and mechanisms of PPD pathogenesis likely differ in those with and without a history of recurrent MDD. In women who were psychiatrically-well during pregnancy, progesterone levels were blunted for those who had a history of MDD and developed PPD compared to women with no history of MDD, even if they developed PPD. Results indicate that this blunted progesterone also influences the ratio of ALLO synthesized compared to precursor progesterone.

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