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Recent research has implicated allopregnanolone (ALLO), a neuroactive steroid and metabolite of progesterone, in perinatal mood and anxiety symptoms. We sought to add to the limited literature examining ALLO and mood and anxiety at multiple time points across the peripartum. We measured mood and anxiety symptoms and ALLO levels by ELISA at the second and third trimester (T2 and T3) and week 6 postpartum (W6) in N = 73 women with prior histories of mood and/or anxiety disorders and N = 38 healthy controls. Analytic methods included multivariate and logistic regressions with linear mixed effect models. Among all participants (N = 111), higher ALLO levels at W6 were associated with higher depression and anxiety scores: each one unit increase in log ALLO at W6 was associated with a 2.54 point increase on the Edinburgh Postnatal Depression Scale (EPDS) (95% CI: 0.73 to 4.33) and an 8.0 point increase on the Perinatal Anxiety Screening Scale (PASS) (95% CI: 3.82 to 12.6). In addition, the nature of the relationship between log ALLO level and psychological measures changed across time; from T2 to W6 for EPDS, β = 3.73 (95% CI:1.16, 6.30), p = 0.0045; for PASS β = 9.78 (95% CI:3.77, 15.79), p = 0.0014); from T3 to W6, for (EPDS, β = 2.52 (95% CI:0.08, 4.96), p = 0.043; for PASS β = 7.33 (95% CI:1.63, 13.02), p = 0.018). The relationship of log ALLO to mood and anxiety symptoms was the same among women with and without psychiatric histories. Our exploratory findings indicate that the relationship between ALLO and mood and anxiety symptoms may change across the peripartum., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Psychiatric symptoms that coincide with reproductive transitions are related to changes in sex steroids, but studies show that this relationship is governed by individual women's vulnerability to change rather than by differences in level. There is growing interest in the role of allopregnanolone (ALLO), a 3- α reduced metabolite of progesterone and a strong allosteric modulator of the GABA A receptor, in such symptoms, with enough evidence now across various times of reproductive transition to offer an overview of the role of this hormone in reproductive psychiatry. This review offers a brief overview, focusing on literature of the last 3 years, of the relationship between allopregnanolone and mood at menarche; in the menstrual cycle; in the peripartum; and in the menopausal transition. ALLO dysregulation is identified in all of these transitions and found to be associated with mood symptoms, although evidence of its exact role; its relationship to other systems; and directionality is not consistent.

Purpose of Review: The purpose of this review is to provide a theoretical explanation and a review of the recent literature concerning the role of neuroactive steroids in perinatal depression, and to use this information to suggest future directions of research., Recent Findings: The bulk of the evidence on neuroactive steroids in perinatal depression concerns allopregnanolone. Recent studies have been mixed, with some studies finding a direct correlation between lower levels of allopregnanolone and increased depressive symptoms but other studies finding no relationship. Evidence concerning other neuroactive steroids and perinatal depression is sparse. Additional research is needed with larger sample sizes and better characterization across the perinatal period (rather than cross-sectionally). Because some studies point to a lag between neuroactive steroid dysregulation and subsequent symptoms, future research should consider interactions with other aspects of neuroactive steroid physiology, such as synthetic enzymes or receptor plasticity.

Current evidence is mixed on the role of progesterone and its metabolites in perinatal mood and anxiety disorders. We measured second and third trimester (T2 and T3) progesterone (PROG) and allopregnanolone (ALLO) levels by ELISA and postpartum depression (PPD) by clinician interview (DSM-IV criteria) in 60 pregnant women with a prior diagnosis of a mood disorder. Methods included multivariate and logistic regression with general linear mixed effect models. We found that, after adjustment, every additional ng/mL of T2 ALLO resulted in a 63% (95% CI 13% to 84%, p=0.022) reduction in the risk of developing PPD. Our findings extend previous work connecting ALLO and depression within pregnancy, and indicate that the relationship between pregnancy ALLO and PPD is worth further exploration in a larger sample., (Copyright © 2017 Elsevier Ltd. All rights reserved.)