Every week we review the most recent publications in women’s mental health, covering topics related to premenstrual symptoms, perinatal mood and anxiety disorders, use of medications in pregnant and breastfeeding women, perinatal substance use, and menopausal mental health. 

The journal Neurobiology of Stress has published two interesting articles on allopregnanolone. The first article reviews the data supporting the role of allopregnanolone in the etiology of postpartum depression, research which ultimately led to the development of brexanolone for the treatment of postpartum depression.  Brexanolone, marketed as Zulresso, is a neurosteroid, an analogue of allopregnanolone which is a positive allosteric modulator of the GABA-A receptor.  

The second article looks at how allopregnanolone may play a role in the pathogenesis of premenstrual mood disorders.  This article raises the possibility of using a brexanolone-type medication for the treatment of PMDD. Sepranolone is an isomer of allopregnanolone and is a GABA-A modulating steroid antagonist (GAMSA).   Sepranolone is currently in Phase II clinical trials for PMDD in Europe.  That’s exciting; we have not had any new treatments for PMDD in quite some time.  

Don’t forget that our online course on women’s mental health will begin on FEBRUARY 10TH.  You can find out more about the course and REGISTER HERE.  

For more detailed descriptions of many of these topics, you can sign up to receive our weekly CWMH NEWSLETTER which comes out every Thursday.  

Ruta Nonacs, MD PhD


Evidence-Based Treatment of Premenstrual Dysphoric Disorder: A Concise Review.

Carlini SV, Deligiannidis KM.  J Clin Psychiatry. 2020 Feb 4;81(2).  Free Article

A great review to guide clinical treatment.  

Allopregnanolone in Premenstrual Dysphoric Disorder (PMDD): Evidence for Dysregulated Sensitivity to GABA-A Receptor Modulating Neuroactive Steroids Across the Menstrual Cycle.

Hantsoo L, Epperson CN. Neurobiology of Stress, February 2020.

The literature supports the hypothesis that PMDD pathophysiology is rooted in impaired GABAA-R response to dynamic ALLO fluctuations across the menstrual cycle, manifesting in affective symptoms and poor regulation of physiologic stress response.


No articles this week


Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression.

Robakis TK, Zhang S, Rasgon NL et al.  Transl Psychiatry 10, 48 (2020).

Looking at adult women with histories of exposure to childhood adversity and/or insecure attachment, researchers were able to identify 1580 regions wheremethylation density was associated with childhood adversity, 3 in which methylation density was associated with insecure attachment style, and 6 in which methylation density was associated with perinatal depression. A detailed analysis of methylation density in the oxytocin receptor gene revealed similar patterns of DNA methylation in association with perinatal depression and with insecure attachment style, a finding which is consistent with the theory that the perinatal period is a time of activation of existing attachment schemas for the purpose of structuring the mother–child relationship, and that such activation may occur in part through specific patterns of methylation of the oxytocin receptor gene.

Global burden of antenatal depression and its association with adverse birth outcomes: an umbrella review.

Dadi AF, Miller ER, Bisetegn TA, Mwanri L.  BMC Public Health. 2020 Feb 4;20(1):173. Free Article

Globally, antenatal depression prevalence ranged from 15 to 65%. The risk of low birth weight and preterm birth was 1.49 (95%CI: 1.32, 1.68; I2 =?0.0%) and 1.40 (95%CI: 1.16, 1.69; I2 =?35.2%) times higher among infants born from depressed mothers.   While the association between antenatal depression and adverse birth outcomes appeared to be modest, its absolute impact would be significant in lower-income countries with a high prevalence of antenatal depression and poor access to quality mental health services.

Treatment and Management of Depression Symptoms in Pregnant Veterans: Varying Experiences of Mental Health Care in the Prenatal Period.

Kroll-Desrosiers AR, Crawford SL, Moore Simas TA, Clark MA, Mattocks KM.  Psychiatr Q. 2020 Feb 1. 

A majority of our sample (70%) had 1 or more mental health visits or antidepressant prescriptions during pregnancy. Women with a history of depression had more mental health visits and a higher percentage of antidepressant use before and during pregnancy than women without a history of depression.

A narrative review of positive psychology interventions for women during the perinatal period.

Corno G, Espinoza M, Maria Baños R.  J Obstet Gynaecol. 2019 Oct;39(7):889-895.

Allopregnanolone in Postpartum Depression: Role in Pathophysiology and Treatment.  

Meltzer-Brody S, Kanes SJ.  Neurobiology of Stress, February 2020.

Data implicating GABAergic signaling and allopregnanolone in PPD are discussed in the context of the development of brexanolone injection, an intravenous formulation of allopregnanolone recently approved by the United States Food and Drug Administration for the treatment of adult women with PPD.


No articles this week


Perinatal depressive symptoms often start in the prenatal rather than postpartum period: results from a longitudinal study.

Wilcox M, McGee BA, Ionescu DF, Leonte M, LaCross L, Reps J, Wildenhaus K.  Arch Womens Ment Health. 2020 Feb 4. 

Nearly 10% of women entered the pregnancy with depressive symptoms’ the prevalence increased to 16% in the third trimester.  The prevalence of depressive symptoms was about the same at 4 weeks and 3 months postpartum. Among women with postpartum depressive symptoms, 80% of the episodes occurred during pregnancy, with 1/3 occurring in the first trimester. 

Perinatal Mixed Affective State: Wherefore Art Thou?

Koukopoulos AE, Angeletti G, Sani G, Janiri D, Manfredi G, Kotzalidis GD, De Chiara L.  Psychiatr Clin North Am. 2020 Mar;43(1):113-126. 

Mixed states in patients with a perinatal mood episode is seldom encountered. Lack of appropriate assessment tools could be partly responsible for this observation.  

Changes in quality of life and sleep across the perinatal period in women with mood disorders.

Kang AW, Pearlstein TB, Sharkey KM.  Qual Life Res. 2020 Feb 3. 

In this sample of women with depression and/or anxiety, quality of life was related to postpartum depressive symptoms, but not to objectively measured sleep quality, quantity, or timing.

Recovery from postpartum psychosis: a systematic review and metasynthesis of women’s and families’ experiences.

Forde R, Peters S, Wittkowski A.  Arch Womens Ment Health. 2020 Feb 4. 

Four main themes incorporating 13 subthemes were identified following synthesis: (1) Experiencing the unspeakable, (2) Loss and disruption, (3) Realigning old self and new self and the integrative theme of (4) Social context.

Pharmacologic labour analgesia and its relationship to postpartum psychiatric disorders: a scoping review.

Munro A, MacCormick H, Sabharwal A, George RB.  Can J Anaesth. 2020 Feb 4.

Most studies relied on screening tests for diagnosing postpartum psychiatric illness and did not assess the impact of labor analgesia on postpartum psychiatric illness as the primary study objective.  More study is needed to better understand the impact of labor analgesia on risk for postpartum psychiatric illness.  

Epidural Labor Analgesia Is Associated with a Decreased Risk of the Edinburgh Postnatal Depression Scale in Trial of Labor after Cesarean: A Multicenter, Prospective Cohort Study.

Sun J, Xiao Y, Zou L, Liu D, Huang T, Zheng Z, Yan X, Yuan A, Li Y, Huang X.

Biomed Res Int. 2020 Jan 16.   Free Article

At 48 hours, women who had received epidural analgesia were less likely to have Edinburgh Postnatal Depression Scale scores ??10 (8.49%) than women who received  no epidural analgesia (26.42%) (OR, 0.209; 95% CI, 0.096-0.429; P < 0.001). At 42 days postpartum, ?the prevalence of EODS scores > 10 was 6.59% in the epidural analgesia group and 25.16% in the no epidural analgesia group (OR, 0.235; 95% CI, 0.113-0.469; P < 0.001). 


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