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. 2022 Oct;146(4):357-369.
doi: 10.1111/acps.13461. Epub 2022 Jul 6.

The role of central serotonergic markers and estradiol changes in perinatal mental health

Camilla Borgsted  1   2   3 , Stinne Høgh  1   3   4 , Emma Sofie Høgsted  1 , Laura Fonnesbech-Sandberg  1 , Kim Ekelund  5 , Charlotte Krebs Albrechtsen  5 , Julie Therese Wiis  6 , Hanne Hegaard  3   4 , Eleonora Cvetanovska  7 , Anders Juul  3   8 , Hanne Frederiksen  8 , Anja Pinborg  3   9 , Pia Weikop  10 , Vibe Frokjaer  1   2   3
Affiliations

The role of central serotonergic markers and estradiol changes in perinatal mental health

Camilla Borgsted et al. Acta Psychiatr Scand. 2022 Oct.

Abstract

Objective: Women have an increased risk for mental distress and depressive symptoms in relation to pregnancy and birth. The serotonin transporter (SERT) may be involved in the emergence of depressive symptoms postpartum and during other sex-hormone transitions. It may be associated with cerebrospinal fluid (CSF) levels of the main serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA). In 100 healthy pregnant women, who were scheduled to deliver by cesarean section (C-section), we evaluated 5-HIAA and estradiol contributions to mental distress 5 weeks postpartum.

Methods: Eighty-two women completed the study. CSF collected at C-section was analyzed for 5-HIAA, with high performance liquid chromatography. Serum estradiol concentrations were quantified by liquid chromatography tandem mass spectrometry before C-section and postpartum. Postpartum mental distress was evaluated with the Edinburgh Postnatal Depression Scale (EPDS). Associations between EPDS, 5-HIAA, and Δestradiol were evaluated in linear regression models adjusted for age, parity and SERT genotype.

Results: Higher levels of postpartum mental distress symptoms were negatively associated with a large decrease in estradiol concentrations (βΔE2 = 0.73, p = 0.007) and, on a trend level, positively associated with high antepartum 5-HIAA levels (β5-HIAA = 0.002, p = 0.06).

Conclusion: In a cohort of healthy pregnant women, postpartum mental distress was higher in women with high antepartum 5-HIAA (trend) and lower in women with a large perinatal estradiol decrease. We speculate that high antepartum 5-HIAA is a proxy of SERT levels, that carry over to the postpartum period and convey susceptibility to mental distress. In healthy women, the postpartum return to lower estradiol concentrations may promote mental well-being.

Keywords: estradiol; mental health; postpartum; pregnancy; serotonin.

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Conflict of interest statement

VGF declares that she has received honorarium as a consultant for Sage Therapeutics and lectures for Lundbeck Pharma A/S. None of the other authors declare any potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Overview of study design
FIGURE 2
FIGURE 2
(A) Association between 5‐HIAA and Edinburgh Postnatal Depression Scale (EPDS) residuals after adjusting for age, parity and 5‐HTTLPR genotype status. Linear regression line has 95% CI. (B) Association between ΔE2 and EPDS residuals after adjusting for age, parity and 5‐HTTLPR genotype status. Linear regression line has 95% CI depicted in gray shade. Note that residuals and not EPDS scores are on the y‐axis
See this image and copyright information in PMC

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