Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Protective Mechanisms in Preeclampsia

Julie A. Vignato; S. Banu Gumusoglu; Heather A. Davis; Sabrina M. Scroggins; Wendy S. Hamilton; Debra S. Brandt; Gary L. Pierce; Boyd A. Knosp; Donna A. Santillan; Mark K. Santillan

doi:10.1007/s43032-022-01065-z

Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Protective Mechanisms in Preeclampsia

Julie A. Vignato, S. Banu Gumusoglu, Heather A. Davis, Sabrina M. Scroggins, Wendy S. Hamilton, Debra S. Brandt, Gary L. Pierce, Boyd A. Knosp, Donna A. Santillan, Mark K. Santillan

Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Depression and preeclampsia share risk factors and are bi-directionally associated with increased risk for each other. Despite epidemiological evidence linking selective serotonin reuptake inhibitors (SSRIs) in pregnancy to preeclampsia, serotonin (5-HT) and vasopressin (AVP) secretion mechanisms suggest that SSRIs may attenuate preeclampsia risk. However, there is a need to clarify the relationship between SSRIs and preeclampsia in humans to determine therapeutic potential. This retrospective cohort study included clinical data from 9558 SSRI-untreated and 9046 SSRI-treated pregnancies. In a subcohort of 233 pregnancies, early pregnancy (< 20 weeks) maternal plasma copeptin, an inert and stable AVP prosegment secreted 1:1 with AVP, was measured by enzyme-linked immunosorbent assay. Diagnoses and depression symptoms (Patient Health Questionnaire-9 [PHQ-9]) were identified via medical records review. Descriptive, univariate, and multivariate regression analyses were conducted (α = 0.05). SSRI use was associated with decreased preeclampsia after controlling for clinical confounders (depression severity, chronic hypertension, diabetes, body mass index, age) (OR = 0.9 [0.7–1.0], p = 0.05). Moderate-to-severe depression symptoms were associated with significantly higher copeptin secretion than mild-to-no depression symptoms (240 ± 29 vs. 142 ± 10 ng/mL, p < 0.001). SSRIs significantly attenuated first trimester plasma copeptin (78 ± 22 users vs. 240 ± 29 ng/ml non-users, p < 0.001). In preeclampsia, SSRI treatment was associated with significantly lower copeptin levels (657 ± 164 vs. 175 ± 134 ng/mL, p = 0.04). Interaction between SSRI treatment and preeclampsia was also significant (p = 0.04). SSRIs may modulate preeclampsia risk and mechanisms, although further studies are needed to investigate the relationships between 5-HT and AVP in depression and preeclampsia. Graphical abstract: [Figure not available: see fulltext.].

Original language	English (US)
Pages (from-to)	701-712
Number of pages	12
Journal	Reproductive Sciences
Volume	30
Issue number	2
DOIs	https://doi.org/10.1007/s43032-022-01065-z
State	Published - Feb 2023

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health (T32NR11147, R01HD089940, T32MH01911328), the American Heart Association (18SCG34350001, 15SFRN 23730000, 15 SFRN 23480000, 908921), and an STTI National Research Grant. Data reported in this publication received research support and financial support from the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR002537, UL1TR002537-S1). The funders play no role in study design, collection/analysis/interpretation of data, writing of this manuscript, and the decision to submit the manuscript.

Publisher Copyright:
© 2022, The Author(s).

Keywords

Copeptin
Depression
Preeclampsia
Pregnancy
Selective serotonin reuptake inhibitors
Symptoms

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1007/s43032-022-01065-z

Find It

Find It at U of M Libraries

Cite this

@article{ab3cd889b9554c94ba13a21899409454,

title = "Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Protective Mechanisms in Preeclampsia",

abstract = "Depression and preeclampsia share risk factors and are bi-directionally associated with increased risk for each other. Despite epidemiological evidence linking selective serotonin reuptake inhibitors (SSRIs) in pregnancy to preeclampsia, serotonin (5-HT) and vasopressin (AVP) secretion mechanisms suggest that SSRIs may attenuate preeclampsia risk. However, there is a need to clarify the relationship between SSRIs and preeclampsia in humans to determine therapeutic potential. This retrospective cohort study included clinical data from 9558 SSRI-untreated and 9046 SSRI-treated pregnancies. In a subcohort of 233 pregnancies, early pregnancy (< 20 weeks) maternal plasma copeptin, an inert and stable AVP prosegment secreted 1:1 with AVP, was measured by enzyme-linked immunosorbent assay. Diagnoses and depression symptoms (Patient Health Questionnaire-9 [PHQ-9]) were identified via medical records review. Descriptive, univariate, and multivariate regression analyses were conducted (α = 0.05). SSRI use was associated with decreased preeclampsia after controlling for clinical confounders (depression severity, chronic hypertension, diabetes, body mass index, age) (OR = 0.9 [0.7–1.0], p = 0.05). Moderate-to-severe depression symptoms were associated with significantly higher copeptin secretion than mild-to-no depression symptoms (240 ± 29 vs. 142 ± 10 ng/mL, p < 0.001). SSRIs significantly attenuated first trimester plasma copeptin (78 ± 22 users vs. 240 ± 29 ng/ml non-users, p < 0.001). In preeclampsia, SSRI treatment was associated with significantly lower copeptin levels (657 ± 164 vs. 175 ± 134 ng/mL, p = 0.04). Interaction between SSRI treatment and preeclampsia was also significant (p = 0.04). SSRIs may modulate preeclampsia risk and mechanisms, although further studies are needed to investigate the relationships between 5-HT and AVP in depression and preeclampsia. Graphical abstract: [Figure not available: see fulltext.].",

keywords = "Copeptin, Depression, Preeclampsia, Pregnancy, Selective serotonin reuptake inhibitors, Symptoms",

author = "Vignato, {Julie A.} and Gumusoglu, {S. Banu} and Davis, {Heather A.} and Scroggins, {Sabrina M.} and Hamilton, {Wendy S.} and Brandt, {Debra S.} and Pierce, {Gary L.} and Knosp, {Boyd A.} and Santillan, {Donna A.} and Santillan, {Mark K.}",

note = "Funding Information: This study was supported by the National Institutes of Health (T32NR11147, R01HD089940, T32MH01911328), the American Heart Association (18SCG34350001, 15SFRN 23730000, 15 SFRN 23480000, 908921), and an STTI National Research Grant. Data reported in this publication received research support and financial support from the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR002537, UL1TR002537-S1). The funders play no role in study design, collection/analysis/interpretation of data, writing of this manuscript, and the decision to submit the manuscript. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2023",

month = feb,

doi = "10.1007/s43032-022-01065-z",

language = "English (US)",

volume = "30",

pages = "701--712",

journal = "Reproductive Sciences",

issn = "1933-7191",

publisher = "SAGE Publications Inc.",

number = "2",

}

TY - JOUR

T1 - Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Protective Mechanisms in Preeclampsia

AU - Vignato, Julie A.

AU - Gumusoglu, S. Banu

AU - Davis, Heather A.

AU - Scroggins, Sabrina M.

AU - Hamilton, Wendy S.

AU - Brandt, Debra S.

AU - Pierce, Gary L.

AU - Knosp, Boyd A.

AU - Santillan, Donna A.

AU - Santillan, Mark K.

N1 - Funding Information: This study was supported by the National Institutes of Health (T32NR11147, R01HD089940, T32MH01911328), the American Heart Association (18SCG34350001, 15SFRN 23730000, 15 SFRN 23480000, 908921), and an STTI National Research Grant. Data reported in this publication received research support and financial support from the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR002537, UL1TR002537-S1). The funders play no role in study design, collection/analysis/interpretation of data, writing of this manuscript, and the decision to submit the manuscript. Publisher Copyright: © 2022, The Author(s).

PY - 2023/2

Y1 - 2023/2

N2 - Depression and preeclampsia share risk factors and are bi-directionally associated with increased risk for each other. Despite epidemiological evidence linking selective serotonin reuptake inhibitors (SSRIs) in pregnancy to preeclampsia, serotonin (5-HT) and vasopressin (AVP) secretion mechanisms suggest that SSRIs may attenuate preeclampsia risk. However, there is a need to clarify the relationship between SSRIs and preeclampsia in humans to determine therapeutic potential. This retrospective cohort study included clinical data from 9558 SSRI-untreated and 9046 SSRI-treated pregnancies. In a subcohort of 233 pregnancies, early pregnancy (< 20 weeks) maternal plasma copeptin, an inert and stable AVP prosegment secreted 1:1 with AVP, was measured by enzyme-linked immunosorbent assay. Diagnoses and depression symptoms (Patient Health Questionnaire-9 [PHQ-9]) were identified via medical records review. Descriptive, univariate, and multivariate regression analyses were conducted (α = 0.05). SSRI use was associated with decreased preeclampsia after controlling for clinical confounders (depression severity, chronic hypertension, diabetes, body mass index, age) (OR = 0.9 [0.7–1.0], p = 0.05). Moderate-to-severe depression symptoms were associated with significantly higher copeptin secretion than mild-to-no depression symptoms (240 ± 29 vs. 142 ± 10 ng/mL, p < 0.001). SSRIs significantly attenuated first trimester plasma copeptin (78 ± 22 users vs. 240 ± 29 ng/ml non-users, p < 0.001). In preeclampsia, SSRI treatment was associated with significantly lower copeptin levels (657 ± 164 vs. 175 ± 134 ng/mL, p = 0.04). Interaction between SSRI treatment and preeclampsia was also significant (p = 0.04). SSRIs may modulate preeclampsia risk and mechanisms, although further studies are needed to investigate the relationships between 5-HT and AVP in depression and preeclampsia. Graphical abstract: [Figure not available: see fulltext.].

AB - Depression and preeclampsia share risk factors and are bi-directionally associated with increased risk for each other. Despite epidemiological evidence linking selective serotonin reuptake inhibitors (SSRIs) in pregnancy to preeclampsia, serotonin (5-HT) and vasopressin (AVP) secretion mechanisms suggest that SSRIs may attenuate preeclampsia risk. However, there is a need to clarify the relationship between SSRIs and preeclampsia in humans to determine therapeutic potential. This retrospective cohort study included clinical data from 9558 SSRI-untreated and 9046 SSRI-treated pregnancies. In a subcohort of 233 pregnancies, early pregnancy (< 20 weeks) maternal plasma copeptin, an inert and stable AVP prosegment secreted 1:1 with AVP, was measured by enzyme-linked immunosorbent assay. Diagnoses and depression symptoms (Patient Health Questionnaire-9 [PHQ-9]) were identified via medical records review. Descriptive, univariate, and multivariate regression analyses were conducted (α = 0.05). SSRI use was associated with decreased preeclampsia after controlling for clinical confounders (depression severity, chronic hypertension, diabetes, body mass index, age) (OR = 0.9 [0.7–1.0], p = 0.05). Moderate-to-severe depression symptoms were associated with significantly higher copeptin secretion than mild-to-no depression symptoms (240 ± 29 vs. 142 ± 10 ng/mL, p < 0.001). SSRIs significantly attenuated first trimester plasma copeptin (78 ± 22 users vs. 240 ± 29 ng/ml non-users, p < 0.001). In preeclampsia, SSRI treatment was associated with significantly lower copeptin levels (657 ± 164 vs. 175 ± 134 ng/mL, p = 0.04). Interaction between SSRI treatment and preeclampsia was also significant (p = 0.04). SSRIs may modulate preeclampsia risk and mechanisms, although further studies are needed to investigate the relationships between 5-HT and AVP in depression and preeclampsia. Graphical abstract: [Figure not available: see fulltext.].

KW - Copeptin

KW - Depression

KW - Preeclampsia

KW - Pregnancy

KW - Selective serotonin reuptake inhibitors

KW - Symptoms

UR - http://www.scopus.com/inward/record.url?scp=85136515404&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85136515404&partnerID=8YFLogxK

U2 - 10.1007/s43032-022-01065-z

DO - 10.1007/s43032-022-01065-z

M3 - Article

C2 - 35984571

AN - SCOPUS:85136515404

SN - 1933-7191

VL - 30

SP - 701

EP - 712

JO - Reproductive Sciences

JF - Reproductive Sciences

IS - 2

ER -

Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Protective Mechanisms in Preeclampsia

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this