Background
Perinatal mood and anxiety disorders encompass a range of mental health disorders
that occur during pregnancy and up to 1 year postpartum, affecting approximately 20%
of women. Traditional risk factors, such as a history of depression and pregnancy
complications including preeclampsia, are known. Their predictive utility, however,
is not specific or sensitive enough to inform clinical decision-making or prevention
strategies for perinatal mood and anxiety disorders. Better diagnostic and prognostic
models are needed for early identification and referral to treatment.
Objective
This study aimed to determine if a panel of novel third-trimester plasma protein biomarkers
in pregnant women can be used to identify those who have a high predisposed risk for
perinatal mood and anxiety disorders within 3 months postpartum.
Study Design
We studied 52 women (n=34 with a risk for perinatal mood and anxiety disorders and
n=18 controls) among whom mental health screening was conducted at 2 time points,
namely in the third trimester and again at 3 months postdelivery. An elevated perinatal
mood and anxiety disorder risk was identified by screening individuals with above-validated
cutoffs for depression (Edinburgh Postnatal Depression Scale ≥12), anxiety (Overall
Anxiety Severity and Impairment Scale ≥7), and/or posttraumatic stress disorder (Impact
of Events Scale >26) at both time points. Plasma samples collected in the third trimester
were screened using the aptamer-based SomaLogic SomaScan proteomic assay technology
to evaluate perinatal mood and anxiety disorder–associated changes in the expression
of 1305 protein analytes. Ingenuity Pathway Analysis was conducted to highlight pathophysiological
relationships between perinatal mood and anxiety disorder–specific proteins found
to be significantly up- or down-regulated in all subjects with perinatal mood and
anxiety disorder and in those with perinatal mood and anxiety disorders and no preeclampsia.
Results
From a panel of 53 significant perinatal mood and anxiety disorder–associated proteins,
a unique 20-protein signature differentiated perinatal mood and anxiety disorder cases
from controls in a principal component analysis (P<.05). This protein signature included NCAM1, NRCAM, and NTRK3 that converge around
neuronal signaling pathways regulating axonal guidance, astrocyte differentiation,
and maintenance of GABAergic neurons. Interestingly, when we restricted the analysis
to subjects without preeclampsia, a 30-protein signature differentiated perinatal
mood and anxiety disorder cases from all controls without overlap on the principal
component analysis (P<.001). In the nonpreeclamptic perinatal mood and anxiety disorder group, we observed
increased expression of proteins, such as CXCL11, CXCL6, MIC-B, and B2MG, which regulate
leucocyte migration, inflammation, and immune function.
Conclusion
Participants with perinatal mood and anxiety disorders had a unique and distinct plasma
protein signature that regulated a variety of neuronal signaling and proinflammatory
pathways. Additional validation studies with larger sample sizes are needed to determine
whether some of these molecules can be used in conjunction with traditional risk factors
for the early detection of perinatal mood and anxiety disorders.
Key words
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Article info
Publication history
Published online: January 14, 2023
Accepted:
January 11,
2023
Received in revised form:
January 5,
2023
Received:
November 18,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
T.L. and S.A.K. contributed equally to this work.
The authors report no conflict of interest.
This study received support from the Cedars-Sinai Center for Research in Women’s Health and Sex Differences (CREWHS), the 2020 CREWHS Research Award (to E.A., S.J.K., and S.A.K.), and the Susan A. Hickman Memorial Research Award from Postpartum Support International, 2021 (EEA). This study was also supported by the National Institutes of Health National Center for Advancing Translational Science and the University of California Los Angeles Clinical and Translational Science Institute under grant number UL1TR001881. We also thank the Cedars-Sinai Obstetrics and Gynecology Department and Los Angeles Helping Hand Miriam Jacobs Chair in Maternal Fetal Medicine for their support of this work.
Cite this article as: Accortt E, Mirocha J, Zhang D, et al. Perinatal mood and anxiety disorders: biomarker discovery using plasma proteomics. Am J Obstet Gynecol 2023:XX.x.ex–x.ex.
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© 2023 Published by Elsevier Inc.
