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Cited by 19Maternal Mental Health During Pregnancy and PostpartumStress Responses and CortisolTryptophan and brain disorders

Maternal Prenatal Depression in Pregnancies With Female and Male Fetuses and Developmental Associations With C-reactive Protein and Cortisol

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Freedman, Robert, Hunter, Sharon K., Noonan, Kathleen, Wyrwa, Anna, Christians, Uwe, Law, Amanda J., Hoffman, M. Camille·2021·Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
DOI 10.1016/j.bpsc.2020.08.003PMC PMC7881057
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Abstract

Background Prenatal depression has lasting effects on development in offspring, including later mental illness risk. Maternal responses to depression include inflammation and hypothalamic-pituitary-adrenal axis stimulation. Effects on development of cerebral inhibitory neurocircuits may differ for female and male fetuses. Methods Mothers (N = 181) were assessed periodically, beginning at 16 weeks' gestation, using the Center for Epidemiologic Studies-Depression Scale. Maternal prenatal C-reactive protein and hair cortisol and cortisone levels were determined. Cortisone was determined in neonatal hair. Development of cerebral inhibitory neurocircuits was assessed in 162 1-month-old newborns by inhibition of P50 electrophysiological responses to repeated sounds. Results Maternal depression was associated with decreased newborn P50 inhibition in both sexes. Maternal C-reactive protein levels were significantly associated with depression only in pregnancies with male fetuses and with decreased newborn P50 inhibition only in male newborns. Maternal cortisol levels were significantly associated with depression only in pregnancies with female fetuses and with decreased newborn P50 inhibition only in female newborns. In pregnancies with male fetuses compared with pregnancies with female fetuses, cortisol was more robustly metabolized to cortisone, which does not activate cortisol receptors. Conclusions This study finds sex-specific associations of C-reactive protein and cortisol levels with prenatal depression in women and with decreased development of newborn P50 inhibition. Sex-based differences in maternal response to depression with inflammation or cortisol and their developmental effects may reflect evolutionary influences to promote survival in adversity. Decreased newborn P50 inhibition is associated with later childhood behavioral problems, and decreased P50 inhibition is a pathophysiological feature of several mental illnesses.

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  • C-reactive protein (CRP) is elevated as prenatal maternal mental distress increases.

    “Additionally, C-reactive protein (CRP), an inflammatory marker, is elevated as prenatal maternal mental distress increases [142, 143], and elevated gestational CRP levels have been associated with increased risk of preterm birth [144], adverse infant and child brain developmental outcomes [144, 145], as well as autism and schizophrenia in the offspring [146, 147].”

    From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [142]

    The Results section reports that greater depressive symptoms at 16 weeks were associated with higher CRP in mothers carrying male fetuses. It found no such association in mothers carrying female fetuses, so the claim overgeneralizes the finding to prenatal maternal mental distress without the fetal-sex qualification. Page numbers are not available in the supplied passages. (LLM, conf=0.90)

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Authors
Freedman, R., Hunter, S. K., Noonan, K., Wyrwa, A., Christians, U., Law, A. J., & Hoffman, M. C.
Affiliations
University of Colorado Anschutz (US)
Corresponding author
Freedman, Robert
ORCID
Venue
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Publisher
Elsevier BV
Published
2021-03
Volume
6
Issue
3
Pages
310-320
ISSN
2451-9022 (ISSN-L)
DOI
10.1016/j.bpsc.2020.08.003
PMC
PMC7881057
OpenAlex
W3049638322
Cited by
19
References
17
Citations by year
2026: 1 · 2024: 10 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 1
FWCI
1.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry Cognitive Neuroscience and Neuroimaging (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Center for Advancing Translational Sciences (UL1TR001082)
  • Anschutz Foundation
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
C-reactive protein, hair cortisol, cortisone, neonates, sex differences, fetal sex, hypothalamic-pituitary-adrenal axis, inflammation, offspring development, maternal mental health
MeSH terms
C-Reactive Protein, Child, Depression, Female, Fetus, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Infant, Newborn, Male, Pituitary-Adrenal System, Pregnancy, Prenatal Exposure Delayed Effects, Stress, Psychological

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