Maternal Cortisol Concentrations During Pregnancy and Sex-Specific Associations With Neonatal Amygdala Connectivity and Emerging Internalizing Behaviors
Open accessAbstract
Background Maternal cortisol during pregnancy has the potential to influence rapidly developing fetal brain systems that are commonly altered in neurodevelopmental and psychiatric disorders. Research examining maternal cortisol concentrations across pregnancy and offspring neurodevelopment proximal to birth is needed to advance understanding in this area and lead to insight into the etiology of these disorders.Methods Participants were 70 adult women recruited during early pregnancy and their infants born after 34 weeks gestation. Maternal cortisol concentrations were assessed serially over 4 days in early, mid, and late gestation. Resting state functional connectivity magnetic resonance imaging of the neonatal amygdala was examined. Mothers reported on children's internalizing behavior problems at 24 months of age.Results Maternal cortisol concentrations during pregnancy were significantly associated with neonatal amygdala connectivity in a sex-specific manner. Elevated maternal cortisol was associated with stronger amygdala connectivity to brain regions involved in sensory processing and integration, as well as the default mode network in girls, and with weaker connectivity to these brain regions in boys. Elevated maternal cortisol was associated with higher internalizing symptoms in girls only, and this association was mediated by stronger neonatal amygdala connectivity.Conclusions Normative variation in maternal cortisol during pregnancy is associated with the coordinated functioning of the amygdala soon after birth in a sex-specific manner. The identified pathway from maternal cortisol to higher internalizing symptoms in girls via alterations in neonatal amygdala connectivity may be relevant for the etiology of sex differences in internalizing psychiatric disorders, which are more prevalent in women.
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In females, higher cortisol levels are correlated with greater amygdala connectivity to diverse networks (e.g., default mode network and emotion regulation); the reverse is true in males.
“In females, higher cortisol levels are correlated with greater amygdala connectivity to diverse networks (e.g., default mode network and emotion regulation); the reverse is true in males [117].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [117]
The Results and Discussion report stronger neonatal amygdala connectivity with default mode and sensory-processing regions as maternal cortisol rises in females, with the reverse pattern in males. But for the DLPFC, a region involved in emotion regulation, the Discussion reports weaker connectivity in females and stronger connectivity in males—the opposite of the claim's example. Page numbers are not available in the supplied passages. (LLM, conf=0.91)
Experimental — accuracy not yet measuredMaternal cortisol predicts internalizing score on the Child Behavior Checklist at 2 years of age.
“One previous study shows that maternal cortisol predicts internalizing score on the Child Behavior Checklist at 2 years of age.”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [117]
The Methods (Internalizing Behavior at 24-months-of-age) identify the outcome as the Child Behavior Checklist internalizing scale. The Results (Association between Maternal Cortisol During Pregnancy and Child Internalizing Behavior) report a significant association at 24 months for girls, but not boys; the claim omits this sex-specific qualification. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn girls, the relationship between maternal cortisol and internalizing score at 2 years is mediated by increased amygdala connectivity.
“In girls, this relationship is mediated by increased amygdala connectivity [117].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [117]
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- Authors
- Graham, A. M., Rasmussen, J. M., Entringer, S., Ben Ward, E., Rudolph, M. D., Gilmore, J. H., Styner, M., Wadhwa, P. D., Fair, D. A., & Buss, C.
- Affiliations
- Oregon Health & Science University (US)
- University of California, Irvine (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Wadhwa, Pathik D.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 85
- Issue
- 2
- Pages
- 172-181
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC6632079
- OpenAlex
- W2859733407
- Cited by
- 203
- References
- 103
- Citations by year
- 2026: 22 · 2025: 16 · 2024: 26 · 2023: 23 · 2022: 24 · 2021: 43 · 2020: 30 · 2019: 15 · 2018: 3 · 2016: 1
- FWCI
- 23.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Child Health and Human Development (R01 HD060628)
- National Institute of Mental Health (R01 MH091351)
- 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 › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- maternal cortisol, pregnancy, amygdala functional connectivity, sex differences, internalizing problems, early childhood, default mode network, prenatal stress, brain development
- MeSH terms
- Adult, Amygdala, Child, Preschool, Female, Humans, Hydrocortisone, Infant, Newborn, Internal-External Control, Magnetic Resonance Imaging, Male, Mothers, Neural Pathways, Pregnancy, Saliva, Sex Characteristics, Time Factors, Young Adult, Functional Neuroimaging
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