Fetal Hippocampal Connectivity Shows Dissociable Associations with Maternal Cortisol and Self-Reported Distress during Pregnancy
Open accessAbstract
Maternal stress can shape long-term child neurodevelopment beginning in utero. One mechanism by which stress is transmitted from mothers to their offspring is via alterations in maternal cortisol, which can cross the placenta and bind to glucocorticoid receptor-rich regions in the fetal brain, such as the hippocampus. Although prior studies have demonstrated associations between maternal prenatal stress and cortisol levels with child brain development, we lack information about the extent to which these associations originate prior to birth and prior to confounding postnatal influences. Pregnant mothers (n = 77) completed questionnaires about current perceived stress, depressive symptoms, and anxiety symptoms, provided three to four salivary cortisol samples, and completed a fetal resting-state functional MRI scan during their second or third trimester of pregnancy (mean gestational age = 32.8 weeks). Voxelwise seed-based connectivity analyses revealed that higher prenatal self-reported distress and higher maternal cortisol levels corresponded to dissociable differences in fetal hippocampal functional connectivity. Specifically, self-reported distress was correlated with increased positive functional coupling between the hippocampus and right posterior parietal association cortex, while higher maternal cortisol was associated with stronger positive hippocampal coupling with the dorsal anterior cingulate cortex and left medial prefrontal cortex. Moreover, the association between maternal distress, but not maternal cortisol, on fetal hippocampal connectivity was moderated by fetal sex. These results suggest that prenatal stress and peripheral cortisol levels may shape fetal hippocampal development through unique mechanisms.
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The association between increased coupling with the medial prefrontal area and dorsal anterior cingulate cortex and maternal cortisol is moderated by fetal sex, but the association with right posterior parietal cortex is not.
“Importantly, the latter association, but not the former, is moderated by fetal sex.”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [107]
The Results (section 3.3) state the opposite of the attributed claim: fetal sex did not moderate the associations between maternal cortisol and hippocampal connectivity with the dACC or mPFC. It did moderate the association between maternal distress and hippocampal–posterior parietal connectivity. (LLM, conf=0.94)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIncreases in hippocampal connectivity due to elevated maternal stress and cortisol have been reported.
“Recently, increases in hippocampal connectivity due to elevated maternal stress and cortisol have also been reported [107].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [107]
The Discussion reports stronger fetal hippocampal connectivity associated with higher maternal cortisol and, separately, greater self-reported distress. The Conclusions suggest a possible strengthening mechanism, but the study reports associations rather than establishing that stress or cortisol caused the increases implied by “due to.” (LLM, conf=0.86)
Experimental — accuracy not yet measuredIncreased coupling with the medial prefrontal area and dorsal anterior cingulate cortex is related to increased maternal cortisol.
“Increased connectivity to the right posterior parietal cortex is associated with elevated maternal stress while increased coupling with the medial prefrontal area and dorsal anterior cingulate cortex is related to increased maternal cortisol.”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [107]
Increased connectivity to the right posterior parietal cortex is associated with elevated maternal stress.
“Increased connectivity to the right posterior parietal cortex is associated with elevated maternal stress while increased coupling with the medial prefrontal area and dorsal anterior cingulate cortex is related to increased maternal cortisol.”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [107]
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- Authors
- Hendrix, C. L., Srinivasan, H., Feliciano, I., Carré, J. M., & Thomason, M. E.
- Affiliations
- NYU Langone Health (US)
- Nipissing University (CA)
- Corresponding author
- Hendrix, Cassandra L.
- Venue
- Life
- Publisher
- MDPI AG
- Published
- 2022-06-23
- Volume
- 12
- Issue
- 7
- Pages
- 943
- ISSN
- 2075-1729 (ISSN-L)
- PMC
- PMC9316091
- OpenAlex
- W4283382384
- Cited by
- 21
- References
- 64
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 13 · 2023: 3 · 2022: 1
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Life (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (MH110793, DA050287, MH122447, ES026022, ES032294)
- 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
- prenatal stress, maternal cortisol, fetal hippocampus, fetal brain development, resting-state functional connectivity, maternal distress, maternal depression, maternal anxiety, salivary cortisol, fetal sex differences, dorsal anterior cingulate cortex, medial prefrontal cortex
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