Fetal Exposure to Maternal Depressive Symptoms Is Associated With Cortical Thickness in Late Childhood
Open accessAbstract
Background Maternal depression is one of the most common prenatal complications. The consequences of fetal exposure to maternal depression are poorly understood. The aim of this study is to examine the association between fetal exposure to maternal depressive symptoms and cortical thickness in children 6-9 years old.Methods A prospective, longitudinal study of maternal depressive symptoms at 19, 25, and 31 weeks' gestation was followed by acquisition of a structural magnetic resonance imaging scan in 81 children (age, 86.1 ± 9.9 months).Results Significant (p < .01) cortical thinning in children primarily in the right frontal lobes was associated with exposure to prenatal maternal depression. The strongest association was at 25 weeks' gestation; exposure to maternal depression at 25 gestational weeks was associated with cortical thinning in 19% of the whole cortex and 24% of the frontal lobes, primarily in the right superior, medial orbital, and frontal pole regions of the prefrontal cortex (p < .01). The significant association between prenatal maternal depression and child externalizing behavior (p < .05) was mediated by cortical thinning in prefrontal areas of the right hemisphere.Conclusions The pattern of cortical thinning in children exposed to prenatal maternal depression is similar to patterns in depressed patients and in individuals with risk for depression. Exposure to prenatal depression coupled with subsequent cortical thinning was associated with presence of externalizing behavior in preadolescent children and may be prodromal markers of risk for dysphoria. Vulnerability to prenatal influences at 25 gestational weeks may result from the enormous growth and dramatic structural changes in the nervous system.
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Exposure to prenatal maternal stress has enduring and wide-ranging consequences on brain development in the offspring, including altered regional brain volumetric growth, cortical folding, metabolism, microstructure, and functional connectivity.
“Importantly, exposure to prenatal maternal stress is shown to have enduring and wide-ranging consequences on brain development in the offspring, including altered regional brain volumetric growth, cortical folding, metabolism, microstructure, and functional connectivity [4, 15, 19, 23–27, 35–39].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [24]
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Experimental — accuracy not yet measuredLong-term neurodevelopmental impairments of the offspring include cognitive, language, social-emotional, learning and memory, and behavioral problems, as well as neuropsychiatric dysfunction.
“In addition, the long-term neurodevelopmental impairments of the offspring include a spectrum of cognitive, language, social-emotional, learning and memory, and behavioral problems, as well as neuropsychiatric dysfunction [13, 24, 26, 34, 40–46].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [24]
The Introduction (page unavailable) reports associations with lower intelligence and verbal intelligence, low social competence, externalizing behavior, and mental-health problems. The Discussion (page unavailable) reports cortical thinning and behavioral problems in children exposed prenatally to maternal depressive symptoms. It does not establish the full claimed spectrum: learning and memory problems are not shown in these offspring, and later neuropsychiatric dysfunction is described as a possible risk rather than an established outcome. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPrenatal maternal psychological distress has enduring consequences on long-term neurobehavioral development in the offspring, partially through altered brain structure and circuitry.
“Prenatal maternal psychological distress has been shown to have enduring consequences on long-term neurobehavioral development in the offspring [13, 24, 26, 34, 40–46], partially through altered brain structure and circuitry [118, 119].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [24]
The Results (Mediational analysis) and Discussion report that frontal cortical thinning partially mediated the association between prenatal maternal depressive symptoms and childhood externalizing problems. This supports altered brain structure as a possible pathway, but the study examined depressive symptoms rather than psychological distress generally and did not demonstrate altered brain circuitry. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPrenatal maternal depression and disaster-related stress are associated with externalizing behaviors in children.
“At later ages, prenatal maternal depression and disaster-related stress are associated with externalizing behaviors in children.”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [24]
The Results (Mediational analysis; page unavailable) report that higher prenatal maternal depression was associated with externalizing problems in children. The paper does not report an association between disaster-related prenatal stress and externalizing behavior; searches for disaster-related and natural-disaster stress found no such passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe association between prenatal maternal depression/disaster-related stress and externalizing behaviors is mediated by child cortical thinning in prefrontal areas of the right hemisphere.
“These associations are mediated by child cortical thinning in prefrontal areas of the right hemisphere [24], amygdala volume [88], and an altered structural connectivity between the amygdala and frontal cortex [95].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [24]
The Results (Mediational analysis) report that right frontal-pole thinning mediated the association between prenatal maternal depressive symptoms and child externalizing problems. The Discussion describes this mediation as partial. The paper does not establish the same mediation for disaster-related stress. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Elevated maternal psychological distress during mid-gestation is associated with a reduction in cortical thickness in the whole cortex and frontal lobes in children at 6-9 years old.
“and the whole cortex and frontal lobes in children at 6–9 years old [21, 24]”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [24]
Prenatal maternal stress exposure has enduring consequences on offspring brain development and long-term neurodevelopment.
“Prenatal maternal stress exposure has been shown to have enduring consequences on brain development in the offspring”
From Association of Elevated Maternal Psychological Distress, Altered Fetal Brain, and Offspring Cognitive and Social-Emotional Outcomes at 18 Months (2022) · cites this paper as [5]
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References 103 · Cited by 219
- Authors
- Sandman, C. A., Buss, C., Head, K., & Davis, E. P.
- Affiliations
- University of California, Irvine (US)
- University of Denver (US)
- Corresponding author
- Sandman, Curt A.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 77
- Issue
- 4
- Pages
- 324-334
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4289467
- OpenAlex
- W2136157075
- Cited by
- 219
- References
- 103
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 19 · 2023: 18 · 2022: 19 · 2021: 22 · 2020: 30 · 2019: 17 · 2018: 23 · 2017: 13 · 2016: 18 · 2015: 10 · 2014: 3 · 2013: 1
- FWCI
- 14.53
- 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)
- Digital Commons - DU (University of Denver) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (MH-96889, HD-51852, HD-28413, NS-41298)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- antenatal depression, cortical thinning, cortical thickness, prefrontal cortex, externalizing problems, late childhood, gestational age, brain development
- MeSH terms
- Adult, Cerebral Cortex, Child, Child Behavior, Depression, Female, Humans, Functional Laterality, Longitudinal Studies, Magnetic Resonance Imaging, Male, Pregnancy, Prenatal Exposure Delayed Effects, Prospective Studies, Pregnant People
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