Maternal Cortisol Concentrations During Pregnancy and Sex-Specific Associations With Neonatal Amygdala Connectivity and Emerging Internalizing Behaviors

Alice M. Graham, Jerod M. Rasmussen, Sonja Entringer, Elizabeth Ben Ward, Marc D. Rudolph, John H. Gilmore, Martin Styner, Pathik D. Wadhwa, Damien A. Fair, Claudia Buss

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)172-181
Number of pages10
JournalBiological psychiatry
Issue number2
StatePublished - Jan 15 2019
Externally publishedYes

Bibliographical note

Funding Information:
Support for this work was provided by the National Institute of Child Health and Human Development (Grant No. R01 HD060628 to PDW [EMA Assessment of Biobehavioral Processes in Human Pregnancy]), National Institute of Mental Health (Grant No. R01 MH091351 to CB and PDW [Fetal Programming of the Newborn and Infant Human Brain], Supplement to Grant No. R01 MH091351 to CB and DAF [Fetal Programming of Brain Functional Connectivity in Neonates and Infants], NIH Office of the Director (Grant No. UG3 OD023349 02 [Pre- and Postnatal Exposure Periods for Child Health: Common Risks and Shared Mechanisms] to CB, Richard K. Miller, Hyagriv N. Simhan, and Pathik D. Wadhwa) and Grant No. K99 MH111805 to AMG [A Targeted Approach to Examine the Influence of Maternal Psychological Stress on Newborn Brain Outcomes]), Gates Foundation Grand Challenges Explorations (to DAF and R. Nardos [Early Markers to Predict Cognition and Brain Development]), and Grant Nos. R00 MH091238 and R01 MH096773 (both to DAF).

Publisher Copyright:
© 2018


  • Amygdala
  • Cortisol
  • Infancy
  • Internalizing
  • Pregnancy
  • Resting state functional connectivity MRI


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