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

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

doi:10.1016/j.biopsych.2018.06.023

Cited by 149 publications

(136 citation statements)

References 100 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…While our prediction for this study was based on findings of amygdala function in relation to prenatal cortisol levels and in relation to CU traits, we did not measure amygdala function and it cannot be assumed that this was the mediator of the association reported here. Nevertheless, our findings together with those showing the same pattern of sex-dependent associations between prenatal cortisol and elevated infant negative emotionality and child internalizing problems (5,6,14), imply the need for further work regarding the circumstances under which prenatal glucocorticoid and postnatal amygdala activity mechanisms are associated on the one hand with increased emotionality, and on the other hand with increased responsiveness to others' negative emotions. Table 2.…”

Section: Discussionsupporting

confidence: 54%

“…There is also direct evidence that elevated maternal cortisol in early, but not late, pregnancy is associated with a larger right amygdala volume in girls, but not boys (8). In the same study, high prenatal cortisol was also positively associated with affective problems in girls, an effect which was, in part, mediated by right amygdala volume (8) and increased amygdala connectivity (14) during infancy. Associations, in girls and not in boys, between prenatal maternal cortisol and brain network properties have been demonstrated, with indications that these were associated with increased internalizing symptoms (15).…”

mentioning

confidence: 78%

“…Based on recent evidence for sex-dependent associations between prenatal maternal cortisol and amygdala function (14), and known associations between amygdala under-activity and CU traits, we predicted that elevated prenatal cortisol would be associated with reduced CU traits and increased internalizing problems only in girls. Using data from a prospective, longitudinal cohort stratified by risk, we examined sex-specific associations between maternal prenatal cortisol at 32 weeks gestation and child CU traits assessed a three time points from ages 2.5 to 5.0 years.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Sex-specific associations between maternal prenatal cortisol and child callous-unemotional traits: Findings from the Wirral Child Health and Development Study

Wright¹,

Pickles²,

Braithwaite³

et al. 2018

Preprint

View full text Add to dashboard Cite

Background: Maternal prenatal stress may impact on fetal development in a sex-dependent way.Evidence from the human and animal literature supports a theory of glucocorticoid-mediated risk in females, which results in elevated affective symptoms via increased amygdala connectivity and activity. We sought to investigate whether this mechanism may be protective against psychopathology associated with reduced amygdala activity, specifically callous-unemotional (CU) traits.Methods: Participants (n=225) were members of a stratified subsample of an epidemiological cohort (n=1233). Maternal diurnal cortisol was measured using the log of the area under the curve (LogAUC) from saliva samples collected over two days at 32 weeks gestation (on waking, 30-min post-waking and during the evening). Mothers reported on child CU traits and internalizing symptoms at 2.5, 3.5 and 5 years of age.Results: Higher maternal prenatal cortisol was significantly associated with lower CU traits in girls.This effect remained when controlling for confounders and internalizing symptoms. The effect in boys was consistently different from girls (interaction term p<0.001), but never different from zero, indicating no association. There was a significant interaction term to predict internalizing symptoms, however the effect became non-significant when confounders and CU traits were included in the model. Conclusions:The findings extend existing understanding of the adaptive model of prenatal programming in females, where exposure to prenatal stress increases risk for affective disorders via glucocorticoid mechanisms and altered amygdala functioning. Our findings suggest that exposure to elevated prenatal cortisol in females may confer risk or be a protective mechanism depending on the outcome.

show abstract

Section: Discussionsupporting

confidence: 54%

mentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sex-specific associations between maternal prenatal cortisol and child callous-unemotional traits: Findings from the Wirral Child Health and Development Study

Wright¹,

Pickles²,

Braithwaite³

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…However, the substantial heritability of both cognitive performance and functional connectivity suggests that topography is at least in part genetically encoded (Colclough et al, 2017;Mollink et al, 2019). Furthermore, accruing evidence from animal models and translational studies in humans emphasizes the likely importance of in-utero and early-life stressors, which could potentially impact developmental initialization of functional network topography (Graham et al, 2019). In the future, it will be possible to test this hypothesis using a combination of studies in animal models and human infants with varying levels of stress exposure.…”

Section: Discussionmentioning

confidence: 99%

Individual Variation in Control Network Topography Supports Executive Function in Youth

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

The spatial distribution of large-scale functional networks on the anatomic cortex differs between individuals, and is particularly variable in networks responsible for executive function.However, it remains unknown how this functional topography evolves in development and supports cognition. Capitalizing upon advances in machine learning and a large sample of youth (n=693, ages 8-23y) imaged with 27 minutes of high-quality fMRI data, we delineate how functional topography evolves during youth. We found that the functional topography of association networks is refined with age, allowing accurate prediction of an unseen individual's brain maturity. Furthermore, the cortical representation of executive networks predicts individual differences in executive function. Finally, variability of functional topography is associated with fundamental properties of brain organization including evolutionary expansion, cortical myelination, and cerebral blood flow. Our results emphasize the importance of considering both the plasticity and diversity of functional neuroanatomy during development, and suggest advances in personalized therapeutics.We conducted several supplementary analyses to confirm that our results were robust to methodological choices. In order to ensure that our matched split of the data was representative, we repeated this procedure with 100 random splits of the data, which returned highly consistent results and feature weights (mean partial r = 0.69, Pperm < 0.001; mean MAE = 1.93 years, Pperm < 0.001; Supplementary Figure 8). For comparison, we repeated this procedure using both the discrete network parcellation derived from NMF and also that from MS-HBM. While still highly significant (Pperm < 0.001), not considering network probability mildly degraded predictive accuracy (see Supplementary Figure 8). Taken together, these results demonstrate that functional network topography encodes brain maturity, is driven by refinement of higher-order association networks, and is constrained by the individual variability of these systems. Control network topography predicts individual differences in executive functionHaving found that functional topography accurately encoded brain maturation, we next evaluated the implications of topographic variability for cognition. Specifically, we investigated whether variation in functional network topography predicted individual differences in executive function. Executive function was summarized using a previously-published factor analysis of the Penn Computerized Neurocognitive Battery (Moore et al., 2015). While controlling for age, sex, and motion, general additive models revealed that the improved executive performance was associated with a greater total cortical representation of bilateral fronto-parietal control networks and the cingulo-opercular ventral attention network (Figure 6A; left fronto-parietal: network 11, Z = 5.88, PBonf = 1.09 ´ 10 -7 , partial r = 0.22, CI = [0.15, 0.29]; right fronto-parietal: network 17, Z = 5.23, PBonf = 3.90 ´ 10 -6 , partial r = 0.19, ...

show abstract

“…Furthermore, elevated endogenous maternal glucocorticoids have been linked to negative outcomes especially regarding brain development 14 . For example, elevated prenatal maternal cortisol was significantly associated with altered neonatal amygdala connectivity, associated with differences in sensory processing and integration, and subsequently internalizing symptoms in girls 15 . In addition, conditions associated with increased maternal GCs and decreased placental 11β-HSD2, such as prenatal stress and prenatal maternal depression 1 , which could lead to increased fetal GC exposure, have repeatedly been associated with long-term negative behavioral outcomes in children, including problems with attention and emotional regulation, as well as changes in brain structure and function, at birth and in childhood [16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

Cell-type specific impact of glucocorticoid receptor activation on the developing brain

Cruceanu

Dony

Krontira

et al. 2020

Preprint

View full text Add to dashboard Cite

A fine-tuned balance of glucocorticoid receptor (GR) activation is essential for organ formation, with disturbances influencing health outcomes. Excess GR-activation in utero has been linked to brain-related negative outcomes, with unclear underlying mechanisms, especially regarding cell-type specific effects. To address this, we used an in vitro model of fetal human brain, induced pluripotent-stem-cell-derived cerebral organoids, and mapped GR-activation effects using single-cell transcriptomics across development. Interestingly, neurons showed targeted regulation of differentiation-and maturation-related transcripts, suggesting a delay of these processes upon GR-activation. Uniquely in neurons, differentially-expressed transcripts were significantly enriched for genes associated with behavior-related phenotypes and disorders. This suggests that aberrant GR-

show abstract

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

Cited by 149 publications

References 100 publications

Sex-specific associations between maternal prenatal cortisol and child callous-unemotional traits: Findings from the Wirral Child Health and Development Study

Sex-specific associations between maternal prenatal cortisol and child callous-unemotional traits: Findings from the Wirral Child Health and Development Study

Individual Variation in Control Network Topography Supports Executive Function in Youth

Cell-type specific impact of glucocorticoid receptor activation on the developing brain

Contact Info

Product

Resources

About