What's the science?
Cortisol is a hormone involved in the body’s physical and psychological stress response. During pregnancy, the hormone can reach the neonate either directly or via fetal corticotropin-releasing hormone. Some cortisol is critical for fetal brain development, but abnormal levels are associated with psychiatric disorders in offspring. The amygdala is a brain region that has many cortisol receptors, and in animal models, high levels of maternal cortisol have been found to result in high negative emotion and stress reactivity in offspring. Sex differences in the effects of maternal cortisol have also been found; negative emotionality may be more likely to be present in female offspring. This week in Biological Psychiatry, Graham and colleagues assessed the effects of in utero cortisol exposure on the amygdala shortly after birth.
How did they do it?
A total of 70 mother-infant dyads participated in the study. Each mother collected 5 saliva samples of cortisol over the course of a day for a 4 day period during each of her 3 trimesters of pregnancy (60 samples per mother total). The area under the curve (similar to assessing overall cortisol output) was calculated for each trimester, resulting in reliable indicators of cortisol levels representative of each of the three trimesters. These values were also log-transformed for normalization purposes. Infants underwent brain functional magnetic resonance imaging (fMRI) at 4 weeks of age. Resting state functional connectivity (a measure of the synchrony of brain activity at rest) was calculated between the right and left amygdala and the rest of the brain, and the relationship between maternal cortisol and these connections was assessed. At 24 months of age, mothers reported on their child's internalizing behavior (e.g. depression or anxiety symptoms) using the Internalizing Behavior Scale of the Children's Behavioral Checklist.
What did they find?
There was an interaction between sex and maternal cortisol in predicting connectivity between the bilateral amygdala and the left supramarginal gyrus and superior temporal gyrus. Probing the interaction revealed that in females, amygdala connectivity with the aforementioned cortical regions was generally stronger with higher maternal cortisol, while it was weaker in males. The results suggest that the relationships between cortisol and connectivity of the amygdala to various regions of the cortex were opposite for males versus females. Further, connectivity between the right amygdala and the supramarginal gyrus was positively correlated with internalizing behaviour in children (not dependent on sex). This association remained even after considering levels of maternal depressive symptoms, another important potential influence on child internalizing behavior. Upon mediation analysis, the authors found that connectivity between the right amygdala and supramarginal gyrus mediated the relationship between maternal cortisol and child internalizing. Therefore, cortisol exposure during pregnancy is associated with higher internalizing behaviors in females through a pathway involving stronger right amygdala connectivity.
What's the impact?
Cortisol levels have been assessed in utero in animals models and at single time points during pregnancy in humans. However, this is the first study to demonstrate a relationship between connectivity of amygdala and maternal cortisol (which differs by sex) using a robust measure for cortisol levels over multiple key time points. The results suggest that this hormone involved in the stress response may alter integration of the amygdala with cortical brain regions during an early phase of brain development.
Graham et al., Maternal Cortisol Concentrations During Pregnancy and Sex Specific Associations with Neonatal Amygdala Connectivity and Emerging Internalizing Behaviors. Biological Psychiatry (2018). Access the original scientific publication here.