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

Abstract

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.