Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems

TLDR

Stress-related variation in the intrauterine environment can affect brain development and function, especially in limbic regions, yet the timing and magnitude of these effects remain poorly understood in humans. The study followed 65 healthy mother–child pairs, measuring maternal cortisol during early, mid, and late pregnancy and assessing child amygdala and hippocampus volumes and affective problems at about age seven. Higher maternal cortisol in early pregnancy was linked to larger right amygdala volumes and increased affective problems in girls, with amygdala size partially mediating this effect, while no associations were found with hippocampal volume, highlighting the early intrauterine influence on neuropsychiatric risk.

Abstract

Stress-related variation in the intrauterine milieu may impact brain development and emergent function, with long-term implications in terms of susceptibility for affective disorders. Studies in animals suggest limbic regions in the developing brain are particularly sensitive to exposure to the stress hormone cortisol. However, the nature, magnitude, and time course of these effects have not yet been adequately characterized in humans. A prospective, longitudinal study was conducted in 65 normal, healthy mother–child dyads to examine the association of maternal cortisol in early, mid-, and late gestation with subsequent measures at approximately 7 y age of child amygdala and hippocampus volume and affective problems. After accounting for the effects of potential confounding pre- and postnatal factors, higher maternal cortisol levels in earlier but not later gestation was associated with a larger right amygdala volume in girls (a 1 SD increase in cortisol was associated with a 6.4% increase in right amygdala volume), but not in boys. Moreover, higher maternal cortisol levels in early gestation was associated with more affective problems in girls, and this association was mediated, in part, by amygdala volume. No association between maternal cortisol in pregnancy and child hippocampus volume was observed in either sex. The current findings represent, to the best of our knowledge, the first report linking maternal stress hormone levels in human pregnancy with subsequent child amygdala volume and affect. The results underscore the importance of the intrauterine environment and suggest the origins of neuropsychiatric disorders may have their foundations early in life.