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

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.

Fig. 1.

Box plots show maternal cortisol concentrations at 15 wk gestation and children’s right amygdala volumes at 7 y of age. For illustrative purposes, right amygdala volumes are depicted based on quartiles of mothers’ cortisol concentrations (lowest and highest cortisol concentration for each of the four cortisol categories are provided). (A) In girls (n = 35), higher maternal cortisol concentrations at 15 wk gestation were associated with larger right amygdala volumes. (B) In boys (n = 30), there was no association between maternal cortisol concentrations at 15 wk gestation and right amygdala volumes.

Fig. 2.

Box plots show maternal cortisol concentrations at 15 wk gestation and children’s scores on the affective problem scale of the CBCL at 7 y of age. For illustrative purposes, right amygdala volumes are depicted based on median of mothers’ cortisol concentrations (lowest and highest cortisol concentration for each of the two cortisol categories are provided). (A) In girls (n = 35), higher maternal cortisol concentrations at 15 wk gestation were associated with more affective problems. (B) In boys (n = 30), there was no association between maternal cortisol concentrations at 15 wk gestation and affective problems.

Fig. P1.

Maternal cortisol concentrations over the course of gestation and the child’s right amygdala volumes. To illustrate the time-specific association between maternal cortisol concentrations and the child’s right amygdala volumes, maternal cortisol concentrations (mean ± SEM) over the course of gestation are depicted for women whose children at 7 y of age have small amygdala volumes (among the smallest 33% in the present sample) and for those women whose children have large amygdala volumes (among the largest 33% in the present sample). (A) In girls (n = 35) with a larger right amygdala volume, mothers had higher cortisol concentrations at 15 wk gestation, but not later in gestation. (B) In boys (n = 30), there was no association between maternal cortisol concentrations and right amygdala volumes at any time point during gestation.