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.developmental programming | fetal origins | hypothalamus-pituitaryadrenal axis | depression | emotion regulation

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

“…In support of this notion, several neuroimaging studies have strengthened the assumption of a close connection between neural activation in core regions of emotion processing and HPA axis regulation (Root et al 2009;Taylor et al 2008;van Stegeren et al 2008). Similarly, elevated glucocorticoid levels have been associated with larger amygdala volumes (Buss et al 2012;Lupien et al 2011). Considering a heightened amygdala response and a larger volume as possible endophenotypes for stress-related disorders, the present findings are in line with previous reports suggesting an important role of the FKBP5 T allele in mood disorders (Appel et al 2011;Binder et al 2004;Lavebratt et al 2010;Lekman et al 2008;Zobel et al 2010) and PTSD (Binder et al 2008).…”

“…No study, so far, has investigated the impact of FKBP5 on amygdala volume. However this issue may be crucial, given the facts that FKBP5 is expressed in the amygdala (Scharf et al 2011) and that amygdala volume is increased following stress (Buss et al 2012;Lupien et al 2011;Tottenham et al 2010).…”

Sex as a Biological Variable: Who, What, When, Why, and How

“…In this sample, amygdala volume mediated the relationship between levels of maternal cortisol during pregnancy and affective problems during childhood (Buss et al, 2012). Similarly, intergenerational transmission of parental experience of childhood adversity has been reported for both females and males in rodents and for female parents in humans (Moog et al, 2016).…”

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…Accumulating evidence suggests that exposure to maternal stress during intrauterine life may result in an increased propensity of the offspring to develop behavioral or emotional problems (Buss et al, 2012), as well as cognitive developmental delays (Bergman et al, 2007; Buss et al, 2011; Glover, 2015). Importantly, these prenatally programmed offspring phenotypes may also influence the mothers’ reaction to the child, an aspect of the reciprocal mother-offspring relationship that is oftentimes underestimated.…”