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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.

SUBMITTER: Buss C

PROVIDER: S-EPMC3356611 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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

Buss Claudia C Davis Elysia Poggi EP Shahbaba Babak B Pruessner Jens C JC Head Kevin K Sandman Curt A CA

Proceedings of the National Academy of Sciences of the United States of America 20120423 20

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 ...[more]

PMID: 22529357

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Project description:Altered hippocampal morphology and reduced volumes have been found in children born preterm compared to full-term. Stress inhibits neurogenesis in the hippocampus, and neonatal stress/noxious stimulation in rodent pups are associated with long-term alterations in hippocampal volumes. We have previously shown reduced cortical thickness and cerebellar volumes in relation to more exposure to pain-related stress of neonatal invasive procedures in children born very preterm. We have reported targeted gene-by-pain environment interactions that contribute to long-term brain development and outcomes in this population. We now aim to determine whether exposure to pain-related stress (adjusted for clinical factors and genotype) differentially impacts regional structures within the limbic system and thalamus, and investigate relationships with outcomes in very preterm children. Our study included 57 children born very preterm (<32 weeks GA) followed longitudinally from birth who underwent 3-D T1 MRI neuroimaging at ∼8 years. Hippocampal subfields and white matter tracts, thalamus and amygdala were automatically segmented using the MAGeT Brain algorithm. The relationship between those subcortical brain volumes (adjusted for total brain volume) and neonatal invasive procedures, gestational age (GA), illness severity, postnatal infection, days of mechanical ventilation, number of surgeries, morphine exposure, and genotype (COMT, SLC6A4, and BDNF) was examined using constrained principal component analysis. We found that neonatal clinical factors and genotypes accounted for 46% of the overall variance in volumes of hippocampal subregions, tracts, basal ganglia, thalamus and amygdala. After controlling for clinical risk factors and total brain volume, greater neonatal invasive procedures was associated with lower volumes in the amygdala and thalamus (p = 0.0001) and an interaction with COMT genotype predicted smaller hippocampal subregional volume (p = 0.0001). More surgeries, days of ventilation, and lower GA were also related to smaller volumes in various subcortical regions (p < 0.002). These reduced volumes were in turn differentially related to poorer cognitive, visual-motor and behavioral outcomes. Our findings highlight the complexity that interplays when examining how exposure to early-life stress may impact brain development both at the structural and functional level, and provide new insight on possible novel avenues of research to discover brain-protective treatments to improve the care of children born preterm.

Dataset Information

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

Publications

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

Similar Datasets

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