Hair cortisol concentrations are associated with hippocampal subregional volumes in children

Abstract

The human hippocampus, a brain structure crucial for memory across the lifespan, is highly sensitive to adverse life events. Stress exposures during childhood have been linked to altered hippocampal structure and memory performance in adulthood. Animal studies suggest that these differences are in part driven by aberrant glucocorticoid secretion during development, with strongest effects on the CA3 region and the dentate gyrus (CA3-DG) of the hippocampus, alongside associated memory impairments. However, only few pediatric studies have examined glucocorticoid associations with hippocampal subfield volumes and their functional relevance. In 84 children (age range: 6-7 years), we assessed whether volumes of hippocampal subregions were related to cumulative glucocorticoid levels (hair cortisol), parenting stress, and performance on memory tasks known to engage the hippocampus. We found that higher hair cortisol levels were specifically related to lower CA3-DG volume. Parenting stress did not significantly correlate with hair cortisol, and there was no evidence to suggest that individual differences in hippocampal subregional volumes manifest in memory performance. Our results suggest that the CA3-DG may be the hippocampal region most closely associated with hair cortisol levels in childhood. Establishing causal pathways underlying this association and its relation to environmental stress and memory development necessitates longitudinal studies.

Figure 1

Illustration of Hippocampal Subfield Segmentations. (a) An example sagittal slice showing the extent of the hippocampal (HC) body segmentations were performed on. (b) The most anterior body slice with traces of all four regions overlaid. The four regions delineated comprised the Subiculum (Sub; with yellow color), a region including Cornu ammoni (CA) regions 1 and 2 (CA1-2; with turquoise color), a region including CA3 and the dentate gyrus (CA3-DG; with dark brown color), and the entorhinal cortex (EC; with red color). CA1-2, CA3-DG, and Subiculum were traced exclusively on HC body slices (from [D] to [F]), whereas EC was traced exclusively on (b) and 5 more slices anterior to it. (c) An additional example slice showing traces of CA1-2, CA3-DG, and Subiculum overlaid. (d) The most anterior HC body slice, defined as the first slice anterior to (e) which in turn was identified as the first slice on which the Uncus (circled) was clearly visible. (f) The most posterior slice of the HC body identified as the last slice on which the lamina quadrigemina (i.e., the inferior and superior colliculi; circled) are still clearly visible. (g) The first slice posterior to (f), where the lamina quadrigemina is not visible anymore. This slice was identified as belonging to the HC tail, and was not traced. Images created in ITK-SNAP. See the Supplemental information for more details on hippocampal subfield volume assessment.

Figure 2

Schematic illustration of the hippocampal measurement model with regressions of hair cortisol concentrations (Cortisol), and covariates (Age and Sex) on hippocampal subfield volumes. DG/CA3: dentate gyrus–CA3, Sub: Subiculum: EC: Entorhinal cortex. Observed and latent variables are represented with rectangles and circles, respectively. Significant regression paths are shown as solid lines (with arrowhead) labeled with standardized parameter estimates. Non-significant paths are shown as dashed lines (with arrowhead). Estimated variances and covariances are also shown as solid lines. Thick solid lines represent path values fixed at 1. All parameter estimates are shown separately in Table 2, for better readability of the figure.