Assessing the Impact of Typical Variations in Stressful Life Events on Hippocampal Development in Childhood

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2021

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Abstract

The negative impact of extreme stress on early brain development is well-documented. An emerging body of work suggests that less extreme and more typical variations in stressful experiences (e.g., parental divorce, changing schools) may also exert an impact on the brain, especially in early childhood; however, more systematic research is needed. Across, three studies, this dissertation addressed this gap by exploring effects of typical variations in stressful life events on development of the hippocampus, a brain region highly susceptible to stress. Study 1a assessed the impact of stressful life events on the development of hippocampal subfield volumes (i.e., CA1, CA2-4/dentate gyrus (DG), subiculum) in an accelerated longitudinal sample of 102 4- or 6-year-old children who were each followed for 3 years. Analyses revealed that experiencing more stressful life events was related to smaller CA1 and CA2-4/DG volumes in the 6- (but not 4-) year-old cohort. Study 1b used the same sample described in Study 1a to investigate the impact of stressful life events on functional connectivity between the hippocampus and stress-related cortical regions. Analyses revealed a significant association in the 4- (but not 6-) year-old cohort, such that experiencing more stressful life events was related to greater connectivity between the hippocampus and the insula, a region important for emotional processing. Study 2 assessed moderating effects of sex and socioeconomic status (SES) on the association between stressful events and hippocampal subfield volumes using a large (n = 4,348), diverse subsample of 9-10-year-old adolescents from the Adolescent Brain and Cognitive Development Study. Analyses revealed that stressful life events were related to smaller subiculum volumes, but these associations did not vary by sex or SES. Overall, these findings provide evidence of the impact of typical variations in stressful life events on both hippocampal structure and functional connectivity. Findings also highlight the complexity of stress effects on the brain as these experiences may impact the hippocampus in an age-dependent manner. These results advance our current understanding of how stress influences hippocampal development and pave the way for studies to assess the implications of findings both for cognitive processes and the development of stress-related disorders.

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