Associations Between Experience of Typical Variations in Stressors and Hippocampal Structure and Functional Connectivity in Childhood

Abstract

Abuse and maltreatment have been associated with negative effects on the developing brain through the hypothalamic–pituitary–adrenal (HPA) axis, the body's central stress response system. Theoretically, similar pathophysiology occurs when children experience more moderate forms of stress (i.e., changing schools); however, evidence for this association is lacking. Therefore, the current study explored the effects of typical variations in stressful life events on the development of the hippocampus, a brain region susceptible to stress. Data from a 3-year accelerated longitudinal sample of 4- and 6-year-old children were used to assess the links between stressful events and the development of hippocampal subfield volumes (N_total = 90) and functional connectivity (N_total = 83). In the 4-year-old cohort, stressful experiences were related to an overall slower growth in CA1 and subiculum volume from age 5 to 6. In the 6-year-old cohort, stressful experiences were related to smaller CA2–4/DG volume at age 6 and an overall faster decrease in subiculum volume from age 6 to 7. Small effects were observed regarding the relations between stress and hippocampal functional connectivity; however, they did not survive multiple comparisons. Results from analyses comparing cohorts showed that the relations between stressful events and CA2–4/DG volume and change in subiculum volume significantly differed between the younger and older cohorts. Overall, these findings demonstrate the links between typical variations in stress and hippocampal development and highlight the region- and age-specific nature of the effects of stress. Together, this work emphasizes the importance of understanding how brain development may be influenced by stress in all forms, as stress-related alterations in hippocampal development have been linked to variations in cognitive processes (e.g., memory) and risk for psychopathology (e.g., major depressive disorder).