The Effect of Early Life Stress on Memory is Mediated by Anterior Hippocampal Network

The experience of early life stress (ELS) is a risk factor for memory dysfunction, but the impact at the neural level is less clear. The aim of this study is to investigate whether healthy people with a higher ELS display more structural and functional changes of hippocampus than people with a lower ELS, and to investigate whether hippocampus changes in turn affects memory. The Childhood Trauma Questionnaire (CTQ) was used to assess ELS in 100 young health participants. They were divided into two groups: "low" CTQ group (limitation of none/minimal ELS) and "high" CTQ group (low to moderate ELS). Verbal memory was assessed by California Verbal Learning Test II and visual memory by Rey-Osterrieth Complex Figure. Resting state fMRI data were acquired and voxel-wise correlation analysis was performed to functionally divide the hippocampus. Gray matter volumes and memory circuits of the anterior and posterior hippocampus were analyzed. We also tested whether changes in hippocampus mediated the relationship between ELS and memory. Compared with participants with a lower ELS, healthy participants with a relatively higher ELS had reduced anterior hippocampal functional connectivity, which positively correlated with visual memory. Among all participants, anterior hippocampal functional connectivity mediated the relationship of ELS on visual memory. These findings suggest that ELS decreased anterior hippocampal-cortical functional connectivity, which, in turn, drives memory decline and highlight a potential pathway in which ELS affects memory by degrading anterior hippocampal functional connectivity changes directly.