Perceived Stress Associations with Hippocampal-dependent Behavior and Hippocampal Subfield Volume

Background: Individual differences in stress appraisals influence trajectories of risk and resilience following exposure to chronic and acute stressors. Smaller hippocampal volume may contribute to elevated stress appraisals via deficient pattern separation, a process depending on dentate gyrus (DG)/CA3 hippocampal subfields. Here, we investigated links between perceived stress, DG/CA3 volume, and behavioral pattern separation to test hypothesized mechanisms underlying stress-related psychopathology.

Methods: We collected the Perceived Stress Scale (PSS) and ratings of subjective stress reactivity during the Trier Social Stress Test (TSST) from 71 adult community participants. We obtained high-resolution T2 MRI scans and used Automatic Segmentation of Hippocampal Subfields to estimate DG/CA3 volume in 56 of these participants. Participants completed the mnemonic similarity task, which provides a behavioral index of pattern separation. Analyses investigated associations between perceived stress, DG/CA3 volume, and behavioral pattern separation, controlling for age, gender, hemisphere, and intracranial volume.

Results: Greater PSS scores and TSST subjective stress reactivity were each independently related to poorer behavioral pattern separation, together accounting for 15% of variance in behavioral performance in a simultaneous regression. Contrary to hypotheses, DG/CA3 volume was not associated with either stress measure, although exploratory analyses suggested a link between hippocampal volume asymmetry and PSS scores.

Conclusions: We observed novel associations between laboratory and questionnaire measures of perceived stress and a behavioral assay of pattern separation. Additional work is needed to clarify the involvement of the hippocampus in this stress-behavior relationship and determine the relevance of behavioral pattern separation for stress-related disorders.