Longitudinal Evidence for Smaller Hippocampus Volume as a Vulnerability Factor for Perceived Stress

Abstract

Hippocampal volume has been found to be smaller in individuals with stress-related disorders, but it remains unclear whether smaller volume is a consequence of stress or rather a vulnerability factor. Here, we examined this issue by relating stress levels to hippocampal volumes in healthy participants examined every 5 years in a longitudinal population-based study. Based on scores of 25- to 60-year–old participants on the perceived stress questionnaire, we defined moderately to high (n = 35) and low (n = 76) stress groups. The groupswere re-examined after 5 years (at the 6th studywave). Historical data on subjective stresswere available up to 10 years prior toWave 5. At the first MRI session, the moderately to high stress group had a significantly smaller hippocampal volume, as measured by FreeSurfer (version 5.3), compared with the low-stress group. At follow-up, group differences in stress levels and hippocampal volume remained unchanged. In retrospective analyses of subjective stress, the observed group difference in stress was found to be stable. The long-term stability of group differences in perceived stress and hippocampal volume suggests that a small hippocampal volume may be a vulnerability factor for stress-related disorders.