Chronic stress modulates the relationship between acute stress-related cortical-limbic circuit functional connectivity and depression symptoms

Abstract

<h3>Background</h3><p>Chronic stress impacts brain function and emotion regulation, increasing depression risk. How chronic stress shapes neural dynamics in response to acute stress remains unclear. This study investigates how chronic stress influences neural responses after acute stress, focusing on ventromedial prefrontal cortex (vmPFC)-amygdala and vmPFC-hippocampus functional connectivity (FC) and their relationship to depression symptoms.</p><h3>Methods</h3><p>Eighty-seven adults underwent resting-state fMRI at baseline, during acute stress, and during recovery. Participants were divided into High and Low chronic stress groups based on perceived stress over the past 4 weeks. Depression symptoms were measured with the Symptom Checklist-90. Linear mixed-effect model and repeated-measures ANOVA were used to analyse neural dynamics and interaction effects. Recovery-related changes in FC were calculated as differences between acute stress and recovery.</p><h3>Results</h3><p>Distinct neural dynamics patterns across stress phases emerged between groups. The Low group showed significant decreases in vmPFC-amygdala and vmPFC-hippocampus connectivity from acute stress to recovery, while the High group exhibited no changes. Chronic stress moderated the association between the recovery-related changes in vmPFC-amygdala connectivity and depression symptoms. In the High chronic stress group, greater decreases in FC from stress to recovery were associated with higher depression symptoms.</p><h3>Conclusions</h3><p>Chronic stress modulates neural dynamics during acute stress response and recovery, and their association with depression symptoms. Individuals with higher chronic stress exhibit blunted cortical-limbic circuit dynamics, potentially increasing depression vulnerability. Rapid disengagement of emotion regulation circuits may represent a maladaptive response supporting the allostatic load model. These findings clarify stress, brain, and depression relationships.</p>