Brain and cardiovascular responses to acute stress in remitted and recurrent late-life depression

In individuals with remitted late-life depression (LLD), stress exposure can increase the likelihood of a new, recurrent depressive episode. Variability in the effect of stress on recurrence risk may reflect underlying brain and physiological processes mediating the stress response. We examined how subjective, physiological, and brain responses to an experimental stressor differs in older adults with and without remitted depression, and how these stress responses relate to future relapse. Participants were recruited through 3 sites and included 76 older adults with remitted LLD and 36 age-matched healthy comparison (HC) adults. Participants completed an acute stressor task during functional brain imaging with behavioral and cardiovascular monitoring. Remitted LLD participants were followed longitudinally to evaluate depression recurrence. Compared to HC, the remitted LLD group exhibited reduced stressor-evoked systolic blood pressure and heart rate responses, as well as reduced stressor-evoked posterior insula activity. This blunted stress response phenotype appeared more specific to the stable remitter group than the relapsing LLD group. Survival analyses demonstrated that greater stressor-evoked bed nucleus of the stria terminalis (BNST) activity was associated with faster time to recurrence. These findings add to a growing literature reporting so-called "blunted" stressor-evoked cardiovascular and brain reactivity in remitted depression. Moreover, they link the stress response in visceral interoceptive brain circuits with relapse vulnerability. Future work involving longer follow-up periods may reveal additional stress-related brain and behavioral predictors of recurrence in remitted LLD.