Default mode network connectivity and treatment response in geriatric depression

Abstract

Objectives: Default mode network (DMN) connectivity is altered in depression. We evaluated the relationship between changes in within-network DMN connectivity and improvement in depression in a subsample of our parent clinical trial comparing escitalopram/memantine (ESC/MEM) to escitalopram/placebo (ESC/PBO) in older depressed adults (NCT01902004). Methods: Twenty-six participants with major depression (age > 60 years) and subjective memory complaints underwent treatment with ESC/MEM (n = 13) or ESC/PBO (n = 13), and completed baseline and 3-month follow-up resting state magnetic resonance imaging scans. Multi-block partial least squares correlation analysis was used to evaluate the impact of treatment on within-network DMN connectivity changes and their relationship with symptom improvement at 3 months (controlling for age and sex). Results: A significant latent variable was identified, reflecting within-network DMN connectivity changes correlated with symptom improvement (p =.01). Specifically, although overall group differences in within-network DMN connectivity changes failed to reach significance, increased within-network connectivity of posterior/lateral DMN regions (precuneus, angular gyrus, superior/middle temporal cortex) was more strongly and positively correlated with symptom improvement in the ESC/MEM group (r = 0.97, 95% confidence interval: 0.86–0.98) than in the ESC/PBO group (r = 0.36, 95% confidence interval: 0.13–0.72). Conclusions: Increased within-network connectivity of core DMN nodes was more strongly correlated with depressive symptom improvement with ESC/MEM than with ESC/PBO, supporting an improved engagement of brain circuitry implicated in the amelioration of depressive symptoms with combined ESC/MEM treatment in older adults with depression and subjective memory complaints.