Resting state functional connectivity and treatment response in late-life depression

Abstract

Indices of functional connectivity in the default mode network (DMN) are promising neural markers of treatment response in late-life depression. We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults. Forty-seven depressed older adults underwent MRI scanning pre- and post-pharmacotherapy. Forty-six never depressed older adults underwent MR scanning as comparison subjects. Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment. We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest. The resulting correlation maps were employed to investigate between-group differences. Additionally we examined the association between white matter hyperintensity burden and functional connectivity results. Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal precentral gyrus. Relative to treatment-responsive participants, treatment-resistant participants had increased functional connectivity in the left striatum. When adjusting for white matter hyperintensity burden, the observed differences lost significance for the PCC-prefrontal functional connectivity, but not for the PCC-striatum functional connectivity. The post-treatment "frontalization" of the DMN connectivity suggests a normalizing effect of antidepressant treatment. Moreover, our study confirms the central role of white matter lesions in disrupting brain functional connectivity.

Trial registration: ClinicalTrials.gov NCT00177294 NCT00177671 NCT00696292.

Keywords: Default Mode Network; Late-life depression; MRI; Treatment response; White matter hyperintensity.

Fig 1

Flowchart of the participants in the study.

Fig 2

Group analysis at baseline between non-depressed elderly [N=46] and depressed elderly participants [N=47] Red: Non-depressed elderly participants > Depressed elderly participants (middle frontal cortex). Blue: Depressed elderly participants > Non-depressed elderly participants (precuneus).

Fig 3

Group analysis of resting state functional connectivity between elderly depressed participants before [N=47] and after treatment [N=21]. Legend. Red: Pre-treatment>Post treatment contrast (precuneus, insula, hippocampus). Blue: Post-treatment>Pre-treatment contrast (medial frontal gyrus, dorsal Anterior Cingulate Cortex = ACC). Color bars list the range of t-values.

Fig 4

Treatment effect analysis using the baseline scan (T1) as outcome variable. Legend. In red: Responders (N=10)>Non-responders (N=11)[medial prefrontal cortex, precuneus]. In blue: Non-responders (N=11) > Responders (N=10)[cuneus, dorsal ACC]

Fig 5

Treatment effect analysis using the difference between the 12-week scan and the baseline scan (T2-T1) as outcome variable. Non-responders [N=11] > Responders [N=10] [left striatum].