Intrinsic functional connectivity in late-life depression: trajectories over the course of pharmacotherapy in remitters and non-remitters

Abstract

Previous studies in late-life depression (LLD) have found that patients have altered intrinsic functional connectivity in the dorsal default mode network (DMN) and executive control network (ECN). We aimed to detect connectivity differences across a treatment trial among LLD patients as a function of remission status. LLD patients (N=37) were enrolled into a 12-week trial of venlafaxine and underwent five functional magnetic resonance imaging resting state scans during treatment. Patients had no history of drug abuse, psychosis, dementia/neurodegenerative diseases or medical conditions with known effects on mood. We investigated whether there were differences in three networks: DMN, ECN and anterior salience network connectivity, as well as a whole brain centrality measure (eigenvector centrality). We found that remitters showed increases in ECN connectivity in the right precentral gyrus and decreases in DMN connectivity in the right inferior frontal gyrus and supramarginal gyrus. The ECN and DMN had regions (middle temporal gyrus and bilateral middle/inferior temporal/fusiform gyrus, respectively) that showed reversed effects (decreased ECN and increased DMN, respectively). Early changes in functional connectivity can occur after initial medication exposure. This study offers new data, indicating that functional connectivity changes differ depending on treatment response and can occur shortly after exposure to antidepressant medication.

Figure 1

The study design protocol. Functional and structural magnetic resonance imaging (fMRI and sMRI, respectively) was performed throughout the treatment period. All scanning was done in the morning. On day 1, participants came in for an fMRI scan (Baseline) and then were given a placebo following the scan. On day 2 (~12 h after placebo), they returned for another fMRI scan (Placebo) and then were started on venlafaxine following the scan. They returned the next day (~12 h later) for another fMRI scan (Day 1, that is, day 1 of treatment). They continued on their medication as normal and came in for scans on week 1 (Week 1) and at the end of the trial (End).

Figure 2

Connectivity changes where the interaction (group × time) was significant. (a) ECN connectivity changes that were significant. (b) DMN connectivity changes that were significant. For a and b, non-remitters are shown in red color and remitters are shown in blue color. The color bar indicates the value of the F-statistic. Error bars represent the 99% CIs. (c) Change score analysis results. Different regions are shown as different colors. The values represent mean and 99% CIs for the parameter estimate that tested whether there was a significant difference between remitters/non-remitters in the change scores (placebo/day 1/week 1/end−baseline). Dotted line represents β-estimate of zero. DMN, default mode network; ECN, executive control network.

Figure 3

Analyses where the interaction (group × time) was not significant, but where the group effect alone (not the time effect) was significant. (a) Regions where the ASN connectivity differed between remitters (blue) and non-remitters (red). (b) Regions where the EVC measure differed between groups. The color bar indicates the value of the F-statistic. Error bars represent the 99% CIs. ASN, anterior salience network; EVC, eigenvector centrality.