Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: an FMRI study

Abstract

It has been hypothesized that one of the effects of antidepressants is to increase functional connectivity between the cortical mood-regulating and the limbic mood-generating regions. One consequence of this antidepressant effect is thought to be decreased limbic activation in response to negative emotional stimuli. Twelve unmedicated unipolar depressed patients and 11 closely matched healthy comparison subjects completed two magnetic resonance imaging (MRI) scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each MRI session, subjects completed a resting state functional connectivity scan and a conventional block-design negative vs. neutral pictures regional brain activation scan. After 6 weeks of sertraline treatment resting state, functional connectivity between the ACC and limbic regions increased while limbic activation in response to negative versus neutral pictures decreased. The results of this study are consistent with the hypothesis that antidepressant treatment has reciprocal effects on corticolimbic functional connectivity and limbic activation in response to emotional stimuli.

FIGURE 1. Region of Interest Placement for Sampling of Low Frequency BOLD Fluctuations for Corticolimbic Connectivity Analysis

FIGURE 2. Depressed Patients Before and After Treatment

Relationship between changes in corticolimbic activation and connectivity before and after six weeks sertraline treatment in depressed patients

FIGURE 3. Healthy Comparison Subjects at Baseline and Repeat Scan

Relationship between changes in activation and connectivity at baseline and repeat scan in healthy comparison subjects

FIGURE 4. Simple Regression Plot Between Change in ACC-Left Pallidostriatal Connectivity and Left Pallidostriatal Activation

After 6 weeks of treatment with sertraline in depressed patients (p < 0.003), increased connectivity was associated with greater decrease in left striatum activation in response to negative vs. neutral pictures.