Partial Amelioration of Medial Visceromotor Network Dysfunction in Major Depression by Sertraline

Objectives Major depression is associated with reduced cardiac vagal control, most commonly indexed by heart rate variability. To examine the dynamics of this abnormality, we examined within-participant covariation over time between brain activity, cardiac vagal control, and depressive symptoms in depressed patients treated with sertraline and in healthy volunteers. Methods Patients with depression and nondepressed control participants were enrolled in a 12-week protocol. After Week 0 assessment, patients began treatment with sertraline. Neural activity and vagal control were measured for all participants at Weeks 0, 2, 6, and 12 using functional magnetic resonance imaging and synchronized electrocardiographic recordings. At each of the four assessments, a moving window analysis was used to estimate vagal control as assessed by respiratory sinus arrhythmia (RSA) from the electrocardiographic data, which was then regressed onto functional magnetic resonance imaging activity. Results At baseline, patients showed reduced blood oxygen level-dependent RSA covariation compared with controls within multiple a priori brain regions associated with vagal control, collectively described as the medial visceromotor network (MVN). Sertraline treatment led to a significant increase in brain-RSA covariation for patients compared with controls, despite a lack of improvement in mean RSA. Conclusions These data suggest a partial normalization of MVN dysfunction in depression during sertraline treatment. Specifically, results indicate a partial recovery of MVN function. However, this recovery was insufficient to cause a significant change in RSA levels. These results may help to explain both improvements with and limitations of sertraline treatment of depression.