Baseline Functional Connectivity in Resting State Networks Associated with Depression and Remission Status after 16 Weeks of Pharmacotherapy: A CAN-BIND Report

Abstract

Understanding the neural underpinnings of major depressive disorder (MDD) and its treatment could improve treatment outcomes. So far, findings are variable and large sample replications scarce. We aimed to replicate and extend altered functional connectivity associated with MDD and pharmacotherapy outcomes in a large, multisite sample. Resting-state fMRI data were collected from 129 patients and 99 controls through the Canadian Biomarker Integration Network in Depression. Symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). Connectivity was measured as correlations between four seeds (anterior and posterior cingulate cortex, insula and dorsolateral prefrontal cortex) and all other brain voxels. Partial least squares was used to compare connectivity prior to treatment between patients and controls, and between patients reaching remission (MADRS ≤ 10) early (within 8 weeks), late (within 16 weeks), or not at all. We replicated previous findings of altered connectivity in patients. In addition, baseline connectivity of the anterior/posterior cingulate and insula seeds differentiated patients with different treatment outcomes. The stability of these differences was established in the largest single-site subsample. Our replication and extension of altered connectivity highlighted previously reported and new differences between patients and controls, and revealed features that might predict remission prior to pharmacotherapy. Trial registration:ClinicalTrials.gov: NCT01655706.

Keywords: fMRI; functional connectivity; major depressive disorder; resting state networks.