Resting state functional connectivity in patients with remitted psychotic depression: A multi-centre STOP-PD study

Abstract

Background: There is paucity of neurobiological knowledge about major depressive disorder with psychotic features ("psychotic depression"). This study addresses this knowledge gap by using resting state functional magnetic resonance imaging (R-fMRI) to compare functional connectivity in patients with psychotic depression and healthy controls.

Methods: We scanned patients who participated in a randomized controlled trial as well as healthy controls. All patients achieved remission from depressive and psychotic symptoms with sertraline and olanzapine. We employed Independent Component Analysis in independent samples to isolate the default mode network (DMN) and compared patients and controls.

Findings: The Toronto sample included 28 patients (mean [SD], age 56·2 [13·7]) and 39 controls (age 55·1 [13·5]). The Replication sample included 29 patients (age 56·1 [17·7]) and 36 controls (age 48·3 [17·9]). Patients in the Toronto sample demonstrated decreased between-network functional connectivity between the DMN and bilateral insular, somatosensory/motor, and auditory cortices with peak activity in the right planum polare (t = 4·831; p = 0·001, Family Wise Error (FWE) corrected). A similar pattern of between-network functional connectivity was present in our Replication sample with peak activity in the right precentral gyrus (t = 4·144; p = 0·003, FWE corrected).

Interpretation: Remission from psychotic depression is consistently associated with an absence of increased DMN-related functional connectivity and presence of decreased between-network functional connectivity. Future research will evaluate this abnormal DMN-related functional connectivity as a potential biomarker for treatment trajectories.

Funding: National Institute of Mental Health.

Keywords: Biomarkers; Default mode network; Functional connectivity; Major depressive disorder; Psychosis; Remission.

Fig. 1

Main effect of group on default mode network (DMN) related functional connectivity in the Toronto and Replication samples. Dual regression was employed and DMN-related functional connectivity was examined in patients relative to healthy controls in both the Toronto and Replication samples. Relative to controls, there were no brain regions in which patients had significantly increased functional connectivity in either sample. However, patients had significantly decreased functional connectivity between the DMN and regions outside the DMN in the Toronto and Replication samples (Family Wise Error (FWE) corrected, p < 0·05).

Fig. 2

Post-hoc analyses of brain regions that overlapped in the Toronto and Replication samples. Regions of interest (ROIs) representing brain regions with the greatest amount of overlap between the Toronto and Replication samples were examined. ROIs were noted to be mainly related to the auditory (AUD), somatomotor (SMN), and default mode (DMN) networks. The mean functional connectivity within the auditory, somatomotor, and default mode networks was then calculated for each participant and included in a linear model for the Toronto and Replication samples with age, sex, years of education, and mean frame displacement as covariates. There was no significant (p < 0·05) difference between patients and controls within the DMN for the Toronto or Replication samples. However, both samples demonstrated significantly decreased within-network functional connectivity in patients for the SMN and AUD networks. In terms of between-network functional connectivity, the SMN to AUD, DMN to SMN, and DMN to AUD between-network functional connectivity was significantly decreased in patients in both the Toronto and Replication samples.