Altered resting-state functional connectome in major depressive disorder: a mega-analysis from the PsyMRI consortium

Abstract

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers ( www.psymri.com ). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8 ± 11.9 y.o.; females: 60.7%) and 476 healthy participants (age: 33.3 ± 11.0 y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN.

Fig. 1. Group differences in FCs between 400 nodes of the seven cortical networks.

In this figure each color in the circle represents a network. The blue lines show lower FC in patients with MDD compared to HCs and the red lines show greater FC in patients with MDD compared to HCs. The FC differences between patients with MDD and healthy controls as estimated mean differences regarding 400 nodes (79,800 FC) were obtained from linear mixed effect model (LMER) with age, gender, mean framewise displacement as fixed variable and site as random variable. The false discovery rate (FDR) was used to correct for multiple comparisons (p-value < 0.05).

Fig. 2. Bar-plots of the averaged FCs for different level of depression severity within SMN and of SMN segregation.

The means reported in these bar-plots are adjusted for age, gender, mean framewise displacement and site according to the linear mixed model and the reported p-values are significant after Bonferroni correction for multiple comparisons (p < 0.05). a The averaged FCs within somatosensory network (SMN) for patients’ groups defined according to depression severity and healthy participants. b The averaged SMN segregation for patients’ groups defined according to depression severity and healthy participants.