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. 2019 Apr 30;116(18):9078-9083.
doi: 10.1073/pnas.1900390116. Epub 2019 Apr 12.

Reduced Default Mode Network Functional Connectivity in Patients With Recurrent Major Depressive Disorder

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Free PMC article

Reduced Default Mode Network Functional Connectivity in Patients With Recurrent Major Depressive Disorder

Chao-Gan Yan et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

Keywords: REST-meta-MDD; default mode network; functional connectivity; major depressive disorder; resting-state fMRI.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
REST-meta-MDD sample characteristics. (A) Total number of participants per group for each contributing site. The MDD patients were subdivided into FEDN, recurrent, and others/unknown types. (B) Number of male subjects and female subjects for each site. (C) Age (in years) for all individuals per site for the MDD group and NC group. The two horizontal lines represent ages 18 and 65 y, the age limits for participants chosen for imaging analysis. (D) The score of HAMD for MDD patients, when available.
Fig. 2.
Fig. 2.
Decreased DMN FC in MDD patients. Mean DMN within-network FC was averaged across 33*32/2 = 528 connections as shown in A. The violin figures show the distribution of mean DMN within-network FC contrasting: MDD and NC groups (B); first episode drug naïve (FEDN) MDD and NC groups (C); recurrent MDD and NC groups (D); and FEDN MDD and recurrent MDD groups (E). Of note, for each comparison, only sites with sample size larger than 10 in each group were included. The t values were the statistics for these comparisons in LMM analyses. Please see SI Appendix, Fig. S3 for the forest plots of effect size per site generated by a metamodel in reproducibility analyses. **P < 0.01; ***P < 0.001.
Fig. 3.
Fig. 3.
The effects of illness duration and medication status on decreased DMN FC in MDD patients. The violin figures show the distribution of mean DMN within-network FC for FEDN MDD patients with long vs. short illness duration (A), for all MDD patients with long vs. short illness duration (B), and for first-episode MDD patients with vs. without medication usage (C). The t values are the statistics for these comparisons in LMM analyses. Please see SI Appendix, Fig. S4 for the forest plots of effect size per site generated by a metamodel in reproducibility analyses. **P < 0.01.
Fig. 4.
Fig. 4.
Exploratory analyses of FC within and between the seven brain networks delineated by Yeo et al. (15): (A) all MDDs vs. NCs; (B) FEDN MDDs vs. NCs; (C) recurrent MDDs vs. NCs; (D) recurrent MDDs vs. FEDN MDDs; and (E) MDDs on medication vs. FEDN MDDs. FDR correction was performed among 7 within-network and 21 between-network connections for the whole-group analysis (comparing all 848 MDDs with 794 NCs). For subgroup analyses, FDR corrected for the six abnormal connections found in the whole-group analysis. Subcortical, subcortical ROIs.

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