PMID- 33540370
OWN - NLM
STAT- MEDLINE
DCOM- 20210730
LR  - 20231110
IS  - 2213-1582 (Electronic)
IS  - 2213-1582 (Linking)
VI  - 30
DP  - 2021
TI  - Reduced functional connectivity of default mode network subsystems in depression: 
      Meta-analytic evidence and relationship with trait rumination.
PG  - 102570
LID - S2213-1582(21)00014-0 [pii]
LID - 10.1016/j.nicl.2021.102570 [doi]
LID - 102570
AB  - Resting-state functional connectivity changes in the default mode network (DMN) 
      of patients with major depressive disorder (MDD) have been linked to rumination. 
      The DMN is divided into three subsystems: a midline Core, a dorsal medial 
      prefrontal cortex (DMPFC) subsystem, and a medial temporal lobe (MTL) subsystem. 
      We examined resting-state functional connectivity within and between DMN 
      subsystems in MDD and its association with rumination. First, we conducted a 
      meta-analysis on a large multi-site dataset of 618 MDD and 683 controls to 
      quantify the differences in DMN subsystem functional connectivity between MDD and 
      controls. Second, we tested the association of DMN subsystem functional 
      connectivity and rumination in a sample of 115 unmedicated participants with 
      symptoms of anxiety/depression and 48 controls. In our meta-analysis, only 
      functional connectivity in the DMN Core was significantly reduced in MDD compared 
      to controls (g = -0.246, CI = [-0.417; -0.074], pFDR = 0.048). Functional 
      connectivity in the DMPFC subsystem and between the Core and DMPFC subsystems was 
      slightly reduced but not significantly (g = -0.162, CI = [-0.310; -0.013], 
      pFDR = 0.096; g = -0.249, CI = [-0.464; -0.034], pFDR = 0.084). Results were 
      heterogeneous across sites for connectivity in the Core and between Core and 
      DMPFC (I(2) = 0.348 and I(2) = 0.576 respectively). Prediction intervals 
      consistently encompassed 0. In the independent sample we collected, functional 
      connectivity within the DMN Core, DMPFC and between Core and DMPFC was not 
      reduced in MDD compared to controls (all pFDR > 0.05). Trait rumination did not 
      predict connectivity within and between DMN subsystems (all pFDR > 0.05). We 
      conclude that MDD as a diagnostic category shows slightly reduced functional 
      connectivity within the DMN Core, independent of illness duration, treatment, 
      symptoms and trait rumination. However, this effect is small, highly variable and 
      heterogeneous across samples, so that we could only detect it at the 
      meta-analytic level, with a sample size of several hundreds. Our results indicate 
      that reduced Core DMN connectivity has significant limitations as a potential 
      clinical or prognostic marker for the diagnosis of MDD and might be more relevant 
      to consider as a characteristic distinguishing a subgroup of individuals within 
      this diagnostic category.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Tozzi, Leonardo
AU  - Tozzi L
AD  - Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 
      USA.
FAU - Zhang, Xue
AU  - Zhang X
AD  - Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 
      USA.
FAU - Chesnut, Megan
AU  - Chesnut M
AD  - Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 
      USA.
FAU - Holt-Gosselin, Bailey
AU  - Holt-Gosselin B
AD  - Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 
      USA.
FAU - Ramirez, Carolina A
AU  - Ramirez CA
AD  - Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 
      USA.
FAU - Williams, Leanne M
AU  - Williams LM
AD  - Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 
      USA; Sierra-Pacific Mental Illness Research, Education, and Clinical Center 
      (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA. 
      Electronic address: leawilliams@stanford.edu.
LA  - eng
GR  - U01 MH109985/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, N.I.H., Extramural
DEP - 20210118
PL  - Netherlands
TA  - Neuroimage Clin
JT  - NeuroImage. Clinical
JID - 101597070
SB  - IM
MH  - Brain/diagnostic imaging
MH  - Brain Mapping
MH  - Default Mode Network
MH  - Depression
MH  - *Depressive Disorder, Major/diagnostic imaging
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Nerve Net/diagnostic imaging
MH  - Neural Pathways/diagnostic imaging
PMC - PMC7856327
OTO - NOTNLM
OT  - Default mode
OT  - Depression
OT  - Functional MRI
OT  - Meta-analysis
OT  - Resting state
OT  - Rumination
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2021/02/05 06:00
MHDA- 2021/07/31 06:00
PMCR- 2021/01/18
CRDT- 2021/02/04 20:20
PHST- 2020/10/27 00:00 [received]
PHST- 2021/01/12 00:00 [revised]
PHST- 2021/01/13 00:00 [accepted]
PHST- 2021/02/05 06:00 [pubmed]
PHST- 2021/07/31 06:00 [medline]
PHST- 2021/02/04 20:20 [entrez]
PHST- 2021/01/18 00:00 [pmc-release]
AID - S2213-1582(21)00014-0 [pii]
AID - 102570 [pii]
AID - 10.1016/j.nicl.2021.102570 [doi]
PST - ppublish
SO  - Neuroimage Clin. 2021;30:102570. doi: 10.1016/j.nicl.2021.102570. Epub 2021 Jan 
      18.