Large-scale network dysfunction in Major Depressive Disorder: Meta-analysis of resting-state functional connectivity

By R. Kaiser, Jessica R. Andrews-Hanna, Tor D. Wager, Diego A. Pizzagalli. JAMA psychiatry, 2015

2,074 citations recorded by the source corpus.

IMPORTANCE Major depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks, as reflected by abnormal resting-state functional connectivity (rsFC). However, given variable methods and results across studies, identifying consistent patterns of network dysfunction in MDD has been elusive. OBJECTIVE To investigate network dysfunction in MDD through the first meta-analysis of rsFC studies. DATA SOURCES Seed-based voxel-wise rsFC studies comparing MDD with healthy individuals (published before June 30, 2014) were retrieved from electronic databases (PubMed, Web-of-Science, EMBASE), and authors contacted for additional data. STUDY SELECTION Twenty-seven datasets from 25 publications (556 MDD adults/teens; 518 controls) were included in the meta-analysis. DATA EXTRACTION AND SYNTHESIS Coordinates of seed regions-of-interest and between-group effects were extracted. Seeds were categorized into “seed-networks” by their location within a priori functional networks. Multilevel kernel density analysis of between-group effects identified brain systems in which MDD was associated with hyperconnectivity (increased positive, or reduced negative, connectivity) or hypoconnectivity (increased negative, or reduced positive, connectivity) with each seed-network. RESULTS MDD was characterized by hypoconnectivity within the frontoparietal network (FN), a set of regions involved in cognitive control of attention and emotion regulation, and hypoconnectivity between frontoparietal systems and parietal regions of the dorsal attention network (DAN) involved in attending to the external environment. MDD was also associated with hyperconnectivity within the default network (DN), a network believed to support internally-oriented and self-referential thought, and hyperconnectivity between FN control systems and regions of DN. Finally, MDD groups exhibited hypoconnectivity between neural systems involved in processing emotion or salience and midline cortical regions that may mediate top-down regulation of such functions. CONCLUSIONS AND RELEVANCE Reduced connectivity within frontoparietal control systems, and imbalanced connectivity between control systems and networks involved in internal- or external-attention, may reflect depressive biases towards internal thoughts at the cost of engaging with the external world. Meanwhile, altered connectivity between neural systems involved in cognitive control and those that support salience or emotion processing may relate to deficits regulating mood. These findings provide an empirical foundation for a neurocognitive model in which network dysfunction underlies core cognitive and affective abnormalities in depression.

Subfields: Cognitive Neuroscience, Experimental and Cognitive Psychology

View Paper: https://www.semanticscholar.org/paper/5c6f2becfb309e5b1323857bddc2c8fbc0c0ace5

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Citations in the corpus

• Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024, methodology): “267,268 Furthermore, resting-state functional magnetic resonance imaging (R-fMRI) is an emerging neuroimaging technique used to study functional connectivity in the brain and holds great potential in aiding clinical diagnosis.”
• Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments (2019, background): “Studies demonstrate an increase in the activity of the DMN in depressed patients and decreases in SAL and CEN, consistent with increased rumination and introspection and decreased association with external inputs in depressed patients (Evans et al., 2018; Greicius et al., 2007; Kaiser et al., 2015).”
• Influences on the Test–Retest Reliability of Functional Connectivity MRI and its Relationship with Behavioral Utility (2017, background): “2009; Whitfield-Gabrieli and Ford 2012; Raichle 2015), and altered connectivity in these networks has been linked to a variety of neuropsychiatric disorders (Uddin and Menon 2009; Öngür et al. 2010; Whitfield-Gabrieli and Ford 2012; Baker et al. 2014; Di Martino et al. 2014; Northoff 2014; Abbott et”