Subgenual Cingulate–Amygdala Functional Disconnection and Vulnerability to Melancholic Depression
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Abstract
The syndromic heterogeneity of major depressive disorder (MDD) hinders understanding of the etiology of predisposing vulnerability traits and underscores the importance of identifying neurobiologically valid phenotypes. Distinctive fMRI biomarkers of vulnerability to MDD subtypes are currently lacking. This study investigated whether remitted melancholic MDD patients, who are at an elevated lifetime risk for depressive episodes, demonstrate distinctive patterns of resting-state connectivity with the subgenual cingulate cortex (SCC), known to be of core pathophysiological importance for severe and familial forms of MDD. We hypothesized that patterns of disrupted SCC connectivity would be a distinguishing feature of melancholia. A total of 63 medication-free remitted MDD (rMDD) patients (33 melancholic and 30 nonmelancholic) and 39 never-depressed healthy controls (HC) underwent resting-state fMRI scanning. SCC connectivity was investigated with closely connected bilateral a priori regions of interest (ROIs) relevant to MDD (anterior temporal, ventromedial prefrontal, dorsomedial prefrontal cortices, amygdala, hippocampus, septal region, and hypothalamus). Decreased (less positive) SCC connectivity with the right parahippocampal gyrus and left amygdala distinguished melancholic rMDD patients from the nonmelancholic rMDD and HC groups (cluster-based familywise error-corrected p⩽0.007 over individual a priori ROIs corresponding to approximate Bonferroni-corrected p⩽0.05 across all seven a priori ROIs). No areas demonstrating increased (more positive) connectivity were observed. Abnormally decreased connectivity of the SCC with the amygdala and parahippocampal gyrus distinguished melancholic from nonmelancholic rMDD. These results provide the first resting-state neural signature distinctive of melancholic rMDD and may reflect a subtype-specific primary vulnerability factor given a lack of association with the number of previous episodes.
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“(2012) and was chosen for its close proximity to subgenual regions implicated in vulnerability to MDD (Green et al. 2012; Herringa et al. 2013; Workman et al. 2016).”
BackgroundMethodResultInfluentialSelf-citation
- Authors
- Workman, C. I., Lythe, K. E., McKie, S., Moll, J., Gethin, J. A., Deakin, J. F., Elliott, R., & Zahn, R.
- Affiliations
- Manchester Academic Health Science Centre (GB)
- D’Or Institute for Research and Education (BR)
- King's College London (GB)
- Corresponding author
- Zahn, Roland
- Venue
- Neuropsychopharmacology
- Published
- 2016-01-19
- Volume
- 41
- Issue
- 8
- Pages
- 2082-2090
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4820084
- OpenAlex
- W2257928093
- Cited by
- 26
- References
- 49
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 7 · 2017: 1 · 2016: 2
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Research Explorer (The University of Manchester) (publishedVersion)
- PsyArXiv (OSF Preprints) (submittedVersion, cc-by)
- PsyArXiv (OSF Preprints) (submittedVersion)
- Funders
- Medical Research Council (G0902304)
- Engineering and Physical Sciences Research Council
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- endogenous depression, major depressive disorder, subgenual anterior cingulate cortex, amygdala, resting-state functional connectivity, parahippocampal gyrus, depression vulnerability, remitted depression, depression subtypes, neural markers
- MeSH terms
- Adult, Amygdala, Brain, Brain Mapping, Depressive Disorder, Major, Major Depressive Disorder, Depressive Disorder, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Neural Pathways
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