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Distinct Regions of Prefrontal Cortex Mediate Resistance and Vulnerability to Depression
Open accessAbstract
The neuroanatomical correlates of depression remain unclear. Functional imaging data have associated depression with abnormal patterns of activity in prefrontal cortex (PFC), including the ventromedial (vmPFC) and dorsolateral (dlPFC) sectors. If vmPFC and dlPFC are critical neural substrates for the pathogenesis of depression, then damage to either area should affect the expression of depressive symptoms. Using patients with brain lesions we show that, relative to nonfrontal lesions, bilateral vmPFC lesions are associated with markedly low levels of depression, whereas bilateral dorsal PFC lesions (involving dorsomedial and dorsolateral areas in both hemispheres) are associated with substantially higher levels of depression. These findings demonstrate that vmPFC and dorsal PFC are critically and causally involved in depression, although with very different roles: vmPFC damage confers resistance to depression, whereas dorsal PFC damage confers vulnerability.
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“damage to VMPFC is associated with low levels of depression, and damage to DLPFC is associated with high levels of depression 206.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [206]
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“damage to VMPFC is associated with low levels of depression, and damage to DLPFC is associated with high levels of depression 206.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [206]
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“By virtue of its well-established capacity for regulating mood, attention, memory, and action34, 54-56”
From Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety (2014) · cites this paper as [56]
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Metadata
- Authors
- Koenigs, M., Huey, E. D., Calamia, M., Raymont, V., Tranel, D., & Grafman, J.
- Affiliations
- University of Wisconsin–Madison (US)
- National Institutes of Health (US)
- University of Iowa (US)
- Henry M. Jackson Foundation (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-11-19
- Volume
- 28
- Issue
- 47
- Pages
- 12341-12348
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2644261
- OpenAlex
- W2128478192
- Cited by
- 243
- References
- 58
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 13 · 2023: 11 · 2022: 15 · 2021: 11 · 2020: 17 · 2019: 16 · 2018: 6 · 2017: 19 · 2016: 13 · 2015: 13 · 2014: 18 · 2013: 18 · 2012: 17
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Civil War Book Review (submittedVersion)
- Funders
- National Institutes of Health (Z99 NS999999)
- National Institute on Drug Abuse (R01DA022549)
- National Institute of Neurological Disorders and Stroke (P01 NS19632, P01NS019632, NS-19632, Z01NS002792)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- depression, prefrontal cortex, ventromedial prefrontal cortex, dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, brain lesions, lesion studies, depression vulnerability
- MeSH terms
- Adult, Brain Injuries, Brain Mapping, Cognition Disorders, Depression, Female, Humans, Functional Laterality, Magnetic Resonance Imaging, Male, Middle Aged, Movement Disorders, Severity of Illness Index, Tomography, X-Ray Computed, Veterans, Prefrontal Cortex
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