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Cited by 124Suicide and Self-Harm StudiesNeural and Behavioral Psychology StudiesBipolar Disorder and Treatment

Prefrontal cortex markers of suicidal vulnerability in mood disorders: a model-based structural neuroimaging study with a translational perspective

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Ding, Y, Lawrence, N, Olié, E, Cyprien, F, le Bars, E, Bonafé, A, Phillips, M L, Courtet, P +1 more·2015·Translational Psychiatry
DOI 10.1038/tp.2015.1PMC PMC4445751
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Abstract

The vulnerability to suicidal behavior has been modeled in deficits in both valuation and cognitive control processes, mediated by ventral and dorsal prefrontal cortices. To uncover potential markers of suicidality based on this model, we measured several brain morphometric parameters using 1.5T magnetic resonance imaging in a large sample and in a specifically designed study. We then tested their classificatory properties. Three groups were compared: euthymic suicide attempters with a past history of mood disorders and suicidal behavior (N=67); patient controls with a past history of mood disorders but not suicidal behavior (N=82); healthy controls without any history of mental disorder (N=82). A hypothesis-driven region-of-interest approach was applied targeting the orbitofrontal cortex (OFC), ventrolateral (VLPFC), dorsal (DPFC) and medial (including anterior cingulate cortex; MPFC) prefrontal cortices. Both voxel-based (SPM8) and surface-based morphometry (Freesurfer) analyses were used to comprehensively evaluate cortical gray matter measure, volume, surface area and thickness. Reduced left VLPFC volume in attempters vs both patient groups was found (P=0.001, surviving multiple comparison correction, Cohen's d=0.65 95% (0.33-0.99) between attempters and healthy controls). In addition, reduced measures in OFC and DPFC, but not MPFC, were found with moderate effect sizes in suicide attempters vs healthy controls (Cohen's d between 0.34 and 0.52). Several of these measures were correlated with suicidal variables. When added to mood disorder history, left VLPFC volume increased within-sample specificity in identifying attempters in a significant but limited way. Our study, therefore, confirms structural prefrontal alterations in individuals with histories of suicide attempts. A future clinical application of these markers will, however, necessitate further research.

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Crossref · 10.1038/tp.2015.1

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  • Individuals without a history of mTBI who attempted suicide or have a history of SI also show diminished VMPFC volume and reduced connectivity between the prefrontal cortex and the limbic system.

    “Interestingly, individuals without a history of mTBI who attempted suicide or have a history of SI also show diminished VMPFC volume and reduced connectivity between the prefrontal cortex and the limbic system, further supporting it as a potential therapeutic target [31,81].”

    From Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial (2024) · cites this paper as [31]

    The Methods define the ventromedial prefrontal cortex as part of the MPFC region studied. The Discussion reports structural impairments in suicide attempters in the VLPFC, DPFC and OFC, but not MPFC—contrary to the claimed VMPFC reduction. This structural imaging study does not establish reduced prefrontal–limbic connectivity or the claim about people with suicidal ideation or no mTBI history. (LLM, conf=0.88)

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  • Diminished VMPFC-limbic connectivity is suspected to be responsible for impulsivity and SI in individuals with mTBI.

    “This diminished connectivity is suspected to be responsible for impulsivity and SI in individuals with mTBI [30-32].”

    From Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial (2024) · cites this paper as [31]

    The Discussion links dysfunction of an interconnected prefrontal network to suicidal ideas, and the Results report correlations between prefrontal structural measures and impulsiveness in patients with mood disorders. The paper does not establish diminished VMPFC–limbic connectivity as the cause of impulsivity or suicidal ideation, and it does not study individuals with mTBI. Page numbers were not available in our copy. (LLM, conf=0.78)

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  • The VMPFC serves as an inhibitory control center for the limbic system.

    “The VMPFC, which serves as an inhibitory control center for the limbic system, is particularly vulnerable to damage in all severities of TBI as this region abuts the cranial floor and frontal cranial bone, making it susceptible to coup and contrecoup forces from nearly all directions [31,44,45].”

    From Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial (2024) · cites this paper as [31]

    The Introduction links prefrontal regions, including the ACC, to cognitive control and emotion regulation; the Methods define the paper’s medial prefrontal region as including the ACC. But neither passage says the VMPFC inhibits the limbic system or serves as its inhibitory control center. Page numbers are unavailable in our copy. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

  • The VMPFC is particularly vulnerable to damage in all severities of TBI because it abuts the cranial floor and frontal cranial bone, making it susceptible to coup and contrecoup forces from nearly all directions.

    “The VMPFC, which serves as an inhibitory control center for the limbic system, is particularly vulnerable to damage in all severities of TBI as this region abuts the cranial floor and frontal cranial bone, making it susceptible to coup and contrecoup forces from nearly all directions [31,44,45].”

    From Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial (2024) · cites this paper as [31]

    The Materials and methods (MRI analyses; page unavailable) identify the ventromedial prefrontal cortex as a region of interest, but the paper studies suicidal vulnerability in mood disorders, not traumatic brain injury. Searches for TBI, cranial-floor anatomy, and coup–contrecoup forces found no passage supporting the claimed vulnerability across TBI severities. (LLM, conf=0.73)

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  1. Hawton K van Heeringen K Suicide Lancet 2009 373 1372 1381 19376453

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Authors
Ding, Y., Lawrence, N., Olié, E., Cyprien, F., le Bars, E., Bonafé, A., Phillips, M. L., Courtet, P., & Jollant, F.
Affiliations
  • Douglas Mental Health University Institute (CA)
  • University of Exeter (GB)
  • Inserm (FR)
  • Centre Hospitalier Universitaire de Montpellier (FR)
  • University of Pittsburgh (US)
Corresponding author
Jollant, F
ORCID
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2015-02-24
Volume
5
Issue
2
Pages
e516-e516
ISSN
2158-3188 (ISSN-L)
DOI
10.1038/tp.2015.1
PMC
PMC4445751
OpenAlex
W2029442436
Cited by
124
References
52
Citations by year
2026: 7 · 2025: 9 · 2024: 9 · 2023: 9 · 2022: 9 · 2021: 12 · 2020: 19 · 2019: 14 · 2018: 16 · 2017: 7 · 2016: 9 · 2015: 4
FWCI
14.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by-nc-sa)
  • eScholarship@McGill (McGill) (submittedVersion, cc-by-nc-sa)
  • Figshare (submittedVersion)
  • Open Research Exeter (University of Exeter) (submittedVersion, cc-by-nc-sa)
Funders
  • American Foundation for Suicide Prevention
  • Royal Society
  • Fondation pour la Recherche Médicale
  • Académie Nationale de Médecine
  • Servier
  • Institut Servier
  • Fonds de Recherche du Québec - Santé
Topics
  • Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Keywords
suicidal behavior, suicide attempts, mood disorders, prefrontal cortex, ventrolateral prefrontal cortex, orbitofrontal cortex, dorsal prefrontal cortex, medial prefrontal cortex, gray matter volume, brain morphometry, cognitive control
MeSH terms
Adult, Brain Mapping, Female, Humans, Image Processing, Computer-Assisted, London, Magnetic Resonance Imaging, Male, Suicide, Suicide, Attempted, Prefrontal Cortex, Mood Disorders, Suicidal Ideation, Neuroimaging

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