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Cited by 126Suicide and Self-Harm StudiesStress Responses and CortisolTryptophan and brain disorders

Blunted HPA axis activity prior to suicide attempt and increased inflammation in attempters

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Melhem, Nadine M., Munroe, Sara, Marsland, Anna, Gray, Katarina, Brent, David, Porta, Giovanna, Douaihy, Antoine, Laudenslager, Mark L. +4 more·2017·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2017.01.001PMC PMC5336407
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Abstract

Background Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation is associated with increased risk for suicidal behavior. However, it is not clear whether such dysregulation exists prior to or is a consequence of attempt. Studies also show an activation of inflammatory responses in suicidal behavior but often combine attempters with those with ideation. Methods The sample consisted of psychiatric inpatients, aged 15-30 years, admitted for suicide attempt (SA, n=38), inpatients admitted for suicidal ideation with no prior history of attempts (SI, n=40), and healthy controls (n=37). We compared SA, SI, and controls on hair cortisol concentrations (HCC), which provides retrospective levels of cortisol and thus prior to the attempt in SA. We also compared them on the expression of genes in the HPA axis and inflammatory pathways previously implicated in suicidal behavior (GR or NR3C1, SKA2, FKBP5, IL-1β, TNF-α); plasma C-Reactive Protein (CRP); and cellular measures of glucocorticoid receptor (GR) sensitivity and stimulated production of IL-6. Results We found lower HCC [β=-0.55, 95% CI (-0.96, -0.13), p=0.01, ES=-0.54] in first-time SA compared to SI and controls. In addition, SA showed lower GR or NR3C1 (α isoform) mRNA [β=-5.11, 95% CI (-10.9, 0.73), p=0.09, ES=-0.46], higher CRP [β=0.94, 95% CI (-0.004, 1.9), p=0.05, ES=0.60], and higher TNF-α mRNA [β=26.4, 95% CI (7.7, 45.2), p=0.006, ES=0.73]. Conclusions This is the first study to differentiate youth who attempt suicide from those with suicidal ideation on HCC and to show that low HCC precedes suicide attempt. Suicide attempters also showed a distinct biological profile on several markers in both the HPA axis and inflammatory pathways. Future longitudinal studies are needed to examine the ability of these biomarkers to predict suicidal behavior.

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  • In adolescents and emerging adults, individuals with a history of suicide attempt had higher TNF-α and C-reactive protein than those with suicidal ideation history or healthy controls.

    “individuals with a history of suicide attempt had higher levels of TNF-α and C-reactive protein compared with those with a history of suicidal ideation and with healthy controls (Melhem et al. 2017)”

    From Adolescent Suicide as a Failure of Acute Stress-Response Systems. (2019) · cites this paper as Melhem et al. 2017

    The Discussion reports higher CRP and TNF-α mRNA in suicide attempters than in the suicidal-ideation and control groups; the Methods describe participants aged 15–30. However, the Discussion explicitly says plasma TNF-α was not measured, so the claim's unqualified reference to higher TNF-α levels overstates that finding. Page numbers are not provided in our copy. (LLM, conf=0.90)

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  • In combined samples of adults and youths, individuals with a lifetime history of suicidal behavior have had lower baseline or hair cortisol concentrations than individuals with only suicidal ideation or healthy controls.

    “individuals with a lifetime history of suicidal behavior have had lower baseline levels or hair concentrations of cortisol compared with individuals with only suicidal ideation or with healthy controls (Keilp et al. 2016, Melhem et al. 2017)”

    From Adolescent Suicide as a Failure of Acute Stress-Response Systems. (2019) · cites this paper as Melhem et al. 2017

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Research works printed but not linked: 1

  1. Yin H Galfalvy H Pantazatos SP Huang YY Rosoklija GB Dwork AJ Burke A Arango V Oquendo MA Mann JJ Glucocorticoid receptor-related genes: genotype and brain gene expression relationships to suicide and major depressive disorder. Depress Anxiety 2016 33 531 540 27030168 PMC4889464

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Authors
Melhem, N. M., Munroe, S., Marsland, A., Gray, K., Brent, D., Porta, G., Douaihy, A., Laudenslager, M. L., DePietro, F., Diler, R., Driscoll, H., & Gopalan, P.
Affiliations
  • University of Pittsburgh (US)
  • University of Pittsburgh Medical Center (US)
  • University of Colorado Anschutz (US)
Corresponding author
Melhem, Nadine M.
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2017-03
Volume
77
Pages
284-294
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2017.01.001
PMC
PMC5336407
OpenAlex
W2570996757
Cited by
124
References
75
Citations by year
2026: 8 · 2025: 12 · 2024: 11 · 2023: 18 · 2022: 16 · 2021: 15 · 2020: 16 · 2019: 14 · 2018: 10 · 2017: 4
FWCI
14.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R21MH101208)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
suicide attempts, suicidal ideation, HPA axis dysregulation, hair cortisol, glucocorticoid receptor, inflammation, C-reactive protein, TNF-α, interleukin-6, FKBP5, SKA2, youth
MeSH terms
Adolescent, Adult, C-Reactive Protein, Female, Hair, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Inflammation, Inpatients, Male, Pituitary-Adrenal System, Retrospective Studies, Suicide, Attempted, Biomarkers, Interleukin-6, Young Adult, Suicidal Ideation

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