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Blunted HPA axis activity prior to suicide attempt and increased inflammation in attempters
Open accessAbstract
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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“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
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“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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Metadata
- 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.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 77
- Pages
- 284-294
- ISSN
- 0306-4530 (ISSN-L)
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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