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Can biological tests assist prediction of suicide in mood disorders?
Open accessAbstract
Predicting suicide is difficult due to its low base-rate and the limited specificity of clinical predictors. Prospective biological studies suggest that dysfunctions in the serotonergic system and hypothalamic-pituitary-adrenal axis have some predictive power for completed suicide in mood disorders. A prediction model that incorporates biological testing to increase specificity and sensitivity of prediction of suicide is of potential clinical value. Meta-analyses of prospective biological studies of suicide and cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) and suicide and the dexamethasone suppression test (DST) in mood disorders using the penalized quasi-likelihood (PQL) and bootstrap method yield odds ratios for prediction of suicide of 4.48 and 4.65 respectively. Two combinatory prediction models, the first requiring positive results on more than one test, and the second requiring a positive result on either one of two tests, were tested to assess their sensitivity, specificity, and predictive power using biological data from published and unpublished studies. The prediction model that requires both DST and CSF 5-HIAA tests to be positive results in 37.5% sensitivity, 88% specificity, and has a positive predictive value of 23%. The prediction model that requires either DST or CSF 5-HIAA tests to be positive results in 87.5% sensitivity, 28% specificity, and has a positive predictive value of 10%. Thus, models attempting to predict a lethal outcome that is uncommon perform very differently making model choice of major importance. Further work on refining biological predictors and integration with clinical predictors is needed to optimize a model to predict suicide in the clinic.
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“Nonsuppression on the dexamethasone suppression test, which assesses this HPA axis glucocorticoid receptor feedback loop, predicts suicide (151-153), but there is disagreement about nonfatal attempts (154-158).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [151]
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Steinberg, L. J., & Mann, J. J. (2020) · Biomarkers in Neuropsychiatry · doi:10.1016/j.bionps.2020.100011 · Cited by 29
Self-citationLifestyle factors and suicide risk: A nationwide population-based study
Kim, H., Ryu, S., Jeon, H. J., & Roh, S. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.02.044 · Cited by 29
Chen, H., Li, W., Cao, X., Liu, P., Liu, J., Chen, X., Luo, C., Liang, X., Guo, H., Zhong, S., et al. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.745470 · Cited by 29
CSF 5-HIAA, attempted suicide and suicide risk in schizophrenia spectrum psychosis
Carlborg, A., Jokinen, J., Nordström, A., Jönsson, E. G., & Nordström, P. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.04.006 · Cited by 29
Genome-wide methylation association with current suicidal ideation in schizophrenia
Bani‐Fatemi, A., Adanty, C., Dai, N., Dada, O. O., Strauss, J., Zai, C. C. H., Gerretsen, P., Graff, A., & Luca, V. D. (2020) · Journal of Neural Transmission · doi:10.1007/s00702-020-02225-8 · Cited by 28
Serum endocannabinoid levels in suicide attempters: A pilot study
Herranz-Herrer, J., Gil-Benito, E., Ponte-López, T., Ortega‐Gutiérrez, S., Macicior, J., Rosado, S., Sánchez, A., & Blasco-Fontecilla, H. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.09.005 · Cited by 29
Relationship of stress-reactive cortisol to suicidal intent of prior attempts in major depression
Herzog, S., Galfalvy, H., Keilp, J. G., Mann, J. J., Sublette, M. E., Burke, A. K., Oquendo, M. A., & Stanley, B. (2023) · Psychiatry Research · doi:10.1016/j.psychres.2023.115315 · Cited by 27
Self-citationPoindexter, E. K., Mitchell, S. M., Brown, S. L., & Cukrowicz, K. C. (2020) · Journal of Interpersonal Violence · doi:10.1177/0886260520917513 · Cited by 28
Preuss, U. W., Wurst, F., Ridinger, M., Rujescu, D., Fehr, C., Koller, G., Bondy, B., Wodarz, N., Soyka, M., & Zill, P. (2013) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2013.07.002 · Cited by 27
Smoking and suicide: biological and social evidence and causal mechanisms
Green, M., Turner, S. E., & Sareen, J. (2017) · Journal of Epidemiology & Community Health · doi:10.1136/jech-2016-207731 · Cited by 26
Zalsman, G., Huang, Y., Oquendo, M. A., Brent, D. A., Giner, L., Haghighi, F. G., Burke, A. K., Ellis, S. P., Currier, D., & Mann, J. J. (2008) · Archives of Suicide Research · doi:10.1080/13811110802324912 · Cited by 26
Self-citationNeuronal tryptophan hydroxylase expression in BALB/cJ and C57Bl/6J mice
Bach, H., Arango, V., Huang, Y., Leong, S., Mann, J. J., & Underwood, M. D. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07379.x · Cited by 24
Self-citationCSF 5-HIAA and DST non-suppression -independent biomarkers in suicide attempters?
Jokinen, J., Mårtensson, B., Nordström, A., & Nordström, P. (2007) · Journal of Affective Disorders · doi:10.1016/j.jad.2007.04.008 · Cited by 22
The Neuroscience of Suicidal Behavior
van Heeringen, K. (2018) · Cambridge University Press eBooks · doi:10.1017/9781316563205 · Cited by 22
HPA-axis hyperactivity and mortality in psychotic depressive disorder: Preliminary findings
Coryell, W. H., Fiedorowicz, J. G., Zimmerman, M. A., & Young, E. A. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.02.005 · Cited by 22
A Computational Model of Hopelessness and Active-Escape Bias in Suicidality
Karvelis, P., & Diaconescu, A. O. (2022) · Computational Psychiatry · doi:10.5334/cpsy.80 · Cited by 21
Implementing Evidence-Based Suicide Prevention Strategies for Greatest Impact
Melhem, N., Moutier, C. Y., & Brent, D. A. (2023) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.20220078 · Cited by 23
Non-Suicidal Self-Injury in Russian Patients with Suicidal Ideation
Зинчук, М. С., Beghi, M., Beghi, E., Bianchi, E., Аведисова, А. С., Yakovlev, A. A., & Guekht, A. B. (2020) · Archives of Suicide Research · doi:10.1080/13811118.2020.1833801 · Cited by 21
Metadata
- Authors
- Mann, J. J., Currier, D., Stanley, B., Oquendo, M. A., Amsel, L. V., & Ellis, S. P.
- Affiliations
- New York State Psychiatric Institute (US)
- Corresponding author
- Mann, J. John
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06-21
- Volume
- 9
- Issue
- 04
- Pages
- 465
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2137625559
- Cited by
- 215
- References
- 55
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 14 · 2020: 16 · 2019: 5 · 2018: 24 · 2017: 6 · 2016: 14 · 2015: 7 · 2014: 12 · 2013: 16 · 2012: 7
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH48514, MH 62184, R01MH048514)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- suicide risk prediction, mood disorders, serotonergic dysfunction, hypothalamic-pituitary-adrenal axis, dexamethasone suppression test, biological predictors, penalized quasi-likelihood
- MeSH terms
- Humans, Predictive Value of Tests, Prospective Studies, Suicide, Biomarkers, Mood Disorders
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