The Extrinsic Coagulation Pathway: a Biomarker for Suicidal Behavior in Major Depressive Disorder
Open accessAbstract
Although an association between major depressive disorder (MDD) and suicide exists, most depressed patients never attempt suicide. An improved understanding of the factors contributing to suicidal risk in MDD can provide direction for suicide predictor development. In MDD suicide attempters (MDD-SA), MDD non-attempters (MDD-NA), and healthy controls (HC) (n = 12 each group), complementary plasma proteomics identified 45 differential proteins mapped to coagulation and inflammation, 25 of which underwent Western blotting. In another cohort including antidepressant-treated patients (n = 49 each group), seven additional extrinsic pathway proteins were selected for ELISA. Two inflammatory proteins and eight coagulatory proteins demonstrated alterations in MDD-SA relative to MDD-NA and HC. Applying a relative mass-action ratio, MDD-SA subjects displayed a higher relative prothrombinase activity than MDD-NA subjects, while healthy controls displayed higher relative prothrombinase activity than both MDD-SA and MDD-NA subjects. Consistent with our human findings, we found that heparin treatment significantly increased forced swimming test (FST) immobility time in rodents. MDD, independent of suicidality, is associated with a proinflammatory state accompanied by a hypothrombotic state. Suicidal behavior in MDD is associated with a more pronounced proinflammatory and prothrombotic phenotype accompanied by extrinsic pathway activation, revealing an extrinsic pathway biomarker that can be applied in predicting and monitoring suicidal risk.
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Yang et al. [54] observed a strong association of genes belonging to the blood coagulation pathway with human psychiatric disorders, such as major depression and suicidal behavior.
“For example, Yang et al. [54] observed a strong association of genes belonging to the blood coagulation pathway with human psychiatric disorders, such as major depression and suicidal behavior.”
From Gene expression profiles underlying aggressive behavior in the prefrontal cortex of cattle (2021) · cites this paper as [54]
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- Authors
- Yang, Y., Chen, J., Liu, C., Fang, L., Liu, Z., Guo, J., Cheng, K., Zhou, C., Zhan, Y., Melgiri, N. D., Zhang, L., Zhong, J., Chen, J., Rao, C., & Xie, P.
- Affiliations
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Chongqing Medical University (CN)
- Corresponding author
- Xie, Peng
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-09-08
- Volume
- 6
- Issue
- 1
- Pages
- 32882-32882
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5015115
- OpenAlex
- W2511532881
- Cited by
- 44
- References
- 56
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 11 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 4
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31271189, 2009CB918300)
- Chinese Academy of Sciences
- Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
- Chongqing Medical University
- Directorate for Biological Sciences
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- major depressive disorder, suicide, extrinsic coagulation pathway, prothrombinase activity, plasma proteomics, biomarkers, inflammation, coagulation, heparin, antidepressant treatment, forced swim test
- MeSH terms
- Adult, Animals, Antidepressive Agents, Blood Coagulation, Depressive Disorder, Major, Major Depressive Disorder, Female, Heparin, Humans, Male, Suicide, Attempted, Signal Transduction, Biomarkers, Rats, Sprague-Dawley, Proteomics
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