The Extrinsic Coagulation Pathway: a Biomarker for Suicidal Behavior in Major Depressive Disorder.
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.
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Yongtao
Y
Yang
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Jin
J
Chen
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
Chengyu
C
Liu
Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
Liang
L
Fang
Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Zhao
Z
Liu
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Jing
J
Guo
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Ke
K
Cheng
Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Chanjuan
C
Zhou
Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Yuan
Y
Zhan
Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Narayan D
ND
Melgiri
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Liang
L
Zhang
Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
Jiaju
J
Zhong
Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Jianjun
J
Chen
Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Chenglong
C
Rao
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
Peng
P
Xie
D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001777:Blood Coagulation; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D008297:Male; D040901:Proteomics; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013406:Suicide, Attempted
D000928:Antidepressive Agents; D015415:Biomarkers; D006493:Heparin