Limits...
The Extrinsic Coagulation Pathway: a Biomarker for Suicidal Behavior in Major Depressive Disorder

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

ELISA Validation of Extrinsic Pathway Proteins.Seven proteins analyzed by ELISA displayed significant changes between MDD-SA, MDD-NA, and HC samples (n = 49 each). (A) FVII, (B) FV, (C) APC, (D) soluble TF, and (E) TFPI were significantly upregulated in MDD-SA subjects compared to both MDD-NA and HC subjects. (F) F1 + 2 was significantly upregulated in MDD-SA compared to MDD-NA subjects and downregulated in MDD-SA compared to HC. (G) There was no significant changes in prothrombin among the three groups. A single asterisk (*) indicates significant change with p < 0.05, ** indicates p < 0.01, and *** indicates p = 0.000. Acronyms: ELISA, enzyme-linked immunosorbent assay; MDD-SA, majorly depressed suicide attempter; MDD-NA, majorly depressed non-attempter; HC, healthy control; TF, tissue factor; TFPI, tissue factor pathway inhibitor; FVII; coagulation factor FVII; APC, activated protein C; F1 + 2, prothrombin fragment 1 + 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5015115&req=5

f3: ELISA Validation of Extrinsic Pathway Proteins.Seven proteins analyzed by ELISA displayed significant changes between MDD-SA, MDD-NA, and HC samples (n = 49 each). (A) FVII, (B) FV, (C) APC, (D) soluble TF, and (E) TFPI were significantly upregulated in MDD-SA subjects compared to both MDD-NA and HC subjects. (F) F1 + 2 was significantly upregulated in MDD-SA compared to MDD-NA subjects and downregulated in MDD-SA compared to HC. (G) There was no significant changes in prothrombin among the three groups. A single asterisk (*) indicates significant change with p < 0.05, ** indicates p < 0.01, and *** indicates p = 0.000. Acronyms: ELISA, enzyme-linked immunosorbent assay; MDD-SA, majorly depressed suicide attempter; MDD-NA, majorly depressed non-attempter; HC, healthy control; TF, tissue factor; TFPI, tissue factor pathway inhibitor; FVII; coagulation factor FVII; APC, activated protein C; F1 + 2, prothrombin fragment 1 + 2.

Mentions: Expression of seven extrinsic pathway proteins – soluble TF, TFPI, FVII, APC, FV, prothrombin, and F1 + 2 – were assessed using individual samples from the MDD-SA, MDD-NA, and HC subjects containing both drug-naïve and antidepressant-treated MDD subjects. FVII, APC, FV, TF, and TFPI were all significantly increased in MDD-SA subjects relative to both MDD-NA and HC subjects with no significant differences observed between MDD-NA and HC subjects (Fig. 3A–E). F1 + 2 was significantly increased in MDD-SA subjects relative to MDD-NA but decreased relative to HC subjects (Fig. 3F). There were no significant differences in prothrombin among the three groups (Fig. 3G).


The Extrinsic Coagulation Pathway: a Biomarker for Suicidal Behavior in Major Depressive Disorder
ELISA Validation of Extrinsic Pathway Proteins.Seven proteins analyzed by ELISA displayed significant changes between MDD-SA, MDD-NA, and HC samples (n = 49 each). (A) FVII, (B) FV, (C) APC, (D) soluble TF, and (E) TFPI were significantly upregulated in MDD-SA subjects compared to both MDD-NA and HC subjects. (F) F1 + 2 was significantly upregulated in MDD-SA compared to MDD-NA subjects and downregulated in MDD-SA compared to HC. (G) There was no significant changes in prothrombin among the three groups. A single asterisk (*) indicates significant change with p < 0.05, ** indicates p < 0.01, and *** indicates p = 0.000. Acronyms: ELISA, enzyme-linked immunosorbent assay; MDD-SA, majorly depressed suicide attempter; MDD-NA, majorly depressed non-attempter; HC, healthy control; TF, tissue factor; TFPI, tissue factor pathway inhibitor; FVII; coagulation factor FVII; APC, activated protein C; F1 + 2, prothrombin fragment 1 + 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015115&req=5

f3: ELISA Validation of Extrinsic Pathway Proteins.Seven proteins analyzed by ELISA displayed significant changes between MDD-SA, MDD-NA, and HC samples (n = 49 each). (A) FVII, (B) FV, (C) APC, (D) soluble TF, and (E) TFPI were significantly upregulated in MDD-SA subjects compared to both MDD-NA and HC subjects. (F) F1 + 2 was significantly upregulated in MDD-SA compared to MDD-NA subjects and downregulated in MDD-SA compared to HC. (G) There was no significant changes in prothrombin among the three groups. A single asterisk (*) indicates significant change with p < 0.05, ** indicates p < 0.01, and *** indicates p = 0.000. Acronyms: ELISA, enzyme-linked immunosorbent assay; MDD-SA, majorly depressed suicide attempter; MDD-NA, majorly depressed non-attempter; HC, healthy control; TF, tissue factor; TFPI, tissue factor pathway inhibitor; FVII; coagulation factor FVII; APC, activated protein C; F1 + 2, prothrombin fragment 1 + 2.
Mentions: Expression of seven extrinsic pathway proteins – soluble TF, TFPI, FVII, APC, FV, prothrombin, and F1 + 2 – were assessed using individual samples from the MDD-SA, MDD-NA, and HC subjects containing both drug-naïve and antidepressant-treated MDD subjects. FVII, APC, FV, TF, and TFPI were all significantly increased in MDD-SA subjects relative to both MDD-NA and HC subjects with no significant differences observed between MDD-NA and HC subjects (Fig. 3A–E). F1 + 2 was significantly increased in MDD-SA subjects relative to MDD-NA but decreased relative to HC subjects (Fig. 3F). There were no significant differences in prothrombin among the three groups (Fig. 3G).

View Article: PubMed Central - PubMed

ABSTRACT

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&thinsp;=&thinsp;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&thinsp;=&thinsp;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.

No MeSH data available.


Related in: MedlinePlus