Molecular regulatory mechanisms of depression-related thrombosis risk

抑郁症相关血栓风险的分子调控机制

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Abstract

BACKGROUND: This is mainly because depression is a COM-mon psychiatric condition affecting more than 280 million people worldwide and is increasingly linked to an increased risk of thrombotic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE). For example, under-lying pathophysiological mechanisms remain inadequately understood, and thus further research on the association between depression, systemic inflammation, platelet acti-vation and coagulation abnormalities is warranted. The objective of this study is to identify biological pathways link-ing thrombosis and depression by examination of inflam-matory and coagulation biomarkers, platelet activation, and risk of thrombosis as independent predictors. In addi-tion, the study investigates the possibility of nursing inter-ventions in reducing thrombotic complications among depressed individuals. METHODS: A case control study was performed with 500 subjects (250 who had major depressive disorder and 250 healthy control subjects) included. Enzyme-linked immuno-sorbent assays (ELISA) and quantitative polymerase chain reaction (qPCR) were employed to quantify key inflamma-tory (IL-6, TNF-a, CRP) and coagulation (D-dimer, fibrino-gen) biomarkers. An assessment of platelet activation (CD62P PAC1 binding, GPIIbIIIa activation) was per-formed by flow cytometry. The study was carried out by a longitudinal follow-up over 12 months and by multivariate regression models to identify independent risk predictors. RESULTS: Thrombophilic and inflammatory parameters were significantly higher in depressed patients as compared to controls (p< 0.001). The system was markedly hyperco-agulable, as platelet activation markers were significantly upregulated. Through multivariate regression analysis, we determined that thrombosis risk was independent of the severity level of depression (O R = 2.10 , p< 0.001), IL-6 levels (O R = 1 .9 2 , p < 0.0 01), and platelet activation (O R = 2.50, p< 0.001). CONCLUSIONS: The results indicate that depression is an independent risk factor for thrombosis, through systemic inflammation and platelet hyperactivity. These results rein-force the value of linking psychiatric screening into throm-bosis risk assessment and suggest the possible benefits of targeted anti-inflammatory or antiplatelet interventions in the psychiatric population at high risk of thrombosis.

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