Abstract
BACKGROUND: Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) was reported to induce inflammatory responses, enhance microglial survival, and contribute to the development of neurodegenerative disorders. We aimed to prospectively investigate the association between plasma sTREM2 levels and poststroke depression (PSD). METHODS: We measured plasma sTREM2 levels in 590 patients with ischemic stroke from 7 participating hospitals of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) trial. The 24-item Hamilton Rating Scale for Depression was used to assess depression at 3 months after ischemic stroke onset, and PSD was defined as a score of ≥8. The predictive performance of sTREM2 was evaluated by calculating the net reclassification index and integrated discrimination improvement. Random forest regression model was used to assess the importance of sTREM2, clinical variables, and other potential biomarkers. RESULTS: Of the 590 participants, 229 (38.8%) patients experienced PSD. The multivariable-adjusted odds ratio for the highest quartile of sTREM2 compared with the lowest quartile was 1.98 (95% CI, 1.16-3.37) for PSD. Multiple adjusted spline regression analysis confirmed the linear dose-response relationship between sTREM2 levels and PSD (P for linearity=0.037). The addition of sTREM2 to the conventional risk factors model improved risk reclassification for PSD, as shown by a category-free net reclassification index of 19.3% (P=0.03) and integrated discrimination improvement of 1.1% (P=0.01). Furthermore, a random forest regression model suggested that sTREM2 was among the top 5 important indicators for PSD prediction. CONCLUSIONS: The present study demonstrated that elevated plasma sTREM2 levels were associated with an increased risk of PSD, suggesting that sTREM2 may be a promising prognostic biomarker for PSD. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT01840072.