Plasma soluble triggering receptor expressed on myeloid cells 2 is associated with depression after acute ischemic stroke

Background Previous studies suggested that elevated levels of plasma soluble triggering receptor expressed on myeloid cells 2 (sTREM2) was related to increased risk of death, cardiovascular events and cognitive impairment after stroke. We aimed to prospectively investigate the association between plasma sTREM2 levels and post-stroke depression (PSD). Methods We measured plasma sTREM2 levels in 590 ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke. 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. Logistic regression analysis was performed to evaluate the risk of PSD associated with plasma sTREM2 levels, and net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to assess the predictive value of sTREM2. Results Of the 590 participants, 229 (38.8%) patients experienced PSD. The risk of PSD elevated significantly with plasma sTREM2 levels ( P for trend=0.034). After adjusting for several covariates, the odds ratio for the highest quartile of sTREM2 compared with the lowest quartile was 2.41 (95% CI=1.35-4.31) for PSD. Multiple adjusted spline regression analysis further confirmed the linear dose-response relationship between sTREM2 levels and PSD ( P for linearity=0.024). The addition of sTREM2 to a conventional model notably improved the risk prediction for PSD (category-free NRI=21.50%, 95% CI=5.92%-37.07%, P =0.011; IDI=1.43%, 95% CI=0.45%-2.42%, P =0.005). Conclusions The present study demonstrated that elevated plasma sTREM2 levels were associated with increased risk of PSD, suggesting that sTREM2 may be a promising prognostic biomarker for PSD. Registration URL: ; Unique identifier: [NCT01840072][1]. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT01840072 ### Funding Statement This study was supported by the National Natural Science Foundation of China (grant number 82273706, 81903387, and 82220108001), and a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions, China. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: the institutional review boards at Soochow University in China the institutional review boards at Tulane University in the United States ethical committees at the participating hospitals I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available from the corresponding author upon reasonable request. * CATIS : China Antihypertensive Trial in Acute Ischemic Stroke NIHSS : National Institutes of Health Stroke Scale sTREM2 : soluble triggering receptor expressed on myeloid cells 2 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01840072&atom=%2Fmedrxiv%2Fearly%2F2023%2F04%2F28%2F2023.04.25.23289122.atom