{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:33:37Z","timestamp":1780547617522,"version":"3.54.1"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Several observational studies have revealed that different neurotrophic factors (NTFs) are associated with delirium, yet the direction and magnitude of the causal association remain poorly understood. Herein, we performed a two\u2010sample Mendelian randomization (MR) analysis to investigate the causal relationship between these factors and delirium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>GWAS data for delirium were sourced from the FINN10 database; GWAS data for risk factors (protein kinase C\u2010binding protein NELL1, neurotrophin\u20103, neurotrophin\u20104, brain\u2010derived neurotrophic factor levels, nerve growth factor, ciliary neurotrophic factor, and glial cell\u2010derived neurotrophic factor levels) were from the IEU Open GWAS. Inverse\u2010variance weighted (IVW) was used as a primary analysis. MR\u2010Egger, weighted median (WM), and weighted model were applied to validate the robustness of the results. The MR\u2010Egger regression method was used to explore the presence of horizontal pleiotropy, and the MR pleiotropy residual sum, and outlier (MR\u2010PRESSO) method was applied to detect potential outliers. Cochran's Q test assessed heterogeneity among instrumental variables (IVs). The leave\u2010one\u2010out (LOO) method was used to enhance the precision and veracity of our findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IVW analyses revealed no association between risk factors and delirium. MR Egger, WM, and the weighted mode approach further confirmed these data. MR\u2010Egger regression analysis confirmed the absence of directional pleiotropy in our analysis. Heterogeneity and sensitivity analyses showed reliable results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>No association between other factors and delirium was identified; however, further research is needed to determine if these results apply to other races. Also, advances in molecular biology and epigenetics may shed light on this topic.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.70494","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T08:34:46Z","timestamp":1746434086000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Causal Relationship Between Neurotrophic Factors and Delirium: A Mendelian Randomization Study"],"prefix":"10.1002","volume":"15","author":[{"given":"Han","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Geriatrics the Second People's Hospital of Lishui  Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilai","family":"Jiang","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaocheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics the Second People's Hospital of Lishui  Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2917-9630","authenticated-orcid":false,"given":"Xiaogang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics the Second People's Hospital of Lishui  Lishui 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