{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T09:02:28Z","timestamp":1780909348091,"version":"3.54.1"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Researchers have postulated a link between higher levels of brain\u2010derived neurotrophic factor (BDNF) and more favorable outcomes in patients with normal pressure hydrocephalus (NPH). However, there is no clear evidence regarding the causal association between neurotrophins and NPH. To delve deeper into this potential connection, scientists employed a rigorous method known as bidirectional Mendelian randomization (MR). This technique was utilized to explore the causal impact of various neurotrophins\u2014such as BDNF, nerve growth factor (NGF), neurotrophin\u20103 (NT\u20103), NT\u20104, ciliary neurotrophic factor (CNTF), and glial cell line\u2010derived neurotrophic factor (GDNF)\u2014on the development or progression of NPH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the causal relationship between five neurotrophin subtypes and NPH, we designed a two\u2010sample Mendelian randomization (MR) study using comprehensive genome\u2010wide association study (GWAS) data. Our primary approach involved the inverse\u2010variance weighted (IVW) method. We also conducted reverse causality analysis to ensure robustness. Furthermore, we implemented complementary methods like the weighted median (WM), weighted mode, and MR\u2010Egger to strengthen our findings. Sensitivity analyses, including MR\u2010Egger, MR\u2010PRESSO, leave\u2010one\u2010out, and Cochran's Q tests, were employed to validate results, explore heterogeneity and pleiotropy, and pinpoint potential biases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MR analysis of genetic prediction showed no statistical association of neurotrophins on NPH. However, a reverse analysis indicated a causal association between NPH and two neurotrophins: CNTF and GDNF. Specifically, individuals with NPH had a lower risk of CNTF (odds ratio: 0.7963, with a 95% confidence interval of 0.6537 to 0.9701,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0237) and a slightly reduced risk of GDNF (odds ratio: 0.9576, with a 95% confidence interval of 0.9226 to 0.9940,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0230). MR\u2010Egger regression showed that pleiotropy did not affect the analysis. In addition, MR\u2010PRESSO detected no outliers, and a leave\u2010one\u2010out analysis verified the robustness of the results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NPH was negatively and causally associated with CNTF and GDNF. Additional research is crucial to uncover the underlying mechanisms and devise strategies, including nutritional guidelines, to prevent NPH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71309","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T06:56:36Z","timestamp":1774940196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Relationship Between Neurotrophins and Normal Pressure Hydrocephalus: Insights From a Bidirectional Two\u2010Sample Mendelian Randomization Study"],"prefix":"10.1002","volume":"16","author":[{"given":"Tao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Nanjing BenQ Medical Center  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Nanjing BenQ Medical Center  Nanjing 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