{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:07:41Z","timestamp":1789542461336,"version":"build-2803163510"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["306580\/2022\u20105"],"award-info":[{"award-number":["306580\/2022\u20105"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychiatry Clin Neurosci"],"abstract":"<jats:p>Substance\u2010use disorders are increasingly linked to structural and functional brain alterations consistent with neuroaxonal injury. Neurofilament light chain (NfL) is a sensitive blood\u2010based marker of axonal damage, but evidence in substance\u2010using populations remains fragmented. We systematically reviewed and meta\u2010analyzed blood NfL levels in individuals who use psychoactive substances compared with controls. This PRISMA\u2010guided systematic review and meta\u2010analysis was registered in PROSPERO (CRD420251270728). MEDLINE, PubMed, Embase, and Scopus were searched from inception through August 23, 2026, without language or publication\u2010date restrictions. Eligible observational studies measured blood NfL in plasma, serum, or whole blood among individuals with psychoactive substance use and controls. Effect sizes were calculated as geometric mean ratios (GMRs). Multilevel random\u2010effects models accounted for correlated comparisons within studies, and meta\u2010regression explored demographic, clinical, and methodological moderators. Eleven studies comprising 16 comparisons were included. Overall, individuals who use substances had significantly higher blood NfL levels than controls (GMR\u2009=\u20091.81, 95% CI: 1.49\u20132.20). Alcohol\u2010specific analyses showed a larger pooled effect (GMR\u2009=\u20092.09, 95% CI: 1.62\u20132.70). In studies restricted to SIMOA assays, the association remained significant, although attenuated (GMR\u2009=\u20091.64, 95% CI: 1.41\u20131.91). Meta\u2010regression indicated that higher male representation was associated with larger effect sizes, while most clinical and methodological moderators were nonsignificant. Graphical diagnostics did not suggest marked publication bias. Overall, substance use was associated with higher circulating NfL, a non\u2010specific signal consistent with increased neurobiological burden but not sufficient on its own to establish the presence, anatomical source, or cause of neuroaxonal injury.<\/jats:p>","DOI":"10.1111\/pcn.70134","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:57:51Z","timestamp":1789541871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated Levels of Blood Neurofilament Light Chain in Substance\u2010Using Populations: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","author":[{"given":"Jo\u00e3o Ant\u00f4nio Valad\u00e3o","family":"Leal","sequence":"first","affiliation":[{"name":"Nanopsychiatry Lab, Brain Institute of Rio Grande do Sul (InsCer) Pontifical Catholic University of Rio Grande do Sul (PUCRS)  Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Wendt","family":"Viola","sequence":"additional","affiliation":[{"name":"Developmental Cognitive Neuroscience Lab, Graduate Program in Medicine and Health Sciences Pontifical Catholic University of Rio Grande do Sul (PUCRS)  Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Grassi\u2010Oliveira","sequence":"additional","affiliation":[{"name":"Nanopsychiatry Lab, Brain Institute of Rio Grande do Sul (InsCer) Pontifical Catholic University of Rio Grande do Sul (PUCRS)  Porto Alegre Brazil"},{"name":"Translational Neuropsychiatry Unit, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2024.52027","article-title":"Neuroanatomical variability and substance use initiation in late childhood and early adolescence","volume":"7","author":"Miller AP","year":"2024","journal-title":"JAMA Netw. 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