{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:49:03Z","timestamp":1785433743756,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004225","name":"Petrobras","doi-asserted-by":"crossref","award":["17511\u2014PETROBRAS SAP 4600686090\u2014ProEx n\u00b0 034763\/2025-59"],"award-info":[{"award-number":["17511\u2014PETROBRAS SAP 4600686090\u2014ProEx n\u00b0 034763\/2025-59"]}],"id":[{"id":"10.13039\/501100004225","id-type":"DOI","asserted-by":"crossref"}]},{"award":["17511\u2014PETROBRAS SAP 4600686090\u2014ProEx n\u00b0 034763\/2025-59"],"award-info":[{"award-number":["17511\u2014PETROBRAS SAP 4600686090\u2014ProEx n\u00b0 034763\/2025-59"]}],"id":[{"id":"https:\/\/ror.org\/0235kyq22","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Substance use disorders (SUDs) are increasingly associated with systemic inflammatory, neuroendocrine, and cardiometabolic dysregulation; however, the biological signatures underlying distinct substance-use patterns remain incompletely characterized. This study compared biomarker profiles among healthy controls and clinical groups comprising alcohol-associated polysubstance users (A + PS), non-alcohol substance users (PS-A), and alcohol-associated polysubstance users with comorbid post-traumatic stress disorder (PTSD+). Plasma levels of interleukin-6 (IL-6), C-reactive protein (CRP), cortisol, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were evaluated through comparative, multivariate, dose\u2013response, and receiver operating characteristic (ROC) curve analyses. All clinical groups exhibited significantly increased IL-6, CRP, cortisol, and NT-proBNP levels compared with controls, indicating systemic physiological dysregulation associated with substance exposure. Among the evaluated biomarkers, IL-6 demonstrated the most robust and consistent performance across all analytical approaches. Multivariate regression identified alcohol consumption as an independent predictor of IL-6 elevation (p = 0.0003), while dose\u2013response analysis revealed progressive increases in IL-6 according to alcohol consumption severity. ROC analysis further demonstrated that IL-6 exhibited the highest discriminatory performance (AUC = 0.844), outperforming CRP, cortisol, and NT-proBNP in distinguishing substance-using individuals from controls. Collectively, these findings were able to identify IL-6 as a central biomarker associated with substance-related systemic inflammatory dysregulation and support its translational potential as a sensitive indicator of physiological burden associated with chronic alcohol and substance exposure.<\/jats:p>","DOI":"10.3390\/biom16081082","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"1082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Biomarker Alterations in Alcohol and Psychoactive Substance Users: A Cross-Sectional Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3166","authenticated-orcid":false,"given":"Lucas A. de Lima","family":"Paula","sequence":"first","affiliation":[{"name":"Laboratory of Inflammation and Infectious Diseases, Federal University of S\u00e3o Carlos (UFSCar), S\u00e3o Carlos 13565-905, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1277-0083","authenticated-orcid":false,"given":"Joice Margareth de A.","family":"Rodolpho","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation and Infectious Diseases, Federal University of S\u00e3o Carlos (UFSCar), S\u00e3o Carlos 13565-905, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krissia F.","family":"Godoy","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation and Infectious Diseases, Federal University of S\u00e3o Carlos (UFSCar), S\u00e3o Carlos 13565-905, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana A.","family":"Prado","sequence":"additional","affiliation":[{"name":"Department of Medicine, Federal University of S\u00e3o Carlos (UFSCar), S\u00e3o Carlos 13565-905, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Jaccottet","family":"Freitas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Federal University of S\u00e3o Carlos (UFSCar), S\u00e3o Carlos 13565-905, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Speglich","sequence":"additional","affiliation":[{"name":"Leopoldo Am\u00e9rico Miguez de Mello Research Center CENPES\/Petrobras, Rio de Janeiro 21941-915, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda F.","family":"Anibal","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation and Infectious Diseases, Federal University of S\u00e3o Carlos (UFSCar), S\u00e3o Carlos 13565-905, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/wps.21073","article-title":"Substance Use Disorders: A Comprehensive Update of Classification, Epidemiology, Neurobiology, Clinical Aspects, Treatment and Prevention","volume":"22","author":"Volkow","year":"2023","journal-title":"World Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.emc.2023.06.023","article-title":"Substance Use Disorder","volume":"42","author":"Swimmer","year":"2024","journal-title":"Emerg. 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