{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:55:29Z","timestamp":1790920529009,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chronic heroin use disturbs body\u2019s redox (oxidant-antioxidant) balance, together with dynamic thiol-disulfide balance and ischemia-modified albumin; which are two distinct blood markers that may reflect the oxidative and ischemic load in substance dependence. It is still unclear whether these markers change across the clinical phases of heroin use disorder (HUD), or whether they relate to the affective and behavioral symptoms that dominate the clinical picture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this cross-sectional study, 101 adults meeting DSM-5 criteria for HUD were split into a remission group (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f52) and a detoxification group (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f49). We measured serum native and total thiol, disulfide, the disulfide\/native thiol, disulfide\/total thiol and native thiol\/total thiol ratios, and IMA. Participants also completed a symptom inventory, a craving measure, and scales for healthy-lifestyle behavior and nutrition attitude. Groups were compared with Student\u2019s\n                      <jats:italic>t<\/jats:italic>\n                      -test or the Mann\u2013Whitney\n                      <jats:italic>U<\/jats:italic>\n                      test, categorical variables with chi-square or Fisher\u2019s exact test; associations were tested with Spearman correlations, and predictors of total thiol and IMA with multiple linear regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients in detoxification group scored markedly higher on depression, anxiety, anger, somatic symptoms, suicidal ideation, psychosis, sleep disturbance, dissociation and craving (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f\u2264\u202f0.001), and lower on healthy-lifestyle and nutrition-attitude scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). In contrast, no thiol\/disulfide measure or IMA differed between phases. IMA correlated positively with depression (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f0.254) and craving (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f0.209); whereas the disulfide\/thiol ratios correlated negatively, and native thiol\/total thiol positively with healthy-lifestyle and nutrition-attitude scores. Regression models for total thiol and IMA were not statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In HUD, redox and ischemia markers appear to follow symptom severity; especially depression, craving and health behavior, rather than the treatment phase itself. IMA, in particular, may reflect an oxidative and inflammatory component of mood regulation and craving.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnbeh.2026.1933257","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:35:59Z","timestamp":1790919359000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A comparative evaluation of thiol\/disulfide homeostasis and ischemia-modified albumin levels in patients with heroin use disorder in remission and detoxification"],"prefix":"10.3389","volume":"20","author":[{"given":"\u015eafak","family":"Yal\u00e7in \u015eahiner","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Department of Psychiatry, Ankara University","place":["Ankara, T\u00fcrkiye"]},{"name":"Combating for Addiction Application and Research Center, Ankara University","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilek","family":"Baysal","sequence":"additional","affiliation":[{"name":"Combating for Addiction Application and Research Center, Ankara University","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tu\u011fberk","family":"Vayiso\u011flu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Psychiatry, Hacettepe University","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehra","family":"U\u00e7ar Hasanli","sequence":"additional","affiliation":[{"name":"Alcohol and Drug Addiction Treatment Center, Ankara Training and Research Hospital","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Ne\u015felio\u011flu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Clinical Biochemistry, Y\u0131ld\u0131r\u0131m Beyaz\u0131t University","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamze","family":"Avcio\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Karadeniz Ere\u011fli State Hospital","place":["Zonguldak, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakk\u0131","family":"Polat","sequence":"additional","affiliation":[{"name":"Institutional Big Data Management Center, Middle East Technical University","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rifat","family":"Serav \u0130lhan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Psychiatry, Ankara University","place":["Ankara, T\u00fcrkiye"]},{"name":"Combating for Addiction Application and Research Center, Ankara University","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zcan","family":"Erel","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Clinical Biochemistry, Y\u0131ld\u0131r\u0131m Beyaz\u0131t University","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2627","DOI":"10.1007\/s00204-021-03068-2","article-title":"Toxicities of opioid analgesics: respiratory depression, histamine release, hemodynamic changes, hypersensitivity, serotonin toxicity","volume":"95","author":"Baldo","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1046\/j.1432-1327.2001.01846.x","article-title":"Characterization of the Co2+ and Ni2+ binding amino-acid residues of the N-terminus of human albumin. An insight into the mechanism of a new assay for myocardial ischemia","volume":"268","author":"Bar-Or","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1080\/15321819.2021.2001001","article-title":"Evaluation of complete blood cell count parameters and lymphocyte-related ratios in patients with opioid use disorder","volume":"43","author":"Baykara","year":"2021","journal-title":"J. Immunoassay Immunochem."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.1111\/febs.14609","article-title":"Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys34","volume":"285","author":"Bocedi","year":"2018","journal-title":"FEBS J."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.neuroscience.2023.07.031","article-title":"Neuroimmune mechanisms of opioid use disorder and recovery: translatability to human studies, and future research directions","volume":"528","author":"Butelman","year":"2023","journal-title":"Neuroscience"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"5","DOI":"10.5455\/apd.228806","article-title":"Reliability and validity of Turkish form of DSM-5 self-rated level 1 cross-cutting symptom scale-adult version","volume":"18","author":"\u00c7\u00f6km\u00fc\u015f","year":"2017","journal-title":"Anatolian J. Psychiatry"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1462612","DOI":"10.3389\/fphar.2024.1462612","article-title":"Effect of N-acetylcysteine on craving in substance use disorders (SUD): a meta-analysis of randomized controlled trials","volume":"15","author":"Cuocina","year":"2024","journal-title":"Front. Pharmacol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.3906\/sag-2003-64","article-title":"Thiol-disulfide homeostasis: an integrated approach with biochemical and clinical aspects","volume":"50","author":"Erel","year":"2020","journal-title":"Turk. J. Med. Sci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.clinbiochem.2014.09.026","article-title":"A novel and automated assay for thiol\/disulphide homeostasis","volume":"47","author":"Erel","year":"2014","journal-title":"Clin. Biochem."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"110719","DOI":"10.1016\/j.pnpbp.2023.110719","article-title":"Thiol disulfide homeostasis in psychiatric disorders: a comprehensive review","volume":"123","author":"Ergin Tuncay","year":"2023","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"53","DOI":"10.14744\/nci.2021.59913","article-title":"Thiol disulfide homeostasis in ionizing radiation and chemotherapeutic drug exposure","volume":"10","author":"Eroglu","year":"2023","journal-title":"North. Clin. Istanb."},{"key":"ref12","first-page":"70","article-title":"Reliability and validity of the Penn alcohol craving scale (PACS) revised version for substance craving in male substance dependent inpatients","volume":"22","author":"Evren","year":"2011","journal-title":"Turk. J. Psychiatry"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1111\/j.1530-0277.1999.tb04349.x","article-title":"Psychometric properties of the Penn alcohol craving scale","volume":"23","author":"Flannery","year":"1999","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.jad.2022.07.018","article-title":"Abnormal brain oscillations and activation of patients with heroin use disorder during emotion regulation: the role of delta- and theta-band power","volume":"315","author":"Jiang","year":"2022","journal-title":"J. Affect. Disord."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.1007\/s00204-023-03562-9","article-title":"Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging","volume":"97","author":"Jomova","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"170","DOI":"10.5152\/pcp.2023.23636","article-title":"Erythrocytic reduced\/oxidized glutathione and serum thiol\/disulfide homeostasis in patients with opioid use disorder","volume":"33","author":"Kabaday\u0131 \u015eahin","year":"2023","journal-title":"Psychiatry Clin. Psychopharmacol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"557","DOI":"10.28982\/josam.598200","article-title":"Evaluation of ischemia modified albumin levels in major depression patients","volume":"3","author":"Karaaslan","year":"2019","journal-title":"J. Surg. Med."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e0265504","DOI":"10.1371\/journal.pone.0265504","article-title":"Impact of illicit opioid use on markers of monocyte activation and systemic inflammation in people living with HIV","volume":"17","author":"Kholodnaia","year":"2022","journal-title":"PLoS One"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/j.jad.2023.07.079","article-title":"Thiol-disulphide homeostasis, ischemia-modified albumin, complete blood count-derived inflammatory markers and C-reactive protein from acute mania to early remission in bipolar disorder","volume":"339","author":"Korkmaz","year":"2023","journal-title":"J. Affect. Disord."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"95","DOI":"10.5350\/DAJPN2017300203","article-title":"Thiol\/disulphide homeostasis in men with heroin addiction","volume":"30","author":"Kotan","year":"2017","journal-title":"Dusunen Adam J. Psychiatry Neurol. Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41398-023-02406-5","article-title":"Heroin and its metabolites: relevance to heroin use disorder","volume":"13","author":"Milella","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1093\/alcalc\/agad044","article-title":"N-acetylcysteine in the treatment of alcohol use disorder: a randomized, double-blind, placebo-controlled trial","volume":"58","author":"Morley","year":"2023","journal-title":"Alcohol Alcohol."},{"key":"ref23","first-page":"616","article-title":"Study of serum malondialdehyde level in opioid and methamphetamine dependent patients","volume":"55","author":"Najafi","year":"2017","journal-title":"Acta Med. Iran."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/35053570","article-title":"Molecular basis of long-term plasticity underlying addiction","volume":"2","author":"Nestler","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1177\/2049463712438493","article-title":"Basic opioid pharmacology: an update","volume":"6","author":"Pathan","year":"2012","journal-title":"Br. J. Pain"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1192\/bjp.2018.144","article-title":"Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar disorder: systematic review and meta-analyses","volume":"213","author":"Rowland","year":"2018","journal-title":"Br. J. Psychiatry"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12982-024-00186-x","article-title":"Development, validity and reliability of the healthy lifestyle behavior scale","volume":"21","author":"Sayili","year":"2024","journal-title":"Discover Public Health"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"9945424","DOI":"10.1155\/2021\/9945424","article-title":"Ischemia-modified albumin: origins and clinical implications","volume":"2021","author":"Shevtsova","year":"2021","journal-title":"Dis. Markers"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.cpr.2017.09.002","article-title":"Emotion regulation as a transdiagnostic treatment construct across anxiety, depression, substance, eating and borderline personality disorders: a systematic review","volume":"57","author":"Sloan","year":"2017","journal-title":"Clin. Psychol. Rev."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"684","DOI":"10.3109\/15376516.2013.843106","article-title":"Oxidative stress enzyme status and frequency of micronuclei in heroin addicts in Turkey","volume":"23","author":"Soykut","year":"2013","journal-title":"Toxicol. Mech. Methods"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"669","DOI":"10.3390\/medicina58050669","article-title":"Ischemia-modified albumin: a potential new marker of oxidative stress in dermatological diseases","volume":"58","author":"Tampa","year":"2022","journal-title":"Medicina"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"256","DOI":"10.31680\/gaunjss.559462","article-title":"Attitude scale for healthy nutrition (ASHN): validity and reliability study","volume":"4","author":"Tekkur\u015fun-Demir","year":"2019","journal-title":"Gaziantep Univ. J. Sport Sci."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1080\/24750573.2018.1517466","article-title":"Ischemia-modified albumin: a unique marker of global metabolic risk in schizophrenia and mood disorders","volume":"29","author":"Tun\u00e7","year":"2019","journal-title":"Psychiatry Clin. Psychopharmacol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"572","DOI":"10.9758\/cpn.22.1047","article-title":"Oxidative stress and inflammatory biomarkers in people with methamphetamine use disorder","volume":"21","author":"Turan","year":"2023","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.freeradbiomed.2013.05.050","article-title":"The thiol pool in human plasma: the central contribution of albumin to redox processes","volume":"65","author":"Turell","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e13254","DOI":"10.1111\/adb.13254","article-title":"Effects of substance use disorder on oxidative and antioxidative stress markers: a systematic review and meta-analysis","volume":"28","author":"Viola","year":"2023","journal-title":"Addict. Biol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1093\/ijnp\/pyac069","article-title":"Association between inflammatory cytokines, executive function, and substance use in patients with opioid use disorder and amphetamine-type stimulants use disorder","volume":"26","author":"Wang","year":"2023","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e70001","DOI":"10.1111\/adb.70001","article-title":"N-acetylcysteine as a treatment for substance use cravings: a meta-analysis","volume":"29","author":"Winterlind","year":"2024","journal-title":"Addict. Biol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.62401\/2531-4122-2025-12","article-title":"Evaluation of thiol\/disulfide homeostasis and ischemia-modified albumin levels in patients diagnosed with heroin use disorder","volume":"27","author":"Yalcin Sahiner","year":"2025","journal-title":"Heroin Addict. Relat. Clin. Probl."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"710","DOI":"10.3390\/antiox10050710","article-title":"Oxidative stress biomarkers in chronic obstructive pulmonary disease exacerbations: a systematic review","volume":"10","author":"Zinellu","year":"2021","journal-title":"Antioxidants"}],"container-title":["Frontiers in Behavioral Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2026.1933257\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:36:00Z","timestamp":1790919360000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2026.1933257\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,2]]},"references-count":40,"alternative-id":["10.3389\/fnbeh.2026.1933257"],"URL":"https:\/\/doi.org\/10.3389\/fnbeh.2026.1933257","relation":{},"ISSN":["1662-5153"],"issn-type":[{"value":"1662-5153","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,2]]},"article-number":"1933257"}}