{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:19:48Z","timestamp":1785435588816,"version":"3.56.0"},"reference-count":94,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008871","name":"Yunnan Fundamental Research Projects","doi-asserted-by":"publisher","award":["202401AT070035"],"award-info":[{"award-number":["202401AT070035"]}],"id":[{"id":"10.13039\/501100008871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401771"],"award-info":[{"award-number":["82401771"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82401771"],"award-info":[{"award-number":["82401771"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Scientific Research Fund of Yunnan Provincial Department of Education","award":["2025Y1082"],"award-info":[{"award-number":["2025Y1082"]}]},{"award":["2025Y1082"],"award-info":[{"award-number":["2025Y1082"]}],"id":[{"id":"https:\/\/ror.org\/02yrxdp92","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Oxidative stress has been recognized as a repeatedly validated pathophysiological factor in schizophrenia, but its mechanistic role and translational relevance remain incompletely defined. Prior work has advanced redox dysregulation, neuroinflammation, and NMDA receptor hypofunction as a putative central hub in schizophrenia. This narrative review proposes an evidence-weighted redox\u2013mitochondria\u2013immune framework that integrates peripheral biomarkers, magnetic resonance spectroscopy, postmortem findings, and preclinical mechanisms while explicitly distinguishing established observations from candidate pathways. Existing studies support increased oxidative damage and altered antioxidant buffering in schizophrenia, particularly involving the glutathione system. However, these abnormalities are neither uniform across disease stages nor equally represented across patient subgroups, and may be markedly prominent only in certain biological subgroups. Mechanistically, redox imbalance may interact with mitochondrial bioenergetic deficits and innate immune signaling; however, pathway-specific links such as cGAS-STING activation, nitrosative\/peroxynitrite stress, and GPx4-ferroptosis should currently be treated as testable extensions rather than validated human mechanisms in schizophrenia. Importantly, the pathological consequences of oxidative stress are unlikely to be cell-type neutral. Parvalbumin-positive interneurons and oligodendrocyte lineage cells are more vulnerable because of their high metabolic load, limited antioxidant buffering capacity, and lipid\/iron-related susceptibility, thereby providing a mechanistic bridge to excitation\u2013inhibition imbalance, myelin abnormalities, and reduced circuit synchrony. Microglial redox\u2013inflammatory signaling may further exacerbate these processes. On the basis of this framework, we argue that the key for future research is not to continue demonstrating the universality of oxidative stress, but to improve the translational efficiency. Biomarker-guided stratification, stage-sensitive study designs, and cell-type-informed therapeutic strategies may therefore provide a more productive path toward redox-targeted interventions in schizophrenia.<\/jats:p>","DOI":"10.3390\/cells15131153","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:48:16Z","timestamp":1782366496000},"page":"1153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Redox\u2013Mitochondria\u2013Immune Network Dysregulation in Schizophrenia: From Selective Cellular Vulnerability to Circuit Dysfunction"],"prefix":"10.3390","volume":"15","author":[{"given":"Tingyan","family":"He","sequence":"first","affiliation":[{"name":"Yunnan Key Laboratory of Cell Therapy for Refractory Diseases, Kunming University, Kunming 650214, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Yu","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Cell Therapy for Refractory Diseases, Kunming University, Kunming 650214, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Qian","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Cell Therapy for Refractory Diseases, Kunming University, Kunming 650214, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonglin","family":"Wu","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Cell Therapy for Refractory Diseases, Kunming University, Kunming 650214, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changguo","family":"Ma","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Cell Therapy for Refractory Diseases, Kunming University, Kunming 650214, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1001\/jama.2019.11073","article-title":"Schizophrenia","volume":"322","author":"Borelli","year":"2019","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s43440-025-00722-9","article-title":"New pharmacological approaches in the treatment of schizophrenia","volume":"77","author":"Muszynski","year":"2025","journal-title":"Pharmacol. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Murray, A.J., Rogers, J.C., Katshu, M., Liddle, P.F., and Upthegrove, R. (2021). Oxidative Stress and the Pathophysiology and Symptom Profile of Schizophrenia Spectrum Disorders. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.703452"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wiedlocha, M., Zborowska, N., Marcinowicz, P., Debowska, W., Debowska, M., Zalewska, A., Maciejczyk, M., Waszkiewicz, N., and Szulc, A. (2023). Oxidative Stress Biomarkers among Schizophrenia Inpatients. Brain Sci., 13.","DOI":"10.3390\/brainsci13030490"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neubiorev.2014.11.005","article-title":"Mitochondrial dysfunction in schizophrenia: Pathways, mechanisms and implications","volume":"48","author":"Rajasekaran","year":"2015","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/7854_2018_88","article-title":"Cytokines, Oxidative Stress and Cellular Markers of Inflammation in Schizophrenia","volume":"44","author":"Upthegrove","year":"2020","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1038\/s41380-021-01374-w","article-title":"Caught in vicious circles: A perspective on dynamic feed-forward loops driving oxidative stress in schizophrenia","volume":"27","author":"Cuenod","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1171","DOI":"10.1038\/tp.2017.138","article-title":"Oxidative stress, prefrontal cortex hypomyelination and cognitive symptoms in schizophrenia","volume":"7","author":"Maas","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.schres.2024.05.018","article-title":"The importance of oxidative biomarkers in diagnosis, treatment, and monitoring schizophrenia patients","volume":"270","author":"Polikowska","year":"2024","journal-title":"Schizophr. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102932","DOI":"10.1016\/j.ajp.2021.102932","article-title":"Blood-based oxidation markers in medicated and unmedicated schizophrenia patients: A meta-analysis","volume":"67","author":"Goh","year":"2022","journal-title":"Asian J. Psychiatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.schres.2014.06.021","article-title":"Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A \u201ccentral hub\u201d in schizophrenia pathophysiology?","volume":"176","author":"Steullet","year":"2016","journal-title":"Schizophr. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/mp.2017.47","article-title":"Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia","volume":"22","author":"Steullet","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.biopsych.2013.03.018","article-title":"Meta-analysis of oxidative stress in schizophrenia","volume":"74","author":"Flatow","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1007\/s12011-025-04789-6","article-title":"Peripheral Oxidative Stress Markers in Schizophrenia: Insights from Erythrocyte Glutathione Peroxidase, Plasma Malondialdehyde, and Trace Element Ratios in Algerian Patients","volume":"204","author":"Saidane","year":"2025","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ab.2016.10.021","article-title":"Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges","volume":"524","author":"Tsikas","year":"2017","journal-title":"Anal. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4578","DOI":"10.1007\/s12035-020-02047-5","article-title":"Lowered Antioxidant Defenses and Increased Oxidative Toxicity Are Hallmarks of Deficit Schizophrenia: A Nomothetic Network Psychiatry Approach","volume":"57","author":"Maes","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Raffa, M., Atig, F., Mhalla, A., Kerkeni, A., and Mechri, A. (2011). Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive first-episode schizophrenic patients. BMC Psychiatry, 11.","DOI":"10.1186\/1471-244X-11-124"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bbi.2023.09.017","article-title":"Measurement of brain glutathione with magnetic Resonance spectroscopy in Schizophrenia-Spectrum disorders\u2014A systematic review and Meta-Analysis","volume":"115","author":"Murray","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/s41380-018-0104-7","article-title":"Glutathione and glutamate in schizophrenia: A 7T MRS study","volume":"25","author":"Kumar","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_20","first-page":"278","article-title":"Oxidative stress biomarkers in treatment-responsive and treatment-resistant schizophrenia patients","volume":"43","author":"Buosi","year":"2021","journal-title":"Trends Psychiatry Psychother."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Djordjevic, V.V., Kostic, J., Krivokapic, Z., Krtinic, D., Rankovic, M., Petkovic, M., and Cosic, V. (2022). Decreased Activity of Erythrocyte Catalase and Glutathione Peroxidase in Patients with Schizophrenia. Medicina, 58.","DOI":"10.3390\/medicina58101491"},{"key":"ref_22","first-page":"23","article-title":"Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity","volume":"10","author":"Beckhauser","year":"2016","journal-title":"J. Exp. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Clemente-Suarez, V.J., Martin-Rodriguez, A., Curiel-Regueros, A., Rubio-Zarapuz, A., and Tornero-Aguilera, J.F. (2025). Neuro-Nutrition and Exercise Synergy: Exploring the Bioengineering of Cognitive Enhancement and Mental Health Optimization. Bioengineering, 12.","DOI":"10.3390\/bioengineering12020208"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lee, K.H., Cha, M., and Lee, B.H. (2020). Neuroprotective Effect of Antioxidants in the Brain. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197152"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Singh, A., Kukreti, R., Saso, L., and Kukreti, S. (2019). Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules, 24.","DOI":"10.3390\/molecules24081583"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Collin, F. (2019). Chemical Basis of Reactive Oxygen Species Reactivity and Involvement in Neurodegenerative Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102407"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1038\/s41401-025-01576-w","article-title":"Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update","volume":"46","author":"Wu","year":"2025","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Trofin, D.M., Sardaru, D.P., Trofin, D., Onu, I., Tutu, A., Onu, A., Onita, C., Galaction, A.I., and Matei, D.V. (2025). Oxidative Stress in Brain Function. Antioxidants, 14.","DOI":"10.3390\/antiox14030297"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5839","DOI":"10.1073\/pnas.1804932115","article-title":"Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine","volume":"115","author":"Radi","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"420","DOI":"10.3109\/10799893.2010.513991","article-title":"Protein tyrosine nitration in cellular signal transduction pathways","volume":"30","author":"Yakovlev","year":"2010","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.pain.2010.01.015","article-title":"NMDA-receptor activation and nitroxidative regulation of the glutamatergic pathway during nociceptive processing","volume":"149","author":"Chen","year":"2010","journal-title":"Pain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.3390\/jcm11092551","article-title":"Increased Markers of Oxidative Stress and Positive Correlation Low-Grade Inflammation with Positive Symptoms in the First Episode of Schizophrenia in Drug-Naive Patients","volume":"11","author":"Dudzinska","year":"2022","journal-title":"J. Clin. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16621","DOI":"10.1073\/pnas.0706778104","article-title":"Impaired glutathione synthesis in schizophrenia: Convergent genetic and functional evidence","volume":"104","author":"Gysin","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/schbul\/sbw038","article-title":"Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling With Brain Glutamate and Peripheral Redox Status in Early Psychosis","volume":"42","author":"Xin","year":"2016","journal-title":"Schizophr. Bull."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_36","first-page":"128","article-title":"Research progress in mitochondrial quality control in schizophrenia","volume":"49","author":"Chu","year":"2024","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Moren, C., Olivares-Berjaga, D., Martinez-Pinteno, A., Bioque, M., Rodriguez, N., Gasso, P., Martorell, L., and Parellada, E. (2025). Mitochondrial Oxidative Phosphorylation System Dysfunction in Schizophrenia. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094415"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.schres.2023.11.013","article-title":"Lactate levels in the brain and blood of schizophrenia patients: A systematic review and meta-analysis","volume":"264","author":"Liu","year":"2024","journal-title":"Schizophr. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Caddye, E., Pineau, J., Reyniers, J., Ronen, I., and Colasanti, A. (2023). Lactate: A Theranostic Biomarker for Metabolic Psychiatry?. Antioxidants, 12.","DOI":"10.3390\/antiox12091656"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.schres.2020.03.070","article-title":"Increased blood lactate levels during exercise and mitochondrial DNA alterations converge on mitochondrial dysfunction in schizophrenia","volume":"220","author":"Torrell","year":"2020","journal-title":"Schizophr. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fizikova, I., Dragasek, J., and Racay, P. (2023). Mitochondrial Dysfunction, Altered Mitochondrial Oxygen, and Energy Metabolism Associated with the Pathogenesis of Schizophrenia. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097991"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12743","DOI":"10.1038\/s41598-018-31122-0","article-title":"Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment","volume":"8","author":"Kumar","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating mitochondrial DAMPs cause inflammatory responses to injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1084\/jem.20151876","article-title":"Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus","volume":"213","author":"Caielli","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_45","first-page":"1452696","article-title":"PGC-1alpha, Inflammation, and Oxidative Stress: An Integrative View in Metabolism","volume":"2020","author":"Millan","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"115403","DOI":"10.1016\/j.celrep.2025.115403","article-title":"The pro-inflammatory cytokine IL6 suppresses mitochondrial function via the gp130-JAK1\/STAT1\/3-HIF1alpha\/ERRalpha axis","volume":"44","author":"Xu","year":"2025","journal-title":"Cell Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/cr.2010.178","article-title":"Crosstalk of reactive oxygen species and NF-kappaB signaling","volume":"21","author":"Morgan","year":"2011","journal-title":"Cell Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/ijnp\/pyad012","article-title":"Redox and Immune Signaling in Schizophrenia: New Therapeutic Potential","volume":"26","author":"Dwir","year":"2023","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/jnen\/nlae066","article-title":"Increased inflammasome protein expression identified in microglia from postmortem brains with schizophrenia","volume":"83","author":"Gober","year":"2024","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1021\/acs.chemrev.7b00568","article-title":"Biochemistry of Peroxynitrite and Protein Tyrosine Nitration","volume":"118","author":"Campolo","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/nrd2222","article-title":"Peroxynitrite: Biochemistry, pathophysiology and development of therapeutics","volume":"6","author":"Szabo","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/s41398-024-03157-7","article-title":"A systematic review and meta-analysis of nitric oxide-associated arginine metabolites in schizophrenia","volume":"14","author":"Zinellu","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Janickova, L., and Schwaller, B. (2020). Parvalbumin-Deficiency Accelerates the Age-Dependent ROS Production in Pvalb Neurons in vivo: Link to Neurodevelopmental Disorders. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.571216"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/jnc.13405","article-title":"Neuroprotective effects of levetiracetam target xCT in astrocytes in parkinsonian mice","volume":"136","author":"Miyazaki","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"10514","DOI":"10.1523\/JNEUROSCI.3178-06.2006","article-title":"Cystine\/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation","volume":"26","author":"Shih","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1007\/s00018-021-03802-0","article-title":"Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders","volume":"78","author":"Spaas","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1038\/s41380-024-02861-6","article-title":"Glial cell deficits are a key feature of schizophrenia: Implications for neuronal circuit maintenance and histological differentiation from classical neurodegeneration","volume":"30","author":"Bernstein","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Schmitt, A., Tatsch, L., Vollhardt, A., Schneider-Axmann, T., Raabe, F.J., Roell, L., Heinsen, H., Hof, P.R., Falkai, P., and Schmitz, C. (2022). Decreased Oligodendrocyte Number in Hippocampal Subfield CA4 in Schizophrenia: A Replication Study. Cells, 11.","DOI":"10.3390\/cells11203242"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1093\/schbul\/sbad065","article-title":"Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis","volume":"49","author":"Falkai","year":"2023","journal-title":"Schizophr. Bull."},{"key":"ref_60","first-page":"143","article-title":"Lipid Peroxidation-Dependent Cell Death Regulated by GPx4 and Ferroptosis","volume":"403","author":"Imai","year":"2017","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.freeradbiomed.2020.02.027","article-title":"Lipid peroxidation and ferroptosis: The role of GSH and GPx4","volume":"152","author":"Ursini","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.tcb.2015.10.014","article-title":"Ferroptosis: Death by Lipid Peroxidation","volume":"26","author":"Yang","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s40035-023-00378-6","article-title":"Role of dopamine in the pathophysiology of Parkinson\u2019s disease","volume":"12","author":"Zhou","year":"2023","journal-title":"Transl. Neurodegener."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"340","DOI":"10.2174\/1570159X20666220706101021","article-title":"Comparative Analysis of the Pre- and Post-Medication Effects of Antipsychotic Agents on the Blood-Based Oxidative Stress Biomarkers in Patients with Schizophrenia: A Meta-Analysis","volume":"21","author":"Yang","year":"2023","journal-title":"Curr. Neuropharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1016\/j.neuropharm.2011.01.049","article-title":"Behavioral and neurochemical consequences of cortical oxidative stress on parvalbumin-interneuron maturation in rodent models of schizophrenia","volume":"62","author":"Powell","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1093\/schbul\/sbae033","article-title":"Adolescent Stress-Induced Ventral Hippocampus Redox Dysregulation Underlies Behavioral Deficits and Excitatory\/Inhibitory Imbalance Related to Schizophrenia","volume":"51","author":"Lopes","year":"2025","journal-title":"Schizophr. Bull."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Raabe, F.J., Slapakova, L., Rossner, M.J., Cantuti-Castelvetri, L., Simons, M., Falkai, P.G., and Schmitt, A. (2019). Oligodendrocytes as A New Therapeutic Target in Schizophrenia: From Histopathological Findings to Neuron-Oligodendrocyte Interaction. Cells, 8.","DOI":"10.3390\/cells8121496"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"15034","DOI":"10.1038\/npjschz.2015.34","article-title":"Disturbed macro-connectivity in schizophrenia linked to oligodendrocyte dysfunction: From structural findings to molecules","volume":"1","author":"Cassoli","year":"2015","journal-title":"npj Schizophr."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lin, C.H., and Lane, H.Y. (2019). Early Identification and Intervention of Schizophrenia: Insight From Hypotheses of Glutamate Dysfunction and Oxidative Stress. Front. Psychiatry, 10.","DOI":"10.3389\/fpsyt.2019.00093"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Rambaud, V., Marzo, A., and Chaumette, B. (2022). Oxidative Stress and Emergence of Psychosis. Antioxidants, 11.","DOI":"10.3390\/antiox11101870"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1097\/YCO.0000000000000054","article-title":"Oxidative stress and schizophrenia: Recent breakthroughs from an old story","volume":"27","author":"Emiliani","year":"2014","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41537-025-00726-7","article-title":"Abnormal plasma oxidative stress markers in first-episode schizophrenia and associations with clinical symptoms and cognitive function","volume":"12","author":"Jiang","year":"2026","journal-title":"Schizophrenia"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41398-025-03801-w","article-title":"Multimodal neuroimaging reveals brain neurochemical disturbances associated with superoxide dismutase in first-episode drug-naive schizophrenia","volume":"16","author":"Zhu","year":"2026","journal-title":"Transl. Psychiatry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41537-025-00555-8","article-title":"The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: A multicenter investigation","volume":"11","author":"Peng","year":"2025","journal-title":"Schizophrenia"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Juchnowicz, D., Dzikowski, M., Rog, J., Waszkiewicz, N., Zalewska, A., Maciejczyk, M., and Karakula-Juchnowicz, H. (2021). Oxidative Stress Biomarkers as a Predictor of Stage Illness and Clinical Course of Schizophrenia. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.728986"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/acps.12862","article-title":"N-acetylcysteine for major mental disorders: A systematic review and meta-analysis of randomized controlled trials","volume":"137","author":"Zheng","year":"2018","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1093\/schbul\/sbac065","article-title":"N-Acetylcysteine (NAC) in Schizophrenia Resistant to Clozapine: A Double-Blind, Randomized, Placebo-Controlled Trial Targeting Negative Symptoms","volume":"48","author":"Neill","year":"2022","journal-title":"Schizophr. Bull."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e2880","DOI":"10.1002\/hup.2880","article-title":"Efficacy and acceptability of adjunctive n-acetylcysteine for psychotic disorders: Systematic review and meta-analysis","volume":"39","author":"Zhang","year":"2024","journal-title":"Hum. Psychopharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"24m15272","DOI":"10.4088\/JCP.24m15272","article-title":"Efficacy and Safety of Sulforaphane Added to Antipsychotics for the Treatment of Negative Symptoms of Schizophrenia: A Randomized Controlled Trial","volume":"86","author":"Huang","year":"2025","journal-title":"J. Clin. Psychiatry"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.jpsychires.2025.03.023","article-title":"Effects of sulforaphane on negative symptoms and cognitive impairments in chronic schizophrenia patients: A randomized double-blind trial","volume":"184","author":"Chen","year":"2025","journal-title":"J. Psychiatr. Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Kassar, O., Mansour, M.E.M., Farag, N., Selim, A., Kewiaa, Y., Yousef, O., and Hassan, O. (2025). Efficacy and safety of sulforaphane in schizophrenia: A systematic review and meta-analysis of randomized controlled trials. BMC Psychiatry, 25.","DOI":"10.1186\/s12888-025-07515-7"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.plefa.2017.05.004","article-title":"Oxidative stress reduction related to the efficacy of n-3 polyunsaturated fatty acids in first episode schizophrenia: Secondary outcome analysis of the OFFER randomized trial","volume":"121","author":"Pawelczyk","year":"2017","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e335","DOI":"10.1038\/tp.2013.110","article-title":"A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia","volume":"3","author":"Bentsen","year":"2013","journal-title":"Transl. Psychiatry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.plefa.2017.10.002","article-title":"Neurocognitive effects of an omega-3 fatty acid and vitamins E+C in schizophrenia: A randomised controlled trial","volume":"136","author":"Bentsen","year":"2018","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/mp.2016.147","article-title":"Myelination of parvalbumin interneurons: A parsimonious locus of pathophysiological convergence in schizophrenia","volume":"22","author":"Stedehouder","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/s41398-018-0266-8","article-title":"N-acetylcysteine add-on treatment leads to an improvement of fornix white matter integrity in early psychosis: A double-blind randomized placebo-controlled trial","volume":"8","author":"Klauser","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Gray, N.E., Farina, M., Tucci, P., and Saso, L. (2022). The Role of the NRF2 Pathway in Maintaining and Improving Cognitive Function. Biomedicines, 10.","DOI":"10.3390\/biomedicines10082043"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.neubiorev.2017.08.025","article-title":"Crosstalk between endoplasmic reticulum stress and oxidative stress in schizophrenia: The dawn of new therapeutic approaches","volume":"83","author":"Patel","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1089\/ars.2012.4907","article-title":"How Nox2-containing NADPH oxidase affects cortical circuits in the NMDA receptor antagonist model of schizophrenia","volume":"18","author":"Wang","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"8881770","DOI":"10.1155\/2021\/8881770","article-title":"Oxidative Stress-Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives","volume":"2021","author":"Ermakov","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Liang, J.Q., Chen, X., and Cheng, Y. (2022). Paeoniflorin Rescued MK-801-Induced Schizophrenia-Like Behaviors in Mice via Oxidative Stress Pathway. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.870032"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/jnen\/nlaf093","article-title":"Proteasomal dysfunction in the mouse forebrain induces mitochondrial DNA release, cGAS-STING signaling activation, and necroptosis","volume":"84","author":"Dwamena","year":"2025","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1097\/YCO.0000000000000699","article-title":"Estrogens in schizophrenia: Progress, current challenges and opportunities","volume":"34","author":"Brand","year":"2021","journal-title":"Curr. Opin. Psychiatry"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/13\/1153\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:32:28Z","timestamp":1782369148000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/13\/1153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":94,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cells15131153"],"URL":"https:\/\/doi.org\/10.3390\/cells15131153","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]}}}