The Journal of Practical Medicine >
Advances in oxidative stress⁃related pathways with diagnostic and predictive value in schizophrenia
Received date: 2024-01-14
Online published: 2024-11-05
Schizophrenia is a severe mental illness with a significant disease burden. The interaction between oxidative stress and pro-inflammatory factors promotes chronic neuroinflammation and immune damage， leads to dysregulation of dopaminergic and glutamatergic pathways and occurrence of psychotic symptoms and is believed to be closely related to the pathogenesis of schizophrenia. In this paper， we aim to identify biomarkers within the tryptophan kynurenine metabolic pathway， the WNT/β-Catenin pathway and the NF-κB pathway， and dopamine metabolism. These pathways have been extensively studied and are known to be involved in the interaction between inflammation and oxidative stress. We will also explore the potential application of related antioxidants in the diagnosis and treatment of schizophrenia， summarizing their current research progress.
Key words： oxidative stress; inflammatory factor; schizophrenia; biomarker
Tianyue YU , Qian GUO , Hao HU , Yujing SU , Jianhua CHEN . Advances in oxidative stress⁃related pathways with diagnostic and predictive value in schizophrenia[J]. The Journal of Practical Medicine, 2024 , 40(20) : 2935 -2940 . DOI: 10.3969/j.issn.1006-5725.2024.20.019
| 1 | JAUHAR S， JOHNSTONE M， MCKENNA P J. Schizophrenia ［J］. Lancet， 2022， 399（10323）： 473-486. doi:10.1016/s0140-6736(21)01730-x |
| 2 | TALUKDAR P M， ABDUL F， MAES M， et al. Maternal Immune Activation Causes Schizophrenia-like Behaviors in the Offspring through Activation of Immune-Inflammatory， Oxidative and Apoptotic Pathways， and Lowered Antioxidant Defenses and Neuroprotection ［J］. Mol Neurobiol， 2020， 57（10）： 4345-4361. doi:10.1007/s12035-020-02028-8 |
| 3 | KUMAR V， BISHAYEE K， PARK S， et al. Oxidative stress in cerebrovascular disease and associated diseases ［J］. Front Endocrinol （Lausanne）， 2023， 14： 1124419. doi:10.3389/fendo.2023.1124419 |
| 4 | ROBERTS R C. Mitochondrial dysfunction in schizophrenia： With a focus on postmortem studies ［J］. Mitochondrion， 2021， 56： 91-101. doi:10.1016/j.mito.2020.11.009 |
| 5 | PALANIYAPPAN L， PARK M T M， JEON P， et al. Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia？ ［J］. Antioxidants （Basel）， 2021， 10（11）：1703. doi:10.3390/antiox10111703 |
| 6 | RAMBAUD V， MARZO A， CHAUMETTE B. Oxidative Stress and Emergence of Psychosis ［J］. Antioxidants （Basel）， 2022， 11（10）：1870. doi:10.3390/antiox11101870 |
| 7 | CAO B， CHEN Y， REN Z， et al. Dysregulation of kynurenine pathway and potential dynamic changes of kynurenine in schizophrenia： A systematic review and meta-analysis ［J］. Neurosci Biobehav Rev， 2021， 123： 203-214. doi:10.1016/j.neubiorev.2021.01.018 |
| 8 | BEHL T， KAUR I， SEHGAL A， et al. The Footprint of Kynurenine Pathway in Neurodegeneration： Janus-Faced Role in Parkinson's Disorder and Therapeutic Implications ［J］. Int J Mol Sci， 2021， 22（13）：6737. doi:10.3390/ijms22136737 |
| 9 | ASLAMKHAN A G， XU Q， LOUGHLIN A， et al. Characterization of indoleamine-2，3-dioxygenase 1， tryptophan-2，3-dioxygenase， and Ido1/Tdo2 knockout mice ［J］. Toxicol Appl Pharmacol， 2020， 406： 115216. doi:10.1016/j.taap.2020.115216 |
| 10 | SAVONIJE K， MEEK A， WEAVER D F. Indoleamine 2，3-Dioxygenase as a Therapeutic Target for Alzheimer's Disease and Geriatric Depression ［J］. Brain Sci， 2023， 13（6）：852. doi:10.3390/brainsci13060852 |
| 11 | KINDLER J， LIM C K， WEICKERT C S， et al. Dysregulation of kynurenine metabolism is related to proinflammatory cytokines， attention， and prefrontal cortex volume in schizophrenia ［J］. Mol Psychiatry， 2020， 25（11）： 2860-2872. doi:10.1038/s41380-019-0401-9 |
| 12 | WURFEL B E， DREVETS W C， BLISS S A， et al. Serum kynurenic acid is reduced in affective psychosis ［J］. Transl Psychiatry， 2017， 7（5）： e1115. doi:10.1038/tp.2017.88 |
| 13 | JOAQUIM H P G， COSTA A C， GATTAZ W F， et al. Kynurenine is correlated with IL-1β in plasma of schizophrenia patients ［J］. J Neural Transm （Vienna）， 2018， 125（5）： 869-873. doi:10.1007/s00702-018-1838-8 |
| 14 | DE PICKER L， FRANSEN E， COPPENS V， et al. Immune and Neuroendocrine Trait and State Markers in Psychotic Illness： Decreased Kynurenines Marking Psychotic Exacerbations ［J］. Front Immunol， 2020， 10： 2971. doi:10.3389/fimmu.2019.02971 |
| 15 | CHIAPPELLI J， POCIVAVSEK A， NUGENT K L， et al. Stress-induced increase in kynurenic acid as a potential biomarker for patients with schizophrenia and distress intolerance ［J］. JAMA Psychiatry， 2014， 71（7）： 761-768. doi:10.1001/jamapsychiatry.2014.243 |
| 16 | AFIA A B， VILA è， MACDOWELL K S， et al. Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia： relationship with monoamines and symptomatology ［J］. J Neuroinflammation， 2021， 18（1）： 198. doi:10.1186/s12974-021-02260-6 |
| 17 | MARX W， MCGUINNESS A J， ROCKS T， et al. The kynurenine pathway in major depressive disorder， bipolar disorder， and schizophrenia： a meta-analysis of 101 studies ［J］. Mol Psychiatry， 2021， 26（8）： 4158-4178. doi:10.1038/s41380-020-00951-9 |
| 18 | SKOROBOGATOV K， AUTIER V， FOISELLE M， et al. Kynurenine pathway abnormalities are state-specific but not diagnosis-specific in schizophrenia and bipolar disorder ［J］. Brain Behav Immun Health， 2023， 27： 100584. doi:10.1016/j.bbih.2022.100584 |
| 19 | STONE T W. Does kynurenic acid act on nicotinic receptors？ An assessment of the evidence ［J］. J Neurochem， 2020， 152（6）： 627-649. doi:10.1111/jnc.14907 |
| 20 | VERDONK F， PETIT A C， ABDEL-AHAD P， et al. Microglial production of quinolinic acid as a target and a biomarker of the antidepressant effect of ketamine ［J］. Brain Behav Immun， 2019， 81： 361-373. doi:10.1016/j.bbi.2019.06.033 |
| 21 | 胡琳， 杨艳娟， 李洁滢， 等. 红景天苷通过激活PI3K/Akt和抑制NF-κB信号通路改善川崎病冠状动脉损伤 ［J］. 实用医学杂志， 2022， 38（21）： 2657-2662，2669. |
| 22 | MARCHETTI B， TIROLO C， L'EPISCOPO F， et al. Parkinson's disease， aging and adult neurogenesis： Wnt/β-catenin signalling as the key to unlock the mystery of endogenous brain repair ［J］. Aging Cell， 2020， 19（3）： e13101. doi:10.1111/acel.13101 |
| 23 | LIU J， XIAO Q， XIAO J， et al. Wnt/β-catenin signalling： function， biological mechanisms， and therapeutic opportunities ［J］. Signal Transduct Target Ther， 2022， 7（1）： 3. doi:10.1038/s41392-021-00762-6 |
| 24 | ALSABBAN A H， MORIKAWA M， TANAKA Y， et al. Kinesin Kif3b mutation reduces NMDAR subunit NR2A trafficking and causes schizophrenia-like phenotypes in mice ［J］. Embo J， 2020， 39（1）： e101090. doi:10.15252/embj.2018101090 |
| 25 | ZHANG L， LUDDEN C M， CULLEN A J， et al. Nuclear factor kappa B expression in non-small cell lung cancer ［J］. Biomed Pharmacother， 2023， 167： 115459. doi:10.1016/j.biopha.2023.115459 |
| 26 | VOLK D W， MOROCO A E， ROMAN K M， et al. The Role of the Nuclear Factor-κB Transcriptional Complex in Cortical Immune Activation in Schizophrenia ［J］. Biol Psychiatry， 2019， 85（1）： 25-34. doi:10.1016/j.biopsych.2018.06.015 |
| 27 | NORTH H F， BRUGGEMANN J， CROPLEY V， et al. Increased peripheral inflammation in schizophrenia is associated with worse cognitive performance and related cortical thickness reductions ［J］. Eur Arch Psychiatry Clin Neurosci， 2021， 271（4）： 595-607. doi:10.1007/s00406-021-01237-z |
| 28 | FRAGUAS D， DíAZ-CANEJA C M， AYORA M， et al. Oxidative Stress and Inflammation in First-Episode Psychosis： A Systematic Review and Meta-analysis ［J］. Schizophrenia Bulletin， 2019， 45（4）： 742-751. doi:10.1093/schbul/sby125 |
| 29 | YAN F， MENG X， CHENG X， et al. Potential role between inflammatory cytokines and Tie-2 receptor levels and clinical symptoms in patients with first-episode schizophrenia ［J］. BMC Psychiatry， 2023， 23（1）： 538. doi:10.1186/s12888-023-04913-7 |
| 30 | GOLDSMITH D R， HAROON E， MILLER A H， et al. Association of baseline inflammatory markers and the development of negative symptoms in individuals at clinical high risk for psychosis ［J］. Brain Behav Immun， 2019， 76： 268-274. doi:10.1016/j.bbi.2018.11.315 |
| 31 | KHANDAKER G M， STOCHL J， ZAMMIT S， et al. Association between circulating levels of C-reactive protein and positive and negative symptoms of psychosis in adolescents in a general population birth cohort ［J］. J Psychiatr Res， 2021， 143： 534-542. doi:10.1016/j.jpsychires.2020.11.028 |
| 32 | NISHIMON S， OHNUMA T， TAKEBAYASHI Y， et al. High serum soluble tumor necrosis factor receptor 1 predicts poor treatment response in acute-stage schizophrenia ［J］. Prog Neuropsychopharmacol Biol Psychiatry， 2017， 76： 145-154. doi:10.1016/j.pnpbp.2017.03.006 |
| 33 | NOTO C， MAES M， OTA V K， et al. High predictive value of immune-inflammatory biomarkers for schizophrenia diagnosis and association with treatment resistance ［J］. World J Biol Psychiatry， 2015， 16（6）： 422-429. doi:10.3109/15622975.2015.1062552 |
| 34 | FOND G， FAUGERE M， RICHIERI R， et al. Depressive symptoms and chronic peripheral inflammation are associated with impaired functional remission in schizophrenia independently of psychotic remission ［J］. J Affect Disord， 2021， 280（Pt A）： 267-271. doi:10.1016/j.jad.2020.11.046 |
| 35 | WIUM-ANDERSEN M K， ?RSTED D D， NORDESTGAARD B G. Elevated C-reactive protein associated with late- and very-late-onset schizophrenia in the general population： A prospective study ［J］. Schizophr Bull， 2014， 40（5）： 1117-1127. doi:10.1093/schbul/sbt120 |
| 36 | BüELER H. Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain ［J］. Int J Mol Sci， 2021， 22（7）：3342. doi:10.3390/ijms22073342 |
| 37 | CHAGRAOUI A， ANOUAR Y， DE DEURWAERDERE P， et al. To what extent may aminochrome increase the vulnerability of dopaminergic neurons in the context of Parkinson's disease ［J］. Int J Biochem Cell Biol， 2024， 168： 106528. doi:10.1016/j.biocel.2024.106528 |
| 38 | ZHANG S， WANG R， WANG G. Impact of Dopamine Oxidation on Dopaminergic Neurodegeneration ［J］. ACS Chem Neurosci， 2019， 10（2）： 945-953. doi:10.1021/acschemneuro.8b00454 |
| 39 | VIDAL P M， PACHECO R. Targeting the Dopaminergic System in Autoimmunity ［J］. J Neuroimmune Pharmacol， 2020， 15（1）： 57-73. doi:10.1007/s11481-019-09834-5 |
| 40 | GOH X X， TANG P Y， TEE S F. Effects of antipsychotics on antioxidant defence system in patients with schizophrenia： A meta-analysis ［J］. Psychiatry Res， 2022， 309： 114429. doi:10.1016/j.psychres.2022.114429 |
| 41 | LAVOIE S， BERGER M， SCHL?GELHOFER M， et al. Erythrocyte glutathione levels as long-term predictor of transition to psychosis ［J］. Transl Psychiatry， 2017， 7（3）： e1064. doi:10.1038/tp.2017.30 |
| 42 | LU Z， WEN T， WANG Y， et al. Peripheral non-enzymatic antioxidants in patients with schizophrenia： A case-control study ［J］. BMC Psychiatry， 2020， 20（1）： 241. doi:10.1186/s12888-020-02635-8 |
| 43 | ZHANG G， LI S， WANG S， et al. The association between serum albumin and depressive symptoms： A cross-sectional study of NHANES data during 2005-2018 ［J］. BMC Psychiatry， 2023， 23（1）： 448. doi:10.1186/s12888-023-04935-1 |
| 44 | MYKEN A N， EBDRUP B H， S?RENSEN M E， et al. Lower Vitamin C Levels Are Associated With Less Improvement in Negative Symptoms in Initially Antipsychotic-Na?ve Patients With First-Episode Psychosis ［J］. Int J Neuropsychopharmacol， 2022， 25（8）： 613-618. doi:10.1093/ijnp/pyac029 |
| 45 | REZAEI ZONOOZ S， HASANI M， MORVARIDZADEH M， et al. Effect of alpha-lipoic acid on oxidative stress parameters： A systematic review and meta-analysis ［J］. J Funct Foods， 2021， 87： 104774. doi:10.1016/j.jff.2021.104774 |
| 46 | DE LIMA D N J， COSTA FILHO C W L， FROTA I J， et al. α-Lipoic Acid as Adjunctive Treatment for Schizophrenia： A Randomized Double-Blind Study ［J］. J Clin Psychopharmacol， 2023， 43（1）： 39-45. doi:10.1097/jcp.0000000000001639 |
| 47 | SEDLAK T W， NUCIFORA L G， KOGA M， et al. Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects： A Clinical Pilot Study ［J］. Mol Neuropsychiatry， 2018， 3（4）： 214-22. doi:10.1159/000487639 |
| 48 | EDEMANN-CALLESEN H， BERNHARDT N， HLUSICKA E B， et al. Supplement Treatment with NAC and Omega-3 Polyunsaturated Fatty Acids during Pregnancy Partially Prevents Schizophrenia-Related Outcomes in the Poly I：C Rat Model ［J］. Antioxidants （Basel）， 2023， 12（5）：1068. doi:10.3390/antiox12051068 |
| 49 | GOH K K， CHEN C Y， CHEN C H， et al. Effects of omega-3 polyunsaturated fatty acids supplements on psychopathology and metabolic parameters in schizophrenia： A meta-analysis of randomized controlled trials ［J］. J Psychopharmacol， 2021， 35（3）： 221-235. doi:10.1177/0269881120981392 |
| 50 | 刘雪情， 宫秀群， 王侠， 等. 依达拉奉右莰醇治疗血管性痴呆的作用机制研究 ［J］. 实用医学杂志， 2023， 39（4）： 505-509. |
/
| 〈 |
|
〉 |