Role of oxidative stress in the pathogenesis of autism spectrum disorders
- Authors: Belokoskova S.G.1, Tsikunov S.G.1
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Affiliations:
- Institute of Experimental Medicine
- Issue: Vol 21, No 3 (2023)
- Pages: 215-230
- Section: Reviews
- URL: https://journals.eco-vector.com/RCF/article/view/567781
- DOI: https://doi.org/10.17816/RCF567781
- ID: 567781
Cite item
Abstract
The literature review reflects the contemporary information on the role of oxidative stress in the pathogenesis of autism spectrum disorders. We present data on the importance of genetic predisposition, environmental factors, and epigenetic influences on the development of oxidative stress, which, during critical periods of early brain development, may influence the induction and progression of the disease. The role of mitochondrial dysfunction, immunological disorders, increased permeability of the blood-brain barrier, hypoperfusion of the brain causing or aggravating the redox imbalance in patients with autism spectrum disorders is shown. Analysis of the literature data indicates that the increased content of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione, ceruloplasmin and transferrin in the blood and brain of patients with autism spectrum disorders reflects the activation of compensatory mechanisms. Increased levels of malondialdehyde, xanthine oxidase, nitric oxide in various biological media indicate insufficiency of antioxidant protection system. Taking into account the role of oxidative stress in the pathogenesis of autism spectrum disorders, therapy including antioxidant drugs is indicated for correction of metabolic disorders.
Full Text
About the authors
Svetlana G. Belokoskova
Institute of Experimental Medicine
Email: belokoskova.sg@iemspb.ru
ORCID iD: 0000-0002-0552-4810
SPIN-code: 4317-6620
Scopus Author ID: 6507716078
Dr. Sci. (Med), senior research associate, Pavlov Department of Physiology
Russian Federation, Saint PetersburgSergey G. Tsikunov
Institute of Experimental Medicine
Author for correspondence.
Email: secikunov@yandex.ru
ORCID iD: 0000-0002-7097-1940
SPIN-code: 7771-1940
Scopus Author ID: 6506948997
Dr. Sci. (Med.), professor, head of the Laboratory of Psychophysiology of Emotions
Russian Federation, Saint PetersburgReferences
- Arushanyan EB, Naumov SS. Oxidative stress as a problem of psychopharmacology. Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(4):297–311. (In Russ.) doi: 10.17816/RCF184297-311
- Belokoskova SG, Malsagova EM, Tsikunov SG. Dynamics of age-related structural and functional changes in the brain of patients with autism spectrum disorders. Medical academic journal. 2019;19(3):21–26. (In Russ.) doi: 10.17816/MAJ19321-26
- Belokoskova SG, Tsikunov SG. Antioxidant and prooxidant systems in patients with ischemic insult. Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):281–290. (In Russ.) doi: 10.17816/RCF193281-290
- Boldyrev AA, Kulebyakin KY, Arzumanyan ES, Berezov TT. Novel mechanism of regulation of brain plasticity. Neurochemical Journal. 2011;28(4):340–344. (In Russ.)
- Maltseva NV, Volchegorskii IA, Shemyakov SE. Age changes of morphometric characteristics of neurons, microglia cells and antioxidant protection enzymes activity in human cortex at the initial stages of postnatal ontogenesis. Morphological newsletter. 2016;24(1):112–115. (In Russ.) doi: 10.20340/mv-mn.2016.24(1):112-115
- Novikov VE, Levchenkova OS, Ivantsova EN, Vorobieva VV. Mitochondrial dysfunctions and antihypoxants. Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(4):31–42. (In Russ.) doi: 10.17816/RCF17431-42
- Porokhovnik LN, Pasekov VP, Yegolina NA, et al. Oxidative stress, RRNA genes, and antioxidant enzymes in pathogenesis of schizophrenia and autism: modeling and clinical advices. Journal of general biology. 2013;74(5):340–353. (In Russ.)
- Rossiiskoe obshchestvo psikhiatrov. Rasstroistva autisticheskogo spektra v detskom vozraste: diagnostika, terapiya, profilaktika, reabilitatsiya. Klinicheskie rekomendatsii. Moscow, 2020. 125 p. (In Russ.)
- Simashkova NV, Makushkin EV, editors. Rasstroistva autisticheskogo spektra: diagnostika, lechenie, nablyudenie. Klinicheskie rekomendatsii (protokol lecheniya). Moscow, 2015. 50 p. (In Russ.)
- Afrazeh M, Saedisar S, Khakzad MR, Hojati M. Measurement of serum superoxide dismutase and its relevance to disease intensity autistic children. Maedica (Buchar). 2015;10(4):315–318.
- Akhondzadeh S, Fallah J, Mohammadi MR, et al. Double-blind placebo-controlled trial of pentoxifylline added to risperidone: effects on aberrant behavior in children with autism. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(1):32–36. doi: 10.1016/j.pnpbp.2009.09.012
- Al-Ayadhi LY, Mostafa GA. A lack of association between elevated serum levels of S100B protein and autoimmunity in autistic children. J Neuroinflammation. 2012;9:54. doi: 10.1186/1742-2094-9-54
- Al-Gadani Y, El-Ansary A, Attas O, Al-Ayadhi L. Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem. 2009;42(10–11):1032–1040. doi: 10.1016/j.clinbiochem.2009.03.011
- Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke. 2009;4(6):461–470. doi: 10.1111/j.1747-4949.2009.00387.x
- Al-Yafee YA, Al-Ayadhi LY, Haq SH, El-Ansary AK. Novel metabolic biomarkers related to sulfur-dependent detoxification pathways in autistic patients of Saudi Arabia. BMC Neurol. 2011;11:139. doi: 10.1186/1471-2377-11-139
- American Psychiatric Association. Diagnostic and statistical manual of mental disorders. American Psychiatric Association, 2013. doi: 10.1176/appi. books.9780890425596
- Aoyama K, Nakaki T. Impaired glutathione synthesis in neurodegeneration. Int J Mol Sci. 2013;14(10):21021–21044. doi: 10.3390/ijms141021021
- Armogida M, Nisticò R, Mercuri NB. Therapeutic potential of targeting hydrogen peroxide metabolism in the treatment of brain ischemia. Br J Pharmacol. 2012;166(4):1211–1224. doi: 10.1111/j.1476-5381.2012.01912.x
- Asadabadi M, Mohammadi M-R, Ghanizadeh A, et al. Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial. Psychopharmacology (Berl). 2013;225(1):51–59. doi: 10.1007/s00213-012-2796-8
- Asanuma M, Miyazaki I, Diaz-Corrales FJ, et al. Neuroprotective effects of zonisamide target astrocyte. Ann Neurol. 2010;67(2):239–249. doi: 10.1002/ana.21885
- Bai J, Cederbaum AI. Mitochondrial catalase and oxidative injury. Biol Signals Recept. 2001;10(3–4):189–199. doi: 10.1159/000046887
- Bauman ML. Medical comorbidities in autism: challenges to diagnosis and treatment. Neurotherapeutics. 2010;7(3):320–327. doi: 10.1016/j.nurt.2010.06.001
- Berk M, Ng F, Dean O, et al. Glutathione: a novel treatment target in psychiatry. Trends Pharmacol Sci. 2008;29(7):346–351. doi: 10.1016/j.tips.2008.05.001
- Bertoglio K, James JS, Deprey L, et al. Pilot study of the effect of methyl B12 treatment on behavioral and biomarker measures in children with autism. J Altern Complement Med. 2010;16(5):555–560. doi: 10.1089/acm.2009.0177
- Bjørklund G, Kern JK, Urbina MA, et al. Cerebral hypoperfusion in autism spectrum disorder. Acta Neurobiol Exp (Wars). 2018;78(1):21–29. doi: 10.21307/ane-2018-005
- Bjørklund G, Meguid NA, El-Ansary A, et al. Diagnostic and severity-tracking biomarkers for autism spectrum disorder. J Mol Neurosci. 2018;66(4):492–511. doi: 10.1007/s12031-018-1192-1
- Bjørklund G, Tinkov AA, Hosnedlová B, et al. The role of glutathione redox imbalance in autism spectrum disorder: A review. Free Radic Biol Med. 2020;160:149–162. doi: 10.1016/j.freeradbiomed.2020.07.017
- Bolotta A, Battistelli M, Falcieri E, et al. Oxidative stress in autistic children alters erythrocyte shape in the absence of quantitative protein alterations and of loss of membrane phospholipid asymmetry. Oxid Med Cell Longev. 2018;2018:6430601. doi: 10.1155/2018/6430601
- Bordet T, Berna P, Abitbol J-L, Pruss RM. Olesoxime (TRO19622): A novel mitochondrial-targeted neuroprotective compound. Pharmaceuticals (Basel). 2010;3(2):345–368. doi: 10.3390/ph3020345
- Chauhan A, Audhya T, Chauhan V. Brain region-specific glutathione redox imbalance in autism. Neurochem Res. 2012;37(8): 1681–1689. doi: 10.1007/s11064-012-0775-4
- Chauhan A, Chauhan V, Brown WT, Cohen I. Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin — the antioxidant proteins. Life Sci. 2004;75(21):2539–2549. doi: 10.1016/j.lfs.2004.04.038
- Chauhan A, Gu F, Essa MM, et al. Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism. J Neurochem. 2011;117(2):209–220. doi: 10.1111/j.1471-4159.2011.07189.x
- Chauhan A, Chauhan V. Oxidative stress in autism. Pathophysiology. 2006;13(3):171–181. doi: 10.1016/j.pathophys.2006.05.007
- Connolly AM, Chez MG, Pestronk A, et al. Serum autoantibodies to brain in Landau–Kleffner variant, autism, and other neurologic disorders. J Pediatr. 1999;134(5):607–613. doi: 10.1016/s0022-3476(99)70248-9
- Courchesne E, Pramparo T, Gazestani VH, et al. The ASD Living Biology: from cell proliferation to clinical phenotype. Mol Psychiatry. 2019;24(1):88–107. doi: 10.1038/s41380-018-0056-y
- Cyr AR, Domann FE. The redox basis of epigenetic modifications: from mechanisms to functional consequences. Antioxid Redox Signal. 2011;15(2):551–589. doi: 10.1089/ars.2010.3492
- Damodaran LPM, Arumugam G. Urinary oxidative stress markers in children with autism. Redox Rep. 2011;16(5):216–222. doi: 10.1179/1351000211Y.0000000012
- Deth R, Muratore C, Benzecry J, et al. How environmental and genetic factors combine to cause autism: a redox/methylation hypothesis. Neurotoxicology. 2008;29(1):190–201. doi: 10.1016/j.neuro.2007.09.010
- Dodd S, Dean O, Copolov DL, et al. N-acetylcysteine for antioxidant therapy: Pharmacology and clinical utility. Expert Opin Biol Ther. 2008;8(12):1955–1962. doi: 10.1517/14728220802517901
- Esnafoglu E, Nur Ayyıldız S, Cırrık S, et al. Evaluation of serum Neuron-specific enolase, S100B, myelin basic protein and glial fibrilliary acidic protein as brain specific proteins in children with autism spectrum disorder. Int J Dev Neurosci. 2017;61(1):86–91. doi: 10.1016/j.ijdevneu.2017.06.011
- Essa MM, Qoronfleh MW, editors. Personalized food intervention and therapy for autism spectrum disorder management. In: Schousboe A, editor. Advances in Neurobiology. Vol. 24. Springer Cham, 2020. doi: 10.1007/978-3-030-30402-7
- Essa MM, Guillemin GJ, Waly MI, et al. Increased markers of oxidative stress in autistic children of the Sultanate of Oman. Biol Trace Elem Res. 2012;147(1–3):25–27. doi: 10.1007/s12011-011-9280-x
- Fatemi SH, Aldinger KA, Ashwood P, et al. Consensus paper: pathological role of the cerebellum in autism. Cerebellum. 2012;11(3):777–807. doi: 10.1007/s12311-012-0355-9
- Feil R. Environmental and nutritional effects on the epigenetic regulation of genes. Mutat Res. 2006;600(1–2):46–57. doi: 10.1016/j.mrfmmm.2006.05.029
- Fiorentino M, Sapone A, Senger S, et al. Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism. 2016;7:49. doi: 10.1186/s13229-016-0110-z
- Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829–837. doi: 10.1093/eurheartj/ehr304
- Franco R, Panayiotidis MI, Cidlowski JA. Glutathione depletion is necessary for apoptosis in lymphoid cells independent of reactive oxygen species formation. J Biol Chem. 2007;282(42):30452–30465. doi: 10.1074/jbc.M703091200
- Froehlich-Santino W, Londono Tobon A, Cleveland S, et al. Prenatal and perinatal risk factors in a twin study of autism spectrum disorders. J Psychiatr Res. 2014;54:100–108. doi: 10.1016/j.jpsychires.2014.03.019
- Frustaci A, Neri M, Cesario A, et al. Oxidative stress-related biomarkers in autism: systematic review and meta-analyses. Free Radic Biol Med. 2012;52(10):2128–2141. doi: 10.1016/j.freeradbiomed.2012.03.011
- Frye RE, Delatorre R, Taylor H, et al. Redox metabolism abnormalities in autistic children associated with mitochondrial disease. Transl Psychiatry. 2013;3(6): e273. doi: 10.1038/tp.2013.51
- Gantner BN, LaFond KM, Bonini MG. Nitric oxide in cellular adaptation and disease. Redox Biol. 2020;34:101550. doi: 10.1016/j.redox.2020.101550
- Gardener H, Spiegelman D, Buka SL. Perinatal and neonatal risk factors for autism: a comprehensive meta-analysis. Pediatrics. 2011;128(2):344–355. doi: 10.1542/peds.2010-1036
- Gebicka L, Krych-Madej J. The role of catalases in the prevention/promotion of oxidative stress. J Inorg Biochem. 2019;197:110699. doi: 10.1016/j.jinorgbio.2019.110699
- Ghaleiha A, Rasa SM, Nikoo M, et al. A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone: Effects on aberrant behavior in children with autism. Psychiatry Res. 2015;229(1–2):181–187. doi: 10.1016/j.psychres.2015.07.043
- Ghanizadeh A. A novel hypothesized clinical implication of zonisamide for autism. Ann Neurol. 2011;69(2):426–426. doi: 10.1002/ana.22153
- Ghanizadeh A. Methionine sulfoximine may improve inflammation in autism, a novel hypothesized treatment for autism. Arch Med Res. 2010;41(8):651–652. doi: 10.1016/j.arcmed.2010.10.012
- Ghanizadeh A, Akhondzadeh S, Hormozi M, et al. Glutathione-related factors and oxidative stress in autism: A review. Curr Med Chem. 2012;19(23):4000–4005. doi: 10.2174/092986712802002572
- Goh S, Dong Z, Zhang Y, et al. Mitochondrial dysfunction as a neurobiological subtype of autism spectrum disorder: evidence from brain imaging. JAMA Psychiatry. 2014;71(6):665–671. doi: 10.1001/jamapsychiatry.2014.179
- Gu F, Chauhan V, Kaur K, et al. Alterations in mitochondrial DNA copy number and the activities of electron transport chain complexes and pyruvate dehydrogenase in the frontal cortex from subjects with autism. Transl Psychiatry. 2013;3(9): e299. doi: 10.1038/tp.2013.68
- Hafizi S, Tabatabaei D, Lai M-C. Review of clinical studies targeting inflammatory pathways for individuals with autism. Front Psychiatry. 2019;10:849. doi: 10.3389/fpsyt.2019.00849
- Heck DE. •NO, RSNO, ONOO–, NO+, •NOO, NOx — dynamic regulation of oxidant scavenging, nitric oxide stores, and cyclic GMP-independent cell signaling. Antioxid Redox Signal. 2001;3(2):249–260. doi: 10.1089/152308601300185205
- Hendren RL, James SJ, Widjaja F, et al. Randomized, placebo-controlled trial of methyl B12 for children with autism. J Child Adolesc Psychopharmacol. 2016;26(9):774–783. doi: 10.1089/cap.2015.0159
- Heo JH, Han SW, Lee SK. Free radicals as triggers of brain edema formation after stroke. Free Radic Biol Med. 2005;39(1):151–170. doi: 10.1016/j.freeradbiomed.2005.03.035
- Hu C-C, Xu X, Xiong G-L, et al. Alterations in plasma cytokine levels in Chinese children with autism spectrum disorder. Autism Res. 2018;11(7):989–999. doi: 10.1002/aur.1940.
- Hu VW. The expanding genomic landscape of autism: discovering the ‘forest’ beyond the ‘trees’. Future Neurol. 2013;8(1):29–42. doi: 10.2217/fnl.12.83
- Ivanov HY, Stoyanova VK, Popov NT, et al. Autism spectrum disorder — a complex genetic disorder. Folia med (Plovdiv). 2015;57(1):19–28. doi: 10.1515/folmed-2015-0015
- Jamain S, Betancur C, Giros B, et al. Genetics of autism: from genome scans to candidate genes. Med Sci (Paris). 2003;19(11): 1081–1090. (In French.) doi: 10.1051/medsci/200319111081
- James SJ, Cutler P, Melnyk S, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004;80(6):1611–1617. doi: 10.1093/ajcn/80.6.1611
- James SJ, Melnyk S, Fuchs G, et al. Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr. 2009;89(1):425–430. doi: 10.3945/ajcn.2008.26615
- James SJ, Melnyk S, Jernigan S, et al. Abnormal transmethylation/transsulfuration metabolism and DNA hypomethylation among parents of children with autism. J Autism Dev Disord. 2008;38(10):1966–1975. doi: 10.1007/s10803-008-0591-5
- James SJ, Melnyk S, Jernigan S, et al. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(8):947–956. doi: 10.1002/ajmg.b.30366
- Kealy J, Greene C, Campbell M. Blood-brain barrier regulation in psychiatric disorders. Neurosci Lett. 2020;726:133664. doi: 10.1016/j.neulet.2018.06.033
- Kondolot M, Ozmert EN, Ascı A, et al. Plasma phthalate and bisphenol a levels and oxidant-antioxidant status in autistic children. Environ Toxicol Pharmacol. 2016;43:149–158. doi: 10.1016/j.etap.2016.03.006
- Kontos HA. Oxygen radicals in cerebral ischemia: the 2001 Willis lecture. Stroke. 2001;32(11):2712–2716. doi: 10.1161/hs1101.098653
- Ladd-Acosta C, Hansen KD, Briem E, et al. Common DNA methylation alterations in multiple brain regions in autism. Mol Psychiatry. 2014;19(8):862–871. doi: 10.1038/mp.2013.114
- László A, Novák Z, Szőllősi-Varga I, et al. Blood lipid peroxidation, antioxidant enzyme activities and hemorheological changes in autistic children. Ideggyogy Sz. 2013;66(1–2):23–28.
- Li H, Horke S, Förstermann U. Oxidative stress in vascular disease and its pharmacological prevention. Trends Pharmacol Sci. 2013;34(6):313–319. doi: 10.1016/j.tips.2013.03.007
- Li W, Busu C, Circu ML, Aw TY. Glutathione in cerebral microvascular endothelial biology and pathobiology: implications for brain homeostasis. Int J Cell Biol. 2012;2012:434971. doi: 10.1155/2012/434971
- Mahadik SP, Scheffer RE. Oxidative injury and potential use of antioxidants in schizophrenia. Prostaglandins Leukot Essent Fatty Acids. 1996;55(1–2):45–54. doi: 10.1016/s0952-3278(96)90144-1
- Main PAE, Angley MT, O’Doherty CE, et al. The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis. Nutr Metab (Lond). 2012;9:35. doi: 10.1186/1743-7075-9-35
- Masini E, Loi E, Vega-Benedetti AF, et al. An overview of the main genetic, epigenetic and environmental factors involved in autism spectrum disorder focusing on synaptic activity. Int J Mol Sci. 2020;21(21):8290. doi: 10.3390/ijms21218290
- Meguid NA, Ghozlan SAS, Mohamed MF, et al. Expression of reactive oxygen species-related transcripts in Egyptian children with autism. Biomark Insights. 2017;12:1177271917691035. doi: 10.1177/1177271917691035
- Melnyk S, Fuchs GJ, Schulz E, et al. Metabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism. J Autism Dev Disord. 2012;42(3):367–377. doi: 10.1007/s10803-011-1260-7
- Menezo YJ, Silvestris E, Dale B, Elder K. Oxidative stress and alterations in DNA methylation: two sides of the same coin in reproduction. Reprod BioMed Online. 2016;33(6):668–683. doi: 10.1016/j.rbmo.2016.09.006
- Ming X, Stein TP, Brimacombe M, et al. Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukot Essent Fatty Acids. 2005;73(5):379–384. DOI: 10.1016/j. plefa.2005.06.002
- Morris G, Anderson G, Dean O, et al. The glutathione system: a new drug target in neuroimmune disorders. Mol Neurobiol. 2014;50(3):1059–1084. doi: 10.1007/s12035-014-8705-x
- Nadeem A, Ahmad SF, Attia SM, et al. Dysregulated enzymatic antioxidant network in peripheral neutrophils and monocytes in children with autism. Prog Neuropsychopharmacol Biol Psychiatry. 2019;88:352–359. doi: 10.1016/j.pnpbp.2018.08.020
- Nagarajan RP, Patzel KA, Martin M, et al. MECP2 promoter methylation and X chromosome inactivation in autism. Autism Res. 2008;1(3):169–178. doi: 10.1002/aur.24
- Nardone S, Sams DS, Reuveni E, et al. DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways. Transl Psychiatry. 2014;4(9):e433. doi: 10.1038/tp.2014.70
- Newschaffer CJ, Croen LA, Daniels J, et al. The epidemiology of autism spectrum disorders. Annu Rev Public Health. 2007;28: 235–258. doi: 10.1146/annurev.publhealth.28.021406.144007
- Nguyen A, Rauch TA, Pfeifer GP, Hu VW. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB J. 2010;24(8):3036–3051. doi: 10.1096/fj.10-154484
- Pangrazzi L, Balasco L, Bozzi Y. Oxidative stress and immune system dysfunction in autism spectrum disorders. Int J Mol Sci. 2020;21(9):3293. doi: 10.3390/ijms21093293
- Paşca SP, Nemeş B, Vlase L, et al. High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism. Life Sci. 2006;78(19):2244–2248. doi: 10.1016/j.lfs.2005.09.040
- Ray PD, Huang B-W, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012;24(5):981–990. doi: 10.1016/j.cellsig.2012.01.008
- Rose S, Melnyk S, Pavliv O, et al. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry. 2012;2(7): e134. doi: 10.1038/tp.2012.61
- Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry. 2012;17(3):290–314. doi: 10.1038/mp.2010.136
- Schanen NC. Epigenetics of autism spectrum disorders. Hum Mol Genet. 2006;15(S2):R138–R150. doi: 10.1093/hmg/ddl213
- Schulz JB, Lindenau J, Seyfried J, Dichgans J. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem. 2000;267(16):4904–4911. doi: 10.1046/j.1432-1327.2000.01595.x
- Shichiri M. The role of lipid peroxidation in neurological disorders. J Clin Biochem Nutr. 2014;54(3):151–160. doi: 10.3164/jcbn.14-10
- Siddiqui MF, Elwell C, Johnson MH. Mitochondrial dysfunction in autism spectrum disorders. Autism Open Access. 2016;6(5):1000190. doi: 10.4172/2165-7890.10001900
- Söğüt S, Zoroğlu SS, Ozyurt H, et al. Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin Chim Acta. 2003;331(1–2):111–117. doi: 10.1016/s0009-8981(03)00119-0
- Srikantha P, Mohajeri MH. The possible role of the microbiota-gut-brain-axis in autism spectrum disorder. Int J Mol Sci. 2019;20(9):2115. doi: 10.3390/ijms20092115
- Tostes MHFS, Teixeira HC, Gattaz WF, et al. Altered neurotrophin, neuropeptide, cytokines and nitric oxide levels in autism. Pharmacopsychiatry. 2012;45(6):241–243. doi: 10.1055/s-0032-1301914
- Valiente-Pallejà A, Torrell H, Muntané G, et al. Genetic and clinical evidence of mitochondrial dysfunction in autism spectrum disorder and intellectual disability. Hum Mol Genet. 2018;27(5): 891–900. doi: 10.1093/hmg/ddy009
- Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44–84. doi: 10.1016/j.biocel.2006.07.001
- Wang Q, Fan W, Cai Y, et al. Protective effects of taurine in traumatic brain injury via mitochondria and cerebral blood flow. Amino Acids. 2016;48(9):2169–2177. doi: 10.1007/s00726-016-2244-x
- Weissman JR, Kelley RI, Bauman ML, et al. Mitochondrial disease in autism spectrum disorder patients: a cohort analysis. PLoS One. 2008;3(11): e3815. doi: 10.1371/journal.pone.0003815
- Xu N, Li X, Zhong Y. Inflammatory cytokines: potential biomarkers of immunologic dysfunction in autism spectrum disorders. Mediators Inflamm. 2015;2015:531518. doi: 10.1155/2015/531518
- Yabuki M, Kariya S, Ishisaka R, et al. Resistance to nitric oxide-mediated apoptosis in HL-60 variant cells is associated with increased activities of Cu, Zn-superoxide dismutase and catalase. Free Radic Biol Med. 1999;26(3–4):325–332. doi: 10.1016/S0891-5849(98)00203-2
- Yenkoyan K, Harutyunyan H, Harutyunyan A. A certain role of SOD/CAT imbalance in pathogenesis of autism spectrum disorders. Free Radic Biol Med. 2018;123:85–95. doi: 10.1016/j.freeradbiomed.2018.05.070
- Yorbik O, Sayal A, Akay C, et al. Investigation of antioxidant enzymes in children with autistic disorder. Prostaglandins Leukot Essent Fatty Acids. 2002;67(5):341–343. doi: 10.1054/plef.2002.0439
- Yui K, Kawasaki Y, Yamada H, Ogawa S. oxidative stress and nitric oxide in autism spectrum disorder and other neuropsychiatric disorders. CNS Neurol Disord Drug Targets. 2016;15(5):587–596. doi: 10.2174/1871527315666160413121751
- Zilbovicius M, Meresse I, Chabane N, et al. Autism, the superior temporal sulcus and social perception. Trends Neurosci. 2006;29(7):359–366. doi: 10.1016/j.tins.2006.06.004
- Zoroglu SS, Armutcu F, Ozen S, et al. Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur Arch Psychiatry Clin Neurosci. 2004;254(3):143–147. doi: 10.1007/s00406-004-0456-7