Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników
2020 | 80 | 2 |

Tytuł artykułu

Putative shared mechanisms in autism spectrum disorders and attention deficit hyperactivity disorder, a systematic review of the role of oxidative stress

Warianty tytułu

Języki publikacji



Oxidative stress is now believed to play a crucial role for neurodevelopment disorders such as autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). To review the most recent literature regarding the role of oxidative stress for the pathophysiology of ASD and ADHD, we conducted a systematic search of the relevant literature and further discuss the clinical and research implications of this knowledge. A systematic search in PubMed database retrieved 132 articles, of which 33 were included in the review. This review found relevant evidence concerning the role of oxidative status in ASD and ADHD, albeit with some contradictory findings. In order to overcome the incongruities found, more studies are needed in the study of neurodevelopmental disorders, with more thorough study designs and particular attention to the accuracy of the diagnostic tools used for the cases included.

Słowa kluczowe








Opis fizyczny



  • Department of Neurosciences and Mental Health, Faculty of Medicine, University of Porto, Porto, Portugal
  • Psychiatry and Mental Health Clinic, Centro Hospitalar Sao Joao, Porto, Portugal
  • I3S‑Instituto de Inovacao e Investigacao em Saude, Porto, Portugal
  • Center for Health Technology and Services Research (CINTESIS), Porto, Portugal,
  • Nutrition and Metabolism, NOVA Medical School, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal
  • Department of Neurosciences and Mental Health, Faculty of Medicine, University of Porto, Porto, Portugal
  • Psychiatry and Mental Health Clinic, Centro Hospitalar Sao Joao, Porto, Portugal
  • Department of Neurosciences and Mental Health, Faculty of Medicine, University of Porto, Porto, Portugal
  • I3S‑Instituto de Inovacao e Investigacao em Saúde, Porto, Portugal
  • Medical Psychology Unit, Department of Clinical Neurosciences and Mental Health Faculty of Medicine, University of Porto, Porto, Portugal


  • Abel MH, Ystrom E, Caspersen IH, Meltzer HM, Aase H, Torheim LE, Askeland RB, Reichborn‑Kjennerud T, Brantsæter AL (2017) Maternal iodine intake and offspring attention‑deficit/hyperactivity disorder: results from a large prospective cohort study. Nutrients 9: pii: E1239.
  • Al‑Ayadhi LY (2012) Relationship between sonic hedgehog protein, brain‑derived neurotrophic factor and oxidative stress in autism spectrum disorders. Neurochem Res 37: 394–400.
  • Al‑Gadani Y, El‑Ansary A, Attas O, Al‑Ayadhi L (2009) Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem 42: 1032–1040.
  • Angelova PR, Abramov AY (2018) Role of mitochondrial ROS in the brain: from physiology to neurodegeneration. FEBS Lett 592: 692–702.
  • Antshel KM, Russo N (2019) Autism spectrum disorders and ADHD: overlapping phenomenology, diagnostic issues, and treatment considerations. Curr Psychiatry Rep 21: 34.
  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders. 5th ed.; Washington, DC. Blazewicz A, Makarewicz A, Korona‑Glowniak I, Dolliver  W, Kocjan R (2016) Iodine in autism spectrum disorders. J Trace Elem Med Biol 34: 32–37.
  • Brieger K, Schiavone S, Miller FJ Jr, Krause KH (2012) Reactive oxygen species: from health to disease. Swiss Med Wkly 142: w13659.
  • Bulut M, Selek S, Bez Y, Cemal Kaya M, Gunes M, Karababa F, Celik H, Savas HA (2013) Lipid peroxidation markers in adult attention deficit hyperactivity disorder: new findings for oxidative stress. Psychiatry Res 209: 638–642.
  • CDC (2018) Centers for Disease Control and Prevention – National prevention of ADHD and treatment.‑prevalence‑adhd‑and‑treatment.html. Accessed 19th July 2019. Ceylan M, Sener S, Bayraktar AC, Kavutcu M (2010) Oxidative imbalance in child and adolescent patients with attention‑deficit/hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry 34: 1491–1494.
  • Ceylan MF, Sener S, Bayraktar AC, Kavutcu M (2012) Changes in oxidative stress and cellular immunity serum markers in attention‑deficit/hyperactivity disorder. Psychiatry Clin Neurosci 66: 220–226.
  • Chauhan A, Audhya T, Chauhan V (2012) Brain region‑specific glutathione redox imbalance in autism. Neurochem Res 37: 1681–1689.
  • Chauhan A, Chauhan  V, Brown WT, Cohen I (2004) Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin – the antioxidant proteins. Life Sci 75: 2539–2549.
  • Ciccoli  L, De Felice C, Paccagnini,E, Leoncini S, Pecorelli A, Signorini C, Belmonte G, Guerranti R, Cortelazzo A, Gentile  M, Zollo G, Durand T, Valacchi G, Rossi  M, Hayek J (2013) Erythrocyte shape abnormalities, membrane oxidative damage, and beta‑actin alterations: an unrecognized triad in classical autism. Mediators Inflamm 2013: 432616.
  • Dalle‑Donne I, Rossi R, Colombo R, Giustarini D, Milzani A (2006) Biomarkers of oxidative damage in human disease. Clin Chem 52: 601–623.
  • Damodaran LP, Arumugam G (2011) Urinary oxidative stress markers in children with autism. Redox Rep 16: 216–222.
  • Davies KJ (1995) Oxidative stress: the paradox of aerobic life. Biochem Soc Symp 61: 1–31.
  • Dickerson AS, Rahbar MH, Han I, Bakian AV, Bilder DA, Harrington RA, Pettygrove S, Durkin M, Kirby RS, Wingate MS, Tian LH, Zahorodny WM, Pearson DA, Moyé LA 3rd, Baio J (2015) Autism spectrum disorder prevalence and proximity to industrial facilities releasing arsenic, lead or mercury. Sci Total Environ 536: 245–251.
  • El‑Ansary A, Al‑Daihan S, Al‑Dbass A, Al‑Ayadhi L (2010) Measurement of selected ions related to oxidative stress and energy metabolism in Saudi autistic children. Clin Biochem 43: 63–70.
  • Guney E, Cetin FH, Alisik M, Tunca H, Tas Torun Y, Iseri E, Cayci B, Erel O (2015) Attention deficit hyperactivity disorder and oxidative stress: A short term follow up study. Psychiatry Res 229: 310–317.
  • Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97: 1634–1658.
  • Happe F, Ronald A, Plomin R (2006) Time to give up on a single explanation for autism. Nat Neurosci 9: 1218–1220.
  • Hodgson NW, Waly MI, Al‑Farsi YM, Al‑Sharbati MM, Al‑Farsi O, Ali A, Ouhtit A, Zang T, Zhou ZS, Deth RC (2014) Decreased glutathione and elevated hair mercury levels are associated with nutritional deficiency‑based autism in Oman. Exp Biol Med 239: 697–706.
  • Hultman CM, Sandin S, Levine SZ, Lichtenstein P, Reichenberg A (2011) Advancing paternal age and risk of autism: new evidence from a population‑based study and a meta‑analysis of epidemiological studies. Mol Psychiatry 16: 1203–1212.
  • James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW (2004) Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 80: 1611–1617.
  • James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH (2006) Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet 141B: 947–956.
  • Kawatani M, Tsukahara H, Mayumi M (2011) Evaluation of oxidative stress status in children with pervasive developmental disorder and attention deficit hyperactivity disorder using urinary‑specific biomarkers. Redox Rep 16: 45–46.
  • Kittel‑Schneider S, Reuss  M, Meyer A, Weber H, Gessner A, Leistner C (2015) Multi‑level biomarker analysis of nitric oxide synthase isoforms in bipolar disorder and adult ADHD. J Psychopharmacol 29: 31–38.
  • Lai MC, Lombardo MV, Baron‑Cohen S (2014) Autism. Lancet 383: 896–910.
  • Lakshmi Priya MD, Geetha A (2011) A biochemical study on the level of proteins and their percentage of nitration in the hair and nail of autistic children. Clin Chim Acta 412: 1036–1042.
  • Meguid NA, Dardir AA, Abdel‑Raouf ER, Hashish A (2011) Evaluation of oxidative stress in autism: defective antioxidant enzymes and increased lipid peroxidation. Biol Trace Elem Res 143: 58–65.
  • Melnyk S, Fuchs GJ, Schulz E, Lopez M, Kahler SG, Fussell JJ (2012) Metabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism. J Autism Dev Disord 42: 367–377.
  • Ming X, Stein TP, Brimacombe M, Johnson WG, Lambert GH, Wagner GC (2005) Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukot Essent Fatty Acids 73: 379–384.
  • Mostafa GA, El‑Hadidi ES, Hewedi DH, Abdou MM (2010) Oxidative stress in Egyptian children with autism: relation to autoimmunity. J Neuroimmunol 219: 114–118.
  • Musser ED, Hawkey E, Kachan‑Liu SS, Lees P, Roullet JB, Goddard K (2014) Shared familial transmission of autism spectrum and attention‑deficit/ hyperactivity disorders. J Child Psychol Psychiatry 557: 819–827.
  • Ng F, Berk M, Dean O, Bush AI (2008) Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol 11: 851–876.
  • Oerlemans AM, Hartman CA, De Bruijn YG, Van Steijn DJ, Franke B, Buitelaar JK (2015) Simplex and multiplex stratification in ASD and ADHD families: a promising approach for identifying overlapping and unique underpinnings of ASD and ADHD? J Autism Dev Disord 45: 645–657.
  • Oztop, D, Altun, H, Baskol, G, Ozsoy S (2012) Oxidative stress in children with attention deficit hyperactivity disorder. Clin Biochem 45: 745–748.
  • Pecorelli A, Leoncini S, De Felice C, Signorini C, Cerrone C, Valacchi G (2013) Non‑protein‑bound iron and 4‑hydroxynonenal protein adducts in classic autism. Brain Dev 35: 146–154.
  • Ranjbar A, Rashedi  V, Rezaei  M (2014) Comparison of urinary oxidative biomarkers in Iranian children with autism. Res Dev Disabil 35: 2751–2755.
  • Rommelse NN, Franke B, Geurts HM, Hartman CA, Buitelaar JK (2010) Shared heritability of attention‑deficit/hyperactivity disorder and autism spectrum disorder. Eur Child Adolesc Psychiatry 19: 281–295.
  • Rose S, Melnyk S, Pavliv O, Bai S, Nick TG, Frye RE (2012) Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry 2: e134.
  • Sajdel‑Sulkowska EM, Xu M, Koibuchi N (2009) Increase in cerebellar neurotrophin‑3 and oxidative stress markers in autism. Cerebellum 8: 366–372.
  • Sandin S, Hultman CM, Kolevzon A, Gross R, MacCabe JH, Reichenberg A (2012) Advancing maternal age is associated with increasing risk for autism: a review and meta‑analysis. J Am Acad Child Adolesc Psychiatry 51: 477–486.
  • Sciberras E, Mulraney M, Silva D, Coghill D (2017) Prenatal risk factors and the etiology of ADHD – review of existing evidence. Curr Psychiatry Rep 19: 1.
  • Selek S, Bulut M, Ocak AR, Kalenderoglu A, Savas HA (2012) Evaluation of total oxidative status in adult attention deficit hyperactivity disorder and its diagnostic implications. J Psychiatr Res 46: 451–455.
  • Selek S, Savas HA, Gergerlioglu HS, Bulut M, Yilmaz HR (2008) Oxidative imbalance in adult attention deficit/hyperactivity disorder. Biol Psychol 79: 256–259.
  • Sogut S, Zoroglu SS, Ozyurt, H, Yilmaz, H. R, Ozugurlu, F, Sivasli, E, Yetkin O, Yanik M, Tutkun, Savaş HA, Tarakçioğlu M, Akyolet O (2003) Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin Chim Acta 331: 111–117.
  • Tran NQV, Miyake K (2017) Neurodevelopmental disorders and environmental toxicants: epigenetics as an underlying mechanism. Int J Genomics 2017: 7526592.
  • Verlaet AAJ, Breynaert A, Ceulemans B, De Bruyne T, Fransen E, Pieters L, Savelkoul HFJ, Hermans N (2019) Oxidative stress and immune aberrancies in attention‑deficit/hyperactivity disorder (ADHD): a  case‑control comparison. Eur Child Adolesc Psychiatry 28: 719–729.
  • Wang C, Geng H, Liu W, Zhang G (2017) Prenatal, perinatal, and postnatal factors associated with autism: a meta‑analysis. Medicine 96: e6696.
  • Yenkoyan K, Harutyunyan H, Harutyunyan A (2018) A certain role of SOD/ CAT imbalance in pathogenesis of autism spectrum disorders. Free Radic Biol Med 123: 85–95.
  • Yorbik O, Sayal A, Akay C, Akbiyik D I, Sohmen T (2002) Investigation of antioxidant enzymes in children with autistic disorder. Prostaglandins Leukot Essent Fatty Acids 67: 341–343.
  • Zoroglu S S, Armutcu F, Ozen S, Gurel A, Sivasli E, Yetkin O, Meram I (2004) Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur Arch Psychiatry Clin Neurosci 254: 143–147.

Typ dokumentu



Identyfikator YADDA

JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.