Skip to main content
SpringerLink
Log in

A Potential Role for Neuroinflammation in ADHD

  • Chapter
  • First Online:
Neuroinflammation, Gut-Brain Axis and Immunity in Neuropsychiatric Disorders

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1411))

Abstract

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioural disorder in children and adolescents. Although increases in oxidative stress and disturbances of neurotransmitter system such as the dopaminergic and abnormalities in several brain regions have been demonstrated, the pathophysiology of ADHD is not fully understood. Nevertheless, ADHD involves several factors that have been associated with an increase in neuroinflammation. This chapter presents an overview of factors that may increase neuroinflammation and play a potential role in the development and pathophysiology of ADHD. The altered immune response, polymorphisms in inflammatory-related genes, ADHD comorbidity with autoimmune and inflammatory disorders and prenatal exposure to inflammation are associated with alterations in offspring brain development and are a risk factor; genetic and environmental risk factors that may increase the risk for ADHD and medications can increase neuroinflammation. Evidence of an association between these factors has been an invaluable tool for research on inflammation in ADHD. Therefore, evidence studies have made it possible to generate alternative therapeutic interventions using natural products as anti-inflammatories that could have great potential against neuroinflammation in ADHD.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Cortese S. Pharmacologic treatment of attention deficit-hyperactivity disorder. N Engl J Med. 2020;383(11):1050–6.

    Article  CAS  PubMed  Google Scholar 

  2. Faraone SV, Asherson P, Banaschewski T, Biederman J, Buitelaar JK, Ramos-Quiroga JA, et al. Attention-deficit/hyperactivity disorder. Nat Rev Dis Prim. 2015;1:15020.

    Article  PubMed  Google Scholar 

  3. Corona JC. Pharmacological approaches for the treatment of attention-deficit/hyperactivity disorder. In: Kyser BM, editor. Attention-deficit hyperactivity disorder: diagnosis, prevalence and treatment. New York, NY: Nova Science Publishers, Inc.; 2021. p. 1–39.

    Google Scholar 

  4. Posner J, Polanczyk GV, Sonuga-Barke E. Attention-deficit hyperactivity disorder. Lancet. 2020;395(10222):450–62.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Faraone SV, Banaschewski T, Coghill D, Zheng Y, Biederman J, Bellgrove MA, et al. The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder. Neurosci Biobehav Rev. 2021;128:789–818.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Polanczyk GV, Willcutt EG, Salum GA, Kieling C, Rohde LA. ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis. Int J Epidemiol. 2014;43(2):434–42.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Simon V, Czobor P, Balint S, Meszaros A, Bitter I. Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. Br J Psychiatry. 2009;194(3):204–11.

    Article  PubMed  Google Scholar 

  8. Song P, Zha M, Yang Q, Zhang Y, Li X, Rudan I. The prevalence of adult attention-deficit hyperactivity disorder: a global systematic review and meta-analysis. J Glob Health. 2021;11:04009.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Fayyad J, Sampson NA, Hwang I, Adamowski T, Aguilar-Gaxiola S, Al-Hamzawi A, et al. The descriptive epidemiology of DSM-IV Adult ADHD in the World Health Organization World Mental Health Surveys. Attent Deficit Hyperact Disord. 2017;9(1):47–65.

    Article  Google Scholar 

  10. Dobrosavljevic M, Solares C, Cortese S, Andershed H, Larsson H. Prevalence of attention-deficit/hyperactivity disorder in older adults: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2020;118:282–9.

    Article  PubMed  Google Scholar 

  11. Sayal K, Prasad V, Daley D, Ford T, Coghill D. ADHD in children and young people: prevalence, care pathways, and service provision. Lancet Psychiatry. 2018;5(2):175–86.

    Article  PubMed  Google Scholar 

  12. Willcutt EG, Nigg JT, Pennington BF, Solanto MV, Rohde LA, Tannock R, et al. Validity of DSM-IV attention deficit/hyperactivity disorder symptom dimensions and subtypes. J Abnorm Psychol. 2012;121(4):991–1010.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007;164(6):942–8.

    Article  PubMed  Google Scholar 

  14. Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005;57(11):1313–23.

    Article  CAS  PubMed  Google Scholar 

  15. Purper-Ouakil D, Ramoz N, Lepagnol-Bestel AM, Gorwood P, Simonneau M. Neurobiology of attention deficit/hyperactivity disorder. Pediatr Res. 2011;69(5 Pt 2):69R–76R.

    Article  PubMed  Google Scholar 

  16. Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat Genet. 2019;51(1):63–75.

    Article  CAS  PubMed  Google Scholar 

  17. Nigg JT, Sibley MH, Thapar A, Karalunas SL. Development of ADHD: etiology, heterogeneity, and early life course. Annu Rev Dev Psychol. 2020;2(1):559–83.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Thapar A. Discoveries on the genetics of ADHD in the 21st century: new findings and their implications. Am J Psychiatry. 2018;175(10):943–50.

    Article  PubMed  Google Scholar 

  19. Grunblatt E, Werling AM, Roth A, Romanos M, Walitza S. Association study and a systematic meta-analysis of the VNTR polymorphism in the 3′-UTR of dopamine transporter gene and attention-deficit hyperactivity disorder. J Neural Transm (Vienna). 2019;126(4):517–29.

    Article  CAS  PubMed  Google Scholar 

  20. Kopeckova M, Paclt I, Petrasek J, Pacltova D, Malikova M, Zagatova V. Some ADHD polymorphisms (in genes DAT1, DRD2, DRD3, DBH, 5-HTT) in case-control study of 100 subjects 6-10 age. Neuro Endocrinol Lett. 2008;29(2):246–51.

    CAS  PubMed  Google Scholar 

  21. Gizer IR, Ficks C, Waldman ID. Candidate gene studies of ADHD: a meta-analytic review. Hum Genet. 2009;126(1):51–90.

    Article  CAS  PubMed  Google Scholar 

  22. Sunohara GA, Roberts W, Malone M, Schachar RJ, Tannock R, Basile VS, et al. Linkage of the dopamine D4 receptor gene and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2000;39(12):1537–42.

    Article  CAS  PubMed  Google Scholar 

  23. Lowe N, Kirley A, Hawi Z, Sham P, Wickham H, Kratochvil CJ, et al. Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes. Am J Hum Genet. 2004;74(2):348–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Biederman J, Kim JW, Doyle AE, Mick E, Fagerness J, Smoller JW, et al. Sexually dimorphic effects of four genes (COMT, SLC6A2, MAOA, SLC6A4) in genetic associations of ADHD: a preliminary study. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(8):1511–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ickowicz A, Feng Y, Wigg K, Quist J, Pathare T, Roberts W, et al. The serotonin receptor HTR1B: gene polymorphisms in attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2007;144B(1):121–5.

    Article  CAS  PubMed  Google Scholar 

  26. Ribases M, Ramos-Quiroga JA, Hervas A, Bosch R, Bielsa A, Gastaminza X, et al. Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB. Mol Psychiatry. 2009;14(1):71–85.

    Article  CAS  PubMed  Google Scholar 

  27. Lee J, Laurin N, Crosbie J, Ickowicz A, Pathare T, Malone M, et al. Association study of the nicotinic acetylcholine receptor alpha4 subunit gene, CHRNA4, in attention-deficit hyperactivity disorder. Genes Brain Behav. 2008;7(1):53–60.

    CAS  PubMed  Google Scholar 

  28. Wallis D, Arcos-Burgos M, Jain M, Castellanos FX, Palacio JD, Pineda D, et al. Polymorphisms in the neural nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) are associated with ADHD in a genetic isolate. Attent Deficit Hyperact Disord. 2009;1(1):19–24.

    Article  Google Scholar 

  29. Huang X, Wang M, Zhang Q, Chen X, Wu J. The role of glutamate receptors in attention-deficit/hyperactivity disorder: from physiology to disease. Am J Med Genet B Neuropsychiatr Genet. 2019;180(4):272–86.

    Article  CAS  PubMed  Google Scholar 

  30. Kim JI, Kim JW, Park S, Hong SB, Lee DS, Paek SH, et al. The GRIN2B and GRIN2A gene variants are associated with continuous performance test variables in ADHD. J Atten Disord. 2020;24(11):1538–46.

    Article  PubMed  Google Scholar 

  31. Feng Y, Crosbie J, Wigg K, Pathare T, Ickowicz A, Schachar R, et al. The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder. Mol Psychiatry. 2005;10(11):998–1005, 973.

    Article  CAS  PubMed  Google Scholar 

  32. Guan L, Wang B, Chen Y, Yang L, Li J, Qian Q, et al. A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population. Mol Psychiatry. 2009;14(5):546–54.

    Article  CAS  PubMed  Google Scholar 

  33. Drtilkova I, Sery O, Theiner P, Uhrova A, Zackova M, Balastikova B, et al. Clinical and molecular-genetic markers of ADHD in children. Neuro Endocrinol Lett. 2008;29(3):320–7.

    CAS  PubMed  Google Scholar 

  34. Alvarez-Arellano L, Gonzalez-Garcia N, Salazar-Garcia M, Corona JC. Antioxidants as a potential target against inflammation and oxidative stress in attention-deficit/hyperactivity disorder. Antioxidants. 2020;9(2):176.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sciberras E, Mulraney M, Silva D, Coghill D. Prenatal risk factors and the etiology of ADHD-review of existing evidence. Curr Psychiatry Rep. 2017;19(1):1.

    Article  PubMed  Google Scholar 

  36. Park S, Cho SC, Kim JW, Shin MS, Yoo HJ, Oh SM, et al. Differential perinatal risk factors in children with attention-deficit/hyperactivity disorder by subtype. Psychiatry Res. 2014;219(3):609–16.

    Article  PubMed  Google Scholar 

  37. Khoshbakht Y, Bidaki R, Salehi-Abargouei A. Vitamin D status and attention deficit hyperactivity disorder: a systematic review and meta-analysis of observational studies. Adv Nutr. 2018;9(1):9–20.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Han JY, Kwon HJ, Ha M, Paik KC, Lim MH, Gyu Lee S, et al. The effects of prenatal exposure to alcohol and environmental tobacco smoke on risk for ADHD: a large population-based study. Psychiatry Res. 2015;225(1–2):164–8.

    Article  CAS  PubMed  Google Scholar 

  39. Sourander A, Sucksdorff M, Chudal R, Surcel HM, Hinkka-Yli-Salomaki S, Gyllenberg D, et al. Prenatal cotinine levels and ADHD among offspring. Pediatrics. 2019;143(3):e20183144.

    Article  PubMed  Google Scholar 

  40. Nigg JT, Breslau N. Prenatal smoking exposure, low birth weight, and disruptive behavior disorders. J Am Acad Child Adolesc Psychiatry. 2007;46(3):362–9.

    Article  PubMed  Google Scholar 

  41. Franz AP, Bolat GU, Bolat H, Matijasevich A, Santos IS, Silveira RC, et al. Attention-deficit/hyperactivity disorder and very preterm/very low birth weight: a meta-analysis. Pediatrics. 2018;141(1):e20171645.

    Article  PubMed  Google Scholar 

  42. Kim JH, Kim JY, Lee J, Jeong GH, Lee E, Lee S, et al. Environmental risk factors, protective factors, and peripheral biomarkers for ADHD: an umbrella review. Lancet Psychiatry. 2020;7(11):955–70.

    Article  PubMed  Google Scholar 

  43. Banerjee TD, Middleton F, Faraone SV. Environmental risk factors for attention-deficit hyperactivity disorder. Acta Paediatr. 2007;96(9):1269–74.

    Article  PubMed  Google Scholar 

  44. Banaschewski T, Becker K, Dopfner M, Holtmann M, Rosler M, Romanos M. Attention-deficit/hyperactivity disorder. Dtsch Arztebl Int. 2017;114(9):149–59.

    PubMed  PubMed Central  Google Scholar 

  45. Li L, Lagerberg T, Chang Z, Cortese S, Rosenqvist MA, Almqvist C, et al. Maternal pre-pregnancy overweight/obesity and the risk of attention-deficit/hyperactivity disorder in offspring: a systematic review, meta-analysis and quasi-experimental family-based study. Int J Epidemiol. 2020;49(3):857–75.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Chen Q, Sjolander A, Langstrom N, Rodriguez A, Serlachius E, D’Onofrio BM, et al. Maternal pre-pregnancy body mass index and offspring attention deficit hyperactivity disorder: a population-based cohort study using a sibling-comparison design. Int J Epidemiol. 2014;43(1):83–90.

    Article  CAS  PubMed  Google Scholar 

  47. Chang Z, Lichtenstein P, D’Onofrio BM, Almqvist C, Kuja-Halkola R, Sjolander A, et al. Maternal age at childbirth and risk for ADHD in offspring: a population-based cohort study. Int J Epidemiol. 2014;43(6):1815–24.

    Article  PubMed  PubMed Central  Google Scholar 

  48. McCann D, Barrett A, Cooper A, Crumpler D, Dalen L, Grimshaw K, et al. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet. 2007;370(9598):1560–7.

    Article  CAS  PubMed  Google Scholar 

  49. Kennedy M, Kreppner J, Knights N, Kumsta R, Maughan B, Golm D, et al. Early severe institutional deprivation is associated with a persistent variant of adult attention-deficit/hyperactivity disorder: clinical presentation, developmental continuities and life circumstances in the English and Romanian Adoptees study. J Child Psychol Psychiatry Allied Discip. 2016;57(10):1113–25.

    Article  Google Scholar 

  50. Biederman J. Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatry. 2005;57(11):1215–20.

    Article  PubMed  Google Scholar 

  51. Gould KL, Coventry WL, Olson RK, Byrne B. Gene-environment interactions in ADHD: the roles of SES and chaos. J Abnorm Child Psychol. 2018;46(2):251–63.

    Article  PubMed  Google Scholar 

  52. Nigg J, Nikolas M, Burt SA. Measured gene-by-environment interaction in relation to attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2010;49(9):863–73.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Unsel Bolat G, Ercan ES, Salum GA, Bilac O, Massuti R, Uysal Ozaslan T, et al. Validity of proposed DSM-5 ADHD impulsivity symptoms in children. Eur Child Adolesc Psychiatry. 2016;25(10):1121–32.

    Article  PubMed  Google Scholar 

  54. Childress AC, Berry SA. Pharmacotherapy of attention-deficit hyperactivity disorder in adolescents. Drugs. 2012;72(3):309–25.

    Article  CAS  PubMed  Google Scholar 

  55. Shellenberg TP, Stoops WW, Lile JA, Rush CR. An update on the clinical pharmacology of methylphenidate: therapeutic efficacy, abuse potential and future considerations. Expert Rev Clin Pharmacol. 2020;13(8):825–33.

    Article  CAS  PubMed  Google Scholar 

  56. Faraone SV. The pharmacology of amphetamine and methylphenidate: relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neurosci Biobehav Rev. 2018;87:255–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Briars L, Todd T. A review of pharmacological management of attention-deficit/hyperactivity disorder. J Pediat Pharmacol Therapeut. 2016;21(3):192–206.

    Article  Google Scholar 

  58. Corona JC. Natural compounds for the management of Parkinson’s disease and attention-deficit/hyperactivity disorder. Biomed Res Int. 2018;2018:4067597.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Clemow DB. Misuse of Methylphenidate. Curr Top Behav Neurosci. 2017;34:99–124.

    Article  CAS  PubMed  Google Scholar 

  60. Morton WA, Stockton GG. Methylphenidate abuse and psychiatric side effects. Primary Care Compan J Clin Psychiatry. 2000;2(5):159–64.

    Article  Google Scholar 

  61. Leonard BE, McCartan D, White J, King DJ. Methylphenidate: a review of its neuropharmacological, neuropsychological and adverse clinical effects. Hum Psychopharmacol. 2004;19(3):151–80.

    Article  CAS  PubMed  Google Scholar 

  62. Koda K, Ago Y, Cong Y, Kita Y, Takuma K, Matsuda T. Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice. J Neurochem. 2010;114(1):259–70.

    CAS  PubMed  Google Scholar 

  63. Reed VA, Buitelaar JK, Anand E, Day KA, Treuer T, Upadhyaya HP, et al. The safety of atomoxetine for the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a comprehensive review of over a decade of research. CNS Drugs. 2016;30(7):603–28.

    Article  CAS  PubMed  Google Scholar 

  64. Mohammadi MR, Akhondzadeh S. Pharmacotherapy of attention-deficit/hyperactivity disorder: nonstimulant medication approaches. Expert Rev Neurother. 2007;7(2):195–201.

    Article  CAS  PubMed  Google Scholar 

  65. Swanson CJ, Perry KW, Koch-Krueger S, Katner J, Svensson KA, Bymaster FP. Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat. Neuropharmacology. 2006;50(6):755–60.

    Article  CAS  PubMed  Google Scholar 

  66. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002;27(5):699–711.

    Article  CAS  PubMed  Google Scholar 

  67. Giovannitti JA Jr, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog. 2015;62(1):31–9.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Alamo C, Lopez-Munoz F, Sanchez-Garcia J. Mechanism of action of guanfacine: a postsynaptic differential approach to the treatment of attention deficit hyperactivity disorder (adhd). Actas Esp Psiquiatr. 2016;44(3):107–12.

    PubMed  Google Scholar 

  69. Arnsten AF. The use of alpha-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Rev Neurother. 2010;10(10):1595–605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Connor DF, Rubin J. Guanfacine extended release in the treatment of attention deficit hyperactivity disorder in children and adolescents. Drugs Today. 2010;46(5):299–314.

    Article  CAS  Google Scholar 

  71. Naguy A. Clonidine use in psychiatry: panacea or panache. Pharmacology. 2016;98(1–2):87–92.

    Article  CAS  PubMed  Google Scholar 

  72. Muthuraman M, Moliadze V, Boecher L, Siemann J, Freitag CM, Groppa S, et al. Multimodal alterations of directed connectivity profiles in patients with attention-deficit/hyperactivity disorders. Sci Rep. 2019;9(1):20028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Cupertino RB, Soheili-Nezhad S, Grevet EH, Bandeira CE, Picon FA, Tavares MEA, et al. Reduced fronto-striatal volume in attention-deficit/hyperactivity disorder in two cohorts across the lifespan. Neuroimage Clin. 2020;28:102403.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Baroni A, Castellanos FX. Neuroanatomic and cognitive abnormalities in attention-deficit/hyperactivity disorder in the era of ‘high definition’ neuroimaging. Curr Opin Neurobiol. 2015;30:1–8.

    Article  CAS  PubMed  Google Scholar 

  75. Greven CU, Bralten J, Mennes M, O’Dwyer L, van Hulzen KJ, Rommelse N, et al. Developmentally stable whole-brain volume reductions and developmentally sensitive caudate and putamen volume alterations in those with attention-deficit/hyperactivity disorder and their unaffected siblings. JAMA Psychiatry. 2015;72(5):490–9.

    Article  PubMed  Google Scholar 

  76. Durston S, van Belle J, de Zeeuw P. Differentiating frontostriatal and fronto-cerebellar circuits in attention-deficit/hyperactivity disorder. Biol Psychiatry. 2011;69(12):1178–84.

    Article  PubMed  Google Scholar 

  77. Cortese S, Kelly C, Chabernaud C, Proal E, Di Martino A, Milham MP, et al. Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies. Am J Psychiatry. 2012;169(10):1038–55.

    Article  PubMed  Google Scholar 

  78. Cubillo A, Halari R, Smith A, Taylor E, Rubia K. A review of fronto-striatal and fronto-cortical brain abnormalities in children and adults with Attention Deficit Hyperactivity Disorder (ADHD) and new evidence for dysfunction in adults with ADHD during motivation and attention. Cortex. 2012;48(2):194–215.

    Article  PubMed  Google Scholar 

  79. Bailey T, Joyce A. The role of the thalamus in ADHD symptomatology and treatment. Appl Neuropsychol Child. 2015;4(2):89–96.

    Article  PubMed  Google Scholar 

  80. Davis AS, Pass LA, Finch WH, Dean RS, Woodcock RW. The canonical relationship between sensory-motor functioning and cognitive processing in children with attention-deficit/hyperactivity disorder. Arch Clin Neuropsychol. 2009;24(3):273–86.

    Article  PubMed  Google Scholar 

  81. Sathyanesan A, Zhou J, Scafidi J, Heck DH, Sillitoe RV, Gallo V. Emerging connections between cerebellar development, behaviour and complex brain disorders. Nat Rev Neurosci. 2019;20(5):298–313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Genro JP, Kieling C, Rohde LA, Hutz MH. Attention-deficit/hyperactivity disorder and the dopaminergic hypotheses. Expert Rev Neurother. 2010;10(4):587–601.

    Article  CAS  PubMed  Google Scholar 

  83. Prince J. Catecholamine dysfunction in attention-deficit/hyperactivity disorder: an update. J Clin Psychopharmacol. 2008;28(3 Suppl 2):S39–45.

    Article  CAS  PubMed  Google Scholar 

  84. Klein MO, Battagello DS, Cardoso AR, Hauser DN, Bittencourt JC, Correa RG. Dopamine: functions, signaling, and association with neurological diseases. Cell Mol Neurobiol. 2019;39(1):31–59.

    Article  PubMed  Google Scholar 

  85. Del Campo N, Chamberlain SR, Sahakian BJ, Robbins TW. The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2011;69(12):e145–57.

    Article  PubMed  Google Scholar 

  86. Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stefanatos GA, Volkow N, et al. Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev. 2007;17(1):39–59.

    Article  PubMed  Google Scholar 

  87. Gold MS, Blum K, Oscar-Berman M, Braverman ER. Low dopamine function in attention deficit/hyperactivity disorder: should genotyping signify early diagnosis in children? Postgrad Med. 2014;126(1):153–77.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Napolitano A, Manini P, d’Ischia M. Oxidation chemistry of catecholamines and neuronal degeneration: an update. Curr Med Chem. 2011;18(12):1832–45.

    Article  CAS  PubMed  Google Scholar 

  89. Goldstein DS, Kopin IJ, Sharabi Y. Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders. Pharmacol Ther. 2014;144(3):268–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Neri M, Cerretani D, Fiaschi AI, Laghi PF, Lazzerini PE, Maffione AB, et al. Correlation between cardiac oxidative stress and myocardial pathology due to acute and chronic norepinephrine administration in rats. J Cell Mol Med. 2007;11(1):156–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Spencer WA, Jeyabalan J, Kichambre S, Gupta RC. Oxidatively generated DNA damage after Cu(II) catalysis of dopamine and related catecholamine neurotransmitters and neurotoxins: role of reactive oxygen species. Free Radic Biol Med. 2011;50(1):139–47.

    Article  CAS  PubMed  Google Scholar 

  92. Joseph N, Zhang-James Y, Perl A, Faraone SV. Oxidative stress and ADHD: a meta-analysis. J Atten Disord. 2015;19(11):915–24.

    Article  PubMed  Google Scholar 

  93. Lopresti AL. Oxidative and nitrosative stress in ADHD: possible causes and the potential of antioxidant-targeted therapies. Attent Deficit Hyperact Disord. 2015;7(4):237–47.

    Article  Google Scholar 

  94. Corona JC. Role of oxidative stress and neuroinflammation in attention-deficit/hyperactivity disorder. Antioxidants. 2020;9(11):1039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Cobley JN, Fiorello ML, Bailey DM. 13 reasons why the brain is susceptible to oxidative stress. Redox Biol. 2018;15:490–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Solleiro-Villavicencio H, Rivas-Arancibia S. Effect of chronic oxidative stress on neuroinflammatory response mediated by CD4(+)T cells in neurodegenerative diseases. Front Cell Neurosci. 2018;12:114.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Simpson DSA, Oliver PL. ROS generation in microglia: understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants. 2020;9(8):743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007;10(11):1387–94.

    Article  CAS  PubMed  Google Scholar 

  99. de Araujo Boleti AP, de Oliveira Flores TM, Moreno SE, Anjos LD, Mortari MR, Migliolo L. Neuroinflammation: an overview of neurodegenerative and metabolic diseases and of biotechnological studies. Neurochem Int. 2020;136:104714.

    Article  PubMed  Google Scholar 

  100. Dunn GA, Nigg JT, Sullivan EL. Neuroinflammation as a risk factor for attention deficit hyperactivity disorder. Pharmacol Biochem Behav. 2019;182:22–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Lurie DI. An integrative approach to neuroinflammation in psychiatric disorders and neuropathic pain. J Exp Neurosci. 2018;12:1179069518793639.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Gilhus NE, Deuschl G. Neuroinflammation - a common thread in neurological disorders. Nat Rev Neurol. 2019;15(8):429–30.

    Article  PubMed  Google Scholar 

  103. Ni Chasaide C, Lynch MA. The role of the immune system in driving neuroinflammation. Brain Neurosci Adv. 2020;4:2398212819901082.

    Article  PubMed  PubMed Central  Google Scholar 

  104. De Nardo D. Toll-like receptors: activation, signalling and transcriptional modulation. Cytokine. 2015;74(2):181–9.

    Article  PubMed  Google Scholar 

  105. Famitafreshi H, Karimian M. Prostaglandins as the agents that modulate the course of brain disorders. Degener Neurol Neuromuscul Dis. 2020;10:1–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Afridi R, Kim JH, Rahman MH, Suk K. Metabolic regulation of glial phenotypes: implications in neuron-glia interactions and neurological disorders. Front Cell Neurosci. 2020;14:20.

    Article  PubMed  PubMed Central  Google Scholar 

  107. DiSabato DJ, Quan N, Godbout JP. Neuroinflammation: the devil is in the details. J Neurochem. 2016;139(Suppl 2):136–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Michael BD, Griffiths MJ, Granerod J, Brown D, Keir G, Wnek M, et al. The interleukin-1 balance during encephalitis is associated with clinical severity, blood-brain barrier permeability, neuroimaging changes, and disease outcome. J Infect Dis. 2016;213(10):1651–60.

    Article  CAS  PubMed  Google Scholar 

  109. Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005;57(2):173–85.

    Article  CAS  PubMed  Google Scholar 

  110. Basu A, Krady JK, Enterline JR, Levison SW. Transforming growth factor beta1 prevents IL-1beta-induced microglial activation, whereas TNFalpha- and IL-6-stimulated activation are not antagonized. Glia. 2002;40(1):109–20.

    Article  PubMed  Google Scholar 

  111. Bazan NG. The docosanoid neuroprotectin D1 induces homeostatic regulation of neuroinflammation and cell survival. Prostaglandins Leukot Essent Fat Acids. 2013;88(1):127–9.

    Article  CAS  Google Scholar 

  112. Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014;510(7503):92–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Tremblay ME, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A. The role of microglia in the healthy brain. J Neurosci. 2011;31(45):16064–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Prinz M, Jung S, Priller J. Microglia biology: one century of evolving concepts. Cell. 2019;179(2):292–311.

    Article  CAS  PubMed  Google Scholar 

  115. Colonna M, Butovsky O. Microglia function in the central nervous system during health and neurodegeneration. Annu Rev Immunol. 2017;35:441–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Boche D, Perry VH, Nicoll JA. Review: activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol. 2013;39(1):3–18.

    Article  CAS  PubMed  Google Scholar 

  117. Reus GZ, Fries GR, Stertz L, Badawy M, Passos IC, Barichello T, et al. The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders. Neuroscience. 2015;300:141–54.

    Article  CAS  PubMed  Google Scholar 

  118. Liddelow SA, Barres BA. Reactive astrocytes: production, function, and therapeutic potential. Immunity. 2017;46(6):957–67.

    Article  CAS  PubMed  Google Scholar 

  119. Nosi D, Lana D, Giovannini MG, Delfino G, Zecchi-Orlandini S. Neuroinflammation: integrated nervous tissue response through intercellular interactions at the “whole system” scale. Cells. 2021;10(5):1195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Philips T, Rothstein JD. Oligodendroglia: metabolic supporters of neurons. J Clin Invest. 2017;127(9):3271–80.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Zeis T, Enz L, Schaeren-Wiemers N. The immunomodulatory oligodendrocyte. Brain Res. 2016;1641(Pt A):139–48.

    Article  CAS  PubMed  Google Scholar 

  122. Tanabe S, Yamashita T. The role of immune cells in brain development and neurodevelopmental diseases. Int Immunol. 2018;30(10):437–44.

    Article  CAS  PubMed  Google Scholar 

  123. Tanabe S, Yamashita T. B lymphocytes: crucial contributors to brain development and neurological diseases. Neurosci Res. 2019;139:37–41.

    Article  CAS  PubMed  Google Scholar 

  124. Hirahara K, Nakayama T. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm. Int Immunol. 2016;28(4):163–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Filiano AJ, Gadani SP, Kipnis J. How and why do T cells and their derived cytokines affect the injured and healthy brain? Nat Rev Neurosci. 2017;18(6):375–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Filiano AJ, Xu Y, Tustison NJ, Marsh RL, Baker W, Smirnov I, et al. Unexpected role of interferon-gamma in regulating neuronal connectivity and social behaviour. Nature. 2016;535(7612):425–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Quinnies KM, Cox KH, Rissman EF. Immune deficiency influences juvenile social behavior and maternal behavior. Behav Neurosci. 2015;129(3):331–8.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Conti P, Lauritano D, Caraffa A, Gallenga CE, Kritas SK, Ronconi G, et al. Microglia and mast cells generate proinflammatory cytokines in the brain and worsen inflammatory state: suppressor effect of IL-37. Eur J Pharmacol. 2020;875:173035.

    Article  CAS  PubMed  Google Scholar 

  129. Hendriksen E, van Bergeijk D, Oosting RS, Redegeld FA. Mast cells in neuroinflammation and brain disorders. Neurosci Biobehav Rev. 2017;79:119–33.

    Article  CAS  PubMed  Google Scholar 

  130. Ishii H, Yoshida M. [Inflammatory cytokines]. Nihon Rinsho. 2010;68(5):819–22.

    Google Scholar 

  131. Segman RH, Meltzer A, Gross-Tsur V, Kosov A, Frisch A, Inbar E, et al. Preferential transmission of interleukin-1 receptor antagonist alleles in attention deficit hyperactivity disorder. Mol Psychiatry. 2002;7(1):72–4.

    Article  CAS  PubMed  Google Scholar 

  132. Widera D, Mikenberg I, Elvers M, Kaltschmidt C, Kaltschmidt B. Tumor necrosis factor alpha triggers proliferation of adult neural stem cells via IKK/NF-kappaB signaling. BMC Neurosci. 2006;7:64.

    Article  PubMed  PubMed Central  Google Scholar 

  133. Kaur N, Chugh H, Sakharkar MK, Dhawan U, Chidambaram SB, Chandra R. Neuroinflammation mechanisms and phytotherapeutic intervention: a systematic review. ACS Chem Neurosci. 2020;11(22):3707–31.

    Article  CAS  PubMed  Google Scholar 

  134. Alvarez-Arellano L, Díaz de León-Guerrero S, Meza-Sosa KF, Jiménez-Ferrer CI, Pérez-Martínez L. Neurodegenerative disorders and inflammation. J Chem Inf Model. 2013;

    Google Scholar 

  135. Montgomery SL, Bowers WJ. Tumor necrosis factor-alpha and the roles it plays in homeostatic and degenerative processes within the central nervous system. J NeuroImmune Pharmacol. 2012;7(1):42–59.

    Article  PubMed  Google Scholar 

  136. Choi SJ, Lee KH, Park HS, Kim SK, Koh CM, Park JY. Differential expression, shedding, cytokine regulation and function of TNFR1 and TNFR2 in human fetal astrocytes. Yonsei Med J. 2005;46(6):818–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Raffaele S, Lombardi M, Verderio C, Fumagalli M. TNF production and release from microglia via extracellular vesicles: impact on brain functions. Cells. 2020;9(10):2145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Wajant H, Scheurich P. TNFR1-induced activation of the classical NF-kappaB pathway. FEBS J. 2011;278(6):862–76.

    Article  CAS  PubMed  Google Scholar 

  139. Wertz IE, Dixit VM. Ubiquitin-mediated regulation of TNFR1 signaling. Cytokine Growth Factor Rev. 2008;19(3–4):313–24.

    Article  CAS  PubMed  Google Scholar 

  140. Hsu MP, Frausto R, Rose-John S, Campbell IL. Analysis of IL-6/gp130 family receptor expression reveals that in contrast to astroglia, microglia lack the oncostatin M receptor and functional responses to oncostatin M. Glia. 2015;63(1):132–41.

    Article  PubMed  Google Scholar 

  141. West PK, Viengkhou B, Campbell IL, Hofer MJ. Microglia responses to interleukin-6 and type I interferons in neuroinflammatory disease. Glia. 2019;67(10):1821–41.

    PubMed  Google Scholar 

  142. Marisa R, Reesha PR, Michal B. Cytokines in the CNS. Handb Exp Pharmacol. 2018;248:397.

    PubMed Central  Google Scholar 

  143. Lobo-Silva D, Carriche GM, Castro AG, Roque S, Saraiva M. Balancing the immune response in the brain: IL-10 and its regulation. J Neuroinflammation. 2016;13(1):297.

    Article  PubMed  PubMed Central  Google Scholar 

  144. Darwish AH, Elgohary TM, Nosair NA. Serum interleukin-6 level in children with attention-deficit hyperactivity disorder (ADHD). J Child Neurol. 2019;34(2):61–7.

    Article  PubMed  Google Scholar 

  145. Donev R, Thome J. Inflammation: good or bad for ADHD? Attent Deficit Hyperact Disord. 2010;2(4):257–66.

    Article  Google Scholar 

  146. Hamed RA, Elmalt HA, Salama AAA, Hammouda SM, Youness ER, Abd-Allah NA, et al. MMP-2, MMP-9, TNF-α levels in relation to subtypes of attention deficit hyperactivity disorder. Biomed Pharmacol J. 2021;14:541–8.

    Article  CAS  Google Scholar 

  147. Cortese S, Angriman M, Comencini E, Vincenzi B, Maffeis C. Association between inflammatory cytokines and ADHD symptoms in children and adolescents with obesity: a pilot study. Psychiatry Res. 2019;278:7–11.

    Article  CAS  PubMed  Google Scholar 

  148. Elsadek AE, Al-Shokary AH, Abdelghani WE, Kamal NM, Ibrahim AO, El-Shorbagy HH, et al. Serum levels of interleukin-6 and tumor necrosis factor alpha in children with attention-deficit hyperactivity disorder. J Pediatr Neurosci. 2020;15(4):402–8.

    Article  PubMed  Google Scholar 

  149. Chang JP, Mondelli V, Satyanarayanan SK, Chiang YJ, Chen HT, Su KP, et al. Cortisol, inflammatory biomarkers and neurotrophins in children and adolescents with attention deficit hyperactivity disorder (ADHD) in Taiwan. Brain Behav Immun. 2020;88:105.

    Article  CAS  PubMed  Google Scholar 

  150. Kozlowska A, Wojtacha P, Rowniak M, Kolenkiewicz M, Huang ACW. ADHD pathogenesis in the immune, endocrine and nervous systems of juvenile and maturating SHR and WKY rats. Psychopharmacology. 2019;236(10):2937–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Allred EN, Dammann O, Fichorova RN, Hooper SR, Hunter SJ, Joseph RM, et al. Systemic inflammation during the first postnatal month and the risk of attention deficit hyperactivity disorder characteristics among 10 year-old children born extremely preterm. J NeuroImmune Pharmacol. 2017;12(3):531–43.

    Article  PubMed  PubMed Central  Google Scholar 

  152. O’Shea TM, Joseph RM, Kuban KC, Allred EN, Ware J, Coster T, et al. Elevated blood levels of inflammation-related proteins are associated with an attention problem at age 24 mo in extremely preterm infants. Pediatr Res. 2014;75(6):781–7.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Oades RD, Dauvermann MR, Schimmelmann BG, Schwarz MJ, Myint AM. Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism--effects of medication. Behav Brain Funct. 2010;6:29.

    Article  PubMed  PubMed Central  Google Scholar 

  154. Donfrancesco R, Nativio P, Di Benedetto A, Villa MP, Andriola E, Melegari MG, et al. Anti-yo antibodies in children with ADHD: first results about serum cytokines. J Atten Disord. 2020;24(11):1497–502.

    Article  PubMed  Google Scholar 

  155. Smith TF, Anastopoulos AD, Garrett ME, Arias-Vasquez A, Franke B, Oades RD, et al. Angiogenic, neurotrophic, and inflammatory system SNPs moderate the association between birth weight and ADHD symptom severity. Am J Med Genet B Neuropsychiatr Genet. 2014;165B(8):691–704.

    Article  PubMed  Google Scholar 

  156. Ribases M, Hervas A, Ramos-Quiroga JA, Bosch R, Bielsa A, Gastaminza X, et al. Association study of 10 genes encoding neurotrophic factors and their receptors in adult and child attention-deficit/hyperactivity disorder. Biol Psychiatry. 2008;63(10):935–45.

    Article  CAS  PubMed  Google Scholar 

  157. Giana G, Romano E, Porfirio MC, D’Ambrosio R, Giovinazzo S, Troianiello M, et al. Detection of auto-antibodies to DAT in the serum: interactions with DAT genotype and psycho-stimulant therapy for ADHD. J Neuroimmunol. 2015;278:212–22.

    Article  CAS  PubMed  Google Scholar 

  158. Corominas-Roso M, Armario A, Palomar G, Corrales M, Carrasco J, Richarte V, et al. IL-6 and TNF-alpha in unmedicated adults with ADHD: relationship to cortisol awakening response. Psychoneuroendocrinology. 2017;79:67–73.

    Article  CAS  PubMed  Google Scholar 

  159. Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science. 2003;302(5651):1760–5.

    Article  CAS  PubMed  Google Scholar 

  160. Beroun A, Mitra S, Michaluk P, Pijet B, Stefaniuk M, Kaczmarek L. MMPs in learning and memory and neuropsychiatric disorders. Cell Mol Life Sci. 2019;76(16):3207–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Glessner JT, Li J, Wang D, March M, Lima L, Desai A, et al. Copy number variation meta-analysis reveals a novel duplication at 9p24 associated with multiple neurodevelopmental disorders. Genome Med. 2017;9(1):106.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Asherson P, Gurling H. Quantitative and molecular genetics of ADHD. Curr Top Behav Neurosci. 2012;9:239–72.

    Article  PubMed  Google Scholar 

  163. Rovira P, Demontis D, Sanchez-Mora C, Zayats T, Klein M, Mota NR, et al. Shared genetic background between children and adults with attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2020;45(10):1617–26.

    Article  PubMed  PubMed Central  Google Scholar 

  164. Toto M, Margari F, Simone M, Craig F, Petruzzelli MG, Tafuri S, et al. Antibasal ganglia antibodies and antistreptolysin O in noncomorbid ADHD. J Atten Disord. 2015;19(11):965–70.

    Article  PubMed  Google Scholar 

  165. Passarelli F, Donfrancesco R, Nativio P, Pascale E, Di Trani M, Patti AM, et al. Anti-Purkinje cell antibody as a biological marker in attention deficit/hyperactivity disorder: a pilot study. J Neuroimmunol. 2013;258(1–2):67–70.

    Article  CAS  PubMed  Google Scholar 

  166. Fan LW, Pang Y. Dysregulation of neurogenesis by neuroinflammation: key differences in neurodevelopmental and neurological disorders. Neural Regen Res. 2017;12(3):366–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Cherkasova MV, Hechtman L. Neuroimaging in attention-deficit hyperactivity disorder: beyond the frontostriatal circuitry. Can J Psychiatr. 2009;54(10):651–64.

    Article  Google Scholar 

  168. Miyazaki C, Koyama M, Ota E, Swa T, Mlunde LB, Amiya RM, et al. Allergic diseases in children with attention deficit hyperactivity disorder: a systematic review and meta-analysis. BMC Psychiatry. 2017;17(1):120.

    Article  PubMed  PubMed Central  Google Scholar 

  169. Mogensen N, Larsson H, Lundholm C, Almqvist C. Association between childhood asthma and ADHD symptoms in adolescence--a prospective population-based twin study. Allergy. 2011;66(9):1224–30.

    Article  CAS  PubMed  Google Scholar 

  170. Schans JV, Cicek R, de Vries TW, Hak E, Hoekstra PJ. Association of atopic diseases and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses. Neurosci Biobehav Rev. 2017;74(Pt A):139–48.

    Article  PubMed  Google Scholar 

  171. Halfon N, Newacheck PW. Evolving notions of childhood chronic illness. JAMA. 2010;303(7):665–6.

    Article  CAS  PubMed  Google Scholar 

  172. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):24–31.

    Article  CAS  PubMed  Google Scholar 

  173. Aguilar-Valles A, Inoue W, Rummel C, Luheshi GN. Obesity, adipokines and neuroinflammation. Neuropharmacology. 2015;96(Pt A):124–34.

    Article  CAS  PubMed  Google Scholar 

  174. Cortese S, Tessari L. Attention-deficit/hyperactivity disorder (ADHD) and obesity: update 2016. Curr Psychiatry Rep. 2017;19(1):4.

    Article  PubMed  PubMed Central  Google Scholar 

  175. Albayrak O, Putter C, Volckmar AL, Cichon S, Hoffmann P, Nothen MM, et al. Common obesity risk alleles in childhood attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2013;162B(4):295–305.

    Article  PubMed  Google Scholar 

  176. Kang SS, Kurti A, Fair DA, Fryer JD. Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring. J Neuroinflammation. 2014;11:156.

    Article  PubMed  PubMed Central  Google Scholar 

  177. Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun. 2011;25(1):40–5.

    Article  CAS  PubMed  Google Scholar 

  178. Gumusoglu SB, Chilukuri ASS, Santillan DA, Santillan MK, Stevens HE. Neurodevelopmental outcomes of prenatal preeclampsia exposure. Trends Neurosci. 2020;43(4):253–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Novak CM, Ozen M, Burd I. Perinatal brain injury: mechanisms, prevention, and outcomes. Clin Perinatol. 2018;45(2):357–75.

    Article  PubMed  Google Scholar 

  180. Grizenko N, Shayan YR, Polotskaia A, Ter-Stepanian M, Joober R. Relation of maternal stress during pregnancy to symptom severity and response to treatment in children with ADHD. J Psychiatry Neurosci. 2008;33(1):10–6.

    PubMed  PubMed Central  Google Scholar 

  181. Grizenko N, Fortier ME, Gaudreau-Simard M, Jolicoeur C, Joober R. The effect of maternal stress during pregnancy on IQ and ADHD symptomatology. J Can Acad Child Adolesc Psychiatry. 2015;24(2):92–9.

    PubMed  PubMed Central  Google Scholar 

  182. Obernier JA, White AM, Swartzwelder HS, Crews FT. Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats. Pharmacol Biochem Behav. 2002;72(3):521–32.

    Article  CAS  PubMed  Google Scholar 

  183. Terasaki LS, Schwarz JM. Effects of moderate prenatal alcohol exposure during early gestation in rats on inflammation across the maternal-fetal-immune interface and later-life immune function in the offspring. J NeuroImmune Pharmacol. 2016;11(4):680–92.

    Article  PubMed  PubMed Central  Google Scholar 

  184. Huang L, Wang Y, Zhang L, Zheng Z, Zhu T, Qu Y, et al. Maternal smoking and attention-deficit/hyperactivity disorder in offspring: a meta-analysis. Pediatrics. 2018;141(1):e20172465.

    Article  PubMed  Google Scholar 

  185. Sengupta SM, Fortier ME, Thakur GA, Bhat V, Grizenko N, Joober R. Parental psychopathology in families of children with attention-deficit/hyperactivity disorder and exposed to maternal smoking during pregnancy. J Child Psychol Psychiatry Allied Discip. 2015;56(2):122–9.

    Article  Google Scholar 

  186. Zhu J, Zhang X, Xu Y, Spencer TJ, Biederman J, Bhide PG. Prenatal nicotine exposure mouse model showing hyperactivity, reduced cingulate cortex volume, reduced dopamine turnover, and responsiveness to oral methylphenidate treatment. J Neurosci. 2012;32(27):9410–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Herrmann M, King K, Weitzman M. Prenatal tobacco smoke and postnatal secondhand smoke exposure and child neurodevelopment. Curr Opin Pediatr. 2008;20(2):184–90.

    Article  PubMed  Google Scholar 

  188. Pineles BL, Park E, Samet JM. Systematic review and meta-analysis of miscarriage and maternal exposure to tobacco smoke during pregnancy. Am J Epidemiol. 2014;179(7):807–23.

    Article  PubMed  PubMed Central  Google Scholar 

  189. Hall HA, Speyer LG, Murray AL, Auyeung B. Prenatal maternal infections and children’s neurodevelopment in the UK millennium cohort study: a focus on ASD and ADHD. J Atten Disord. 2022;26:616.

    Article  PubMed  Google Scholar 

  190. Ginsberg Y, D’Onofrio BM, Rickert ME, Class QA, Rosenqvist MA, Almqvist C, et al. Maternal infection requiring hospitalization during pregnancy and attention-deficit hyperactivity disorder in offspring: a quasi-experimental family-based study. J Child Psychol Psychiatry Allied Discip. 2019;60(2):160–8.

    Article  Google Scholar 

  191. Rand KM, Austin NC, Inder TE, Bora S, Woodward LJ. Neonatal Infection and Later Neurodevelopmental Risk in the Very Preterm Infant. J Pediatr. 2016;170:97–104.

    Article  PubMed  Google Scholar 

  192. Ystrom E, Gustavson K, Brandlistuen RE, Knudsen GP, Magnus P, Susser E, et al. Prenatal exposure to acetaminophen and risk of ADHD. Pediatrics. 2017;140(5):e20163840.

    Article  PubMed  Google Scholar 

  193. Chen MH, Pan TL, Wang PW, Hsu JW, Huang KL, Su TP, et al. Prenatal exposure to acetaminophen and the risk of attention-deficit/hyperactivity disorder: a nationwide study in Taiwan. J Clin Psychiatry. 2019;80(5):18m12612.

    Article  PubMed  Google Scholar 

  194. Gustavson K, Ask H, Ystrom E, Stoltenberg C, Lipkin WI, Suren P, et al. Maternal fever during pregnancy and offspring attention deficit hyperactivity disorder. Sci Rep. 2019;9(1):9519.

    Article  PubMed  PubMed Central  Google Scholar 

  195. Gustafsson HC, Sullivan EL, Battison EAJ, Holton KF, Graham AM, Karalunas SL, et al. Evaluation of maternal inflammation as a marker of future offspring ADHD symptoms: a prospective investigation. Brain Behav Immun. 2020;89:350–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Han VX, Patel S, Jones HF, Dale RC. Maternal immune activation and neuroinflammation in human neurodevelopmental disorders. Nat Rev Neurol. 2021;17(9):564–79.

    Article  PubMed  Google Scholar 

  197. Tessari L, Angriman M, Diaz-Roman A, Zhang J, Conca A, Cortese S. Association between exposure to pesticides and ADHD or autism spectrum disorder: a systematic review of the literature. J Atten Disord. 2022;26:48.

    Article  PubMed  Google Scholar 

  198. Roberts JR, Karr CJ. Council on environmental H. Pesticide exposure in children. Pediatrics. 2012;130(6):e1765–88.

    Article  PubMed  Google Scholar 

  199. Rochester JR. Bisphenol A and human health: a review of the literature. Reprod Toxicol. 2013;42:132–55.

    Article  CAS  PubMed  Google Scholar 

  200. Hansen JB, Bilenberg N, Timmermann CAG, Jensen RC, Frederiksen H, Andersson AM, et al. Prenatal exposure to bisphenol A and autistic- and ADHD-related symptoms in children aged 2 and5 years from the Odense Child Cohort. Environ Health. 2021;20(1):24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Minatoya M, Kishi R. A review of recent studies on bisphenol a and phthalate exposures and child neurodevelopment. Int J Environ Res Public Health. 2021;18(7):3585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Choi G, Villanger GD, Drover SSM, Sakhi AK, Thomsen C, Nethery RC, et al. Prenatal phthalate exposures and executive function in preschool children. Environ Int. 2021;149:106403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Papalou O, Kandaraki EA, Papadakis G, Diamanti-Kandarakis E. Endocrine disrupting chemicals: an occult mediator of metabolic disease. Front Endocrinol. 2019;10:112.

    Article  Google Scholar 

  204. Lenters V, Iszatt N, Forns J, Cechova E, Kocan A, Legler J, et al. Early-life exposure to persistent organic pollutants (OCPs, PBDEs, PCBs, PFASs) and attention-deficit/hyperactivity disorder: a multi-pollutant analysis of a Norwegian birth cohort. Environ Int. 2019;125:33–42.

    Article  CAS  PubMed  Google Scholar 

  205. Skogheim TS, Villanger GD, Weyde KVF, Engel SM, Suren P, Oie MG, et al. Prenatal exposure to perfluoroalkyl substances and associations with symptoms of attention-deficit/hyperactivity disorder and cognitive functions in preschool children. Int J Hyg Environ Health. 2020;223(1):80–92.

    Article  CAS  PubMed  Google Scholar 

  206. Simoes LR, Sangiogo G, Tashiro MH, Generoso JS, Faller CJ, Dominguini D, et al. Maternal immune activation induced by lipopolysaccharide triggers immune response in pregnant mother and fetus, and induces behavioral impairment in adult rats. J Psychiatr Res. 2018;100:71–83.

    Article  PubMed  Google Scholar 

  207. Carias E, Hamilton J, Robison LS, Delis F, Eiden R, Quattrin T, et al. Chronic oral methylphenidate treatment increases microglial activation in rats. J Neural Transm (Vienna). 2018;125(12):1867–75.

    Article  CAS  PubMed  Google Scholar 

  208. Sadasivan S, Pond BB, Pani AK, Qu C, Jiao Y, Smeyne RJ. Methylphenidate exposure induces dopamine neuron loss and activation of microglia in the basal ganglia of mice. PLoS One. 2012;7(3):e33693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Schmidt AJ, Krieg JC, Clement HW, Gebhardt S, Schulz E, Heiser P. Impact of drugs approved for treating ADHD on the cell survival and energy metabolism: an in-vitro study in human neuronal and immune cells. J Psychopharmacol. 2010;24(12):1829–33.

    Article  CAS  PubMed  Google Scholar 

  210. Motaghinejad M, Motevalian M, Shabab B, Fatima S. Effects of acute doses of methylphenidate on inflammation and oxidative stress in isolated hippocampus and cerebral cortex of adult rats. J Neural Transm (Vienna). 2017;124(1):121–31.

    Article  CAS  PubMed  Google Scholar 

  211. O’Sullivan JB, Ryan KM, Curtin NM, Harkin A, Connor TJ. Noradrenaline reuptake inhibitors limit neuroinflammation in rat cortex following a systemic inflammatory challenge: implications for depression and neurodegeneration. Int J Neuropsychopharmacol. 2009;12(5):687–99.

    Article  PubMed  Google Scholar 

  212. Park JH, Shin BN, Chen BH, Kim IH, Ahn JH, Cho JH, et al. Neuroprotection and reduced gliosis by atomoxetine pretreatment in a gerbil model of transient cerebral ischemia. J Neurol Sci. 2015;359(1–2):373–80.

    Article  CAS  PubMed  Google Scholar 

  213. Verlaet AAJ, Maasakkers CM, Hermans N, Savelkoul HFJ. Rationale for dietary antioxidant treatment of ADHD. Nutrients. 2018;10(4):405.

    Article  PubMed  PubMed Central  Google Scholar 

  214. Moghadas M, Essa MM, Ba-Omar T, Al-Shehi A, Qoronfleh MW, Eltayeb EA, et al. Antioxidant therapies in attention deficit hyperactivity disorder. Front Biosci. 2019;24:313–33.

    Article  Google Scholar 

  215. Alvarez-Arellano L, Salazar-Garcia M, Corona JC. Neuroprotective effects of quercetin in pediatric neurological diseases. Molecules. 2020;25(23):5597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Richardson AJ. Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. Int Rev Psychiatry. 2006;18(2):155–72.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge support from Fondos Federales (Grant number HIM 2019/029 SSA 1575).

Author information

Authors and Affiliations

  1. Laboratory of Neurosciences, Hospital Infantil de México Federico Gómez, Mexico City, Mexico

    Daniela Vázquez-González, Sonia Carreón-Trujillo, Daniela Melissa Abarca-Merlin & Juan Carlos Corona

  2. CONACYT-Hospital Infantil de México Federico Gómez, Mexico City, Mexico

    Lourdes Alvarez-Arellano

  3. Unidad de Investigación Médica en Medicina Reproductiva, Hospital Gineco-Obstetricia, IMSS, Mexico City, Mexico

    Pablo Domínguez-López

  4. Laboratorio de Investigación en Biología del Desarrollo y Teratogénesis Experimental, Hospital Infantil de México Federico Gómez, Mexico City, Mexico

    Marcela Salazar-García

Authors
  1. Daniela Vázquez-González
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sonia Carreón-Trujillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lourdes Alvarez-Arellano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniela Melissa Abarca-Merlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pablo Domínguez-López
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marcela Salazar-García
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Juan Carlos Corona
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juan Carlos Corona .

Editor information

Editors and Affiliations

  1. Department of Psychiatry, Korea University Ansan Hospital, Ansan, Korea (Republic of)

    Yong-Ku Kim

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Vázquez-González, D. et al. (2023). A Potential Role for Neuroinflammation in ADHD. In: Kim, YK. (eds) Neuroinflammation, Gut-Brain Axis and Immunity in Neuropsychiatric Disorders. Advances in Experimental Medicine and Biology, vol 1411. Springer, Singapore. https://doi.org/10.1007/978-981-19-7376-5_15

Download citation

Publish with us

Policies and ethics

Search

Navigation