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Decreased serum orexin A levels in drug-naive children with attention deficit and hyperactivity disorder

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Abstract

Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood and characterized by inattention, hyperactivity, and impulsivity. ADHD is a neurodevelopmental disorder, and its etiology has not yet been determined precisely. Orexin A is thought to play an important role in different forms of learning, memory, and attention. Despite its importance in attention and learning, no study has investigated serum orexin levels in patients with ADHD. In the present study, we aimed to compare serum orexigenic neuropeptides such as orexin A and orexin B, neuropeptide Y, and ghrelin between drug naive children with ADHD and healthy children. Fifty-six drug-naive children with ADHD and 40 healthy controls were enrolled in the study. After comparison of serum orexin A and orexin B, neuropeptide Y, and ghrelin, we found that serum orexin A levels were significantly lower in the ADHD group (p = 0.001). Furthermore, serum orexin A levels were compared between ADHD subgroups. Orexin A levels were significantly lower in the inattentive subtype compared with the hyperactive subtype and combined subtype (p = 0.009). Our results indicate that orexin A might be a neurobiological etiological factor in ADHD, particularly associated with attention symptoms. The present study is the first to demonstrate decreased serum orexin A levels in drug-naive children with ADHD. Further studies are needed to confirm our results and to show the effects of treatments involving orexin A in patients with ADHD.

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References

  1. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (5th ed). American Psychiatric Publishing, Arlington

  2. Rohani M, Fasano A, Lang AE, Zamani B, Javanparast L, Bidgoli MR, Alavi A (2018) Pantothenate kinase-associated neurodegeneration mimicking Tourette syndrome: a case report and review of the literature. Neurol Sci 39:1797–1800. https://doi.org/10.1007/s10072-018-3472-5

    Article  PubMed  Google Scholar 

  3. Pliszka SR (2015) Conceptual issues in understanding comorbidity in ADHD. In: Adler LA, Spencer TJ, Wilens TE (eds) Attention-deficit hyperactivity disorder in adults and children, 1st edn. Cambridge University Press, UK, pp 63–72

    Chapter  Google Scholar 

  4. Tripp G, Wickens JR (2009) Neurobiology of ADHD. Neuropharmacology 57(7–8):579–589

    Article  CAS  PubMed  Google Scholar 

  5. Caye A, Swanson JM, Coghill D, Rohde LA (2018) Treatment strategies for ADHD: an evidence-based guide to select optimal treatment. Mol Psychiatry. https://doi.org/10.1038/s41380-018-0116-3

  6. Quarta D, Smolders I (2014) Rewarding, reinforcing and incentive salient events involve orexigenic hypothalamic neuropeptides regulating mesolimbic dopaminergic neurotransmission. Eur J Pharm Sci 57:2–10

    Article  CAS  PubMed  Google Scholar 

  7. Kastin AJ, Akerstrom V (1999) Nonsaturable entry of neuropeptide Y into brain. Am J Phys:E479–E482

  8. De la Herrán-Arita AK, Guerra-Crespo M, Drucker-Colín R (2011) Narcolepsy and orexins: an example of progress in sleep research. Front Neurol 2:26

    PubMed  PubMed Central  Google Scholar 

  9. Uriarte M, De Francesco PN, Fernandez G, Cabral A, Castrogiovanni D, Lalonde T, Luyt LG, Trejo S, Perello M (2018) Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brain. Mol Neurobiol. https://doi.org/10.1007/s12035-018-1362-8

  10. Cortese S, Konofal E, Lecendreux M (2008) Alertness and feeding behaviors in ADHD: does the hypocretin/orexin system play a role? Med Hypotheses 71(5):770–775

    Article  CAS  PubMed  Google Scholar 

  11. Li SB, Jones JR, de Lecea L (2016) Hypocretins, neural systems, physiology, and psychiatric disorders. Curr Psychiatry Rep 18(1):7

    Article  PubMed  Google Scholar 

  12. Faraone SV (2018) The pharmacology of amphetamine and methylphenidate: relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neurosci Biobehav Rev 87:255–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Achenbach TM, Edelbrock C (1983) Manual for the child behavior checklist and revised child behavior profile. Queen City Printers, Burlington

    Google Scholar 

  14. Kaufman J, Birmaher B, Brent D (1997) Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (KSADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36:980–988

    Article  CAS  PubMed  Google Scholar 

  15. Matthews M, Nigg JT, Fair DA (2014) Attention deficit hyperactivity disorder. Curr Top Behav Neurosci 16:235–266

    Article  PubMed  PubMed Central  Google Scholar 

  16. Cook EH Jr, Stein MA, Krasowski MD, Cox NJ, Olkon DM, Kieffer JE, Leventhal BL (1995) Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet 56:993–998

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Madras BK, Miller GM, Fischman AJ (2005) The dopamine transporter and attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1397–1409

    Article  CAS  PubMed  Google Scholar 

  18. VanNess SH, Owens MJ, Kilts CD (2005) The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density. BMC Genet 6(55):55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Borodovitsyna O, Flamini M, Chandler D (2017) Noradrenergic modulation of cognition in health and disease. Neural Plast 2017:6031478

  20. Zajo KN, Fadel JR, Burk JA (2016) Orexin A-induced enhancement of attentional processing in rats: role of basal forebrain neurons. Psychopharmacology 233(4):639–647

    Article  CAS  PubMed  Google Scholar 

  21. Mahler SV, Smith RJ, Moorman DE, Sartor GC, Aston-Jones G (2012) Multiple roles for orexin/hypocretin in addiction. Prog Brain Res 198:79–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JRS, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–585

    Article  CAS  PubMed  Google Scholar 

  23. Ritchie C, Okuro M, Kanbayashi T, Nishino S (2010) Hypocretin ligand deficiency in narcolepsy: recent basic and clinical insights. Curr Neurol Neurosci Rep 10:180–189

    Article  CAS  PubMed  Google Scholar 

  24. Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM (2000) Reduced number of hypocretin neurons in human narcolepsy. Neuron 27:469–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Arrigoni E, Mochizuki T, Scammell TE (2010) Activation of the basal forebrain by the orexin/hypocretin neurones. Acta Physiol (Oxf) 198:223–235

    Article  CAS  Google Scholar 

  26. Fadel J, Burk JA (2010) Orexin/hypocretin modulation of the basal forebrain cholinergic system: role in attention. Brain Res 1314:112–123

    Article  CAS  PubMed  Google Scholar 

  27. Boschen KE, Fadel JR, Burk JA (2009) Systemic and intrabasalis administration of the orexin-1 receptor antagonist, SB-334867, disrupts attentional performance in rats. Psychopharmacology (Berlin) 206:205–213

    Article  CAS  Google Scholar 

  28. Fadel J, Jolivalt CG, Reagan LP (2013) Food for thought: the role of appetitive peptides in age-related cognitive decline. Ageing Res Rev 12:764–776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Fronczek R, van Geest S, Frolich M, Overeem S, Roelandse FW, Lammers GJ, Swaab DF (2012) Hypocretin (orexin) loss in Alzheimer’s disease. Neurobiol Aging 33:1642–1650

    Article  CAS  PubMed  Google Scholar 

  30. Slats D, Claassen JA, Lammers GJ, Melis RJ, Verbeek MM, Overseem S (2012) Association between hypocretin-1 and amyloid-β42 cerebrospinal fluid levels in Alzheimer’s disease and healthy controls. Curr Alzheimer Res 9:1119–1125

    Article  CAS  PubMed  Google Scholar 

  31. Wennstrom M, Londos E, Minthon L, Nielsen HM (2012) Altered CSF orexin and α-synuclein levels in dementia patients. J Alzheimers Dis 29:125–132

    Article  CAS  PubMed  Google Scholar 

  32. Deadwyler SA, Porrino L, Siegel JM, Hampson RE (2007) Systemic and nasal delivery of orexin-A (hypocretin-1) reduces the effects of sleep deprivation on cognitive performance in nonhuman primates. J Neurosci 27:14239–14247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Akbari E, Naghdi N, Motamedi F (2007) The selective orexin 1 receptor antagonist SB-334867-A impairs acquisition and consolidation but not retrieval of spatial memory in Morris water maze. Peptides 28:650–656

    Article  CAS  PubMed  Google Scholar 

  34. Aou S, Li XL, Li AJ, Oomura Y, Shiraishi T, Sasaki K, Imamura T, Wayner MJ (2003) Orexin-A (hypocretin-1) impairs Morris water maze performance and CA1-Schaffer collateral long-term potentiation in rats. Neuroscience 119:1221–1228

    Article  CAS  PubMed  Google Scholar 

  35. Jaeger LB, Farr SB, Banks WA, Morley JE (2002) Effects of orexin-A on memory processing. Peptides 23:1683–1688

    Article  CAS  PubMed  Google Scholar 

  36. Yang L, Zou B, Xiong X, Pascual C, Xie J, Malik A, Xie J, Sakurai T, Xie XS (2013) Hypocretin/orexin neurons contribute to hippocampus dependent social memory and synaptic plasticity in mice. J Neurosci 33:5275–5284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lundberg JM, Terenius L, Hokfelt T et al (1982) Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effect of NPY on sympathetic function. Acta Physiol Scand 116:477–480

    Article  CAS  PubMed  Google Scholar 

  38. Hashimoto K (2010) Brain-derived neurotrophic factor as a biomarker for mood disorders: an historical overview and future directions. Psychiatr Clin Neurosci 64:341–357

    Article  CAS  Google Scholar 

  39. Lindell SG, Schwandt ML, Sun H, Sparenborg JD, Björk K, Kasckow JW, Sommer WH, Goldman D, Higley JD, Suomi SJ, Heilig M, Barr CS (2010) Functional NPY variation as a factor in stress resilience and alcohol consumption in rhesus macaques. Arch Gen Psychiatry 67:423–431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhu G, Pollak L, Mottagui-Tabar S, Wahlestedt C, Taubman J, Virkkunen M, Goldman D, Heilig M (2003) NPY Leu7Pro and alcohol dependence in Finnish and Swedish populations. Alcohol Clin Exp Res 27:19–24

    Article  CAS  PubMed  Google Scholar 

  41. Heilig M, Zachrisson O, Thorsell A, Ehnvall A, Mottagui-Tabar S, Sjögren M, Åsberg M, Ekman R, Wahlestedt C, Ågren H (2004) Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism. J Psychiatr Res 38:113–121

    Article  PubMed  Google Scholar 

  42. Oades RD, Daniels R, Rascher W (1998) Plasma neuropeptide-Y levels, monoamine metabolism, electrolyte excretion and drinking behavior in children with attention-deficit hyperactivity disorder. Psychiatry Res 80:177–186

    Article  CAS  PubMed  Google Scholar 

  43. Özcan Ö, Arslan M, Güngör S, Yüksel T, Selimoğlu MA (2018) Plasma leptin, adiponectin, neuropeptide Y levels in drug naive children with ADHD. J Atten Disord 22(9):896–900

    Article  PubMed  Google Scholar 

  44. Hekim Bozkurt Ö, Güney E, Göker Z, Şenses Dinç G, Alışık M, Erel Ö, Çöp E, Üneri ÖŞ (2018) Neuropeptide Y levels in children and adolescents with attention deficit hyperactivity disorder. Turk Psikiyatri Derg 29(1):31–35

    PubMed  Google Scholar 

  45. Colldén G, Tschöp MH, Müller TD (2017) Therapeutic potential of targeting the ghrelin pathway. Int J Mol Sci 18(4):E798

  46. Gurbuz F, Gurbuz BB, Celik GG, Yildirim V, Ucakturk SA, Seydaoglu G, Ucakturk EM, Topaloglu AK, Yuksel B (2016) Effects of methylphenidate on appetite and growth in children diagnosed with attention deficit and hyperactivity disorder. Pediatr Endocrinol Metab 29(1):85–92

    CAS  Google Scholar 

  47. Sahin S, Yuce M, Alacam H, Karabekiroglu K, Say GN, Salıs O (2014) Effect of methylphenidate treatment on appetite and levels of leptin, ghrelin, adiponectin, and brain-derived neurotrophic factor in children and adolescents with attention deficit and hyperactivity disorder. Int J Psychiatry Clin Pract 18(4):280–287

    Article  CAS  PubMed  Google Scholar 

  48. Pakdaman F, Irani F, Tajikzadeh F, Jabalkandi SA (2018) The efficacy of Ritalin in ADHD children under neurofeedback training. Neurol Sci 39:2071–2078. https://doi.org/10.1007/s10072-018-3539-3

    Article  PubMed  Google Scholar 

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Funding

The present study was supported by Tekirdağ Namık Kemal University Scientific Research Community (Grant Number: NKUBAP.02.GA.17.09)

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Authors and Affiliations

  1. Faculty of Medicine, Department of Child and Adolescent Psychiatry, Tekirdağ Namık Kemal University, Tekirdag, Turkey

    Saliha Baykal

  2. Faculty of Medicine, Department of Psychiatry, Tekirdağ Namık Kemal University, Tekirdag, Turkey

    Yakup Albayrak, Özlem Abbak & Murat Beyazyüz

  3. Faculty of Medicine, Department of Pediatrics, Okan University, Istanbul, Turkey

    Ferit Durankuş

  4. Faculty of Medicine, Department of Biochemistry, Tekirdağ Namık Kemal University, Tekirdag, Turkey

    Savaş Güzel

  5. Faculty of Economics and Administrative Science, Department of Healthcare Management, Gazi University, Ankara, Turkey

    Nihan Potas

  6. Faculty of Medicine, Department of Child and Adolescent Psychiatry, Ondokuz Mayıs University, Samsun, Turkey

    Koray Karabekiroğlu

  7. Faculty of Medicine, Department of Pediatrics, Tekirdağ Namık Kemal University, Tekirdag, Turkey

    Mustafa Metin Donma

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  1. Saliha Baykal
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Correspondence to Saliha Baykal.

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The present study was approved by the Namık Kemal University Non-Invasive Clinic Research Ethical Committee.

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Baykal, S., Albayrak, Y., Durankuş, F. et al. Decreased serum orexin A levels in drug-naive children with attention deficit and hyperactivity disorder. Neurol Sci 40, 593–602 (2019). https://doi.org/10.1007/s10072-018-3692-8

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