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Nuclear neurotransmitter molecular imaging of autism spectrum disorder

1 Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, 601 North Caroline Street, Suite 3245, Baltimore Maryland, USA 21287-0006
2 Liaquat University of Medical & Health Sciences, Jamshoro 76090, Sindh, Pakistan

Special Issues: Molecular Mechanisms and Therapy of Autism Spectrum Disorders

Autism spectrum disorder (ASD) is a group of developmental disabilities characterized by marked deficits in social communication and interaction, including limited and repetitive patterns of behavior. We selected key nuclear neurotransmitter molecular imaging reports of ASD by combining “autism” AND “positron” AND “dopamine” OR “serotonin” OR “glutamate” OR “GABA” utilizing databases as follows: PubMed, Scopus, Web of Science, Science Direct, and Google Scholar. This review reports important findings in ASD utilizing positron emission tomography (PET) and single-photon emission computed tomography (SPECT). We studied major neurotransmitter systems, dopamine, serotonin, glutamate, and gamma-aminobutyric acid (GABA). Dopamine neurotransmission was decreased in the anterior medial prefrontal cortex in children with autism. Dopamine transporter was increased in the orbital frontal cortex of adults with ASD and decreased in the striatum of children with ASD. Decreased tryptophan metabolism, an estimate of serotonin synthesis, (A) in left frontal cortex correlated with severe language impairment and (B) in the right frontal cortex correlated with left and mixed handedness. Although not confirmed by some investigators, serotonin transporter was decreased in the cingulate, the medial frontal cortex, the midbrain, and the temporal lobes. Serotonin receptors were decreased in the thalamus in individuals with ASD and in the cortices of parents of children with ASD. Metabotropic glutamate receptor subtype 5 (mGluR 5 ) was increased in the post-central gyrus and the cerebellum of men with autism. PET studies for GABA did not differentiate people with ASD from controls. The increasing incidence of ASD and the inconsistent findings of different nuclear molecular imaging studies are evidence for the urgent need for further investigations utilizing nuclear molecular imaging to identify the key neurophysiological mechanisms underlying the pathophysiology of ASD.
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Keywords cortex; dopamine; gamma-aminobutyric acid; glutamate; midbrain; positron emission tomography; serotonin; single-photon emission computed tomography; striatum; thalamus

Citation: Alveena Batool Syed, James Robert Brašić. Nuclear neurotransmitter molecular imaging of autism spectrum disorder. AIMS Molecular Science, 2019, 6(4): 87-106. doi: 10.3934/molsci.2019.4.87

References

  • 1. Division of Birth Defects, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Data & statistics on autism spectrum disorder, 2019. Available from: https://www.cdc.gov/ncbddd/autism/data.html.
  • 2. Baio J, Wiggins L, Christensen D, et al. (2018) Prevalence of autism spectrum disorder among children aged 8 years-Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2014. MMWR Surveill Summ: 67: 1–23.
  • 3. Brasic J, Farhadi F, Asperger Syndrome, Medscape Drugs & Diseases, 2018. Available from: http://emedicine.medscape.com/article/912296-overview.
  • 4. Brasic J, Farhadi F, Autism Spectrum Disorder, Medscape Drugs & Diseases, 2018. Available from: http://emedicine.medscape.com/article/912781-overview.
  • 5. Office of Communication, Eunice Kennedy Shriver National Institute of Child Health and Human development, Autism spectrum disorder (ASD), 2019. Available from: https://www.nichd.nih.gov/health/topics/autism.
  • 6. Mayo Clinic, Autism spectrum disorder, 2019. Available from: https://www.mayoclinic.org/diseases-conditions/autism-spectrum-disorder/symptoms-causes/syc-20352928.
  • 7. Healthline, Everything you need to know about autism, 2018. Available from: https://www.healthline.com/health/autism#the-autism-spectrum.
  • 8. Brasic J, Barnett J, Kaplan D, et al. (1994) Clomipramine ameliorates adventitious movements and compulsions in prepubertal boys with autistic disorder and severe mental retardation. Neurology 44: 1309–1312.    
  • 9. Brasić J (1999) Movements in autistic disorder. Med Hypotheses 53: 48–49.    
  • 10. Brasic J, Gianutsos J (2000) Neuromotor assessment and autistic disorder. Autism 4: 287–298.    
  • 11. Brašić J (2003) Treatment of movement disorders in autism spectrum disorders, In: Hollander E (Editor), Autism Spectrum Disorders, The Medical Psychiatry Series, Marcel Dekker, Inc., New York 24: 273–346.
  • 12. Brasić J, Barnett J, Aisemberg P, et al. (1997) Dyskinesias subside off all medication in a boy with autistic disorder and severe mental retardation. Psychol Rep 81: 755–767.    
  • 13. Brasić J, Barnett J (1997) Hyperkinesias in a prepubertal boy with autistic disorder treated with haloperidol and valproic acid. Psychol Rep 80: 163–170.    
  • 14. Brasić J, Zagzag D, Kowalik S, et al. (1999) Progressive catatonia. Psychol Rep 84: 239–246.    
  • 15. Brašić J, Barnett J, Will M, et al. (2000) Dyskinesias differentiate autistic disorder from catatonia. CNS Spectr 5: 19–22.
  • 16. Brašić J, Zagzag D, Kowalik S (2000) Clinical manifestations of progressive catatonia. Ger J Psychiatry 3: 13–24.
  • 17. Brasic J, A 20-year-old man who stopped speaking, Medscape, 2017. Available from: http://reference.medscape.com/viewarticle/883207_6.
  • 18. Hwang B, Mohamed M, Brašić J (2017) Molecular imaging of autism spectrum disorder. Int Rev Psychiatry 29: 530–554.    
  • 19. American Psychiatric Association, (2013) Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Washington, DC: American Psychiatric Association.
  • 20. Lord C, Rutter M, Le Couteur A (1994) Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 24: 659–685.    
  • 21. Le Couteur A, Lord C, Rutter M (2003) Autism Diagnostic Interview‐Revised (ADI‐R), Los Angeles: Western Psychological Services (WPS).
  • 22. Lord C, Rutter M, Goode S, et al. (1989) Autism Diagnostic Observation Schedule: a standardized observation of communicative and social behavior. J Autism Dev Disord 19: 185–212.    
  • 23. Lord C, Rutter M, Dilavore P, et al. (2012) Autism Diagnostic Observation Schedule TM, Second Edition, Torrance, CA: Western Psychological Services (WPS).
  • 24. Schopler E, Reichler R, Rochen Renner B (1988) The childhood autism rating scale, Western Psychological Services.
  • 25. Gilliam JE (2013) Gilliam Autism Rating scale, third edition (GARS-3). Torrance, CA: WPS Publish. Available from: https://www.wpspublish.com/gars-3-gilliam-autism-rating-scale-third-edition.
  • 26. Wong D, Brasić J (2001) In vivo imaging of neurotransmitter systems in neuropsychiatry. Clin Neurosci Res 1: 35–45.    
  • 27. Wong D, Gründer G, Brašić J (2007) Brain imaging research: does the science serve clinical practice? Int Rev Psychiatry 19: 541–558.    
  • 28. Brasic J, Mohamed M (2014) Human brain imaging of autism spectrum disorders, In: Seeman P, Madras B (Editors), Imaging of the human brain in health and disease, Academic Press, Elsevier Science, Oxford, UK, 373–406.
  • 29. Brasic J, Wong D, PET Scanning in Autism Spectrum Disorders. Medscape Drugs & Diseases, 2015. Available from: http://emedicine.medscape.com/article/1155568-overview.
  • 30. Lu F, Yuan Z (2015) PET/SPECT molecular imaging in clinical neuroscience: recent advances in the investigation of CNS diseases. Quant Imaging Med Surg 5: 433–447.
  • 31. Wong D, Maini A, Rousset O, et al. (2003) Positron emission tomography--a tool for identifying the effects of alcohol dependence on the brain. Alcohol Res Health 27: 161–173.
  • 32. Munro C, McCaul M, Wong D, et al. (2006) Sex differences in striatal dopamine release in healthy adults. Biol Psychiatry 59: 966–974.    
  • 33. Lammertsma AA (2001) PET/SPECT: functional imaging beyond flow. Vision Res 41: 1277–1281.    
  • 34. Sheffler Z, Pillarisetty L (2019) Physiology, Neurotransmitters, In: StatPearls [Internet], Treasure Island (FL): StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539894/.
  • 35. Chugani D (2012) Neuroimaging and neurochemistry of autism. Pediatr Clin North Am 59: 63–73.    
  • 36. Zürcher N, Bhanot A, McDougle C, et al. (2015) A systematic review of molecular imaging (PET and SPECT) in autism spectrum disorder: current state and future research opportunities. Neurosci Biobehav Rev 52: 56–73.    
  • 37. Ernst M, Zametkin A, Matochik J, et al. (1997) Low medial prefrontal dopaminergic activity in autistic children. Lancet 350: 638.
  • 38. Makkonen I, Riikonen R, Kokki H, et al. (2008) Serotonin and dopamine transporter binding in children with autism determined by SPECT. Dev Med Child Neurol 50: 593–597.    
  • 39. Xiao-mian S, Jing Y, Chongxuna Z, et al. (2005) Study of 99mTc-TRODAT-1 imaging on human brain with children autism by single photon emission computed tomography. IEEE Engineering in Medicine and Biology 27th Annual Conference, Shanghai, 5: 5328–5330.
  • 40. Nakamura K, Sekine Y, Ouchi Y, et al. (2010) Brain serotonin and dopamine transporter bindings in adults with high-functioning autism. Arch Gen Psychiatry 67: 59–68.    
  • 41. American Psychiatry Association, (1987) Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, Washington, DC: American Psychiatric Association.
  • 42. American Psychiatry Association, (2000) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, Washington, DC: American Psychiatric Association.
  • 43. Frost J, Rosier A, Reich S, et al. (1993) Positron emission tomographic imaging of the dopamine transporter with 11C-WIN 35,428 reveals marked declines in mild Parkinson's disease. Ann Neurol 34: 423–431.    
  • 44. Kung H, Kim H, Kung M, et al. (1996) Imaging of dopamine transporters in humans with technetium-99m TRODAT-1. Eur J Nucl Med 23: 1527–1530.    
  • 45. Kung M, Stevenson D, Plössl K, et al. (1997) [99mTc]TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent. Eur J Nucl Med 24: 372–380.
  • 46. Chugani D, Chugani H, Wiznitzer M, et al. (2016) Efficacy of low-dose buspirone for restricted and repetitive behavior in young children with autism spectrum disorder: a randomized trial. J Pediatr 170: 45–53.    
  • 47. Blue ME, Johnston MV, Moloney CB, et al. (2008) Serotonin dysfunction in autism, In: Zimmerman, A.W. Author, Autism, Totowa, NJ: Humana Press, 111–132.
  • 48. Chandana S, Behen M, Juhász C, et al. (2005) Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism. Int J Dev Neurosci 23: 171–182.    
  • 49. Chugani, D, Muzik O, Behen M, et al. (1999) Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children. Ann Neurol 45: 287–295.    
  • 50. Chugani D, Muzik O, Rothermel R, et al. (1997) Altered serotonin synthesis in the dentatothalamocortical pathway in autistic boys. Ann Neurol 42: 666–669.    
  • 51. Girgis R, Slifstein M, Xu X, et al. (2011) The 5-HT (2A) receptor and serotonin transporter in asperger's disorder: A PET study with [¹¹C]MDL 100907 and [¹¹C]DASB. Psychiatry Res 194: 230–234.    
  • 52. Beversdorf D, Nordgren R, Bonab A, et al. (2012) 5-HT2 receptor distribution shown by [18F] setoperone PET in high-functioning autistic adults. J Neuropsychiatry Clin Neurosci 24: 191–197.    
  • 53. Goldberg J, Anderson G, Zwaigenbaum L, et al. (2009) Cortical serotonin type-2 receptor density in parents of children with autism spectrum disorders. J Autism Dev Disord 39: 97–104.    
  • 54. American Psychiatry Association, (1994) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC: American Psychiatric Association.
  • 55. Huang X, Xiao X, Gillies R, et al. (2016) Design and automated production of 11C-alpha- methyl-l-tryptophan (11C-AMT). Nucl Med Biol 43: 303–308.    
  • 56. Mazurek M, Kanne S (2018) Leiter international performance scale, In: Kreutzer J, DeLuca J, Caplan B, (eds) Encyclopedia of Clinical Neuropsychology, Third Edition, Springer, Cham.
  • 57. Fatemi S, Wong D, Brašić J, et al. (2018) Metabotropic glutamate receptor 5 tracer [18F]-FPEB displays increased binding potential in postcentral gyrus and cerebellum of male individuals with autism: a pilot PET study. Cerebellum Ataxias 5: 3.    
  • 58. Wong D, Waterhouse R, Kuwabara H, et al. (2013) 18F-FPEB, a PET radiopharmaceutical for quantifying metabotropic glutamate 5 receptors: a first-in-human study of radiochemical safety, biokinetics, and radiation dosimetry. J Nucl Med 54: 388–396.    
  • 59. Mendez M, Horder J, Myers J, et al. (2013) The brain GABA-benzodiazepine receptor alpha-5 subtype in autism spectrum disorder: A pilot [11C]Ro15-4513 positron emission tomography study. Neuropharmacology 68: 195–201.    
  • 60. Horder J, Andersson M, Mendez M, et al. (2018) GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models. Sci Transl Med 10.
  • 61. Halldin C, Farde L, Litton J, et al. (1992) [11C]Ro 15-4513, a ligand for visualization of benzodiazepine receptor binding. Psychopharmacology (Berl) 108: 16–22.    
  • 62. Brasic J, Mathur A, Budimirovic D (2019) The urgent need for molecular imaging to confirm target engagement for clinical trials of fragile X syndrome and other subtypes of autism spectrum disorder. Arch Neurosci 6: e91831.
  • 63. Budimirovic D, Kravis E, Ercikson C, et al. (2017) Updated report on tools to measure outcomes of clinical trials in fragile X syndrome. J Neurodev Disord 9: 14.    
  • 64. World Health Organization, International Classification of Diseases, Tenth Revision, 2019. Available from: www.who.int/classifications/en/.

 

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