Skip to main content

Autism Spectrum Disorder

  • Chapter
The Medical Basis of Psychiatry

Abstract

This chapter identifies the biological underpinnings, phenomenology, assessment and medical treatment of Autism Spectrum Disorder, a complex neurodevelopmental disorder. Basic science has made great strides in identifying the brain pathology of autism at various levels of scrutiny. This chapter reviews genetic, molecular, histological, anatomical and epidemiological levels of the disorder. Also, new assessment technologies have come on line to provide greater clarity in what collection of observations should be called autism and what would not. Although interventions that alter the newly identified pathophysiological processes are yet to be formulated, approaches to treatment that fail to take into account the current scientific evidence of the causes of autism can and should be avoided. The chapter describes an orientation to autism from the perspective of the scientific literature to provide a foundation for clinical decision-making for the practitioner.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
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. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association Publishing; 2013.

    Google Scholar 

  2. Kanner L. Autistic disturbance of affective contact. Nerv Child 1943;2:217–250.

    Google Scholar 

  3. American Academy of Child and Adolescent Psychiatry CQI. Practice Parameter for the Assessment and Treatment of Children and Adolescents with Autism Spectrum Disorder J Am Acad Child Adolesc Psychiatry 2014;53:237–257.

    Google Scholar 

  4. McGrew SG, Peters BR, Crittendon JA, Veenstra-Vanderweele J. Diagnostic yield of chromosomal microarray analysis in an autism primary care practice: Which guidelines to implement? Journal of Autism and Developmental Disorders 2012;42:1582–1591.

    Google Scholar 

  5. The ICD-10 Classification of Mental and Behavioral Disorders: Diagnostic Criteria for Research. World Health Organization, Geneva; 1993.

    Google Scholar 

  6. Rogers SJ. Developmental regression in autism spectrum disorders. Ment Retard Dev Disabil Res Rev 2004;10:139–143.

    Article  PubMed  Google Scholar 

  7. Mouridsen SE. Childhood disintegrative disorder. Brain Dev 2003;25:225–228.

    Article  PubMed  Google Scholar 

  8. Volkmar FR, Klin A, Siegel B, Szatmari P, Lord C, Campbell M, Freeman BJ, Cicchetti DV, Rutter M, Kline W. Field trial for autistic disorder in DSM-IV. Am J Psychiatry 1994;151:1361–1367.

    Article  CAS  PubMed  Google Scholar 

  9. Cohen DJ, Volkmar F, Anderson G, Klin A. Integrating biological and behavioral perspectives in the study and care of autistic individuals: the future. Isr J Psychiatr Rel Sci 1993;30:15–32.

    CAS  Google Scholar 

  10. Lord C, Rutter M, Le Couteur A. Autism Dioagnostic Interview –Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 1994;24:659–685.

    Article  CAS  PubMed  Google Scholar 

  11. Lord C, Pickles A, McLennan J, Rutter M, Bregman J, Folstein S, Fombonne E, Leboyer M, Minshew N. Diagnosing autism: analyses of data from the Autism Diagnostic Interview. J Autism Dev Disord 1997;27:501–517.

    Article  CAS  PubMed  Google Scholar 

  12. Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC, Pickles A, Rutter M. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord 2000;30:205–223.

    Article  CAS  PubMed  Google Scholar 

  13. Berument SK, Starr E, Pickles A, Tomlins M, Papanikolauou K, Lord C, Rutter M. Pre-linguistic Autism Diagnostic Observation Schedule adapted for older individuals with severe to profound mental retardation: a pilot study. J Autism Dev Disord 2005;35:821–829.

    Article  PubMed  Google Scholar 

  14. Wadden NP, Bryson SE, Rodger RS. A closer look at the Autism Behavior Checklist: discriminant validity and factor structure. J Autism Dev Disord 1991;21:529–541.

    Article  CAS  PubMed  Google Scholar 

  15. Volkmar FR, Cicchetti DV, Dykens E, Sparrow SS, Leckman JF, Cohen DJ. An evaluation of the Autism Behavior Checklist. J Autism Dev Disord 1988;18:81–97

    Article  CAS  PubMed  Google Scholar 

  16. Marteleto MR, Pedromonico MR. Validity of Autism Behavior Checklist. Revista Brasileira de Psiquiatria 2005;27:295–301.

    Article  PubMed  Google Scholar 

  17. Rellini E, Tortolani D, Trillo S, Carbone S, Montecchi F. Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC) correspondence and conflicts with DSM-IV criteria in diagnosis of autism. J Autism Dev Disord 2004;34:703–708.

    Article  CAS  PubMed  Google Scholar 

  18. Gilliam JE. Gilliam Autism Rating Scale. Dallas, TX: PRO-ED; 1995.

    Google Scholar 

  19. Constantino JN, Hudziak JJ, Todd RD. Deficits in reciprocal social behavior in male twins: evidence for a genetically independent domain of psychopathology. J Amer Acad Child Adolesc Psych 2003;42:458–467.

    Article  Google Scholar 

  20. Stone WL, Coonrod EE, Pozdol SL, Turner LM. The Parent Interview for Autism-clinical version (PIA_CV): A measure of behavioral change for young children with autism. Autism 2003;7:9–30.

    Article  PubMed  Google Scholar 

  21. Tsatsanis KD, Dartnall B, Cuicchetti D, Sparrow SS, Klin A, Volkmar FR. Concurrent validity and classification accuracy of the Leiter and Leiter-R in low functioning children with autism. J Autism Dev Disord 2003;33:23–30.

    Article  PubMed  Google Scholar 

  22. Bishop DV, Baird G. Parent and teacher report of pragmatic aspects of communication: Use of the Children's Communication Checklist in a clinical setting. Dev Med Child Neurol 2001;43:809–818.

    Article  CAS  PubMed  Google Scholar 

  23. Sparrow S, Balla D, Cecchetti D. Vineland Adaptive Behavior Scales, Circle Pines, MN: American Guidance Service; 1984.

    Google Scholar 

  24. Lord C, Leventhal B, Cook E. Quantifying the phenotype in autism spectrum disorders. Am J Med Genetics 2001;105:36–38.

    Google Scholar 

  25. Folstien S, Rutter M. Infantile autism: A genetic study of 21 twin pairs. J Child Psychol Psychiatry 1977;18:297–321.

    Article  Google Scholar 

  26. Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 1989;30:405–416.

    Article  CAS  PubMed  Google Scholar 

  27. Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995;25:63–77.

    Article  CAS  PubMed  Google Scholar 

  28. Veensra-VanderWeele J, Christian SL, Cook EH Jr. Autism as a paradigmatic complex genetic disorder. Annu Rev Genom Hum Benet 2004;5:397–405.

    Google Scholar 

  29. Pickels A, Bolton P, Macdonald H, Bailey A, Le Couteur A, Sim CH, Rutter M. Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: A twin and family history study of autism. Am J Hum Genet 1995;57:717–726.

    Google Scholar 

  30. International Molecular Genetic Study of Autism Consortium. A full genome screen for autism with evidence for linkage to a region on chromosome 7q. Hum Mol Genet 1998; 7:571–578.

    Article  CAS  Google Scholar 

  31. International Molecular Genetic Study of Autism Consortium. A genome-wide screen for autism: strong evidence for linkage to chromosomes 2q, 7q and 16p. Am J Hum Genet 2001;69:570–581.

    Article  Google Scholar 

  32. Steele MM, Al-Adeimi M, Siu VM, Fan YS. Brief report: A case of autism with interstitial deletion of chromosome13. J Autism Dev Disorder 2001;31:231–234.

    Article  CAS  Google Scholar 

  33. McCauley JL, Li C, Jiang L, Olson LM, Crockett G, Gainer K, Folstein SE, Haines JL, Sutcliffe JS. Genome-wide and Ordered-Subset Linkage analyses provide support for autism loce on 17q and 19p with evidence of phenotypic and interlocus genetic correlates. BMC Medical Genetics 2005;6:1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Shao Y, Wolpert CM, Raiford KL, Menold MM, Donnelly SL, Ravan SA, Bass MP, McClain C, von Wendt L, Vance JM, Abramson RH, Wright HH, Ashley-Koch A, Gilbert JR, Delong RG, Cuccaro ML, Pericak-Vance MA, McCoy PA. Genomic screen and follow up analysis for autistic disorder. AM J Med Genet 2002;114:99–105.

    Article  PubMed  Google Scholar 

  35. Philippe A, Martinez M, Guilloud-Batalle M, Gillberg C, Rastam M, Sponheim E, Coleman M, Zappella M, Aschauer H, van Malldergerme L, Penet C, Feingold J, Brice A, Leboyer M. Genome-wide scan for autism susceptibility genes. Hum Mol Genet 1999;8:805–812.

    Article  CAS  PubMed  Google Scholar 

  36. Buxbaum JD, Silverman J, Keddache M, Smith CJ, Hollander E, Ramoz N, Reichert JG. Linkage analysis for autism in a subset of families with obsessive-compulsive behavior: evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19. Mol Psychiatry 2004;9:144–150.

    Article  CAS  PubMed  Google Scholar 

  37. Van den Veyver IB, Zoghbi HY. Genetic basis of Rett syndrome. Mental Retard Dev Disabil Res Rev 2002;8:82–86.

    Article  Google Scholar 

  38. Kjelgaard MM, Tager-Flusberg H. An investigation of language impairment in autism: Implications for genetic subgourps. Lang Cogn Processes 2001;16:287–308.

    Article  Google Scholar 

  39. Bartlett CW, Flax JF, Logue MW, Smith BJ, Vieland VJ, Tallal P, Brzustowicz LM. Examination of Potential Overlap in Autism and Language Loci on Chromosomes 2, 7, and 13 in two Independent samples ascertained for specific language impairment. Hum Hered 2004;57:10–20.

    Google Scholar 

  40. Gottesman I, Gould T. The endophenotype concept in Psychiatry: etymology and strategic intentions. Am J Psychiatry 2003;160:636–645.

    Article  PubMed  Google Scholar 

  41. Rutter M, Bailey A, Bolton P, Le Couteur A. Autism and known medical conditions: myth and substance. J Child Psychol Psychiatry 1994;35:311–322.

    Article  CAS  PubMed  Google Scholar 

  42. Klauck SM, Munstermann E, Bieber-Martig B, Rühl D, Lisch S, Schmötzer G, Poustka A, Poustka F. Molecular genetic analysis of the FMR-1 gene in a large collection of autistic patients. Hum Genet 1997;100:224–229.

    Article  CAS  PubMed  Google Scholar 

  43. Gutierrez GC, Smalley SL, Tanguay PE. Autism in tuberous sclerosis complex. J Autism Dev Disord 1998;28:97–103.

    Article  CAS  PubMed  Google Scholar 

  44. Jacobsen J, King BH, Leventhal BL, Christian SL, Ledbetter DH, Cook EH Jr. Molecular Screening for Proximal 15q abnormalities in a mentally retarded population. J Med Genet 1998;35:534–538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Steffenburg S, Gillberg CL, Steffenburg U. Autism in Angelman syndrome: a population-based study. Pediatr Neurol 1996;14:131–136.

    Article  CAS  PubMed  Google Scholar 

  46. American College of Obstetrics and Gynecologists Committee on Genetics. ACOG committee opinion No. 338: Screening for fragile X syndrome. Obstet Gynecol 2006;107:1483–1485.

    Google Scholar 

  47. Murray J, Cuckle H, Taylor G, Hewison J. Screening for fragile X syndrome. Health Tech Assess 1997;1:1–71.

    Google Scholar 

  48. Bailey DB Jr, Mesibov GB, Hatton DD, Clark RD, Roberts JE, Mayhew L. Autistic behavior in young boys with fragile X syndrome. J Autism Dev Disord 1998;28:499–508.

    Article  PubMed  Google Scholar 

  49. Hagerman R. Medical aspects of the fragile X syndrome. In: The Fragile X Child, Singular Publishing Group; 1992. p. 19-29.

    Google Scholar 

  50. Hallmayer J, Pintado E, Lotspeich L, Spiker D, McMahon W, Petersen PB, Nicholas P, Pingree C, Kraemer HC, Wong DL. Molecular analysis and test of linkage between the FMR-1 gene and infantile autism in multiplex families. Am J Hum Genet 1994; 55:951–959.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Piven J, Gayle J, Landa R, Wzorek M, Folstein S. The prevalence of fragile X in a sample of autistic individuals diagnosed using a standardized interview. J Am Acad Child Adolesc Psychiatry 1991;30:825–830.

    Google Scholar 

  52. Payton JB, Steele MW, Wenger SL, Minshew NJ. The fragile X marker and autism in perspective. J Am Acad Child Adolesc Psychiatry 1989;28:417–421.

    Article  CAS  PubMed  Google Scholar 

  53. Septer S, Thompson ES, Willemsen-Dunlap A. Anesthesia concerns for children with tuberous sclerosis. AANA J 2006;74:219–225.

    PubMed  Google Scholar 

  54. Wiznitzer M. Autism and tuberous sclerosis. J Child Neurology 2004;19:675–679.

    Google Scholar 

  55. Smalley SL. Autism and tuberous sclerosis. J Autism Dev Disord 1998;28:407–414.

    Article  CAS  PubMed  Google Scholar 

  56. Baker P, Piven J, Sato Y. Autism and tuberous sclerosis complex: prevalence and clinical features. J Autism Dev Disord 1998;28:279–285.

    Article  CAS  PubMed  Google Scholar 

  57. Starr EM, Berument SK, Tomlins M, Papnikolaou K, Rutter M. Brief report: autism in individuals with Down syndrome. J Autism Dev Disord 2005;35:665–673.

    Article  PubMed  Google Scholar 

  58. Kroeger KA, Nelson WM. A language program to increase the verbal production of a child dually diagnosed with Down syndrome and autism. J Intellect Disabil Res 2006;50:101–108.

    Article  CAS  PubMed  Google Scholar 

  59. Rasmussen P, Borjesson O, Wentz E, Gillberg C. Autistic disorders in Down syndrome: background factors and clinical correlates. Dev Med Child Neurol 2001;43:750–754.

    Article  CAS  PubMed  Google Scholar 

  60. Marui T, Hashimoto O, Nanba E, Kato C, Tochigi M, Umekage T, Ishijima M, Kohda K, Kato N, Sasaki T. Association between the neurofibromatosis-1 (NF1) locus and autism in the Japanese population; Am J Med B Neuropsychiatr Genet 2004;131:43–47.

    Article  Google Scholar 

  61. Mbarek O, Marouillat S, Martineau J, Barthelemy C, Muh JP, Andres C. Association study of the NF1 gene and autistic disorder. Am J Med Genet 1999;88:729–732.

    Article  CAS  PubMed  Google Scholar 

  62. Plank SM, Copeland-Yates SA, Sossey-Alaoui K, Bell JM, Schroer RJ, Skinner C, Michaelis RC. Lack of association of the (AAAT)6 allele of the GXAlu tetranucleotide repeat in intron 27b of the NF1 gene with autism. Am J Med Genet 2001;105:404–405.

    Article  CAS  PubMed  Google Scholar 

  63. Smith AC, McGavran L, Robinson J, Waldstein G, Macfarlane J, Zonona J, Reiss J, Lahr M, Allen L, Magenis E. Interstitial deletion of (17)(P11.2p11.2) in nine patients. Am J Med Genet 1986;24:393–414.

    Article  CAS  PubMed  Google Scholar 

  64. Hobson RP, Bishop M. The pathogenesis of autism: insights from congenital blindness. Philos Trans R Soc of Lond B Biol Sci 2003;358:335–344.

    Article  Google Scholar 

  65. Carvill S. Sensory impairments, intellectual disability and psychiatry. J Intellect Disabil Res 2001;45:467–483.

    Article  CAS  PubMed  Google Scholar 

  66. Hobson RP, Lee A, Brown R. Autism and congenital blindness. J Autism Dev Disord 1999;29:45–56.

    Article  CAS  PubMed  Google Scholar 

  67. Brown R, Hobson RP, Lee A, Stevenson J. Are there “autistic like” features in congenitally blind children? J Child Psychol Psychiatry 1997;38:693–703.

    Article  CAS  PubMed  Google Scholar 

  68. Deggouj N, Eliot MM. Autistic like behavioural disorders and deafness in children (French). Revue de Laryngologie Otologie Rhinologie 2005;126:365–367.

    CAS  PubMed  Google Scholar 

  69. Gayda M, Saleh D. Peripheral, central and psychic deafness: diagnosis difficulties in case of autism child (French). Revue de Laryngologie Otologie Rhinologie 2004;125:277–280.

    CAS  PubMed  Google Scholar 

  70. Roper L, Arnold P, Monteiro B. Co-occurrence of autism and deafness: diagnostic considerations. Autism 2003;7:245–253.

    Article  PubMed  Google Scholar 

  71. Rosenhall U, Nordin V, Sandstrom M, Ahlsen G, Gillberg C. Autism and hearing loss. J Autism Dev Disord 1999;29:349–357.

    Article  CAS  PubMed  Google Scholar 

  72. Piven J, Arndt S, Bailey J, Havercamp S, Andreasen N, Palmer P. An MRI study of brain size in autism. Am J Psychiatry 1995;152:1145–1149.

    Article  CAS  PubMed  Google Scholar 

  73. Hardan AY, Minshew NJ, Mallikarjuhn M, Keshavan MS. Brain Volume in Autism. J Child Neurol 2001;16:421–424.

    Article  CAS  PubMed  Google Scholar 

  74. Hardan AY, Minshew N, Harenski K, Keshavan MS. Posterior fossa magnetic resonance imaging in autism. J Am Acad Child Adolesc Psychiatry 2001;40:666–672.

    Article  CAS  PubMed  Google Scholar 

  75. Piven J, Arndt S, Bailey J, Andreasen N. Regional brain enlargement in autism: a magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry 1996;35:530–536.

    Article  CAS  PubMed  Google Scholar 

  76. Courchesne E, Karns CM, Davis HR, Ziccardi R, Carper RA, Tigue ZD, Chisum HJ, Moses P, Pierce K, Lord C, Lincoln AJ, Pizzo S, Schreibman L, Hass RH, Akshoomoff NA, Courchesne RY. Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology 2001;57:245–254.

    Article  CAS  PubMed  Google Scholar 

  77. Kates W, Burnette C, Eliez S, Strunge LA, Kaplan D, Landa R, Reiss A, Perlson GD. Neuroanatomic variation in monozygotic twin pairs discordant for the narrow phenotype for autism. Am J Psychiatry 2004;161:539–546.

    Article  PubMed  Google Scholar 

  78. Castelli F, Frith C, Happe F, Frith U. Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. Brain 2002;125:1839–1849.

    Article  PubMed  Google Scholar 

  79. Frances A, Krams M, Ashburner J, Passingham R, Friston K, Frackowiak R, Happe F, Frith C, Frith U. The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans. Nueroreport 1999;10:1647–1651.

    Article  Google Scholar 

  80. Happe F, Ehlers S, Fletcher P, Frith U, Johansson M, Gillberg C, Dolan R, Frackowiak R, Frith C. 'Theory of mind' in the brain. Evidence from a PET scan study of Asperger syndrome. Neuroreport 1996;8:197–201.

    Article  CAS  PubMed  Google Scholar 

  81. Courchesne E, Townsend J, Saitoh O. The brain in infantile autism: posterior fossa structures are abnormal. Neurology 1994;44:214–223.

    Article  CAS  PubMed  Google Scholar 

  82. Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism. In: Bauman ML and Kemper TL, editors, The neurobiology of Autism, Baltimore: Johns Hopkins Press; 1994. p. 119–145.

    Google Scholar 

  83. Bauman M, Kemper TL. Neuroanatomic Observations of the brain in autism: a review and future directions. Int J Dev Neurosci 2005;23:183–187.

    Article  PubMed  Google Scholar 

  84. Fatemi SH, Halt AR, Earle J, Kist DA, Realmuto GM, Thuras PD, Merz A. Purkinje cell size is reduced in cerebellum of patients with autism. Cell Mol Neurobiol 2002;22:171–175.

    Article  PubMed  Google Scholar 

  85. Arin ML, Bauman M, Kemper TL. The distribution of Purkinje cell loss in the cerebellum in autism. Neurology 1991;41:307.

    Google Scholar 

  86. Bauman M and Kemper T. Histoanatomic observations of the brain in early infantile autism. Neurology 1985;35:866–874.

    Article  CAS  PubMed  Google Scholar 

  87. Raymond ML, Bauman M, Kemper TL. The hippocampus in autism: Golgi analysis. Acta Neuropathol 1996;91:117–119.

    Article  CAS  PubMed  Google Scholar 

  88. Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, Rutter M, Lantos P. A clinicopathological study of autism. Brain 1998;121:889–905.

    Article  PubMed  Google Scholar 

  89. Casanova MF, Buxhoeveden D, Switala A, Roy E. Minicolumnar pathology in autism. Neurology 2002;58:428–432.

    Article  PubMed  Google Scholar 

  90. Bauman M, Kemper T. Observation of the Purkinje cells in the cerebellar vermis in autism. J Neuropathol Exp Neurol 1996;55:613.

    Article  Google Scholar 

  91. Kemper TL, Bauman M. Neuropathology of infantile autism. J Neuropathol Exp Neurol 1998;57:645–652.

    Article  CAS  PubMed  Google Scholar 

  92. Bauman ML, Kemper TL. The neurobiology of autism. 2nd ed. Baltimore, MD: The Johns Hopkins University Press; 2005.

    Google Scholar 

  93. Palmen SJ, Hulshoff Pol HE, Kemner C, Schnack HG, Sitskoorn MM, Appels MC, Kahn RS, Van Engeland H. Brain anatomy in non-affected parents of autistic probands: a MRI study. Psychol Med 2005;35:1411–1420.

    Article  PubMed  Google Scholar 

  94. Fatemi SH, Halt AR, Stary JM, Realmuto GM, Jalali-Mousavi M. Reduction in anti-apoptotic protein Bcl-2 in autistic cerebellum. Neuroreprot 2001;12:929–933.

    Article  CAS  Google Scholar 

  95. Araki N, Morimasa T, Sakai T, Tokuoh H, Yyunoue S, Kama M, Miyazaki K, Abe K, Saya H, Tsugita A. Comparative analysis of brain proteins from p53 deficient mice by two-dimensional electrophoresis. Electorphoresis 2000;21:1880–1889.

    Article  CAS  Google Scholar 

  96. Fatemi SH, Halt AR. Altered levels of Bcl2 and p53 proteins in parietal cortex reflect deranged apoptotic regulation in autism. Synapse 2001;42:281–284.

    Article  CAS  PubMed  Google Scholar 

  97. Fatemi SH, Snow AV, Stary JM, Araghi-Niknam M, Reutiman TJ, Lee S, Brooks A, Pearce D. Reelin signaling is impaired in autism. Biol Psychiatry 2005;57:777–787.

    Article  CAS  PubMed  Google Scholar 

  98. Fatemi SH, Emamian ES, Kist D, Sidwell RW, Nakajima K, Akhter P, Shier A, Sheikh S, Bailey K. Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prentally infected neonatal mice. Mol Psychiatry 1999;4:145–154.

    Article  CAS  PubMed  Google Scholar 

  99. Persico AM, D’Agruma L, Maiorano N, Totaro A, Militerni R, Bravaccio C, Wassink T, Schneider C, Melmed R, Trillo S, Montecchi R, Palermo M, Pascucci T, Publisi Allegra S, Reichelt K, Conciatori M, Marion R, Quattrocchi C, Baldi A, Zelante L, Gasparini P, Keller F. Rellin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry 2001;6:150–159.

    Article  CAS  PubMed  Google Scholar 

  100. Fatemi SH, Stary JM, Halt A, Realmuto G. Dysregulation of Reelin and Bcl-2 in autistic cerebellum. J Autsim Dev Disord 2001;31:529–535.

    Article  CAS  Google Scholar 

  101. Fatemi SH, Stary JM, Egan EA. Reduced blood levels of reelin as a vulnerability factor in pathophysiology of autistic disorder. Cell Mol Neurobiol 2002;22:139–152.

    Article  CAS  PubMed  Google Scholar 

  102. Rolf LH, Haarmann FY, Grotemeyer KH, Keher H. Serotonin and amino acid content in platelets or autistic children. Acta Psychiatr Scand 1993;87:312–316.

    Article  CAS  PubMed  Google Scholar 

  103. Moreno-Fuenmayor H, Borjas L, Arrieta A, Valera V, Socorro-Candanoza L. Plasma excitatory amino acids in autism, Invest Clin 1996;37:113–128.

    Google Scholar 

  104. Fatemi SH, Halt AR, Stary J, Kenodio R, Schulz SC, Realmuto GM. Glutamic acid deearboxylase 65 and 67 k Da proteins are reduced on autistic parietal and cerebellar corticies. Biol Psychiatry 2002;52:805–810.

    Article  CAS  PubMed  Google Scholar 

  105. Blatt GJ. GABAergic cerebellar system in autism: a neuropathological and developmental perspective. Int Rev Neurobiol 2005; 71:167–178.

    Article  CAS  PubMed  Google Scholar 

  106. Blatt GJ, Fitzgerald CM, Guptill JT, Booker AB, Kemper TL. Density and distribution of hippocampal neurotransmitter receptors in autism. J Autism Dev Disord 2001;31:537–543.

    Article  CAS  PubMed  Google Scholar 

  107. Vargas DL, Nascimbene C, Krishnan C, Aimmerman AW, Pardo CA. Nerogligla activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005;57:67–81.

    Article  CAS  PubMed  Google Scholar 

  108. Pliopys AV, Greaves A, Yoshida W. Anti CNS antibodies in childhood neurologic diseases. Neuropediatrics 1989;20:93–102.

    Article  Google Scholar 

  109. Ahlsén G, Rosengren L, Belfrage M, Palm A, Haglid K, Hamberger A, Gillberg C. Glial fibrillary acidic protein in the cerebrospinbal fluid of children with autism and other neuropsychiatric disorders. Biol Psychiatry 1993;33:734–743.

    Article  PubMed  Google Scholar 

  110. Laurence JA, Fatemi SH. Glial fibrillary acidic protein is elevated in superior frontal, parietal and cerebellar cortices of autistic subjects. Cerebellum 2005;4:206–210.

    Article  CAS  PubMed  Google Scholar 

  111. Todd RD, Ciaranello RD. Demonstration of inter-and intraspecies differences in serotonin binding sites by antibodies from an autistic child. Proc Natl Acad Sci USA 1985;82:612–616.

    Google Scholar 

  112. Shi L, Fatemi SH, Sidwell TW, Patterson PH. Maternal influenza infection causes marked behavior and pharmacological changes in the offspring. J Neurosci 2003;23:297–302.

    PubMed  Google Scholar 

  113. Warren RP, Foster A, Margaretten NC. Reduced natural killer cell activity in autism. J Am Acad Child Adoelsc Psychiatry 1987;26:333–335.

    Article  CAS  Google Scholar 

  114. Gupta S, Aggarwal S, Rashanravan R, Lee T. TH1-and TH2-like cytokins in CD4+ and CD8+ T cells in autism. J Neuroimmunol 1998;85:106–109.

    Article  CAS  PubMed  Google Scholar 

  115. Kagan-Kushnir T, Roberts SW, Snead OC. Screening electroencephalogram in autism spectrum disorders: evidence-based guideline. J Child Neurol 2005;20:197–206.

    Article  PubMed  Google Scholar 

  116. Kim HL, Donnelly JH, Tournay AE, Book TM, Filipek P. Absence of seizures despite high prevalence of epileptiform EEG abnormalities in children with autism monitored in a tertiary care center. Epilepsia 2006;47:394–398.

    Article  PubMed  Google Scholar 

  117. Chez MG, Chang M, Krasne V, Coughlan C, Kominsky M, Schwartz A. Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996 to 2005. Epilepsy Behav 2006;8:267–271.

    Article  PubMed  Google Scholar 

  118. Reinhold JA, Molloy CA, Manning-Courtney P. Electroencephalogram abnormalities in children with autism spectrum disorders. J Neurosci Nurs 2005;37:136–138.

    Article  PubMed  Google Scholar 

  119. Canitano R, Luchetti A, Zappella M. Epilepsy, electroencephalogramic abnormalities, and regression in children with autism. J Child Neurol 2005;20:27–31.

    Article  PubMed  Google Scholar 

  120. Hughes JR, Melyn M. EEG and seizures in autistic children and adolescents: further findings with therapeutic implications. Clin EEG Neurosci 2005;36:15–20.

    Article  PubMed  Google Scholar 

  121. Hashimoto T, Sasaki M, Sugai K, Hanaoka S, Fukumizu M, Kato T. Paroxysmal discharges on EEG in young autistic patients are frequent in frontal regions. J Med Invest 2001;48:175–180.

    CAS  PubMed  Google Scholar 

  122. Hrdlicka M, Komarek V, Propper L, Kulisek R, Zumrova A, Faladova L Havlovicova M, Sedlacek Z, Blatny M, Urbanek T. Not EEG abnormalities but epilepsy is associated with autistic regression and mental functioning in childhood autism. Eur Child Adoles Psychiatry 2004;13:209–213.

    Article  Google Scholar 

  123. Yeargin-Allsopp M, Rice C, Karapurkar T, Doernberg NH, Boyle C, Murphy C. Prevalence of autism in a US Metropoloitan Area. JAMA 2003;289:45–55.

    Article  Google Scholar 

  124. Fombonne E. The epidemiology of autism: a review. Psychol Med 1999;29:769–786.

    Article  CAS  PubMed  Google Scholar 

  125. Lotter V. Methodological problems in cross-cultural epidemiologic research: illustrations from a survey of childhood autism in Africa. In: Earls F, editor, Studies of Children, New York: Neale Watson; 1980. p. 126–144.

    Google Scholar 

  126. Fombonne E. The prevalence of autism. JAMA 2003;289:87–89.

    Article  PubMed  Google Scholar 

  127. Centers for Disease Control and Prevention (CDC). Mental health in the United States: parental report of diagnosed autism in children aged 4–17 years—United States, 2003–2004. MMWR Morb Mortal Wkly Rep 2006;55:481–486.

    Google Scholar 

  128. Fombonne E. Epidemiological surveys of autism and other pervasive developmental disorders: an update. J Autism Dev Disord 2003;33:365–382.

    Article  PubMed  Google Scholar 

  129. Fombonne E. The prevalence of autism. JAMA 2003;289:87–89.

    Article  PubMed  Google Scholar 

  130. Jick H, Kaye JA. Epidemiology and possible causes of autism. Pharmacotherapy 2003;23:1524–1530.

    Article  PubMed  Google Scholar 

  131. Volkmar F, Siegel M, Woodbury-Smith M, King B, McCracken J, State M, American Academy of Child and Adolescent Psychiatry (AACAP) Committee on Quality Issues (CQI). 2014 Practice parameters for the assessment and treatment of children and adolescents with ASD. J Am Acad Child Adolesc Psychiatry 2014;53:237–257.

    Article  PubMed  Google Scholar 

  132. Charlop-Christy MH, Carperter M, LeBlanc LA, Kellet K. Using the picture exchange communication system (PECS) with children with autism: assessment of PECS acquisition, speech, social-communicative behavior and problem behavior. J Appl Behav Anal 2002;35:213–231.

    Article  PubMed  PubMed Central  Google Scholar 

  133. Sundberg CT, Sundberg ML. Comparing topography based verbal behavior with stimulus selection-based verbal behavior. Anal Verbal Behav 1990;8:31–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Lovaas OI, Berberich JP, Perloff BF, Schaeffer B. Acquisition of imitative speech in schizophrenic children. Science 1966;151:705–707.

    Article  CAS  PubMed  Google Scholar 

  135. Lovaas OI, Smith T. A comprehensive behavior theory of autistic children: Paradigm for research and treatment. J Behav Ther Exp Psychiatry 1989;20:17–29.

    Article  CAS  PubMed  Google Scholar 

  136. Schlosser R, Blischak D, Belfiore P, Bartley C, Barnett N. The effectiveness of synthetic speech output and orthographic feedback in a student with autism: A preliminary study. J Autism Dev Disord 1998;28:309–315.

    Article  CAS  PubMed  Google Scholar 

  137. Gray C. The New Social Stories Book. Arlington, TX: Future Horizons; 2000.

    Google Scholar 

  138. Zanolli KJ, Daggert J, Adams T. Teaching preschool age autistic children to make spontaneous initiations to peers using priming. J Autism Dev Disord 1996;26:407–422.

    Article  CAS  PubMed  Google Scholar 

  139. Schreibman L, Whalen L. The use of video priming to reduce disruptive transition behavior in children with autism. J Posit Behav Interv 2000;2:3–14.

    Article  Google Scholar 

  140. Pierce KL, Schreibman L. Increasing complex social behaviors in children with autism: effects of peer-implemented pivotal response training. J Appl Behav Anal 1995;27:471–481.

    Article  Google Scholar 

  141. Aman MG, Lam KS, Collier-Crespin A. Prevalence and patterns of use of psychoactive medicines among individuals with autism in the Autism Society of Ohio. J Autism Dev Disord 2003;33:527–534.

    Article  PubMed  Google Scholar 

  142. Langworthy-Lam KS, Aman MG, Van Bourgondien ME. Prevalence and patterns of use of psychoactive medicines in individuals with autism in the Autism Society of North Carolina. J Child Adolesc Psychopharmacol 2002;12:311–321.

    Article  PubMed  Google Scholar 

  143. Martin A, Scahill L, Klin A, Volkmar FR. Higher-functioning pervasive developmental disorders: rates and patterns of psychotropic drug use. J Am Acad Child Adolesc Psychiatry 1999;38:923–931.

    Article  CAS  PubMed  Google Scholar 

  144. Di Martino A, Melis G, Cianchetti C, Zuddas A. Methylphenidate for pervasive developmental disorders: safety and efficacy of acute single dose test and ongoing therapy: an open pilot study. J Child Adolesc Psychopharmacol 2004;14:207–218.

    Article  PubMed  Google Scholar 

  145. Hadden BL, Johnson CR, Lubetsky M. Efficacy of methylphenidate among children with autism and symptoms of attention-deficit hyperactivity disorder. J Autism Dev Disord 2000;30:245–255.

    Article  Google Scholar 

  146. Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch Gen Psychiatry 2005;62:1266–1274.

    Article  Google Scholar 

  147. Hollander E, Phillips A, Chaplin W, Zagursky K, Novotny S, Wasserman S, Iyengar R. A placebo controlled trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism. Neuropsychopharmacology 2005;30:582–589.

    Article  CAS  PubMed  Google Scholar 

  148. McDougle CJ, Naylor ST, Cohen DJ, Volkmar FR, Heninger GR, Price LH. A double- blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Arch Gen Psychiatry 1996;53:1001–1008.

    Article  CAS  PubMed  Google Scholar 

  149. Gordon CT, State RC, Nelson JE, Hamburger SD, Rapoport JL. A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Arch Gen Psychiatry 1993;50:441–447.

    Article  CAS  PubMed  Google Scholar 

  150. DeLong GR, Ritch CR, Burch S. Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement. Dev Med Child Neurol 2002;44:652–659.

    Article  PubMed  Google Scholar 

  151. DeLong GR, Teague LA, McSwain Kamran M. Effects of fluoxetine treatment in young children with idiopathic autism. Dev Med Child Neurol 1998;40:551–562.

    Article  CAS  PubMed  Google Scholar 

  152. Fatemi SH, Realmuto GM, Khan L, Thuras P. Fluoxetine in the treatment of adolescent patients with autism: a longitudinal open trial. J Autism Dev Disord 1998;28:303–307.

    Article  CAS  PubMed  Google Scholar 

  153. McDougle CJ, Brodkin ES, Naylor ST, Carlson DC, Cohen DJ, Price LH. Sertraline in adults with pervasive developmental disorders: a prospective open-label investigation. J Clin Psychopharmacol 1998;18:62–66.

    Article  CAS  PubMed  Google Scholar 

  154. Hellings JA, Kelley LA, Gabrielli WF, Kilgore E, Shah P. Sertraline response in adults with mental retardation and autistic disorder. J Clin Psychiatry 1996;57:333–336.

    CAS  PubMed  Google Scholar 

  155. Namerow LB, Thomas P, Bostic JQ, Prince J, Monuteaux MC. Use of citalopram in pervasive developmental disorders. J Dev Behav Pediatr 2003;24:104–108.

    Article  PubMed  Google Scholar 

  156. Couturier JL, Nicolson R. A retrospective assessment of citalopram in children and adolescents with pervasive developmental disorders. J Child Adolesc Psychopharmacol 2002;12:243–248.

    Article  PubMed  Google Scholar 

  157. Owley T, Walton L, Salt J, Guter SJ Jr, Winnega M, Leventhal BL, Cook EH Jr. An open-label trial of escitalopram in pervasive developmental disorders. J Am Acad Child Adolesc Psychiatry 2005;44:343–348.

    Article  PubMed  Google Scholar 

  158. Garber HJ, McGonigle JJ, Slomka GT, Monteverde E. Clomipramine treatment of stereotypic behaviors and self-injury in patients with developmental disabilities. J Am Acad Child Adolesc Psychiatry 1992;31:1157–1160.

    Article  CAS  PubMed  Google Scholar 

  159. Lewis MH, Bodfish JW, Powell SB, Golden RN. Clomipramine treatment for stereotypy and related repetitive movement disorders associated with mental retardation. Am J Ment Retard 1995;100:299–312.

    CAS  PubMed  Google Scholar 

  160. Anderson LT, Campbell M, Grega DM, Perry R, Small AM, Green WH. Haloperidol in the treatment of infantile autism: effects on learning and behavioral symptoms. Am J Psychiatry 1984;141:1195–1202.

    Article  CAS  PubMed  Google Scholar 

  161. Remington G, Sloman L, Konstantareas M, Parker K, Gow R. Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo- controlled, crossover study. J Clin Psychopharmacol 2001;21:440–444.

    Article  CAS  PubMed  Google Scholar 

  162. Locascio JJ, Malone RP, Small AM, Kafantaris V, Ernst M, Lynch NS, Overall JE, Campbell M. Factors related to haloperidol response and dyskinesias in autistic children. Psychopharmacol Bull 1991;27:119–126.

    CAS  PubMed  Google Scholar 

  163. Campbell M, Armenteros JL, Malone RP, Adams PB, Eisenberg ZW, Overall JE. Antipsychotic-related dyskinesias in autistic children: a prospective, longitudinal study. J Am Acad Child Adolesc Psychiatry 1997;36:835–843.

    Article  CAS  PubMed  Google Scholar 

  164. Armenteros JL, Adams PB, Campbell M, Eisenberg ZW. Haloperidol- related dyskinesias and pre- and perinatal complications in autistic children. Psychopharmacol Bull 1995;31:363–369.

    CAS  PubMed  Google Scholar 

  165. Masi G, Cosenza A, Mucci M, Brovedani P. Open trial of risperidone in 24 young children with pervasive developmental disorders. J Am Acad Child Adolesc Psychiatry 2001;40:1206–1214.

    Article  CAS  PubMed  Google Scholar 

  166. McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D, Research Units on Pediatric Psychopharmacology Autism Network. Risperidone in children with autism and serious behavioral problems. N Eng J Med 2002;347:314–321.

    Article  CAS  Google Scholar 

  167. Troost PW, Lahuis BE, Steenhuis MP, Ketelaars CE, Buitelaar JK, Van Engeland H, Scahill L, Minderaa RB, Hoekstra PJ. Long term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study. J Am Acad Child Adolesc Psychiatry 2005;11:1137–1144.

    Article  Google Scholar 

  168. Research Units on Pediatric Psychopharmacology Autism Network. Risperidone treatment of autistic disorder: longer-term benefits and blinded discontinuation after 6 months. Am J Psychiatry 2005;62:1361–1369.

    Article  Google Scholar 

  169. McDougle CJ, Scahill L, Aman MG, McCracken JT, Tierney E, Davies M, Arnold LE, Posey DJ, Martin A, Ghuman JK, Shah B, Chuang SZ, Swiezy NB, Gonzalez NM, Hollway J, Koenig K, McGough JJ, Ritz L, Vitiello B. Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology. Am J Psychiatry 2005;1142–1148.

    Google Scholar 

  170. Shea S, Turgay A, Carroll A, Schulz M, Orlik H, Smith I, Dunbar F. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics 2004;114:634–641.

    Article  Google Scholar 

  171. Stigler KA, Posey DJ, McDougle CJ. Aripiprazole for maladaptive behavior in pervasive developmental disorders. J Child Adolesc Psychopharmacol 2004;14:455–463.

    Article  PubMed  Google Scholar 

  172. Marcus RN, Owen R, Kame L, Manos G, McQuade RD, Carson WH, Aman MG. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J Am Acad Child Adolesc Psychiatry 2009;48:1110–1119.

    Article  PubMed  Google Scholar 

  173. Owen R, Sikich L, Marcus RN, Corey-Lisle P, Manos G, McQuade RD, Carson WH, Findling RL. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics 2009;124:1533–1540.

    Article  PubMed  Google Scholar 

  174. Potenza MN, Holmes JP, Kanes SJ, McDougle CJ. Olanzapine treatment of children, adolescents, and adults with pervasive developmental disorders: an open label pilot study. J Clin Psychopharmacol 1999;19:37–44.

    Article  CAS  PubMed  Google Scholar 

  175. Malone RP, Cater J, Sheikh RM, Choudary MS, Delaney MA. Olanzapine versus haldol in children with autistic disorder: an open pilot study. J Am Acad Child Adolesc Psychiatry 2001;40:887–894.

    Article  CAS  PubMed  Google Scholar 

  176. Hollander E, Wasserman S, Swanson EN, Chaplin W, Schapiro ML, Zagursky K, Novotny S. A double-blind placebo-controlled pilot study of olanzapine in childhood/adolescent pervasive developmental disorder. J Child Adolesc Psychopharmacol 2006;16:541–548.

    Article  PubMed  Google Scholar 

  177. Martin A, Koenig K, Scahill L, Bregman J. Open-label quetiapine in the treatment of children and adolescents with autistic disorder. J Child Adolesc Psychopharmacol 1999; 9:99–107.

    Article  CAS  PubMed  Google Scholar 

  178. Findling RL, McNamara NK, Gracious BL, O’Riordan MA, Reed MD, Demeter C, Blumer JL. Quetiapine in nine youths with autistic disorder. J Child Adolesc Psychopharmacol 2004;14:287–294.

    Article  PubMed  Google Scholar 

  179. McDougle CJ, Kem DL, Posey DJ. Case series: use of ziprasidone for maladaptive symptoms in youths with autism. J Am Acad Child Adolesc Psychiatry 2002;41:921–927.

    Article  PubMed  Google Scholar 

  180. Malone RP, Delaney MA, Hyman SB, Cater JR. Ziprasidone in adolescents with autism: an open-label pilot study. J Child Adolesc Psychopharmacol 2007;17:779–790.

    Article  PubMed  Google Scholar 

  181. Hollander E, Soorya L, Wasserman S, Esposito K, Chaplin W, Anagnostou E. Divalproex sodium vs. placebo in the treatment of repetitive behaviors in autism spectrum disorder. Int J Neuropsychopharmacol 2006;9:209–213.

    Article  CAS  PubMed  Google Scholar 

  182. Hollander E, Dolgoff-Kaspar R, Cartwright C, Rawitt R, Novotny S. An open trial of divalproex sodium in autism spectrum disorders. J Clin Psychiatry 2001;62:530–534.

    Article  CAS  PubMed  Google Scholar 

  183. Rugino TA, Samsock TC. Levetiracetam in autistic children. J Dev Behav Pediatr 2002;23:225–230.

    Article  PubMed  Google Scholar 

  184. Wasserman S, Iyengar R, Chaplin WF. Watner D, Waldoks SE, Anagnostou E, Soorya L, Hollander E. Levetiracetam versus placebo in childhood and adolescent autism: a double-blind placebo-controlled study. Int Clin Psychopharmacol 2006;21:363–367.

    Article  PubMed  Google Scholar 

  185. Belsito KM, Law PA, Kirk KS, Landa RJ, Zimmerman AW. Lamotrigine therapy for autistic disorder: a randomized, double-blind, placebo-controlled trial. J Autism Dev Disord 2001;31:175–181.

    Article  CAS  PubMed  Google Scholar 

  186. Fankhauser MP, Karumanchi VC, German ML, Yates A, Karumanchi SD. A double-blind, placebo-controlled study of the efficacy of transdermal clonidine in autism. J Clin Psychiatry 1992;53:77–82.

    CAS  PubMed  Google Scholar 

  187. Jaselskis CA, Cook EH Jr, Fletcher KE, Leventhal BL. Clonidine treatment of hyperactive and impulsive children with autistic disorder. J Clin Psychopharmacol 1992;12:322–327.

    Article  CAS  PubMed  Google Scholar 

  188. Posey DJ, Puntney JI, Sasher TM, Kem DL, McDougle CJ. Guanfacine treatment of hyperactivity and inattention in pervasive developmental disorders: a retrospective analysis of 80 cases. J Child Adolesc Psychopharmacol 2004;14:233–241.

    Article  PubMed  Google Scholar 

  189. Ratey JJ, Mikkelsen E, Sorgi P, Zuckerman HS, Polakoff S, Bemporad J, Bick P, Kadish W. Autism: the treatment of aggressive behaviors. J Clin Psychopharmacol 1987;7:35–41.

    CAS  PubMed  Google Scholar 

  190. Sandman CA. The opiate hypothesis in autism and self-injury. J Child Adolesc Psychopharmacol 1990/1991;1:237–248.

    Google Scholar 

  191. Kolmen BK, Feldman HM, Handen BL, Janosky JE. Naltrexone in young children: a double blind, placebo-controlled crossover study. J Am Acad Child Adolesc Psychiatry 1995;34:223–231.

    Article  CAS  PubMed  Google Scholar 

  192. Campbell M, Anderson LT, Small AM, Adams P, Gonzalez NM, Ernst M. Naltrexone in autistic children: behavioral symptoms and attentional learning. J Am Acad Child Adolesc Psychiatry 1993;32:1283–1291.

    Article  CAS  PubMed  Google Scholar 

  193. Campbell M, Overall JE, Small AM, Sokol MS, Spencer EK, Adams P, Foltz RL, Monti KM, Perry R, Nobler M. Naltrexone in autistic children: an acute open dose range tolerance trial. J Am Acad of Child Adolesc Psychiatry 1989;28:200–206.

    Article  CAS  Google Scholar 

  194. Herman BH, Hammock MK, Arthur-Smith A, Kuehl K, Appelgate K. Effects of acute administration of naltrexone on cardiovascular function, body temperature, body weight and serum concentrations of liver enzymes in autistic children. Dev Pharmacol Ther 1989;12:118–127.

    CAS  PubMed  Google Scholar 

  195. Feldman HM, Kolmen BK, Gonzaga AM. Naltrexone and communication skills in young children with autism. J Am Acad Child Adolesc Psychiatry 1999;38:587–593.

    Article  CAS  PubMed  Google Scholar 

  196. Willemsen-Swinkles SH, Buitelaar JK, van England H. The effects of chronic naltrexone treatment in young children: a double-blind placebo-controlled crossover study. Biol Psychiatry 1996;39:1023–1031.

    Article  Google Scholar 

  197. Willemsen-Swinkles SH, Buitelaar JK, Nijhof GJ, van England H. Failure of naltrexone hydrochloride to reduce self- injurious and autistic behavior in mentally retarded adults. Double-blind placebo-controlled studies. Arch Gen Psychiatry 1995;52:766–773.

    Article  Google Scholar 

  198. Welch MG, Ruggiero DA. Predicted role of secretin and oxytocin in the treatment of behavioral and developmental disorders: implications for autism. Int Rev Neurobiol 2005;71:273–315.

    Article  CAS  PubMed  Google Scholar 

  199. Pfeiffer SI, Norton J, Nelson L, Shott S. Efficacy of vitamin B6 and magnesium in the treatment of autism: a methodology review and summary of outcomes. J Autism Dev Disord 1995;25:481–493.

    Article  CAS  PubMed  Google Scholar 

  200. Green V, Pituch K, Itchon J, Choi A, O’Reilly M, Sigafoos J. Internet survey of treatments used by parents of children with autism. Res Dev Disabil 2006;27:170–184.

    Article  Google Scholar 

  201. Levy S, Hyman S. Novel treatment for autistic spectrum disorders. Ment Retard Dev Disabil Res Rev 2005;11:131–142.

    Article  PubMed  Google Scholar 

  202. Fatemi SH, Aldinger KA, Ashwood P, Bauman ML, Blaha CD, Blatt GJ, Chauhan A, Chauhan V, Dager SR, Dickson PE, Estes AM, Goldowitz D, Heck DH, Kemper TL, King BH, Martin LA, Millen KJ, Mittleman G, Mosconi MW, Persico AM, Sweeney JA, Webb SJ, Welsh JP. Consensus paper: pathological role of the cerebellum in autism. Cerebellum 2012;11:777–807.

    Article  PubMed  PubMed Central  Google Scholar 

  203. Blatt GJ, Fatemi SH. Alterations in GABAergic biomarkers in the autism brain: research findings and clinical implications. Anat Rec (Hoboken) 2011;294:1646–1652.

    Article  CAS  Google Scholar 

  204. Fatemi SH, Reutiman TJ, Folsom TD, Thuras PD. GABA(A) receptor downregulation in brains of subjects with autism. J Autism Dev Disord 2009;39:223–230.

    Article  PubMed  PubMed Central  Google Scholar 

  205. Fatemi SH, Reutiman TJ, Folsom TD, Rooney RJ, Patel DH, Thuras PD. mRNA and protein levels for GABAA α4, α5, β1, and GABAB R1 receptors are altered in brains from subjects with autism. J Autism Dev Disord 2010;40:743–750.

    Google Scholar 

  206. Fatemi SH, Reutiman TJ, Folsom TD, Rustan OG, Rooney RJ, Thuras PD. Downregulation of GABAA receptor protein subunits α6, β2, δ, ε, γ2, θ, and ρ2 in superior frontal cortex of subjects with autism. J Autism Dev Disord 2014, in press.

    Google Scholar 

  207. Hagberg B. Rett syndrome. Swedish approach to analysis of prevalence and cause. Brain Dev 1985;7:276–280.

    CAS  PubMed  Google Scholar 

  208. Suren P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie K, Lipkin I, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Smith G, Øyen A, Susser E, Stoltenberg C. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA 2013;309:570–577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Research Units on Pediatric Psychopharmacology Autism Network. Risperidone treatment of autistic disorder: longer-term benefits and blinded discontinuation after 6 months. Am J Psychiatry 2005;162:1361–1369.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to George M. Realmuto M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this chapter

Cite this chapter

Realmuto, G.M. (2016). Autism Spectrum Disorder. In: Fatemi, S., Clayton, P. (eds) The Medical Basis of Psychiatry. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2528-5_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2528-5_20

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-2527-8

  • Online ISBN: 978-1-4939-2528-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics