ASD: Psychopharmacologic Treatments and Neurophysiologic Underpinnings

  • Ian Kodish
  • Carol M. Rockhill
  • Sara J. WebbEmail author
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 21)


Autism Spectrum Disorder encompasses a range of neurodevelopmental disorders characterized by early deficits in social communication in addition to restricted and repetitive behaviors. Symptoms are increasingly understood to be associated with abnormalities in the coordination of neuronal assemblies responsible for processing information essential for early adaptive behaviors. Pharmacologic treatments carry evidence for clinically significant benefit of multiple impairing symptoms of ASD, yet these benefits are limited and range across a broad spectrum of medication classes, making it difficult to characterize associated neurochemical impairments. Increasing prevalence of both ASD and its pharmacologic management calls for greater understanding of the neurophysiologic basis of the disorder. This paper reviews underlying alterations in local brain regions and coordination of brain activation patterns during both resting state and task-related processes. We propose that new pharmacologic treatments may focus on realigning trajectories of network specialization across development by working in combination with behavioral treatments to enhance social and emotional learning by bolstering the impact of experience-induced plasticity on neuronal network connectivity.


ASD Autism Neuroimaging Pharmacology Physiology Review 



Support for this project was provided to Dr. Webb by the National Institutes of Health (R01-HD064820, R01-MH10028, HHSN271201200005I).


  1. Aman MG, Langworthy KS (2000) Pharmacotherapy for hyperactivity in children with autism and other pervasive developmental disorders. J Autism Dev Disord 30(5):451–459PubMedCrossRefGoogle Scholar
  2. Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McCracken JT, Shah B, McMahon D (2005) Risperidone treatment of autistic disorder: longer-term benefits and blinded discontinuation after 6 months. Am J Psychiatry 162(7):1361–1369CrossRefGoogle Scholar
  3. American Psychological Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5). American Psychiatric Publishing, ArlingtonGoogle Scholar
  4. Arnold LE, Aman MG, Cook AM, Witwer AN, Hall KL, Thompson S, Ramadan Y (2006) Atomoxetine for hyperactivity in autism spectrum disorders: placebo-controlled crossover pilot trial. J Am Acad Child Adolesc Psychiatry 45(10):1196–1205PubMedCrossRefGoogle Scholar
  5. Ashwin C, Baron-Cohen S, Wheelwright S, O’Riordan M, Bullmore ET (2007) Differential activation of the amygdala and the ‘social brain’during fearful face-processing in Asperger Syndrome. Neuropsychologia 45(1):2–14PubMedCrossRefGoogle Scholar
  6. Assaf M, Jagannathan K, Calhoun VD, Miller L, Stevens MC, Sahl R, O’Boyle J, Schultz R, Pearlson GD (2010) Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients. Neuroimage 53(1):247–256PubMedCentralPubMedCrossRefGoogle Scholar
  7. Aylward EH, Minshew NJ, Field K, Sparks BF, Singh N (2002) Effects of age on brain volume and head circumference in autism. Neurology 59(2):175–183PubMedCrossRefGoogle Scholar
  8. Baron-Cohen S, Ring HA, Bullmore ET, Wheelwright S, Ashwin C, Williams SCR (2000) The amygdala theory of autism. Neurosci Biobehav Rev 24(3):355–364PubMedCrossRefGoogle Scholar
  9. Barttfeld P, Wicker B, Cukier S, Navarta S, Lew S, Sigman M (2011) A big-world network in ASD: dynamical connectivity analysis reflects a deficit in long-range connections and an excess of short-range connections. Neuropsychologia 49(2):254–263PubMedCrossRefGoogle Scholar
  10. Bernier R, Dawson G, Webb S, Murias M (2007) EEG mu rhythm and imitation impairments in individuals with autism spectrum disorder. Brain Cogn 64(3):228–237PubMedCentralPubMedCrossRefGoogle Scholar
  11. Bird G, Catmur C, Silani G, Frith C, Frith U (2006) Attention does not modulate neural responses to social stimuli in autism spectrum disorders. Neuroimage 31(4):1614–1624PubMedCrossRefGoogle Scholar
  12. Blume WT (2006) Drug effects on EEG. J Clin Neurophysiol 23(4):306–311PubMedCrossRefGoogle Scholar
  13. Boeschoten MA, Kenemans JL, Engeland HV, Kemner C (2007) Abnormal spatial frequency processing in high-functioning children with pervasive developmental disorder (PDD). Clin Neurophysiol 118(9):2076–2088PubMedCrossRefGoogle Scholar
  14. Canive JM, Lewine JD, Edgar JC, Davis JT, Miller GA, Torres F, Tuason VB (1998) Spontaneous brain magnetic activity in schizophrenia patients treated with aripiprazole. Psychopharmacol Bull 34(1):101PubMedGoogle Scholar
  15. Cardinale RC, Shih P, Fishman I, Ford LM, Müller RA (2013) Pervasive rightward asymmetry shifts of functional networks in Autism Spectrum Disorder. JAMA Psychiatry 70(9):975–982PubMedCentralPubMedCrossRefGoogle Scholar
  16. Carper RA, Courchesne E (2005) Localized enlargement of the frontal cortex in early autism. Biol Psychiatry 57(2):126–133PubMedCrossRefGoogle Scholar
  17. Carrasco M, Volkmar FR, Bloch MH (2012) Pharmacologic treatment of repetitive behaviors in autism spectrum disorders: evidence of publication bias. Pediatrics 129(5):e1301–e1310PubMedCentralPubMedCrossRefGoogle Scholar
  18. Casanova MF, van Kooten IA, Switala AE, van Engeland H, Heinsen H, Steinbusch HW, Hof P, Trippe J, Stone J, Schmitz C (2006) Minicolumnar abnormalities in autism. Acta Neuropathol 112(3):287–303PubMedCrossRefGoogle Scholar
  19. Castrén E (2013) Neuronal network plasticity and recovery from depression. JAMA Psychiatry 70(9):983–989PubMedCrossRefGoogle Scholar
  20. Center for Disease Control (2012) Prevalence of autism spectrum disorders–autism and developmental disabilities monitoring network, 14 Sites, United States, 2008Google Scholar
  21. Courchesne E, Karns CM, Davis HR, Ziccardi R, Carper RA, Tigue ZD, Chisum H, Courchesne RY (2001) Unusual brain growth patterns in early life in patients with autistic disorder an MRI study. Neurology 57(2):245–254PubMedCrossRefGoogle Scholar
  22. Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, Barnes C, Pierce K (2011) Neuron number and size in prefrontal cortex of children with autism. J Am Med Assoc 306(18):2001–2010CrossRefGoogle Scholar
  23. Dakin S, Frith U (2005) Vagaries of visual perception in autism. Neuron 48(3):497–507PubMedCrossRefGoogle Scholar
  24. Dalton KM, Nacewicz BM, Johnstone T, Schaefer HS, Gernsbacher MA, Goldsmith HH, Alexander A, Davidson RJ (2005) Gaze fixation and the neural circuitry of face processing in autism. Nat Neurosci 8(4):519–526PubMedGoogle Scholar
  25. Dapretto M, Davies MS, Pfeifer JH, Scott AA, Sigman M, Bookheimer SY, Iacoboni M (2005) Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders. Nat Neurosci 9(1):28–30PubMedCentralPubMedCrossRefGoogle Scholar
  26. Dawson G, Jones EJ, Merkle K, Venema K, Lowy R, Faja S, Kamara D, Murias M, Greenson J, Winter J, Smith M, Rogers S, Webb SJ (2012) Early behavioral intervention is associated with normalized brain activity in young children with autism. J Am Acad Child Adolesc Psychiatry 51(11):1150–1159PubMedCentralPubMedCrossRefGoogle Scholar
  27. Dawson G, Webb SJ, Carver L, Panagiotides H, McPartland J (2004) Young children with autism show atypical brain responses to fearful versus neutral facial expressions of emotion. Dev Sci 7(3):340–359PubMedCrossRefGoogle Scholar
  28. Dichter GS, Belger A (2007) Social stimuli interfere with cognitive control in autism. Neuroimage 35(3):1219–1230PubMedCentralPubMedCrossRefGoogle Scholar
  29. Duffy FH, Als H (2012) A stable pattern of EEG spectral coherence distinguishes children with autism from neuro-typical controls-a large case control study. BMC Med 10(1):64PubMedCentralPubMedCrossRefGoogle Scholar
  30. Dumont GJH, De Visser SJ, Cohen AF, Van Gerven JMA (2005) Biomarkers for the effects of selective serotonin reuptake inhibitors (SSRIs) in healthy subjects. Br J Clin Pharmacol 59(5):495–510PubMedCentralPubMedCrossRefGoogle Scholar
  31. Dupuy FE, Clarke AR, Barry RJ, McCarthy R, Selikowitz M (2010) EEG coherence in children with attention-deficit/hyperactivity disorder: differences between good and poor responders to methylphenidate. Psychiatry Res 180(2–3):114–119PubMedCrossRefGoogle Scholar
  32. Ecker C, Suckling J, Deoni S.C, Lombardo M.V, Bullmore E.T, Baron-Cohen S, Williams C (2012) Brain anatomy and its relationship to behavior in adults with autism spectrum disorder: a multicenter magnetic resonance imaging study. Arch Gen Psychiatry 69(2):195–209Google Scholar
  33. Elbe D, Lalani Z (2012) Review of the pharmacotherapy of irritability in autism. J Can Acad Child Adolesc Psychiatry 21(2):130–146PubMedCentralPubMedGoogle Scholar
  34. Eyler LT, Pierce K, Courchesne E (2012) A failure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism. Brain 135(Pt 3):949–960PubMedCentralPubMedCrossRefGoogle Scholar
  35. Geschwind M, Pourtois G, Schwartz S, Van De Ville D, Vuilleumier P (2012) White-matter connectivity between face-responsive regions in the human brain. Cereb Cortex 22(7):1564–1576CrossRefGoogle Scholar
  36. Ghanbari Y, Bloy L, Edgar JC., Blaskey L, Verma R, Roberts TP (2013) Joint analysis of band-specific functional connectivity and signal complexity in autism. J. Autism Dev Disord 2(1):17Google Scholar
  37. Gilbert SJ, Bird G, Brindley R, Frith CD, Burgess PW (2008) Atypical recruitment of medial prefrontal cortex in autism spectrum disorders: an fMRI study of two executive function tasks. Neuropsychologia 46(9):2281–2291PubMedCentralPubMedCrossRefGoogle Scholar
  38. Gogtay N, Thompson PM (2010) Mapping gray matter development: implications for typical development and vulnerability to psychopathology. Brain Cogn 72(1):6–15PubMedCentralPubMedCrossRefGoogle Scholar
  39. Gordon I, Vander Wyk BC, Bennett RH, Cordeaux C, Lucas MV, Eilbott JA, Pelphrey KA (2013) Oxytocin enhances brain function in children with autism. Proc Nat Acad Sci U.S.A 110(52):20953–20958Google Scholar
  40. Greenough WT, Black JE, Wallace CS (1987) Experience and brain development. Child Dev 58(3), 539–559Google Scholar
  41. Grèzes J, Wicker B, Berthoz S, De Gelder B (2009) A failure to grasp the affective meaning of actions in autism spectrum disorder subjects. Neuropsychologia 47(8):1816–1825PubMedCrossRefGoogle Scholar
  42. Grice SJ, Halit H, Farroni T, Baron-Cohen S, Bolton P, Johnson MH (2005) Neural correlates of eye-gaze detection in young children with autism. Cortex 41(3):342–353PubMedCrossRefGoogle Scholar
  43. Guastella AJ, Einfeld SL, Gray KM, Rinehart NJ, Tonge BJ, Lambert TJ, Hickie IB (2010) Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry 67(7):692–694PubMedCrossRefGoogle Scholar
  44. Hadjikhani N, Joseph RM, Snyder J, Chabris CF, Clark J, Steele S, McGrath L, Tager-Flusberg H (2004) Activation of the fusiform gyrus when individuals with autism spectrum disorder view faces. Neuroimage 22(3):1141–1150PubMedCrossRefGoogle Scholar
  45. Hamilton AF (2013) The mirror neuron system contributes to social responding. Cortex 49(10):2957–2959PubMedCrossRefGoogle Scholar
  46. Handen BL, Sahl R, Hardan AY (2008) Guanfacine in children with autism and/or intellectual disabilities. J Dev Behav Pediatr 29(4):303–308PubMedCrossRefGoogle Scholar
  47. Hardan AY, Libove RA, Keshavan MS, Melhem NM, Minshew NJ (2009) A preliminary longitudinal magnetic resonance imaging study of brain volume and cortical thickness in autism. Biol Psychiatry 66(4):320–326PubMedCentralPubMedCrossRefGoogle Scholar
  48. Harris JC, Carter CS (2013) Therapeutic interventions with oxytocin: current status and concerns. J Am Acad Child Adolesc Psychiatry 52(10):998–1000PubMedCrossRefGoogle Scholar
  49. Hellings JA, Zarcone JR, Reese RM, Valdovinos MG, Marquis JG, Fleming KK, Schroeder SR (2006) A crossover study of risperidone in children, adolescents and adults with mental retardation. J Autism Dev Disord 36(3):401–411PubMedCrossRefGoogle Scholar
  50. Herbert MR, Ziegler DA, Makris N, Filipek PA, Kemper TL, Normandin JJ, Caviness, VS (2004). Localization of white matter volume increase in autism and developmental language disorder. Ann Neurol 55(4):530–540Google Scholar
  51. Hsia Y, Wong AY, Murphy DG, Simonoff E, Buitelaar JK, Wong, IC (2013) Psychopharmacological prescriptions for people with autism spectrum disorder (ASD): a multinational study. Psychopharmacology 13:1–11Google Scholar
  52. Hurwitz R, Blackmore R, Hazell P, Williams K, Woolfenden S (2012) Tricyclic antidepressants for autism spectrum disorders (ASD) in children and adolescents. Cochrane Database Syst Rev (3)Google Scholar
  53. Hutsler JJ, Zhang H (2010) Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders. Brain Res 1309:83–94PubMedCrossRefGoogle Scholar
  54. Huttenlocher PR, Dabholkar AS (1997) Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 387(2):167–178Google Scholar
  55. Kennedy DP, Courchesne E (2008) The intrinsic functional organization of the brain is altered in autism. Neuroimage 39(4):1877–1885Google Scholar
  56. Keown CL, Shih P, Nair A, Peterson N, Mulvey ME, Müller RA (2013) Local functional over connectivity in posterior brain regions is associated with symptom severity in autism spectrum disorders. Cell Rep 5(3):567–572Google Scholar
  57. Kim E, Yu KS, Cho JY, Shin YW, Yoo SY, Kim YY, Jang I-J, Shin S-G, Kwon JS (2006) Effects of DRD2 and CYP2D6 genotypes on delta EEG power response to aripiprazole in healthy male volunteers: a preliminary study. Hum Psychopharmacol: Clin Exp 21(8):519–528CrossRefGoogle Scholar
  58. King BH, Wright D, Handen BL, Sikich L, Zimmerman AW, McMahon W, Cantwell E, Cook EH Jr (2001) Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder. J Am Acad Child Adolesc Psychiatry 40(6):658–665PubMedCrossRefGoogle Scholar
  59. Kleinhans NM, Richards T, Sterling L, Stegbauer KC, Mahurin R, Johnson LC, Greenson J, Dawson G, Aylward E (2008) Abnormal functional connectivity in autism spectrum disorders during face processing. Brain 131(4):1000–1012PubMedCrossRefGoogle Scholar
  60. Kolevzon A, Mathewson KA, Hollander E (2006) Selective serotonin reuptake inhibitors in autism: a review of efficacy and tolerability. J Clin Psychiatry 67(3):407–414PubMedCrossRefGoogle Scholar
  61. Koshino H, Kana RK, Keller TA, Cherkassky VL, Minshew NJ, Just MA (2008) fMRI investigation of working memory for faces in autism: visual coding and underconnectivity with frontal areas. Cereb Cortex 18(2):289–300PubMedCrossRefGoogle Scholar
  62. Kylliäinen A, Braeutigam S, Hietanen JK, Swithenby SJ, Bailey AJ (2006) Face- and gaze-sensitive neural responses in children with autism: a magnetoencephalographic study. Eur J Neurosci 24(9):2679–2690PubMedCrossRefGoogle Scholar
  63. Lauvin MA, Martineau J, Destrieux C, Andersson F, Bonnet-Brilhault F, Gomot M, El-Hage W, Cottier JP (2012) Functional morphological imaging of autism spectrum disorders: current position and theories proposed. Diagn Interv Imaging 93(3):139–147PubMedCrossRefGoogle Scholar
  64. LeBlanc JJ, Fagiolini M (2011) Autism: a “critical period” disorder? Neural Plasticity 18(3):264–276Google Scholar
  65. Liem-Moolenaar M, Rad M, Zamuner S, Cohen AF, Lemme F, Franson KL, van Gerven J, Pich EM (2011) Central nervous system effects of the interaction between risperidone (single dose) and the 5-HT6 antagonist SB742457 (repeated doses) in healthy men. Br J Clin Pharmacol 71(6):907–916PubMedCentralPubMedCrossRefGoogle Scholar
  66. Lo YC, Soong WT, Gau SSF, Wu YY, Lai MC, Yeh FC, Chiang W-Y, Kuo L-W, Jaw F-S, Tseng WYI (2011) The loss of asymmetry and reduced interhemispheric connectivity in adolescents with autism: a study using diffusion spectrum imaging tractography. Psychiatry Res: Neuroimaging 192(1):60–66PubMedCrossRefGoogle Scholar
  67. Loo SK, Teale PD, Reite ML (1999) EEG correlates of methylphenidate response among children with ADHD: a preliminary report. Biol Psychiatry 45(12):1657–1660PubMedCrossRefGoogle Scholar
  68. Lopata C, Toomey JA, Fox JD, Thomeer ML, Volker MA, Lee GK (2013) Prevalence and predictors of psychotropic use in children with high-functioning ASDs. Autism Res Treat 103(5):881–888Google Scholar
  69. Luby J, Mrakotsky C, Stalets MM ABelden A, Heffelfinger A, Williams M, Spitsnagel E (2006) Risperidone in preschool children with autistic spectrum disorders: An investigation of safety and efficacy. J Child Adolesc Psychopharmacol 16(5):575–587Google Scholar
  70. Mahajan R, Bernal MP, Panzer R, Whitaker A, Roberts W, Handen B, Veenstra-VanderWeele J (2012) Clinical practice pathways for evaluation and medication choice for attention-deficit/hyperactivity disorder symptoms in autism spectrum Disorders. Pediatrics 130(Supplement 2):S125–S138Google Scholar
  71. Malow B, Adkins KW, McGrew SG, Wang L, Goldman SE, Fawkes D, Burnette C (2012) Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes. J Autism Dev Disord 42(8):1729–1737PubMedCentralPubMedCrossRefGoogle Scholar
  72. Marcus RN, Owen R, Kamen L, Manos G, McQuade R, Carson WH, Aman MG (2009) A placebo-controlled fixed dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J Am Acad Child Adolesc Psychiatry 48(11):1110–1119PubMedCrossRefGoogle Scholar
  73. Marsh LE, Hamilton AFDC (2011) Dissociation of mirroring and mentalising systems in autism. Neuroimage 56(3):1511–1519PubMedCrossRefGoogle Scholar
  74. Martineau J, Andersson F, Barthélémy C, Cottier JP, Destrieux C (2010) Atypical activation of the mirror neuron system during perception of hand motion in autism. Brain Res 12(1320):168–175CrossRefGoogle Scholar
  75. McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, McMahon D (2002) Risperidone in children with autism and serious behavioral problems. N Engl J Med 347(5):314–321PubMedCrossRefGoogle Scholar
  76. Ming X, Gordon E, Kang N, Wagner GC (2008) Use of clonidine in children with autism spectrum disorders. Brain Dev 30(7):454–460PubMedCrossRefGoogle Scholar
  77. Miral S, Gencer O, Baykara B, Baykara A, Dirik E (2008) Risperidone versus haloperidol in children and adolescents with Autistic Disorder. Eur Child Adolesc Psychiatry 17(1):1–8PubMedCrossRefGoogle Scholar
  78. Mire SS, Nowell KP, Kubiszyn T, Goin-Kochel RP (2013) Psychotropic medication use among children with autism spectrum disorders within the Simons Simplex Collection: are core features of autism spectrum disorder related? AutismGoogle Scholar
  79. Monk CS, Peltier SJ, Wiggins JL, Weng SJ, Carrasco M, Risi S, Lord C (2009) Abnormalities of intrinsic functional connectivity in autism spectrum disorders. Neuroimage 47(2):764–772PubMedCentralPubMedCrossRefGoogle Scholar
  80. Mottron L, Dawson M, Soulieres I, Hubert B, Burack J (2006) Enhanced perceptual functioning in autism: an update, and eight principles of autistic perception. J Autism Dev Disord 36(1):27–43PubMedCrossRefGoogle Scholar
  81. Mottron L, Mineau S, Martel G, Bernier CS, Berthiaume C, Dawson M, Faubert, J (2007) Lateral glances toward moving stimuli among young children with autism: early regulation of locally oriented perception? Dev Psychopathol 19(1):23–36Google Scholar
  82. Murias M, Webb SJ, Greenson J, Dawson G (2007) Resting state cortical connectivity reflected in EEG coherence in individuals with autism. Biol Psychiatry 62(3):270–273PubMedCentralPubMedCrossRefGoogle Scholar
  83. Murray M (2010) Attention-deficit/hyperactivity disorder in the context of autism spectrum disorders. Curr Psychiatry Rep 123(5):382–388CrossRefGoogle Scholar
  84. Nagaraj R, Singhi P, Malhi P (2006) Risperidone in children with autism: randomized, placebo-controlled, double-blind study. J Child Neurol 21(6):450–455PubMedGoogle Scholar
  85. Nordahl CW, Scholz R, Yang X, Buonocore MH, Simon T, Rogers S, Amaral DG (2012) Increased rate of amygdala growth in children aged 2 to 4 years with autism spectrum disorders: a longitudinal study. Arch Gen Psychiatry 69(1):53–61PubMedCentralPubMedCrossRefGoogle Scholar
  86. Oberman LM, Hubbard EM, McCleery JP, Altschuler EL, Ramachandran VS, Pineda JA (2005) EEG evidence for mirror neuron dysfunction in autism spectrum disorders. Cogn Brain Res 24(2):190–198CrossRefGoogle Scholar
  87. Ohnishi T, Matsuda H, Hashimoto T, Kunihiro T, Nishikawa M, Uema T, Sasaki M (2000) Abnormal regional cerebral blood flow in childhood autism. Brain 123(Pt 9):1838–1844PubMedCrossRefGoogle Scholar
  88. Owen R, Sikich L, Marcus RN, Corey-Lisle P, Manos G, McQuade RD, Findling RL (2009) Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics 124(6):1533–1540Google Scholar
  89. Palmer CJ, Paton B, Hohwy J, Enticott PG (2013) Movement under uncertainty: the effects of the rubber-hand illusion vary along the nonclinical autism spectrum. Neuropsychologia 51(10):1942–1951PubMedCrossRefGoogle Scholar
  90. Pandina GJ, Bossie CA, Youssef E, Zhu Y, Dunbar F (2007) Risperidone improves behavioral symptoms in children with autism in a randomized, double-blind, placebo-controlled trial. J Autism Dev Disord 37(2):367–373PubMedCrossRefGoogle Scholar
  91. Parikh MS, Kolevzon A, Hollander E (2008) Psychopharmacology of aggression in children and adolescents with autism: A critical review of efficacy and tolerability. J Child Adolesc Psychopharmacol 18(2):157–178PubMedCrossRefGoogle Scholar
  92. Pinkham AE, Hopfinger JB, Pelphrey KA, Piven J, Penn DL (2008) Neural bases for impaired social cognition in schizophrenia and autism spectrum disorders. Schizophr Res 99(1):164–175PubMedCentralPubMedCrossRefGoogle Scholar
  93. Pringsheim T, Gorman D (2012) Second-generation antipsychotics for the treatment of disruptive behaviour disorders in children: a systematic review. Can J Psychiatry 57(12):722–727PubMedGoogle Scholar
  94. Redcay E, Courchesne E (2005) When is the brain enlarged in autism? A meta-analysis of all brain size reports. Biol Psychiatry 58(1):1–9PubMedCrossRefGoogle Scholar
  95. Rossignol DA, Frye RE (2013) Melatonin in Autism Spectrum Disorders. Curr Clin Pharmacol. [Epub ahead of print]Google Scholar
  96. Schubart JR, Camacho F, Leslie D (2013) Psychotropic medication trends among children and adolescents with autism spectrum disorder in the Medicaid program. Autism. [Epub ahead of print]Google Scholar
  97. Schulte-Rüther M, Markowitsch HJ, Fink GR, Piefke M (2007) Mirror neuron and theory of mind mechanisms involved in face-to-face interactions: a functional magnetic resonance imaging approach to empathy. J Cogn Neurosci 19(8):1354–1372PubMedCrossRefGoogle Scholar
  98. Schultz RT (2005) Developmental deficits in social perception in autism: the role of the amygdala and fusiform face area. Int J Dev Neurosci 23(2):125–141PubMedCrossRefGoogle Scholar
  99. Schumann CM, Bloss CS, Barnes CC, Wideman GM, Carper RA, Akshoomoff N, Courchesne E (2010) Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism. J Neurosci 30(12):4419–4427PubMedCentralPubMedCrossRefGoogle Scholar
  100. Shafritz KM, Dichter GS, Baranek GT, Belger A (2008) The neural circuitry mediating shifts in behavioral response and cognitive set in autism. Biol Psychiatry 63(10):974–980PubMedCentralPubMedCrossRefGoogle Scholar
  101. Sharma A, Shaw SR (2012) Efficacy of risperidone in managing maladaptive behaviors for children with autistic spectrum disorder: a meta-analysis. J Pediatric Health Care 26(4):291–299CrossRefGoogle Scholar
  102. Shea S, Turgay A, Carroll A, Schulz M, Orlik H, Smith I, Dunbar F (2004) Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics 114(5):e634–e641PubMedCrossRefGoogle Scholar
  103. Silberberg G, Gupta A, Markram H (2002) Stereotypy in neocortical microcircuits. Trends Neurosci 25(5):227–230PubMedCrossRefGoogle Scholar
  104. Simmons DR, Robertson AE, McKay LS, Toal E, McAleer P, Pollick FE (2009) Vision in autism spectrum disorders. Vision Res 49(22):2705–2739PubMedCrossRefGoogle Scholar
  105. Sparks BF, Friedman SD, Shaw DW, Aylward EH, Echelard D, Artru AA, Maravilla K, Dager SR (2002) Brain structural abnormalities in young children with autism spectrum disorder. Neurology 59(2):184–192PubMedCrossRefGoogle Scholar
  106. Supekar K, Uddin LQ, Khouzam A, Phillips J, Gaillard WD, Kenworthy LE, Yerys B, Vaidya C, Menon V (2013) Brain hyperconnectivity in children with autism and its links to social deficits. Cell Reports 5(3):738–747PubMedCentralPubMedCrossRefGoogle Scholar
  107. Troost PW, Lahuis BE, Steenhuis MP, Ketelaars CE, Buitelaar JK, van Engeland H, Hoekstra PJ (2005) Long-term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study. J Am Acad Child Adolesc Psychiatry 44(11):1137–1144Google Scholar
  108. Uddin LQ, Superkar K, Lynch CJ, Khouzam A, Phillips J, Feinstein C et al (2013) Salience network based classification and prediction of symptom severity in children with autism. JAMA Psychiatry 70(8):869–879Google Scholar
  109. Uddin LQ, Supekar K, Menon V (2010) Typical and atypical development of functional human brain networks: insights from resting-state FMRI. Frontiers Syst Neurosci 4(21)Google Scholar
  110. Vidal CN, Nicolson R, DeVito TJ, Hayashi KM, Geaga JA, Drost DJ, Williamson P, Thompson PM (2006) Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity. Biol Psychiatry 60(3):218–225PubMedCrossRefGoogle Scholar
  111. Wang AT, Lee SS, Sigman M, Dapretto M (2007) Reading affect in the face and voice: neural correlates of interpreting communicative intent in children and adolescents with autism spectrum disorders. Arch Gen Psychiatry 64(6):698PubMedCentralPubMedCrossRefGoogle Scholar
  112. Webb SJ, Dawson G, Bernier R, Panagiotides H (2006) ERP evidence of atypical face processing in young children with autism. J Autism Dev Disord 36(7):881–890PubMedCentralPubMedCrossRefGoogle Scholar
  113. Webb S, Bernier R, Burner K, Murias M (2009) Electrophysiology and evoked potentials in autism research. In: Amaral D, Dawson G, Geschwind D (eds) Autism spectrum disorders. Oxford Library of Psychology, New YorkGoogle Scholar
  114. Webb SJ, Jones EJ, Merkle K, Venema K, Greenson J, Murias M, Dawson G (2011) Developmental change in the ERP responses to familiar faces in toddlers with autism spectrum disorders versus typical development. Child Dev 82(6):1868–1886PubMedCentralPubMedCrossRefGoogle Scholar
  115. Weng SJ, Carrasco M, Swartz JR, Wiggins JL, Kurapati N, Liberzon I, Monk CS (2011) Neural activation to emotional faces in adolescents with autism spectrum disorders. J Child Psychol Psychiatry 52(3):296–305Google Scholar
  116. Williams JH, Whiten A, Singh T (2004) A systematic review of action imitation in autistic spectrum disorder. J Autism Dev Disord 34(3):285–299PubMedCrossRefGoogle Scholar
  117. Williams K, Wheeler DM, Silove N, Hazell P (2013) Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database of Syst Rev (8)Google Scholar
  118. Williams JH, Waiter GD, Gilchrist A, Perrett DI, Murray AD, Whiten A (2006) Neural mechanisms of imitation and ‘mirror neuron’functioning in autistic spectrum disorder. Neuropsychologia 44(4):610–621PubMedCrossRefGoogle Scholar
  119. Wolff JJ, Gu H, Gerig G, Elison JT, Styner M, Gouttard S, Botteron K, Piven J (2012) Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. Am J Psychiatry 169(6):589–600PubMedCentralPubMedCrossRefGoogle Scholar
  120. Won H, Mah W, Kim E (2013) Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses. Front Mol Neurosci 6(19)Google Scholar
  121. Wong TK, Fung PC, Chua SE, McAlonan GM (2008) Abnormal spatiotemporal processing of emotional facial expressions in childhood autism: dipole source analysis of event-related potentials. Eur J Neurosci 28(2):407–416PubMedCrossRefGoogle Scholar
  122. Wright B, Sims D, Smart S, Alwazeer A, Alderson-Day B, Allgar V, Whitton C, Miles J (2011) Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: a randomised controlled crossover trial. J Autism Dev Disord 41(2):175–184PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.University of Washington Department of Psychiatry and Behavioral SciencesSeattleUnited States of America
  2. 2.University of Washington Department of Psychiatry and Behavioral SciencesSeattle Children’s Research InstituteSeattleUnited States of America

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