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Neural Targets in the Study and Treatment of Social Cognition in Autism Spectrum Disorder

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Book cover Cognitive Enhancement

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 228))

Abstract

The purpose of this chapter is to present results from recent research on social cognition in autism spectrum disorder (ASD). The clinical phenomenology and neuroanatomical circuitry of ASD are first briefly described. The neuropharmacology of social cognition in animal models of ASD and humans is then addressed. Next, preclinical and clinical research on the neurohormone oxytocin is reviewed. This is followed by a presentation of results from preclinical and clinical studies on the excitatory amino acid glutamate. Finally, the role of neuroinflammation in ASD is addressed from the perspectives of preclinical neuroscience and research involving humans with ASD.

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References

  • Akhondzadeh S, Tajdar H, Mohammadi MR, Mohammadi M, Nouroozinejad GH, Shabstari OL, Ghelichnia HA (2008) A double-blind placebo controlled trial of piracetam added to risperidone in patients with autistic disorder. Child Psychiatry Hum Dev 39(3):237–245. doi:10.1007/s10578-007-0084-3

    Article  PubMed  Google Scholar 

  • American Psychiatric Association APADSMTF (2013) Diagnostic and statistical manual of mental disorders: DSM-5. Available via http://worldcat.org. http://dsm.psychiatryonline.org/book.aspx?bookid=556.

    Google Scholar 

  • Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S, Wang AT, Pepa L, Tanel N, Kushki A, Hollander E (2012) Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism 3(1):16. doi:10.1186/2040-2392-3-16

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A (2010) Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci USA 107(9):4389–4394. doi:10.1073/pnas.0910249107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Annaz D, Campbell R, Coleman M, Milne E, Swettenham J (2012) Young children with autism spectrum disorder do not preferentially attend to biological motion. J Autism Dev Disord 42(3):401–408

    Article  PubMed  Google Scholar 

  • Asadabadi M, Mohammadi MR, Ghanizadeh A, Modabbernia A, Ashrafi M, Hassanzadeh E, Forghani S, Akhondzadeh S (2013) Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial. Psychopharmacology (Berl) 225(1):51–59. doi:10.1007/s00213-012-2796-8

    Article  CAS  Google Scholar 

  • Baio J, Centers for Disease Control and Prevention (2012) Prevalence of autism spectrum disorders: Autism and Developmental Disabilities Monitoring Network, 14 Sites, United States, 2008. MMWR Surveill Summ 61(3):1–19

    Google Scholar 

  • Bales KL, Perkeybile AM, Conley OG, Lee MH, Guoynes CD, Downing GM, Yun CR, Solomon M, Jacob S, Mendoza SP (2013) Chronic intranasal oxytocin causes long-term impairments in partner preference formation in male prairie voles. Biol Psychiatry 74(3):180–188. doi:10.1016/j.biopsych.2012.08.025

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bear MF, Huber KM, Warren ST (2004) The mGluR theory of fragile X mental retardation. Trends Neurosci 27(7):370–377. doi:10.1016/j.tins.2004.04.009

    Article  CAS  PubMed  Google Scholar 

  • Becker JA, Clesse D, Spiegelhalter C, Schwab Y, Le Merrer J, Kieffer BL (2014) Autistic-like syndrome in mu opioid receptor null mice is relieved by facilitated mGluR4 activity. Neuropsychopharmacology 39(9):2049–2060. doi:10.1038/npp.2014.59

    Article  CAS  PubMed  Google Scholar 

  • Bernardi S, Anagnostou E, Shen J, Kolevzon A, Buxbaum JD, Hollander E, Hof PR, Fan J (2011) In vivo 1H-magnetic resonance spectroscopy study of the attentional networks in autism. Brain Res 1380:198–205. doi:10.1016/j.brainres.2010.12.057

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bielsky IF, Young LJ (2004) Oxytocin, vasopressin, and social recognition in mammals. Peptides 25(9):1565–1574. doi:10.1016/j.peptides.2004.05.019

    Article  CAS  PubMed  Google Scholar 

  • Blaylock RL, Strunecka A (2009) Immune-glutamatergic dysfunction as a central mechanism of the autism spectrum disorders. Curr Med Chem 16(2):157–170

    Article  CAS  PubMed  Google Scholar 

  • Boraston ZL, Corden B, Miles LK, Skuse DH, Blakemore SJ (2008) Brief report: perception of genuine and posed smiles by individuals with autism. J Autism Dev Disord 38(3):574–580. doi:10.1007/s10803-007-0421-1

    Article  PubMed  Google Scholar 

  • Boris M, Goldblatt A, Edelson SM (2005) Improvement in children with autism treated with intravenous gamma globulin. J Nutr Environ Med 15(4):169–176

    Article  CAS  Google Scholar 

  • Borrell J, Vela JM, Arevalo-Martin A, Molina-Holgado E, Guaza C (2002) Prenatal immune challenge disrupts sensorimotor gating in adult rats. Implications for the etiopathogenesis of schizophrenia. Neuropsychopharmacology 26(2):204–215. doi:10.1016/S0893-133X(01)00360-8

    Article  CAS  PubMed  Google Scholar 

  • Buitelaar JK, van Engeland H, van Ree JM, de Wied D (1990) Behavioral effects of Org 2766, a synthetic analog of the adrenocorticotrophic hormone (4-9), in 14 outpatient autistic children. J Autism Dev Disord 20(4):467–478

    Article  CAS  PubMed  Google Scholar 

  • Buitelaar JK, van Engeland H, de Kogel K, de Vries H, van Hooff J, van Ree J (1992a) The adrenocorticotrophic hormone (4-9) analog ORG 2766 benefits autistic children: report on a second controlled clinical trial. J Am Acad Child Adolesc Psychiatry 31(6):1149–1156

    Article  CAS  PubMed  Google Scholar 

  • Buitelaar JK, van Engeland H, de Kogel KH, de Vries H, van Hooff JA, van Ree JM (1992b) The use of adrenocorticotrophic hormone (4-9) analog ORG 2766 in autistic children: effects on the organization of behavior. Biol Psychiatry 31(11):1119–1129

    Article  CAS  PubMed  Google Scholar 

  • Carlson GC (2012) Glutamate receptor dysfunction and drug targets across models of autism spectrum disorders. Pharmacol Biochem Behav 100(4):850–854. doi:10.1016/j.pbb.2011.02.003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Carlsson ML (1998) Hypothesis: is infantile autism a hypoglutamatergic disorder? Relevance of glutamate—serotonin interactions for pharmacotherapy. J Neural Transm 105(4–5):525–535

    Article  CAS  PubMed  Google Scholar 

  • Carroll LS, Owen MJ (2009) Genetic overlap between autism, schizophrenia and bipolar disorder. Genome Med 1(10):102–102.7. doi:10.1186/gm102

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Cheung C, Yu K, Fung G, Leung M, Wong C, Li Q, Sham P, Chua S, McAlonan G (2010) Autistic disorders and schizophrenia: related or remote? An anatomical likelihood estimation. PLoS One 5(8):e12233

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Chez ML, Loeffel M, Buchanan CP, Field-Chez M (1998) Pulse high dose steroids as combination therapy with valproic acid in epileptic aphasia patients with pervasive developmental delay or autism. Ann Neurol 44(3):53–59. doi:10.1002/ana.410440345

    Google Scholar 

  • Chez MG, Burton Q, Dowling T, Chang M, Khanna P, Kramer C (2007) Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability. J Child Neurol 22(5):574–579. doi:10.1177/0883073807302611

    Article  PubMed  Google Scholar 

  • Crespi B, Stead P, Elliot M (2010) Comparative genomics of autism and schizophrenia. Proc Natl Acad Sci 107(suppl 1):1736–1741

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dalton KM, Nacewicz BM, Johnstone T, Schaefer HS, Gernsbacher MA, Goldsmith HH, Alexander AL, Davidson RJ (2005) Gaze fixation and the neural circuitry of face processing in autism. Nat Neurosci 8(4):519–526. doi:10.1038/nn1421

    PubMed Central  CAS  PubMed  Google Scholar 

  • DelGiudice-Asch G, Simon L, Schmeidler J, Cunningham-Rundles C, Hollander E (1999) Brief report: a pilot open clinical trial of intravenous immunoglobulin in childhood autism. J Autism Dev Disord 29(2):157–160

    Article  CAS  PubMed  Google Scholar 

  • DeVito TJ, Drost DJ, Neufeld RW, Rajakumar N, Pavlosky W, Williamson P, Nicolson R (2007) Evidence for cortical dysfunction in autism: a proton magnetic resonance spectroscopic imaging study. Biol Psychiatry 61(4):465–473. doi:10.1016/j.biopsych.2006.07.022

    Article  PubMed  Google Scholar 

  • Domes G, Kumbier E, Heinrichs M, Herpertz SC (2013) Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome. Neuropsychopharmacology 39(3):698–706. doi:10.1038/npp.2013.254

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Donaldson ZR, Young LJ (2008) Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322(5903):900–904. doi:10.1126/science.1158668

    Article  CAS  PubMed  Google Scholar 

  • Erickson CA, Posey DJ, Stigler KA, Mullett J, Katschke AR, McDougle CJ (2007) A retrospective study of memantine in children and adolescents with pervasive developmental disorders. Psychopharmacology (Berl) 191(1):141–147. doi:10.1007/s00213-006-0518-9

    Article  CAS  Google Scholar 

  • Evins AE, Amico E, Posever TA, Toker R, Goff DC (2002) d-Cycloserine added to risperidone in patients with primary negative symptoms of schizophrenia. Schizophr Res 56(1–2):19–23

    Article  PubMed  Google Scholar 

  • Ey E, Leblond CS, Bourgeron T (2011) Behavioral profiles of mouse models for autism spectrum disorders. Autism Res 4(1):5–16. doi:10.1002/aur.175

    Article  PubMed  Google Scholar 

  • Farroni T, Csibra G, Simion F, Johnson MH (2002) Eye contact detection in humans from birth. Proc Natl Acad Sci U S A 99(14):9602–9605. doi:10.1073/pnas.152159999

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ferguson JN, Young LJ, Hearn EF, Matzuk MM, Insel TR, Winslow JT (2000) Social amnesia in mice lacking the oxytocin gene. Nat Genet 25(3):284–288. doi:10.1038/77040

    Article  CAS  PubMed  Google Scholar 

  • Ferguson JN, Aldag JM, Insel TR, Young LJ (2001) Oxytocin in the medial amygdala is essential for social recognition in the mouse. J Neurosci 21(20):8278–8285

    CAS  PubMed  Google Scholar 

  • Friedman SD, Shaw DW, Artru AA, Dawson G, Petropoulos H, Dager SR (2006) Gray and white matter brain chemistry in young children with autism. Arch Gen Psychiatry 63(7):786–794. doi:10.1001/archpsyc.63.7.786

    Article  CAS  PubMed  Google Scholar 

  • Frith CD (2008) Social cognition. Philos Trans R Soc Lond B Biol Sci 363(1499):2033–2039. doi:10.1098/rstb.2008.0005

    Article  PubMed Central  PubMed  Google Scholar 

  • Gantois I, Pop AS, de Esch CE, Buijsen RA, Pooters T, Gomez-Mancilla B, Gasparini F, Oostra BA, D'Hooge R, Willemsen R (2013) Chronic administration of AFQ056/Mavoglurant restores social behaviour in Fmr1 knockout mice. Behav Brain Res 239:72–79. doi:10.1016/j.bbr.2012.10.059

    Article  CAS  PubMed  Google Scholar 

  • Garay PA, Hsiao EY, Patterson PH, McAllister AK (2013) Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development. Brain Behav Immun 31:54–68. doi:10.1016/j.bbi.2012.07.008

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ghaleiha A, Asadabadi M, Mohammadi MR, Shahei M, Tabrizi M, Hajiaghaee R, Hassanzadeh E, Akhondzadeh S (2013) Memantine as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial. Int J Neuropsychopharmacol 16(4):783–789. doi:10.1017/S1461145712000880

    Article  CAS  PubMed  Google Scholar 

  • Goff DC, Cather C, Gottlieb JD, Evins AE, Walsh J, Raeke L, Otto MW, Schoenfeld D, Green MF (2008) Once-weekly d-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study. Schizophr Res 106(2–3):320–327. doi:10.1016/j.schres.2008.08.012

    Article  PubMed Central  PubMed  Google Scholar 

  • Gordon I, Vander Wyk BC, Bennett RH, Cordeaux C, Lucas MV, Eilbott JA, Zagoory-Sharon O, Leckman JF, Feldman R, Pelphrey KA (2013) Oxytocin enhances brain function in children with autism. Proc Natl Acad Sci USA 110(52):20953–20958. doi:10.1073/pnas.1312857110

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gotts SJ, Simmons WK, Milbury LA, Wallace GL, Cox RW, Martin A (2012) Fractionation of social brain circuits in autism spectrum disorders. Brain 135(Pt 9):2711–2725. doi:10.1093/brain/aws160

    Article  PubMed Central  PubMed  Google Scholar 

  • 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):342–353

    Article  PubMed  Google Scholar 

  • Guastella AJ, Mitchell PB, Dadds MR (2008) Oxytocin increases gaze to the eye region of human faces. Biol Psychiatry 63(1):3–5. doi:10.1016/j.biopsych.2007.06.026

    Article  CAS  PubMed  Google Scholar 

  • 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):692–694. doi:10.1016/j.biopsych.2009.09.020

    Article  CAS  PubMed  Google Scholar 

  • Gupta S, Aggarwal S, Heads C (1996) Dysregulated immune system in children with autism: beneficial effects of intravenous immune globulin on autistic characteristics. J Autism Dev Disord 26(4):439–452

    Article  CAS  PubMed  Google Scholar 

  • Haith M, Bergman T, Moore M (1977) Eye contact and face scanning in early infancy. Science 198(4319):853–855. doi:10.1126/science.918670

    Article  CAS  PubMed  Google Scholar 

  • Hamza RT, Hewedi DH, Ismail MA (2010) Basal and adrenocorticotropic hormone stimulated plasma cortisol levels among Egyptian autistic children: relation to disease severity. Ital J Pediatr 36:71. doi:10.1186/1824-7288-36-71

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Handen BL, Melmed RD, Hansen RL, Aman MG, Burnham DL, Bruss JB, McDougle CJ (2009) A double-blind, placebo-controlled trial of oral human immunoglobulin for gastrointestinal dysfunction in children with autistic disorder. J Autism Dev Disord 39(5):796–805. doi:10.1007/s10803-008-0687-y

    Article  PubMed  Google Scholar 

  • Harada M, Taki MM, Nose A, Kubo H, Mori K, Nishitani H, Matsuda T (2011) Non-invasive evaluation of the GABAergic/glutamatergic system in autistic patients observed by MEGA-editing proton MR spectroscopy using a clinical 3 T instrument. J Autism Dev Disord 41(4):447–454. doi:10.1007/s10803-010-1065-0

    Article  PubMed  Google Scholar 

  • Hardan AY, Minshew NJ, Melhem NM, Srihari S, Jo B, Bansal R, Keshavan MS, Stanley JA (2008) An MRI and proton spectroscopy study of the thalamus in children with autism. Psychiatry Res 163(2):97–105. doi:10.1016/j.pscychresns.2007.12.002

    Article  PubMed Central  PubMed  Google Scholar 

  • Haxby JV, Hoffman EA, Gobbini MI (2002) Human neural systems for face recognition and social communication. Biol Psychiatry 51(1):59–67

    Article  PubMed  Google Scholar 

  • Heresco-Levy U, Javitt DC (2004) Comparative effects of glycine and d-cycloserine on persistent negative symptoms in schizophrenia: a retrospective analysis. Schizophr Res 66(2–3):89–96. doi:10.1016/S0920-9964(03)00129-4

    Article  PubMed  Google Scholar 

  • Heuer L, Ashwood P, Schauer J, Goines P, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen LA, Pessah IN, Van de Water J (2008) Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms. Autism Res 1(5):275–283. doi:10.1002/aur.42

    Article  PubMed Central  PubMed  Google Scholar 

  • Higashida H, Yokoyama S, Munesue T, Kikuchi M, Minabe Y, Lopatina O (2011) CD38 gene knockout juvenile mice: a model of oxytocin signal defects in autism. Biol Pharm Bull 34(9):1369–1372

    Article  CAS  PubMed  Google Scholar 

  • Higashida H, Yokoyama S, Kikuchi M, Munesue T (2012) CD38 and its role in oxytocin secretion and social behavior. Horm Behav 61(3):351–358. doi:10.1016/j.yhbeh.2011.12.011

    Article  CAS  PubMed  Google Scholar 

  • Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR, Mosovich S (2003) Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology 28(1):193–198. doi:10.1038/sj.npp.1300021

    Article  CAS  PubMed  Google Scholar 

  • Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L, Anagnostou E, Wasserman S (2007) Oxytocin increases retention of social cognition in autism. Biol Psychiatry 61(4):498–503. doi:10.1016/j.biopsych.2006.05.030

    Article  CAS  PubMed  Google Scholar 

  • Horder J, Lavender T, Mendez MA, O'Gorman R, Daly E, Craig MC, Lythgoe DJ, Barker GJ, Murphy DG (2013) Reduced subcortical glutamate/glutamine in adults with autism spectrum disorders: a [(1)H]MRS study. Transl Psychiatry 3:e279. doi:10.1038/tp.2013.53

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Huang H, Michetti C, Busnelli M, Manago F, Sannino S, Scheggia D, Giancardo L, Sona D, Murino V, Chini B, Scattoni ML, Papaleo F (2014) Chronic and acute intranasal oxytocin produce divergent social effects in mice. Neuropsychopharmacology 39(5):1102–1114. doi:10.1038/npp.2013.310

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jin D, Liu HX, Hirai H, Torashima T, Nagai T, Lopatina O, Shnayder NA, Yamada K, Noda M, Seike T, Fujita K, Takasawa S, Yokoyama S, Koizumi K, Shiraishi Y, Tanaka S, Hashii M, Yoshihara T, Higashida K, Islam MS, Yamada N, Hayashi K, Noguchi N, Kato I, Okamoto H, Matsushima A, Salmina A, Munesue T, Shimizu N, Mochida S, Asano M, Higashida H (2007) CD38 is critical for social behaviour by regulating oxytocin secretion. Nature 446(7131):41–45. doi:10.1038/nature05526

    Article  CAS  PubMed  Google Scholar 

  • Jones W, Carr K, Klin A (2008) Absence of preferential looking to the eyes of approaching adults predicts level of social disability in 2-year-old toddlers with autism spectrum disorder. Arch Gen Psychiatry 65(8):946–954. doi:10.1001/archpsyc.65.8.946

    Article  PubMed  Google Scholar 

  • Just MA, Keller TA, Malave VL, Kana RK, Varma S (2012) Autism as a neural systems disorder: a theory of frontal-posterior underconnectivity. Neurosci Biobehav Rev 36(4):1292–1313. doi:10.1016/j.neubiorev.2012.02.007

    Article  PubMed Central  PubMed  Google Scholar 

  • Kannan S, Saadani-Makki F, Muzik O, Chakraborty P, Mangner TJ, Janisse J, Romero R, Chugani DC (2007) Microglial activation in perinatal rabbit brain induced by intrauterine inflammation: detection with 11C-(R)-PK11195 and small-animal PET. J Nucl Med 48(6):946–954. doi:10.2967/jnumed.106.038539

    Article  CAS  PubMed  Google Scholar 

  • Kaytor MD, Orr HT (2001) RNA targets of the fragile X protein. Cell 107(5):555–557

    Article  CAS  PubMed  Google Scholar 

  • Kenna HA, Poon AW, de los Angeles CP, Koran LM (2011) Psychiatric complications of treatment with corticosteroids: review with case report. Psychiatry Clin Neurosci 65(6):549–560. doi:10.1111/j.1440-1819.2011.02260.x

    Article  CAS  PubMed  Google Scholar 

  • Kimura M, Toth LA, Agostini H, Cady AB, Majde JA, Krueger JM (1994) Comparison of acute phase responses induced in rabbits by lipopolysaccharide and double-stranded RNA. Am J Physiol 267(6 Pt 2):R1596–R1605

    CAS  PubMed  Google Scholar 

  • Kleinhans NM, Richards T, Johnson LC, Weaver KE, Greenson J, Dawson G, Aylward E (2011) fMRI evidence of neural abnormalities in the subcortical face processing system in ASD. Neuroimage 54(1):697–704. doi:10.1016/j.neuroimage.2010.07.037

    Article  PubMed Central  PubMed  Google Scholar 

  • Klin A, Sparrow SS, de Bildt A, Cicchetti DV, Cohen DJ, Volkmar FR (1999) A normed study of face recognition in autism and related disorders. J Autism Dev Disord 29(6):499–508

    Article  CAS  PubMed  Google Scholar 

  • Klin A, Lin DJ, Gorrindo P, Ramsay G, Jones W (2009) Two-year-olds with autism orient to non-social contingencies rather than biological motion. Nature 459(7244):257–261

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lim MM, Bielsky IF, Young LJ (2005) Neuropeptides and the social brain: potential rodent models of autism. Int J Dev Neurosci 23(2–3):235–243. doi:10.1016/j.ijdevneu.2004.05.006

    Article  PubMed  CAS  Google Scholar 

  • Liu HX, Lopatina O, Higashida C, Tsuji T, Kato I, Takasawa S, Okamoto H, Yokoyama S, Higashida H (2008) Locomotor activity, ultrasonic vocalization and oxytocin levels in infant CD38 knockout mice. Neurosci Lett 448(1):67–70. doi:10.1016/j.neulet.2008.09.084

    Article  CAS  PubMed  Google Scholar 

  • Lukas M, Neumann ID (2013) Oxytocin and vasopressin in rodent behaviors related to social dysfunctions in autism spectrum disorders. Behav Brain Res 251:85–94. doi:10.1016/j.bbr.2012.08.011

    Article  CAS  PubMed  Google Scholar 

  • Lynch CJ, Uddin LQ, Supekar K, Khouzam A, Phillips J, Menon V (2013) Default mode network in childhood autism: posteromedial cortex heterogeneity and relationship with social deficits. Biol Psychiatry 74(3):212–219. doi:10.1016/j.biopsych.2012.12.013

    Article  PubMed Central  PubMed  Google Scholar 

  • Malkova NV, Yu CZ, Hsiao EY, Moore MJ, Patterson PH (2012) Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain Behav Immun 26(4):607–616. doi:10.1016/j.bbi.2012.01.011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marinovic-Curin J, Marinovic-Terzic I, Bujas-Petkovic Z, Zekan L, Skrabic V, Dogas Z, Terzic J (2008) Slower cortisol response during ACTH stimulation test in autistic children. Eur Child Adolesc Psychiatry 17(1):39–43. doi:10.1007/s00787-007-0632-1

    Article  PubMed  Google Scholar 

  • Markram K, Rinaldi T, La Mendola D, Sandi C, Markram H (2008) Abnormal fear conditioning and amygdala processing in an animal model of autism. Neuropsychopharmacology 33(4):901–912. doi:10.1038/sj.npp.1301453

    Article  PubMed  Google Scholar 

  • McCall C, Singer T (2012) The animal and human neuroendocrinology of social cognition, motivation and behavior. Nat Neurosci 15(5):681–688. doi:10.1038/nn.3084

    Article  CAS  PubMed  Google Scholar 

  • McDougle CJ, Carlezon WA Jr (2013) Neuroinflammation and autism: toward mechanisms and treatments. Neuropsychopharmacology 38(1):241–242. doi:10.1038/npp.2012.174

    Article  PubMed Central  PubMed  Google Scholar 

  • Mens WB, Witter A, van Wimersma Greidanus TB (1983) Penetration of neurohypophyseal hormones from plasma into cerebrospinal fluid (CSF): half-times of disappearance of these neuropeptides from CSF. Brain Res 262(1):143–149

    Article  CAS  PubMed  Google Scholar 

  • Meyer U, Nyffeler M, Engler A, Urwyler A, Schedlowski M, Knuesel I, Yee BK, Feldon J (2006) The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. J Neurosci 26(18):4752–4762. doi:10.1523/JNEUROSCI. 0099-06.2006

    Article  CAS  PubMed  Google Scholar 

  • Meyer U, Murray PJ, Urwyler A, Yee BK, Schedlowski M, Feldon J (2008) Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling. Mol Psychiatry 13(2):208–221. doi:10.1038/sj.mp.4002042

    Article  CAS  PubMed  Google Scholar 

  • Monk CS, Weng SJ, Wiggins JL, Kurapati N, Louro HM, Carrasco M, Maslowsky J, Risi S, Lord C (2010) Neural circuitry of emotional face processing in autism spectrum disorders. J Psychiatry Neurosci 35(2):105–114

    Article  PubMed Central  PubMed  Google Scholar 

  • Mordekar SR, Prendergast M, Chattopadhyay AK, Baxter PS (2009) Corticosteroid treatment of behaviour, language and motor regression in childhood disintegrative disorder. Eur J Paediatr Neurol 13(4):367–369. doi:10.1016/j.ejpn.2008.06.001

    Article  PubMed  Google Scholar 

  • Mundy P, Sullivan L, Mastergeorge AM (2009) A parallel and distributed-processing model of joint attention, social cognition and autism. Autism Res 2(1):2–21. doi:10.1002/aur.61

    Article  PubMed Central  PubMed  Google Scholar 

  • Niederhofer H (2007) Glutamate antagonists seem to be slightly effective in psychopharmacologic treatment of autism. J Clin Psychopharmacol 27(3):317–318. doi:10.1097/01.jcp.0000270082.30500.69

    Article  PubMed  Google Scholar 

  • O’Connor EC, Bariselli S, Bellone C (2014) Synaptic basis of social dysfunction: a focus on postsynaptic proteins linking group-I mGluRs with AMPARs and NMDARs. Eur J Neurosci 39(7):1114–1129. doi:10.1111/ejn.12510

    Article  PubMed  Google Scholar 

  • Onore CE, Schwartzer JJ, Careaga M, Berman RF, Ashwood P (2014) Maternal immune activation leads to activated inflammatory macrophages in offspring. Brain Behav Immun 38:220–226. doi:10.1016/j.bbi.2014.02.007

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Oskvig DB, Elkahloun AG, Johnson KR, Phillips TM, Herkenham M (2012) Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response. Brain Behav Immun 26(4):623–634. doi:10.1016/j.bbi.2012.01.015

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Owley T, Salt J, Guter S, Grieve A, Walton L, Ayuyao N, Leventhal BL, Cook EH Jr (2006) A prospective, open-label trial of memantine in the treatment of cognitive, behavioral, and memory dysfunction in pervasive developmental disorders. J Child Adolesc Psychopharmacol 16(5):517–524. doi:10.1089/cap.2006.16.517

    Article  PubMed  Google Scholar 

  • Page LA, Daly E, Schmitz N, Simmons A, Toal F, Deeley Q, Ambery F, McAlonan GM, Murphy KC, Murphy DG (2006) In vivo 1H-magnetic resonance spectroscopy study of amygdala-hippocampal and parietal regions in autism. Am J Psychiatry 163(12):2189–2192. doi:10.1176/appi.ajp.163.12.2189

    PubMed  Google Scholar 

  • Patterson PH (2009) Immune involvement in schizophrenia and autism: etiology, pathology and animal models. Behav Brain Res 204(2):313–321. doi:10.1016/j.bbr.2008.12.016

    Article  CAS  PubMed  Google Scholar 

  • Pelphrey KA, Sasson NJ, Reznick JS, Paul G, Goldman BD, Piven J (2002) Visual scanning of faces in autism. J Autism Dev Disord 32(4):249–261

    Article  PubMed  Google Scholar 

  • Pelphrey K, Adolphs R, Morris JP (2004) Neuroanatomical substrates of social cognition dysfunction in autism. Ment Retard Dev Disabil Res Rev 10(4):259–271. doi:10.1002/mrdd.20040

    Article  PubMed  Google Scholar 

  • Peng D, Yuan X, Zhu R (2013) Memantine hydrochloride in the treatment of dementia subtypes. J Clin Neurosci 20(11):1482–1485. doi:10.1016/j.jocn.2013.02.041

    Article  CAS  PubMed  Google Scholar 

  • Perlman SB, Hudac CM, Pegors T, Minshew NJ, Pelphrey KA (2011) Experimental manipulation of face-evoked activity in the fusiform gyrus of individuals with autism. Soc Neurosci 6(1):22–30. doi:10.1080/17470911003683185

    Article  PubMed Central  PubMed  Google Scholar 

  • Plioplys AV (1998) Intravenous immunoglobulin treatment of children with autism. J Child Neurol 13(2):79–82

    Article  CAS  PubMed  Google Scholar 

  • Posey DJ, Kem DL, Swiezy NB, Sweeten TL, Wiegand RE, McDougle CJ (2004) A pilot study of d-cycloserine in subjects with autistic disorder. Am J Psychiatry 161(11):2115–2117. doi:10.1176/appi.ajp.161.11.2115

    Article  PubMed  Google Scholar 

  • Rinaldi T, Kulangara K, Antoniello K, Markram H (2007) Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid. Proc Natl Acad Sci U S A 104(33):13501–13506. doi:10.1073/pnas.0704391104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Robinson IC, Jones PM (1982) Oxytocin and neurophysin in plasma and CSF during suckling in the guinea-pig. Neuroendocrinology 34(1):59–63

    Article  CAS  PubMed  Google Scholar 

  • Ros-Bernal F, Hunot S, Herrero MT, Parnadeau S, Corvol JC, Lu L, Alvarez-Fischer D, Carrillo-de Sauvage MA, Saurini F, Coussieu C, Kinugawa K, Prigent A, Hoglinger G, Hamon M, Tronche F, Hirsch EC, Vyas S (2011) Microglial glucocorticoid receptors play a pivotal role in regulating dopaminergic neurodegeneration in Parkinsonism. Proc Natl Acad Sci USA 108(16):6632–6637. doi:10.1073/pnas.1017820108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sala M, Braida D, Lentini D, Busnelli M, Bulgheroni E, Capurro V, Finardi A, Donzelli A, Pattini L, Rubino T, Parolaro D, Nishimori K, Parenti M, Chini B (2011) Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: a neurobehavioral model of autism. Biol Psychiatry 69(9):875–882. doi:10.1016/j.biopsych.2010.12.022

    Article  CAS  PubMed  Google Scholar 

  • Sasson NJ, Pinkham AE, Carpenter KL, Belger A (2011) The benefit of directly comparing autism and schizophrenia for revealing mechanisms of social cognitive impairment. J Neurodev Disord 3(2):87–100. doi:10.1007/s11689-010-9068-x

    Article  PubMed Central  PubMed  Google Scholar 

  • Schaefer GB, Mendelsohn NJ (2013) Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med 15(5):399–407. doi:10.1038/gim.2013.32

    Article  CAS  PubMed  Google Scholar 

  • Schneider T, Przewlocki R (2005) Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology 30(1):80–89. doi:10.1038/sj.npp.1300518

    Article  CAS  PubMed  Google Scholar 

  • Schneider CK, Melmed RD, Barstow LE, Enriquez FJ, Ranger-Moore J, Ostrem JA (2006) Oral human immunoglobulin for children with autism and gastrointestinal dysfunction: a prospective, open-label study. J Autism Dev Disord 36(8):1053–1064. doi:10.1007/s10803-006-0141-y

    Article  PubMed  Google Scholar 

  • Schweingruber N, Reichardt SD, Luhder F, Reichardt HM (2012) Mechanisms of glucocorticoids in the control of neuroinflammation. J Neuroendocrinol 24(1):174–182. doi:10.1111/j.1365-2826.2011.02161.x

    Article  CAS  PubMed  Google Scholar 

  • Seckl J, Lightman S (1988) Cerebrospinal fluid neurohypophysial peptides in benign intracranial hypertension. J Neurol Neurosurg Psychiatry 51(12):1538–1541

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shahrestani S, Kemp AH, Guastella AJ (2013) The impact of a single administration of intranasal oxytocin on the recognition of basic emotions in humans: a meta-analysis. Neuropsychopharmacology 38(10):1929–1936. doi:10.1038/npp.2013.86

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shenoy S, Arnold S, Chatila T (2000) Response to steroid therapy in autism secondary to autoimmune lymphoproliferative syndrome. J Pediatr 136(5):682–687. doi:10.1067/mpd.2000.105355

    Article  CAS  PubMed  Google Scholar 

  • Shi L, Fatemi SH, Sidwell RW, Patterson PH (2003) Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci 23(1):297–302

    PubMed  Google Scholar 

  • Smith SE, Li J, Garbett K, Mirnics K, Patterson PH (2007) Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci 27(40):10695–10702. doi:10.1523/JNEUROSCI. 2178-07.2007

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Smith SE, Zhou YD, Zhang G, Jin Z, Stoppel DC, Anderson MP (2011) Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice. Sci Transl Med 3(103):103ra97. doi:10.1126/scitranslmed.3002627

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Soto D, Altafaj X, Sindreu C, Bayes A (2014) Glutamate receptor mutations in psychiatric and neurodevelopmental disorders. Commun Integr Biol 7(1):e27887. doi:10.4161/cib.27887

    Article  PubMed Central  PubMed  Google Scholar 

  • Stefanatos GA, Grover W, Geller E (1995) Case study: corticosteroid treatment of language regression in pervasive developmental disorder. J Am Acad Child Adolesc Psychiatry 34(8):1107–1111. doi:10.1097/00004583-199508000-00022

    Article  CAS  PubMed  Google Scholar 

  • Sterling L, Dawson G, Webb S, Murias M, Munson J, Panagiotides H, Aylward E (2008) The role of face familiarity in eye tracking of faces by individuals with autism spectrum disorders. J Autism Dev Disord 38(9):1666–1675. doi:10.1007/s10803-008-0550-1

    Article  PubMed Central  PubMed  Google Scholar 

  • Stigler KA, Sweeten TL, Posey DJ, McDougle CJ (2009) Autism and immune factors: a comprehensive review. Res Autism Spectrum Disord 3(4):840–860. doi:10.1016/j.rasd. 2009.01-007

    Article  Google Scholar 

  • Supekar K, Uddin LQ, Khouzam A, Phillips J, Gaillard WD, Kenworthy LE, Yerys BE, Vaidya CJ, Menon V (2013) Brain hyperconnectivity in children with autism and its links to social deficits. Cell Rep 5(3):738–747. doi:10.1016/j.celrep.2013.10.001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Suzuki K, Sugihara G, Ouchi Y, Nakamura K, Futatsubashi M, Takebayashi K, Yoshihara Y, Omata K, Matsumoto K, Tsuchiya K, Iwata Y, Tsujii M, Sugiyama T, Mori N (2013) Microglial activation in young adults with autism spectrum disorders. JAMA Psychiatry 70(1):49–58. doi:10.1001/jamapsychiatry.2013.272

    Article  PubMed  Google Scholar 

  • Takayanagi Y, Yoshida M, Bielsky IF, Ross HE, Kawamata M, Onaka T, Yanagisawa T, Kimura T, Matzuk MM, Young LJ, Nishimori K (2005) Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proc Natl Acad Sci USA 102(44):16096–16101. doi:10.1073/pnas.0505312102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Teng BL, Nonneman RJ, Agster KL, Nikolova VD, Davis TT, Riddick NV, Baker LK, Pedersen CA, Jarstfer MB, Moy SS (2013) Prosocial effects of oxytocin in two mouse models of autism spectrum disorders. Neuropharmacology 72:187–196. doi:10.1016/j.neuropharm.2013.04.038

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Trajkovski V, Ajdinski L, Spiroski M (2004) Plasma concentration of immunoglobulin classes and subclasses in children with autism in the Republic of Macedonia: retrospective study. Croat Med J 45:746–749

    PubMed  Google Scholar 

  • Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62(3):405–496. doi:10.1124/pr.109.002451

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Uljarevic M, Hamilton A (2013) Recognition of emotions in autism: a formal meta-analysis. J Autism Dev Disord 43(7):1517–1526. doi:10.1007/s10803-012-1695-5

    Article  PubMed  Google Scholar 

  • Veening JG, Olivier B (2013) Intranasal administration of oxytocin: behavioral and clinical effects, a review. Neurosci Biobehav Rev 37(8):1445–1465. doi:10.1016/j.neubiorev.2013.04.012

    Article  CAS  PubMed  Google Scholar 

  • von dem Hagen EA, Stoyanova RS, Baron-Cohen S, Calder AJ (2013) Reduced functional connectivity within and between ‘social’ resting state networks in autism spectrum conditions. Soc Cogn Affect Neurosci 8(6):694–701. doi:10.1093/scan/nss053

    Article  Google Scholar 

  • Watanabe T, Abe O, Kuwabara H, Yahata N, Takano Y, Iwashiro N, Natsubori T, Aoki Y, Takao H, Kawakubo Y, Kamio Y, Kato N, Miyashita Y, Kasai K, Yamasue H (2013) Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: a randomized trial. JAMA Psychiatry 71(2):166–175. doi:10.1001/jamapsychiatry.2013.3181

    Article  Google Scholar 

  • Weigelt S, Koldewyn K, Kanwisher N (2012) Face identity recognition in autism spectrum disorders: a review of behavioral studies. Neurosci Biobehav Rev 36(3):1060–1084

    Article  PubMed  Google Scholar 

  • Weng SJ, Carrasco M, Swartz JR, Wiggins JL, Kurapati N, Liberzon I, Risi S, Lord C, Monk CS (2011) Neural activation to emotional faces in adolescents with autism spectrum disorders. J Child Psychol Psychiatry 52(3):296–305. doi:10.1111/j.1469-7610.2010.02317.x

    Article  PubMed Central  PubMed  Google Scholar 

  • Winslow JT, Insel TR (2002) The social deficits of the oxytocin knockout mouse. Neuropeptides 36(2–3):221–229

    Article  CAS  PubMed  Google Scholar 

  • Winslow JT, Hearn EF, Ferguson J, Young LJ, Matzuk MM, Insel TR (2000) Infant vocalization, adult aggression, and fear behavior of an oxytocin null mutant mouse. Horm Behav 37(2):145–155. doi:10.1006/hbeh.1999.1566

    Article  CAS  PubMed  Google Scholar 

  • Won H, Lee HR, Gee HY, Mah W, Kim JI, Lee J, Ha S, Chung C, Jung ES, Cho YS, Park SG, Lee JS, Lee K, Kim D, Bae YC, Kaang BK, Lee MG, Kim E (2012) Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function. Nature 486(7402):261–265. doi:10.1038/nature11208

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This work was supported, in part, by the Nancy Lurie Marks Family Foundation and the Robert and Donna Landreth Fund.

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Authors and Affiliations

  1. Massachusetts General Hospital, 02114, Boston, MA, USA

    Arshya Vahabzadeh & Christopher J. McDougle

  2. McLean Hospital, 02478, Belmont, MA, USA

    Arshya Vahabzadeh

  3. Harvard Medical School, 02115, Boston, MA, USA

    Arshya Vahabzadeh, Beate C. Finger, William A. Carlezon Jr. & Christopher J. McDougle

  4. Behavioral Genetics Laboratory, McLean Hospital, 02478, Belmont, MA, USA

    Samantha M. Landino, Beate C. Finger & William A. Carlezon Jr.

  5. Lurie Center for Autism, One Maguire Road, 02421, Lexington, MA, USA

    Christopher J. McDougle

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  1. Arshya Vahabzadeh
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  2. Samantha M. Landino
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  3. Beate C. Finger
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  4. William A. Carlezon Jr.
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  5. Christopher J. McDougle
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Correspondence to Christopher J. McDougle .

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  1. Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts, USA

    Kathleen M. Kantak

  2. Roche Pharmaceutical Research and Early Development; Neuroscience, Ophthalmology and Rare Diseases, F. Hoffmann-La Roche Ltd., Basel, Switzerland

    Joseph G. Wettstein

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Vahabzadeh, A., Landino, S.M., Finger, B.C., Carlezon, W.A., McDougle, C.J. (2015). Neural Targets in the Study and Treatment of Social Cognition in Autism Spectrum Disorder. In: Kantak, K., Wettstein, J. (eds) Cognitive Enhancement. Handbook of Experimental Pharmacology, vol 228. Springer, Cham. https://doi.org/10.1007/978-3-319-16522-6_11

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