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The neurobiology of autism spectrum disorders

Published online by Cambridge University Press:  15 April 2020

M. Parellada*
Affiliation:
Child and Adolescent Psychiatry Department, Instituto de Investigación Sanitaria Gregorio Marañón, IiSGM, Hospital General Universitario Gregorio Marañón, CIBERSAM, Ibiza 43, 28009Madrid, Spain
M.J. Penzol
Affiliation:
Child and Adolescent Psychiatry Department, Instituto de Investigación Sanitaria Gregorio Marañón, IiSGM, Hospital General Universitario Gregorio Marañón, CIBERSAM, Ibiza 43, 28009Madrid, Spain
L. Pina
Affiliation:
Child and Adolescent Psychiatry Department, Instituto de Investigación Sanitaria Gregorio Marañón, IiSGM, Hospital General Universitario Gregorio Marañón, CIBERSAM, Ibiza 43, 28009Madrid, Spain
C. Moreno
Affiliation:
Child and Adolescent Psychiatry Department, Instituto de Investigación Sanitaria Gregorio Marañón, IiSGM, Hospital General Universitario Gregorio Marañón, CIBERSAM, Ibiza 43, 28009Madrid, Spain
E. González-Vioque
Affiliation:
Child and Adolescent Psychiatry Department, Instituto de Investigación Sanitaria Gregorio Marañón, IiSGM, Hospital General Universitario Gregorio Marañón, CIBERSAM, Ibiza 43, 28009Madrid, Spain
G. Zalsman
Affiliation:
Child and Adolescent Psychiatry, Geha Hospital, Petach Tiqva, 49100Tel Aviv, Israel
C. Arango
Affiliation:
Child and Adolescent Psychiatry Department, Instituto de Investigación Sanitaria Gregorio Marañón, IiSGM, Hospital General Universitario Gregorio Marañón, CIBERSAM, Ibiza 43, 28009Madrid, Spain
*
*Corresponding author. Tel.: +34 91 586 8133; fax: +34 91 426 5108. E-mail address:parellada@hggm.es (M. Parellada).
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Abstract

Data is progressively and robustly accumulating regarding the biological basis of autism. Autism spectrum disorders (ASD) are currently considered a group of neurodevelopmental disorders with onset very early in life and a complex, heterogeneous, multifactorial aetiology. A comprehensive search of the last five years of the Medline database was conducted in order to summarize recent evidence on the neurobiological bases of autism. The main findings on genetic influence, neuropathology, neurostructure and brain networks are summarized. In addition, findings from peripheral samples of subjects with autism and animal models, which show immune, oxidative, mitochondrial dysregulations, are reported. Then, other biomarkers from very different systems associated with autism are reported. Finally, an attempt is made to try and integrate the available evidence, which points to a oligogenetic, multifactorial aetiology that converges in an aberrant micro-organization of the cortex, with abnormal functioning of the synapses and abnormalities in very general physiological pathways (such as inflammatory, immune and redox systems).

Type
Review
Copyright
Copyright © 2013 Elsevier Masson SAS

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References

Amaral, D.G.Schumann, C.M.Nordahl, C.W.Neuroanatomy of autism. Trends Neurosci 2008;31:137145.CrossRefGoogle ScholarPubMed
Anagnostou, E.Taylor, M.J.Review of neuroimaging in autism spectrum disorders: what have we learned and where we go from here. Mol Autism 2011;2:4.CrossRefGoogle Scholar
Anney, R.Klei, L.Pinto, D.Almeida, J.Bacchelli, E.Baird, G.et al.Individual common variants exert weak effects on the risk for autism spectrum disorderspi. Hum Mol Genet 2012;21:47814792.CrossRefGoogle Scholar
Ashwood, P.Krakowiak, P.Hertz-Picciotto, I.Hansen, R.Pessah, I.Van de Water, J.Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 2011;25:4045.CrossRefGoogle ScholarPubMed
Ashwood, P.Corbett, B.A.Kantor, A.Schulman, H.Van de Water, J.Amaral, D.G.In search of cellular immunophenotypes in the blood of children with autism. PLoS One 2011;6:e19299.CrossRefGoogle ScholarPubMed
Atladottir, H.O.Pedersen, M.G.Thorsen, P.Mortensen, P.B.Deleuran, B.Eaton, W.W.et al.Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics 2009;124:687694.CrossRefGoogle ScholarPubMed
Auerbach, B.D.Osterweil, E.K.Bear, M.F.Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature 2011;480:6368.CrossRefGoogle ScholarPubMed
Bailey, A.Le Couteur, A.Gottesman, I.Bolton, P.Simonoff, E.Yuzda, E.et al.Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995;25:6377.CrossRefGoogle ScholarPubMed
Barnea-Goraly, N.Lotspeich, L.J.Reiss, A.L.Similar white matter aberrations in children with autism and their unaffected siblings: a diffusion tensor imaging study using tract-based spatial statistics. Arch Gen Psychiatry 2010;67:10521060.CrossRefGoogle ScholarPubMed
Baron-Cohen, S.The extreme male brain theory of autism. Trends Cogn Sci 2002;6:248254.CrossRefGoogle ScholarPubMed
Baron-Cohen, S.Empathizing, systemizing, and the extreme male brain theory of autism. Prog Brain Res 2010;186:167175.CrossRefGoogle ScholarPubMed
Barreda, Ede Castro, PParellada, M. Etiological diagnosis in ASD. unpublished 2013.Google Scholar
Bernardi, S.Anagnostou, E.Shen, J.Kolevzon, A.Buxbaum, J.D.Hollander, E.et al.In vivo 1H-magnetic resonance spectroscopy study of the attentional networks in autism. Brain Res 2011;1380:198205.CrossRefGoogle ScholarPubMed
Bozdagi, O.Sakurai, T.Papapetrou, D.Wang, X.Dickstein, D.L.Takahashi, N.et al.Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol Autism 2010;1:15.CrossRefGoogle ScholarPubMed
Bressler, J.P.Gillin, P.K.O’Driscoll, C.Kiihl, S.Solomon, M.Zimmerman, A.W.Maternal antibody reactivity to lymphocytes of offspring with autism. Pediatr Neurol 2012;47:337340.CrossRefGoogle ScholarPubMed
Buie, T.Campbell, D.B.Fuchs, G.J. 3rdFuruta, G.T.Levy, J.Vandewater, J.et al.Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 2010;125(Suppl 1):S1S18.CrossRefGoogle ScholarPubMed
Campbell, D.B.Sutcliffe, J.S.Ebert, P.J.Militerni, R.Bravaccio, C.Trillo, S.et al.A genetic variant that disrupts MET transcription is associated with autism. Proc Natl Acad Sci U S A 2006;103:1683416839.CrossRefGoogle ScholarPubMed
Campbell, D.B.Li, C.Sutcliffe, J.S.Persico, A.M.Levitt, P.Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder. Autism Res 2008;1:159168.CrossRefGoogle ScholarPubMed
Chauhan, A.Chauhan, V.Brown, A.Autism: Oxidative Stress inflammation and immune abnormalities. Boca Raton, FL: Taylor and Francis/CRC; 2010.Google Scholar
Chez, M.G.Dowling, T.Patel, P.B.Khanna, P.Kominsky, M.Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol 2007;36:361365.CrossRefGoogle ScholarPubMed
Constantino, J.N.Zhang, Y.Frazier, T.Abbacchi, A.M.Law, P.Sibling recurrence and the genetic epidemiology of autism. Am J Psychiatry 2010;167:13491356.CrossRefGoogle ScholarPubMed
Corbett, B.A.Schupp, C.W.Levine, S.Mendoza, S.Comparing cortisol, stress, and sensory sensitivity in children with autism. Autism Res 2009;2:3949.CrossRefGoogle ScholarPubMed
Courchesne, E.Pierce, K.Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection. Curr Opin Neurobiol 2005;15:225230.CrossRefGoogle ScholarPubMed
Courchesne, E.Redcay, E.Kennedy, D.P.The autistic brain: birth through adulthood. Curr Opin Neurol 2004;17:489496.CrossRefGoogle ScholarPubMed
Courchesne, E.Campbell, K.Solso, S.Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res 2011;1380:138145.CrossRefGoogle ScholarPubMed
Crawley, J.N.What's wrong with my mouse? Behavioral phenotyping of transgenic and knockout mice; Wiley; 2007.CrossRefGoogle Scholar
Darnell, J.C.Van Driesche, S.J.Zhang, C.Hung, K.Y.Mele, A.Fraser, C.E.et al.FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 2011;146:247261.CrossRefGoogle ScholarPubMed
De Rubeis, S.Bagni, C.Regulation of molecular pathways in the Fragile X Syndrome: insights into Autism Spectrum Disorders. J Neurodev Disord 2011;3:257269.CrossRefGoogle ScholarPubMed
Deth, R.C.Muratone, C.R.The redox/methylation hypothesis of autism: a molecular mechanism for havy metal-induced neurotoxicity. In: Chauhan, A.Chauhan, V.Brown, W.T., Autism Oxidative Stress, Inflammation and Immune Abnormalities.Google Scholar
DiCicco-Bloom, E.Lord, C.Zwaigenbaum, L.Courchesne, E.Dager, S.R.Schmitz, C.et al.The developmental neurobiology of autism spectrum disorder. J Neurosci 2006;26:2010. p. 68976906.CrossRefGoogle ScholarPubMed
Eagleson, K.L.Campbell, D.B.Thompson, B.L.Bergman, M.Y.Levitt, P.The autism risk genes MET and PLAUR differentially impact cortical development. Autism Res 2011;4:6883.CrossRefGoogle ScholarPubMed
Ecker, C.Ginestet, C.Feng, Y.Johnston, P.Lombardo, M.V.Lai, M.C.et al.Brain surface anatomy in adults with autism: the relationship between surface area, cortical thickness, and autistic symptoms. JAMA Psychiatry 2013;70:5970.CrossRefGoogle ScholarPubMed
Emanuele, E.Orsi, P.Boso, M.Broglia, D.Brondino, N.Barale, F.et al.Low-grade endotoxemia in patients with severe autism. Neurosci Lett 2010;471:162165.CrossRefGoogle ScholarPubMed
Emanuele, E.Colombo, R.Martinelli, V.Brondino, N.Marini, M.Boso, M.et al.Elevated urine levels of bufotenine in patients with autistic spectrum disorders and schizophrenia. Neuro Endocrinol Lett 2010;31:117121.Google Scholar
Fatemi, S.H.Folsom, T.D.Reutiman, T.J.Thuras, P.D.Expression of GABA(B) receptors is altered in brains of subjects with autism. Cerebellum 2009;8:6469.CrossRefGoogle ScholarPubMed
Frazier, T.W.Hardan, A.Y.A meta-analysis of the corpus callosum in autism. Biol Psychiatry 2009;66:935941.CrossRefGoogle ScholarPubMed
Fujii, E.Mori, K.Miyazaki, M.Hashimoto, T.Harada, M.Kagami, S.Function of the frontal lobe in autistic individuals: a proton magnetic resonance spectroscopic study. J Med Invest 2010;57:3544.CrossRefGoogle ScholarPubMed
Gandal, M.J.Edgar, J.C.Ehrlichman, R.S.Mehta, M.Roberts, T.P.Siegel, S.J.Validating gamma oscillations and delayed auditory responses as translational biomarkers of autism. Biol Psychiatry 2010;68:11001106.CrossRefGoogle ScholarPubMed
Geschwind, D.H.Levitt, P.Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol 2007;17:103111.CrossRefGoogle ScholarPubMed
Giaume, C.Kirchhoff, F.Matute, C.Reichenbach, A.Verkhratsky, A.Glia: the fulcrum of brain diseases. Cell Death Differ 2007;14:13241335.CrossRefGoogle ScholarPubMed
Gilman, S.R.Iossifov, I.Levy, D.Ronemus, M.Wigler, M.Vitkup, D.Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses. Neuron 2011;70:898907.CrossRefGoogle ScholarPubMed
Giulivi, C.Zhang, Y.F.Omanska-Klusek, A.Ross-Inta, C.Wong, S.Hertz-Picciotto, I.et al.Mitochondrial dysfunction in autism. JAMA 2010;304:23892396.CrossRefGoogle ScholarPubMed
Hallmayer, J.Cleveland, S.Torres, A.Phillips, J.Cohen, B.Torigoe, T.et al.Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 2011;68:10951102.CrossRefGoogle ScholarPubMed
Hammock, E.A.Young, L.J.Microsatellite instability generates diversity in brain and sociobehavioral traits. Science 2005;308:16301634.CrossRefGoogle ScholarPubMed
Herbert, M.R.Autism: a brain disorder or a disorder that affects the brain. Clinical Neuropsychiatry 2005;2:354379.Google Scholar
Herbert, M.R.Autism: the centrality of active pathophysiology and the shift from static to chronic dynamic encephalopathy. In: Chauhan, A.Chauhan, V.Brown, T.Autism: oxidative stress, inflammation and immune abnormalities Boca Raton, FL: Taylor and Francis/CRC Press; 2010. p. 343388.Google Scholar
Herbert, M.R.Ziegler, D.A.Deutsch, C.K.O’Brien, L.M.Lange, N.Bakardjiev, A.et al.Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain 2003;126:11821192.CrossRefGoogle ScholarPubMed
Heuer, L.Braunschweig, D.Ashwood, P.Van de Water, J.Campbell, D.B.Association of a MET genetic variant with autism-associated maternal autoantibodies to fetal brain proteins and cytokine expression. Transl Psychiatry 2011;1:e48.CrossRefGoogle ScholarPubMed
Hollander, E.Anagnostou, E.Chaplin, W.Esposito, K.Haznedar, M.M.Licalzi, E.et al.Striatal volume on magnetic resonance imaging and repetitive behaviors in autism. Biol Psychiatry 2005;58:226232.CrossRefGoogle ScholarPubMed
Hussman, J.P.Chung, R.H.Griswold, A.J.Jaworski, J.M.Salyakina, D.Ma, D.et al.A noise-reduction GWAS analysis implicates altered regulation of neurite outgrowth and guidance in autism. Mol Autism 2011;2:1.CrossRefGoogle ScholarPubMed
Iseri, E.Guney, E.Ceylan, M.F.Yucel, A.Aral, A.Bodur, S.et al.Increased serum levels of epidermal growth factor in children with autism. J Autism Dev Disord 2011;41:237241.CrossRefGoogle ScholarPubMed
Jacob, S.Brune, C.W.Carter, C.S.Leventhal, B.L.Lord, C.Cook, E.H. Jr.Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett 2007;417:69.CrossRefGoogle ScholarPubMed
James, S.J.Cutler, P.Melnyk, S.Jernigan, S.Janak, L.Gaylor, D.W.et al.Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 2004;80:16111617.CrossRefGoogle ScholarPubMed
James, S.J.Melnyk, S.Jernigan, S.Cleves, M.A.Halsted, C.H.Wong, D.H.et al.Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet 141B 2006 947956.CrossRefGoogle ScholarPubMed
James, S.J.Melnyk, S.Jernigan, S.Hubanks, A.Rose, S.Gaylor, D.W.Abnormal transmethylation/transsulfuration metabolism and DNA hypomethylation among parents of children with autism. J Autism Dev Disord 2008;38:19661975.CrossRefGoogle ScholarPubMed
James, S.J.Melnyk, S.Jernigan, S.Pavliv, O.Trusty, T.Lehman, S.et al.A functional polymorphism in the reduced folate carrier gene and DNA hypomethylation in mothers of children with autism. Am J Med Genet B Neuropsychiatr Genet 2010;153B 12091220.Google ScholarPubMed
Kajizuka, M.Miyachi, T.Matsuzaki, H.Iwata, K.Shinmura, C.Suzuki, K.et al.Serum levels of platelet-derived growth factor BB homodimers are increased in male children with autism. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:154158.CrossRefGoogle ScholarPubMed
Kanner, L.Autistic disturbances of affective contact. Pathology 1943 217250.Google Scholar
Kates, W.R.Ikuta, I.Burnette, C.P.Gyrification patterns in monozygotic twin pairs varying in discordance for autism. Autism Res 2009;2:267278.CrossRefGoogle ScholarPubMed
Kazek, B.Huzarska, M.Grzybowska-Chlebowczyk, U.Kajor, M.Ciupinska-Kajor, M.Wos, H.et al.Platelet and intestinal 5-HT2A receptor mRNA in autistic spectrum disorders – results of a pilot study. Acta Neurobiol Exp (Wars) 2010;70:232238.Google ScholarPubMed
Keil, A.Daniels, J.L.Forssen, U.Hultman, C.Cnattingius, S.Soderberg, K.C.et al.Parental autoimmune diseases associated with autism spectrum disorders in offspring. Epidemiology 2010;21:805808.CrossRefGoogle ScholarPubMed
Kenet, T.Orekhova, E.V.Bharadwaj, H.Shetty, N.R.Israeli, E.Lee, A.K.et al.Disconnectivity of the cortical ocular motor control network in autism spectrum disorders. Neuroimage 2012;61:12261234.CrossRefGoogle ScholarPubMed
King, M.D.Fountain, C.Dakhlallah, D.Bearman, P.S.Estimated autism risk and older reproductive age. Am J Public Health 2009;99:16731679.CrossRefGoogle ScholarPubMed
Knickmeyer, R.C.Baron-Cohen, S.Fetal testosterone and sex differences in typical social development and in autism. J Child Neurol 2006;21:825845.CrossRefGoogle ScholarPubMed
Kong, A.Frigge, M.L.Masson, G.Besenbacher, S.Sulem, P.Magnusson, G.et al.Rate of de novo mutations and the importance of father's age to disease risk. Nature 2012;488:471475.CrossRefGoogle ScholarPubMed
Kumar, A.Swanwick, C.C.Johnson, N.Menashe, I.Basu, S.N.Bales, M.E.et al.A brain region-specific predictive gene map for autism derived by profiling a reference gene set. PLoS One 2011;6:e28431.CrossRefGoogle ScholarPubMed
Landrigan, P.J.What causes autism? Exploring the environmental contribution. Curr Opin Pediatr 2010;22:219225.CrossRefGoogle ScholarPubMed
Levy, D.Ronemus, M.Yamrom, B.Lee, Y.H.Leotta, A.Kendall, J.et al.Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron 2011;70:886897.CrossRefGoogle ScholarPubMed
Li, X.Chauhan, A.Sheikh, A.M.Patil, S.Chauhan, V.Li, X.M.et al.Elevated immune response in the brain of autistic patients. J Neuroimmunol 2009;207:111116.CrossRefGoogle ScholarPubMed
Lindgren, K.A.Folstein, S.E.Tomblin, J.B.Tager-Flusberg, H.Language and reading abilities of children with autism spectrum disorders and specific language impairment and their first-degree relatives. Autism Res 2009;2:2238.CrossRefGoogle ScholarPubMed
MacFabe, D.F.Cain, D.P.Rodriguez-Capote, K.Franklin, A.E.Hoffman, J.E.Boon, F.et al.Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behav Brain Res 2007;176:149169.CrossRefGoogle ScholarPubMed
Main, P.A.Angley, M.T.Thomas, P.O’Doherty, C.E.Fenech, M.Folate and methionine metabolism in autism: a systematic review. Am J Clin Nutr 2010;91:15981620.CrossRefGoogle ScholarPubMed
Malhotra, D.Sebat, J.CNVs: harbingers of a rare variant revolution in psychiatric genetics. Cell 2012;148:12231241.CrossRefGoogle ScholarPubMed
Manji, H.Kato, T.Di Prospero, N.A.Ness, S.Beal, M.F.Krams, M.et al.Impaired mitochondrial function in psychiatric disorders. Nat Rev Neurosci 2012;13:293307.CrossRefGoogle ScholarPubMed
Marin, O.Interneuron dysfunction in psychiatric disorders. Nat Rev Neurosci 2012;13:107120.CrossRefGoogle ScholarPubMed
Michalon, A.Sidorov, M.Ballard, T.M.Ozmen, L.Spooren, W.Wettstein, J.G.et al.Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron 2012;74:4956.CrossRefGoogle ScholarPubMed
Miles, J.H.Autism spectrum disorders – a genetics review. Genet Med 2011;13:278294.CrossRefGoogle ScholarPubMed
Minshew, N.J.Williams, D.L.The new neurobiology of autism: cortex, connectivity, and neuronal organization. Arch Neurol 2007;64:945950.CrossRefGoogle ScholarPubMed
Modahl, C.Green, L.Fein, D.Morris, M.Waterhouse, L.Feinstein, C.et al.Plasma oxytocin levels in autistic children. Biol Psychiatry 1998;43:270277.CrossRefGoogle ScholarPubMed
Molloy, C.A.Morrow, A.L.Meinzen-Derr, J.Schleifer, K.Dienger, K.Manning-Courtney, P.et al.Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol 2006;172:198205.CrossRefGoogle ScholarPubMed
Mostafa, G.A.Al-Ayadhi, L.Y.Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity. J Neuroinflammation 2011;8:39.CrossRefGoogle ScholarPubMed
Mostafa, G.A.Kitchener, N.Serum anti-nuclear antibodies as a marker of autoimmunity in Egyptian autistic children. Pediatr Neurol 2009;40:107112.CrossRefGoogle ScholarPubMed
Mulder, E.J.Anderson, G.M.Kema, I.P.de Bildt, A.van Lang, N.D.den Boer, J.A.et al.Platelet serotonin levels in pervasive developmental disorders and mental retardation: diagnostic group differences, within-group distribution, and behavioral correlates. J Am Acad Child Adolesc Psychiatry 2004;43:491499.CrossRefGoogle ScholarPubMed
Neale, B.M.Kou, Y.Liu, L.Ma’ayan, A.Samocha, K.E.Sabo, A.et al.Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 2012;485:242245.CrossRefGoogle ScholarPubMed
Neumann, N.Dubischar-Krivec, A.M.Poustka, F.Birbaumer, N.Bolte, S.Braun, C.Electromagnetic evidence of altered visual processing in autism. Neuropsychologia 2011;49:30113017.CrossRefGoogle ScholarPubMed
Nissenkorn, A.Zeharia, A.Lev, D.Watemberg, N.Fattal-Valevski, A.Barash, V.et al.Neurologic presentations of mitochondrial disorders. J Child Neurol 2000;15:4448.CrossRefGoogle ScholarPubMed
Oberman, L.M.McCleery, J.P.Hubbard, E.M.Bernier, R.Wiersema, J.R.Raymaekers, R.et al.Developmental changes in mu suppression to observed and executed actions in autism spectrum disorders. Soc Cogn Affect Neurosci 2012.Google ScholarPubMed
Onore, C.Van de Water, J.Ashwood, P.Decreased levels of EGF in plasma of children with autism spectrum disorder. Autism Res Treat 2012;2012:205362.Google ScholarPubMed
O’Roak, B.J.Vives, L.Girirajan, S.Karakoc, E.Krumm, N.Coe, B.P.et al.Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 2012;485:246250.CrossRefGoogle ScholarPubMed
O’Roak, B.J.Vives, L.Fu, W.Egertson, J.D.Stanaway, I.B.Phelps, I.G.et al.Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science 2012;338:16191622.CrossRefGoogle ScholarPubMed
Palmieri, L.Persico, A.M.Mitochondrial dysfunction in autism spectrum disorders: cause or effect?. Biochim Biophys Acta 2010;1797:11301137.CrossRefGoogle ScholarPubMed
Palmieri, L.Papaleo, V.Porcelli, V.Scarcia, P.Gaita, L.Sacco, R.et al.Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1. Mol Psychiatry 2010;15:3852.CrossRefGoogle ScholarPubMed
Pardo, C.A.Vargas, D.L.Zimmerman, A.W.Immunity, neuroglia and neuroinflammation in autism. Int Rev Psychiatry 2005;17:485495.CrossRefGoogle ScholarPubMed
Parellada, M.Moreno, C.Mac-Dowell, K.Leza, J.C.Giraldez, M.Bailon, C.et al.Plasma antioxidant capacity is reduced in Asperger syndrome. J Psychiatr Res 2012;46:394401.CrossRefGoogle ScholarPubMed
Peca, J.Feliciano, C.Ting, J.T.Wang, W.Wells, M.F.Venkatraman, T.N.et al.Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 2011;472:437442.CrossRefGoogle ScholarPubMed
Peca, J.Ting, J.Feng, G.SnapShot:, Autism and the synapse. Cell 2011;147:706 e1.CrossRefGoogle ScholarPubMed
Penagarikano, O.Geschwind, D.H.What does CNTNAP2 reveal about autism spectrum disorder?. Trends Mol Med 2012;18:156163.CrossRefGoogle ScholarPubMed
Philip, R.C.Dauvermann, M.R.Whalley, H.C.Baynham, K.Lawrie, S.M.Stanfield, A.C.A systematic review and meta-analysis of the fMRI investigation of autism spectrum disorders. Neurosci Biobehav Rev 2012;36:901942.CrossRefGoogle ScholarPubMed
Pina-Camacho, L.Villero, S.Fraguas, D.Boada, L.Janssen, J.Navas-Sanchez, F.J.et al.Autism spectrum disorder: does neuroimaging support the DSM-5 proposal for a symptom dyad?. A systematic review of functional magnetic resonance imaging and diffusion tensor imaging studies. J Autism Dev Disord 2012;42:13261341.CrossRefGoogle ScholarPubMed
Postel, J.Quétel, C.Historia de la Psiquiatría. Fondo de Cultura Económica; 1987.Google Scholar
Ritvo, E.R.Jorde, L.B.Mason-Brothers, A.Freeman, B.J.Pingree, C.Jones, M.B.et al.The UCLA-University of Utah epidemiologic survey of autism: recurrence risk estimates and genetic counseling. Am J Psychiatry 1989;146:10321036.Google ScholarPubMed
Robinson, E.B.Koenen, K.C.McCormick, M.C.Munir, K.Hallett, V.Happe, F.et al.Evidence that autistic traits show the same etiology in the general population and at the quantitative extremes (5%, 2.5%, and 1%). Arch Gen Psychiatry 2011;68:11131121.CrossRefGoogle Scholar
Rosenberg, R.E.Law, J.K.Yenokyan, G.McGready, J.Kaufmann, W.E.Law, P.A.Characteristics and concordance of autism spectrum disorders among 277 twin pairs. Arch Pediatr Adolesc Med 2009;163:907914.CrossRefGoogle ScholarPubMed
Rossignol, E.Genetics and function of neocortical GABAergic interneurons in neurodevelopmental disorders. Neural Plast 2011;2011:649325.CrossRefGoogle ScholarPubMed
Rossignol, D.A.Frye, R.E.A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol Psychiatry 2012;17:389401.CrossRefGoogle ScholarPubMed
Sacco, R.Curatolo, P.Manzi, B.Militerni, R.Bravaccio, C.Frolli, A.et al.Principal pathogenetic components and biological endophenotypes in autism spectrum disorders. Autism Res 2010;3:237252.CrossRefGoogle ScholarPubMed
Sacco, R.Lenti, C.Saccani, M.Curatolo, P.Manzi, B.Bravaccio, C.et al.Cluster analysis of autistic patients based on principal pathogenetic components. Autism Res 2012;5:137147.CrossRefGoogle ScholarPubMed
Sanders, S.J.Ercan-Sencicek, A.G.Hus, V.Luo, R.Murtha, M.T.Moreno-De-Luca, D.et al.Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 2011;70:863885.CrossRefGoogle ScholarPubMed
Sanders, S.J.Murtha, M.T.Gupta, A.R.Murdoch, J.D.Raubeson, M.J.Willsey, A.J.et al.De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 2012;485:237241.CrossRefGoogle ScholarPubMed
Schafer, D.P.Lehrman, E.K.Kautzman, A.G.Koyama, R.Mardinly, A.R.Yamasaki, R.et al.Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 2012;74:691705.CrossRefGoogle Scholar
Schipul, S.E.Keller, T.A.Just, M.A.Inter-regional brain communication and its disturbance in autism. Front Syst Neurosci 2011;5:10.CrossRefGoogle ScholarPubMed
Schmidt, R.J.Hansen, R.L.Hartiala, J.Allayee, H.Schmidt, L.C.Tancredi, D.J.et al.Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiology 2011;22:476485.CrossRefGoogle ScholarPubMed
Shelton, J.F.Hertz-Picciotto, I. Environ Health Perspect. 2012.Google Scholar
Shen, Y.Dies, K.A.Holm, I.A.Bridgemohan, C.Sobeih, M.M.Caronna, E.B.et al.Clinical genetic testing for patients with autism spectrum disorders. Pediatrics 2010;125:e727e735.CrossRefGoogle ScholarPubMed
Singh, V.K.Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism. Ann Clin Psychiatry 2009;21:148161.Google Scholar
Sogut, S.Zoroglu, S.S.Ozyurt, H.Yilmaz, H.R.Ozugurlu, F.Sivasli, E.et al.Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin Chim Acta 2003;331:111117.CrossRefGoogle ScholarPubMed
Song, Y.Liu, C.Finegold, S.M.Real-time PCR, quantitation of clostridia in feces of autistic children. Appl Environ Microbiol 2004;70:64596465.CrossRefGoogle ScholarPubMed
Stanfield, A.C.McIntosh, A.M.Spencer, M.D.Philip, R.Gaur, S.Lawrie, S.M.Towards a neuroanatomy of autism: a systematic review and meta-analysis of structural magnetic resonance imaging studies. Eur Psychiatry 2008;23:289299.CrossRefGoogle ScholarPubMed
State, M.W.Sestan, N.Neuroscience. The emerging biology of autism spectrum disorders. Science 2012;337:13011303.CrossRefGoogle ScholarPubMed
Thomas, R.H.Meeking, M.M.Mepham, J.R.Tichenoff, L.Possmayer, F.Liu, S.et al.The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders. J Neuroinflammation 2012;9:153.CrossRefGoogle ScholarPubMed
Vargas, D.L.Nascimbene, C.Krishnan, C.Zimmerman, A.W.Pardo, C.A.Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005;57:6781.CrossRefGoogle ScholarPubMed
Wass, S.Distortions and disconnections: disrupted brain connectivity in autism. Brain Cogn 2011;75:1828.CrossRefGoogle ScholarPubMed
Weintraub, K.The prevalence puzzle: autism counts. Nature 2011;479:2224.CrossRefGoogle ScholarPubMed
Williams, E.L.Casanova, M.F.Above genetics: lessons from cerebral development in autism. Transl Neurosci 2011;2:106120.CrossRefGoogle ScholarPubMed
Wu, S.Jia, M.Ruan, Y.Liu, J.Guo, Y.Shuang, M.et al.Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol Psychiatry 2005;58:7477.CrossRefGoogle ScholarPubMed
Xu, J.Y.Xia, Q.Q.Xia, J.A review on the current neuroligin mouse models. Sheng Li Xue Bao 2012;64:550562.Google ScholarPubMed
Yamasue, H.Yee, J.R.Hurlemann, R.Rilling, J.K.Chen, F.S.Meyer-Lindenberg, A.et al.Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction. J Neurosci 2012;32:1410914117.CrossRefGoogle ScholarPubMed
Yap, I.K.Angley, M.Veselkov, K.A.Holmes, E.Lindon, J.C.Nicholson, J.K.Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls. J Proteome Res 2010;9:29963004.CrossRefGoogle ScholarPubMed
Young, L.J.Nilsen, R.Waymire, K.G.MacGregor, G.R.Insel, T.R.Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole. Nature 1999;400:766768.CrossRefGoogle ScholarPubMed
Zimmerman, A.W.Jyonouchi, H.Comi, A.M.Connors, S.L.Milstien, S.Varsou, A.et al.Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr Neurol 2005;33:195201.CrossRefGoogle ScholarPubMed
Zoroglu, S.S.Armutcu, F.Ozen, S.Gurel, A.Sivasli, E.Yetkin, O.et al.Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur Arch Psychiatry Clin Neurosci 2004;254:143147.CrossRefGoogle ScholarPubMed
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