Consensus paper: Pathological role of the cerebellum in Autism

Cerebellum

Volumn 11, Issue 3, 2012, Pages 777-807

  Fatemi, S Hossein ^a   Aldinger, Kimberly A ^b   Ashwood, Paul ^c   Bauman, Margaret L ^d,e   Blaha, Charles D ^f   Blatt, Gene J ^g   Chauhan, Abha ^h   Chauhan, Ved ^h   Dager, Stephen R ⁱ   Dickson, Price E ^f   Estes, Annette M ⁱ   Goldowitz, Dan ^j   Heck, Detlef H ^k   Kemper, Thomas L ^g   King, Bryan H ^l   Martin, Loren A ^m   Millen, Kathleen J ^l   Mittleman, Guy ^f   Mosconi, Matthew W ⁿ   Persico, Antonio M ^o   Sweeney, John A ⁿ   Webb, Sara J ^m   Welsh, John P ^l   more..

^a UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e MASSACHUSETTS GENERAL HOSPITAL   (United States)

^f University of Memphis   (United States)

^g BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^h NEW YORK STATE INSTITUTE FOR BASIC RESEARCH IN DEVELOPMENTAL DISABILITIES   (United States)

ⁱ UNIVERSITY OF WASHINGTON   (United States)

^j UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^k UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^l UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^m AZUSA PACIFIC UNIVERSITY   (United States)

ⁿ UNIVERSITY OF TEXAS AT DALLAS   (United States)

^o UNIVERSITY CAMPUS BIO MEDICO   (Italy)

more..

Author keywords

Autism; Cerebellum

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID B RECEPTOR STIMULATING AGENT; ACETYLCHOLINE; ANTICONVULSIVE AGENT; ARBACLOFEN; BENZODIAZEPINE; DOPAMINE; FLUOXETINE; GLUTAMIC ACID; ORGANOPHOSPHATE PESTICIDE; OXYTOCIN; POLYCHLORINATED BIPHENYL; REELIN; SCATTER FACTOR RECEPTOR; SEROTONIN; SEROTONIN AGONIST; SEROTONIN UPTAKE INHIBITOR;

ATP2B2 GENE; AUTISM; BRAIN DISEASE; BRAIN FUNCTION; BRAIN MALFORMATION; CENTRAL NERVOUS SYSTEM; CEREBELLUM; CEREBELLUM DISEASE; CEREBELLUM HYPOPLASIA; CHOLINERGIC ACTIVITY; CLINICAL FEATURE; COGNITION; COGNITIVE DEFECT; DISEASE ACTIVITY; DISEASE ASSOCIATION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DOPAMINERGIC ACTIVITY; DRUG TARGETING; EXPERIMENTAL MODEL; GABAERGIC SYSTEM; GENE; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENOTYPE ENVIRONMENT INTERACTION; GLUTAMATERGIC SYSTEM; HUMAN; IMAGE ANALYSIS; IMMUNE DEFICIENCY; IMMUNE RESPONSE; MOTOR CONTROL; MOTOR COORDINATION; MOTOR DYSFUNCTION; NERVOUS SYSTEM INFLAMMATION; NEUROIMAGING; NEUROTRANSMISSION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OXIDATIVE STRESS; PATHOGENESIS; PON1 GENE; PRIORITY JOURNAL; PROTEIN FUNCTION; RELN GENE; REVIEW; SCL25A12 GENE; SEROTONINERGIC TRANSMISSION;

ANIMALS; AUTISTIC DISORDER; CELL ADHESION MOLECULES, NEURONAL; CEREBELLAR DISEASES; CEREBELLUM; COGNITION DISORDERS; DISEASE MODELS, ANIMAL; EXTRACELLULAR MATRIX PROTEINS; GAMMA-AMINOBUTYRIC ACID; GENE-ENVIRONMENT INTERACTION; GLUTAMIC ACID; HUMANS; MAGNETIC RESONANCE IMAGING; MITOCHONDRIA; MOVEMENT DISORDERS; NERVE TISSUE PROTEINS; NEUROTRANSMITTER AGENTS; OXIDATIVE STRESS; SERINE ENDOPEPTIDASES;

EID: 84864666011     PISSN: 14734222     EISSN: 14734230     Source Type: Journal    
DOI: 10.1007/s12311-012-0355-9     Document Type: Review

References (311)

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed (DSM-4). Washington, DC: APA; 1994.
2. Wassink TH, Brzustowicz LM, Bartlett CW, Szatmari P. The search for autism disease genes. Ment Retard Dev Disabil Res Rev. 2004;10:272-83.
3. Bauman ML, Kemper T.L. Histoanatomic observations of the brain in early infantile autism. Neurology. 1985;35:866-74.
4. ArinDM, BaumanML, Kemper T.L. The distribution of Purkinje cell loss in the cerebellum in autism. Neurology. 1991;41(Suppl):307.
5. Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, et al. A clinicopathological study of autism. Brain. 1998;121: 889-905.
6. Whitney ER, Kemper TL, Bauman ML, Rosene DL, Blatt G.J. Cerebellar Purkinje cells are reduced in a subpopulation of autistic brains: a stereological experiment using calbindin-D28k. Cerebellum. 2008;7(3):406-16.
7. Bauman ML, Kemper TL, editors. The neurobiology of autism. Baltimore: Johns Hopkins University Press; 2005.
8. Courchesne E, Saitoh O, Yeung-Courchesne R, Press GA, Lincoln AJ, et al. Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: identification of hypoplastic and hyperplastic subgroups by MR imaging. AJR. 1994;162: 123-30.
9. Whitney ER, Kemper TL, Rosene DL, Bauman ML, Blatt G.J. Density of cerebellar basket and stellate cells in autism: Evidence for a late developmental loss of Purkinje cells. J Neurosci Res. 2009;87:2245-54.
10. Holmes G, Stewart T.G. On the connection of the inferior olives with the cerebellum in man. Brain. 1908;31:125-37.
11. Greenfield JG, Greenfield J.G. The spino-cerebellar degenerations. Springfield: CC Thomas; 1954.
12. DeBassio WA, Kemper TL, Knoefel J.E. Coffin-Siris syndrome: neuropathological findings. Arch Neurol. 1985;42:350-3.
13. Kemper T.L. The developmental neuropathology of autism. In: Blatt G, editor. The neurochemical basis of autism. New York: Springer; 2010. p. 69-82.
14. Kemper TL, Bauman M.L. Neuropathology of infantile autism. J Neuropath Exp Neurol. 1998;57:645-52.
15. Hazlett HC, Poe M, Gerig G, Smith RG, Provenzale J, Ross A, et al. Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years. Arch Gen Psychiatry. 2005;62:11366-76.
16. Lainhart JE, Bigler ED, Bocian M, Coon H, Dinh E, Dawson G, et al. Head circumference and height in autism: a study by the collaborative program of excellence in autism. Am J Med Genet A. 2006;140:2257-74.
17. Hardan AY, Libove RA, Keshavan MS, Melhem NM, Minshew N.J. A preliminary longitudinal magnetic resonance imaging study of brain volume and cortical thickness in autism. Biol Psychiatry. 2009;66:313-5.
18. Schmahmann J. The cerebellum and cognition. International review of neurobiology, vol. 41. San Diego: Academic; 1997.
19. Schmahmann JD, Rosene DL, Pandya D.N. Motor projections to the basis pontis in rhesus monkey. J Comp Neurol. 2004;478: 248-68.
20. Fournier KA, Hass CJ, Naik SK, Lodha N, Cauraugh J.H.. Motor coordination in autism spectrum disorders: a synthesis and metaanalysis. J Autism Dev Disord. 2010;40(10):1227-40.
21. Minshew NJ, Sung K, Jones B, Furman J.M. Underdevelopment of the postural control system in autism. Neurology. 2004;63(11): 2056-61.
22. Ozonoff S, Young GS, Goldring S, Greiss-Hess L, Herrera AM, Steele J, et al. Gross motor development, movement abnormalities, and early identification of autism. J Autism Dev Disord. 2008; 38:644-56.
23. Brettler SC, Fuchs AF, Ling L. Discharge patterns of cerebellar output neurons in the caudal fastigial nucleus during head-free gaze shifts in primates. Ann NY Acad Sci. 2003;1004:61-8.
24. Takarae Y, Minshew NJ, Luna B, Sweeney J.A. Oculomotor abnormalities parallel cerebellar histopathology in autism. J Neurol Neurosurg Psychiatry. 2004;75(9):1359-61.
25. Nowinski CV, Minshew NJ, Luna B, Takarae Y, Sweeney J.A. Oculomotor studies of cerebellar function in autism. Psychiatry Res. 2005;137(1-2):11-9.
26. Strick P, Dum R, Fiez J. Cerebellum and nonmotor function. Ann Rev Neurosci. 2009;32(1):413-34.
27. Ackermann H, Wildgruber D, Daum I, Grodd W. Does the cerebellum contribute to cognitive aspects of speech production? A functional magnetic resonance imaging (fMRI) study in humans. Neurosci Lett. 1998;247(2-3):187-90.
28. Tager-Flusberg H, Caronna E. Language disorders: autism and other pervasive developmental disorders. Pediatr Clin North Am. 2007;54(3):469-81.
29. Shriberg L, Paul R, Black L, van Santen J. The hypothesis of apraxia of speech in children with autism spectrum disorder. J Autism Dev Disord. 2011;41(4):405-26.
30. Steinlin M. The cerebellum in cognitive processes: supporting studies in children. Cerebellum. 2007;6:237-41.
31. Schmahmann JD, Sherman J.C. The cerebellar cognitive affective syndrome. Brain. 1998;121(4):561-79.
32. Scott JA, Schumann CM, Goodlin-Jones BL, Amaral D.G. A comprehensive volumetric analysis of the cerebellum in children and adolescents with autism spectrum disorder. Autism Res. 2009;2(5):246-57.
33. Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Guthrie D, et al. Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC autopsy research project. Am J Psychiatry. 1986;143(7): 862-6.
34. Courchesne E, Saitoh O, Townsend J, Yeung-Courchesne R, Press G, Lincoln A, et al. Cerebellar hypoplasia and hyperplasia in infantile autism. Lancet. 1994;343:63-4.
35. Ciesielski KT, Harris RJ, Hart BL, Pabst HF. Cerebellar hypoplasia and frontal lobe cognitive deficits in disorders of early childhood. Neuropsychologia. 1997;35(5):643-55.
36. Webb SJ, Sparks BF, Friedman SD, Shaw DW, Giedd J, Dawson G, et al. Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder. Psychiatry Res. 2009;172 (1):61-7.
37. Welsh JP, Yuen G, Placantonakis DG, Vu TQ, Haiss F, O'Hearn E, et al. Why do Purkinje cells die so easily after global brain ischemia? Aldolase C, EAAT4, and the cerebellar contribution to post-hypoxic myoclonus. Adv Neurol. 2002;89:331-59.
38. Sarna JR, Hawkes R. Patterned Purkinje cell death in the cerebellum. Prog Neurobiol. 2003;70:473-507.
39. Welsh JP, Llinas R. Some organizing principles for the control of movement based on olivocerebellar physiology. Prog Brain Res. 1997;114:449-61.
40. Hawkes R, Colonnier M, Leclerc N. Monoclonal antibodies reveal sagittal banding in the rodent cerebellar cortex. Brain Res. 1985;333(2):359-65.
41. Hawkes R, Gravel C. The modular cerebellum. Prog Neurobiol. 1991;36(4):309-27.
42. Williams BL, Yaddanapudi K, Hornig M, Lipkin WI. Spatiotemporal analysis of Purkinje cell degeneration relative to parasagittal expression domains in a model of neonatal viral infection. J Virol. 2007;81:2675-87.
43. O'Hearn E, Molliver ME. The olivocerebellar projection mediates ibogaine-induced degeneration of Purkinje cells: a model of indirect, trans-synaptic excitotoxicity. J Neurosci. 1997;17:8828-41.
44. Llinas R, Lang EJ, Welsh JP. The cerebellum, LTD, and memory: alternative views. Learn Mem. 1997;3:445-55.
45. Dager SR, Corrigan NM, Richards TL, Posse S. Research applications of magnetic resonance spectroscopy (MRS) to investigate psychiatric disorders. Top Magn Reson Imaging. 2008;19(2):81-96.
46. Dager SR, Corrigan NM, Richards TL, Shaw DWW. Brain cy: magnetic resonance spectroscopy. In: Amaral D, Dawson G, Geshwind D, editors. Autism spectrum disorders. England: Oxford University Press; 2011.
47. Welsh JP, Han VZ, Rossi D, Mohr C, Odagari M, Daunais J, et al. Bidirectional plasticity in the primate inferior olive induced by chronic ethanol intoxication and sustained abstinence. Proc Natl Acad Sci USA. 2011;108:10314-9.
48. Welsh JP, Lang EJ, Sugihara I, Llinas R. Dynamic organization of motor control within the olivocerebellar system. Nature. 1995; 374:453-7.
49. Oristaglio J, Ghaffari M, Hyman West S, Welsh JP, Malone R. A sensory timing abnormality in autism revealed by classical eyeblink conditioning. Soc Neurosci Abstr. 2012; (in press)
50. Gerwig M, Esser AC, Guberina H, Frings M, Kolb FP, Forsting M, et al. Trace eyeblink conditioning in patients with cerebellar degeneration: comparison of short and long trace intervals. Exp Brain Res. 2008;187:85-96.
51. Welsh JP, Ahn ES, Placantonakis DG. Is autism due to brain desynchronization? Int J Dev Neurosci. 2005;23:253-63.
52. Miles JH. Autism spectrum disorders-a genetics review. Genet Med. 2011;13(4):278-94.
53. Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet. 2008;9 (5):341-55.
54. Banerjee-Basu S, Packer A. SFARI Gene: an evolving database for the autism research community. Dis Model Mech. 2010;3 (3-4):133-5.
55. Schaaf CP, Zoghbi HY. Solving the autism puzzle a few pieces at a time. Neuron. 2011;70(5):806-8.
56. Bill BR, Geschwind DH. Genetic advances in autism: heterogeneity and convergence on shared pathways. Curr Opin Genet Dev. 2009;19(3):271-8.
57. Geschwind DH. Autism: many genes, common pathways? Cell. 2008;135(3):391-5.
58. Geschwind DH, Levitt P. Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol. 2007;17 (1):103-11.
59. Kaufmann WE, Cooper KL, Mostofsky SH, Capone GT, Kates WR, Newschaffer CJ, et al. Specificity of cerebellar vermian abnormalities in autism: a quantitative magnetic resonance imaging study. J Child Neurol. 2003;18(7):463-70.
60. Eluvathingal TJ, Behen ME, Chugani HT, Janisse J, Bernardi B, Chakraborty P, et al. Cerebellar lesions in tuberous sclerosis complex: neurobehavioral and neuroimaging correlates. J Child Neurol. 2006;21(10):846-51.
61. Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, et al. Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet. 2007;81(6):1289-97.
62. Philippe A, Boddaert N, Vaivre-Douret L, Robel L, Danon- Boileau L, Malan V, et al. Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood. Pediatrics. 2008;122(2):e376-82.
63. Johnson MB, Kawasawa YI, Mason CE, Krsnik Z, Coppola G, Bogdanovic D, et al. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron. 2009;62(4):494-509.
64. Alvarez Retuerto AI, Cantor RM, Gleeson JG, Ustaszewska A, Schackwitz WS, Pennacchio LA, et al. Association of common variants in the Joubert syndrome gene (AHI1) with autism. Hum Mol Genet. 2008;17(24):3887-96.
65. Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, et al. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature. 2011;474(7351):380-4.
66. Descipio C, Schneider L, Young TL,Wasserman N, Yaeger D, Lu F, et al. Subtelomeric deletions of chromosome 6p: molecular and cytogenetic characterization of three new cases with phenotypic overlap with Ritscher-Schinzel (3 C) syndrome. Am J Med Genet A. 2005;134A(1):3-11.
67. Miles JH, Hillman RE. Value of a clinical morphology examination in autism. Am J Med Genet. 2000;91(4):245-53.
68. Cheh MA, Millonig JH, Roselli LM, Ming X, Jacobsen E, Kamdar S, et al. En2 knockout mice display neurobehavioral and neurochemical alterations relevant to autism spectrum disorder. Brain Res. 2006;1116(1):166-76.
69. Ieraci A, Forni PE, Ponzetto C. Viable hypomorphic signaling mutant of the Met receptor reveals a role for hepatocyte growth factor in postnatal cerebellar development. Proc Natl Acad Sci U S A. 2002;99(23):15200-5.
70. Fatemi SH, Reutiman TJ, Folsom TD, Thuras PD. GABA(A) receptor downregulation in brains of subjects with autism. J Autism Dev Disord. 2009;39(2):223-30.
71. DeLorey TM, Sahbaie P, Hashemi E, Homanics GE, Clark JD. Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: a potential model of autism spectrum disorder. Behav Brain Res. 2008;187(2):207-20.
72. Careaga M, Van de Water J, Ashwood P. Immune dysfunction in autism: a pathway to treatment. Neurotherapeutics. 2010;7(3): 283-92.
73. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57(1):67-81.
74. ChezMG, Dowling T, Patel PB, Khanna P, Kominsky M. Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol. 2007;36(6):361-5.
75. Li X, Chauhan A, Sheikh AM, Patil S, Chauhan V, Li XM, et al. Elevated immune response in the brain of autistic patients. J Neuroimmunol. 2009;207:111-6.
76. Wei H, Zou H, Sheikh AM, Malik M, Dobkin C, Brown WT, et al. IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J Neuroinflammation. 2011;8:52.
77. Garbett K, Ebert PJ, Mitchell A, Lintas C, Manzi B, Mirnics K, et al. Immune transcriptome alterations in the temporal cortex of subjects with autism. Neurobiol Dis. 2008;30:303-11.
78. Cabanlit M, Wills S, Goines P, Ashwood P, Van de Water J. Brain-specific autoantibodies in the plasma of subjects with autistic spectrum disorder. Ann NYAcad Sci. 2007;1107:92-103.
79. Goines P, Haapanen L, Boyce R, Duncanson P, Braunschweig D, Delwiche L, et al. Autoantibodies to cerebellum in children with autism associate with behavior. Brain Behav Immun. 2011; 25:514-23.
80. Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral DG, Van de Water J. Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders. Brain Behav Immun. 2009;23(1):64-74.
81. Wills S, Rossi CC, Bennett J, Cerdeño VM, Ashwood P, Amaral DG, et al. Further characterization of autoantibodies to GABAergic neurons in the central nervous system produced by a subset of children with autism. Mol Autism. 2011;2:5.
82. 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;25:40-5.
83. Ashwood P, Anthony A, Torrente F, Wakefield AJ. Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune activation and reduced counter regulatory interleukin-10. J Clin Immunol. 2004;24:664-73.
84. Ashwood P, Wakefield AJ. Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J Neuroimmunol. 2006;173:126-34.
85. Heuer L, Ashwood P, Goines P, Krakowiak P, Hertz-Picciotto I, Hansen R, et al. Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms. Autism Research. 2008;1:275-83.
86. Enstrom A, Krakowiak P, Onore C, Pessah IN, Hertz-Picciotto I, Hansen RL, et al. Increased IgG4 levels in children with autism disorder. Brain Behav Immun. 2009;23:389-95.
87. Corbett BA, Kantor AB, Schulman H,WalkerWL, Lit L, Ashwood P, et al. A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins. Mol Psychiatry. 2007;12:292-306.
88. Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. J Neuroimmunol. 2011;232(1-2):196-201.
89. Enstrom AM, Lit L, Onore CE, Gregg JP, Hansen R, Pessah IN, et al. Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain Behav Immun. 2009;23:124-33.
90. Ashwood P, Schauer J, Pessah IN, Van de Water J. Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders. J Neuroimmunol. 2009;208:149-53.
91. Enstrom AM, Onore CE, Van de Water JA, Ashwood P. Differential monocyte responses to TLR ligands in children with autism spectrum disorders. Brain Behav Immun. 2010; 24:64-71.
92. Ashwood P, Corbett BA, 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.
93. Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J. Altered T cell responses in children with autism. Brain Behav Immun. 2011;25(5):840-9.
94. Ashwood P, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen RL, Croen LA, et al. Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes. J Neuroimmunol. 2008;204:149-53.
95. Onore C, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen R, Van de Water J, et al. Decreased cellular IL-23 but not IL-17 production in children with autism spectrum disorders. J Neuroimmunol. 2009;216:126-34.
96. Chauhan A, Chauhan V, Brown WT, editors. Autism: oxidative stress, inflammation and immune abnormalities. Boca Raton: CRC Press; 2009.
97. Deth R, Muratore C, Benzecry J, Power-Charnitsky VA, Waly M. How environmental and genetic factors combine to cause autism: a redox/methylation hypothesis. Neurotoxicology. 2008;29:190-201.
98. Chauhan A, Chauhan V. Oxidative stress in autism. Pathophysiology. 2006;13:171-81.
99. Kern JK, Jones AM. Evidence of toxicity, oxidative stress, and neuronal insult in autism. J Toxicol Environ Health B Crit Rev. 2006;9:485-99.
100. Wells PG, McCallum GP, Chen CS, Henderson JT, Lee CJ, Perstin J, et al. Oxidative stress in developmental origins of disease: teratogenesis, neurodevelopmental deficits, and cancer. Toxicol Sci. 2009;108:4-18.
101. Kinney DK, Munir KM, Crowley DJ, Miller AM. Prenatal stress and risk for autism. Neurosci Biobehav Rev. 2008;32:1519-32.
102. Kolevzon A, Gross R, Reichenberg A. Prenatal and perinatal risk factors for autism: a review and integration of findings. Arch Pediatr Adolesc Med. 2007;161:326-33.
103. Chauhan A, Gu F, Essa MM, Wegiel J, Kaur K, Brown WT, et al. Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism. J Neurochem. 2011; 117:209-20.
104. Muthaiyah B, Essa MM, Chauhan V, Brown WT, Wegiel J, Chauhan A. Increased lipid peroxidation in cerebellum and temporal cortex of brain in autism. J Neurochem. 2009;108 Suppl 1:73.
105. Chauhan A, Audhya T, Chauhan V. Increased DNA oxidation in the cerebellum, frontal and temporal cortex of brain in autism. Transactions of the American Society for Neurochemistry. Windermere: American Society for Neurochemistry; 2011. p. 81.
106. Sajdel-Sulkowska EM, Xu M, Koibuchi N. Increase in cerebellar neurotrophin-3 and oxidative stress markers in autism. Cerebellum. 2009;8:366-72.
107. Chauhan A, Essa MM, Muthaiyah B, Brown WT,Wegiel J, Chauhan V. Increased protein oxidation in cerebellum, frontal and temporal cortex in autism. International Meeting for Autism Research (Abstract), May 2010.
108. Sajdel-Sulkowska EM, Lipinski B, Windom H, Audhya T, McGinnis W. Oxidative stress in autism: elevated cerebellar 3- nitrotyrosine levels. Am J Biochem Biotech. 2008;4:73-84.
109. Evans TA, Siedlak SL, Lu L, Fu X, Wang Z, McGinnis WR, et al. The autistic phenotype exhibits a remarkably localized modification of brain protein by products of free radical-induced lipid oxidation. Am J Biochem Biotech. 2008;4:61-72.
110. López-Hurtado E, Prieto JJ. A microscopic study of languagerelated cortex in autism. Am J Biochem Biotech. 2008;4:130-45.
111. Chauhan A, Audhya T, Chauhan V. Brain region-specific glutathione redox imbalance and increased DNA oxidation in autism. J Neurochem. 2011;118(suppl 1):217.
112. Ji L, Chauhan A, Brown WT, Chauhan V. Increased activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase in the frontal cortex and cerebellum of autistic individuals. Life Sci. 2009;85:788-93.
113. Lenaz G. The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. IUBMB Life. 2001;52:159-64.
114. Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry. 2011; (in press), doi:10.1038/mp.2010.136.
115. Courchesne E. New evidence of cerebellar and brainstem hypoplasia in autistic infants, children and adolescents: the MR imaging study by Hashimoto and colleagues. J Autism Dev Disord. 1995;25:19-22.
116. Zilbovicius M, Boddaert N, Belin P, Poline JB, Remy P, Mangin JF, et al. Temporal lobe dysfunction in childhood autism: a PET study. Positron emission tomography. Am J Psychiatry. 2000;157: 1988-93.
117. Schmitz C, Rezaie P. The neuropathology of autism: where do we stand? Neuropathol Appl Neurobiol. 2008;34:4-11.
118. Bauman ML, Kemper T.L. Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci. 2005;23:183-7.
119. Casanova MF. The neuropathology of autism. Brain Pathol. 2007; 17:422-33.
120. Palmen SJ, van Engeland H, Hof PR, Schmitz C. Neuropathological findings in autism. Brain. 2004;127:2572-83.
121. Wegiel J, Wisniewski T, Chauhan A, Chauhan V, Kuchna I, Nowicki K, et al. Type, topology, and sequelae of neuropathological changes shaping clinical phenotype of autism. In: Chauhan A, Chauhan V, Brown WT, editors. Autism: oxidative stress, inflammation and immune abnormalities. Boca Raton: CRC Press; 2009. p. 1-34.
122. Fatemi SH, Halt AR, Stary JM, Kanodia R, Schulz SC, Realmuto GR. Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biol Psychiatry. 2002;52(8):805-10.
123. Fatemi SH, Folsom TD. Dysregulation of fragile X mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of individuals with autism: a postmortem brain study. Mol Autism. 2011;2:6.
124. Fatemi SH, Folsom TD, Reutiman TJ, Thuras PD. Expression of GABA(B) receptors is altered in brains of subjects with autism. Cerebellum. 2009;8:64-9.
125. Yip J, Soghomonian JJ, Blatt G.J. Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications. Acta Neuropathol. 2007;113(5):559-68.
126. Fatemi SH, Stary JM, Halt AR, Realmuto GR. Dysregulation of Reelin and Bcl-2 proteins in autistic cerebellum. J Autism Dev Disord. 2001;31:529-35.
127. Yip J, Soghomonian JJ, Blatt G.J. Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: an in situ hybridization study. Autism Res. 2009;2(1):50-9.
128. Fatemi SH, Folsom TD, Kneeland RE, Liesch SB. Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both Fragile X mental retardation protein and GABA A receptor beta 3 in adults with Autism. Anat Rec. 2011;294(10):1635-45.
129. Blatt GJ, Fitzgerald CM, Guptill JT, Booker AB, Kemper TL, Bauman M.L. Density and distribution of hippocampal neurotransmitter receptors in autism: an autoradiographic study. J Autism Dev Disord. 2001;31(6):537-43.
130. Fatemi SH, Reutiman TJ, Folsom TD, Rooney PJ, Patel DH, Thuras PD. mRNA and protein levels for GABAAalpha4, alpha5, beta1, and GABABR1 receptors are altered in brains from subjects with autism. J Autism Dev Disord. 2010;40:743-50.
131. Oblak AL, Gibbs TT, Blatt G.J. Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism. Autism Res. 2009;2(4):205-19.
132. Oblak AL, Gibbs TT, Blatt G.J. Decreased GABA(B) receptors in the cingulate cortex and fusiform gyrus in autism. J Neurochem. 2010;114(5):1414-23.
133. Pesold C, Pisu MG, Impagnatiello F, Uzunov DP, Caruncho HJ. Reelin is preferentially expressed in neurons synthesizing gamma-aminobutyric acid in cortex and hippocampus of adult rats. Proc Natl Acad Sci. 1998;95:3221-6.
134. Sinagra M, Gonzalez Campo C, Verrier D, Moustié O, Manzoni OJ, Chavis P. Glutamatergic cerebellar granule neurons synthesize and secrete reelin in vitro. Neuron Glia Biol. 2008;4:189-96.
135. Quattrocchi CC,Wannenes F, Persico AM, Ciafré SA, D'Arcangelo G, Farace MG, et al. Reelin is a serine protease of the extracellular matrix. J Biol Chem. 2002;277:303-9.
136. Weeber EJ, Beffert U, Jones C, Christian JM, Forster E, Sweatt JD, et al. Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning. J Biol Chem. 2002;277:39944-52.
137. Forster E, Tielsch A, Saum B,Weiss KH, Johanssen C, Graus-Porta D, et al. Reelin, Disabled 1, and beta 1 integrins are required for the formation of the radial glial scaffold in the hippocampus. Proc Natl Acad Sci. 2002;99:13178-83.
138. Nullmeier S, Panther P, Dobrowolny H, Frotscher M, Zhao S, Schwegler H, et al. Region-specific alteration of GABAergic markers in the brain of heterozygous reeler mice. Eur J Neurosci. 2011;33:689-98.
139. Cremer CM, Lubke JH, Palomero-Gallagher N, Zilles K. Laminar distribution of neurotransmitter receptors in different reeler mouse brain regions. Brain Struct Funct. 2011;216:201-18.
140. Kelemenova S, Schmidtova E, Ficek A, Celec P, Kubranska A, Ostatnikova D. Polymorphisms of candidate genes in Slovak autistic patients. Psychiatr Genet. 2010;20:137-9.
141. Persico AM, D'Agruma L, Maiorano N, Totaro A, Militerni R, Bravaccio C, et al. Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry. 2001;6:150-9.
142. Fatemi SH, Snow AV, Stary JM, Araghi-Niknam M, Reutiman TJ, Lee S, et al. Reelin signaling is impaired in autism. Biol Psychiatry. 2005;57(7):777-87.
143. Fatemi SH, Stary JM, Egan EA. Reduced blood levels of reelin as a vulnerability factor in pathophysiology of autistic disorder. Cell Mol Neurobiol. 2002;22:139-52.
144. D'Arcangelo G, Homayouni R, Keshvara L, Rice DS, Sheldon M, Curran T. Reelin is a ligand for lipoprotein receptors. Neuron. 1999;24:471-9.
145. Hiesberger T, Trommsdorff M, Howell BW, Goffinet A, Mumby MC, Cooper JA, et al. Direct binding of Reelin to VLDL receptor andApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation. Neuron. 1999;24:481-9.
146. Dulabon L, Olson EC, Taglienti MG, Eisenhuth S, McGrath B, Walsh CA, et al. Reelin binds alpha3beta1 integrin and inhibits neuronal migration. Neuron. 2000;27:33-44.
147. Strasser V, Fasching D, Hauser C, Mayer H, Bock HH, Hiesberger T, et al. Receptor clustering is involved in Reelin signaling. Mol Cell Biol. 2004;24:1378-86.
148. Mattson MP. Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann N Y Acad Sci. 2008;1144:97-112.
149. Hoehn-Saric R, McLeod DR, Glowa JR. The effects NMDA receptor blockade on the acquisition of a conditioned emotional response. Biol Psychiatry. 1991;30:170-6.
150. Lisman J. Long-term potentiation: outstanding questions and attempted synthesis. Philos Trans R Soc Lond B Biol Sci. 2003;358:829-42.
151. Silverman JM, Buxbaum JD, Ramoz N, Schmeidler J, Reichenberg A, Hollander E, et al. Autism-related routines and rituals associated with a mitochondrial aspartate/glutamate carrier SLC25A12 polymorphism. Am J Med Genet B Neuropsychiatr Genet. 2008;147:408-10.
152. Strutz-Seebohm N, Korniychuk G, Schwarz R, Baltaev R, Ureche ON, Mack AF, et al. Functional significance of the kainate receptor GluR6(M836I) mutation that is linked to autism. Cell Physiol Biochem. 2006;18:287-94.
153. Kim SA, Kim JH, Park M, Cho IH, Yoo HJ. Family-based association study between GRIK2 polymorphisms and autism spectrum disorders in Korean trios. Neurosci Res. 2007;58:332-5.
154. Purcell AE, Jeon OH, Zimmerman AW, Blue ME, Pevsner J. Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology. 2001;57:1618-28.
155. Lepagnol-Bestel AM, Maussion G, Boda B, Cardona A, Iwayama Y, Delezoide AL, et al. SLC25A12 expression is associated with neurite outgrowth and is upregulated in the prefrontal cortex of autistic subjects. Mol Psychiatry. 2008;13:385-97.
156. Demark JL, Feldman MA, Holden J.J. Behavioral relationship between autism and fragile X syndrome. Am J Ment Retard. 2003;108:314-26.
157. De Rubeis S, Bagni C. Fragile X mental retardation protein control of neuronal mRNA metabolism: insights into mRNA stability. Mol Cell Neurosci. 2010;43:43-50.
158. Bassell GJ, Warren ST. Fragile X Syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron. 2008;60:201-14.
159. Muddashetty RS, Kelić S, Gross C,XuM, BassellGJ.Dysregulated metabotropic glutamate receptor-dependent translation of AMPA receptor and postsynaptic density-95 mRNAs at synapses in a mouse model of fragile x syndrome. J Neurosci. 2007;27:5338-48.
160. Bear MF, Huber KM, Warren ST. The mGluR theory of fragile X mental retardation. Trends Neurosci. 2004;27:370-7.
161. Hashimoto H, Fukui K, Noto T, Nakajima T, Kato N. Distribution of vasopressin and oxytocin in rat brain. Endocrinol Jpn. 1985;32 (1):89-97.
162. Kirsch P, Meyer-Lindenberg A. Oxytocin and autism. In: Blatt Gene J, editor. The neurochemical basis of autism: from molecules to minicolumns. New York: Springer; 2010. p. 163-73.
163. Ferguson JN, Aldag JM, Insel TR, Young LJ. Oxytocin in the medial amygdala is essential for social recognition in the mouse. J Neurosci. 2001;21:8278-85.
164. McCarthy MM, McDonald CH, Brooks PJ, Goldman D. An anxiolytic action of oxytocin is enhanced by estrogen in the mouse. Physiol Behav. 1996;60:1209-15.
165. Insel TR, Young LJ. The neurobiology of attachment. Nat Rev Neurosci. 2001;2:129-36.
166. Winslow JT, Insel TR. Neuroendocrine basis of social recognition. Curr Opin Neurobiol. 2004;14:248-53.
167. Liu W, Pappas GD, Carter CS. Oxytocin receptors in brain cortical regions are reduced in the haploinsufficient (+/-) reeler mice. Neurol Res. 2005;27(4):339-45.
168. Baskerville TA, Douglas AJ. Dopamine and oxytocin interactions underlying behaviors: potential contributions to behavioral disorders. CNS Neurosci Ther. 2010;16(3):e92-e123.
169. Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR, et al. Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger's disorders. Neuropsychopharm. 2003;28:193-8.
170. Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L, et al. Oxytocin increases retention of social cognition in autism. Biol Psychiatry. 2007;61:498-503.
171. Bartz JA, Hollander E. Oxytocin and experimental therapeutics in autism spectrum disorders. Prog Brain Res. 2008;170: 451-62.
172. Lee M, Martin-Ruiz C, Graham A, Court J, Jaros E, Perry R, et al. Nicotinic receptor abnormalities in the cerebellar cortex in autism. Brain. 2002;125(Pt 7):1483-95.
173. Martin-Ruiz CM, Lee M, Perry RH, Baumann M, Court JA, Perry EK. Molecular analysis of nicotinic receptor expression in autism. Brain Res Mol Brain Res. 2004;123(1-2):81-90.
174. Deutsch SI, Urbano MR, Neumann SA, Burket JA, Katz E. Cholinergic abnormalities in autism: is there a rationale for selective nicotinic agonist interventions? Clin Neuropharmacol. 2010;33(3):114-20.
175. Lippiello PM. Nicotinic cholinergic antagonists: a novel approach for the treatment of autism. Med Hypotheses. 2006;66(5):985-90.
176. Blatt GJ, VanSluytman G, Marcon RG. Decreased density of 3[H]
177. Armstrong DD, Assman S, Kinney HC. Early developmental changes in the chemoarchitecture of the human inferior olive: a review. J Neuropathol Exp Neurol. 1999;58:1-11.
178. Kolasiewicz W, Kuter K, Nowak P, Pastuszka A, Ossowska K. Lesion of the cerebellar noradrenergic innervation enhances the harmaline-induced tremor in rats. Cerebellum. 2011;10 (2):267-80.
179. Rogers TD, Dickson PE, Heck DH, Goldowitz D, Mittleman G, Blaha CD. Connecting the dots of the cerebro-cerebellar role in cognitive function: neuronal pathways for cerebellar modulation of dopamine release in the prefrontal cortex. Synapse. 2011;65 (11):1204-12.
180. Mittleman G, Goldowitz D, Heck DH, Blaha CD. Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia. Synapse. 2008;62(7): 544-50.
181. Crandall JE, McCarthy DM, Araki KY, Sims JR, Ren J-Q, Bhide PG. Dopamine receptor activation modulates GABA neuron migration from the basal forebrain to the cerebral cortex. J Neurosci. 2007;27(14):3813-22.
182. Nakamura K, Sekine Y, Ouchi Y, Tsujii M, Yoshikawa E, Futatsubashi M, et al. Brain serotonin and dopamine transporter bindings in adults with high-functioning autism. Arch Gen Psychiatry. 2010;67(1):58-68.
183. Buitelaar JK, Willemsen-Swinkels SH. Medication treatment in subjects with autistic spectrum disorders. Eur Child Adolesc Psychiatry. 2000;9(1):185-97.
184. Kish SJ, Furukawa Y, Chang L-J, Tong J, Ginovart N, Wilson A, et al. Regional distribution of serotonin transporter protein in post-mortem human brain: is the cerebellum a SERT-free brain region? Nucl Med Biol. 2005;32(2):123-8.
185. Marazziti D. A further support to the hypothesis of a link between serotonin, autism, and the cerebellum. Biol Psychiatry. 2002;52 (2):143.
186. Makkonen I, Riikonen R, Kokki H, Airaksinen MM, Kuikka JT. Serotonin and dopamine transporter binding in children with autism determined by SPECT. Dev Med Child Neurol. 2008;50 (8):593-7.
187. Azmitia EC, Singh JS, Whitaker-Azmitia PM. Increased serotonin axons (immunoreactive to 5-HT transporter) in postmortem brains from young autism donors. Neuropharm. 2011;60: 1347-54.
188. Williams K, Wheeler DM, Silove N, Hazell P. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2010;4(8):CD004677.
189. Stanfield AC, McIntosh AM, Spencer MD, Philip R, Gaur S, Lawrie SM. Towards a neuroanatomy of autism: a systematic review and meta-analysis of structural magnetic resonance imaging studies. Eur Psychiatry. 2008;23(4):289-99.
190. Abrahams BS, Geschwind DH. Connecting genes to brain in the autism spectrum disorders. Arch Neurol. 2010;67(4):395-9.
191. Leiner HC, Leiner AL, Dow R.S. Does the cerebellum contribute to mental skills? Behav Neurosci. 1986;100(4):443-54.
192. Stoodley CJ, Schmahmann J.D. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. NeuroImage. 2009;44(2):489-501.
193. Middleton FA, Strick PL. Cerebellar output channels. Int Rev Neurobiol. 1997;41:61-82.
194. Bloedel JR, Bantli H. A spinal action of the dentate nucleus mediated by descending systems originating in the brain stem. Brain Res. 1978;153(3):602-7.
195. Kanner L. Autistic disturbances of affective contact. The Nervous Child. 1943;2:217-50.
196. Asperger H. 'Autistic psychopathy' in childhood. In: Frith U, editor. Autism and Asperger syndrome. New York: Cambridge University Press; 1991. p. 37-92.
197. Molloy CA, Dietrich KN, Bhattacharya A. Postural stability in children with autism spectrum disorder. J Autism Dev Disord. 2003;33(6):643-52.
198. Freitag CM, Kleser C, Schneider M, von Gontard A. Quantitative assessment of neuromotor function in adolescents with high functioning autism and Asperger Syndrome. J Autism Dev Disord. 2007;37(5):948-59.
199. Mostofsky SH, Powell SK, Simmonds DJ, Goldberg MC, Caffo B, Pekar JJ. Decreased connectivity and cerebellar activity in autism during motor task performance. Brain. 2009;132(9): 2413-25.
200. Allen G, Courchesne E. Differential effects of developmental cerebellar abnormality on cognitive and motor functions in the cerebellum: an fMRI study of autism. Am J Psychiatry. 2003;160 (2):262-73.
201. Muller RA, Pierce K, Ambrose JB, Allen G, Courchesne E. Atypical patterns of cerebral motor activation in autism: a functional magnetic resonance study. Biol Psychiatry. 2001;49 (8):665-76.
202. Takarae Y, Minshew NJ, Luna B, Krisky CM, Sweeney JA. Pursuit eye movement deficits in autism. Brain. 2004;127 (Pt 12):2584-94.
203. Takarae Y, Minshew NJ, Luna B, Sweeney JA. Atypical involvement of frontostriatal systems during sensorimotor control in autism. Psychiatry Res. 2007;156(2):117-27.
204. Mosconi MW, Kay M, D'Cruz AM, Guter S, Kapur K, Macmillan C, et al. Neurobehavioral abnormalities in firstdegree relatives of individuals with autism. Arch Gen Psychiatry. 2010;67(8):830-40.
205. Williams DL, Goldstein G, Minshew NJ. The profile of memory function in children with autism. Neuropsychology. 2006;20 (1):21-9.
206. Townsend J, Courchesne E, Covington J, Westerfield M, Harris NS, Lyden P, et al. Spatial attention deficits in patients with acquired or developmental cerebellar abnormality. J Neurosci. 1999;19(13):5632-43.
207. Herbert MR, Harris GJ, Adrien KT, Ziegler DA, Makris N, Kennedy DN, et al. Abnormal asymmetry in language association cortex in autism. Ann Neurol. 2002;52(5):588-96.
208. Hodge SM, Makris N, Kennedy DN, Caviness Jr VS, Howard J, McGrath L, et al. Cerebellum, language, and cognition in autism and specific language impairment. J Autism Dev Disord. 2010;40 (3):300-16.
209. Stoodley CJ. The cerebellum and cognition: evidence from functional imaging studies. Cerebellum. 2012; (in press)
210. Gordon N. The cerebellum and cognition. Eur J Paediatr Neurol. 2007;11:232-4.
211. Kelly RM, Strick PL. Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. J Neurosci. 2003;23: 8432-44.
212. Middleton FA, Strick PL. Cerebellar projections to the prefrontal cortex of the primate. J Neurosci. 2001;21:700-12.
213. Courchesne E. Brainstem, cerebellar and limbic neuroanatomical abnormalities in autism. Curr Opin Neurobiol. 1997;7:269-78.
214. Llinas R. I of the vortex. From neurons to self. Cambridge: MIT Press; 2002.
215. Sasaki K, Gemba H. Cerebro-cerebellar interactions: for fast and stable timing of voluntary movement. In: Mano N, Hamada I, DeLong MR, editors. Role of the cerebellum and basal ganglia in voluntary movement. Amsterdam: Elsevier; 1993. p. 41-50.
216. Ivry RB, Keele SW, Diener HC. Dissociation of the lateral and medial cerebellum in movement timing and movement execution. Exp Brain Res. 1988;73:167-80.
217. Braitenberg V. Is the cerebellar cortex a biological clock in the millisecond range? In: Fox CA, Snider RS, editors. Progress in Brain Research. Vol.25. The Cerebellum. Amsterdam: Elsevier; 1967. p. 334-46.
218. Yuste R, MacLean JN, Smith J, Lansner A. The cortex as a central pattern generator. Nat Rev Neurosci. 2005;6:477-83.
219. Ayzenshtat I, Meirovithz E, Edelman H, Werner-Reiss U, Bienenstock E, Abeles M, et al. Precise spatiotemporal patterns among visual cortical areas and their relation to visual stimulus processing. J Neurosci. 2010;30:11232-45.
220. Ben-Shaul Y, Drori R, Asher I, Stark E, Nadasdy Z, Abeles M. Neuronal activity in motor cortical areas reflects the sequential context of movement. J Neurophysiol. 2004;91: 1748-1762. 7.
221. Prut Y, Vaadia E, Bergman H, Haalman I, Slovin H, Abeles M. Spatiotemporal structure of cortical activity: properties and behavioral relevance. J Neurophysiol. 1998;79:2857-74.
222. Braitenberg V, Atwood RP. Morphological observations on the cerebellar cortex. J Comp Neurol. 1958;109:1-33.
223. Heck DH. Rat cerebellar cortex in vitro responds specifically to moving stimuli. Neurosci Lett. 1993;157:95-8.
224. Heck DH. Sequential input to guinea pig cerebellar cortex in vitro strongly affects Purkinje cells via parallel fibers. Naturwissenschaften. 1995;82:201-3.
225. Braitenberg V, Heck DH, Sultan F. The detection and generation of sequences as a key to cerebellar function. Experiments and theory. Behav Brain Sci. 1997;20:229-45.
226. Molinari M, Chiricozzi FR, Clausi S, Tedesco AM, De Lisa M, Leggio MG. Cerebellum and detection of sequences, from perception to cognition. Cerebellum. 2008;7:611-5.
227. Andreasen NC, Paradiso S, O'Leary DS. "Cognitive dysmetria" as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical- cerebellar circuitry? Schizophr. Bull. 1998; 24:203-18.
228. Courchesne E, Yeung-Courchesne R, Press GA, Hesselink JR, Jernigan TL. Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med. 1988;318:1349-54.
229. Bauman M.L. Microscopic neuroanatomic abnormalities in autism. Pediatrics. 1991;87:791-6.
230. Persico AM, Bourgeron T. Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends Neurosci. 2006;29:349-58.
231. Rice D, Barone Jr S. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect. 2000;108 Suppl 3:511-33.
232. Fombonne E. Epidemiology of autistic disorder and other pervasive developmental disorders. J Clin Psychiatry. 2005;66 Suppl 10:3-8.
233. Landrigan PJ. What causes autism? Exploring the environmental contribution. Curr Opin Pediatr. 2010;22:219-25.
234. 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;25:63-77.
235. 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 (11):1095-102.
236. Gaita L, Manzi B, Sacco R, Lintas C, Altieri L, Lombardi F, et al. Decreased serum arylesterase activity in autism spectrum disorders. Psychiatry Res. 2010;180:105-13.
237. Paşca SP, Nemeş B, Vlase L, Gagyi CE, Dronca E, Miu AC, et al. High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism. Life Sci. 2006; 78:2244-8.
238. Lugli G, Krueger JM, Davis JM, Persico AM, Keller F, Smalheiser NR. Methodological factors influencing measurement and processing of plasma reelin in humans. BMC Biochem. 2003;4:9.
239. D'Amelio M, Ricci I, Sacco R, Liu X, D'Agruma L, Muscarella LA, et al. Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions. Mol Psychiatry. 2005;10: 1006-16.
240. Persico AM, Levitt P, Pimenta AF. Polymorphic GGC repeat differentially regulates human reelin gene expression levels. J Neural Transm. 2006;113:1373-82.
241. Eskenazi B, Huen K, Marks A, Harley KG, Bradman A, Barr DB, et al. PON1 and neurodevelopment in children from the CHAMACOS study exposed to organophosphate pesticides in utero. Environ Health Perspect. 2010;118:1775-81.
242. Mullen B, Khialeeva E, Carpenter EM. Dab1-lacZ reporter reveals CNS lamination defects in a mouse model for autism. Program no. 147.12, 2010 Neuroscience Meeting Planner. Society for Neuroscience, San Diego CA. online.
243. Krey J, Dolmetsch R. Molecular mechanisms of autism: a possible role for Ca2+ signaling. Curr Opin Neurobiol. 2007;17:112-9.
244. Empson RM, Garside ML, Knöpfel T. Plasma membrane Ca2+ ATPase 2 contributes to short-term synapse plasticity at the parallel fiber to Purkinje neuron synapse. J Neurosci. 2007;27: 3753-8.
245. Burette AC, Strehler EE, Weinberg RJ. "Fast" plasma membrane calcium pump PMCA2a concentrates in GABAergic terminals in the adult rat brain. J Comp Neurol. 2009;512:500-13.
246. Garside ML, Turner PR, Austen B, Strehler EE, Beesley PW, Empson RM. Molecular interactions of the plasma membrane calcium ATPase 2 at pre- and post-synaptic sites in rat cerebellum. Neuroscience. 2009;162:383-95.
247. Carayol J, Sacco R, Tores F, Rousseau F, Lewin P, Hager J, et al. Converging evidence for an association of ATP2B2 allelic variants with autism in males. Biol Psychiatry. 2011;70(9): 880-7.
248. Pessah IN, Cherednichenko G, Lein PJ. Minding the calcium store: ryanodine receptor activation as a convergent mechanism of PCB toxicity. Pharmacol Ther. 2010;125:260-85.
249. Palmieri L, Persico AM. Mitochondrial dysfunction in autism spectrum disorders: cause or effect? Biochim Biophys Acta. 2010;1797:1130-7.
250. Elsen GE, Choi LY, Prince VE, Ho RK. The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration. Dev Biol. 2009;335:78-92.
251. Campbell DB, D'Oronzio R, Garbett K, Ebert PJ, Mirnics K, Levitt P, et al. Disruption of cerebral cortex MET signaling in autism spectrum disorder. Ann Neurol. 2007;62:243-50.
252. Campbell DB, Sutcliffe JS, Ebert PJ, Militerni R, Bravaccio C, Trillo S, et al. A genetic variant that disrupts MET transcription is associated with autism. Proc Natl Acad Sci USA. 2006;103: 16834-9.
253. Sheng L, Ding X, Ferguson M, McCallister M, Rhoades R, Maguire M, et al. Prenatal polycyclic aromatic hydrocarbon exposure leads to behavioral deficits and downregulation of receptor tyrosine kinase, MET. Toxicol Sci. 2010;118:625-34.
254. Campbell DB, Li C, Sutcliffe JS, Persico AM, Levitt P. Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder. Autism Res. 2008; 1:159-68.
255. Carlson GC. Glutamate receptor dysfunction and drug targets across models of autism spectrum disorders. Pharmacol Biochem Behav. 2012;100(4):850-4.
256. Steinlin M. Cerebellar disorders in childhood: cognitive problems. Cerebellum. 2008;7:607-10.
257. Rojas DC, Peterson E, Winterrowd E, Reite ML, Rogers SJ, Tregellas JR. Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms. BMC Psychiatry. 2006;6:56.
258. Schmahmann JD, Weilburg JB, Sherman JC. The neuropsychiatry of the cerebellum-insights from the clinic. Cerebellum. 2007;6:254-67.
259. Anderson CM, Polcari A, Lowen SB, Renshaw PF, Teicher MH. Effects of methylphenidate on functional magnetic resonance relaxometry of the cerebellar vermis in boys with ADHD. Am J Psychiatry. 2002;159:1322-8.
260. Takahashi T, Kobayashi T, Ozaki M, Takamatsu Y, Ogai Y, Ohta M, et al. G protein-activated inwardly rectifying K+ channel inhibition and rescue of weaver mouse motor functions by antidepressants. Neurosci Res. 2006;54:104-11.
261. Blatt G.J. GABAergic cerebellar system in autism: a neuropathological and developmental perspective. Int Rev Neurobiol. 2005;71:167-78.
262. Johannessen Landmark C. Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of action and clinical efficacy. CNS Drugs. 2008;22:27-47.
263. Fink M, Taylor MA, Ghaziuddin N. Catatonia in autistic spectrum disorders: a medical treatment algorithm. Int Rev Neurobiol. 2006;72:233-44.
264. Wang P, Erickson CA, Ginsberg G, Rathmell B, Cerubini M, Zarevics P, et al. Effects of STX209 (arbaclofen) on social and communicative function in ASD: results of an 8 week open label trial. International Meeting for Autism Research. 2011 May. San Diego, CA.
265. Lory P, Mezghrani A. Calcium channelopathies in inherited neurological disorders: relevance to drug screening for acquired channel disorders. IDrugs. 2010;13:467-71.
266. Placantonakis DG, Schwarz C, Welsh JP. Serotonin suppresses subthreshold and suprathreshold oscillatory activity of rat inferior olive neurons in vitro. J Physiol (Lond). 2000;524:833-51.
267. Placantonakis DG, Welsh JP. Two distinct oscillatory states determined by the NMDA receptor in rat inferior olive. J Physiol (Lond). 2001;534:123-40.
268. Welsh JP, Han VZ. The NMDA receptor potentiates electrotonic coupling between inferior olive neurons. Society for Neuroscience Abstracts. 2010; 525-5.
269. Park YG, Park HY, Lee CJ, Choi S, Jo S, Choi H, et al. Ca(V)3.1 is a tremor rhythm pacemaker in the inferior olive. Proc Nat Acad Sci (USA). 2010;107:10731-6.
270. Cheung C, Chua S, Cheung V, Khong P, Tai K, Wong T, et al. White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism. J Child Psychol Psychiatry. 2009;50:1102-12.
271. Catani M, Jones DK, Daly E, Embiricos N, Deeley Q, Pugliese L, et al. Altered cerebellar feedback projections in Asperger syndrome. NeuroImage. 2008;41:1184-91.
272. Kates WR, Burnette CP, Eliez S, Strunge LA, Kaplan D, Landa R, et al. Neuroanatomic variation in monozygotic twin pairs discordant for the narrow phenotype for autism. Am J Psychiatry. 2004;161:539-46.
273. Amaral DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends Neurosci. 2008;31:137-45.
274. Bellebaum C, Daum I. Cerebellar involvement in executive control. Cerebellum. 2007;6:184-92.
275. Pennington BF, Ozonoff S. Executive functions and developmental psychopathology. J Child Psychol Psychiatry. 1996;37:51-87.
276. Lopez BR, Lincoln AJ, Ozonoff S, Lai Z. Examining the relationship between executive functions and restricted, repetitive symptoms of autistic disorder. J Autism Dev Disord. 2005; 35:445-60.
277. Giza J, Urbanski MJ, Prestori F, Bandyopadhyay B, Yam A, Friedrich V, et al. Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2. J Neurosci. 2010;30:14805-16.
278. Swanson DJ, Goldowitz D. Experimental Sey mouse chimeras reveal the developmental deficiencies of Pax6-null granule cells in the postnatal cerebellum. Dev Biol. 2011;351(1):1-12.
279. Umeda T, Takashima N, Nakagawa R, Maekawa M, Ikegami S, Yoshikawa T, et al. Evaluation of Pax6 mutant rat as a model for a autism. PLoS One. 2010;5(12):e15500.
280. Kuemerle B, Gulden F, Cherosky N, Williams E, Herrup K. The mouse Engrailed genes: a window into autism. Behav Brain Res. 2007;176(1):121-32.
281. Rasalam AD, Hailey H, Williams JH, Moore SJ, Turnpenny PD, Lloyd DJ, et al. Characteristics of fetal anticonvulsant syndrome associated autistic disorder. Dev Med Child Neurol. 2005;47 (8):551-5.
282. Ingram JL, Stodgell CJ, Hyman SL, Figlewicz DA, Weitkamp LR, Rodier PM. Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders. Teratology. 2000;62(6):393-405.
283. Zuo J, De Jager PL, Takahashi KA, Jiang W, Linden DJ, Heintz N. Neurodegeneration in Lurcher mice caused by mutation in delta2 glutamate receptor gene. Nature. 1997;388:769-73.
284. Dickson PE, Rogers TD, DelMar N,Martin LA, Heck D, Blaha CD, et al. Behavioral flexibility in a mouse model of developmental cerebellar Purkinje cell loss. Neurobiol LearnMem. 2010;94:220-8.
285. Martin LA, Escher T, Goldowitz D, Mittleman G. A relationship between cerebellar Purkinje cells and spatial working memory demonstrated in a lurcher/chimera mouse model system. Genes Brain Behav. 2004;3:158-66.
286. Martin LA, Goldowitz D, Mittleman G. Sustained attention in the mouse: a study of the relationship with the cerebellum. Behav Neurosci. 2006;120(2):477-81.
287. Martin LA, Goldowitz D, Mittleman G. Repetitive behavior and increased activity in mice with Purkinje cell loss: a model for understanding the role of cerebellar pathology in autism. Eur J Neurosci. 2010;31:544-55.
288. Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, et al. Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011;306 (18):2001-32.
289. Fatemi SH, Folsom TD. The role of fragile X mental retardation protein in major mental disorders. Neuropharmacology. 2011; 60:1221-6.
290. Martin LA, Goldowitz D, Mittleman G. Sustained attention in the mouse: a study of the relationship with the cerebellum. Behav Neurosci. 2006;120(2):477-81.
291. Ozonoff S, Williams BJ, Gale S, Miller JN. Autism and autistic behavior in Joubert syndrome. J Child Neurol. 1999;14 (10):636-41.
292. Lancaster MA, Gopal DJ, Kim J, Saleem SN, Silhavy JL, Louie CM, et al. Defective Wnt-dependent cerebellar midline fusion in a mouse model of Joubert syndrome. Nat Med. 2011;17(6):726-31.
293. Garcia CA, McGarry PA, Voirol M, Duncan C. Neurological involvement in the Smith-Lemli-Opitz syndrome: clinical and neuropathological findings. Dev Med Child Neurol. 1973;15 (1):48-55.
294. Ellegood J, Pacey LK, Hampson DR, Lerch JP, Henkelman RM. Anatomical phenotyping in a mouse model of fragile X syndrome with magnetic resonance imaging. NeuroImage. 2010;53 (3):1023-9.
295. Bauman ML, Kemper TL, Arin D.M. Microscopic observations of the brain in Rett syndrome. Neuropediatrics. 1995;26(2):105-8.
296. Belichenko NP, Belichenko PV, Li HH, Mobley WC, Francke U. Comparative study of brain morphology in Mecp2 mutant mouse models of Rett syndrome. J Comp Neurol. 2008;508(1):184-95.
297. Alkan A, Sigirci A, Kutlu R, Ozcan H, Erdem G, Aslan M, et al. Neurofibromatosis type 1: diffusion weighted imaging findings of brain. Eur J Radiol. 2005;56(2):229-34.
298. van der Vaart T, van Woerden GM, Elgersma Y, de Zeeuw CI, Schonewille M. Motor deficits in neurofibromatosis type 1 mice: the role of the cerebellum. Genes Brain Behav. 2011;10 (4):404-9.
299. Padberg GW, Schot JD, Vielvoye GJ, Bots GT, de Beer FC. Lhermitte-Duclos disease and Cowden disease: a single phakomatosis. Ann Neurol. 1991;29(5):517-23.
300. Kwon CH, Zhu X, Zhang J, Knoop LL, Tharp R, Smeyne RJ, et al. Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease. Nat Genet. 2001;29(4):404-11.
301. Reith RM,Way S, McKenna 3rd J, Haines K, Gambello MJ. Loss of the tuberous sclerosis complex protein tuberin causes Purkinje cell degeneration. Neurobiol Dis. 2011;43(1):113-22.
302. Asahina N, Shiga T, Egawa K, Shiraishi H, Kohsaka S, Saitoh S. [(11)C]flumazenil positron emission tomography analyses of brain gamma-aminobutyric acid type A receptors in Angelman syndrome. J Pediatr. 2008;152(4):546-9. 9 e1-3.
303. Dindot SV, Antalffy BA, Bhattacharjee MB, Beaudet AL. The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Hum Mol Genet. 2008;17(1): 111-8.
304. Uemura T, Lee SJ, Yasumura M, Takeuchi T, Yoshida T, Ra M, et al. Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum. Cell. 2010;141(6):1068-79.
305. Tan GC, Doke TF, Ashburner J, Wood NW, Frackowiak RS. Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2. NeuroImage. 2010;53(3):1030-42.
306. Crepel F. Developmental changes in retrograde messengers involved in depolarization-induced suppression of excitation at parallel fiber-Purkinje cell synapses in rodents. J Neurophysiol. 2007;97(1):824-36.
307. Hong SE, Shugart YY, Huang DT, Shahwan SA, Grant PE, Hourihane JO, et al. Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nat Genet. 2000;26(1):93-6.
308. D'Arcangelo G, Miao GG, Chen SC, Soares HD, Morgan JI, Curran T. A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature. 1995;374(6524): 719-23.
309. Sakurai T, Ramoz N, Barreto M, Gazdoiu M, Takahashi N, Gertner M, et al. Slc25a12 disruption alters myelination and neurofilaments: a model for a hypomyelination syndrome and childhood neurodevelopmental disorders. Biol Psychiatry. 2010; 67(9):887-94.
310. Manni E, Petrosini L. A century of cerebellar somatotopy: a debated representation. Nat Rev Neurosci. 2004;5(3):241-9.
311. Fatemi SH, Halt AR, Realmuto G, Earle J, Kist DA, Thuras P, et al. Purkinje cell size is reduced in the cerebellum of patients with autism. Cell Mol Neurobiol. 2002;22(2):171-5.