Autism: The centrality of active pathophysiology and the shift from static to chronic dynamic encephalopathy

Autism: Oxidative Stress, Inflammation, and Immune Abnormalities

Volumn , Issue , 2009, Pages 343-387

  Herbert, Martha R ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

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[No Author keywords available]

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EID: 85057427818     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (196)

1. Afzal, N., S. Murch, K. Thirrupathy, L. Berger, A. Fagbemi, and R. Heuschkel. 2003. Constipation with acquired megarectum in children with autism. Pediatrics 112:939-942.
2. Alverdy, J. C. and E. B. Chang. 2008. The re-emerging role of the intestinal microflora in critical illness and inflammation: Why the gut hypothesis of sepsis syndrome will not go away. J. Leukoc. Biol. 83:461-466.
3. American Psychiatric Association. 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM IV). Washington DC: APA.
4. Anderson, M. P., B. S. Hooker, and M. R. Herbert. 2008. Bridging from cells to cognition in autism pathophysiology: Biological pathways to defective brain function and plasticity. Am. J. Biochem. Biotechnol. (Special Issue on Autism Spectrum Disorders) 4:167-176.
5. Arnold, S. E. 2001. Contributions of neuropathology to understanding schizophrenia in late life. Harv. Rev. Psychiatry 9:69-76.
6. Aschner, M., U. Sonnewald, and K. H. Tan. 2002. Astrocyte modulation of neurotoxic injury. Brain Pathol. 12:475-481.
7. Aschner, M., J. W. Allen, H. K. Kimelberg, R. M. LoPachin, and W. J. Streit. 1999. Glial cells in neurotoxicity development. Annu. Rev. Pharmacol. Toxicol. 39:151-173.
8. Ashwood, P. and J. Van de Water. 2004a. A review of autism and the immune response. Clin. Dev. Immunol. 11:165-174.
9. Ashwood, P. and J. Van de Water. 2004b. Is autism an autoimmune disease? Autoimmun. Rev. 3:557-562.
10. Ashwood, P., S. Wills, and J. Van de Water. 2006. The immune response in autism: A new frontier for autism research. J. Leukoc. Biol. 80:1-15.
11. Aylward, E. H., N. J. Minshew, K. Field, B. F. Sparks, and N. Singh. 2002. Effects of age on brain volume and head circumference in autism. Neurology 59:175-183.
12. Bauman, M. 2006. Beyond behavior: Biomedical diagnoses in autism spectrum disorders. Autism Advocate 45:27-29.
13. Bauman, M. L. and T. L. Kemper. 2005. Neuroanatomic observations of the brain in autism: A review and future directions. Int. J. Dev. Neurosci. 23:183-187.
14. Belmonte, M. K. and T. Bourgeron. 2006. Fragile X syndrome and autism at the intersection of genetic and neural networks. Nat. Neurosci. 9:1221-1225.
15. Blaylock, R. L. and A. Strunecka. 2009. Immune-glutamatergic dysfunction as a central mechanism of the autism spectrum disorders. Curr. Med. Chem. 16:157-170.
16. Braunschweig, D., P. Ashwood, P. Krakowiak, I. Hertz-Picciotto, R. Hansen, L. A. Croen, I. N. Pessah, and J. Van de Water. 2008. Autism: Maternally derived antibodies specific for fetal brain proteins. Neurotoxicology 29:226-231.
17. Bu, B., P. Ashwood, D. Harvey, I. B. King, J. V. Water, and L. W. Jin. 2006. Fatty acid compositions of red blood cell phospholipids in children with autism. Prostaglandins Leukot. Essent. Fatty Acids 74:215-221.
18. Buller, K. M. and T. A. Day. 2002. Systemic administration of interleukin-1beta activates select populations of central amygdala afferents. J. Comp. Neurol. 452:288-296.
19. Buller, K. M., A. S. Hamlin, and P. B. Osborne. 2005. Dissection of peripheral and central endogenous opioid modulation of systemic interleukin-1beta responses using c-fos expression in the rat brain. Neuropharmacology 49:230-242.
20. Calderon-Garciduenas, L., A. Mora-Tiscareno, E. Ontiveros, G. Gomez-Garza, G. Barragan-Mejia, J. Broadway, S. Chapman, G. Valencia-Salazar, V. Jewells, R. R. Maronpot, C. Henriquez-Roldan, B. Perez-Guille, R. Torres-Jardon, L. Herrit, D. Brooks, N. Osnaya-Brizuela, M. E. Monroy, A. Gonzalez-Maciel, R. Reynoso-Robles, R. Villarreal-Calderon, A. C. Solt, and R. W. Engle. 2008a. Air pollution, cognitive deficits and brain abnormalities: A pilot study with children and dogs. Brain Cogn. 68:117-127.
21. Calderon-Garciduenas, L., A. C. Solt, C. Henriquez-Roldan, R. Torres-Jardon, B. Nuse, L. Herritt, R. Villarreal-Calderon, N. Osnaya, I. Stone, R. Garcia, D. M. Brooks, A. Gonzalez-Maciel, R. Reynoso-Robles, R. Delgado-Chavez, and W. Reed. 2008b. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults. Toxicol. Pathol. 36:289-310.
22. Campbell, D. B., J. S. Sutcliffe, P. J. Ebert, R. Militerni, C. Bravaccio, S. Trillo, M. Elia, C. Schneider, R. Melmed, R. Sacco, A. M. Persico, and P. Levitt. 2006. A genetic variant that disrupts MET transcription is associated with autism. Proc. Natl. Acad. Sci. U.S.A. 103:16834-16839.
23. Campbell, D. B., C. Li, J. S. Sutcliffe, A. M. Persico, and P. Levitt. 2008. Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder. Autism Res. 1:159-168.
24. Canitano, R. 2007. Epilepsy in autism spectrum disorders. Eur. Child Adolesc. Psychiatry 16:61-66.
25. Carson, M. J., J. M. Doose, B. Melchior, C. D. Schmid, and C. C. Ploix. 2006. CNS immune privilege: Hiding in plain sight. Immunol. Rev. 213:48-65.
26. Caspi, A. and T. E. Moffitt. 2006. Gene-environment interactions in psychiatry: Joining forces with neuroscience. Nat. Rev. Neurosci. 7:583-590.
27. Caviness, V. S., Jr, N. T. Lange, N. Makris, M. R. Herbert, and D. N. Kennedy. 1999. MRI-based brain volumetrics: Emergence of a developmental brain science. Brain Dev. 21:289-295.
28. Chauhan, A. and V. Chauhan. 2006. Oxidative stress in autism. Pathophysiology 13:171-181.
29. Chauhan, V., A. Chauhan, I. L. Cohen, W. T. Brown, and A. Sheikh. 2004. Alteration in amino-glycerophospholipids levels in the plasma of children with autism: A potential biochemical diagnostic marker. Life Sci. 74:1635-1643.
30. Chugani, D. C., B. S. Sundram, M. Behen, M. L. Lee, and G. J. Moore. 1999. Evidence of altered energy metabolism in autistic children. Prog. Neuropsychopharmacol. Biol. Psychiatry 23:635-641.
31. Churchill, L., P. Taishi, M. Wang, J. Brandt, C. Cearley, A. Rehman, and J. M. Krueger. 2006. Brain distribution of cytokine mRNA induced by systemic administration of interleukin-1beta or tumor necrosis factor alpha. Brain Res. 1120:64-73.
32. Ciaranello, R. D., S. R. VandenBerg, and T. F. Anders. 1982. Intrinsic and extrinsic determinants of neuronal development: Relation to infantile autism. J. Autism Dev. Disord. 12:115-145.
33. Coleman, M. 1979. Studies of the autistic syndromes. In Congenital and Acquired Cognitive Disorders, ed. R. Katzman. New York: Raven Press, pp. 265-275.
34. Coleman, N. 1989. Autism: Nondrug biological treatments. In Diagnosis and Treatment of Autism, ed. C. Gillberg. New York: Plenum Press, pp. 219-235.
35. Coleman, P. D., J. Romano, L. Lapham, and W. Simon. 1985. Cell counts in cerebral cortex of an autistic patient. J. Autism Dev. Disord. 15:245-255.
36. Connors, S. L., P. Levitt, S. G. Matthews, T. A. Slotkin, M. V. Johnston, H. C. Kinney, W. G. Johnson, R. M. Dailey, and A. W. Zimmerman. 2008. Fetal mechanisms in neurodevelopmental disorders. Pediatr. Neurol. 38:163-176.
37. Conturo, T. E., D. L. Williams, C. D. Smith, E. Gultepe, E. Akbudak, and N. J. Minshew. 2008. Neuronal fiber pathway abnormalities in autism: An initial MRI diffusion tensor tracking study of hippocampo-fusiform and amygdalo-fusiform pathways. J. Int. Neuropsychol. Soc. 14:933-946.
38. Corrales, M. and M. Herbert. Autism and environmental genomics: Synergistic systems approaches to autism complexity. In Autism Spectrum Disorders, eds. D. Amaral, G, Dawson, and D. Geschwind. New York: Oxford University Press. (in press).
39. Correia, C., A. M. Coutinho, L. Diogo, M. Grazina, C. Marques, T. Miguel, A. Ataide, J. Almeida, L. Borges, C. Oliveira, G. Oliveira, and A. M. Vicente. 2006. Brief report: High frequency of biochemical markers for mitochondrial dysfunction in autism: No association with the mitochondrial aspartateaglutamate carrier SLC25A12 gene. J. Autism Dev. Disord. 36:1137-1140.
40. Courchesne, E. and K. Pierce. 2005. Why the frontal cortex in autism might be talking only to itself: Local over-connectivity but long-distance disconnection. Curr. Opin. Neurobiol. 15:225-230.
41. Coyle, J. T. and R. Schwarcz. 2000. Mind glue: implications of glial cell biology for psychiatry. Arch: Gen. Psychiatry 57:90-93.
42. Croen, L. A., J. K. Grether, C. K. Yoshida, R. Odouli, and J. Van de Water. 2005. Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders: A case-control study. Arch. Pediatr. Adolesc. Med. 159:151-157.
43. Curran, L. K., C. J. Newschaffer, L. C. Lee, S. O. Crawford, M. V. Johnston, and A. W. Zimmerman. 2007. Behaviors associated with fever in children with autism spectrum disorders. Pediatrics 120:e1386-e1392.
44. D’Amelio, M., I. Ricci, R. Sacco, X. Liu, L. D’Agruma, L. A. Muscarella, V. Guarnieri, R. Militerni, C. Bravaccio, M. Elia, C. Schneider, R. Melmed, S. Trillo, T. Pascucci, S. Puglisi-Allegra, K. L. Reichelt, F. Macciardi, J. J. Holden, and A. M. Persico. 2005. Paraoxonase gene variants are associated with autism in North America, but not in Italy: Possible regional specificity in gene-environment interactions. Mol. Psychiatry 10:1006-1016.
45. Dager, S. R., S. D. Friedman, H. Pegropoulos, and D. W. W. Shaw. 2008. Imaging evidence for pathological brain development in autism spectrum disorders. In Autism: Current Theories and Evidence, ed. A. Zimmerman. Totowa, NJ: Humana Press.
46. Davis, J. O., J. A. Phelps, and H. S. Bracha. 1995. Prenatal development of monozygotic twins and concordance for schizophrenia. Schizophr. Bull. 21:357-366.
47. DeMyer, M. K., J. N. Hingtgen, and R. K. Jackson. 1981. Infantile autism reviewed: A decade of research. Schizophr. Bull. 7:388-451.
48. DeVito, T. J., D. J. Drost, R. W. Neufeld, N. Rajakumar, W. Pavlosky, P. Williamson, and R. Nicolson. 2007. Evidence for cortical dysfunction in autism: A proton magnetic resonance spectroscopic imaging study. Biol. Psychiatry 61:465-473.
49. Dietert, R. R. and J. M. Dietert. 2008. Potential for early-life immune insult including developmental immunotoxicity in autism and autism spectrum disorders: Focus on critical windows of immune vulnerability. J. Toxicol. Environ. Health B. Crit. Rev. 11:660-680.
50. Ehninger, D., S. Han, C. Shilyansky, Y. Zhou, W. Li, D. J. Kwiatkowski, V. Ramesh, and A. J. Silva. 2008. Reversal of learning deficits in a Tsc2AAA mouse model of tuberous sclerosis. Nat. Med. 14:843-848.
51. Endo, T., T. Shioiri, H. Kitamura, T. Kimura, S. Endo, N. Masuzawa, and T. Someya. 2007. Altered chemical metabolites in the amygdala-hippocampus region contribute to autistic symptoms of autism spectrum disorders. Biol. Psychiatry 62:1030-1037.
52. Evans, T. A., S. L. Siedlak, Lian Lu, X. Fu, Z. Wang, W. R. McGinnis, E. Fakhoury, R. J. Castellanio, S. L. Hazen, W. H. Walsh, A. T. Lewis, R. G. Salomon, M. A. Smith, and G. Zhu X. Perry. 2008. The autistic phenotype exhibits a remarkably localized modification of brain protein by products of free radical-induced lipid oxidation. Am. J. Biochem. Biotechnol. (Special Issue on Autism Spectrum Disorders) 4:61-72.
53. Fatemi, S. H., J. Earle, R. Kanodia, D. Kist, E. S. Emamian, P. H. Patterson, L. Shi, and R. Sidwell. 2002. Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in adulthood: Implications for genesis of autism and schizophrenia. Cell. Mol. Neurobiol. 22:25-33.
54. Fein, D., P. Dixon, J. Paul, and H. Levin. 2005. Pervasive developmental disorder can evolve into ADHD: Case illustrations. J. Autism Dev. Disord. 35:525-534.
55. Felicetti, T. 1981. Parents of autistic children: Some notes on the chemical connection. Milieu Ther. 1:13-16.
56. Fernell, E., Y. Watanabe, I. Adolfsson, Y. Tani, M. Bergstrom, P. Hartvig, A. Lilja, A. L. von Knorring, C. Gillberg, and B. Langstrom. 1997. Possible effects of tetrahydrobiopterin treatment in six children with autism-clinical and positron emission tomography data: A pilot study. Dev. Med. Child Neurol. 39:313-318.
57. Fields, R. D. 2006. Advances in understanding neuron-glia interactions. Neuron Glia Biol. 2:23-26.
58. Fields, R. D. 2008. Oligodendrocytes changing the rules: Action potentials in glia and oligodendrocytes controlling action potentials. Neuroscientist 14:540-543.
59. Filipek, P. A., J. Juranek, M. T. Nguyen, C. Cummings, and J. J. Gargus. 2004. Relative carnitine deficiency in autism. J. Autism Dev. Disord. 34:615-623.
60. Finegold, S. M., D. Molitoris, Y. Song, C. Liu, M. L. Vaisanen, E. Bolte, M. McTeague, R. Sandler, H. Wexler, E. M. Marlowe, M. D. Collins, P. A. Lawson, P. Summanen, M. Baysallar, T. J. Tomzynski, E. Read, E. Johnson, R. Rolfe, P. Nasir, H. Shah, D. A. Haake, P. Manning, and A. Kaul. 2002. Gastrointestinal microflora studies in lateonset autism. Clin. Infect. Dis. 35:S6-S16.
61. Friedman, S. D., D. W. Shaw, A. A. Artru, T. L. Richards, J. Gardner, G. Dawson, S. Posse, and S. R. Dager. 2003. Regional brain chemical alterations in young children with autism spectrum disorder. Neurology 60:100-107.
62. Friedman, S. D., D. W. Shaw, A. A. Artru, G. Dawson, H. Petropoulos, and S. R. Dager. 2006. Gray and white matter brain chemistry in young children with autism. Arch. Gen. Psychiatry 63:786-794.
63. Gajzago, G. and M. Prior. 1974. Two cases of “recovery” in Kanner syndrome. Arch. Gen. Psychiatry. 31:264-268.
64. Giaume, C., F. Kirchhoff, C. Matute, A. Reichenbach, and A. Verkhratsky. 2007. Glia: The fulcrum of brain diseases. Cell Death Differ. 14:1324-1335.
65. Gillberg, C. and M. Coleman (eds.). 2000. The Biology of the Autistic Syndromes (Clinics in Developmental Medicine). Cambridge, U.K.: Cambridge University Press.
66. Gold, D. R. and B. H. Cohen. 2001. Treatment of mitochondrial cytopathies. Semin. Neurol. 21:309-325.
67. Goldman, L. R. and S. Koduru. 2000. Chemicals in the environment and developmental toxicity to children: A public health and policy perspective. Environ. Health Perspect. 108(Suppl. 3):443-448.
68. Goodwin, M. S., J. Groden, W. F. Velicer, L. P. Lipsitt, M. G. Baron, S. G. Hofmann, and G Groden. 2006. Cardiovascular arousal in individuals with autism. Focus Autism Other Dev. Disabil. 21:100-123.
69. Grandjean, P. and P. J. Landrigan. 2006. Developmental neurotoxicity of industrial chemicals. Lancet 368:2167-2178.
70. Groden, J., M. S. Goodwin, M. G. Baron, G. Groden, W. F. Velicer, L. P. Lipsitt, S. G. Hofmann, and B. Plummer. 2005. Assessing cardiovascular responses to stressors in individuals with autism spectrum disorders. Focus Autism Other Dev. Disabil. 20:244-252.
71. Gustafsson, L. 2004. Comment on disruption in the inhibitory architecture of the cell minicolumn: Implications for autism. Neuroscientist 10:189-191.
72. Guy, J., J. Gan, J. Selfridge, S. Cobb, and A. Bird. 2007. Reversal of neurological defects in a mouse model of Rett syndrome. Science 315:1143-1147.
73. Halassa, M. M., T. Fellin, and P. G. Haydon. 2007. The tripartite synapse: Roles for gliotransmission in health and disease. Trends Mol. Med. 13:54-63.
74. Hallmayr, J. 2008. Personal communication.
75. Han, B. C., S. B. Koh, E. Y. Lee, and Y. H. Seong. 2004. Regional difference of glutamate-induced swelling in cultured rat brain astrocytes. Life Sci. 76:573-583.
76. Hanisch, U. K. 2002. Microglia as a source and target of cytokines. Glia 40:140-155.
77. Happe, F. and A. Ronald. 2008. The fractionable autism triad: A review of evidence from behavioural, genetic, cognitive and neural research. Neuropsychol. Rev. 18:287-304.
78. Happe, F., A. Ronald, and R. Plomin. 2006. Time to give up on a single explanation for autism. Nat. Neurosci. 9:1218-1220.
79. Hayashi, M. L., B. S. Rao, J. S. Seo, H. S. Choi, B. M. Dolan, S. Y. Choi, S. Chattarji, and S. Tonegawa. 2007. Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proc. Natl. Acad. Sci. U.S.A. 104:11489-11494.
80. Helt, M., E. Kelley, M. Kinsbourne, J. Pandey, H. Boorstein, M. Herbert, and D. Fein. 2008. Can children with autism recover? If so, how? Neuropsychol. Rev. 18:339-366.
81. Hendry, J., T. DeVito, N. Gelman, M. Densmore, N. Rajakumar, W. Pavlosky, P. C. Williamson, P. M. Thompson, D. J. Drost, and R. Nicolson. 2006. White matter abnormalities in autism detected through transverse relaxation time imaging. Neuroimage 29:1049-1057.
82. Herbert, M. 2007. Transcending the gaps in autism research. Interview with Martha Herbert, MD by Frank Lampe and Suzanne Snyder. Altern. Ther. Health Med. 13:62-73 or http:/www.alternative-therapies.com/at/web_pdfs/herbert_long.pdf.
83. Herbert, M. R. 2002. Genetics finding its place in larger living schemes. Crit. Pub. Health 12:221-236.
84. Herbert, M. R. 2005a. Autism: A brain disorder or a disorder that affects the brain? Clin. Neuropsychiatry 2:354-379.
85. Herbert, M. R. 2005b. Large brains in autism: The challenge of pervasive abnormality. Neuroscientist 11:417-440.
86. Herbert, M. R. and M. P. Anderson. 2008. An expanding spectrum of autism models: From fixed developmental defects to reversible functional impairments. In Autism: Current Theories and Evidence, ed. A. Zimmerman. Totowa, NJ: Humana Press, pp. 429-463.
87. Herbert, M. R. and V. S. Caviness. 2006. Neuroanatomy and imaging studies. In Autism: A Neurobiological Disorder of Early Brain Development, eds. R. Tuchman and I. Rapin. London: Mac Keith Press, 115-140.
88. Hertz-Picciotto, I. and L. Delwiche. 2009. The rise in autism and the role of age at diagnosis. Epidemiology 20:84-90.
89. Hertz-Picciotto, I., H. Y. Park, M. Dostal, A. Kocan, T. Trnovec, and R. Sram. 2008. Prenatal exposures to persistent and non-persistent organic compounds and effects on immune system development. Basic Clin. Pharmacol. Toxicol. 102:146-154.
90. Holtzman, D. 2008. Autistic spectrum disorders and mitochondrial encephalopathies. Acta Paediatr. 97:859-860.
91. Hugg, J. W., R. I. Kuzniecky, F. G. Gilliam, R. B. Morawetz, R. E. Fraught, and H. P. Hetherington. 1996. Normalization of contralateral metabolic function following temporal lobectomy demonstrated by 1H magnetic resonance spectroscopic imaging. Ann. Neurol. 40:236-239.
92. James, S. J., S. Melnyk, S. Jernigan, M. A. Cleves, C. H. Halsted, D. H. Wong, P. Cutler, K. Bock, M. Boris, J. J. Bradstreet, S. M. Baker, and D. W. Gaylor. 2006. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141:947-956.
93. James, S. J., S. Melnyk, S. Jernigan, A. Hubanks, S. Rose, and D. W. Gaylor. 2008. Abnormal transmethylationAtranssulfuration metabolism and DNA hypomethylation among parents of children with autism. J. Autism Dev. Disord. 38:1966-1975.
94. Jones, D. S. 2005. Textbook of Functional Medicine. Gig Harbor, WA: Institute for Functional Medicine.
95. Just, M. A., V. L. Cherkassky, T. A. Keller, and N. J. Minshew. 2004. Cortical activation and synchronization during sentence comprehension in high-functioning autism: Evidence of underconnectivity. Brain 127:1811-1821.
96. Just, M. A., V. L. Cherkassky, T. A. Keller, R. K. Kana, and N. J. Minshew. 2007. Functional and anatomical cortical underconnectivity in autism: Evidence from an FMRI study of an executive function task and corpus callosum morphometry. Cereb. Cortex 17:951-961.
97. Kanner, L. 1943. Autistic disturbances of affective contact. Nerv. Child 10:217-250.
98. Kanner, L. 1968. Early infantile autism revisited. Psychiatry Dig. 29:17-28.
99. Kanner, L. 1971. Follow-up study of eleven autistic children originally reported in 1943. J. Autism Child Schizophr. 1:119-145.
100. Kelley, E., J. J. Paul, D. Fein, and L. R. Naigles. 2006. Residual language deficits in optimal outcome children with a history of autism. J. Autism Dev. Disord. 36:807-828.
101. Kern, J. K. 2003. Purkinje cell vulnerability and autism: A possible etiological connection. Brain Dev. 25:377-382.
102. Kielian, T. 2008. Glial connexins and gap junctions in CNS inflammation and disease. J. Neurochem. 106:1000-1016.
103. Kim, W. G., R. P. Mohney, B. Wilson, G. H. Jeohn, B. Liu, and J. S. Hong. 2000. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: Role of microglia. J. Neurosci. 20:6309-6316.
104. Kleinhans, N. M., B. C. Schweinsburg, D. N. Cohen, R. A. Muller, and E. Courchesne. 2007. N-acetyl aspartate in autism spectrum disorders: Regional effects and relationship to fMRI activation. Brain Res. 1162:85-97. [Epub 2007 May 21. 1162:85-97].
105. Koehler, R. C., D. Gebremedhin, and D. R. Harder. 2006. Role of astrocytes in cerebrovascular regulation. J. Appl. Physiol. 100:307-317.
106. Leekam, S. R., C. Nieto, S. J. Libby, L. Wing, and J. Gould. 2007. Describing the sensory abnormalities of children and adults with autism. J. Autism Dev. Disord. 37:894-910.
107. Li, M., B. Wang, M. Zhang, M. Rantalainen, S. Wang, H. Zhou, Y. Zhang, J. Shen, X. Pang, M. Zhang, H. Wei, Y. Chen, H. Lu, J. Zuo, M. Su, Y. Qiu, W. Jia, C. Xiao, L. M. Smith, S. Yang, E. Holmes, H. Tang, G. Zhao, J. K. Nicholson, L. Li, and L. Zhao. 2008. Symbiotic gut microbes modulate human metabolic phenotypes. Proc. Natl. Acad. Sci. U.S.A. 105:2117-2122.
108. Li, X., A. Chauhan, A. M. Sheikh, S. Patil, V. Chauhan, X. M. Li, L. Ji, T. Brown, and M. Malik. 2009. Elevated immune response in the brain of autistic patients. J. Neuroimmunol. 207:111-116.
109. Liang, J., H. Takeuchi, Y. Doi, J. Kawanokuchi, Y. Sonobe, S. Jin, I. Yawata, H. Li, S. Yasuoka, T. Mizuno, and A. Suzumura. 2008. Excitatory amino acid transporter expression by astrocytes is neuroprotective against microglial excitotoxicity. Brain Res. 1210:11-19.
110. Lovaas, O. I. 1987. Behavioral treatment and normal educational and intellectual functioning in young autistic children. J. Consult. Clin. Psychol. 55:3-9.
111. Lowry, C. A., J. H. Hollis, A. de Vries, B. Pan, L. R. Brunet, J. R. Hunt, J. F. Paton, E. van Kampen, D. M. Knight, A. K. Evans, G. A. Rook, and S. L. Lightman. 2007. Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior. Neuroscience 146:756-772.
112. Lozovaya, N. and A. D. Miller. 2003. Chemical neuroimmunology: Health in a nutshell bidirectional communication between immune and stress (limbic-hypothalamicpituitary-adrenal) systems. Chembiochem 4:466-484.
113. MacFabe, D. F., D. P. Cain, K. Rodriguez-Capote, A. E. Franklin, J. E. Hoffman, F. Boon, A. R. Taylor, M. Kavaliers, and K. P. Ossenkopp. 2007. 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. 176:149-169.
114. Maes, M., R. Verkerk, E. Vandoolaeghe, F. Van Hunsel, H. Neels, A. Wauters, P. Demedts, and S. Scharpe. 1997. Serotonin-immune interactions in major depression: Lower serum tryptophan as a marker of an immune-inflammatory response. Eur. Arch. Psychiatry Clin. Neurosci. 247:154-161.
115. Malow, B. A. 2004. Sleep disorders, epilepsy, and autism. Ment. Retard. Dev. Disabil. Res. Rev. 10:122-125.
116. Malow, B. A., M. L. Marzec, S. G. McGrew, L. Wang, L. M. Henderson, and W. L. Stone. 2006. Characterizing sleep in children with autism spectrum disorders: A multidimensional approach. Sleep 29:1563-1571.
117. Mattson, M. P. 2007. Mitochondrial regulation of neuronal plasticity. Neurochem. Res. 32:707-715.
118. Mattson, M. P. 2008. Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann. N.Y. Acad. Sci. 1144:97-112.
119. Mattson, M. P. and D. Liu. 2002. Energetics and oxidative stress in synaptic plasticity and neurodegenerative disorders. Neuromolecular Med. 2:215-231.
120. McDougle, C. J., S. T. Naylor, D. J. Cohen, G. K. Aghajanian, G. R. Heninger, and L. H. Price. 1996. Effects of tryptophan depletion in drug-free adults with autistic disorder. Arch. Gen. Psychiatry 53:993-1000.
121. McGinnis, W. R. 2007. Could oxidative stress from psychosocial stress affect neurodevelopment in autism? J. Autism Dev. Disord. 37:993-994.
122. Mehler, M. F. and D. P. Purpura. 2009. Autism, fever, epigenetics and the locus coeruleus. Brain Res. Rev. 59:388-392.
123. Miller, A. H., V. Maletic, and C. L. Raison. 2009. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol. Psychiatry 65:732-741.
124. Ming, X., P. O. Julu, J. Wark, F. Apartopoulos, and S. Hansen. 2004. Discordant mental and physical efforts in an autistic patient. Brain Dev. 26:519-524.
125. Minshew, N. J., G. Goldstein, S. M. Dombrowski, K. Panchalingam, and J. W. Pettegrew. 1993. A preliminary 31P MRS study of autism: Evidence for undersynthesis and increased degradation of brain membranes. Biol. Psychiatry 33:762-773.
126. Moretti, P., T. Sahoo, K. Hyland, T. Bottiglieri, S. Peters, D. del Gaudio, B. Roa, S. Curry, H. Zhu, R. H. Finnell, J. L. Neul, V. T. Ramaekers, N. Blau, C. A. Bacino, G. Miller, and F. Scaglia. 2005. Cerebral folate deficiency with developmental delay, autism, and response to folinic acid. Neurology 64:1088-1090.
127. Morrow, E. M., S. Y. Yoo, S. W. Flavell, T. K. Kim, Y. Lin, R. S. Hill, N. M. Mukaddes, S. Balkhy, G. Gascon, A. Hashmi, S. Al-Saad, J. Ware, R. M. Joseph, R. Greenblatt, D. Gleason, J. A. Ertelt, K. A. Apse, A. Bodell, J. N. Partlow, B. Barry, H. Yao, K. Markianos, R. J. Ferland, M. E. Greenberg, and C. A. Walsh. 2008. Identifying autism loci and genes by tracing recent shared ancestry. Science 321:218-223.
128. Morton, J. and U. Frith. 1995. Causal modelling: A structural approach to developmental psychopathology. In Manual of Developmental Psychopathology, eds. D. Cicchetti and D. J. Cohen. New York: John Wiley, pp. 357-390.
129. Muller, R. A. 2007. The study of autism as a distributed disorder. Ment. Retard. Dev. Disabil. Res. Rev. 13:85-95.
130. Natowicz, M. 2004. Personal communication.
131. Nelson, K. B., J. K. Grether, L. A. Croen, J. M. Dambrosia, B. F. Dickens, L. L. Jelliffe, R. L. Hansen, and T. M. Phillips. 2001. Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. Ann. Neurol.49:597-606.
132. Newschaffer, C. J., L. A. Croen, J. Daniels, E. Giarelli, J. K. Grether, S. E. Levy, D. S. Mandell, L. A. Miller, and J. Pinto-Martin. 2007. The epidemiology of autism spectrum disorders. Annu. Rev. Pub. Health 28:235-256.
133. Nicholson, J. K., E. Holmes, and I. D. Wilson. 2005. Gut microorganisms, mammalian metabolism and personalized health care. Nat. Rev. Microbiol. 3:431-438.
134. Noble, D. 2008. The Music of Life. New York: Oxford University Press.
135. Nyffeler, M., U. Meyer, B. K. Yee, J. Feldon, and I. Knuesel. 2006. Maternal immune activation during pregnancy increases limbic GABAA receptor immunoreactivity in the adult offspring: Implications for schizophrenia. Neuroscience 143:51-62.
136. Oliveira, G., L. Diogo, M. Grazina, P. Garcia, A. Ataide, C. Marques, T. Miguel, L. Borges, A. M. Vicente, and C. R. Oliveira. 2005. Mitochondrial dysfunction in autism spectrum disorders: A population-based study. Dev. Med. Child Neurol. 47:185-189.
137. Olmsted, D. 2005. The age of autism: Case 1 revisited. American Chronicle. Available online at http:/www.americanchronicle.com/articles/view/1872
138. Opler, M. G. and E. S. Susser. 2005. Fetal environment and schizophrenia. Environ. Health Perspect. 113:1239-1242.
139. Orellana, J. A., P. J. Saez, K. F. Shoji, K. A. Schalper, N. Palacios-Prado, V. Velarde, C. Giaume, M. V. Bennett, and J. C. Saez. 2009. Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration. Antioxid. Redox Signal. 11:369-399.
140. Page, T. 2000. Metabolic approaches to the treatment of autism spectrum disorders. J. Autism Dev. Disord. 30:463-469.
141. Page, T. and C. Moseley. 2002. Metabolic treatment of hyperuricosuric autism. Prog. Neuropsychopharmacol. Biol Psychiatry 26:397-400.
142. Pan, J. W., A. Williamson, I. Cavus, H. P. Hetherington, H. Zaveri, O. A. Petroff, and D. D. Spencer. 2008. Neurometabolism in human epilepsy. Epilepsia 49(Suppl. 3):31-41.
143. Pardo, C. A., D. Wheeler, Vargas. D., N. Haughey, and A. Zimmerman. 2008. Abnormalities in cholesterol, ceramides and markers of oxidative stress are revealed by lipidomic analysis of brain tissues in autism. IMFAR: Poster #155.13.
144. Parracho, H. M., M. O. Bingham, G. R. Gibson, and A. L. McCartney. 2005. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J. Med. Microbiol. 54:987-991.
145. Patterson, P. H. 2002. Maternal infection: Window on neuroimmune interactions in fetal brain development and mental illness. Curr. Opin. Neurobiol. 12:115-118.
146. Persico, A. M. and T. Bourgeron. 2006. Searching for ways out of the autism maze: Genetic, epigenetic and environmental clues. Trends Neurosci. 29:349-358.
147. Peschanski, M. 1991. Le temps venu de la “Neurogliobiologie.” Médecine Sciences 7:766-767.
148. Pessah, I. N. and P. J. Lein. 2008. Evidence for environmental susceptibility in autism: What we need to know about gene x environment interactions. In Autism: Current Theories and Models, ed. A. Zimmerman, Totowa, NJ: Humana Press, pp. 409-428.
149. Qin, L., X. Wu, M. L. Block, Y. Liu, G. R. Breese, J. S. Hong, D. J. Knapp, and F. T. Crews. 2007. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55:453-462.
150. Raymond, G. V., M. L. Bauman, and T. L. Kemper. 1996. Hippocampus in autism: A Golgi analysis. Acta Neuropathol. 91:117-119.
151. Rose, G. 2001. Sick individuals and sick populations. Int. J. Epidemiol. 30:427-432; discussion 433-434.
152. Rosenberger-Debiesse, J. and M. Coleman. 1986. Preliminary evidence for multiple etiologies in autism. J. Autism Dev. Disord. 16:385-392.
153. Rossignol, D. A. and J. J. Bradstreet. 2008. Evidence of mitochondrial dysfunction in autism and implications for treatment. Special Issue on Autism Spectrum Disorders, Am. J. Biochem. Biotechnol. 4:208-217.
154. Rothman, K. J. and S. Greenland. 1998. Modern Epidemiology. Philadelphia, PA: Lippincott Williams and Wilkins.
155. Ruhl, A. 2005. Glial cells in the gut. Neurogastroenterol. Motil. 17:777-790.
156. Rutter, M. 2007. Gene-environment interdependence. Dev. Sci. 10:12-18.
157. Rutter, M. 2008. Biological implications of gene-environment interaction. J. Abnorm. Child Psychol. 36:969-975.
158. Rutter, M. and L. Lockyer. 1967. A five to fifteen year follow-up study of infantile psychosis. I. Description of sample. Br. J. Psychiatry 113:1169-1182.
159. Rutter, M., D. Greenfeld, and L. Lockyer. 1967. A five to fifteen year follow-up study of infantile psychosis. II. Social and behavioural outcome. Br. J. Psychiatry 113:1183-1199.
160. Sajdel-Sulkowska, E. M., B. Lipinski, H. Windom, T. Audhya, and W. McGinnis. 2008. Oxidative stress in autism: Elevated cerebellar 3-nitrotyrosine levels. Am. J. Biochem. Biotechnol. (Special Issue on Autism Spectrum Disorders) 4:73-84.
161. Sandler, R. H., S. M. Finegold, E. R. Bolte, C. P. Buchanan, A. P. Maxwell, M. L. Vaisanen, M. N. Nelson, and H. M. Wexler. 2000. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J. Child Neurol. 15:429-435.
162. Schousboe, A. and H. S. Waagepetersen. 2005. Role of astrocytes in glutamate homeostasis: Implications for excitotoxicity. Neurotox. Res. 8:221-225.
163. Schwarz, E. and S. Bahn. 2008. The utility of biomarker discovery approaches for the detection of disease mechanisms in psychiatric disorders. Br. J. Pharmacol. 153(Suppl. 1): S133-S136.
164. Serles, W., L. M. Li, S. B. Antel, F. Cendes, J. Gotman, A. Olivier, F. Andermann, F. Dubeau, and D. L. Arnold. 2001. Time course of postoperative recovery of N-acetyl-aspartate in temporal lobe epilepsy. Epilepsia 42:190-197.
165. Shi, L., S. H. Fatemi, R. W. Sidwell, and P. H. Patterson. 2003. Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J. Neurosci. 23:297-302.
166. Shultz, S. R., D. F. Macfabe, S. Martin, J. Jackson, R. Taylor, F. Boon, K. P. Ossenkopp, and D. P. Cain. 2009. Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long-Evans rat: Further development of a rodent model of autism. Behav. Brain Res. 200: 33-41.
167. Shultz, S. R., D. F. MacFabe, K. P. Ossenkopp, S. Scratch, J. Whelan, R. Taylor, and D. P. Cain. 2008b. Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: Implications for an animal model of autism. Neuropharmacology 54:901-911.
168. Slikker, W. and L. W. Chang. 1998. Handbook of Developmental Neurotoxicology. San Diego, CA: Academic Press.
169. Smith, S. E., J. Li, K. Garbett, K. Mirnics, and P. H. Patterson. 2007. Maternal immune activation alters fetal brain development through interleukin-6. J. Neurosci. 27:10695-106702.
170. Song, Y., C. Liu, and S. M. Finegold. 2004. Real-time PCR quantitation of clostridia in feces of autistic children. Appl. Environ. Microbiol. 70:6459-6465.
171. Standridge, J. B. 2006. Vicious cycles within the neuropathophysiologic mechanisms of Alzheimer’s disease. Curr. Alzheimer Res. 3:95-108.
172. Sundaram, S. K., A. Kumar, M. I. Makki, M. E. Behen, H. T. Chugani, and D. C. Chugani. 2008. Diffusion tensor imaging of frontal lobe in autism spectrum disorder. Cereb. Cortex 18:2659-2665.
173. Sutera, S., J. Pandey, E. L. Esser, M. A. Rosenthal, L. B. Wilson, M. Barton, J. Green, S. Hodgson, D. L. Robins, T. Dumont-Mathieu, and D. Fein. 2007. Predictors of optimal outcome in toddlers diagnosed with autism spectrum disorders. J. Autism Dev. Disord. 37:98-107.
174. Theis, M., G. Sohl, J. Eiberger, and K. Willecke. 2005. Emerging complexities in identity and function of glial connexins. Trends Neurosci. 28:188-195.
175. Thevarkunnel, S., M. A. Martchek, T. L. Kemper, M. B. Bauman, and G. J. Blatt. 2004. A neuroanatomical study of the brainstem nuclei in autism. Society for Neuroscience Abstract 1028.14.
176. Tilleux, S. and E. Hermans. 2007. Neuroinflammation and regulation of glial glutamate uptake in neurological disorders. J. Neurosci. Res. 85:2059-2070.
177. Tobinick, E. L. and H. Gross. 2008a. Rapid cognitive improvement in Alzheimer’s disease following perispinal etanercept administration. J. Neuroinflammation 5:2.
178. Tobinick, E. L. and H. Gross. 2008b. Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer’s disease. BMC Neurol. 8:27.
179. Tomchek, S. D. and W. Dunn. 2007. Sensory processing in children with and without autism: A comparative study using the short sensory profile. Am. J. Occup. Ther. 61:190-200.
180. Torrente, F., P. Ashwood, R. Day, N. Machado, R. I. Furlano, A. Anthony, S. E. Davies, A. J. Wakefield, M. A. Thomson, J. A. Walker-Smith, and S. H. Murch. 2002. Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism. Mol. Psychiatry 7: 334, 375-382.
181. Tsuang, M. T., J. L. Bar, W. S. Stone, and S. V. Faraone. 2004. Gene-environment interactions in mental disorders. World Psychiatry 3:73-83.
182. Tuchman, R. and I. Rapin. 2006. Autism: A Neurobiological Disorder of Early Brain Development. London, U.K.: Mac Keith Press.
183. Valicenti-McDermott, M., K. McVicar, I. Rapin, B. K. Wershil, H. Cohen, and S. Shinnar. 2006. Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease. J. Dev. Behav. Pediatr. 27:S128-S136.
184. Vancassel, S., G. Durand, C. Barthelemy, B. Lejeune, J. Martineau, D. Guilloteau, C. Andres, and S. Chalon. 2001. Plasma fatty acid levels in autistic children. Prostaglandins Leukot. Essent. Fatty Acids 65:1-7.
185. Vargas, D. L., C. Nascimbene, C. Krishnan, A. W. Zimmerman, and C. A. Pardo. 2005. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann. Neurol. 57:67-81.
186. Vargas, D. L., V. Bandaru, M. C. Zerrate, A. W. Zimmerman, N. Haughey, and C. A. Pardo. 2006. Oxidative stress in brain tissues from autistic patients: Increased concentration of isoprostanes. IMFAR: Poster #PS2.6.
187. Vasconcelos, M. M., A. R. Brito, R. C. Domingues, L. C. da Cruz, Jr., E. L. Gasparetto, J. Werner, Jr., and J. P. Goncalves. 2008. Proton magnetic resonance spectroscopy in school-aged autistic children. J. Neuroimaging 18:288-295.
188. Visscher, P. M., W. G. Hill, and N. R. Wray. 2008. Heritability in the genomics era: Concepts and misconceptions. Nat. Rev. Genet. 9:255-266.
189. Wallace, K. B. and A. A. Starkov. 2000. Mitochondrial targets of drug toxicity. Annu. Rev. Pharmacol. Toxicol. 40:353-388.
190. Whitney, E. R., T. L. Kemper, M. L. Bauman, D. L. Rosene, and G. J. Blatt. 2008. Cerebellar Purkinje cells are reduced in a subpopulation of autistic brains: A stereological experiment using Calbindin-D28k. Cerebellum 7:406-416.
191. Wrona, D. 2006. Neural-immune interactions: An integrative view of the bidirectional relationship between the brain and immune systems. J. Neuroimmunol. 172:38-58.
192. Yao, Y., W. J. Walsh, W. R. McGinnis, and D. Pratico. 2006. Altered vascular phenotype in autism: Correlation with oxidative stress. Arch. Neurol. 63:1161-1164.
193. Yip, J., J. J. Soghomonian, and G. J. Blatt. 2008. Increased GAD67 mRNA expression in cerebellar interneurons in autism: Implications for Purkinje cell dysfunction. J. Neurosci. Res. 86:525-530.
194. Zeegers, M., J. van der Grond, E. van Daalen, J. Buitelaar, and H. van Engeland. 2007. Proton magnetic resonance spectroscopy in developmentally delayed young boys with or without autism. J. Neural Transm. 114:289-295.
195. Zimmerman, A. 2008. Personal communication.
196. Zoghbi, H. Y. 2003. Postnatal neurodevelopmental disorders: Meeting at the synapse? Science 302:826-830.