Current progress and challenges in the search for autism biomarkers

Disease Markers

Volumn 35, Issue 1, 2013, Pages 55-65

  Voineagu, Irina ^a   Yoo, Hee Jeong ^b  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

^b Seoul National University Bundang Hospital   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; BIOLOGICAL MARKER; GAMMA INTERFERON; IMMUNOGLOBULIN G; INTERLEUKIN 1; INTERLEUKIN 12; INTERLEUKIN 6; INTERLEUKIN 8; MACROPHAGE MIGRATION INHIBITION FACTOR; SEROTONIN;

ADAPTIVE IMMUNITY; AUTISM; BEHAVIOR THERAPY; BLOOD SAMPLING; DIFFUSION TENSOR IMAGING; DISEASE MARKER; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DNA SEQUENCE; EARLY DIAGNOSIS; EARLY INTERVENTION; ELECTROPHYSIOLOGY; EVOKED AUDITORY RESPONSE; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENE EXPRESSION PROFILING; GENETIC MARKER; HEAD CIRCUMFERENCE; HUMAN; METABOLIC DISORDER; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; OXIDATIVE STRESS; PRIORITY JOURNAL; PROGNOSIS; REVIEW; RISK ASSESSMENT; SUPERIOR TEMPORAL GYRUS; URINALYSIS;

ANIMALS; BRAIN; CEPHALOMETRY; CHILD DEVELOPMENT DISORDERS, PERVASIVE; GENETIC MARKERS; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MITOCHONDRIA; OXIDATIVE STRESS; SEROTONIN; TRANSCRIPTOME;

EID: 84883065688     PISSN: 02780240     EISSN: 18758630     Source Type: Journal    
DOI: 10.1155/2013/476276     Document Type: Review

References (121)

1. S. H. Kim and C. Lord, "The behavioral manifestations for autism spectrum disorders," in The Neuroscience for autism Spectrum Disorders, pp. 25-37, 2013.
2. B. S. Abrahams and D. H. Geschwind, "Advances in autism genetics: on the threshold for a new neurobiology," Nature Reviews Genetics, vol. 9, no. 5, pp. 341-355, 2008.
3. A. P. Association, Diagnostic and Statistical Manual for Mental Disorders: DSM-IV, American Psychiatric Association, Washington, DC, USA, 2000.
4. M. Elsabbagh, G. Divan, Y. J. Koh et al., "Global prevalence for autism and other pervasive developmental disorders," Autism Research, vol. 5, no. 3, pp. 160-179, 2012.
5. C. Lord, E. Petkova, V. Hus et al., "A multisite study for the clinical diagnosis for different autism spectrum disorders," Archives for General Psychiatry, vol. 69, no. 3, pp. 306-313, 2012.
6. D. H. Skuse, "DSM-5's conceptualization for autistic disorders," Journal for the American Academy for Child & Adolescent Psychiatry, vol. 51, no. 4, pp. 344-346, 2012.
7. J. C. McPartland, B. Reichow, and F. R. Volkmar, "Sensitivity and specificity for proposed DSM-5 diagnostic criteria for autism spectrum disorder," Journal for the American Academy for Child and Adolescent Psychiatry, vol. 51, no. 4, pp. 368-383, 2012.
8. C. Ecker, W. Spooren, and D. G. Murphy, "Translational approaches to the biology for Autism: false dawn or a new era?" Molecular Psychiatry, vol. 18, no. 4, pp. 435-442, 2013.
9. L. Kanner, "The original description for autism, with excellent case examples," Nervous Child, vol. 2, pp. 217-250, 1943.
10. J. Atkinson, W. A. Colburn, V G DeGruttola et al., "Biomarkers and surrogate endpoints: preferred definitions and conceptual framework," Clinical Pharmacology and Therapeutics, vol. 69, no. 3, pp. 89-95, 2001.
11. P. Walsh, M. Elsabbagh, P. Bolton, and I. Singh, "In search for biomarkers for autism: scientific, social and ethical challenges," Nature Reviews Neuroscience, vol. 12, no. 10, pp. 603-612, 2011.
12. E. Ben Itzchak, E. Lahat, R. Burgin, and A. D. Zachor, "Cognitive, behavior and intervention outcome in young children with autism," Research in Developmental Disabilities, vol. 29, no. 5, pp. 447-458, 2008.
13. G. Dawson, S. Rogers, J. Munson et al., "Randomized, controlled trial for an intervention for toddlers with autism: the early start Denver model," Pediatrics, vol. 125, no. 1, pp. e17-e23, 2010.
14. S. J. Rogers and L. A. Vismara, "Evidence-based comprehensive treatments for early autism," Journal for Clinical Child and Adolescent Psychology, vol. 37, no. 1, pp. 8-38, 2008.
15. L. D. Wiggins, J. Baio, and C. Rice, "Examination for the time between first evaluation and first autism spectrum diagnosis in a population-based sample," Journal for Developmental and Behavioral Pediatrics, vol. 27, supplement 2, pp. S79-S87, 2006.
16. M. W. State and P. Levitt, "The conundrums for understanding genetic risks for autism spectrum disorders," Nature Neuroscience, vol. 14, no. 12, pp. 1499-1506, 2011.
17. R. M. Cantor, "Molecular genetics for autism," Current Psychiatry Reports, vol. 11, no. 2, pp. 137-142, 2009.
18. V. W. Hu, "Subphenotype-dependent disease markers for diagnosis and personalized treatment for autism spectrum disorders," Disease Markers, vol. 33, no. 5, pp. 277-288, 2012.
19. D. M. Werling and D. H. Geschwind, "Sex differences in autism spectrum disorders," Current Opinion in Neurology, vol. 26, no. 2, pp. 146-153, 2013.
20. E. Schwarz, P. C. Guest, H. Rahmoune et al., "Sex-specific serum biomarker patterns in adults with Asperger's syndrome," Molecular Psychiatry, vol. 16, no. 12, pp. 1213-1220, 2011.
21. J. M. Lattin, J. D. Carroll, and P. E. Green, Analyzing Multivariate Data, Thomson Brooks/Cole, Pacific Grove, Calif, USA, 2003.
22. H. V. Ratajczak, "Theoretical aspects for autism: biomarkersa review," Journal for Immunotoxicology, vol. 8, no. 1, pp. 80-94, 2011.
23. K. A. Stigler and C. J. McDougley, "Structural and functional MRI studies for autism spectrum disorders," in The Neuroscience for autism Spectrum Disorders, pp. 251-266, 2013.
24. R. A. Carper, P. Moses, Z. D. Tigue, and E. Courchesne, "Cerebral lobes in autism: early hyperplasia and abnormal age effects," NeuroImage, vol. 16, no. 4, pp. 1038-1051, 2002.
25. C. C. Brun, R. Nicolson, N. Leporé et al., "Mapping brain abnormalities in boys with autism," Human Brain Mapping, vol. 30, no. 12, pp. 3887-3900, 2009.
26. S. J. M. C. Palmen, H. E. Hulshof Pol, C. Kemner et al., "Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder," Psychological Medicine, vol. 35, no. 4, pp. 561-570, 2005.
27. C. Ecker, A. Marquand, J. Mourão-Miranda et al., "Describing the brain in autism in five dimensions - magnetic resonance imaging-assisted diagnosis for autism spectrum disorder using a multiparameter classification approach," Journal for Neuroscience, vol. 30, no. 32, pp. 10612-10623, 2010.
28. L. Q. Uddin, V. Menon, C. B. Young et al., "Multivariate searchlight classification for structural magnetic resonance imaging in children and adolescents with autism," Biological Psychiatry, vol. 70, no. 9, pp. 833-841, 2011.
29. M. Ingalhalikar, D. Parker, L. Bloy, T. P. L. Roberts, and R. Verma, "Diffusion based abnormality markers for pathology: toward learned diagnostic prediction for ASD," NeuroImage, vol. 57, no. 3, pp. 918-927, 2011.
30. N. Lange, M. B. Dubray, J. E. Lee et al., "Atypical diffusion tensor hemispheric asymmetry in autism," Autism Research, vol. 3, no. 6, pp. 350-358, 2010.
31. N. J. Minshew and T. A. Keller, "The nature for brain dysfunction in autism: functional brain imaging studies," Current Opinion in Neurology, vol. 23, no. 2, pp. 124-130, 2010.
32. K. Pierce, R.-A. Müller, J. Ambrose, G. Allen, and E. Courchesne, "Face processing occurs outside the fusiform 'face area' in autism: evidence from functional MRI," Brain, vol. 124, no. 10, pp. 2059-2073, 2001.
33. R. T. Schultz, I. Gauthier, A. Klin et al., "Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome," Archives for General Psychiatry, vol. 57, no. 4, pp. 331-340, 2000.
34. D. Hubl, S. Bölte, S. Feineis-Matthews et al., "Functional imbalance for visual pathways indicates alternative face processing strategies in autism," Neurology, vol. 61, no. 9, pp. 1232-1237, 2003.
35. B. A. Corbett, V. Carmean, S. Ravizza et al., "A functional and structural study for emotion and face processing in children with autism," Psychiatry Research, vol. 173, no. 3, pp. 196-205, 2009.
36. K. A. Pelphrey, J. P. Morris, G. Mccarthy, and K. S. Labar, "Perception for dynamic changes in facial affect and identity in autism," Social Cognitive and Affective Neuroscience, vol. 2, no. 2, pp. 140-149, 2007.
37. M. Dapretto, M. S. Davies, J. H. Pfeifer et al., "Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders," Nature Neuroscience, vol. 9, no. 1, pp. 28-30, 2006.
38. E. Redcay and E. Courchesne, "Deviant functional magnetic resonance imaging patterns for brain activity to speech in 23-year-old children with autism spectrum disorder," Biological Psychiatry, vol. 64, no. 7, pp. 589-598, 2008.
39. D. P. Kennedy and E. Courchesne, "The intrinsic functional organization for the brain is altered in autism," NeuroImage, vol. 39, no. 4, pp. 1877-1885, 2008.
40. C. S. Monk, S. J. Peltier, J. L. Wiggins et al., "Abnormalities for intrinsic functional connectivity in autism spectrum disorders," NeuroImage, vol. 47, no. 2, pp. 764-772, 2009.
41. J. S. Anderson, J. A. Nielsen, A. L. Froehlich et al., "Functional connectivity magnetic resonance imaging classification for autism," Brain, vol. 134, no. 12, pp. 3742-3754, 2011.
42. W. Bosl, A. Tierney, H. Tager-Flusberg, and C. Nelson, "EEG complexity as a biomarker for autism spectrum disorder risk," BMC Medicine, vol. 9, article 18, 2011.
43. G. Dawson, E. J. H. Jones, K. Merkle et al., "Early behavioral intervention is associated with normalized brain activity in young children with autism," Journal for the American Academy for Child & Adolescent Psychiatry, vol. 51, no. 11, pp. 1150-1159, 2012.
44. T. P. L. Roberts, S. Y. Khan, M. Rey et al., "MEG detection for delayed auditory evoked responses in autism spectrum disorders: towards an imaging biomarker for autism," Autism Research, vol. 3, no. 1, pp. 8-18, 2010.
45. S. J. Webb, G. Dawson, R. Bernier, and H. Panagiotides, "ERP evidence for atypical face processing in young children with autism," Journal for autism and Developmental Disorders, vol. 36, no. 7, pp. 881-890, 2006.
46. R. Griffin and C. Westbury, "Infant EEG activity as a biomarker for autism: a promising approach or a false promise?" BMC Medicine, vol. 9, article 61, 2011.
47. A. Bailey, A. Le Couteur, I. Gottesman et al., "Autism as a strongly genetic disorder: evidence from a British twin study," Psychological Medicine, vol. 25, no. 1, pp. 63-77, 1995.
48. S. Steffenburg, C. Gillberg, L. Hellgren et al., "A twin study for autism in Denmark, Finland, Iceland, Norway and Sweden," Journal for Child Psychology and Psychiatry and Allied Disciplines, vol. 30, no. 3, pp. 405-416, 1989.
49. J. Hallmayer, S. Cleveland, A. Torres et al., "Genetic heritability and shared environmental factors among twin pairs with autism," Archives for General Psychiatry, vol. 68, no. 11, pp. 1095-1102, 2011.
50. A. L. Beaudet, "The utility for chromosomal microarray analysis in developmental and behavioral pediatrics," Child Development, vol. 84, no. 1, pp. 121-132, 2013.
51. K. M. Heil and C. P. Schaaf, "The genetics for autism spectrum disorders - a guide for clinicians," Current Psychiatry Reports, vol. 15, no. 1, article 334, 2013.
52. D. T. Miller, M. P. Adam, S. Aradhya et al., "Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies," American Journal for Human Genetics, vol. 86, no. 5, pp. 749-764, 2010.
53. H.-T. Chao, H. Chen, R. C. Samaco et al., "Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes," Nature, vol. 468, no. 7321, pp. 263-269, 2010.
54. G. Dolen, E. Osterweil, B. S. Shankaranarayana Rao et al., "Correction for fragile X syndrome in mice," Neuron, vol. 56, no. 6, pp. 955-962, 2007.
55. O. Peñagarikano, B. S. Abrahams, E. I. Herman et al., "Absence for CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits," Cell, vol. 147, no. 1, pp. 235-246, 2011.
56. S. E. P. Smith, Y.-D. Zhou, G. Zhang, Z. Jin, D. C. Stoppel, and M. P. Anderson, "Increased gene dosage for Ube3a results in autism traits and decreased glutamate synaptic transmission in mice," Science Translational Medicine, vol. 3, no. 103, article 103ra97, 2011.
57. M. W. State, "The genetics for child psychiatric disorders: focus on autism and tourette syndrome," Neuron, vol. 68, no. 2, pp. 254-269, 2010.
58. B. M. Neale, Y. Kou, L. Liu et al., "Patterns and rates for exonic de novo mutations in autism spectrum disorders," Nature, vol. 485, no. 7397, pp. 242-245, 2012.
59. B. J. O'Roak, L. Vives, S. Girirajan et al., "Sporadic autism exomes reveal a highly interconnected protein network for de novo mutations," Nature, vol. 485, no. 7397, pp. 246-250, 2012.
60. S. J. Sanders, M. T. Murtha, A. R. Gupta et al., "De novo mutations revealed by whole-exome sequencing are strongly associated with autism," Nature, vol. 485, no. 7397, pp. 237-241, 2012.
61. E. T. Lim, S. Raychaudhuri, S. J. Sanders et al., "Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders," Neuron, vol. 77, no. 2, pp. 235-242, 2013.
62. T. W. Yu, M. H. Chahrour, M. E. Coulter et al., "Using whole-exome sequencing to identify inherited causes for autism," Neuron, vol. 77, no. 2, pp. 259-273, 2013.
63. E. Skafidas, R. Testa, D. Zantomio, G. Chana, I. P. Everall, and C. Pantelis, "Predicting the diagnosis for autism spectrum disorder using gene pathway analysis," Molecular Psychiatry, 2012.
64. Y. Jiao, R. Chen, X. Ke et al., "Predictive models for subtypes for autism spectrum disorder based on single-nucleotide polymorphisms and magnetic resonance imaging," Advances in Medical Sciences, vol. 56, no. 2, pp. 334-342, 2011.
65. A. M. Enstrom, L. Lit, C. E. Onore et al., "Altered gene expression and function for peripheral blood natural killer cells in children with autism," Brain, Behavior, and Immunity, vol. 23, no. 1, pp. 124-133, 2009.
66. J. P. Gregg, L. Lit, C. A. Baron et al., "Gene expression changes in children with autism," Genomics, vol. 91, no. 1, pp. 22-29, 2008.
67. V. W. Hu, B. C. Frank, S. Heine, N. H. Lee, and J. Quackenbush, "Gene expression profiling for lymphoblastoid cell lines from monozygotic twins discordant in severity for autism reveals differential regulation for neurologically relevant genes," BMC Genomics, vol. 7, article 118, 2006.
68. V. W. Hu, A. T. Nguyen, K. S. Kim et al., "Gene expression profiling for lymphoblasts from autistic and nonaffected sib pairs: altered pathways in neuronal development and steroid biosynthesis," PLoS ONE, vol. 4, no. 6, article e5775, 2009.
69. V. W. Hu and M. E. Steinberg, "Novel clustering for items from the autism diagnostic interview-revised to define phenotypes within autism spectrum disorders," Autism Research, vol. 2, no. 2, pp. 67-77, 2009.
70. C. Lintas, R. Sacco, and A. M. Persico, "Genome-wide expression studies in autism spectrum disorder, Rett syndrome, and Down syndrome," Neurobiology for Disease, vol. 45, no. 1, pp. 57-68, 2012.
71. I. Voineagu, "Gene expression studies in autism: moving from the genome to the transcriptome and beyond," Neurobiology for Disease, vol. 45, no. 1, pp. 69-75, 2012.
72. K. Garbett, P. J. Ebert, A. Mitchell et al., "Immune transcriptome alterations in the temporal cortex for subjects with autism," Neurobiology for Disease, vol. 30, no. 3, pp. 303-311, 2008.
73. I. Voineagu, X. Wang, P. Johnston et al., "Transcriptomic analysis for autistic brain reveals convergent molecular pathology," Nature, vol. 474, no. 7351, pp. 380-386, 2011.
74. J. T. Morgan, G. Chana, C. A. Pardo et al., "Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism," Biological Psychiatry, vol. 68, no. 4, pp. 368-376, 2010.
75. D. L. Vargas, C. Nascimbene, C. Krishnan, A. W. Zimmerman, and C. A. Pardo, "Neuroglial activation and neuroinflammation in the brain for patients with autism," Annals for Neurology, vol. 57, no. 1, pp. 67-81, 2005.
76. S. J. Glatt, M. T. Tsuang, M. Winn et al., "Blood-based gene expression signatures for infants and toddlers with autism," Journal for the American Academy for Child & Adolescent Psychiatry, vol. 51, no. 9, pp. 934.e2-944.e2, 2012.
77. S. W. Kong, C. D. Collins, Y. Shimizu-Motohashi et al., "Characteristics and predictive value for blood transcriptome signature in males with autism spectrum disorders," PLoS One, vol. 7, no. 12, article e49475, 2012.
78. C. Onore, M. Careaga, and P. Ashwood, "The role for immune dysfunction in the pathophysiology for autism," Brain, Behavior, and Immunity, vol. 26, no. 3, pp. 383-392, 2012.
79. P. Ashwood, A. Enstrom, P. Krakowiak et al., "Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes," Journal for Neuroimmunology, vol. 204, no. 1-2, pp. 149-153, 2008.
80. P. Ashwood, P. Krakowiak, I. Hertz-Picciotto, R. Hansen, I. Pessah, and J. Van de Water, "Elevated plasma cytokines in autism spectrum disorders provide evidence for immune dysfunction and are associated with impaired behavioral outcome," Brain, Behavior, and Immunity, vol. 25, no. 1, pp. 40-45, 2011.
81. E. L. Grigorenko, S. S. Han, C. M. Yrigollen et al., "Macrophage migration inhibitory factor and autism spectrum disorders," Pediatrics, vol. 122, no. 2, pp. e438-e445, 2008.
82. K. Okada, K. Hashimoto, Y. Iwata et al., "Decreased serum levels for transforming growth factor-beta1 in patients with autism," Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 31, no. 1, pp. 187-190, 2007.
83. J. Croonenberghs, A. Wauters, K. Devreese et al., "Increased serum albumin, γ globulin, immunoglobulin IgG, and IgG2 and IgG4 in autism," Psychological Medicine, vol. 32, no. 8, pp. 1457-1463, 2002.
84. C. A. Molloy, A. L. Morrow, J. Meinzen-Derr et al., "Elevated cytokine levels in children with autism spectrum disorder," Journal for Neuroimmunology, vol. 172, no. 1-2, pp. 198-205, 2006.
85. A. M. Connolly, M. Chez, E. M. Streif et al., "Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera for children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy," Biological Psychiatry, vol. 59, no. 4, pp. 354-363, 2006.
86. P. Goines, L. Haapanen, R. Boyce et al., "Autoantibodies to cerebellum in children with autism associate with behavior," Brain, Behavior, and Immunity, vol. 25, no. 3, pp. 514-523, 2011.
87. C. C. Rossi, J. van de Water, S. J. Rogers, and D. G. Amaral, "Detection for plasma autoantibodies to brain tissue in young children with and without autism spectrum disorders," Brain, Behavior, and Immunity, vol. 25, no. 6, pp. 1123-1135, 2011.
88. S. Wills, M. Cabanlit, J. Bennett, P. Ashwood, D. Amaral, and J. van de Water, "Autoantibodies in autism Spectrum Disorders (ASD)," Annals for the New York Academy for Sciences, vol. 1107, pp. 79-91, 2007.
89. S. Wills, M. Cabanlit, J. Bennett, P. Ashwood, D. G. Amaral, and J. Van de Water, "Detection for autoantibodies to neural cells for the cerebellum in the plasma for subjects with autism spectrum disorders," Brain, Behavior, and Immunity, vol. 23, no. 1, pp. 64-74, 2009.
90. T. C. Theoharides, S. Asadi, and A. B. Patel, "Focal brain inflammation and autism," Journal for Neuroinflammation, vol. 10, article 46, 2013.
91. K. Suzuki, G. Sugihara, Y. Ouchi et al., "Microglial activation in young adults with autism spectrum disorder," JAMA Psychiatry, vol. 70, no. 1, pp. 49-58, 2013.
92. N. Momeni, J. Bergquist, L. Brudin et al., "A novel blood-based biomarker for detection for autism spectrum disorders," Translational Psychiatry, vol. 2, article e91, 2012.
93. L. M. Boulanger, "Immune proteins in brain development and synaptic plasticity," Neuron, vol. 64, no. 1, pp. 93-109, 2009.
94. L. Kanner, "Autistic disturbances for affective contact," Acta Paedopsychiatrica, vol. 35, no. 4, pp. 100-136, 1968.
95. M. L. Barton et al., "Early manifestations for autism spectrum disorders," in The Neuroscience for autism Spectrum Disorders, pp. 39-53, 2013.
96. G. Dawson, "Early behavioral intervention, brain plasticity, and the prevention for autism spectrum disorder," Development and Psychopathology, vol. 20, no. 3, pp. 775-803, 2008.
97. E. van Daalen, S. H. N. Swinkels, C. Dietz, H. van Engeland, and J. K. Buitelaar, "Body length and head growth in the first year for life in Autism," Pediatric Neurology, vol. 37, no. 5, pp. 324-330, 2007.
98. N. N. J. Rommelse, C. T. R. Peters, I. J. Oosterling et al., "A pilot study for abnormal growth in autism spectrum disorders and other childhood psychiatric disorders," Journal for autism and Developmental Disorders, vol. 41, no. 1, pp. 44-54, 2011.
99. L. Barnard-Brak, T. Sulak, and J. K. Ivey Hatz, "Macrocephaly in children with autism spectrum disorders," Pediatric Neurology, vol. 44, no. 2, pp. 97-100, 2011.
100. W. Froehlich, S. Cleveland, A. Torres et al., "Head circumferences in twins with and without autism spectrum disorders," Journal for autism and Developmental Disorders, 2013.
101. E. J. Mulder, G. M. Anderson, I. P. Kema et al., "Platelet serotonin levels in pervasive developmental disorders and mental retardation: diagnostic group differences, within-group distribution, and behavioral correlates," Journal for the American Academy for Child and Adolescent Psychiatry, vol. 43, no. 4, pp. 491-499, 2004.
102. R. J. Schain and D. X. Freedman, "Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children," The Journal for Pediatrics, vol. 58, no. 3, pp. 315-320, 1961.
103. M. Abney, M. S. McPeek, and C. Ober, "Broad and narrow heritabilities for quantitative traits in a founder population," American Journal for Human Genetics, vol. 68, no. 5, pp. 1302-1307, 2001.
104. L. A. Weiss, M. Abney, E. H. Cook Jr., and C. Ober, "Sex-specific genetic architecture for whole blood serotonin levels," American Journal for Human Genetics, vol. 76, no. 1, pp. 33-41, 2005.
105. J. Veenstra-VanderWeele, C. L. Muller, H. Iwamoto et al., "Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior," Proceedings for the National Academy for Sciences for the United States for America, vol. 109, no. 14, pp. 5469-5474, 2012.
106. D. A. Rossignol and R. E. Frye, "Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis," Molecular Psychiatry, vol. 17, no. 3, pp. 290-314, 2012.
107. J. R. Weissman, R. I. Kelley, M. L. Bauman et al., "Mitochondrial disease in autism spectrum disorder patients: a cohort analysis," PLoS ONE, vol. 3, no. 11, article e3815, 2008.
108. C. Correia, A. M. Coutinho, L. Diogo et al., "Brief report: high frequency for biochemical markers for mitochondrial dysfunction in autism: no association with the mitochondrial aspartate/glutamate carrier SLC25A12 gene," Journal for autism and Developmental Disorders, vol. 36, no. 8, pp. 1137-1140, 2006.
109. G. Oliveira, L. Diogo, M. Grazina et al., "Mitochondrial dysfunction in autism spectrum disorders: a population-based study," Developmental Medicine and Child Neurology, vol. 47, no. 3, pp. 185-189, 2005.
110. D. A. Rossignol and R. E. Frye, "A review for research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mito-chondrial dysfunction and environmental toxicant exposures," Molecular Psychiatry, vol. 17, no. 4, pp. 389-401, 2012.
111. D. W. Austin and K. Shandley, "An investigation for porphyrinuria in Australian children with autism," Journal for Toxicology and Environmental Health A, vol. 71, no. 20, pp. 1349-1351, 2008.
112. J. S. Woods, S. E. Armel, D. I. Fulton et al., "Urinary porphyrin excretion in neurotypical and autistic children," Environmental Health Perspectives, vol. 118, no. 10, pp. 1450-1457, 2010.
113. N. J. Heyer, D. Echeverria, and J. S. Woods, "Disordered porphyrin metabolism: a potential biological marker for autism risk assessment," Autism Research, vol. 5, no. 2, pp. 84-92, 2012.
114. I. K. S. Yap, M. Angley, K. A. Veselkov, E. Holmes, J. C. Lindon, and J. K. Nicholson, "Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls," Journal for Proteome Research, vol. 9, no. 6, pp. 2996-3004, 2010.
115. A. Frustaci, M. Neri, A. Cesario et al., "Oxidative stress-related biomarkers in autism: systematic review and meta-analyses," Free Radical Biology and Medicine, vol. 52, no. 10, pp. 2128-2141, 2012.
116. S. J. James, P. Cutler, S. Melnyk et al., "Metabolic biomarkers for increased oxidative stress and impaired methylation capacity in children with autism," American Journal for Clinical Nutrition, vol. 80, no. 6, pp. 1611-1617, 2004.
117. S. J. James, S. Melnyk, S. Jernigan et al., "Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism," American Journal for Medical Genetics B: Neuropsychiatric Genetics, vol. 141, no. 8, pp. 947-956, 2006.
118. S. Rose, S. Melnyk, O. Pavliv et al., "Evidence for oxidative damage and inflammation associated with low glutathione redox status in the autism brain," Translational Psychiatry, vol. 2, article e134, 2012.
119. B. R. Jordan and D. F. C. Tsai, "Whole-genome association studies for multigenic diseases: ethical dilemmas arising from commercializationd the case for genetic testing for autism," Journal for Medical Ethics, vol. 36, no. 7, pp. 440-444, 2010.
120. S. W. Scherer and G. Dawson, "Risk factors for autism: translating genomic discoveries into diagnostics," Human Genetics, vol. 130, no. 1, pp. 123-148, 2011.
121. Center for Disease Control, "Public Health Genomics: Genetic Testing - ACCE Model System for Collecting, Analyzing and Disseminating Information on Genetic Tests," 2010, http://www.cdc.gov/genomics/gtesting/ACCE/FBR/index. htm.