Skip to main content

Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism

Journal of Autism and Developmental Disorders volume 42, pages 367–377 (2012)Cite this article

Abstract

Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of autism. We investigated the dynamics of an integrated metabolic pathway essential for cellular antioxidant and methylation capacity in 68 children with autism, 54 age-matched control children and 40 unaffected siblings. The metabolic profile of unaffected siblings differed significantly from case siblings but not from controls. Oxidative protein/DNA damage and DNA hypomethylation (epigenetic alteration) were found in autistic children but not paired siblings or controls. These data indicate that the deficit in antioxidant and methylation capacity is specific for autism and may promote cellular damage and altered epigenetic gene expression. Further, these results suggest a plausible mechanism by which pro-oxidant environmental stressors may modulate genetic predisposition to autism.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  • Allan, A. M., Liang, X., Luo, Y., Pak, C., Li, X., Szulwach, K. E., et al. (2008). The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits. Human Molecular Genetics, 17, 2047–2057.

    PubMed  Article  Google Scholar 

  • Andreazza, A. C., Kapczinski, F., Kauer-Sant’Anna, M., Walz, J. C., Bond, D. J., Goncalves, C. A., et al. (2009). 3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder. Journal of Psychiatry & Neuroscience, 34, 263–271.

    Google Scholar 

  • Belmonte, M. K., Cook, E. H., Jr., Anderson, G. M., Rubenstein, J. L., Greenough, W. T., Beckel-Mitchener, A., et al. (2004). Autism as a disorder of neural information processing: Directions for research and targets for therapy. Molecular Psychiatry, 9, 646–663.

    PubMed  Google Scholar 

  • Berk, M., Copolov, D., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., et al. (2008a). N-acetyl cysteine as a glutathione precursor for schizophrenia—A double-blind, randomized, placebo-controlled trial. Biological Psychiatry, 64, 361–368.

    PubMed  Article  Google Scholar 

  • Berk, M., Ng, F., Dean, O., Dodd, S., & Bush, A. I. (2008b). Glutathione: A novel treatment target in psychiatry. Trends in Pharmacological Sciences, 29, 346–351.

    PubMed  Article  Google Scholar 

  • Biswas, S., Chida, A. S., & Rahman, I. (2006). Redox modifications of protein-thiols: Emerging roles in cell signaling. Biochemical Pharmacology, 71, 551–564.

    PubMed  Article  Google Scholar 

  • Bourgeron, T. (2009). A synaptic trek to autism. Current Opinion in Neurobiology, 19, 231–234.

    PubMed  Article  Google Scholar 

  • Castro, R., Rivera, I., Struys, E. A., Jansen, E. E. W., Ravasco, P., Camilo, M. E., et al. (2003). Increased, homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease. Clinical Chemistry, 49, 1292–1296.

    PubMed  Article  Google Scholar 

  • Chan, A., Tchantchou, F., Graves, V., Rozen, R., & Shea, T. B. (2008). Dietary and genetic compromise in folate availability reduces acetylcholine, cognitive performance and increases aggression: Critical role of S-adenosyl methionine. The Journal of Nutrition, Health & Aging, 12, 252–261.

    Article  Google Scholar 

  • Chauhan, A., & Chauhan, V. (2006). Oxidative stress in autism. Pathophysiology, 13, 171–181.

    PubMed  Article  Google Scholar 

  • Costa, E., Chen, Y., Dong, E., Grayson, D. R., Kundakovic, M., Maloku, E., et al. (2009). GABAergic promoter hypermethylation as a model to study the neurochemistry of schizophrenia vulnerability. Expert Review of Neurotherapeutics, 9, 87–98.

    PubMed  Article  Google Scholar 

  • Dahlmann, H. A., Vaidyanathan, V. G., & Sturla, S. J. (2009). Investigating the biochemical impact of DNA damage with structure-based probes: Abasic sites, photodimers, alkylation adducts, and oxidative lesions. Biochemistry, 48, 9347–9359.

    PubMed  Article  Google Scholar 

  • Dean, W., & Ferguson-Smith, A. (2001). Genomic imprinting: Mother maintains methylation marks. Current Biology, 11, R527–R530.

    PubMed  Article  Google Scholar 

  • Dean, O. M., van den Buuse, M., Bush, A. I., Copolov, D. L., Ng, F., Dodd, S., et al. (2009). A role for glutathione in the pathophysiology of bipolar disorder and schizophrenia? Animal models and relevance to clinical practice. Current Medicinal Chemistry, 16, 2965–2976.

    PubMed  Article  Google Scholar 

  • Do, K. Q., Trabesinger, A. H., Kirsten-Kruger, M., Lauer, C. J., Dydak, U., Hell, D., et al. (2000). Schizophrenia: Glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. European Journal of Neuroscience, 12, 3721–3728.

    PubMed  Article  Google Scholar 

  • Dodd, S., Dean, O., Copolov, D. L., Malhi, G. S., & Berk, M. (2008). N-acetylcysteine for antioxidant therapy: Pharmacology and clinical utility. Expert Opinion on Biological Therapy, 8, 1955–1962.

    PubMed  Article  Google Scholar 

  • Dunlevy, L. P., Burren, K. A., Mills, K., Chitty, L. S., Copp, A. J., & Greene, N. D. (2006). Integrity of the methylation cycle is essential for mammalian neural tube closure. Birth Defects Research. Part A, Clinical and Molecular Teratology, 76, 544–552.

    PubMed  Article  Google Scholar 

  • Ehrlich, M. (2002). DNA methylation in cancer: Too much, but also too little. Oncogene, 21, 5400–5413.

    PubMed  Article  Google Scholar 

  • Eklow, L., Thor, H., & Orrenius, S. (1981). Formation and efflux of glutathione disulfide studied in isolated rat hepatocytes. FEBS Letters, 127, 125–128.

    PubMed  Article  Google Scholar 

  • Filomeni, G., Rotilio, G., & Ciriolo, M. R. (2002). Cell signalling and the glutathione redox system. Biochemical Pharmacology, 64, 1057–1064.

    PubMed  Article  Google Scholar 

  • Finkelstein, J. D. (2007). Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine. Clinical Chemistry and Laboratory Medicine, 45, 1694–1699.

    PubMed  Article  Google Scholar 

  • Frankenburg, F. R. (2007). The role of one-carbon metabolism in schizophrenia and depression. Harvard Review of Psychiatry, 15, 146–160.

    PubMed  Article  Google Scholar 

  • Fratelli, M., Goodwin, L. O., Orom, U. A., Lombardi, S., Tonelli, R., Mengozzi, M., et al. (2005). Gene expression profiling reveals a signaling role of glutathione in redox regulation. PNAS, 102, 13998–14003.

    PubMed  Article  Google Scholar 

  • Friso, S., Choi, S. W., Dolnikowski, G. G., & Selhub, J. (2002). A method to assess genomic DNA methylation using high-performance liquid chromatography/electrospray ionization mass spectrometry. Analytical Chemistry, 74, 4526–4531.

    PubMed  Article  Google Scholar 

  • Gauthier, J., Spiegelman, D., Piton, A., Lafreniere, R. G., Laurent, S., St-Onge, J., et al. (2009). Novel de novo SHANK3 mutation in autistic patients. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics, 150B, 421–424.

    Google Scholar 

  • Giorgio, A., Watkins, K. E., Chadwick, M., James, S., Winmill, L., Douaud, G., et al. (2010). Longitudinal changes in grey and white matter during adolescence. Neuroimage, 49, 94–103.

    PubMed  Article  Google Scholar 

  • Gottesman, I. I., & Gould, T. D. (2003). The endophenotype concept in psychiatry: Etymology and strategic intentions. American Journal of Psychiatry, 160, 636–645.

    PubMed  Article  Google Scholar 

  • Graff, J., & Mansuy, I. M. (2009). Epigenetic dysregulation in cognitive disorders. European Journal of Neuroscience, 30, 1–8.

    PubMed  Article  Google Scholar 

  • Grayson, D. R., Chen, Y., Dong, E., Kundakovic, M., & Guidotti, A. (2009). From trans-methylation to cytosine methylation: Evolution of the methylation hypothesis of schizophrenia. Epigenetics, 4, 144–149.

    PubMed  Article  Google Scholar 

  • Gregory, S. G., Connelly, J. J., Towers, A. J., Johnson, J., Biscocho, D., Markunas, C. A., et al. (2009). Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Medicine, 7, 62.

    PubMed  Article  Google Scholar 

  • Guerri, C., & Pascual, M. (2010). Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence. Alcohol, 44, 15–26.

    PubMed  Article  Google Scholar 

  • Gysin, R., Kraftsik, R., Sandell, J., Bovet, P., Chappuis, C., Conus, P., et al. (2007). Impaired glutathione synthesis in schizophrenia: Convergent genetic and functional evidence. PNAS, 104, 16621–16626.

    PubMed  Article  Google Scholar 

  • Helbock, H. J., Beckman, K. B., Shigenaga, M. K., Walter, P. B., Woodall, A. A., Yeo, H. C., et al. (1998). DNA oxidation matters: The HPLC-electrochemical detection assay of 8-oxo-deoxyguanosine and 8-oxo-guanine. PNAS, 95, 288–293.

    PubMed  Article  Google Scholar 

  • James, S. J., Melnyk, S., Fuchs, G., Reid, T., Jernigan, S., Pavliv, O., et al. (2009a). Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. American Journal of Clinical Nutrition, 89, 425–430.

    PubMed  Article  Google Scholar 

  • James, S. J., Melnyk, S., Jernigan, S., Cleves, M. A., Halsted, C. H., Wong, D. H., et al. (2006). Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 141, 947–956.

    Article  Google Scholar 

  • James, S. J., Rose, S., Melnyk, S., Jernigan, S., Blossom, S., Pavliv, O., et al. (2009b). Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. FASEB Journal, 23, 2374–2383.

    PubMed  Article  Google Scholar 

  • Jiang, Y. H., Sahoo, T., Michaelis, R. C., Bercovich, D., Bressler, J., Kashork, C. D., et al. (2004). A mixed epigenetic/genetic model for oligogenic inheritance of autism with a limited role for UBE3A. American Journal of Medical Genetics, 131A, 1–10.

    Article  Google Scholar 

  • Jones, D. P., Go, Y. M., Anderson, C. L., Ziegler, T. R., Kinkade, J. M., Jr., & Kirlin, W. G. (2004). Cysteine/cystine couple is a newly recognized node in the circuitry for biologic redox signaling and control. FASEB Journal, 18, 1246–1248.

    PubMed  Google Scholar 

  • Kern, J. K., & Jones, A. M. (2006). Evidence of toxicity, oxidative stress, and neuronal insult in autism. Journal of Toxicology and Environmental Health. Part B, Critical Reviews, 9, 485–499.

    PubMed  Article  Google Scholar 

  • Krebs, M. O., Bellon, A., Mainguy, G., Jay, T. M., & Frieling, H. (2009). One-carbon metabolism and schizophrenia: Current challenges and future directions. Trends in Molecular Medicine, 15, 562–570.

    PubMed  Article  Google Scholar 

  • Kwon, Y. W., Masutani, H., Nakamura, H., Ishii, Y., & Yodoi, J. (2003). Redox regulation of cell growth and cell death. Biological Chemistry, 384, 991–996.

    PubMed  Article  Google Scholar 

  • Lahiri, D. K., Maloney, B., & Zawia, N. H. (2009). The LEARn model: An epigenetic explanation for ideopathic neurobiologic diseases. Molecular Psychiatry, 14, 992–1003.

    PubMed  Article  Google Scholar 

  • Lenton, K. J., Therriault, H., & Wagner, J. R. (1999). Analysis of glutathione and glutathione disulfide in whole cells and mitochondria by postcolumn derivatization high-performance liquid chromatography with ortho-phthalaldehyde. Analytical Biochemistry, 274, 125–130.

    PubMed  Article  Google Scholar 

  • Li, Y., Liu, Y., Strickland, F. M., & Richardson, B. (2010). Age-dependent decreases in DNA methyltransferase levels and low transmethylation micronutrient levels synergize to promote overexpression of genes implicated in autoimmunity and acute coronary syndromes. Experimental Gerontology, 45, 312–322.

    PubMed  Article  Google Scholar 

  • Lord, C., Rutter, M., Goode, S., et al. (1989). Autism diagnostic observation schedule: A standardized observation of communicative and social behavior. Journal of Autism and Developmental Disorders, 19, 185–212.

    PubMed  Article  Google Scholar 

  • Melnyk, S., Pogribna, M., Pogribny, I., Hine, R. J., & James, S. J. (1999). A new HPLC method for the simultaneous determination of oxidized and reduced plasma aminothiols using coulometric electrochemical detection. The Journal Of Nutritional Biochemistry, 10, 490–497.

    PubMed  Article  Google Scholar 

  • Melnyk, S., Pogribna, M., Pogribny, I. P., & James, S. J. (2000). Measurement of plasma and intracellular S-adenosylmethionine and S-adenosylhomocysteine utilizing coulemetric electrochemical detection: Alteration with plasma homocysteine and pyridoxal 5’-phosphate concentrations. Clinical Chemistry, 46, 265–272.

    PubMed  Google Scholar 

  • Mill, J., Tang, T., Kaminsky, Z., Khare, T., Yazdanpanah, S., Bouchard, L., et al. (2008). Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. American Journal of Human Genetics, 82, 696–711.

    PubMed  Article  Google Scholar 

  • Miller, A. L. (2008). The methylation, neurotransmitter, and antioxidant connections between folate and depression. Alternative Medicine Review, 13, 216–226.

    PubMed  Google Scholar 

  • Ming, X., Stein, T. P., Brimacombe, M., Johnson, W. G., Lambert, G. H., & Wagner, G. C. (2005). Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukotrienes and Essential Fatty Acids, 73, 379–384.

    Article  Google Scholar 

  • Mohiuddin, I., Chai, H., Lin, P. H., Lumsden, A. B., Yao, Q., & Chen, C. (2006). Nitrotyrosine and chlorotyrosine: Clinical significance and biological functions in the vascular system. Journal of Surgical Research, 133, 143–149.

    PubMed  Article  Google Scholar 

  • Nagarajan, R. P., Patzel, K. A., Martin, M., Yasui, D. H., Swanberg, S. E., Hertz-Picciotto, I., et al. (2008). MECP2 promoter methylation and X chromosome inactivation in autism. Autism Research, 1, 169–178.

    PubMed  Article  Google Scholar 

  • Noble, M., Smith, J., Power, J., & Mayer-Proschel, M. (2003). Redox state as a central modulator of precursor cell function. Annals of the New York Academy of Sciences, 991, 251–271.

    PubMed  Article  Google Scholar 

  • Pastore, A., Federici, G., Bertini, E., & Piemonte, F. (2003). Analysis of glutathione: Implication in redox and detoxification. Clinica Chimica Acta, 333, 19–39.

    Article  Google Scholar 

  • Pilger, A., & Rudiger, H. W. (2006). 8-Hydroxy-2’-deoxyguanosine as a marker of oxidative DNA damage related to occupational and environmental exposures. International Archives of Occupational and Environmental Health, 80, 1–15.

    PubMed  Article  Google Scholar 

  • Reed, M. C., Thomas, R. L., Pavisic, J., James, S. J., Ulrich, C. M., & Nijhout, H. F. (2008). A mathematical model of glutathione metabolism. Theoretical Biology & Medical Modelling, 5, 8.

    Article  Google Scholar 

  • Reik, W. (2007). Stability and flexibility of epigenetic gene regulation in mammalian development. Nature, 447, 425–432.

    PubMed  Article  Google Scholar 

  • Reik, W., & Dean, W. (2001). DNA methylation and mammalian epigenetics. Electrophoresis, 22, 2838–2843.

    PubMed  Article  Google Scholar 

  • Rizwana, R., & Hahn, P. J. (1999). CPG methylation reduces genomic instability. Journal of Cell Science, 112, 4513–4519.

    PubMed  Google Scholar 

  • Rubenstein, J. L. (2010). Three hypotheses for developmental defects that may underlie some forms of autism spectrum disorder. Current Opinion in Neurology, 23, 18–23.

    Article  Google Scholar 

  • Rubenstein, J. L., & Merzenich, M. M. (2003). Model of autism: Increased ratio of excitation/inhibition in key neural systems. Genes, Brain, Behaviour, 2, 255–267.

    Article  Google Scholar 

  • Sajdel-Sulkowska, E. M., Xu, M., & Koibuchi, N. (2009). Increase in cerebellar neurotrophin-3 and oxidative stress markers in autism. Cerebellum, 8, 366–372.

    PubMed  Article  Google Scholar 

  • Samaco, R. C., Hogart, A., & LaSalle, J. M. (2005). Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Human Molecular Genetics, 14, 483–492.

    PubMed  Article  Google Scholar 

  • Schafer, F. Q., & Buettner, G. R. (2001). Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radical Biology and Medicine, 30, 1191–1212.

    PubMed  Article  Google Scholar 

  • Schanen, N. C. (2006). Epigenetics of autism spectrum disorders. Human Molecular Genetics 15(Spec No 2), R138–R150.

    Google Scholar 

  • Schmutte, C., Yang, A. S., Nguyen, T. T., Beart, R. W., & Jones, P. A. (1996). Mechanisms for the involvement of DNA methylation in colon carcinogenesis. Cancer Research, 56, 2375–2381.

    PubMed  Google Scholar 

  • Schopler, E., Reichler, R. J., DeVellis, R. F., & Daly, K. (1980). Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). Journal of Autism and Developmental Disorders, 10(1), 91–103.

    PubMed  Article  Google Scholar 

  • Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., et al. (2007). Strong association of de novo copy number mutations with autism. Science, 316, 445–449.

    PubMed  Article  Google Scholar 

  • Shigenaga, M. K., Park, J. W., Cundy, K. C., Gimeno, C. J., & Ames, B. N. (1990). In vivo oxidative DNA damage: measurement of 8-hydroxy-2’-deoxyguanosine in DNA and urine by high-performance liquid chromatography with electrochemical detection. Methods in Enzymology, 186, 521–530.

    PubMed  Article  Google Scholar 

  • Small, G. W., Ercoli, L. M., Silverman, D. H., Huang, S. C., Komo, S., Bookheimer, S. Y., et al. (2000). Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer’s disease. PNAS, 97, 6037–6042.

    PubMed  Article  Google Scholar 

  • Smith, M., Spence, M. A., & Flodman, P. (2009). Nuclear and mitochondrial genome defects in autisms. Annals of the New York Academy of Sciences, 1151, 102–132.

    PubMed  Article  Google Scholar 

  • Smythies, J. R., Gottfries, C. G., & Regland, B. (1997). Disturbances of one-carbon metabolism in neuropsychiatric disorders: A review. Biological Psychiatry, 41, 230–233.

    PubMed  Article  Google Scholar 

  • Sogut, S., Zoroglu, S. S., Ozyurt, H., Ramazan, Y. H., Ozugurlu, F., Sivasli, E., et al. (2003). Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clinica Chimica Acta, 331, 111–117.

    Article  Google Scholar 

  • Strous, R. D., Ritsner, M. S., Adler, S., Ratner, Y., Maayan, R., Kotler, M., et al. (2009). Improvement of aggressive behavior and quality of life impairment following S-adenosyl-methionine (SAM-e) augmentation in schizophrenia. European Neuropsychopharmacology, 19, 14–22.

    PubMed  Article  Google Scholar 

  • Tchantchou, F., Graves, M., Ashline, D., Morin, A., Pimenta, A., Ortiz, D., et al. (2004). Increased transcription and activity of glutathione synthase in response to deficiencies in folate, vitamin E, and apolipoprotein E. Journal of Neuroscience Research, 75, 508–515.

    PubMed  Article  Google Scholar 

  • Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005). Neuroglial activation and neuroinflammation in the brain of patients with autism. Annals of Neurology, 57, 67–81.

    PubMed  Article  Google Scholar 

  • Vitvitsky, V., Mosharov, E., Tritt, M., Ataullakhanov, F., & Banerjee, R. (2003). Redox regulation of homocysteine-dependent glutathione synthesis. Redox Report, 8, 57–63.

    PubMed  Article  Google Scholar 

  • Yan, Z., & Banerjee, R. (2010). Redox remodeling as an immunoregulatory strategy. Biochemistry, 49, 1059–1066.

    PubMed  Article  Google Scholar 

  • Yan, Z., Garg, S. K., Kipnis, J., & Banerjee, R. (2009). Extracellular redox modulation by regulatory T cells. Nature Chemical Biology, 5, 721–723.

    PubMed  Article  Google Scholar 

  • Yao, Y., Walsh, W. J., McGinnis, W. R., & Pratico, D. (2006). Altered vascular phenotype in autism: Correlation with oxidative stress. Archives of Neurology, 63, 1161–1164.

    PubMed  Article  Google Scholar 

  • Yorbik, O., Sayal, A., Akay, C., Akbiyik, D. I., & Sohmen, T. (2002). Investigation of antioxidant enzymes in children with autistic disorder. Prostaglandins Leukotrienes and Essential Fatty Acids, 67, 341–343.

    Article  Google Scholar 

  • Zecavati, N., & Spence, S. J. (2009). Neurometabolic disorders and dysfunction in autism spectrum disorders. Current Neurology and Neuroscience Reports, 9, 129–136.

    PubMed  Article  Google Scholar 

  • Zeisel, S. H. (2009). Importance of methyl donors during reproduction. American Journal of Clinical Nutrition, 89, 673S–677S.

    PubMed  Article  Google Scholar 

  • Zoroglu, S. S., Armutcu, F., Ozen, S., Gurel, A., Sivasli, E., Yetkin, O., et al. (2004). Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. European Archives of Psychiatry and Clinical Neuroscience, 254, 143–147.

    PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to express their gratitude to the families in Arkansas affected by autism whose participation made this study possible. We also acknowledge the invaluable help of the nurses and clinicians at the Dennis Developmental Center for referral and evaluation. This research was supported, in part, with funding from the National Institute of Child Health and Development (RO1 HD051873; SJJ), the Department of Defense (AS073218P1; SJJ) and by grants from the Arkansas Children’s Hospital and Arkansas Biosciences Institute (SJJ).

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Stepan Melnyk, George J. Fuchs, Eldon Schulz, Maya Lopez, Stephen G. Kahler, Jill J. Fussell, Jayne Bellando, Oleksandra Pavliv, Shannon Rose, Lisa Seidel & S. Jill James

  2. Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    David W. Gaylor

  3. Department of Pediatrics, Arkansas Children’s Hospital Research Institute, 13 Children’s Way, Slot 512-41B, Little Rock, AR, 72202, USA

    Stepan Melnyk, George J. Fuchs, Eldon Schulz, Maya Lopez, Stephen G. Kahler, Jill J. Fussell, Jayne Bellando, Oleksandra Pavliv, Shannon Rose, Lisa Seidel & S. Jill James

Authors
  1. Stepan Melnyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. George J. Fuchs
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eldon Schulz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maya Lopez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stephen G. Kahler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jill J. Fussell
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jayne Bellando
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Oleksandra Pavliv
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shannon Rose
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lisa Seidel
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. David W. Gaylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. S. Jill James
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Jill James.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Melnyk, S., Fuchs, G.J., Schulz, E. et al. Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism. J Autism Dev Disord 42, 367–377 (2012). https://doi.org/10.1007/s10803-011-1260-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-011-1260-7

Keywords

  • Autism
  • Oxidative stress
  • Metabolic
  • Epigenetics
  • Glutathione
  • DNA methylation