Journal of Autism and Developmental Disorders

, Volume 42, Issue 4, pp 643–646 | Cite as

Further Commentary on Mitochondrial Dysfunction in Autism Spectrum Disorder: Assessment and Treatment Considerations

  • Stephen R. Dager
  • Neva M. Corrigan
  • Annette Estes
  • Dennis W. W. Shaw
Letter to the Editor


The authors respond to a recent letter (Rossignol and Frye 2011) critical of their paper, “Proton magnetic resonance spectroscopy and MRI reveal no evidence for brain mitochondrial dysfunction in children with autism spectrum disorder” (Corrigan et al. 2011). Further considerations regarding the assessment of mitochondrial dysfunction in autism spectrum disorder, and related treatment considerations, are discussed.


Autism Developmental disorders MRS MRI Mitochondrial disorders Brain lactate 


  1. Amundsen, L. B., Artru, A. A., Dager, S. R., Shaw, D. W. W., Friedman, S., Sparks, B., et al. (2005). Propofol sedation for longitudinal pediatric neuroimaging research. Journal of Neurosurg Anesthesiology, 17(4), 180–192.CrossRefGoogle Scholar
  2. Bianchi, M. C., Sgandurra, G., Tosetti, M., Battini, R., & Cioni, G. (2007). Brain magnetic resonance in the diagnostic evaluation of mitochondrial encephalopathies. Biosciene Reports, 27(1–3), 69–85.CrossRefGoogle Scholar
  3. Coleman, M., & Blass, J. P. (1985). Autism and lactic acidosis. Journal of Autism and Developmental Disorders, 15(1), 1–8.PubMedCrossRefGoogle Scholar
  4. Correia, C., Coutinho, A. M., Diogo, L., Grazina, M., Marques, C., Miguel, T., et al. (2006). Brief report: High frequency of biochemical markers for mitochondrial dysfunction in autism: no association with the mitochondrial aspartate/glutamate carrier SLC25A12 gene. Journal of Autism and Developmental Disorders, 36(8), 1137–1140.PubMedCrossRefGoogle Scholar
  5. Corrigan, N. M., Richards, T. L., Friedman, S. D., Petropoulos, H., & Dager, S. R. (2010). Improving 1H MRSI measurement of cerebral lactate for clinical applications. Psychiatry Research Neuroimaging, 182(1), 40–47.CrossRefGoogle Scholar
  6. Corrigan, N. M., Shaw, D. W. W., Richards, T. L., Estes, A. M., Friedman, S. D., Petropoulos, H., et al. (2011). Proton magnetic resonance spectroscopy and MRI reveal no evidence for brain mitochondrial dysfunction in children with autism spectrum disorder. Journal of Autism and Developmental Disorders. doi:10.1007/s10803-011-1216-y.
  7. Dager, S. R. (2010). The vexing role of baseline: Implications for neuroimaging studies of panic disorder. International Journal of Psychophysiology, 78(1), 20–26.PubMedCrossRefGoogle Scholar
  8. Dager, S. R., & Steen, R. G. (1992). Applications of magnetic resonance spectroscopy to the investigation of neuropsychiatric disorders. Neuropsychopharmacology, 6(4), 249–266.PubMedGoogle Scholar
  9. Dager, S. R., Friedman, S. D., Heide, A., Layton, M. E., Richards, T., Artru, A., et al. (1999). Two-dimensional proton echo-planar spectroscopic imaging of brain metabolic changes during lactate-induced panic. Archieves of General Psychiatry, 56(1), 70–77.CrossRefGoogle Scholar
  10. Dager, S. R., Friedman, S. D., Parow, A., Demopulos, C., Stoll, A. L., Lyoo, I. K., et al. (2004). Brain metabolic alterations in medication-free patients with bipolar disorder. Archieves of General Psychiatry, 61(5), 450–458.CrossRefGoogle Scholar
  11. Dager, S. R., Corrigan, N. M., Richards, T. L., & Posse, S. (2008). Research applications of magnetic resonance spectroscopy to investigate psychiatric disorders. Topics in Magnetic Resonance Imaging, 19(2), 81–96.PubMedCrossRefGoogle Scholar
  12. Dager, S., Corrigan, N., Richards, T., & Shaw, D. (2011). Brain chemistry: Magnetic resonance spectroscopy. In D. Amaral, G. Dawson, & D. Geshwind (Eds.), Autism Spectrum Disorder. Oxford: Oxford University Press.Google Scholar
  13. Dawson, G., Rogers, S., Munson, J., Smith, M., Winter, J., Greenson, J., et al. (2010). Randomized, controlled trial of an intervention for toddlers with autism: The early start denver model. Pediatrics, 125(1), e17–e23.PubMedCrossRefGoogle Scholar
  14. Friedman, S. D., Dager, S. R., Richards, T. L., Petropoulos, H., & Posse, S. (2000). Modeling brain compartmental lactate response to metabolic challenge: A feasibility study. Psychiatry Research, 98(1), 55–66.PubMedCrossRefGoogle Scholar
  15. Friedman, S. D., Shaw, D. W., Artru, A. A., Richards, T. L., Gardner, J., Dawson, G., et al. (2003). Regional brain chemical alterations in young children with autism spectrum disorder. Neurology, 60(1), 100–107.PubMedGoogle Scholar
  16. Friedman, S. D., Shaw, D. W. W., Artru, A. A., Dawson, G., Petropoulos, H., & Dager, S. R. (2006). Gray and white matter brain chemistry in young children with autism. Archives of General Psychiatry, 63(7), 786–794.PubMedCrossRefGoogle Scholar
  17. Granpeesheh, D., Tarbox, J., Dixon, D., Wilke, A. E., Allen, S., & Bradstreet, J. J. (2010). Randomized trial of hyperbaric oxygen therapy for children with autism. Research in Autism Spectrum Disorders, 4, 265–268.Google Scholar
  18. Haas, R. H., Parikh, S., Falk, M. J., Saneto, R. P., Wolf, N. I., Darin, N., et al. (2008). The in-depth evaluation of suspected mitochondrial disease. Molecular Genetics and Metabolism, 94(1), 16–37.PubMedCrossRefGoogle Scholar
  19. Jepson, B., Granpeesheh, D., Tarbox, J., Olive, M. L., Stott, C., Braud, S., et al. (2011). Controlled evaluation of the effects of hyperbaric oxygen therapy on the behavior of 16 children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 41(5), 575–588.PubMedCrossRefGoogle Scholar
  20. Lyoo, I. K., Dager, S. R., Kim, J. E., Yoon, S. J., Friedman, S. D., Dunner, D. L., et al. (2010). Lithium-induced gray matter volume increase as a neural correlate of treatment response in bipolar disorder: A longitudinal brain imaging study. Neuropsychopharmacology, 35(8), 1743–1750.PubMedGoogle Scholar
  21. Morgan, P. (2007). When propofol is problematic. Paper presented at the12th annual joint winter meeting of the society of pediatric anesthesia and American academy of pediatrics., Phoenix, Arizona.Google Scholar
  22. Oliveira, G., Diogo, L., Grazina, M., Garcia, P., Ataíde, A., Marques, C., et al. (2005). Mitochondrial dysfunction in autism spectrum disorders: A population-based study. Developmental Medicine and Child Neurology, 47(3), 185–189.PubMedCrossRefGoogle Scholar
  23. Parikh, S., Saneto, R., Falk, M. J., Anselm, I., Cohen, B. H., Haas, R., et al. (2009). A modern approach to the treatment of mitochondrial disease. Current Treatment Options in Neurology, 11(6), 414–430.PubMedCrossRefGoogle Scholar
  24. Posse, S., Dager, S. R., Richards, T. L., Yuan, C., Ogg, R., Artru, A. A., et al. (1997). In vivo measurement of regional brain metabolic response to hyperventilation using magnetic resonance: Proton echo planar spectroscopic imaging (PEPSI). Magnetic Resonance in Medicine, 37(6), 858–865.PubMedCrossRefGoogle Scholar
  25. Ramocki, M. B., & Zoghbi, H. Y. (2008). Failure of neuronal homeostasis results in common neuropsychiatric phenotypes. Nature, 455(7215), 912–918.PubMedCrossRefGoogle Scholar
  26. Rossignol, D. A., & Bradstreet, J. J. (2008). Evidence of mitochondrial dysfunction in autism and implications for treatment. American Journal of Biochemistry and Biotechnology, 4(2), 208–217.CrossRefGoogle Scholar
  27. Rossignol, D. A., & Frye, R. E. (2011). Substantial problems with measuring brain mitochondrial dysfunction in autism spectrum disorder using magnetic resonance spectroscopy. Journal of Autism and Developmental Disorders. doi:10.1007/s10803-011-1276-z.
  28. Rossignol, D. A., Rossignol, L. W., Smith, S., Schneider, C., Logerquist, S., Usman, A., et al. (2009). Hyperbaric treatment for children with autism: A multicenter, randomized, double-blind, controlled trial. BMC Pediatrics, 9, 21.PubMedCrossRefGoogle Scholar
  29. Saneto, R. P., Friedman, S. D., & Shaw, D. W. W. (2008). Neuroimaging of mitochondrial disease. Mitochondrion, 8(5–6), 396–413.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Stephen R. Dager
    • 1
    • 2
    • 3
  • Neva M. Corrigan
    • 1
  • Annette Estes
    • 2
    • 4
  • Dennis W. W. Shaw
    • 1
    • 5
  1. 1.Department of RadiologyUniversity of WashingtonSeattleUSA
  2. 2.University of Washington Autism CenterSeattleUSA
  3. 3.Department of BioengineeringUniversity of WashingtonSeattleUSA
  4. 4.Department of Speech and Hearing SciencesUniversity of WashingtonSeattleUSA
  5. 5.Seattle Children’s HospitalSeattleUSA

Personalised recommendations