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Magnetic Resonance Spectroscopy Studies of Autistic Spectrum Disorders

  • Jennifer G. Levitt
  • Joseph O’Neill
  • Jeffry R. Alger
Chapter

Abstract

This chapter reviews magnetic resonance spectroscopy studies of Autism Spectrum Disorders. We present a brief clinical overview of autism and related pervasive developmental disorders, and then summarize the neuropathology findings in ASD and neuroimaging investigations of ASD using techniques other than MRS. We then review all published MRS studies of ASD known to us, with some emphasis upon the impact of varying spectroscopic imaging techniques. Finally, we suggest potential future MRS research applications in ASD.

Keywords

Autistic Spectrum Disorder Autistic Spectrum Disorder Group Magnetic Resonance Spectroscopic Imaging Anterior Cingulate Gyrus Autistic Subject 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    American Psychiatric Association. Diagnostic and statistical manual of mental health disorders. 4th ed. Washington DC: American Psychiatric Association; 1994.Google Scholar
  2. 2.
    Filipek PA, Accardo PJ, Baranek GT, Cook EH, Dawson G, Gordon B, Gravel JS, Johnson CP, Kallen RJ, Levy SE, Minshew NJ, Prizant BM, Rapin I, Rogers SJ, Stone W, Teplin S, Tuchman RF, Volkmar FR. The Screening and Diagnosis of Autistic Spectrum Disorders (1999). J Autism Dev Disord. 1999;29:439–84.PubMedCrossRefGoogle Scholar
  3. 3.
    Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009;65:591–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D, Charman T. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). Lancet. 2006;368:210–15.PubMedCrossRefGoogle Scholar
  5. 5.
    Fernell E, Gillberg C. Autism spectrum disorder diagnoses in Stockholm preschoolers. Res Dev Disabil. 2010;31:680–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Baron-Cohen S, Scott FJ, Allison C, Williams J, Bolton P, Matthews FE, Brayne C. Prevalence of autism-spectrum conditions: UK school-based population study. Br J Psychiatry. 2009;194:500–9.PubMedCrossRefGoogle Scholar
  7. 7.
    King M, Bearman P. Diagnostic change and the increased prevalence of autism. Int J Epidemiol. 2009;38:1224–34.PubMedCrossRefGoogle Scholar
  8. 8.
    Bauman ML, Kemper TL. Histoanatomic observations of the brain in early infantile autism. Neurology. 1985;35:866–74.PubMedCrossRefGoogle Scholar
  9. 9.
    Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism. In: Bauman ML, Kemper TL, editors. The neurobiology of autism. Baltimore: Johns Hopkins University Press; 1994. p. 119–45.Google Scholar
  10. 10.
    Bauman ML, Kemper TL. Observations on the Purkinje cells in the cerebellar vermis in autism. J Neuropathol Exp Neurol. 1996;55:613.CrossRefGoogle Scholar
  11. 11.
    Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci. 2005;23:183–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Gurthrie D, Ritvo A. Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report. Am J Psychiatry. 1986;143:862–6.PubMedGoogle Scholar
  13. 13.
    Bauman ML, Kemper TL. Developmental cerebellar abnormalities: a consistent finding in early infantile autism. Neurology. 1986;36 Suppl 1:190.Google Scholar
  14. 14.
    Kemper TL, Bauman ML. The contribution of neuropathologic studies to the understanding of autism. Neurol Clin. 1993;11:175–87.PubMedGoogle Scholar
  15. 15.
    Bailey A, Luther P, Dean A, et al. Clinicopathological study of autism. Brain. 1998;121:889–905.PubMedCrossRefGoogle Scholar
  16. 16.
    Schumann CM, Amaral DG. Stereological analysis of amygdala neuron number in autism. J Neurosci. 2006;26(29):7674–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Casanova MF, Buxhoeveden DP, Switala AE, Roy E. Minicolumnar pathology in autism. Neurology. 2002;58:428–32.PubMedCrossRefGoogle Scholar
  18. 18.
    Blatt GJ, Fitzgerald CM, Guptill JT, Booker AB, Kemper TL, Bauman ML. Density and distribution of hippocampal neuro- transmitter receptors in autism. J Autism Dev Disord. 2001;31:537–43.PubMedCrossRefGoogle Scholar
  19. 19.
    Perry EK, Lee MLW, Martin-Ruiz CM, Court J, Volsen S, Merritt JB, Folly E, Iversen P, Bauman ML, Perry RH, Wenk G. Cholinergic activity in autism: abnormalities in the cerebral cortex and basal forebrain. Am J Psychiatry. 2001;158:1058–66.PubMedCrossRefGoogle Scholar
  20. 20.
    Lee M, Martin-Ruiz C, Graham A, Court J, Jaros E, Perry E, Iversen P, Bauman M, Perry RH. Nicotinic receptor abnormalities in the cerebellar cortex in autism. Brain. 2002;125:1483–95.PubMedCrossRefGoogle Scholar
  21. 21.
    Mountz JM, Tolbert LC, Lill DW, Katholi CR, Liu HG. Functional deficits in autistic disorder: characterization by technetium-99 m-HMPAO and SPECT. J Nucl Med. 1995;36(7):1156–62.PubMedGoogle Scholar
  22. 22.
    Abell F, Krams M, Ashburner J, Passingham R, Friston K, Frackowiak R, Happé F, Frith C, Frith U. The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans. Neuroreport. 1999;10(8):1647–51.PubMedCrossRefGoogle Scholar
  23. 23.
    Aylward EH, Minshew NJ, Goldstein G, Honeycutt NA, Augustine AM, Yates KO, Barta PE, Pearlson GD. MRI volumes of amygdala and hippocampus in nom-mentally retarded autistic adolescents and adults. Neurology. 1999;53(9):2145–50.PubMedCrossRefGoogle Scholar
  24. 24.
    Haznedar MM, Buchsbaum MS, Wei TC, Hof PR, Cartwright C, Bienstock CA, Hollander E. Limic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging. Am J Psychiatry. 2000;157(12):1994–2001.PubMedCrossRefGoogle Scholar
  25. 25.
    Howard MA, Cowell PE, Boucher J, Broks P, Mayes A, Farrant A, Roberts N. Convergent neuroanatomical and behavioral evidence of an amygdala hypothesis of autism. Neuroreport. 2000;11(13):2931–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Sparks BF, Friedman SD, Shaw DW, Aylward EH, Echelard D, Artru AA, Maravilla KR, Giedd JN, Munson J, Dawson G, Dager SR. Brain structural abnormalities in young children with autism spectrum disorder. Neurology. 2002;59:184–92.PubMedCrossRefGoogle Scholar
  27. 27.
    Schumann CM, Hamstra J, Goodlin-Jones BL, Lotspeich LJ, Kwon H, Buonocore MH, Lammers CR, Reiss AL, Amaral DG. The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci. 2004;24:6392–401.PubMedCrossRefGoogle Scholar
  28. 28.
    Munson J, Dawson G, Abbott R, Faja S, Webb SJ, Friedman SD, Shaw D, Artru A, Dager SR. Amygdalar volume and behavioral development in autism. Arch Gen Psychiatry. 2006;63(6):686–93.PubMedCrossRefGoogle Scholar
  29. 29.
    Courchesne E, Yeung-Courchesne R, Press GA, Hesselink JR, Jernigan TL. Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med. 1988;318(21):1349–54.PubMedCrossRefGoogle Scholar
  30. 30.
    Courchesne E, Saitoh O, Yeung-Courchesne R, Press GA, Lincoln AJ, Haas RH, Schreibman L. Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: identification of hypoplastic and hyperplastic subgroups with MR imaging. AJR Am J Roentgenol. 1994;162(1):123–30.PubMedGoogle Scholar
  31. 31.
    Kates WR, Mostofsky SH, Zimmerman AW, Mazzocco MM, Landa R, Warsofsky IS, Kaufmann WE, Reiss AL. Neuroanatomical and neurocognitive differences in a pair of monozygous twins discordant for strictly defined autism. Ann Neurol. 1998;43(6):782–91.PubMedCrossRefGoogle Scholar
  32. 32.
    Carper RA, Courchesne E. Inverse correlation between frontal lobe and cerebellum sizes in children with autism. Brain. 2000;123(4):836–44.PubMedCrossRefGoogle Scholar
  33. 33.
    Holttum JR, Minshew NJ, Sanders RS, Phillips NE. Magnetic resonance imaging of the posterior fossa in autism. Biol Psychiatry. 1992;32(12):1091–101.PubMedCrossRefGoogle Scholar
  34. 34.
    Rorke LB. A perspective: the role of disordered genetic control of neurogenesis in the pathogenesis of migration disorders. J Neuropathol Exp Neurol. 1994;53(2):105–17.PubMedCrossRefGoogle Scholar
  35. 35.
    Piven J, Berthier ML, Starkstein SE, Nehme E, Pearlson G, Folstein S. Magnetic resonance imaging evidence for a defect of cerebral cortical development in autism. Am J Psychiatr. 1990;147:734–9.PubMedGoogle Scholar
  36. 36.
    Levitt JG, Blanton RE, Smalley S, Thompson PM, Guthrie D, McCracken JT, Sadoun T, Heinichen L, Toga AW. Cortical sulcal maps in autism. Cereb Cortex. 2003;13:728–35.PubMedCrossRefGoogle Scholar
  37. 37.
    Hardan AY, Jou RJ, Keshavan MS, Varma R, Minshew NJ. Increased frontal cortical folding in autism: a preliminary MRI study. Psychiatry Res. 2004;131:263–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Courchesne E, Press GA, Yeung-Courchesne R. Parietal lobe abnormalities detected with MR in patients with infantile autism. AJR Am J Roentgenol. 1993;160(2):387–93.PubMedGoogle Scholar
  39. 39.
    Carper RA, Moses P, Tigue ZD, Courchesne E. Cerebral lobes in autisjm: early hyperplasia and abnormal age effects. Neuroimage. 2002;16(4):1038–51.PubMedCrossRefGoogle Scholar
  40. 40.
    Carper RA, Courchesne E. Localized enlargement of the frontal cortex in early autism. Biol Psychiatry. 2005;57:126–33.PubMedCrossRefGoogle Scholar
  41. 41.
    McAlonan GM, Daly E, Jumari V, Critchley HD, van Amelsvoort T, Suckling J, Simmons A, Sigmundsson T, Greenwood K, Russel A, Schmitz N, Happe F, Howlin P, Murphy DG. Brain anatomy and sensorimotor gating in Asperger syndrome. Brain. 2002;125:1594–606.PubMedCrossRefGoogle Scholar
  42. 42.
    McAlonan GM, Cheung V, Cheung C, Sucking J, Lam GY, Tai KS, Murphy DG YL, Chua SE. Mapping the brain in autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism. Brain. 2005;128:268–76.PubMedCrossRefGoogle Scholar
  43. 43.
    McAlonan GM, Suckling J, Wong N, Cheung V, Lienenkaemper N, Cheung C, Chua SE. Distinct patterns of grey matter abnormality in high-functioning autism and Asperger’s syndrome. J Child Psychol Psychiatry. 2008;49:1287–95.PubMedCrossRefGoogle Scholar
  44. 44.
    Amaral DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends Neurosci. 2008;31:137–45.PubMedCrossRefGoogle Scholar
  45. 45.
    Stanfield AC, McIntosh AM, Spencer MD, Phillip R, Gaur S, Lawrie SM. Towards a neuroanatomy of autism: A systematic review and meta-analysis of structural magnetic resonance imaging studies. Eur Psychiatry. 2008;23:289–99.PubMedCrossRefGoogle Scholar
  46. 46.
    Jou RJ, Minshew NJ, Keshavan MS, Hardan AY. Cortical gyrification in autistic and asperger disorders: a preliminary magnetic resonance imaging study. J Child Neurol. 2010;25:1462–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Chung MK, Rbbins SM, Dalton DJ, Davidson RJ, Alexander AL, Evans AC. Cortical thickness analysis in autism with heat kernal smoothing. Neuroimage. 2005;25:256–1265.CrossRefGoogle Scholar
  48. 48.
    Hadjikhani N, Joseph RM, Snyder J, Tager-Flusberg H. Anatomical differences in the mirror neuron system and social cognition network in autism. Cereb Cortex. 2006;16:1276–82.PubMedCrossRefGoogle Scholar
  49. 49.
    Hyde KL, Samson F, Evans AC, Mottron L. Neuroanatomical differences in brain areas implicated in perceptual and other core features of autism revealed by cortical thickness analysis and voxel-based morphometry. Hum Brain Mapp. 2010;31(4):556–66.PubMedGoogle Scholar
  50. 50.
    Kanner L. Autistic disturbance of affective contact. Nerv Child. 1943;2:217–50.Google Scholar
  51. 51.
    Lainhart JE, Piven J, Wzorek M, et al. Macrocephaly in children and adults with autism. J Am Acad Child Adolesc Psychiatry. 1997;36:282.PubMedCrossRefGoogle Scholar
  52. 52.
    Courchesne E, Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA. 2003;290:337–44.PubMedCrossRefGoogle Scholar
  53. 53.
    Piven J, Nehme E, Simon J, Barta P, Pearlson G, Folstein SE. Magnetic resonance imaging in autism: measurement of the cerebellum, pons, and fourth ventricle. Biol Psychiatry. 1992;31(5):491–504.PubMedCrossRefGoogle Scholar
  54. 54.
    Piven J, Arndt S, Bailey J, Havercamp S, Andreasen NC, Palmer P. An MRI study of brain size in autism. Am J Psychiatry. 1995;152:1145–9.PubMedGoogle Scholar
  55. 55.
    Courchesne E, Karns CM, Davids HR, Ziccardi R, Carper RA, Tigue ZD, Chisum HJ, Moses P, Pierce K, Lord C, Lincoln AJ, Pizzo S, Schreibman L, Haas RH, Akshoomoff NA, Yeung-Courchesne R. Unusual brain growth patterns in early life in patients with autistic disorder. Neurology. 2001;57:245–54.PubMedCrossRefGoogle Scholar
  56. 56.
    Hardan AY, Minshew NJ, Mallikarjuhn M, Keshavan MS. Brain volume in autism. J Child Neurol. 2001;16(6):421–4.PubMedGoogle Scholar
  57. 57.
    Hazlett HC, Poe M, Gerig G, Smith RG, Provenzale J, Ross A, Gilmore J, Piven J. Magnetic resonance imaging and head circumference study of brain size in autism: Birth through age 2 years. Arch Gen Psychiatry. 2005;62:1366–76.PubMedCrossRefGoogle Scholar
  58. 58.
    Redcay E, Courchesne E. When is the brain enlarged in autism? A meta-analysis of all brain size reports. Biol Psychiatry. 2005;58(1):1–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Schumann CM, Bloss CS, Barnes CC, Wideman GM, Carper RA, Akshoomoff N, Pierce K, Hagler D, Schork N, Lord C, Courchesne E. Longitudinal magnetic renonance imaging study of corical development through early childhood in autism. J Neurosci. 2010;30:4419–27.PubMedCrossRefGoogle Scholar
  60. 60.
    Aylward EH, Minshew NJ, Field K, Sparks BF, Singh N. Effects of age on brain volume and head circumference in autism. Neurology. 2002;59:175–83.PubMedCrossRefGoogle Scholar
  61. 61.
    Hazlett HC, Poe MD, Gerig G, Smith RG, Piven J. Cortical gray and white brain tissue volume in adolescents and adults with autism. Biol Psychiatry. 2006;59:1–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Freitag CM, Luders E, Hulst HE, Narr KL, Thompson PM, Toga AW, Krick C, Konrad C. Total brain volume and corpus callosum size in medication-naïve adolescents and young adults with autism spectrum disorder. Biol Psychiatry. 2009;66:316–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Keller TA, Kana RK, Just MA. A developmental study of the structural integrity of white matter in autism. Neuroreport. 2007;18:23–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Sundaram SK, Kumar A, Makki MI, Behen ME, Chugani HT, Chugani DC. Diffusion tensor imaging of frontal lobe in autism spectrum disorder. Cereb Cortex. 2008;18:2659–65.PubMedCrossRefGoogle Scholar
  65. 65.
    Barnea-Goraly N, Lotspeich LJ, Reiss AL. Similar white matter aberrations in children with autism and their unaffected siblings: a diffusion tensor imaging study using tract-based spatial statistics. Arch Gen Psychiatry. 2010;67:1052–60.PubMedCrossRefGoogle Scholar
  66. 66.
    Lee JE, Bigler EDH, Alexander AL, Lazar M, DuBray MB, Chung MK, Johnson M, Morgan J, Miller JN, McMahon WM, Lu J, Jeong EK, Lainhart JE. Diffusion tensor imaging of white matter in the superior temporal gyrus and temporal stem in autism. Neurosci Lett. 2007;424:127–32.PubMedCrossRefGoogle Scholar
  67. 67.
    Friedman SD, Shaw DW, Artru AA, Dawson G, Petropoulos H, Dager SR. Gray and white matter brain chemistry in young children with autism. Arch Gen Psychiatry. 2006;63:786–94.PubMedCrossRefGoogle Scholar
  68. 68.
    DeVito TJ, Drost DJ, Neufeld RW, Rajakumar N, Pavlosky W, Williamson P, Nicolson R. Evidence for cortical dysfunction in autism: a proton magnetic resonance spectroscopic imaging study. Biol Psychiatry. 2007;61(4):465–73.PubMedCrossRefGoogle Scholar
  69. 69.
    Rumsey JM, Duara R, Grady C, Rapoport JL, Margolin RA, Rapoport SI, Cutler NR. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography. Arch Gen Psychiatry. 1985;42:448–55.PubMedCrossRefGoogle Scholar
  70. 70.
    Ohnishi T, Matsuda H, Hashimoto T, Kuhihiro T, Ishikawa M, Uema T, Sasaki M. Abnormal regional cerebral blood flow in childhood autism. Brain. 2000;123:1838–44.PubMedCrossRefGoogle Scholar
  71. 71.
    Zilbovicius M, Boddaert N, Belin P, Poline JB, Remy P, Mangin JF, Thivard L, Barthelemy C, Samson Y. Temporal lobe dysfunction in childhood autism: a PET study. Am J Psychiatry. 2000;157:1988–93.PubMedCrossRefGoogle Scholar
  72. 72.
    Critchley HD, Daly EM, Bullmore ET, Williams SC, an Amelsvoort T, Robertson DM. The functional neuroanatomy of social behavior: changes in cerebral blood flow when people with autistic disorder process facial expressions. Brain. 2000;123:2203–12.PubMedCrossRefGoogle Scholar
  73. 73.
    Schultz RT, Gauthier I, Klin A, Fulbright RK, Anderson AW, Volkmar F, Skudlarski P, Lacadie C, Cohen DJ, Gore JC. Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome. Arch Gen Psychiatry. 2000;57:331–40.PubMedCrossRefGoogle Scholar
  74. 74.
    Pierce K, Muller RA, Ambrose J, Allen G, Courchesne E. Face processing occurs outside the fusiform ‘face area’in autism: evidence from functional MRI. Brain. 2001;124:2059–73.PubMedCrossRefGoogle Scholar
  75. 75.
    Boddaert N, Chabane N, Barthelemy C, Bourgeois M, Poline JB, Brunelle F, Samson Y, Zilbovicius M. Bitmeporal lobe dysfunction in infantile autism: positron emission tomography study. J Radiol. 2002;32:1–7.Google Scholar
  76. 76.
    Williams JH, Whiten A, Suddendorf T, Perrett DI. Imitation, mirror neurons and autism. Neurosci Biobehav Rev. 2001;25(4):287–95.PubMedCrossRefGoogle Scholar
  77. 77.
    Toth K, Munson J. Meltzoff aN, Dawson g. Early predictors of communication development in young children with autism spectrum disorder: joint attention, imitation, and toy play. J Autism Dev Disord. 2006;36:993–1005.PubMedCrossRefGoogle Scholar
  78. 78.
    Just MA, Cherkassky VL, Keller TA, Minshew NJ. Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity. Brain. 2004;127:1811–21.PubMedCrossRefGoogle Scholar
  79. 79.
    Jones TB, Bandettini PA, Kenworthy L, Case LK, Milleville SC, Martin A, Birn RM. Sources of group differences in functional connectivity: an investigation applied to autism spectrum disorder. Neuroimage. 2010;49:401–14.PubMedCrossRefGoogle Scholar
  80. 80.
    Welchew D, Ashwin C, Berkouk K, Salvador R, Suckling J. Functional disconnectivity of the medial temporal lobe in Asperger’s syndrome. Biol Psychiatry. 2005;57:991–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Page LA, Daly E, Schmitz N, Simmons A, Toal F, Deeley Q, Ambery F, McAlonan GM, Murphy KC, Murphy DG. In vivo 1 H-magnetic resonance spectroscopy study of amygdala-hippocampal and parietal regions in autism. Am J Psychiatry. 2006;163(12):2189–92.PubMedCrossRefGoogle Scholar
  82. 82.
    Minshew NJ, Goldstein G, Dombrowski SM, Panchalingam K, Pettegrew JW. A preliminary 31P MRS study of autism: evidence for undersynthesis and increased degradation of brain membranes. Biol Psychiatry. 1993;33:762–73.PubMedCrossRefGoogle Scholar
  83. 83.
    Arias-Mendoza F, Brown TR. In vivo measurement of phosphorous markers of disease. Dis Markers. 2004;19:49–68.Google Scholar
  84. 84.
    Hashimoto T, Tayama M, Miyazaki M, Yoneda Y, Yoshimoto T, Harada M, Miyoshi H, Tanouchi M, Kuroda Y. Differences in brain metabolites between patients with autism and mental retardation as detected by in vivo localized proton magnetic resonance spectroscopy. J Child Neurol. 1997;12(2):91–6.PubMedCrossRefGoogle Scholar
  85. 85.
    Murphy DG, Critchley HD, Schmitz N, McAlonan G, Van Amelsvoort T, Robertson D, Daly E, Rowe A, Russell A, Simmons A, Murphy KC, Howlin P. Asperger syndrome: a proton magnetic resonance spectroscopy study of brain. Arch Gen Psychiatry. 2002;59(10):885–91.PubMedCrossRefGoogle Scholar
  86. 86.
    American Psychiatric Association. Diagnostic and statistical manual of mental health disorders, 3rd edn, revised. Washington DC: American Psychiatric Association; 1987.Google Scholar
  87. 87.
    Hisaoka S, Harada M, Nishitani H, Mori K. Regional magnetic resonance spectroscopy of the brain in autistic individuals. Neuroradiology. 2001;43(6):496–8.PubMedCrossRefGoogle Scholar
  88. 88.
    Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry. 1989;46:1006–16.PubMedCrossRefGoogle Scholar
  89. 89.
    Lord C, Rutter M, Le Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of indiviguals with possible pervasive developmental disorders. J Autsim Dev Disord. 1994;24:659–85.CrossRefGoogle Scholar
  90. 90.
    Friedman SD, Shaw DW, Artru AA, Richards TL, Gardner J, Dawson G, Posse S, Dager SR. Regional brain chemical alterations in young children with autism spectrum disorder. Neurology. 2003;60:100–7.PubMedCrossRefGoogle Scholar
  91. 91.
    Provencher SW. Automatic quantitation of localized in vivo 1 H spectra with LCModel. NMR Biomed. 2001;14:260–4.PubMedCrossRefGoogle Scholar
  92. 92.
    Mullen E. Mullen Scales of Early Learning TOTAL. Cranston, RI: Child; 1989.Google Scholar
  93. 93.
    Zeegers M, van der Grond J, van Daalen E, Buitelaar J, van Engeland H. Proton magnetic resonance spectroscopy in developmentally delayed young boys with or without autism. J Neural Transm. 2007;114(2):289–95.PubMedCrossRefGoogle Scholar
  94. 94.
    Rosenberg DR, MacMaster FP, Kehavan MS, Fitzgerald KD. Steward Cm, Moore GJ. Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry. 2000;39:1096–103.PubMedCrossRefGoogle Scholar
  95. 95.
    Bernardi S, Anagnostou E, Shen J, Kolevzon A, Buxbaum JD, Hollander E, Hof PR, Fan J. In vivo (1)H-magnetic resonance spectroscopy study of the attentional networks in autism. Brain Res. 2011;1380:198–205.PubMedCrossRefGoogle Scholar
  96. 96.
    Harada M, Taki MM, Nose A, Kubo H, Mori K, Nishitani H, Matsuda T. Fucntion of the frontal lobe in autistic individuals: a proton magnetic resonance study. J Med Invest. 2010;57:35–44.PubMedCrossRefGoogle Scholar
  97. 97.
    Mescher M, Merkle H, Kirsch J, Garwood M, Gruetter R. Simultaneous in vivo spectral editing and water suppression. NMR Biomed. 1998;11:266–72.PubMedCrossRefGoogle Scholar
  98. 98.
    Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med. 1993;30:672–9.PubMedCrossRefGoogle Scholar
  99. 99.
    Fatemi SH, Folsom TD, Reutiman TJ, Thuras PD. Expression of GABA(B) receptors is altered in rains of subjects with autism. Cerebellum. 2009;8:64–9.PubMedCrossRefGoogle Scholar
  100. 100.
    Fatemi SH, Reutiman TJ, Folsom TD, Thuras PD. GABA(A) receptor downregulation in brains of subjects with autism. J Autism Dev Disord. 2009;39:223–30.PubMedCrossRefGoogle Scholar
  101. 101.
    Brand A, Richter-Landsberg C, Leibfritz D. Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci. 1993;15:289–98.PubMedCrossRefGoogle Scholar
  102. 102.
    Urenjak J, Williams SR, Gadian DG, Noble M. Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci. 1993;13:981–9.PubMedGoogle Scholar
  103. 103.
    Stork C, Renshaw PF. Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol Psychiatry. 2005;10:900–19.PubMedCrossRefGoogle Scholar
  104. 104.
    Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: Validation of method. Ann Neurol. 1979;6:371–88.PubMedCrossRefGoogle Scholar
  105. 105.
    Harris GJ, Chabris CF, Clark J, Urban T, Aharon I, Steele S, McGrath L, Condouris K, Tager-Flusberg H. Brain activation during semantic processing in autism spectrum disorders via functional magnetic resonance imaging. Brain Cogn. 2006;61(1):54–68.PubMedCrossRefGoogle Scholar
  106. 106.
    Kleinhans NM, Schweinsburg BC, Cohen DN, Müller RA, Courchesne E. N-acetyl aspartate in autism spectrum disorders: regional effects and relationship to fMRI activation. Brain Res. 2007;1162:85–97.PubMedCrossRefGoogle Scholar
  107. 107.
    Turken AU, Dronkers NF. The nueral architecture of the language comprehension network: Converging evidence from lesion and connectivity analyses. Front Syst Neurosci. 2011;5:1.PubMedCrossRefGoogle Scholar
  108. 108.
    Gill SS, Thomas DG, Van Bruggen N, Gadian DG, Peden CJ, Bell JD, Cox IJ, Menon DK, Iles RA, Bryant DJ, et al. Proton MR spectroscopy of intracranial tumours: in vivo and in vitro studies. J Comput Assist Tomogr. 1990;14:497–504.PubMedCrossRefGoogle Scholar
  109. 109.
    Speck O, Thiel T, Hennig J. Grading and therapy monitoring of astrocytomas with 1 H-spectroscopy: preliminary study. Anticancer Res. 1996;16:1581–5.PubMedGoogle Scholar
  110. 110.
    Rubenstein JLR, Merzenich MM. Model of autism: Increased ration of excitation/inhibition in key neural systems. Genes Brain Behav. 2003;2:255–67.PubMedCrossRefGoogle Scholar
  111. 111.
    Pardo JV, Pardo J, Janer KW, Raichle ME. The anterior cingulate cortex mediates processing in the Stroop attentional conflic paradigm. Proc Natl Acad Sci USA. 1990;87:256–9.PubMedCrossRefGoogle Scholar
  112. 112.
    Lane RD, Reiman EM, Axelrod B, Yun LS, Holmes A, Schwartz GE. Neuroal correlates of levels of emotional awareness. Evidence of an interaction between emotion and attention in the anterior cingulate cortex. J Cogn Neurosci. 1998;10:525–35.PubMedCrossRefGoogle Scholar
  113. 113.
    Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci. 2000;4:215–22.PubMedCrossRefGoogle Scholar
  114. 114.
    Devinsky O, Morrell MJ, Vogt BA. Contributions of anterior cingulate cortex to behaviors. Brain. 1995;118:279–306.PubMedCrossRefGoogle Scholar
  115. 115.
    Baron-Cohen S. Mindblindness: an essay on autism and theory of mind. Boston: MIT Press/Bradford Books; 1995.Google Scholar
  116. 116.
    Brunet-Gouet E, Decety J. Social brain dysfunctions in schizophrenia: A review of neuroimaging studies. Psychiatry Res: Neuroimaging. 2006;148:75–92.PubMedCrossRefGoogle Scholar
  117. 117.
    Schlosser RG, Wagner G, Schachtzabel C, Peikert G, Koch K, Reichenbach JR, Sauer H. Fronto-cingulate effective connectivity in obsessive compulsive disorder: a study with fMRI and dynamic causal modeling. Hum Brain Mapp. 2010;31(12):1834–50.PubMedCrossRefGoogle Scholar
  118. 118.
    Sears LL, Vest C, Mohamed S, Bailery J, Ranson BJ, Piven J. An MRI study of the basal ganglia in autism. Prog Neuropsychopharmacol Biol Psychiatry. 1999;23:613–24.PubMedCrossRefGoogle Scholar
  119. 119.
    Vasconcelos MM, Brito AR, Domingues RC, da Cruz LC, Jr GEL, Werner Jr J, Gonçalves JP. Proton magnetic resonance spectroscopy in school-aged autistic children. J Neuroimaging. 2008;18(3):288–95.PubMedCrossRefGoogle Scholar
  120. 120.
    Oblak A, Gibbs TT, Blatt GJ. Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism. Autism Res. 2009;2:205–19.PubMedCrossRefGoogle Scholar
  121. 121.
    Oner O, Devrimci-Ozguven H, Oktem F, Yagmurlu B, Baskak B, Munir KM. Proton MR spectroscopy: higher right anterior Cingulate N-Acetylaspartate/Choline ratio in asperger syndrome compared with healthy controls. Am J Neuroradiol. 2007;28:1494–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Baxter LR, Saxena S, Brody AL, Ackermann RF, Colgan M, Schwartz JM. Brain mediation of obsessive-compulsive disorder symptoms: evidence from functional brain imaging studies in the human and nonhuman primate. Semin Clin Neuropsychiatry. 1996;1:32–47.PubMedGoogle Scholar
  123. 123.
    Insel TR. Toward a neuroanatomy of obsessive compulsive disorder. Psychiatr Clin North Am. 1992;15:813–24.PubMedGoogle Scholar
  124. 124.
    Modell JG, Mountz JM, Curtis GC, Greden JF. Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci. 1989;1:27–36.PubMedGoogle Scholar
  125. 125.
    Rapoport JL, Wise SP. Obsessive-compulsive disorderL Evidence fo basas ganglia dysfunction. Psychopharmacol Bull. 1988;24:380–4.PubMedGoogle Scholar
  126. 126.
    Maia TV, Cooney RE, Peterson BS. The neural bases of obsessive-compulsive disorder in children and adults. Dev Psychopathol. 2008;20:1251–83.PubMedCrossRefGoogle Scholar
  127. 127.
    Horwitz B, Rumsey JM, Grady CL, Rapoport SI. The cerebral metabolic landscape in autism: intercorrelations of regional glucose utilization. Arch Neurol. 1988;45:749–55.PubMedCrossRefGoogle Scholar
  128. 128.
    Shafritz KM, Dichter GS, Baranek GT, Belger A. The neural circuitry mediating shifts in behavioral response and cognitive set in autism. Biol Psychiatry. 2008;63:974–80.PubMedCrossRefGoogle Scholar
  129. 129.
    Takarae Y, Minshew NJ, Luna B, Sweeney JA. Atypical involvement of frontostriatal systems during sensorimotor control in autism. Psychiatry Res. 2007;156:117–27.PubMedCrossRefGoogle Scholar
  130. 130.
    Di Martino A, Kelly C, Grzadzinski R, Zuo X, Mennes M, Mairena MA, Lord C, Castellanos FX, Milham MP. Aberrant striatal functional connectivity in children with autism. Biol Psychiatry. 2011;69(9):847–56.PubMedCrossRefGoogle Scholar
  131. 131.
    Hardan AY, Minshew NJ, Melhem NM, Srihari S, Jo B, Bansal R, Keshavan MS, Stanley JA. An MRI and proton spectroscopy study of the thalamus in children with autism. Psychiatry Res. 2008;163(2):97–105.PubMedCrossRefGoogle Scholar
  132. 132.
    Dunn W. Performance of typical children on the Sensory Profile: an item analysis. Am J Occup Ther. 1994;48:967–74.PubMedCrossRefGoogle Scholar
  133. 133.
    Frahm J, Bruhn H, Gyngell ML, Merboldt KD, Hanicke W, Sauter R. Localized high-resolution proton NMR spectrsocopy using stimulated echoes: initial applications to human brain in vivo. Magn Reson Med. 1989;9:79–93.PubMedCrossRefGoogle Scholar
  134. 134.
    Perich-Alsina J, Aduna de Paz M, Valls A, Munoz-Yanta JA. Thalamic spectrsocopy using magnetic resonance in autism. Rev Neurol. 2002;34:S68–71.PubMedGoogle Scholar
  135. 135.
    Tsatsanis KD, Rourke BP, Klin A, Volkmar FR, Cicchetti D, Schuiltz RT. Reduced thalamic volume in high-functioning individuals with autism. Biol Psychiatry. 2003;15:121–9.CrossRefGoogle Scholar
  136. 136.
    Haznedar MM, Buchsbaum MS, Hazlett EA, KiCalzi EM, Cartwright C, Hollander E. Volumetric analysis and three-dimensional glucose metabolic mapping of the striatum and thalamus in patients with autism spectrum disorders. Am J Psychiatry. 2006;163:1252–63.PubMedCrossRefGoogle Scholar
  137. 137.
    Hardan AY, Girgis RR, Adams J, Gilbert AR, Keshavan MS, Minshew NJ. Abnormal brain size effect on the thalamus in autism. Psychiatry Res. 2006;147:145–51.PubMedCrossRefGoogle Scholar
  138. 138.
    Adolphs R, Tranel D, Hamann S, Young AW, Calder AJ, Phelps EA, et al. Recognition of facial emotion in nine individuals with bilateral amygdala damage. Neuropsychologia. 1999;37(10):1111–7.PubMedCrossRefGoogle Scholar
  139. 139.
    Adolphs R. The neurobiology of social cognition. Curr Opin Neurobiol. 2001;11(2):231–9.PubMedCrossRefGoogle Scholar
  140. 140.
    Adolphs R, Sears L, Piven J. Abnormal processing of social information from faces in autism. J Cogn Neurosci. 2001;13(2):232–40.PubMedCrossRefGoogle Scholar
  141. 141.
    Bachevalier J, Loveland KA. The orbitofrontal-amygdala circuit and self-regulation of social-emotional behavior in autism. Neurosci Biobehav Rev. 2006;30:87–117.CrossRefGoogle Scholar
  142. 142.
    Nacewicz BM, Dalton KM, Johnstone T, Long MT, McAuliff EM, Oakes TR, Alexander AL, Davidson RJ. Amygdala volume and nonverbal social impairment in adolescent and adult males with autis. Arch Gen Psychiarty. 2006;63:1417–28.CrossRefGoogle Scholar
  143. 143.
    Wang AT, Dapretto M, Hariri AR, Sigman M, Bookheimer SY. Neural correlates of facial affect processing in children and adolescents with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2004;43:481–90.PubMedCrossRefGoogle Scholar
  144. 144.
    Dalton KM, Kalin NH, Grist TM, Davidson RJ. Neural-cardiac coupling in threat-evoked anxiety. J Cogn Neurosci. 2005;17:969–80.PubMedCrossRefGoogle Scholar
  145. 145.
    Ashwin C, Wheelwright S, Baron-Cohen S. Finding a face in the crowd: testing the anger superiority effect in Asperger Syndrome. Brain Cogn. 2006;61:78–95.PubMedCrossRefGoogle Scholar
  146. 146.
    Kleinhans NM, Richards T, Sterling L, Stegbauer KC, Mahurin R, Johnson LC, et al. Abnormal functional connectivity in autism spectrum disorders during face processing. Brain. 2008;131(4):1000–12.PubMedCrossRefGoogle Scholar
  147. 147.
    Otsuka H, Harada M, Mori K, Hisaoka S, Nishitani H. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an 1 H-MR spectroscopy study. Neuroradiology. 1999;41(7):517–9.PubMedCrossRefGoogle Scholar
  148. 148.
    Endo T, Shioiri T, Kitamura H, Kimura T, Endo S, Masuzawa N, Someya T. Altered chemical metabolites in the amygdala-hippocampus region contribute to autistic symptoms of autism spectrum disorders. Biol Psychiatry. 2007;62(9):1030–7.PubMedCrossRefGoogle Scholar
  149. 149.
    Gabis L, Huang W, Azizian A, DeVincent C, Tudorica A, Kesner-Baruch Y, Roche P, Pomeroy J. 1H-magnetic resonance spectroscopy markers of cognitive and language ability in clinical subtypes of autism spectrum disorders. J Child Neurol. 2008;23(7):766–74.PubMedCrossRefGoogle Scholar
  150. 150.
    Chugani DC, Sundram BS, Behen M, Lee ML, Moore GJ. Evidence of altered energy metabolism in autistic children. Prog Neuropsychopharmacol Biol Psychiatry. 1999;23(4):635–41.PubMedCrossRefGoogle Scholar
  151. 151.
    Kurita H, Miyake Y, Katsuno K. Reliability and validity of the Childhood Autism Rating Scale- Tokyo version (CARS-TV). J Autism Dev Disord. 1989;19:389–96.PubMedCrossRefGoogle Scholar
  152. 152.
    Kleinhans NM, Richards T, Weaver KE, Liang O, Dawson G, Aylward E. Brief Report: Biochemical Correlates of Clinical Impairment in High Functioning Autism and Asperger’s Disorder. J Autism Dev Disord. 2009;39:1079–86.PubMedCrossRefGoogle Scholar
  153. 153.
    Sokol DK, Dunn DW, Edwards-Brown M, Feinberg J. Hydrogen proton magnetic resonance spectroscopy in autism: preliminary evidence of elevated choline/creatine ratio. J Child Neurol. 2002;17(4):245–9.PubMedCrossRefGoogle Scholar
  154. 154.
    Suzuki K, Nishimura K, Sugihara G, Nakamura K, Tsuchiya KJ, Matsumoto K, Takebayahsi K, Isoda H, Sakahara H, Sugiyama T, Tsujii M, Takei N, Mori N. Metabolite alterations in the hippocampus of high-fucntioning adult subjects with autism. Int J Neuropsychopharmacol. 2010;13:529–34.PubMedCrossRefGoogle Scholar
  155. 155.
    Fontani G, Vegni V. Hippocampal electrical activity during social interactions in rabbits living in a seminatural environment. Physiol Behav. 1990;47:175–83.PubMedCrossRefGoogle Scholar
  156. 156.
    Tebartz van Elst L, Woermann FG, Lemieux L, Thompson PJ, et al. Affective aggression in patients with temporal lobe epilepsy: a quantitative MRI study of the amygdala. Brain. 2000;123:234–43.CrossRefGoogle Scholar
  157. 157.
    Gregg TR, Siegel A. Brain structures and neurotransmitters regulating aggression in cats: implications for human aggression. Prog Neuropsychopharmacol Biol Psychiatry. 2001;25:91–140.PubMedCrossRefGoogle Scholar
  158. 158.
    Zetzsche T, Preuss UW, Frodl T, Schmitt G, et al. Hippocampal volume reduction and history of aggressive behaviour in patients with borderline personality disorder. Psychiatry Res. 2007;154:157–70.PubMedCrossRefGoogle Scholar
  159. 159.
    Ando A, Soga S, Yamasaki K, Shimai T, et al. Development of the Japanese version of the Development of the Japanese version of the Buss-Perry Aggression Questionnaire (BAQ) [in Japanese]. Jap J Psychol. 1999;70:384–92.CrossRefGoogle Scholar
  160. 160.
    Palmen SJ, van Engeland H, Hof PR, Schmitz C. Neuropathological findings in autism. Brain. 2004;127:2575–83.CrossRefGoogle Scholar
  161. 161.
    Schmahmann JD, Pandya DN. There cerebrocerebellar system. In: Schmahmann J, editor. The cerebellum and cognition. San Diego: Academic; 1997. p. 31–60.Google Scholar
  162. 162.
    Ito M. Control of mental activities by internal models in the cerebellum. Nat Rev Neurosci. 2008;9:304–13.PubMedCrossRefGoogle Scholar
  163. 163.
    Courchesne E, Redcay E, Morgan JT, Kennedy DP. Autism at the beginning: microstructural and growth abnormalities underlying the cognitive and behavioral phenotype of autism. Dev Psychopathol. 2005;17:577–97.PubMedCrossRefGoogle Scholar

Further Reading

  1. Bluml S, Seymour KJ, Ross BD. Developmental changes in choline- and ethanolamine-containing compounds measured with proton-decoupled (31)P MRS in vivo human brain. Magn Reson Med. 1999;42:643–54.PubMedCrossRefGoogle Scholar
  2. Castelli F, Frith C, Happe F, Frith U. Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. Brain. 2002;125:1839–49.PubMedCrossRefGoogle Scholar
  3. Davis MH. Measuring individual differences in empathy: evidence for a multidimensional approach. J Pers Soc Psychol. 1983;44(1):113–26.CrossRefGoogle Scholar
  4. Filler A. MR Neurography and Diffusion Tensor Imaging: Origins, history and clinical impact. Neurosurgery. 2009;65:29–43.CrossRefGoogle Scholar
  5. Gupta RK, Cloughesy TF, Sinha U, Garakian J, Rubino G, Rubino L, Becker DP, Vinters HV, Alger JR. Relationships between choline magnetic resonance spectroscopy, apparent diffusion coefficient and quantitative histopathology in human glioma. J Neuro-Oncol. 2000;50:215–26.CrossRefGoogle Scholar
  6. Hashimoto T, Kawano N, Fukuda K, Endo S, Mori K, Yoneda Y, Yamaue T, Harada M, Miyoshi K. Proton magnetic resonance spectroscopy of the brain in three cases of Rett syndrome: comparison with autism and normal controls. Acta Neurol Scand. 1998;98(1):8–14.PubMedCrossRefGoogle Scholar
  7. Kahne D, Tudorica A, Borella A, Shapiro L, Johnstone F, Huang W, Whitaker-Azmitia PM. Behavioral and magnetic resonance spectroscopic studies in the rat hyperserotonemic model of autism. Physiol Behav. 2002;75(3):403–10.PubMedCrossRefGoogle Scholar
  8. Kemper TL, Bauman ML. Neuropathology of infantile autism. J Neuropathol Exp Neurol. 1998;57:645–52.PubMedCrossRefGoogle Scholar
  9. Langen M, Durston S, Staal WG, Palmen SJ, van Engeland H. Caudate nucleus is enlarged in high-functioning medication-naïve subjects with autism. Biol Psychiatry. 2007;62:262–6.PubMedCrossRefGoogle Scholar
  10. Minshew NJ, Dombrowski SM. In vivo neuroanatomy of autism: neuro- imaging studies. In: Bauman ML, Kemper TL, editors. The neurobiology of autism. Baltimore: Johns Hopkins University Press; 1994. p. 67–85.Google Scholar
  11. Montag C, Schubert F, Heinz A, Gallinat J. Prefrontal cortex glutamate correlates with mental perspective-taking. PLoS One. 2008;3(12):e3890.PubMedCrossRefGoogle Scholar
  12. Paulus C. Empathie, Kompetenz und Altruismus. 1992. http://www.uni-saarland.de/fak5/ezw/abtell/motiv/paper/empathie.htm.
  13. Pons R, Andreu AL, Checcarelli N, Vilà MR, Engelstad K, Sue CM, Shungu D, Haggerty R, de Vivo DC, DiMauro S. Mitochondrial DNA abnormalities and autistic spectrum disorders. J Pediatr. 2004;144(1):81–5.PubMedCrossRefGoogle Scholar
  14. Provencher SW. LcModel and LcMgui user’s manual. Available at: http://s-provencher.com/pages/lcm-manual.shtml. Accessed January 19, 2000.
  15. Redcay E, Courchesne E. When is the brain enlarged in autism? A meta-analysis of all brain size reports. Biol Psychiatry. 2004;58:1–9.CrossRefGoogle Scholar
  16. Rosenberg DR, Keshavan MS, O’Hearn KM, Dick EL, Bagwell WW, Seymour AB, Montrose DM, Pierri JN, Birmaher B. Frontostriatal measurement in treatment-naïve children with obsessive-compulsive disorder. Arch Gen Psychiatry. 1997;54:824–30.PubMedCrossRefGoogle Scholar
  17. Rosenberg DR, Keshavan MS. AE Bennett Research Award. Toward a neurodevelopmental model of obsessive—compulsive disorder. Biol Psychiatry. 1998;43:623–40.PubMedCrossRefGoogle Scholar
  18. Rothman DL, Behar KL, Hyder F, Shulman RG. In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: Implications for brain function. Annu Rev Physiol. 2003;65:401–27.PubMedCrossRefGoogle Scholar
  19. Strauss WL, Unis AS, Cowan C, Dawson G, Dager SR. Fluorine magnetic resonance spectroscopy measurement of brain fluvoxamine and fluoxetine in pediatric patients treated for pervasive developmental disorders. Am J Psychiatry. 2002;159(5):755–60.PubMedCrossRefGoogle Scholar
  20. Zilbovicius M, Garreau B, Samson Y, Remy P. Delayed maturation of the frontal cortex in childhood autism. Am J Psychiatry. 1995;152:248–52.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Jennifer G. Levitt
    • 1
  • Joseph O’Neill
    • 2
  • Jeffry R. Alger
    • 3
  1. 1.Department of PsychiatrySemel Institute for Neuroscience and Human Behavior, UCLALos AngelesUSA
  2. 2.Division of Child and Adolescent PsychiatrySemel Institute for Neuroscience and Human Behavior, UCLALos AngelesUSA
  3. 3.Department of Radiological SciencesUCLALos AngelesUSA

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