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Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study

Published online by Cambridge University Press:  06 November 2009

F. Toal ,
E. M. Daly ,
L. Page ,
Q. Deeley ,
B. Hallahan ,
O. Bloemen ,
W. J. Cutter ,
M. J. Brammer ,
S. Curran  and
D. Robertson
...Show all authors
F. Toal*
Affiliation:
Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
E. M. Daly
Affiliation:
Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
L. Page
Affiliation:
Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
Q. Deeley
Affiliation:
Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
B. Hallahan
Affiliation:
Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
O. Bloemen
Affiliation:
Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
W. J. Cutter
Affiliation:
Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
M. J. Brammer
Affiliation:
Section of Image Analysis, Centre for Neuroimaging Science, Institute of Psychiatry, King's College, London, UK
S. Curran
Affiliation:
Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
D. Robertson
Affiliation:
Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
C. Murphy
Affiliation:
Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
K. C. Murphy
Affiliation:
Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland
D. G. M. Murphy
Affiliation:
Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
*
*Address for correspondence: Dr F. Toal, MRCPsych, Institute of Forensic Mental Health, Thomas Embling Hospital, Yarra Bend Road, Melbourne, Australia. (Email: [email protected])
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Abstract

Background

Autistic spectrum disorder (ASD) is characterized by stereotyped/obsessional behaviours and social and communicative deficits. However, there is significant variability in the clinical phenotype; for example, people with autism exhibit language delay whereas those with Asperger syndrome do not. It remains unclear whether localized differences in brain anatomy are associated with variation in the clinical phenotype.

Method

We used voxel-based morphometry (VBM) to investigate brain anatomy in adults with ASD. We included 65 adults diagnosed with ASD (39 with Asperger syndrome and 26 with autism) and 33 controls who did not differ significantly in age or gender.

Results

VBM revealed that subjects with ASD had a significant reduction in grey-matter volume of medial temporal, fusiform and cerebellar regions, and in white matter of the brainstem and cerebellar regions. Furthermore, within the subjects with ASD, brain anatomy varied with clinical phenotype. Those with autism demonstrated an increase in grey matter in frontal and temporal lobe regions that was not present in those with Asperger syndrome.

Conclusions

Adults with ASD have significant differences from controls in the anatomy of brain regions implicated in behaviours characterizing the disorder, and this differs according to clinical subtype.

Keywords

Asperger syndromeautismbrain anatomyclinical phenotypeneuroimaging
Type
Original Articles
Information
Psychological Medicine , Volume 40 , Issue 7 , July 2010 , pp. 1171 - 1181
Copyright
Copyright © Cambridge University Press 2009

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References

Abell, F, Krams, M, Ashburner, J, Passingham, R, Friston, K, Frackowiak, R, Happé, F, Frith, C, Frith, U (1999). The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans. NeuroReport 10, 1647–1651.CrossRefGoogle ScholarPubMed
Allen, G, Müller, RA, Courchesne, E (2004). Cerebellar function in autism: functional magnetic resonance image activation during a simple motor task. Biological Psychiatry 56, 269–278.CrossRefGoogle ScholarPubMed
Ashburner, J, Friston, KJ (2000). Voxel-based morphometry –the methods. NeuroImage 11, 805–821.CrossRefGoogle ScholarPubMed
Aylward, EH, Minshew, NJ, Goldstein, G, Honeycutt, NA, Augustine, AM, Yates, KO, Barta, PE, Pearlson, GD (1999). MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults. Neurology 53, 2145–2150.CrossRefGoogle ScholarPubMed
Bailey, A, Luthert, P, Dean, A, Harding, B, Janota, I, Montgomery, M, Rutter, M, Lantos, P (1998). A clinicopathological study of autism. Brain 121, 889–905.CrossRefGoogle ScholarPubMed
Baird, G, Simonoff, E, Pickles, A, Chandler, S, Loucas, T, Meldrum, D, Charman, T (2006). Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). Lancet 368, 210–215.CrossRefGoogle Scholar
Bauman, ML, Kemper, TL (2005). Neuroanatomic observations of the brain in autism: a review and future directions. International Journal of Developmental Neuroscience 23, 183–187.Google Scholar
Bigler, ED, Mortensen, S, Neeley, ES, Ozonoff, S, Krasny, L, Johnson, M, Lu, J, Provencal, SL, McMahon, W, Lainhart, JE (2007). Superior temporal gyrus, language function, and autism. Developmental Neuropsychology 31, 217–238.CrossRefGoogle ScholarPubMed
Boddaert, N, Chabane, N, Gervais, H, Good, CD, Bourgeois, M, Plumet, MH, Barthélémy, C, Mouren, MC, Artiges, E, Samson, Y, Brunelle, F, Frackowiak, RS, Zilbovicius, M (2004). Superior temporal sulcus anatomical abnormalities in childhood autism: a voxel-based morphometry MRI study. NeuroImage 23, 364–369.CrossRefGoogle ScholarPubMed
Bolton, PF, Griffiths, PD (1997). Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet 349, 392–395.CrossRefGoogle ScholarPubMed
Bolton, PF, Pickles, A, Murphy, M, Rutter, M (1998). Autism, affective and other psychiatric disorders: patterns of familial aggregation. Psychological Medicine 28, 385–395.CrossRefGoogle ScholarPubMed
Bullmore, ET, Suckling, J, Overmeyer, S, Rabe-Hesketh, S, Taylor, E, Brammer, MJ (1999). Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain. IEEE Transactions on Medical Imaging 18, 32–42.CrossRefGoogle ScholarPubMed
Campbell, LE, Daly, E, Toal, F, Stevens, A, Azuma, R, Catani, M, Ng, V, van Amelsvoort, T, Chitnis, X, Cutter, W, Murphy, DG, Murphy, KC (2006). Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and voxel-based morphometry MRI study. Brain 129, 1218–1228.Google Scholar
Courchesne, E, Yeung-Courchesne, R, Press, GA, Hesselink, JR, Jernigan, TL (1988). Hypoplasia of cerebellar vermal lobules VI and VII in autism. New England Journal of Medicine 318, 1349–1354.CrossRefGoogle ScholarPubMed
Courchesne, E, Townsend, J, Saitoh, O (1994). The brain in infantile autism: posterior fossa structures are abnormal. Neurology 44, 214–223.CrossRefGoogle ScholarPubMed
Courchesne, E (1997). Brainstem, cerebellar and limbic neuroanatomical abnormalities in autism. Current Opinion in Neurobiology 7, 269–278.CrossRefGoogle ScholarPubMed
Courchesne, E (1999). An MRI study of autism: the cerebellum revisited. Neurology 52, 1106–1107.CrossRefGoogle ScholarPubMed
Courchesne, E, Karns, CM, Davis, 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, Courchesne, RY (2001). Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology 57, 245–254.CrossRefGoogle ScholarPubMed
Critchley, HD, Daly, EM, Bullmore, ET, Williams, SC, Van Amelsvoort, T, Robertson, DM, Rowe, A, Phillips, M, McAlonan, G, Howlin, P, Murphy, DG (2000). The functional neuroanatomy of social behaviour: changes in cerebral blood flow when people with autistic disorder process facial expressions. Brain 123, 2203–2212.CrossRefGoogle ScholarPubMed
Cutter, WJ, Daly, EM, Robertson, DM, Chitnis, XA, van Amelsvoort, TA, Simmons, A, Ng, VW, Williams, BS, Shaw, P, Conway, GS, Skuse, DH, Collier, DA, Craig, M, Murphy, DG (2006). Influence of X chromosome and hormones on human brain development: a magnetic resonance imaging and proton magnetic resonance spectroscopy study of Turner syndrome. Biological Psychiatry 59, 273–283.CrossRefGoogle ScholarPubMed
Dunn, LlM, Dunn, LM, Whetton, C, Burley, J (1997). British Picture Vocabulary Scale, 2nd edn (BPVS-II). NFER-Nelson: Windsor, Berks.Google Scholar
Dalton, KM, Nacewicz, BM, Johnstone, T, Schaefer, HS, Gernsbacher, MA, Goldsmith, HH, Alexander, AL, Davidson, RJ (2005). Gaze fixation and the neural circuitry of face processing in autism. Nature Neuroscience 8, 519–526.CrossRefGoogle ScholarPubMed
Frith, U, Frith, CD (2003). Development and neurophysiology of mentalizing. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 358, 459–473.CrossRefGoogle Scholar
Gilchrist, A, Green, J, Cox, A, Burton, D, Rutter, M, Le Couteur, A (2001). Development and current functioning in adolescents with Asperger syndrome: a comparative study. Journal of Child Psychology and Psychiatry, and Allied Disciplines 42, 227–240.Google Scholar
Good, CD, Johnsrude, IS, Ashburner, J, Henson, RN, Friston, KJ, Frackowiak, RS (2001). A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage 14, 21–36.CrossRefGoogle ScholarPubMed
Hallahan, B, Daly, EM, McAlonan, G, Loth, E, Toal, F, O'Brien, F, Robertson, D, Hales, S, Murphy, C, Murphy, KC, Murphy, DG (2009). Brain morphometry volume in autistic spectrum disorder: a magnetic resonance imaging study of adults. Psychological Medicine 39, 337–346.CrossRefGoogle ScholarPubMed
Haxby, JV, Hoffman, EA, Gobbini, MI (2002). Human neural systems for face recognition and social communication. Biological Psychiatry 51, 59–67.CrossRefGoogle ScholarPubMed
Herbert, MR, Harris, GJ, Adrien, KT, Ziegler, DA, Makris, N, Kennedy, DN, Lange, NT, Chabris, CF, Bakardjiev, A, Hodgson, J, Takeoka, M, Tager-Flusberg, H, Caviness, VS Jr. (2002). Abnormal asymmetry in language association cortex in autism. Annals of Neurology 52, 588–596.CrossRefGoogle ScholarPubMed
Hollander, E, Anagnostou, E, Chaplin, W, Esposito, K, Haznedar, MM, Licalzi, E, Wasserman, S, Soorya, L, Buchsbaum, M (2005). Striatal volume on magnetic resonance imaging and repetitive behaviors in autism. Biological Psychiatry 58, 226–232.CrossRefGoogle ScholarPubMed
Howard, MA, Cowell, PE, Boucher, J, Broks, P, Mayes, A, Farrant, A, Roberts, N (2000). Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of autism. NeuroReport 11, 2931–2935.CrossRefGoogle ScholarPubMed
Jarbrink, K, McCrone, P, Fombonne, E, Zanden, H, Knapp, M (2007). Cost-impact of young adults with high-functioning autistic spectrum disorder. Research in Developmental Disabilities 28, 94–104.CrossRefGoogle ScholarPubMed
Just, MA, Cherkassky, VL, Keller, TA, Minshew, NJ (2004). Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity. Brain 127, 1811–1821.CrossRefGoogle ScholarPubMed
Kemper, TL, Bauman, ML (1993). The contribution of neuropathologic studies to the understanding of autism. Neurologic Clinics 11, 175–187.Google Scholar
Kemper, TL, Bauman, ML (2002). Neuropathology of infantile autism. Molecular Psychiatry 7 (Suppl. 2), S12–S13.CrossRefGoogle ScholarPubMed
Klin, A, Volkmar, FR (2003). Asperger syndrome: diagnosis and external validity. Child and Adolescent Psychiatric Clinics of North America 12, 1–13.CrossRefGoogle ScholarPubMed
Kwon, H, Ow, AW, Pedatella, KE, Lotspeich, LJ, Reiss, AL (2004). Voxel-based morphometry elucidates structural neuroanatomy of high-functioning autism and Asperger syndrome. Developmental Medicine and Child Neurology 46, 760–764.CrossRefGoogle ScholarPubMed
Lainhart, JE, Bigler, ED, Bocian, M, Coon, H, Dinh, E, Dawson, G, Deutsch, CK, Dunn, M, Estes, A, Tager-Flusberg, H, Folstein, S, Hepburn, S, Hyman, S, McMahon, W, Minshew, N, Munson, J, Osann, K, Ozonoff, S, Rodier, P, Rogers, S, Sigman, M, Spence, MA, Stodgell, CJ, Volkmar, F (2006). Head circumference and height in autism: a study by the Collaborative Program of Excellence in Autism. American Journal of Medical Genetics. Part A 140, 2257–2274.CrossRefGoogle Scholar
Lord, C, Rutter, M, Goode, S, Heemsbergen, J, Jordan, H, Mawhood, L, Schopler, E (1989). Autism diagnostic observation schedule: a standardized observation of communicative and social behavior. Journal of Autism and Developmental Disorders 19, 185–212.CrossRefGoogle ScholarPubMed
Lord, C, Rutter, M, Le Couteur, A (1994). Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders 24, 659–685.CrossRefGoogle ScholarPubMed
Lotspeich, LJ, Kwon, H, Schumann, CM, Fryer, SL, Goodlin-Jones, BL, Buonocore, MH, Lammers, CR, Amaral, DG, Reiss, AL (2004). Investigation of neuroanatomical differences between autism and Asperger syndrome. Archives of General Psychiatry 61, 291–298.Google Scholar
Mayes, SD, Calhoun, SL, Crites, DL (2001). Does DSM-IV Asperger's disorder exist? Journal of Abnormal Child Psychology 29, 263–271.CrossRefGoogle ScholarPubMed
McAlonan, GM, Daly, E, Kumari, V, Critchley, HD, van Amelsvoort, T, Suckling, J, Simmons, A, Sigmundsson, T, Greenwood, K, Russell, A, Schmitz, N, Happe, F, Howlin, P, Murphy, DG (2002). Brain anatomy and sensorimotor gating in Asperger's syndrome. Brain 125, 1594–1606.CrossRefGoogle ScholarPubMed
McAlonan, GM, Cheung, V, Cheung, C, Suckling, J, Lam, GY, Tai, KS, Yip, L, Murphy, DG, Chua, SE (2005). Mapping the brain in autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism. Brain 128, 268–276.CrossRefGoogle ScholarPubMed
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 (2002). Asperger syndrome: a proton magnetic resonance spectroscopy study of brain. Archives of General Psychiatry 59, 885–891.CrossRefGoogle ScholarPubMed
Murphy, DG, Daly, E, Schmitz, N, Toal, F, Murphy, K, Curran, S, Erlandsson, K, Eersels, J, Kerwin, R, Ell, P, Travis, M (2006). Cortical serotonin 5-HT2A receptor binding and social communication in adults with Asperger's syndrome: an in vivo SPECT study. American Journal of Psychiatry 163, 934–936.CrossRefGoogle ScholarPubMed
Ozonoff, S, Rogers, SJ, Pennington, BF (1991). Asperger's syndrome: evidence of an empirical distinction from high-functioning autism. Journal of Child Psychology and Psychiatry, and Allied Disciplines 32, 1107–1122.Google Scholar
Pierce, K, Courchesne, E (2001). Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism. Biological Psychiatry 49, 655–664.CrossRefGoogle ScholarPubMed
Piven, J, Arndt, S, Bailey, J, Havercamp, S, Andreasen, NC, Palmer, P (1995). An MRI study of brain size in autism. American Journal of Psychiatry 152, 1145–1149.Google ScholarPubMed
Piven, J, Bailey, J, Ranson, BJ, Arndt, S (1998). No difference in hippocampus volume detected on magnetic resonance imaging in autistic individuals. Journal of Autism and Developmental Disorders 28, 105–110.Google Scholar
Piven, J, Saliba, K, Bailey, J, Arndt, S (1997). An MRI study of autism: the cerebellum revisited. Neurology 49, 546–551.CrossRefGoogle ScholarPubMed
Raven, JC (1938). Progressive Matrices: A Perceptual Test of Intelligence. H. K. Lewis: London.Google Scholar
Rinehart, NJ, Bradshaw, JL, Brereton, AV, Tonge, BJ (2002). A clinical and neurobehavioural review of high-functioning autism and Asperger's disorder. Australian and New Zealand Journal of Psychiatry 36, 762–770.CrossRefGoogle ScholarPubMed
Rojas, DC, Peterson, E, Winterrowd, E, Reite, ML, Rogers, SJ, Tregellas, JR (2006). Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms. BMC Psychiatry 6, 56.CrossRefGoogle ScholarPubMed
Saitoh, O, Karns, CM, Courchesne, E (2001). Development of the hippocampal formation from 2 to 42 years: MRI evidence of smaller area dentata in autism. Brain 124, 1317–1324.CrossRefGoogle ScholarPubMed
Salmond, CH, Vargha-Khadem, F, Gadian, DG, de Haan, M, Baldeweg, T (2007). Heterogeneity in the patterns of neural abnormality in autistic spectrum disorders: evidence from ERP and MRI. Cortex 43, 686–699.CrossRefGoogle ScholarPubMed
Schultz, RT, Gauthier, I, Klin, A, Fulbright, RK, Anderson, AW, Volkmar, F, Skudlarski, P, Lacadie, C, Cohen, DJ, Gore, JC (2000). Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome. Archives of General Psychiatry 57, 331–340.CrossRefGoogle ScholarPubMed
Sears, LL, Vest, C, Mohamed, S, Bailey, J, Ranson, BJ, Piven, J (1999). An MRI study of the basal ganglia in autism. Progress in Neuro-Psychopharmacology and Biological Psychiatry 23, 613–624.Google Scholar
Sokol, DK, Edwards-Brown, M (2004). Neuroimaging in autistic spectrum disorder (ASD). Journal of Neuroimaging 14, 8–15.CrossRefGoogle ScholarPubMed
Sparks, BF, Friedman, SD, Shaw, DW, Aylward, EH, Echelard, D, Artru, AA, Maravilla, KR, Giedd, JN, Munson, J, Dawson, G, Dager, SR (2002). Brain structural abnormalities in young children with autism spectrum disorder. Neurology 59, 184–192.CrossRefGoogle ScholarPubMed
Volkmar, FR, Klin, A, Pauls, D (1998). Nosological and genetic aspects of Asperger syndrome. Journal of Autism and Developmental Disorders 28, 457–463.CrossRefGoogle ScholarPubMed
Waiter, GD, Williams, JH, Murray, AD, Gilchrist, A, Perrett, DI, Whiten, A (2004). A voxel-based investigation of brain structure in male adolescents with autistic spectrum disorder. NeuroImage 22, 619–625.Google Scholar
Wechsler, D (1981). Wechsler Adult Intelligence Scale – Revised (WAIS-R). The Psychological Corporation: New York.Google Scholar
WHO (1992). The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Description and Diagnostic Guidelines. World Health Organization: Geneva, Switzerland.Google Scholar
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