Skip to main content
Log in

A Two-Year Longitudinal MRI Study of the Corpus Callosum in Autism

  • Original Paper
  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

A growing body of literature has identified size reductions of the corpus callosum (CC) in autism. However, to our knowledge, no published studies have reported on the growth of CC volumes in youth with autism. Volumes of the total CC and its sub-divisions were obtained from 23 male children with autism and 23 age- and gender-matched controls at baseline and 2-year follow-up. Persistent reductions in total CC volume were observed in participants with autism relative to controls. Only the rostral body subdivision showed a normalization of size over time. Persistent reductions are consistent with the diagnostic stability and life-long impairment observed in many individuals with autism. Multi-modal imaging studies are needed to identify specific fiber tracks contributing to CC reductions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Achenbach, T. M. (1991). Manual for the child behavior checklist/4-18 and 1991 profile. Burlington: University of Vermont, Department of Psychiatry.

    Google Scholar 

  • Alexander, A. L., Lee, J. E., Lazar, M., Boudos, R., DuBray, M. B., & Oakes, T. R. (2007). Diffusion tensor imaging of the corpus callosum in autism. Neuroimage, 34, 61–73.

    Article  PubMed  Google Scholar 

  • Amaral, D. G., Schumann, C. M., & Nordahl, C. W. (2008). Neuroanatomy of autism. Trends in Neurosciences, 31(3), 137–145.

    Article  PubMed  Google Scholar 

  • American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th edition, text revision ed.). Washington, DC: American Psychiatric Association.

    Book  Google Scholar 

  • Bailey, A., Luthert, P., Bolton, P., Le Couteur, A., Rutter, M., & Harding, B. (1993). Autism and megalencephaly. Lancet, 341(8854), 1225–1226. doi:0140-6736(93)91065-T.

    Article  PubMed  Google Scholar 

  • Bailey, A., Luthert, P., Dean, A., Harding, B., Janota, I., & Montgomery, M. (1998). A clinicopathological study of autism. Brain, 121(Pt 5), 889–905.

    Article  PubMed  Google Scholar 

  • Barnea-Goraly, N., Kwon, H., Menon, V., Eliez, S., Lotspeich, L., & Reiss, A. L. (2004). White matter structure in autism: Preliminary evidence from diffusion tensor imaging. Biological Psychiatry, 55(3), 323–326. doi:S000632230301151X.

    Article  PubMed  Google Scholar 

  • Bennetto, L., Pennington, B. F., & Rogers, S. J. (1996). Intact and impaired memory functions in autism. Child Development, 67(4), 1816–1835.

    Article  PubMed  Google Scholar 

  • Billstedt, E., Gillberg, I. C., & Gillberg, C. (2005). Autism after adolescence: Population-based 13- to 22-year follow-up study of 120 individuals with autism diagnosed in childhood. Journal of Autism and Developmental Disorders, 35(3), 351–360.

    Article  PubMed  Google Scholar 

  • Boger-Megiddo, I., Shaw, D. W., Friedman, S. D., Sparks, B. F., Artru, A. A., & Giedd, J. N. (2006). Corpus callosum morphometrics in young children with autism spectrum disorder. Journal of Autism and Developmental Disorders, 36, 733–739.

    Article  PubMed  Google Scholar 

  • Bolte, S., Dickhut, H., & Poustka, F. (1999). Patterns of parent-reported problems indicative in autism. Psychopathology, 32(2), 93–97. doi:psp32093.

    Article  PubMed  Google Scholar 

  • Brambilla, P., Hardan, A., di Nemi, S. U., Perez, J., Soares, J. C., & Barale, F. (2003). Brain anatomy and development in autism: Review of structural MRI studies. Brain Research Bulletin, 61(6), 557–569. doi:S0361923003002235.

    Article  PubMed  Google Scholar 

  • Bryk, A. S., & Raudenbush, S. W. (1992). Hierarchical linear models: Applications and data analysis methods. Newbury Park, CA: Sage.

    Google Scholar 

  • Charman, T., Taylor, E., Drew, A., Cockerill, H., Brown, J. A., & Baird, G. (2005). Outcome at 7 years of children diagnosed with autism at age 2: Predictive validity of assessments conducted at 2 and 3 years of age and pattern of symptom change over time. Journal of Child Psychology and Psychiatry and Allied Disciplines, 46(5), 500–513. doi:10.1111/j.1469-7610.2004.00377.x.

    Article  Google Scholar 

  • Chung, M. K., Dalton, K. M., Alexander, A. L., & Davidson, R. J. (2004). Less white matter concentration in autism: 2D voxel-based morphometry. Neuroimage, 23, 242–251.

    Article  PubMed  Google Scholar 

  • Cohen, J. (1987). Statistical power analysis for the behavioral sciences (2nd ed.). Hillsdale, NJ: Erlbaum.

    Google Scholar 

  • Courchesne, E., Carper, R., & Akshoomoff, N. (2003). Evidence of brain overgrowth in the first year of life in autism. Journal of the American Medical Association, 290, 337–344.

    Article  PubMed  Google Scholar 

  • Courchesne, E., Karns, C. M., Davis, H. R., Ziccardi, R., Carper, R. A., & Tigue, Z. D. (2001). Unusual brain growth patterns in early life in patients with autistic disorder: An MRI study. Neurology, 57, 245–254.

    Article  PubMed  Google Scholar 

  • Courchesne, E., & Pierce, K. (2005). Why the frontal cortex in autism might be talking only to itself: Local over-connectivity but long-distance disconnection. Current Opinion in Neurobiology, 15(2), 225–230. doi:10.1016/j.conb.2005.03.001.

    Article  PubMed  Google Scholar 

  • Dunn, W. (1999). Sensory profile. San Antonio, TX: Psychological Corporation.

    Google Scholar 

  • Eaves, L. C., & Ho, H. H. (2008). Young adult outcome of autism spectrum disorders. Journal of Autism and Developmental Disorders, 38(4), 739–747. doi:10.1007/s10803-007-0441-x.

    Article  PubMed  Google Scholar 

  • Egaas, B., Courchesne, E., & Saitoh, O. (1995). Reduced size of corpus callosum in autism. Archives of Neurology, 52, 794–801.

    Article  PubMed  Google Scholar 

  • Esbensen, A. J., Seltzer, M. M., Lam, K. S., & Bodfish, J. W. (2009). Age-related differences in restricted repetitive behaviors in autism spectrum disorders. Journal of Autism and Developmental Disorders, 39(1), 57–66. doi:10.1007/s10803-008-0599-x.

    Article  PubMed  Google Scholar 

  • Frazier, T. W., & Hardan, A. Y. (2009). A meta-analysis of the corpus callosum in autism. Biological Psychiatry, 66(10), 935–941. doi:10.1016/j.biopsych.2009.07.022.

    Article  PubMed  Google Scholar 

  • Gallese, V. (2006). Intentional attunement: A neurophysiological perspective on social cognition and its disruption in autism. Brain Research, 1079(1), 15–24.

    Article  PubMed  Google Scholar 

  • Gallese, V., Eagle, M. N., & Migone, P. (2007). Intentional attunement: Mirror neurons and the neural underpinnings of interpersonal relations. Journal of the American Psychoanalytic Association, 55(1), 131–176.

    PubMed  Google Scholar 

  • Geschwind, D. (2007). Autism: Searching for coherence. Biological Psychiatry, 62, 949–950.

    Article  PubMed  Google Scholar 

  • Giedd, J. N., Blumenthal, J., Jeffries, N. O., Rajapakse, J. C., Vaituzis, A. C., & Liu, H. (1999). Development of the human corpus callosum during childhood and adolescence: A longitudinal MRI study. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 23(4), 571–588. doi:S0278584699000172.

    Article  PubMed  Google Scholar 

  • Giedd, J. N., Lalonde, F. M., Celano, M. J., White, S. L., Wallace, G. L., & Lee, N. R. (2009). Anatomical brain magnetic resonance imaging of typically developing children and adolescents. Journal of the American Academy of Child and Adolescent Psychiatry, 48(5), 465–470. doi:10.1097/CHI.0b013e31819f2715.

    Article  PubMed  Google Scholar 

  • Hardan, A. Y., Kilpatrick, M., Keshavan, M. S., & Minshew, N. J. (2003). Motor performance and anatomic magnetic resonance imaging (MRI) of the basal ganglia in autism. Journal of Child Neurology, 18(5), 317–324.

    Article  PubMed  Google Scholar 

  • Hardan, A. Y., Libove, R. A., Keshavan, M. S., Melhem, N. M., & Minshew, N. J. (2009a). A preliminary longitudinal magnetic resonance imaging study of brain volume and cortical thickness in autism. Biological Psychiatry, 66(4), 320–326. doi:10.1016/j.biopsych.2009.04.024.

    Article  PubMed  Google Scholar 

  • Hardan, A. Y., Minshew, N. J., & Keshavan, M. S. (2000). Corpus callosum size in autism. Neurology, 55(7), 1033–1036.

    Article  PubMed  Google Scholar 

  • Hardan, A. Y., Minshew, N. J., Mallikarjuhn, M., & Keshavan, M. S. (2001). Brain volume in autism. Journal of Child Neurology, 16(6), 421–424.

    PubMed  Google Scholar 

  • Hardan, A. Y., Pabalan, M., Gupta, N., Bansal, R., Melhem, N. M., & Fedorov, S. (2009b). Corpus callosum volume in children with autism. Psychiatry Research, 174(1), 57–61. doi:10.1016/j.pscychresns.2009.03.005.

    Article  PubMed  Google Scholar 

  • Hollingshead, A. (1975). Four factor index of social status. New Haven, CT: Yale University Department of Sociology.

    Google Scholar 

  • Howlin, P., Goode, S., Hutton, J., & Rutter, M. (2004). Adult outcome for children with autism. Journal of Child Psychology and Psychiatry and Allied Disciplines, 45(2), 212–229.

    Article  Google Scholar 

  • Just, M. A., Cherkassky, V. L., Keller, T. A., Kana, R. K., & Minshew, N. J. (2007). Functional and anatomical cortical underconnectivity in autism: Evidence from an FMRI study of an executive function task and corpus callosum morphometry. Cerebral Cortex, 17(4), 951–961. doi:10.1093/cercor/bhl006.

    Article  PubMed  Google Scholar 

  • Kanner, L. (1971). Follow-up study of eleven autistic children originally reported in 1943. Journal of Autism and Childhood Schizophrenia, 1(2), 119–145.

    Article  PubMed  Google Scholar 

  • Keary, C. J., Minshew, N. J., Bansal, R., Goradia, D., Fedorov, S., & Keshavan, M. S. (2009). Corpus callosum volume and neurocognition in autism. Journal of Autism and Developmental Disorders, 39(6), 834–841. doi:10.1007/s10803-009-0689-4.

    Article  PubMed  Google Scholar 

  • Keller, T. A., Kana, R. K., & Just, M. A. (2007). A developmental study of the structural integrity of white matter in autism. Neuroreport, 18(1), 23–27. doi:10.1097/01.wnr.0000239965.21685.99.

    Article  PubMed  Google Scholar 

  • Kemper, T. L., & Bauman, M. (1998). Neuropathology of infantile autism. Journal of Neuropathology and Experimental Neurology, 57(7), 645–652.

    Article  PubMed  Google Scholar 

  • Kobayashi, R., Murata, T., & Yoshinaga, K. (1992). A follow-up study of 201 children with autism in Kyushu and Yamaguchi areas, Japan. Journal of Autism and Developmental Disorders, 22(3), 395–411.

    Article  PubMed  Google Scholar 

  • Kreft, I. G. G. (1995). Hierarchical linear models: Problems and prospects. Journal of Educational and Behavioral Statistics, 20(2), 109–113.

    Article  Google Scholar 

  • Lainhart, J. E. (2003). Increased rate of head growth during infancy in autism. Journal of the American Medical Association, 290, 393–394.

    Article  PubMed  Google Scholar 

  • Larson, J. C., & Mostofsky, S. H. (2006). Motor deficits in autism. In R. Tuchman & I. Rapin (Eds.), Autism: A neurological disorder of early brain development. London: Mac Keith Press.

    Google Scholar 

  • Lenroot, R. K., & Giedd, J. N. (2006). Brain development in children and adolescents: Insights from anatomical magnetic resonance imaging. Neuroscience and Biobehavioral Reviews, 30(6), 718–729. doi:10.1016/j.neubiorev.2006.06.001.

    Article  PubMed  Google Scholar 

  • Levitt, J. G., O’Neill, J., Blanton, R. E., Smalley, S., Fadale, D., & McCracken, J. T. (2003). Proton magnetic resonance spectroscopic imaging of the brain in childhood autism. Biological Psychiatry, 54(12), 1355–1366. doi:S0006322303006887.

    Article  PubMed  Google Scholar 

  • Lord, C., Risi, S., DiLavore, P. S., Shulman, C., Thurm, A., & Pickles, A. (2008). Autism from 2 to 9 years of age. Archives of General Psychiatry, 63, 694–701.

    Article  Google Scholar 

  • Lord, C., Rutter, M., DiLavore, P. C., & Risi, S. (2002). Autism diagnostic observation schedule: ADOS manual. Los Angeles, CA: Western Psychological Services.

    Google Scholar 

  • Lotter, V. (1974). Social adjustment and placement of autistic children in Middlesex: A follow-up study. Journal of Autism and Childhood Schizophrenia, 4(1), 11–32.

    Article  PubMed  Google Scholar 

  • Magnotta, V. A., Harris, G., Andreasen, N. C., O’Leary, D. S., Yuh, W. T., & Heckel, D. (2002). Structural MR image processing using the BRAINS2 toolbox. Computerized Medical Imaging and Graphics, 26(4), 251–264. doi:S0895611102000113.

    Article  PubMed  Google Scholar 

  • Manes, F., Piven, J., Vrancic, D., Nanclares, V., Plebst, C., & Starkstein, S. E. (1999). An MRI study of the corpus callosum and cerebellum in mentally retarded autistic individuals. The Journal of Neuropsychiatry and Clinical Neurosciences, 11, 470–474.

    PubMed  Google Scholar 

  • Mosconi, M. W., Cody-Hazlett, H., Poe, M. D., Gerig, G., Gimpel-Smith, R., & Piven, J. (2009). Longitudinal study of amygdala volume and joint attention in 2- to 4-year-old children with autism. Archives of General Psychiatry, 66(5), 509–516. doi:10.1001/archgenpsychiatry.2009.19.

    Article  PubMed  Google Scholar 

  • Nacewicz, B. M., Dalton, K. M., Johnstone, T., Long, M. T., McAuliff, E. M., & Oakes, T. R. (2006). Amygdala volume and nonverbal social impairment in adolescent and adult males with autism. Archives of General Psychiatry, 63(12), 1417–1428. doi:10.1001/archpsyc.63.12.1417.

    Article  PubMed  Google Scholar 

  • Oberman, L. M., & Ramachandran, V. S. (2007). The simulating social mind: The role of the mirror neuron system and simulation in the social and communicative deficits of autism spectrum disorders. Psychological Bulletin, 133(2), 310–327.

    Article  PubMed  Google Scholar 

  • Ozonoff, S., & McEvoy, R. (1994). A longitudinal study of executive function and theory of mind development in autism. Development and Psychopathology, 6(3), 415–431.

    Article  Google Scholar 

  • Ozonoff, S., Pennington, B. F., & Rogers, S. J. (1991a). Executive function deficits in high-functioning autistic individuals: Relationship to theory of mind. Journal of Child Psychology and Psychiatry and Allied Disciplines, 32(7), 1081–1105.

    Article  Google Scholar 

  • Ozonoff, S., Rogers, S. J., & Pennington, B. F. (1991b). Asperger’s Syndrome: Evidence of an empirical distinction from high-functioning autism. Journal of Child Psychology and Psychiatry, 32(7), 1107–1122.

    Article  PubMed  Google Scholar 

  • Pardo, C. A., & Eberhart, C. G. (2007). The neurobiology of autism. Brain Pathology, 17(4), 434–447. doi:10.1111/j.1750-3639.2007.00102.x.

    Article  PubMed  Google Scholar 

  • Peugh, J. L., & Enders, C. K. (2005). Using the SPSS mixed procedure to fit cross-sectional and longitudinal multilevel models. Educational and Psychological Measurement, 65(5), 717–741.

    Article  Google Scholar 

  • Piven, J., Arndt, S., Bailey, J., Havercamp, S., Andreasen, N. C., & Palmer, P. (1995). An MRI study of brain size in autism. The American Journal of Psychiatry, 152(8), 1145–1149.

    PubMed  Google Scholar 

  • Piven, J., Bailey, J., Ranson, B. J., & Arndt, S. (1997). An MRI study of the corpus callosum in autism. American Journal of Psychiatry, 154(8), 1051–1056.

    PubMed  Google Scholar 

  • Piven, J., Harper, J., Palmer, P., & Arndt, S. (1996). Course of behavioral change in autism: A retrospective study of high-IQ adolescents and adults. Journal of the American Academy of Child and Adolescent Psychiatry, 35(4), 523–529.

    Article  PubMed  Google Scholar 

  • Redcay, E., & Courchesne, E. (2005). When is the brain enlarged in autism? A meta-analysis of all brain size reports. Biological Psychiatry, 58(1), 1–9. doi:10.1016/j.biopsych.2005.03.026.

    Article  PubMed  Google Scholar 

  • Rosenthal, R. (1991). Meta-analytic procedures for social research, Vol. 6. Newbury Park, CA: Sage Publications.

    Google Scholar 

  • Rutter, M. (1967). The autistic child. Royal Institute of Public Health and Hygiene Journal, 30(4), 130–132.

    PubMed  Google Scholar 

  • Rutter, M., Le Couteur, A., & Lord, C. (2003). Autism diagnostic interview-revised manual. Los Angeles: Western Psychological Services.

    Google Scholar 

  • Schumann, C. M., Barnes, C. C., Lord, C., & Courchesne, E. (2009). Amygdala enlargement in toddlers with autism related to severity of social and communication impairments. Biological Psychiatry, 66(10), 942–949. doi:10.1016/j.biopsych.2009.07.007.

    Article  PubMed  Google Scholar 

  • Seltzer, M. M., Krauss, M. W., Shattuck, P. T., Orsmond, G., Swe, A., & Lord, C. (2003). The symptoms of autism spectrum disorders in adolescence and adulthood. Journal of Autism and Developmental Disorders, 33(6), 565–581.

    Article  PubMed  Google Scholar 

  • Spencer, M. D., Moorhead, W. J., Lymer, K. S., Job, D. E., Muir, W. J., & Hoare, P. (2006). Structural correlates of intellectual impairment and autistic features in adolescents. Neuroimage, 33, 1136–1144.

    Article  PubMed  Google Scholar 

  • Spiker, D., Lotspeich, L. J., Dimiceli, S., Myers, R. M., & Risch, N. (2002). Behavioral phenotypic variation in autism multiplex families: Evidence for a continuous severity gradient. American Journal of Medical Genetics, 114(2), 129–136. doi:10.1002/ajmg.10188.

    Article  PubMed  Google Scholar 

  • Talairach, J., & Tournoux, P. (1988). Co-planar stereotaxic atlas of the human brain: 3-dimensional proportional system—an approach to cerebral imaging. New York: Thieme Medical Publishers.

    Google Scholar 

  • Tepest, R., Jacobi, E., Gawronski, A., Krug, B., Moller-Hartmann, W., & Lehnhardt, F. G. (2010). Corpus callosum size in adults with high-functioning autism and the relevance of gender. Psychiatry Research, 183(1), 38–43. doi:10.1016/j.pscychresns.2010.04.007.

    Article  PubMed  Google Scholar 

  • Vidal, C. N., Nicolson, R., DeVito, T. J., Hayashi, K. M., Geaga, J. A., & Drost, D. J. (2006). Mapping corpus callosum deficits in autism: An index of aberrant cortical connectivity. Biological Psychiatry, 60, 218–225.

    Article  PubMed  Google Scholar 

  • Waiter, G. D., Williams, J. H., Murray, A. D., Gilchrist, A., Perrett, D. I., & Whiten, A. (2005). Structural white matter deficits in high-functioning individuals with autistic spectrum disorder: A voxel-based investigation. Neuroimage, 24(2), 455–461. doi:10.1016/j.neuroimage.2004.08.049.

    Article  PubMed  Google Scholar 

  • White, T., Andreasen, N. C., Nopoulos, P., & Magnotta, V. (2003). Gyrification abnormalities in childhood- and adolescent-onset schizophrenia. Biological Psychiatry, 54(4), 418–426. doi:S0006322303000659.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Dr. Frazier has received federal funding or research support from, acted as a consultant to, or received travel support from Shire Development, Inc., Bristol-Myers Squibb, National Institute of Health, and NARSAD. Dr. Hardan has received research grants from Bristol-Myers Squibb and Forest Pharmaceuticals. None of these directly relate to the present study. This work was directly supported by NIMH research grant MH64027 to Dr. Hardan. This publication was made possible by the Case Western Reserve University/Cleveland Clinic CTSA Grant Number UL1 RR024989 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. The authors wish to acknowledge the patients with autism, typically developing participants, and their families. Their effort and engagement was essential to the successful completion of this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas W. Frazier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frazier, T.W., Keshavan, M.S., Minshew, N.J. et al. A Two-Year Longitudinal MRI Study of the Corpus Callosum in Autism. J Autism Dev Disord 42, 2312–2322 (2012). https://doi.org/10.1007/s10803-012-1478-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-012-1478-z

Keywords

Navigation