Skip to main content
SpringerLink
Log in

Age-related changes in the corpus callosum in early-onset bipolar disorder assessed using volumetric and cross-sectional measurements

  • Original Research
  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

Corpus callosum (CC) area abnormalities have been reported in magnetic resonance imaging (MRI) studies of adults and youths with bipolar disorder (BPD), suggesting interhemispheric communication may be abnormal in BPD and may be present early in the course of illness and affect normal neuromaturation of this structure throughout the lifecycle. Neuroimaging scans from 44 youths with DSM-IV BPD and 22 healthy controls (HC) were analyzed using cross-sectional area measurements and a novel method of volumetric parcellation. Univariate analyses of variance were conducted on CC subregions using both volume and traditional area measurements. Youths with BPD had smaller middle and posterior callosal regions, and reduced typical age-related increases in CC size. The cross-sectional area and novel volumetric methodologies resulted in similar findings. Future longitudinal assessments of CC development would track the evolution of callosal abnormalities in youths with BPD and allow exploration of the functional significance of these findings.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Adler, C. M., Delbello, M. P., Mills, N. P., Schmithorst, V., Holland, S., & Strakowski, S. M. (2005). Comorbid ADHD is associated with altered patterns of neuronal activation in adolescents with bipolar disorder performing a simple attention task. Bipolar Disorders, 7(6), 577–588.

    Article  PubMed  Google Scholar 

  • American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington: American Psychiatric Association.

    Google Scholar 

  • Atmaca, M., Ozdemir, H., Cetinkaya, S., Parmaksiz, S., Belli, H., Poyraz, A. K., et al. (2007a). Cingulate gyrus volumetry in drug free bipolar patients and patients treated with valproate or valproate and quetiapine. Journal of Psychiatric Research, 41(10), 821–827.

    Article  Google Scholar 

  • Atmaca, M., Ozdemir, H., & Yildirim, H. (2007b). Corpus callosum areas in first-episode patients with bipolar disorder. Psychological Medicine, 37(5), 699–704.

    Article  Google Scholar 

  • Barkovich, A. J. (1990). Normal development of the neonatal and infant brain. In A. J. Barkovich (Ed.), Pediatric neuroimaging (pp. 5–34). New York: Raven Press.

    Google Scholar 

  • Barnea-Goraly, N., Chang, K. D., Karchemskiy, A., Howe, M. E., & Reiss, A. L. (2009). Limbic and corpus callosum aberrations in adolescents with bipolar disorder: a tract-based spatial statistics analysis. Biological Psychiatry, 66(3), 238–244.

    Article  PubMed  Google Scholar 

  • Bastin, M. E., Piatkowski, J. P., Storkey, A. J., Brown, L. J., Maclullich, A. M., & Clayden, J. D. (2008). Tract shape modelling provides evidence of topological change in corpus callosum genu during normal ageing. Neuroimage, 43(1), 20–28.

    Article  PubMed  Google Scholar 

  • Bielecka, A. M., & Obuchowicz, E. (2008). Antiapoptotic action of lithium and valproate. Pharmacological Reports, 60(6), 771–782.

    CAS  PubMed  Google Scholar 

  • Brambilla, P., Nicoletti, M. A., Sassi, R. B., Mallinger, A. G., Frank, E., Kupfer, D. J., et al. (2003). Magnetic resonance imaging study of corpus callosum abnormalities in patients with bipolar disorder. Biological Psychiatry, 54(11), 1294–1297.

    Article  PubMed  Google Scholar 

  • Brambilla, P., Nicoletti, M., Sassi, R. B., Mallinger, A. G., Frank, E., Keshavan, M. S., et al. (2004). Corpus callosum signal intensity in patients with bipolar and unipolar disorder. Journal of Neurology, Neurosurgery and Psychiatry, 75(2), 221–225.

    CAS  Google Scholar 

  • Burke, H. L., & Yeo, R. A. (1994). Systematic variations in callosal morphology: the effects of age, gender, hand preference, and anatomic asymmetry. Neuropsychology, 8(4), 563–571.

    Article  Google Scholar 

  • Caetano, S. C., Silveira, C. M., Kaur, S., Nicoletti, M., Hatch, J. P., Brambilla, P., et al. (2008). Abnormal corpus callosum myelination in pediatric bipolar patients. Journal of Affective Disorders, 108(3), 297–301.

    Article  PubMed  Google Scholar 

  • Cahill, C. M., Green, M. J., Jairam, R., & Malhi, G. S. (2007). Do cognitive deficits in juvenile bipolar disorder persist into adulthood? The Journal of Nervous and Mental Disease, 195(11), 891–896.

    Article  PubMed  Google Scholar 

  • Caviness, V. S., Makris, N., Meyer, D. A., & Kennedy, D. N. (1996). MRI-based topographic parcellation of human neocortex: an anatomically specified method with estimate of reliability. Journal of Cognitive Neuroscience, 8(6), 566–588.

    Article  Google Scholar 

  • Chaddock, C. A., Barker, G. J., Marshall, N., Schulze, K., Hall, M. H., Fern, A., et al. (2009). White matter microstructural impairments and genetic liability to familial bipolar I disorder. The British Journal of Psychiatry, 194(6), 527–534.

    Article  PubMed  Google Scholar 

  • Chang, K., Adleman, N. E., Dienes, K., Simeonova, D. I., Menon, V., & Reiss, A. (2004). Anomalous prefrontal-subcortical activation in familial pediatric bipolar disorder. Archives of General Psychiatry, 61, 781–792.

    Article  PubMed  Google Scholar 

  • Coffman, J. A., Bornstein, R. A., Olson, S. C., Schwarzkopf, S. B., & Nasrallah, H. A. (1990). Cognitive impairment and cerebral structure by MRI in bipolar disorder. Biological Psychiatry, 27, 1188–1196.

    Article  CAS  PubMed  Google Scholar 

  • de Lacoste, M. C., Kirkpatrick, J. B., & Ross, E. D. (1985). Topography of the human corpus callosum. Journal of Neuropathology and Experimental Neurology, 44(6), 578–591.

    Article  PubMed  Google Scholar 

  • Dickstein, D. P., Rich, B. A., Roberson-Nay, R., Berghorst, L., Vinton, D., Pine, D. S., et al. (2007). Neural activation during encoding of emotional faces in pediatric bipolar disorder. Bipolar Disorders, 9(7), 679–692.

    Article  PubMed  Google Scholar 

  • Farrow, T. F., Whitford, T. J., Williams, L. M., Gomes, L., & Harris, A. W. (2005). Diagnosis-related regional gray matter loss over two years in first episode schizophrenia and bipolar disorder. Biological Psychiatry, 58(9), 713–723.

    Article  PubMed  Google Scholar 

  • Filipek, P. A., Kennedy, D. N., Caviness, V. S., Jr., Rossnick, S. L., Spraggins, T. A., & Starewicz, P. M. (1989). Magnetic resonance imaging-based morphometry: development and applications to normal controls. Annals of Neurology, 25(1), 61–67.

    Article  CAS  PubMed  Google Scholar 

  • Frazier, J. A., Breeze, J. L., Makris, N., Giuliano, A. J., Herbert, M. R., Seidman, L. J., et al. (2005a). Cortical gray matter differences identified by structural magnetic resonance imaging in pediatric bipolar disorder. Bipolar Disorders, 7, 555–569.

    Article  Google Scholar 

  • Frazier, J. A., Chiu, S., Breeze, J. L., Makris, N., Lange, N., Kennedy, D. N., et al. (2005b). Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder. The American Journal of Psychiatry, 162(7), 1256–1265.

    Article  Google Scholar 

  • Frazier, J. A., Breeze, J. L., Papadimitriou, G., Kennedy, D. N., Hodge, S. M., Moore, C. M., et al. (2007). White matter abnormalities in children with and at risk for bipolar disorder. Bipolar Disorders, 9(8), 799–809.

    Article  PubMed  Google Scholar 

  • Frazier, J. A., Hodge, S. M., Breeze, J. L., Giuliano, A. J., Terry, J. E., Moore, C. M., et al. (2008). Diagnostic and sex effects on limbic volumes in early-onset bipolar disorder and schizophrenia. Schizophrenia Bulletin, 34(1), 37–46.

    Article  PubMed  Google Scholar 

  • Gazzaniga, M. S. (2000). Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition? Brain, 123(Pt 7), 1293–1326.

    Article  PubMed  Google Scholar 

  • Giedd, J. N., Rumsey, J. M., Castellanos, F. X., Rajapakse, J. C., Kaysen, D., Vaituzis, A. C., et al. (1996). A quantitative MRI study of the corpus callosum in children and adolescents. Brain Research. Developmental Brain Research, 91(2), 274–280.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Hauser, P., Dauphinais, I. D., Berrettini, W., DeLisi, L. E., Gelernter, J., & Post, R. M. (1989). Corpus callosum dimensions measured by magnetic resonance imaging in bipolar affective disorder and schizophrenia. Biological Psychiatry, 26(7), 659–668.

    Article  CAS  PubMed  Google Scholar 

  • Hutchinson, A. D., Mathias, J. L., & Banich, M. T. (2008). Corpus callosum morphology in children and adolescents with attention deficit hyperactivity disorder: a meta-analytic review. Neuropsychology, 22(3), 341–349.

    Article  CAS  PubMed  Google Scholar 

  • Jacobsen, L. K., Giedd, J. N., Rajapakse, J. C., Hamburger, S. D., Vaituzis, A. C., Frazier, J. A., et al. (1997). Quantitative magnetic resonance imaging of the corpus callosum in childhood onset schizophrenia. Psychiatry Research, 68(2–3), 77–86.

    Article  CAS  PubMed  Google Scholar 

  • Joseph, M. F., Frazier, T. W., Youngstrom, E. A., & Soares, J. C. (2008). A quantitative and qualitative review of neurocognitive performance in pediatric bipolar disorder. Journal of Child and Adolescent Psychopharmacology, 18(6), 595–605.

    Article  PubMed  Google Scholar 

  • Keshavan, M. S., Diwadkar, V. A., DeBellis, M., Dick, E., Kotwal, R., Rosenberg, D. R., et al. (2002). Development of the corpus callosum in childhood, adolescence and early adulthood. Life Sciences, 70(16), 1909–1922.

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Larson, M. P., Michael, E. S., Terry, J. E., Breeze, J. L., Hodge, S. M., Tang, L., et al. (2009). Subcortical differences among youths with ADHD compared to those with bipolar disorder with and without ADHD. Journal of Child and Adolescent Psychopharmacology, 19(1).

  • Makris, N., Meyer, J. W., Bates, J. F., Yeterian, E. H., Kennedy, D. N., & Caviness, V. S. (1999). MRI-based topographic parcellation of human cerebral white matter and nuclei II. Rationale and applications with systematics of cerebral connectivity. Neuroimage, 9(1), 18–45.

    Article  CAS  PubMed  Google Scholar 

  • Meyer, J. W., Makris, N., Bates, J. F., Caviness, V. S., & Kennedy, D. N. (1999). MRI-based topographic parcellation of human cerebral white matter. Neuroimage, 9(1), 1–17.

    Article  CAS  PubMed  Google Scholar 

  • Nelson, E. E., Vinton, D. T., Berghorst, L., Towbin, K. E., Hommer, R. E., Dickstein, D. P., et al. (2007). Brain systems underlying response flexibility in healthy and bipolar adolescents: an event-related fMRI study. Bipolar Disorders, 9(8), 810–819.

    Article  PubMed  Google Scholar 

  • Oldfield, R. C. (1971). The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia, 9, 97–113.

    Article  CAS  PubMed  Google Scholar 

  • Orvaschel, H., & Puig-Antich, J. (1987). Schedule for affective disorders and schizophrenia for school-age children: Epidemiologic 4th Version. Ft. Lauderdale: Nova University, Center for Psychological Study.

    Google Scholar 

  • Pagani, E., Agosta, F., Rocca, M. A., Caputo, D., & Filippi, M. (2008). Voxel-based analysis derived from fractional anisotropy images of white matter volume changes with aging. Neuroimage, 41(3), 657–667.

    Article  PubMed  Google Scholar 

  • Pandya, D. N., & Seltzer, B. (1986). The topography of commissural fibers. In F. Lepore, M. Ptito, & H. H. Jasper (Eds.), Two hemispheres, one brain: Functions of the corpus callosum (pp. 47–73). New York: Wiley.

    Google Scholar 

  • Paus, T., Collins, D. L., Evans, A. C., Leonard, G., Pike, B., & Zijdenbos, A. (2001). Maturation of white matter in the human brain: a review of magnetic resonance studies. Brain Research Bulletin, 54(3), 255–266.

    Article  CAS  PubMed  Google Scholar 

  • Pavuluri, M. N., O’Connor, M. M., Harral, E., & Sweeney, J. A. (2007). Affective neural circuitry during facial emotion processing in pediatric bipolar disorder. Biological Psychiatry, 62(2), 158–167.

    Article  PubMed  Google Scholar 

  • Pujol, J., Vendrell, P., Junque, C., Marti-Vilalta, J. L., & Capdevila, A. (1993). When does human brain development end? Evidence of corpus callosum growth up to adulthood. Annals of Neurology, 34(1), 71–75.

    Article  CAS  PubMed  Google Scholar 

  • Rich, B. A., Vinton, D. T., Roberson-Nay, R., Hommer, R. E., Berghorst, L. H., McClure, E. B., et al. (2006). Limbic hyperactivation during processing of neutral facial expressions in children with bipolar disorder. Proceedings of the National Academy of Sciences of the United States of America, 103(23), 8900–8905.

    Article  CAS  PubMed  Google Scholar 

  • Rich, B. A., Fromm, S. J., Berghorst, L. H., Dickstein, D. P., Brotman, M. A., Pine, D. S., et al. (2008). Neural connectivity in children with bipolar disorder: impairment in the face emotion processing circuit. Journal of Child Psychology and Psychiatry, 49(1), 88–96.

    Article  PubMed  Google Scholar 

  • Seidman, L. J., Faraone, S. V., Goldstein, J. M., Goodman, J. M., Kremen, W. S., Matsuda, G., et al. (1997). Reduced subcortical brain volumes in nonpsychotic siblings of schizophrenic patients: a pilot magnetic resonance imaging study. American Journal of Medical Genetics, 74(5), 507–514.

    Article  CAS  PubMed  Google Scholar 

  • Soares, J. C., & Mann, J. J. (1997). The anatomy of mood disorders: review of structural neuroimaging studies. Biological Psychiatry, 41(1), 86–106.

    Article  CAS  PubMed  Google Scholar 

  • Tomasch, J. (1954). Size, distribution, and number of fibres in the human corpus callosum. The Anatomical Record, 119(1), 119–135.

    Article  CAS  PubMed  Google Scholar 

  • Valera, E. M., Faraone, S. V., Murray, K. E., & Seidman, L. J. (2007). Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biological Psychiatry, 61(12), 1361–1369.

    Article  PubMed  Google Scholar 

  • Walterfang, M., Malhi, G. S., Wood, A. G., Reutens, D. C., Chen, J., Barton, S., et al. (2009). Corpus callosum size and shape in established bipolar affective disorder. Australian and New Zealand Journal of Psychiatry, 43(9), 838–845.

    Article  PubMed  Google Scholar 

  • Wang, F., Kalmar, J. H., Edmiston, E., Chepenik, L. G., Bhagwagar, Z., Spencer, L., et al. (2008). Abnormal corpus callosum integrity in bipolar disorder: a diffusion tensor imaging study. Biological Psychiatry, 64(8), 730–733.

    Article  PubMed  Google Scholar 

  • Wilder-Willis, K. E., Sax, K. W., Rosenberg, H. L., Fleck, D. E., Shear, P. K., & Strakowski, S. M. (2001). Persistent attentional dysfunction in remitted bipolar disorder. Bipolar Disorders, 3(2), 58–62.

    Article  CAS  PubMed  Google Scholar 

  • Witelson, S. F. (1989). Hand and sex differences in the isthmus and genu of the human corpus callosum: a postmortem morphological study. Brain, 112(Pt 3), 799–835.

    Article  PubMed  Google Scholar 

  • Woodruff, P. W., Phillips, M. L., Rushe, T., Wright, I. C., Murray, R. M., & David, A. S. (1997). Corpus callosum size and inter-hemispheric function in schizophrenia. Schizophrenia Research, 23(3), 189–196.

    Article  CAS  PubMed  Google Scholar 

  • Yasar, A. S., Monkul, E. S., Sassi, R. B., Axelson, D., Brambilla, P., Nicoletti, M. A., et al. (2006). MRI study of corpus callosum in children and adolescents with bipolar disorder. Psychiatry Research, 146(1), 83–85.

    Article  PubMed  Google Scholar 

  • Young, R. C., Biggs, J. T., Ziegler, V. E., & Meyer, D. A. (1978). A rating scale for mania: reliability, validity and sensitivity. The British Journal of Psychiatry, 133, 429–435.

    Article  CAS  PubMed  Google Scholar 

  • Yurgelun-Todd, D. A., Silveri, M. M., Gruber, S. A., Rohan, M. L., & Pimentel, P. J. (2007). White matter abnormalities observed in bipolar disorder: a diffusion tensor imaging study. Bipolar Disorders, 9(5), 504–512.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by several research grants from NIH: K08 MH01573 to JAF, U24 RR021382 to DNK, and K01 MH01798 to CM

Author information

Authors and Affiliations

  1. The Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City, UT, 84108, USA

    Melissa Lopez-Larson

  2. University of Utah Medical School, Salt Lake City, UT, USA

    Melissa Lopez-Larson

  3. Harvard Medical School, Boston, MA, USA

    Janis L. Breeze, David N. Kennedy, Constance Moore, Anthony J. Giuliano, Nikos Makris & Verne S. Caviness

  4. Child and Adolescent Neuropsychiatric Research Program, Cambridge Health Alliance, Cambridge, MA, USA

    Janis L. Breeze

  5. Department of Neurology, Massachusetts General Hospital (MGH), Boston, MA, USA

    David N. Kennedy, Nikos Makris & Verne S. Caviness

  6. Center for Morphometric Analysis, MGH, Charlestown, MA, USA

    David N. Kennedy, Steven M. Hodge, Lena Tang, Nikos Makris & Verne S. Caviness

  7. Brain Imaging Center, McLean Hospital, Belmont, MA, USA

    Constance Moore

  8. Child and Adolescent Neurodevelopment Initiative, University of Massachusetts Medical School, Worcester, MA, USA

    David N. Kennedy, Steven M. Hodge & Jean A. Frazier

  9. Psychiatry Department, UMASS Memorial Medical Center, Worcester, MA, USA

    David N. Kennedy, Steven M. Hodge & Jean A. Frazier

Authors
  1. Melissa Lopez-Larson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Janis L. Breeze
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David N. Kennedy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steven M. Hodge
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lena Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Constance Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anthony J. Giuliano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nikos Makris
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Verne S. Caviness
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jean A. Frazier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Melissa Lopez-Larson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lopez-Larson, M., Breeze, J.L., Kennedy, D.N. et al. Age-related changes in the corpus callosum in early-onset bipolar disorder assessed using volumetric and cross-sectional measurements. Brain Imaging and Behavior 4, 220–231 (2010). https://doi.org/10.1007/s11682-010-9101-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-010-9101-4

Keywords

Search

Navigation