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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2004 Feb;75(2):221–225.

Corpus callosum signal intensity in patients with bipolar and unipolar disorder

P Brambilla 1, M Nicoletti 1, R Sassi 1, A Mallinger 1, E Frank 1, M Keshavan 1, J Soares 1
PMCID: PMC1738899  PMID: 14742592

Abstract

Background: Anatomical abnormalities in the corpus callosum have been reported in magnetic resonance imaging (MRI) studies in patients with bipolar but not unipolar disorder. MRI signal intensity can be used as a putative index of corpus callosum myelination.

Objectives: To measure MRI signal intensity in patients with bipolar and unipolar disorder to investigate abnormalities of corpus callosum myelination.

Methods: The study involved 29 DSM-IV bipolar patients (mean (SD) age, 35 (11) years; 16 male, 13 female), 23 DSM-IV unipolar patients (41 (10) years; 4 male, 19 female), and 36 healthy controls (37 (10) years; 23 male, 13 female). A 1.5T GE Signa magnet was employed, with a fast spin echo sequence. Corpus callosum signal intensity was obtained blindly using the semiautomated software NIH Image 1.62.

Results: Bipolar patients had lower corpus callosum signal intensity for all callosal subregions (genu, anterior and posterior body, isthmus, splenium) than healthy controls (ANCOVA, age and sex as covariates, p<0.05). No significant differences were found between unipolar and healthy subjects (ANCOVA, age and sex as covariates, p>0.05).

Conclusions: The findings suggest abnormalities in corpus callosum white matter in bipolar but not unipolar patients, possibly because of altered myelination. Such abnormalities could lead to impaired interhemispheric communication in bipolar disorder. Longitudinal MRI studies involving first episode and early onset bipolar patients will be necessary for a better understanding of the potential role of abnormalities of corpus callosum myelination in the pathophysiology of bipolar disorder.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aboitiz F., Scheibel A. B., Fisher R. S., Zaidel E. Fiber composition of the human corpus callosum. Brain Res. 1992 Dec 11;598(1-2):143–153. doi: 10.1016/0006-8993(92)90178-c. [DOI] [PubMed] [Google Scholar]
  2. Ali S. O., Denicoff K. D., Altshuler L. L., Hauser P., Li X., Conrad A. J., Mirsky A. F., Smith-Jackson E. E., Post R. M. A preliminary study of the relation of neuropsychological performance to neuroanatomic structures in bipolar disorder. Neuropsychiatry Neuropsychol Behav Neurol. 2000 Jan;13(1):20–28. [PubMed] [Google Scholar]
  3. Allen L. S., Richey M. F., Chai Y. M., Gorski R. A. Sex differences in the corpus callosum of the living human being. J Neurosci. 1991 Apr;11(4):933–942. doi: 10.1523/JNEUROSCI.11-04-00933.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baumgardner T. L., Singer H. S., Denckla M. B., Rubin M. A., Abrams M. T., Colli M. J., Reiss A. L. Corpus callosum morphology in children with Tourette syndrome and attention deficit hyperactivity disorder. Neurology. 1996 Aug;47(2):477–482. doi: 10.1212/wnl.47.2.477. [DOI] [PubMed] [Google Scholar]
  5. Bird C. R., Hedberg M., Drayer B. P., Keller P. J., Flom R. A., Hodak J. A. MR assessment of myelination in infants and children: usefulness of marker sites. AJNR Am J Neuroradiol. 1989 Jul-Aug;10(4):731–740. [PMC free article] [PubMed] [Google Scholar]
  6. Borkowska A., Rybakowski J. K. Neuropsychological frontal lobe tests indicate that bipolar depressed patients are more impaired than unipolar. Bipolar Disord. 2001 Apr;3(2):88–94. doi: 10.1034/j.1399-5618.2001.030207.x. [DOI] [PubMed] [Google Scholar]
  7. Brizzolara D., Ferretti G., Brovedani P., Casalini C., Sbrana B. Is interhemispheric transfer time related to age? A developmental study. Behav Brain Res. 1994 Oct 20;64(1-2):179–184. doi: 10.1016/0166-4328(94)90130-9. [DOI] [PubMed] [Google Scholar]
  8. Coffman J. A., Bornstein R. A., Olson S. C., Schwarzkopf S. B., Nasrallah H. A. Cognitive impairment and cerebral structure by MRI in bipolar disorder. Biol Psychiatry. 1990 Jun 1;27(11):1188–1196. doi: 10.1016/0006-3223(90)90416-y. [DOI] [PubMed] [Google Scholar]
  9. Duara R., Kushch A., Gross-Glenn K., Barker W. W., Jallad B., Pascal S., Loewenstein D. A., Sheldon J., Rabin M., Levin B. Neuroanatomic differences between dyslexic and normal readers on magnetic resonance imaging scans. Arch Neurol. 1991 Apr;48(4):410–416. doi: 10.1001/archneur.1991.00530160078018. [DOI] [PubMed] [Google Scholar]
  10. Egaas B., Courchesne E., Saitoh O. Reduced size of corpus callosum in autism. Arch Neurol. 1995 Aug;52(8):794–801. doi: 10.1001/archneur.1995.00540320070014. [DOI] [PubMed] [Google Scholar]
  11. El-Badri S. M., Ashton C. H., Moore P. B., Marsh V. R., Ferrier I. N. Electrophysiological and cognitive function in young euthymic patients with bipolar affective disorder. Bipolar Disord. 2001 Apr;3(2):79–87. doi: 10.1034/j.1399-5618.2001.030206.x. [DOI] [PubMed] [Google Scholar]
  12. Gazzaniga M. S. Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition? Brain. 2000 Jul;123(Pt 7):1293–1326. doi: 10.1093/brain/123.7.1293. [DOI] [PubMed] [Google Scholar]
  13. Giedd J. N., Blumenthal J., Jeffries N. O., Rajapakse J. C., Vaituzis A. C., Liu H., Berry Y. C., Tobin M., Nelson J., Castellanos F. X. Development of the human corpus callosum during childhood and adolescence: a longitudinal MRI study. Prog Neuropsychopharmacol Biol Psychiatry. 1999 May;23(4):571–588. doi: 10.1016/s0278-5846(99)00017-2. [DOI] [PubMed] [Google Scholar]
  14. Giedd J. N., Castellanos F. X., Casey B. J., Kozuch P., King A. C., Hamburger S. D., Rapoport J. L. Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder. Am J Psychiatry. 1994 May;151(5):665–669. doi: 10.1176/ajp.151.5.665. [DOI] [PubMed] [Google Scholar]
  15. Giedd J. N., Rumsey J. M., Castellanos F. X., Rajapakse J. C., Kaysen D., Vaituzis A. C., Vauss Y. C., Hamburger S. D., Rapoport J. L. A quantitative MRI study of the corpus callosum in children and adolescents. Brain Res Dev Brain Res. 1996 Feb 26;91(2):274–280. doi: 10.1016/0165-3806(95)00193-x. [DOI] [PubMed] [Google Scholar]
  16. Girard N., Raybaud C., du Lac P. MRI study of brain myelination. J Neuroradiol. 1991;18(4):291–307. [PubMed] [Google Scholar]
  17. Hardan A. Y., Minshew N. J., Keshavan M. S. Corpus callosum size in autism. Neurology. 2000 Oct 10;55(7):1033–1036. doi: 10.1212/wnl.55.7.1033. [DOI] [PubMed] [Google Scholar]
  18. Hellige J. B., Cox P. J., Litvac L. Information processing in the cerebral hemispheres: selective hemispheric activation and capacity limitations. J Exp Psychol Gen. 1979 Jun;108(2):251–279. doi: 10.1037//0096-3445.108.2.251. [DOI] [PubMed] [Google Scholar]
  19. Hynd G. W., Semrud-Clikeman M., Lorys A. R., Novey E. S., Eliopulos D., Lyytinen H. Corpus callosum morphology in attention deficit-hyperactivity disorder: morphometric analysis of MRI. J Learn Disabil. 1991 Mar;24(3):141–146. doi: 10.1177/002221949102400302. [DOI] [PubMed] [Google Scholar]
  20. Inder T. E., Huppi P. S. In vivo studies of brain development by magnetic resonance techniques. Ment Retard Dev Disabil Res Rev. 2000;6(1):59–67. doi: 10.1002/(SICI)1098-2779(2000)6:1<59::AID-MRDD8>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  21. Jäncke L., Steinmetz H. Interhemispheric transfer time and corpus callosum size. Neuroreport. 1994 Nov 21;5(17):2385–2388. doi: 10.1097/00001756-199411000-00043. [DOI] [PubMed] [Google Scholar]
  22. Kendall B. E. Inborn errors and demyelination: MRI and the diagnosis of white matter disease. J Inherit Metab Dis. 1993;16(4):771–786. doi: 10.1007/BF00711909. [DOI] [PubMed] [Google Scholar]
  23. Keshavan M. S., Diwadkar V. A., Harenski K., Rosenberg D. R., Sweeney J. A., Pettegrew J. W. Abnormalities of the corpus callosum in first episode, treatment naive schizophrenia. J Neurol Neurosurg Psychiatry. 2002 Jun;72(6):757–760. doi: 10.1136/jnnp.72.6.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Keshavan Matcheri S., Diwadkar Vaibhav A., DeBellis Michael, Dick Elizabeth, Kotwal Rupali, Rosenberg David R., Sweeney John A., Minshew Nancy, Pettegrew Jay W. Development of the corpus callosum in childhood, adolescence and early adulthood. Life Sci. 2002 Mar 8;70(16):1909–1922. doi: 10.1016/s0024-3205(02)01492-3. [DOI] [PubMed] [Google Scholar]
  25. Lamantia A. S., Rakic P. Cytological and quantitative characteristics of four cerebral commissures in the rhesus monkey. J Comp Neurol. 1990 Jan 22;291(4):520–537. doi: 10.1002/cne.902910404. [DOI] [PubMed] [Google Scholar]
  26. Lammers C. H., Doraiswamy P. M., Husain M. M., Figiel G. S., Lurie S. N., Boyko O. B., Ellinwood E. H., Jr, Nemeroff C. B., Krishnan K. R. MRI of corpus callosum and septum pellucidum in depression. Biol Psychiatry. 1991 Feb 1;29(3):300–301. doi: 10.1016/0006-3223(91)91297-5. [DOI] [PubMed] [Google Scholar]
  27. Levy J., Trevarthen C. Perceptual, semantic and phonetic aspects of elementary language processes in split-brain patients. Brain. 1977 Mar;100(Pt 1):105–118. doi: 10.1093/brain/100.1.105. [DOI] [PubMed] [Google Scholar]
  28. Mac Master F. P., Keshavan M. S., Dick E. L., Rosenberg D. R. Corpus callosal signal intensity in treatment-naive pediatric obsessive compulsive disorders. Prog Neuropsychopharmacol Biol Psychiatry. 1999 May;23(4):601–612. doi: 10.1016/s0278-5846(99)00019-6. [DOI] [PubMed] [Google Scholar]
  29. Martínez-Arán A., Vieta E., Colom F., Reinares M., Benabarre A., Gastó C., Salamero M. Cognitive dysfunctions in bipolar disorder: evidence of neuropsychological disturbances. Psychother Psychosom. 2000;69(1):2–18. doi: 10.1159/000012361. [DOI] [PubMed] [Google Scholar]
  30. Moriarty J., Varma A. R., Stevens J., Fish M., Trimble M. R., Robertson M. M. A volumetric MRI study of Gilles de la Tourette's syndrome. Neurology. 1997 Aug;49(2):410–415. doi: 10.1212/wnl.49.2.410. [DOI] [PubMed] [Google Scholar]
  31. Parashos I. A., Tupler L. A., Blitchington T., Krishnan K. R. Magnetic-resonance morphometry in patients with major depression. Psychiatry Res. 1998 Nov 9;84(1):7–15. doi: 10.1016/s0925-4927(98)00042-0. [DOI] [PubMed] [Google Scholar]
  32. Paus T., Collins D. L., Evans A. C., Leonard G., Pike B., Zijdenbos A. Maturation of white matter in the human brain: a review of magnetic resonance studies. Brain Res Bull. 2001 Feb;54(3):255–266. doi: 10.1016/s0361-9230(00)00434-2. [DOI] [PubMed] [Google Scholar]
  33. Peterson B. S., Leckman J. F., Duncan J. S., Wetzles R., Riddle M. A., Hardin M. T., Cohen D. J. Corpus callosum morphology from magnetic resonance images in Tourette's syndrome. Psychiatry Res. 1994 Jun;55(2):85–99. doi: 10.1016/0925-4927(94)90003-5. [DOI] [PubMed] [Google Scholar]
  34. Pfefferbaum A., Sullivan E. V., Hedehus M., Lim K. O., Adalsteinsson E., Moseley M. Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging. Magn Reson Med. 2000 Aug;44(2):259–268. doi: 10.1002/1522-2594(200008)44:2<259::aid-mrm13>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  35. Phelps E. A., Hirst W., Gazzaniga M. S. Deficits in recall following partial and complete commissurotomy. Cereb Cortex. 1991 Nov-Dec;1(6):492–498. doi: 10.1093/cercor/1.6.492. [DOI] [PubMed] [Google Scholar]
  36. Poduslo S. E., Jang Y. Myelin development in infant brain. Neurochem Res. 1984 Nov;9(11):1615–1626. doi: 10.1007/BF00964595. [DOI] [PubMed] [Google Scholar]
  37. Pujol J., Vendrell P., Junqué C., Martí-Vilalta J. L., Capdevila A. When does human brain development end? Evidence of corpus callosum growth up to adulthood. Ann Neurol. 1993 Jul;34(1):71–75. doi: 10.1002/ana.410340113. [DOI] [PubMed] [Google Scholar]
  38. Rauch R. A., Jinkins J. R. Analysis of cross-sectional area measurements of the corpus callosum adjusted for brain size in male and female subjects from childhood to adulthood. Behav Brain Res. 1994 Oct 20;64(1-2):65–78. doi: 10.1016/0166-4328(94)90119-8. [DOI] [PubMed] [Google Scholar]
  39. Robichon F., Bouchard P., Démonet J., Habib M. Developmental dyslexia: re-evaluation of the corpus callosum in male adults. Eur Neurol. 2000;43(4):233–237. doi: 10.1159/000008182. [DOI] [PubMed] [Google Scholar]
  40. Rosenberg D. R., Keshavan M. S., Dick E. L., Bagwell W. W., MacMaster F. P., Birmaher B. Corpus callosal morphology in treatment-naive pediatric obsessive compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 1997 Nov;21(8):1269–1283. doi: 10.1016/s0278-5846(97)00163-2. [DOI] [PubMed] [Google Scholar]
  41. Rueckert L., Levy J. Further evidence that the callosum is involved in sustaining attention. Neuropsychologia. 1996 Sep;34(9):927–935. doi: 10.1016/0028-3932(96)00009-7. [DOI] [PubMed] [Google Scholar]
  42. Rumsey J. M., Casanova M., Mannheim G. B., Patronas N., De Vaughn N., Hamburger S. D., Aquino T. Corpus callosum morphology, as measured with MRI, in dyslexic men. Biol Psychiatry. 1996 May 1;39(9):769–775. doi: 10.1016/0006-3223(95)00225-1. [DOI] [PubMed] [Google Scholar]
  43. Semrud-Clikeman M., Filipek P. A., Biederman J., Steingard R., Kennedy D., Renshaw P., Bekken K. Attention-deficit hyperactivity disorder: magnetic resonance imaging morphometric analysis of the corpus callosum. J Am Acad Child Adolesc Psychiatry. 1994 Jul-Aug;33(6):875–881. doi: 10.1097/00004583-199407000-00014. [DOI] [PubMed] [Google Scholar]
  44. Shanks M. F., Rockel A. J., Powell T. P. The commissural fibre connections of the primary somatic sensory cortex. Brain Res. 1975 Nov 7;98(1):166–171. doi: 10.1016/0006-8993(75)90516-8. [DOI] [PubMed] [Google Scholar]
  45. Soares J. C., Mann J. J. The anatomy of mood disorders--review of structural neuroimaging studies. Biol Psychiatry. 1997 Jan 1;41(1):86–106. doi: 10.1016/s0006-3223(96)00006-6. [DOI] [PubMed] [Google Scholar]
  46. Soares J. C., Mann J. J. The functional neuroanatomy of mood disorders. J Psychiatr Res. 1997 Jul-Aug;31(4):393–432. doi: 10.1016/s0022-3956(97)00016-2. [DOI] [PubMed] [Google Scholar]
  47. Strakowski S. M., DelBello M. P., Adler C., Cecil D. M., Sax K. W. Neuroimaging in bipolar disorder. Bipolar Disord. 2000 Sep;2(3 Pt 1):148–164. doi: 10.1034/j.1399-5618.2000.020302.x. [DOI] [PubMed] [Google Scholar]
  48. Sánchez M. M., Hearn E. F., Do D., Rilling J. K., Herndon J. G. Differential rearing affects corpus callosum size and cognitive function of rhesus monkeys. Brain Res. 1998 Nov 23;812(1-2):38–49. doi: 10.1016/s0006-8993(98)00857-9. [DOI] [PubMed] [Google Scholar]
  49. Waxman S. G., Swadlow H. A. Ultrastructure of visual callosal axons in the rabbit. Exp Neurol. 1976 Oct;53(1):115–127. doi: 10.1016/0014-4886(76)90287-9. [DOI] [PubMed] [Google Scholar]
  50. Wilder-Willis K. E., Sax K. W., Rosenberg H. L., Fleck D. E., Shear P. K., Strakowski S. M. Persistent attentional dysfunction in remitted bipolar disorder. Bipolar Disord. 2001 Apr;3(2):58–62. doi: 10.1034/j.1399-5618.2001.030202.x. [DOI] [PubMed] [Google Scholar]
  51. Witelson S. F. Hand and sex differences in the isthmus and genu of the human corpus callosum. A postmortem morphological study. Brain. 1989 Jun;112(Pt 3):799–835. doi: 10.1093/brain/112.3.799. [DOI] [PubMed] [Google Scholar]
  52. Wu J. C., Buchsbaum M. S., Johnson J. C., Hershey T. G., Wagner E. A., Teng C., Lottenberg S. Magnetic resonance and positron emission tomography imaging of the corpus callosum: size, shape and metabolic rate in unipolar depression. J Affect Disord. 1993 May;28(1):15–25. doi: 10.1016/0165-0327(93)90073-s. [DOI] [PubMed] [Google Scholar]
  53. de Lacoste M. C., Kirkpatrick J. B., Ross E. D. Topography of the human corpus callosum. J Neuropathol Exp Neurol. 1985 Nov;44(6):578–591. doi: 10.1097/00005072-198511000-00004. [DOI] [PubMed] [Google Scholar]
  54. van der Knaap M. S., Valk J. The reflection of histology in MR imaging of Pelizaeus-Merzbacher disease. AJNR Am J Neuroradiol. 1989 Jan-Feb;10(1):99–103. [PMC free article] [PubMed] [Google Scholar]

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