Schizophrenia
Research,
4 (1991)
63-64
63
Elsevier
SCHIZO
Letter
00152
to the editors
Sexual dimorphism in corpus callosum and schizophrenia Richard
Lewine,
Emory
University
Laura
Flashman, Marsha
School
(Received
oJ Medicine,
15 February
Lawrence Gulley, Scott Beardsley, Lucas and S. Craig Risch Depurtmenl
Dear Editors, Dubbed the ‘association area of the association areas’ of the brain (Randall, 1983) the corpus callosum is critical to successful interhemispheric communication and has been implicated in the maintenance of ‘conscious unity’ (Selnes, 1974). Because of its sensitivity to damage and its role in the integration of brain hemispheric and behavioral functions, it is an excellent area in which to search for morphological deviations associated with psychopathology (e.g., Nasrallah et al., 1986). There is evidence, furthermore, of sexual dimorphism in the corpus callosum: women reportedly have a larger corpus callosum area (on analysis of midsagittal slice) and a more bulbous and rounded splenium (posterior fifth) than men (De LacosteUtamsing and Holloway, 1982; Holloway and De Lacoste, 1986; Clarke et al., 1989) (see Kertesz et al., 1987; Byne et al., 1988; Demeter et al., 1988; Weis et al., 1989 for evidence failing to support sexual dimorphism). This putative sexual dimorphism is of considerable interest in light of the growing body of evidence documenting pervasive sex differences in schizophrenia, especially those in brain morphology (Lewine, 1988; Gur and Gut-, 1990; Kopala and Clark, 1990; Lewine et al., 1990; Nasrallah et al., 1990). We have found in preliminary analyses not only support for sexual dimorphism in splenial shape among normal controls and nonschizophrenic patients, but also a possible absence of this morCorrespondence
to: R. Lewine,
Emory University School of of Psychiatry, P.O. Box AF, Atlanta,
Medicine, Department GA 30322, U.S.A.
0920-9964/91/$03.50
0
of Psychiatry,
1990, revised received
1991 Elsevier Science Publishers
P.O. Box AF, Atlanra.
24 July 1990, accepted
Amy
Wasserman,
GA 30322,
U.S.A.
26 July 1990)
phological sexual dimorphism in schizophrenia (Beardsley et al., 1989; Gulley et al., 1989). Using mean bulbousness ratings (from 1 = least bulbous to 5 = most bulbous) of tracings from MR midsagittal slices, we dichotomized male and female subjects as having either bulbous (rating >3) or nonbulbous (rating < 3) splenia. The odds ratio for DSM-III-R schizophrenic women (n = 7) for being classified as having a bulbous splenium was 1.00; among nonschizophrenic women (n = 15), the odds ratio was 2.33 and among women with no psychiatric disorder (n = 30) the odds ratio was 2.59. In other words, among the nonschizophrenic samples in our study women were over two times more likely than men to be classified as having a bulbous corpus callosum splenium; in the schizophrenia sample, men were as likely as women to be so classified. Although the functional significance of such morphological differences (assuming replication) are unknown, the data we have briefly summarized suggest another area of sex differences in brain morphology that may advance our understanding of schizophrenia. Furthermore, such data may provide some clues regarding sex differences in neurodevelopment that may be relevant to schizophrenia ontogeny. While these findings are encouraging, themethodological difficulties in assessing splenial shape are considerable. We chose for our initial analysis, for example, to use raters’ judgements of splenial shape, a strategy used with success by others such as De Lacoste. Quantitative procedures are available, however, and do not always yield the same results as rating data visually (Clarke et al., 1989; Weis et al., 1989). While an argument can be made
B.V. (Biomedical
Division)
64
for the superiority of visual inspection over quantification in the analysis of complex visual information from brain imaging (see Devous, 1989) this remains to be determined empirically, a project currently under way in our laboratory. We believe that the corpus callosum sex differences data from both post-mortem studies and brain imaging are sufficiently provocative as to warrant attention from other schizophrenia researchers.
REFERENCES
Beardsley, S., Flashman, L., Gulley, L., Lucas, M., Wasserman, A., Jewart, R., Risch, S. and Lewine, R. (1989) Sexual dimorphism in corpus callosum as a biological marker in schizophrenia. Presented at Society for Research in Psychopathology, Coral Gables, FL, November 9-12, 1989. Byne, W., Bher, R. and Houston, L. (1988) Variations in human corpus callosum do not predict gender: A study using magnetic resonance imaging. Behav. Neurosci. 102, 2222227. Clarke, S.. Kraftsik, R., Van der Loos. H. and Innocenti, G. (1989) Forms and measures of adult and developing human corpus callosum: Is there sexual dimorphism? J. Comp. Neural. 280, 213-230. De Lacoste-Utamsing. C. and Holloway, R.L. (1982) Sexual dimorphism in the human corpus callosum. Science 216, 1431-1432. Demeter, S., Ringo, J. and Doty, R. (1988) Morphometric analysis of the human corpus callosum and anterior commissure. Hum. Neurobiol. 6, 219-226. Devous, M. (1989) Imaging brain function by single-photon emission computer tomography. In: N. Andreasen (Ed.), Brain Imaging Applications in Psychiatry. American Psychiatric Press, Washington, DC, pp. 1477234.
Gulley, L.. Schwartzberg, D., Risch, S.C. and Lewine. R. (1989) Gender, psychopathology and corpus callosal shape. International Congress on Schizophrenia Research. San Diego, CA. April I-5, 1989. Gur. R.E. and Gur, R.C. (1990) Gender differences in regional cerebral blood flow. Schizophr. Bull. 16, 247-254. Holloway, R.L. and De Lacoste. M.C. (1986) Sexual dimorphism in the human corpus callosum: An extension and replication study. Hum. Neurobiol. 5, 87791. Kertesz. A., Polk, M. and Howell, J. (1987) Cerebral dominance, sex, and callosal size in MRI. Neurology 37. 138551388. Kopala, L. and Clark, C. (1990) Implications of olfactory agnosia for understanding sex differences in schizophrenia. Schizophr. Bull. 16, 2555261. Lewine, R. (1988) Gender and Schizophrenia. In: M. Tsuang and J. Simpson (Eds.), Handbook of Schizophrenia, Vol. 3, Nosology, Epidemiology and Genetics. Elsevier Science Press, Amsterdam, pp. 379-398. Lewine. R., Gulley, L., Risch, S.C., Jewart, R.D. and Houpt, J. (1990) Sexual dimorphism, brain morphology and schizophrenia. Schizophr. Bull. 16, 1955204. Nasrallah, H.A., Andreasen, N.. Coffman, J.. et al. (1986) A controlled magnetic resonance imaging study of corpus callosum thickness in schizophrenia. Biol. Psychiatry 2 1, 2744282. Nasrallah, H., Schwarzkopf. B., Olson, S., et al. (199Oj Gender differences in schizophrenia on MRI brain scans. Schizophr. Bull. 16. 2055210. Randall, P. (1983) Schizophrenia, abnormal connection, and brain evolution. Med. Hypotheses IO, 2477280. Seines. 0. (1974) The corpus callosum: Some anatomical and functional considerations with special references to language. Brain Lang. 1, 111-139. Weis, S., Weber, G., Wenger, E., et al. (1989) The controversy about a sexual dimorphism of the human corpus callosum. Int. J. Neurosci. 47, 1699173.
Research,
4 (1991)
63-64
63
Elsevier
SCHIZO
Letter
00152
to the editors
Sexual dimorphism in corpus callosum and schizophrenia Richard
Lewine,
Emory
University
Laura
Flashman, Marsha
School
(Received
oJ Medicine,
15 February
Lawrence Gulley, Scott Beardsley, Lucas and S. Craig Risch Depurtmenl
Dear Editors, Dubbed the ‘association area of the association areas’ of the brain (Randall, 1983) the corpus callosum is critical to successful interhemispheric communication and has been implicated in the maintenance of ‘conscious unity’ (Selnes, 1974). Because of its sensitivity to damage and its role in the integration of brain hemispheric and behavioral functions, it is an excellent area in which to search for morphological deviations associated with psychopathology (e.g., Nasrallah et al., 1986). There is evidence, furthermore, of sexual dimorphism in the corpus callosum: women reportedly have a larger corpus callosum area (on analysis of midsagittal slice) and a more bulbous and rounded splenium (posterior fifth) than men (De LacosteUtamsing and Holloway, 1982; Holloway and De Lacoste, 1986; Clarke et al., 1989) (see Kertesz et al., 1987; Byne et al., 1988; Demeter et al., 1988; Weis et al., 1989 for evidence failing to support sexual dimorphism). This putative sexual dimorphism is of considerable interest in light of the growing body of evidence documenting pervasive sex differences in schizophrenia, especially those in brain morphology (Lewine, 1988; Gur and Gut-, 1990; Kopala and Clark, 1990; Lewine et al., 1990; Nasrallah et al., 1990). We have found in preliminary analyses not only support for sexual dimorphism in splenial shape among normal controls and nonschizophrenic patients, but also a possible absence of this morCorrespondence
to: R. Lewine,
Emory University School of of Psychiatry, P.O. Box AF, Atlanta,
Medicine, Department GA 30322, U.S.A.
0920-9964/91/$03.50
0
of Psychiatry,
1990, revised received
1991 Elsevier Science Publishers
P.O. Box AF, Atlanra.
24 July 1990, accepted
Amy
Wasserman,
GA 30322,
U.S.A.
26 July 1990)
phological sexual dimorphism in schizophrenia (Beardsley et al., 1989; Gulley et al., 1989). Using mean bulbousness ratings (from 1 = least bulbous to 5 = most bulbous) of tracings from MR midsagittal slices, we dichotomized male and female subjects as having either bulbous (rating >3) or nonbulbous (rating < 3) splenia. The odds ratio for DSM-III-R schizophrenic women (n = 7) for being classified as having a bulbous splenium was 1.00; among nonschizophrenic women (n = 15), the odds ratio was 2.33 and among women with no psychiatric disorder (n = 30) the odds ratio was 2.59. In other words, among the nonschizophrenic samples in our study women were over two times more likely than men to be classified as having a bulbous corpus callosum splenium; in the schizophrenia sample, men were as likely as women to be so classified. Although the functional significance of such morphological differences (assuming replication) are unknown, the data we have briefly summarized suggest another area of sex differences in brain morphology that may advance our understanding of schizophrenia. Furthermore, such data may provide some clues regarding sex differences in neurodevelopment that may be relevant to schizophrenia ontogeny. While these findings are encouraging, themethodological difficulties in assessing splenial shape are considerable. We chose for our initial analysis, for example, to use raters’ judgements of splenial shape, a strategy used with success by others such as De Lacoste. Quantitative procedures are available, however, and do not always yield the same results as rating data visually (Clarke et al., 1989; Weis et al., 1989). While an argument can be made
B.V. (Biomedical
Division)
64
for the superiority of visual inspection over quantification in the analysis of complex visual information from brain imaging (see Devous, 1989) this remains to be determined empirically, a project currently under way in our laboratory. We believe that the corpus callosum sex differences data from both post-mortem studies and brain imaging are sufficiently provocative as to warrant attention from other schizophrenia researchers.
REFERENCES
Beardsley, S., Flashman, L., Gulley, L., Lucas, M., Wasserman, A., Jewart, R., Risch, S. and Lewine, R. (1989) Sexual dimorphism in corpus callosum as a biological marker in schizophrenia. Presented at Society for Research in Psychopathology, Coral Gables, FL, November 9-12, 1989. Byne, W., Bher, R. and Houston, L. (1988) Variations in human corpus callosum do not predict gender: A study using magnetic resonance imaging. Behav. Neurosci. 102, 2222227. Clarke, S.. Kraftsik, R., Van der Loos. H. and Innocenti, G. (1989) Forms and measures of adult and developing human corpus callosum: Is there sexual dimorphism? J. Comp. Neural. 280, 213-230. De Lacoste-Utamsing. C. and Holloway, R.L. (1982) Sexual dimorphism in the human corpus callosum. Science 216, 1431-1432. Demeter, S., Ringo, J. and Doty, R. (1988) Morphometric analysis of the human corpus callosum and anterior commissure. Hum. Neurobiol. 6, 219-226. Devous, M. (1989) Imaging brain function by single-photon emission computer tomography. In: N. Andreasen (Ed.), Brain Imaging Applications in Psychiatry. American Psychiatric Press, Washington, DC, pp. 1477234.
Gulley, L.. Schwartzberg, D., Risch, S.C. and Lewine. R. (1989) Gender, psychopathology and corpus callosal shape. International Congress on Schizophrenia Research. San Diego, CA. April I-5, 1989. Gur. R.E. and Gur, R.C. (1990) Gender differences in regional cerebral blood flow. Schizophr. Bull. 16, 247-254. Holloway, R.L. and De Lacoste. M.C. (1986) Sexual dimorphism in the human corpus callosum: An extension and replication study. Hum. Neurobiol. 5, 87791. Kertesz. A., Polk, M. and Howell, J. (1987) Cerebral dominance, sex, and callosal size in MRI. Neurology 37. 138551388. Kopala, L. and Clark, C. (1990) Implications of olfactory agnosia for understanding sex differences in schizophrenia. Schizophr. Bull. 16, 2555261. Lewine, R. (1988) Gender and Schizophrenia. In: M. Tsuang and J. Simpson (Eds.), Handbook of Schizophrenia, Vol. 3, Nosology, Epidemiology and Genetics. Elsevier Science Press, Amsterdam, pp. 379-398. Lewine. R., Gulley, L., Risch, S.C., Jewart, R.D. and Houpt, J. (1990) Sexual dimorphism, brain morphology and schizophrenia. Schizophr. Bull. 16, 1955204. Nasrallah, H.A., Andreasen, N.. Coffman, J.. et al. (1986) A controlled magnetic resonance imaging study of corpus callosum thickness in schizophrenia. Biol. Psychiatry 2 1, 2744282. Nasrallah, H., Schwarzkopf. B., Olson, S., et al. (199Oj Gender differences in schizophrenia on MRI brain scans. Schizophr. Bull. 16. 2055210. Randall, P. (1983) Schizophrenia, abnormal connection, and brain evolution. Med. Hypotheses IO, 2477280. Seines. 0. (1974) The corpus callosum: Some anatomical and functional considerations with special references to language. Brain Lang. 1, 111-139. Weis, S., Weber, G., Wenger, E., et al. (1989) The controversy about a sexual dimorphism of the human corpus callosum. Int. J. Neurosci. 47, 1699173.
