Recent neuroradiologic and neuropathological studies indicate that at least some patients with schizophrenia have slightly enlarged cerebral ventricles and subtle anatomical abnormalities in the region of the anterior hippocampus. Using magnetic resonance imaging (MRI), we studied 15 sets of monozygotic twins who were discordant for schizophrenia (age range, 25 to 44 years; 8 male and 7 female pairs). For each pair of twins, T1-weighted contiguous coronal sections (5 mm thick) were compared blindly, and quantitative measurements of brain structures were made with a computerized image-analysis system. In 12 of the 15 discordant pairs, the twin with schizophrenia was identified by visual inspection of cerebrospinal fluid spaces. In two pairs no difference could be discerned visually, and in one the twin with schizophrenia was misidentified. Quantitative analysis of sections through the level of the pes hippocampi showed the hippocampus to be smaller on the left in 14 of the 15 affected twins, as compared with their normal twins, and smaller on the right in 13 affected twins (both P less than 0.001). In the twins with schizophrenia, as compared with their normal twins, the lateral ventricles were larger on the left in 14 (P less than 0.003) and on the right in 13 (P less than 0.001). The third ventricle also was larger in 13 of the twins with schizophrenia (P less than 0.001). None of these differences were found in seven sets of monozygotic twins without schizophrenia who were studied similarly as controls. We conclude that subtle abnormalities of cerebral anatomy (namely, small anterior hippocampi and enlarged lateral and third ventricles) are consistent neuropathologic features of schizophrenia and that their cause is at least in part not genetic. Further study is required to determine whether these changes are primary or secondary to the disease.
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Neuropsychiatry Branch, National Institute of Mental Health, Washington, DC 20032.
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[Abstract][Full Text]
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[Abstract][Full Text]
Velakoulis, D., Pantelis, C., McGorry, P. D., Dudgeon, P., Brewer, W., Cook, M., Desmond, P., Bridle, N., Tierney, P., Murrie, V., Singh, B., Copolov, D.
(1999). Hippocampal Volume in First-Episode Psychoses and Chronic Schizophrenia: A High-Resolution Magnetic Resonance Imaging Study. Arch Gen Psychiatry
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[Abstract][Full Text]
Cannon, T. D., van Erp, T. G. M., Huttunen, M., Lonnqvist, J., Salonen, O., Valanne, L., Poutanen, V.-P., Standertskjold-Nordenstam, C.-G., Gur, R. E., Yan, M.
(1998). Regional Gray Matter, White Matter, and Cerebrospinal Fluid Distributions in Schizophrenic Patients, Their Siblings, and Controls. Arch Gen Psychiatry
55: 1084-1091
[Abstract][Full Text]
Bertolino, A., Kumra, S., Callicott, J. H., Mattay, V. S., Lestz, R. M., Jacobsen, L., Barnett, l. S., Duyn, J. H., Frank, J. A., Rapoport, J. L., Weinberger, D. R.
(1998). Common Pattern of Cortical Pathology in Childhood-Onset and Adult-Onset Schizophrenia as Identified by Proton Magnetic Resonance Spectroscopic Imaging. Am. J. Psychiatry
155: 1376-1383
[Abstract][Full Text]
Wolkin, A., Rusinek, H., Vaid, G., Arena, L., Lafargue, T., Sanfilipo, M., Loneragan, C., Lautin, A., Rotrosen, J.
(1998). Structural Magnetic Resonance Image Averaging in Schizophrenia. Am. J. Psychiatry
155: 1064-1073
[Abstract][Full Text]
Altshuler, L. L., Bartzokis, G., Grieder, T., Curran, J., Mintz, J.
(1998). Amygdala Enlargement in Bipolar Disorder and Hippocampal Reduction in Schizophrenia: An MRI Study Demonstrating Neuroanatomic Specificity. Arch Gen Psychiatry
55: 663-664
[Full Text]
Carmelli, D., DeCarli, C., Swan, G. E., Jack, L. M., Reed, T., Wolf, P. A., Miller, B. L.
(1998). Evidence For Genetic Variance in White Matter Hyperintensity Volume in Normal Elderly Male Twins. Stroke
29: 1177-1181
[Abstract][Full Text]
Jacobsen, L. K., Giedd, J. N., Castellanos, F. X., Vaituzis, A. C., Hamburger, S. D., Kumra, S., Lenane, M. C., Rapoport, J. L.
(1998). Progressive Reduction of Temporal Lobe Structures in Childhood-Onset Schizophrenia. Am. J. Psychiatry
155: 678-685
[Abstract][Full Text]
Nelson, M. D., Saykin, A. J., Flashman, L. A., Riordan, H. J.
(1998). Hippocampal Volume Reduction in Schizophrenia as Assessed by Magnetic Resonance Imaging: A Meta-analytic Study. Arch Gen Psychiatry
55: 433-440
[Abstract][Full Text]
Chikama, M., McFarland, N. R., Amaral, D. G., Haber, S. N.
(1997). Insular Cortical Projections to Functional Regions of the Striatum Correlate with Cortical Cytoarchitectonic Organization in the Primate. J. Neurosci.
17: 9686-9705
[Abstract][Full Text]
Prassopoulos, P., Cavouras, D., Ioannidou, M., Golfinopoulos, S.
(1996). Study of Subarachnoid Spaces in Children With Idiopathic Mental Retardation. J Child Neurol
11: 197-200
[Abstract]
Crow, T.J.
(1996). Sexual selection as the mechanism of evolution of Machiavellian intelligence: a Darwinian theory of the origins of psychosis. J Psychopharmacol
10: 77-87
Carpenter, W. T., Buchanan, R. W.
(1994). Schizophrenia. NEJM
330: 681-690
[Full Text]
Michels, R., Marzuk, P. M.
(1993). Progress in Psychiatry- First of Two Parts. NEJM
329: 552-560
[Full Text]
Kerwin, R.
(1992). Merck, Sharp & Dohme Prize for Young Psychopharmacologists: A history of frontal and temporal lobe aspects of the neuropharmacology of schizophrenia. J Psychopharmacol
6: 230-240
[Abstract]
(1990). A CHARACTERISTIC ANATOMIC ABNORMALITY FOUND IN BRAINS OF SCHIZOPHRENICS. JWatch General
1990: 9-9
[Full Text]
Cannon, T. D., Thompson, P. M., van Erp, T. G. M., Toga, A. W., Poutanen, V.-P., Huttunen, M., Lonnqvist, J., Standerskjold-Nordenstam, C.-G., Narr, K. L., Khaledy, M., Zoumalan, C. I., Dail, R., Kaprio, J.
(2002). Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia. Proc. Natl. Acad. Sci. USA
99: 3228-3233
[Abstract][Full Text]
