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A three dimensional mid sagittal plane for brain asymmetry measurement
183
XI. Structural brain imaging XI.A. Anomalous asymmetry ANOMALOUS CEREBRAL ASYMMETRY SCHIZOPHRENIA: A STUDY OF FIRST EPISODES
IN
L.E. DeLisi*, M. Sakuma*, S.-H. Xie*, M. Kushner*, D.L. Finer*, A.L. Hoff* a n d T.J. C r o w t
*Department of Psychiatry, HSC, T-IO SUNY Stony Brook, Stony Brook, New York 11794, U.S.A. tPOWIC, University Department of Psychiatry, Warneford Hospital, Oxford, UK OX3 7JX. Asymmetries of brain widths and segments of the Sylvian fissure were assessed in an MRI study of 87 patients with a first episode of schizophrenia and 52 normal controls. These were correlated with specific measures of language processing, memory and hand-skill. An independent group of 14 siblings with schizophrenia were also evaluated for evidence of heritability of cerebral asymmetries. Width asymmetries were reduced in patients compared with controls in the posterior (p<0.02) and occipital (p<0.05) regions. Brain horizontal length, on the other hand, was significantly more asymmetric in patients ( L > R ; p<.04). For Sylvian fissure measurements ( L > R ) , asymmetries in controls were greatest for the horizontal component; this asymmetry failed to detect significant difference in patients by comparison with controls (p < .06). In a range of tests of language, memory, and cognition, few significant correlations between performance and cerebral asymmetries were detected. In 14 pairs of psychotic siblings, within-pair correlations for the horizontal Sylvian fissure asymmetry were significantly greater than between pair correlations. These findings are consistent with the early presence (possibly genetic ) of anomalous cerebral asymmetry.
Reference Crow, T.J. (1990) Temporal lobe asymmetries as the key to the etiology of schizophrenia. Schiz Bull 16: 433-443.
NORMAL PLANUM TEMPORALE ASYMMETRY IN FAMILIAL SCHIZOPHRENIA: A VOLUMETRIC STUDY
MRI
S. Frangou ~, T. Sharma ~, P. Barta 2, G. Pearlson 2 a n d R. M u r r a y ~
1Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, U.K. 2Department of Psychiatry and Behavioural Sciences, Johns Hopkins University, 600 N Wolfe St., 3-166 Meyer, Baltimore, MD21205, U.S,A.
Previous studies have reported loss or reversal of the normal asymmetry of the planum temporale. It has been postulated that this represents an abnormality in the mechanisms controlling cerebral asymmetries. The development of brain asymmetries is established in utero and is thought to be under genetic control. Abnormalities in brain lateralization are therefore assumed to be indicative of genetic vulnerability to schizophrenia. We tested this hypothesis is a sample of schizophrenics from multiply affected families where genetic factors appear to operate predominantly. We compared 31 (20 men and 11 women) right-handed schizophrenics from multiplex families to 35 (18 men and 17 women) right-handed age and sex matched controls recruited from the community. Volumetric measures of the planum temporale were obtained from 3D reconstructed MRI images. Volumes were calculated by using the Cavalieri method. Asymmetry coefficients obtained from the patients did not differ significantly from those obtained from the controls. The same results were obtained when the analysis was repeated separately for male and females. Our study suggests that abnormalities in the planum temporale asymmetry are not present in familial schizophrenia.
A THREE DIMENSIONAL MID SAGITTAL PLANE FOR BRAIN ASYMMETRY MEASUREMENT R. Guillemaud*, P. Marais**, A. Zisserman**, B. M c D o n a l d * , T.J. Crow* a n d M. Brady**
*MRC Schizophrenia Research Group, Department of Neuropathology Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, U.K. **Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, U.I( Asymmetry of the brain hemispheres, from a geometric point of view, is defined with respect to the plane of the interhemispheric fissure. We have developed a method to estimate this symmetry plane from scans of serial consecutive MRI slices. Multiple points are manually placed on each slice to identify the inter-hemispheric fissure, then the symmetry plane is computed in three dimensions by fitting a plane to the set of 3D points (defined in the previous step) using orthogonal regression. Orthogonal regression minimizes the average perpendicular distance of the points from the plane. Applying this estimation to a set of scans we conclude that a plane seems to be a good approximation of the interhemispheric region even if the error (the distance of the 3D points from the plane) is smoothly varying (maximum error 4 mm). The major interest of the plane is that we will now be able to perform a robust asymmetry measurement even if the brain is not well orientated with respect to the MRI acquisition system. This will be a useful tool to assess if there is a change of brain asymmetry in schizophrenic patients and will be relevant to the suggestion that deviations in asymmetry are involved in the disease process [Crow 1990].
184
Reference Crow T.J. Temporal lobe asymmetry as the key to the aetiology of schizophrenia Schizophrenia Bulletin 1990; 16, 433 443.
THE TEMPORAL LOBES, REVERSED ASYMMETRY, AND SCHIZOPHRENIA GENETICS W.G. Honer, A.S. Bassett, E. Squires-Wheeler, P. Falkai, G.N. Smith, J.S. Lapointe, C. C a n e r o a n d D.J. Lang
Department of Psychiatry, University of British Columbia, 2660 Oak St., Vancouver, BC, Canada V6H 3Z6 Mechanisms determining temporal lobe structural asymmetries may be involved in the pathogenesis of schizophrenia. To investigate the temporal lobes in familial schizophrenia, computed tomographic scans were obtained from 51 subjects (7 families), stratified into three risk-groups: schizophrenia/schizoaffective (n = 25), schizophrenia spectrum/obligate carriers (n = 8), and unaffected, but from the affected side of the family (n= 18). Volumetric measurements of temporal CSF spaces were normalized to intracranial volume. Enlargement of sylvian fissure and temporal lobe sulcal volumes was observed in family members with schizophrenia compared to unaffected individuals (p~<.05), controlling for age, sex and family of origin effects. Schizophrenia spectrum subjects had larger sylvian fissures than unaffecteds (p~<.05), but were intermediate between schizophrenics and unaffecteds in temporal sulcal volume. The posterior one-third of the sylvian fissure was larger on the left side in subjects with schizophrenia, and larger on the right side in unaffected individuals (risk-group by segment interaction p ~<.007). This disturbed pattern of posterior sylvian fissure asymmetry suggests adjacent language regions may be affected in schizophrenia. An intermediate degree of disturbance in subjects who had schizophrenia-related illnesses or were obligate carriers suggests genetic factors may be important determinants of temporal lobe asymmetries in familial schizophrenia.
LOSS OF CEREBRAL ASYMMETRY FAMILIAL SCHIZOPHRENIA--A VOLUMETRIC MRI STUDY USING UNBIASED STEREOLOGY
IN
T. Sharma, S. Lewis, P. Barta, T. Sigmundsson, E. Lancaster, H. Gurling, G. Pearlson a n d R.M. Murray
Institute of Psychiatry, Denmark Hill, London SE5 8AF, U.K. The goal of the study was to determine whether familial schizophrenic patients and their unaffected first degree relatives differed from healthy subjects in regional cerebral asymmetries.
Regional volumes corresponding to prefrontal, premotor, sensorimotor, occipitoparietal, and temporal lobes in each hemisphere were measured on contiguous 1.5 mm 3D MRI images in 28 patients, 55 relatives and 39 controls using a new software based on stereological principles and capable of unbiased volume estimation. This study revealed a significant abnormality of cerebral hemispheric volume asymmetries in patients with schizophrenia. The healthy comparison subjects showed a systematic pattern of asymmetries, with prefrontal, premotor and temporal regions larger on the right and sensory motor and occipito-parietal regions larger on the left. In contrast, the patients did not show this pattern; they had low absolute asymmetry of all regions and reversed asymmetry of the occipito-parietal and prefrontal regions. In addition, transmitting parents (presumed obligate carriers), who are themselves unaffected, showed the same reversal as the schizophrenic family members. The absence of normal cortical asymmetry in familial schizophrenia and the unaffected parents lends support to an early neurodevelopmental abnormality that is likely to be genetic in origin.
MESIOTEMPORAL VOLUMES AND ASYMMETRY IN FIRST EPISODE SCHIZOPHRENICS: A BASELINE AND FOLLOW-UP
STUDY
R.D. Strous, M. Ashtari, R.M. Bilder a n d J.A. Lieberman
Hillside Hospital/Long Island Jewish Medical Center, Research, Glen Oaks, NYl1004, U.S.A. Structural abnormalities of the mesiotemporal (MT) lobe have been proposed as a possible neurodevelopmental defect in schizophrenia. However it is poorly understood to what extent these observed changes may be present in first episode (FE) patients, and whether these changes may be progressive or stable over time. This study investigates anterior and posterior MT volumes in 15 FE schizophrenics and 14 age and gender matched controls at baseline and at a follow-up examination (approximately 2-3 years later). Images were acquired on a 1.0 Tesla whole body MR system providing 3.1 mm slices and in-plane resolution of 1 mm x 1 mm. Measurements were made by a rater blind to both group and time using a semiautomated computer mensuration system. Delineation of regions of interest were based on post-mortem histological studies. Results indicated smaller patient MT volumes at baseline and an absence of volume changes over time. No group by time interaction was noted thereby excluding differential time changes. Furthermore, schizophrenics showed a significant reduction or reversal of the normal MT asymmetry; a consistent finding over time. Our results support the hypothesis that MT volume reductions are not progressive, although longer followup durations and larger samples would be important to rule this out definitively.
XI. Structural brain imaging XI.A. Anomalous asymmetry ANOMALOUS CEREBRAL ASYMMETRY SCHIZOPHRENIA: A STUDY OF FIRST EPISODES
IN
L.E. DeLisi*, M. Sakuma*, S.-H. Xie*, M. Kushner*, D.L. Finer*, A.L. Hoff* a n d T.J. C r o w t
*Department of Psychiatry, HSC, T-IO SUNY Stony Brook, Stony Brook, New York 11794, U.S.A. tPOWIC, University Department of Psychiatry, Warneford Hospital, Oxford, UK OX3 7JX. Asymmetries of brain widths and segments of the Sylvian fissure were assessed in an MRI study of 87 patients with a first episode of schizophrenia and 52 normal controls. These were correlated with specific measures of language processing, memory and hand-skill. An independent group of 14 siblings with schizophrenia were also evaluated for evidence of heritability of cerebral asymmetries. Width asymmetries were reduced in patients compared with controls in the posterior (p<0.02) and occipital (p<0.05) regions. Brain horizontal length, on the other hand, was significantly more asymmetric in patients ( L > R ; p<.04). For Sylvian fissure measurements ( L > R ) , asymmetries in controls were greatest for the horizontal component; this asymmetry failed to detect significant difference in patients by comparison with controls (p < .06). In a range of tests of language, memory, and cognition, few significant correlations between performance and cerebral asymmetries were detected. In 14 pairs of psychotic siblings, within-pair correlations for the horizontal Sylvian fissure asymmetry were significantly greater than between pair correlations. These findings are consistent with the early presence (possibly genetic ) of anomalous cerebral asymmetry.
Reference Crow, T.J. (1990) Temporal lobe asymmetries as the key to the etiology of schizophrenia. Schiz Bull 16: 433-443.
NORMAL PLANUM TEMPORALE ASYMMETRY IN FAMILIAL SCHIZOPHRENIA: A VOLUMETRIC STUDY
MRI
S. Frangou ~, T. Sharma ~, P. Barta 2, G. Pearlson 2 a n d R. M u r r a y ~
1Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, U.K. 2Department of Psychiatry and Behavioural Sciences, Johns Hopkins University, 600 N Wolfe St., 3-166 Meyer, Baltimore, MD21205, U.S,A.
Previous studies have reported loss or reversal of the normal asymmetry of the planum temporale. It has been postulated that this represents an abnormality in the mechanisms controlling cerebral asymmetries. The development of brain asymmetries is established in utero and is thought to be under genetic control. Abnormalities in brain lateralization are therefore assumed to be indicative of genetic vulnerability to schizophrenia. We tested this hypothesis is a sample of schizophrenics from multiply affected families where genetic factors appear to operate predominantly. We compared 31 (20 men and 11 women) right-handed schizophrenics from multiplex families to 35 (18 men and 17 women) right-handed age and sex matched controls recruited from the community. Volumetric measures of the planum temporale were obtained from 3D reconstructed MRI images. Volumes were calculated by using the Cavalieri method. Asymmetry coefficients obtained from the patients did not differ significantly from those obtained from the controls. The same results were obtained when the analysis was repeated separately for male and females. Our study suggests that abnormalities in the planum temporale asymmetry are not present in familial schizophrenia.
A THREE DIMENSIONAL MID SAGITTAL PLANE FOR BRAIN ASYMMETRY MEASUREMENT R. Guillemaud*, P. Marais**, A. Zisserman**, B. M c D o n a l d * , T.J. Crow* a n d M. Brady**
*MRC Schizophrenia Research Group, Department of Neuropathology Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, U.K. **Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, U.I( Asymmetry of the brain hemispheres, from a geometric point of view, is defined with respect to the plane of the interhemispheric fissure. We have developed a method to estimate this symmetry plane from scans of serial consecutive MRI slices. Multiple points are manually placed on each slice to identify the inter-hemispheric fissure, then the symmetry plane is computed in three dimensions by fitting a plane to the set of 3D points (defined in the previous step) using orthogonal regression. Orthogonal regression minimizes the average perpendicular distance of the points from the plane. Applying this estimation to a set of scans we conclude that a plane seems to be a good approximation of the interhemispheric region even if the error (the distance of the 3D points from the plane) is smoothly varying (maximum error 4 mm). The major interest of the plane is that we will now be able to perform a robust asymmetry measurement even if the brain is not well orientated with respect to the MRI acquisition system. This will be a useful tool to assess if there is a change of brain asymmetry in schizophrenic patients and will be relevant to the suggestion that deviations in asymmetry are involved in the disease process [Crow 1990].
184
Reference Crow T.J. Temporal lobe asymmetry as the key to the aetiology of schizophrenia Schizophrenia Bulletin 1990; 16, 433 443.
THE TEMPORAL LOBES, REVERSED ASYMMETRY, AND SCHIZOPHRENIA GENETICS W.G. Honer, A.S. Bassett, E. Squires-Wheeler, P. Falkai, G.N. Smith, J.S. Lapointe, C. C a n e r o a n d D.J. Lang
Department of Psychiatry, University of British Columbia, 2660 Oak St., Vancouver, BC, Canada V6H 3Z6 Mechanisms determining temporal lobe structural asymmetries may be involved in the pathogenesis of schizophrenia. To investigate the temporal lobes in familial schizophrenia, computed tomographic scans were obtained from 51 subjects (7 families), stratified into three risk-groups: schizophrenia/schizoaffective (n = 25), schizophrenia spectrum/obligate carriers (n = 8), and unaffected, but from the affected side of the family (n= 18). Volumetric measurements of temporal CSF spaces were normalized to intracranial volume. Enlargement of sylvian fissure and temporal lobe sulcal volumes was observed in family members with schizophrenia compared to unaffected individuals (p~<.05), controlling for age, sex and family of origin effects. Schizophrenia spectrum subjects had larger sylvian fissures than unaffecteds (p~<.05), but were intermediate between schizophrenics and unaffecteds in temporal sulcal volume. The posterior one-third of the sylvian fissure was larger on the left side in subjects with schizophrenia, and larger on the right side in unaffected individuals (risk-group by segment interaction p ~<.007). This disturbed pattern of posterior sylvian fissure asymmetry suggests adjacent language regions may be affected in schizophrenia. An intermediate degree of disturbance in subjects who had schizophrenia-related illnesses or were obligate carriers suggests genetic factors may be important determinants of temporal lobe asymmetries in familial schizophrenia.
LOSS OF CEREBRAL ASYMMETRY FAMILIAL SCHIZOPHRENIA--A VOLUMETRIC MRI STUDY USING UNBIASED STEREOLOGY
IN
T. Sharma, S. Lewis, P. Barta, T. Sigmundsson, E. Lancaster, H. Gurling, G. Pearlson a n d R.M. Murray
Institute of Psychiatry, Denmark Hill, London SE5 8AF, U.K. The goal of the study was to determine whether familial schizophrenic patients and their unaffected first degree relatives differed from healthy subjects in regional cerebral asymmetries.
Regional volumes corresponding to prefrontal, premotor, sensorimotor, occipitoparietal, and temporal lobes in each hemisphere were measured on contiguous 1.5 mm 3D MRI images in 28 patients, 55 relatives and 39 controls using a new software based on stereological principles and capable of unbiased volume estimation. This study revealed a significant abnormality of cerebral hemispheric volume asymmetries in patients with schizophrenia. The healthy comparison subjects showed a systematic pattern of asymmetries, with prefrontal, premotor and temporal regions larger on the right and sensory motor and occipito-parietal regions larger on the left. In contrast, the patients did not show this pattern; they had low absolute asymmetry of all regions and reversed asymmetry of the occipito-parietal and prefrontal regions. In addition, transmitting parents (presumed obligate carriers), who are themselves unaffected, showed the same reversal as the schizophrenic family members. The absence of normal cortical asymmetry in familial schizophrenia and the unaffected parents lends support to an early neurodevelopmental abnormality that is likely to be genetic in origin.
MESIOTEMPORAL VOLUMES AND ASYMMETRY IN FIRST EPISODE SCHIZOPHRENICS: A BASELINE AND FOLLOW-UP
STUDY
R.D. Strous, M. Ashtari, R.M. Bilder a n d J.A. Lieberman
Hillside Hospital/Long Island Jewish Medical Center, Research, Glen Oaks, NYl1004, U.S.A. Structural abnormalities of the mesiotemporal (MT) lobe have been proposed as a possible neurodevelopmental defect in schizophrenia. However it is poorly understood to what extent these observed changes may be present in first episode (FE) patients, and whether these changes may be progressive or stable over time. This study investigates anterior and posterior MT volumes in 15 FE schizophrenics and 14 age and gender matched controls at baseline and at a follow-up examination (approximately 2-3 years later). Images were acquired on a 1.0 Tesla whole body MR system providing 3.1 mm slices and in-plane resolution of 1 mm x 1 mm. Measurements were made by a rater blind to both group and time using a semiautomated computer mensuration system. Delineation of regions of interest were based on post-mortem histological studies. Results indicated smaller patient MT volumes at baseline and an absence of volume changes over time. No group by time interaction was noted thereby excluding differential time changes. Furthermore, schizophrenics showed a significant reduction or reversal of the normal MT asymmetry; a consistent finding over time. Our results support the hypothesis that MT volume reductions are not progressive, although longer followup durations and larger samples would be important to rule this out definitively.