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Stereological estimation of gyrification index and related measures of cortical folding from MR data in schizophrenia
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4A+ Background: Although it is well-known that patients with schizophrenia have abnormal smooth pursuit eye movements and abnormal brain structure, the relationship between these two areas of research is not clear. It would be interesting to examine the relationship between changes of the volume of the caudate nucleus and poor smooth pursuit, because the caudate is part of a cortical-subcortical oculomotor circu it and incr~sed metabolism in the caudate has been found to be associated with poor smooth pursuit in schizophrenia. Objective: To compare . caud~te vol~me betwer:n normal controls and schizophrenic patients WIth and WIthout eye tracking disorder (ETD). Methods: Thirteen schizophrenic patients have undergone MRI scanning of the brain using the spoiled grass method (SPGR). They also had smooth pw:uit ~ye movements tested . response to a sinusoidal target using Infrared oculography. ~o lume of the caudate nucleus and putamen will be measured. position RMS M ea surements of eye movements will include . k . or gain and catch-up saccades. Previous wor In our ~~o:atOry has shown that the distribution ~f position .R MS r in schizophrenic patients is best charactenzed by a mixture errO . d fin' . f b of two normal distributions, allowing e ition 0 su groups with and without eye tracking disorder (ETD).
(4"!> PROGRESSIVE BRAIN CHANGES AND AGE AT ONSET OF ILLNESS IN SCHIZOPHRENIA Geoffrey N. Smith, uu C. Kopala, Jo.cel~ne S Lapointe G . William MacEwan, Siemion Altman, S~an W. Fl;nn, Thomas Schneider, Peter Falkai, William G. Honer Department ofPsychiatry, University ofBritish Columbia. 2660 Oak St. Vancouver. B.C; Canada V6H 326
P tients with schizophrenia show substantial variability in aa~ onset of illness and course of illness. Recent studies age st that age at onset of illness may be useful in defining sugge . n, db' biologically distinct subgroups of patients. we assesse ram tomy from cr scans in 117 early onset «21) and 153 anda It onset (21--45) pat ients with DSM-III-R diagnosed schizoa U f . . d an treatment h ia. Obstetric history , clinical unctionmg pren f nati V '1 ' response were assessed in a subgroup ~ p.atien~. ent~c e Size increased with increas ing illness ~urauon m pattents WIth adult onset but not in early onset patients. ~ese changes occurred . the first ten years of illness. Progressive enlargement of the In rtical sulci was evident in both early and adult onset patients ~ t ~as greater in adult onset patients. Obstetric complications were significantly more common in early onset patients. Adult nset but not early onset patients became more treatment ~efractory with increased illness dura~on. The.se results suggest two biologically distinct types of schizophrenia: I. A neurodevelopmental group with early onset, bi~ ~roblems .and .no progressive ventricular enlargement or clinical detenoratton after the onset of psychosis, 2. A neurodegenerative group with few birth problems, adulthood onset, progressive brain changes, and clinical decline after the onset of psychosis .
STEREOLOGICAL ESTIMATION OF GYRIFICATION INDEX AND RELATED MEASURES OF CORTICAL FOLDING FROM MR DATA IN SCHIZOPHRENIA Martin D. Stefan, Tonmoy Sharma, Zoe Ellison, Robin Murray, Ian Everall Department of Psychological Medicine. Institute of Psychiatry, De Crespigny Park. London SE58AF, UK
Abnormalities of gyrification in schizophrenia have previously been reported, and are consistent with aberrant brain development. In this study we applied stereological techniques to the estimation of various indices of cortical folding . These are efficient and do not require automated image segmentation. Tl weighted SPGR images (1.5 mm contiguous slices) were available from the Maudsley family study of schizophrenia and were analysed using commercially available image analysis software (Analyze, Mayo Foundation). Images from 10 schizophrenic patients and 10 age- and sex-matched controls were scalp edited and placed in standard orientation. A spatial grid with dimensions in the coronal plane of 10 mm x 10 mm was superimposed and sampled at 8 10m intervals along the intercommisural line; intersections of the grid with the cortical surface of the left hemisphere at the grey-csf boundary were directly counted in the coronal (x, y) plane (and the number of intersections in z could therefore be inferred). The procedure was repeated for the superficially exposed surface of the hemisphere, so Gyrification Index (GI, defined as the ratio between the total length of the cortical contour and that of the superficially exposed contour in a given plane) could be estimated. Volume and surface area estimates were calculated for a subset of 10 images (5 control, 5 schizophrenic), and an analogous measure of cortical folding based on surface area rather than contour length was found to correlate strongly with GI (Pearson's r=0.9). All estimations were performed by a single rater and test-retest reliability was satisfactory (intraclass correlation coefficient =0.82 for GI measured on two occasions for S images). Mean GI for the group as a whole was 2.41 (about 6% less than available post-mortem data). There was no significant difference in GI or other measures ofcortical folding between images from schizophrenic patients and controls, nor was there any evidence of regional differences in GI between these groups; a non-s ignificant trend towards increased surface area in the schizophrenic group requ ires further evaluation.
"$ PREGNANCY AND BIRTH COMPLICATIONS (PBC)-ASSOCIATED HIPPOCAMPAL VOLUME REDUCTION IN SPORADIC SCHIZOPHRENIA N. Stefanis, J . Yakeley, S. Frangou, T. Sharma, P . O'Connell, K. Morgan, R. Murray Department of Psychological Medicine, Institute of Psychiatry, London SE5 8AF, UK PBC have emerged as a strong environmental factor that may have a particular bearing for the later development of
4A+ Background: Although it is well-known that patients with schizophrenia have abnormal smooth pursuit eye movements and abnormal brain structure, the relationship between these two areas of research is not clear. It would be interesting to examine the relationship between changes of the volume of the caudate nucleus and poor smooth pursuit, because the caudate is part of a cortical-subcortical oculomotor circu it and incr~sed metabolism in the caudate has been found to be associated with poor smooth pursuit in schizophrenia. Objective: To compare . caud~te vol~me betwer:n normal controls and schizophrenic patients WIth and WIthout eye tracking disorder (ETD). Methods: Thirteen schizophrenic patients have undergone MRI scanning of the brain using the spoiled grass method (SPGR). They also had smooth pw:uit ~ye movements tested . response to a sinusoidal target using Infrared oculography. ~o lume of the caudate nucleus and putamen will be measured. position RMS M ea surements of eye movements will include . k . or gain and catch-up saccades. Previous wor In our ~~o:atOry has shown that the distribution ~f position .R MS r in schizophrenic patients is best charactenzed by a mixture errO . d fin' . f b of two normal distributions, allowing e ition 0 su groups with and without eye tracking disorder (ETD).
(4"!> PROGRESSIVE BRAIN CHANGES AND AGE AT ONSET OF ILLNESS IN SCHIZOPHRENIA Geoffrey N. Smith, uu C. Kopala, Jo.cel~ne S Lapointe G . William MacEwan, Siemion Altman, S~an W. Fl;nn, Thomas Schneider, Peter Falkai, William G. Honer Department ofPsychiatry, University ofBritish Columbia. 2660 Oak St. Vancouver. B.C; Canada V6H 326
P tients with schizophrenia show substantial variability in aa~ onset of illness and course of illness. Recent studies age st that age at onset of illness may be useful in defining sugge . n, db' biologically distinct subgroups of patients. we assesse ram tomy from cr scans in 117 early onset «21) and 153 anda It onset (21--45) pat ients with DSM-III-R diagnosed schizoa U f . . d an treatment h ia. Obstetric history , clinical unctionmg pren f nati V '1 ' response were assessed in a subgroup ~ p.atien~. ent~c e Size increased with increas ing illness ~urauon m pattents WIth adult onset but not in early onset patients. ~ese changes occurred . the first ten years of illness. Progressive enlargement of the In rtical sulci was evident in both early and adult onset patients ~ t ~as greater in adult onset patients. Obstetric complications were significantly more common in early onset patients. Adult nset but not early onset patients became more treatment ~efractory with increased illness dura~on. The.se results suggest two biologically distinct types of schizophrenia: I. A neurodevelopmental group with early onset, bi~ ~roblems .and .no progressive ventricular enlargement or clinical detenoratton after the onset of psychosis, 2. A neurodegenerative group with few birth problems, adulthood onset, progressive brain changes, and clinical decline after the onset of psychosis .
STEREOLOGICAL ESTIMATION OF GYRIFICATION INDEX AND RELATED MEASURES OF CORTICAL FOLDING FROM MR DATA IN SCHIZOPHRENIA Martin D. Stefan, Tonmoy Sharma, Zoe Ellison, Robin Murray, Ian Everall Department of Psychological Medicine. Institute of Psychiatry, De Crespigny Park. London SE58AF, UK
Abnormalities of gyrification in schizophrenia have previously been reported, and are consistent with aberrant brain development. In this study we applied stereological techniques to the estimation of various indices of cortical folding . These are efficient and do not require automated image segmentation. Tl weighted SPGR images (1.5 mm contiguous slices) were available from the Maudsley family study of schizophrenia and were analysed using commercially available image analysis software (Analyze, Mayo Foundation). Images from 10 schizophrenic patients and 10 age- and sex-matched controls were scalp edited and placed in standard orientation. A spatial grid with dimensions in the coronal plane of 10 mm x 10 mm was superimposed and sampled at 8 10m intervals along the intercommisural line; intersections of the grid with the cortical surface of the left hemisphere at the grey-csf boundary were directly counted in the coronal (x, y) plane (and the number of intersections in z could therefore be inferred). The procedure was repeated for the superficially exposed surface of the hemisphere, so Gyrification Index (GI, defined as the ratio between the total length of the cortical contour and that of the superficially exposed contour in a given plane) could be estimated. Volume and surface area estimates were calculated for a subset of 10 images (5 control, 5 schizophrenic), and an analogous measure of cortical folding based on surface area rather than contour length was found to correlate strongly with GI (Pearson's r=0.9). All estimations were performed by a single rater and test-retest reliability was satisfactory (intraclass correlation coefficient =0.82 for GI measured on two occasions for S images). Mean GI for the group as a whole was 2.41 (about 6% less than available post-mortem data). There was no significant difference in GI or other measures ofcortical folding between images from schizophrenic patients and controls, nor was there any evidence of regional differences in GI between these groups; a non-s ignificant trend towards increased surface area in the schizophrenic group requ ires further evaluation.
"$ PREGNANCY AND BIRTH COMPLICATIONS (PBC)-ASSOCIATED HIPPOCAMPAL VOLUME REDUCTION IN SPORADIC SCHIZOPHRENIA N. Stefanis, J . Yakeley, S. Frangou, T. Sharma, P . O'Connell, K. Morgan, R. Murray Department of Psychological Medicine, Institute of Psychiatry, London SE5 8AF, UK PBC have emerged as a strong environmental factor that may have a particular bearing for the later development of