- Email: [email protected]
Structural MRI and neuropsychological assessments in adolescent patients with either schizophrenia or affective disorders
189
MRI studies investigating frontal brain volume in schizophrenia are inconsistent. The fact that these studies did not measure frontal lobe subregions may have contributed to this inconsistency. MR imaging was performed with a 0.5 T magnet. Coronal Tl-weighted 3D gradient echo MRI scans (1 x 1 x 1.2 mm 3, TR=30 ms, T E = 13 ms) were obtained from 13 male schizophrenic patients and 14 age, sex, handedness, and parental SES matched healthy controls. Volume measurements were obtained from medial, dorsolateral and orbitofrontal subregions. Groups did not differ in absolute or relative (/total brain volume) volumes as evidenced by MANOVA. Patients performed significantly worse on several neuropsychological tests such as the Verbal Fluency Task and the Californian Verbal Learning Test. Impaired neuropsychological test performance significantly correlated with smaller frontal volumes. Furthermore, significant negative correlations between the total score of negative symptoms (SANS) and relative frontal volumes were found (rs = -.66; p < .01 for total orbitofrontal gray matter volume).
XI.E.2 STRUCTURE-FUNCTION RELATIONS FIRST EPISODE SCHIZOPHRENIA
IN
R.M. Bilder, H. Wu, B. Bogerts, G. Degreef, M. Chakos, J.A. Lieberman
Hillside Hospital--Research, 75-59 263rd Street, Glen Oaks, NYl1004, U.S.A. We report combined results of studies conducted in 94 first episode patients, examining relations between brain structures (measured on MR images), and functions (measured on a comprehensive neuropsychological [NP] battery). Structural indices include the volumes and asymmetries of the major cortical regions (prefrontal, premotor, sensorimotor, parietooccipital, and temporal), components of the ventricular system (frontal, body, occipital, and temporal horns of the lateral ventricle, and third ventricle), mesiotemporal regions (amygdala, anterior hippocampus, posterior hippocampus), caudate nucleus, superior temporal gyrus. NP indices include scales loading on language, memory, attentional, executive, motor, and visuospatial functions, along with an index of 'premorbid' ability. Larger cortical volume was moderately correlated with better NP function, especially among men. Ventricular enlargement was correlated with memory deficits, after controlling for 'premorbid' ability. Among the mesiotemporal measures, only anterior hippocampal volume reductions were associated with NP deficits, specifically with executive and motor functions usually attributed to the frontal lobes. Larger caudate volume was associated with nonspecifically poorer NP function. Superior temporal gyrus volume was not associated with any NP deficit, after controlling for overall cortical volume. The results are consistent with the hypothesis that NP deficits in schizophrenia reflect multiple dissociable cerebral risk factors, with some occurring earlier and others later in ontogeny.
XI.E.3 CORRELATION BETWEEN GREY MATTER VOLUME AND SYNDROME SCORES IN SCHIZOPHRENIA: A DATA-LED APPROACH S.E. Chua 1, P.K. McGuire 1'2, I.C. Wright 1, J.-B. Poline 2, P.F. Liddle 3, R.M. Murray 1, R.S.J. Frackowiak 2, K.J. Friston 2.
1Institute of Psychiatry, De Crespigny Park, London SEF 8AF, U.K. 2WellcomeDept. of Cognitive Neurology. 3Dept. of Psychiatry, University of British Columbia, Vancouver, Canada We examined the correlation between the relative volume of cerebral grey matter in structural magnetic resonance images (MRI) of schizophrenic subjects and ratings of the three syndromes of psychomotor poverty, disorganization and reality distortion. These subjects had previously had positron emission tomographic (PET) scans, which had demonstrated specific patterns of cerebral blood flow correlating with each syndrome. The magnetic resonance data revealed that there was a significant negative correlation between psychomotor poverty score and the volume of the left orbito-medial cortical grey matter (relative to whole brain volume), and a significant positive correlation between disorganization score and the relative volumes of the hippocampi and the parahippocampal gyri bilaterally. The correlation between left prefrontal grey matter volume and psychomotor poverty resembles that seen in these same subjects between this syndrome and prefrontal blood flow, suggesting that the functional resting abnormality may reflect underlying anatomical change.
XI.E.4 STRUCTURAL MRI AND NEUROPSYCHOLOGICAL ASSESSMENTS IN ADOLESCENT PATIENTS WITH EITHER SCHIZOPHRENIA OR AFFECTIVE DISORDERS L. Friedman, R.L. Findling, J. Buck, D.M. Cola, T.P. Swales, J.T. Kenny and S.C. Schulz
Department of Psychiatry, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, U.S..4. Adolescent schizophrenia is of interest because of proximity to illness onset. Also, adolescent schizophrenics may comprise a distinct subtype. We have assessed structural MRI and neuropsychological function in a group of 17 patients with schizophrenia during adolescence (mean 14.9 yrs, range=9 to 18) as well as 13 age-matched community controls. Eight adolescents with affective disorder (6 with bipolar and 2 with
190
unipolar disorder) have also been evaluated for comparison. MRI: We find no evidence for ventricular enlargement in the schizophrenics, but we do find statistically significant reductions in brain volume in this group when compared to controls. Patients with schizophrenia have a statistically significant reduction in the ratio of left to right hippocampal volume when compared to controls. Interestingly, there is a statistical trend (p = 0.0506) for adolescent patients with affective disorders to exhibit increased sulcal fluid spaces when compared to controls. NEUROPSYCHOLOGY: Both patient groups had reduced performance on one or more measures of attention, when compared to controls. In addition, the patients with schizophrenia had significant reductions in measures of short-term memory and recent long-term memory. Thus, our findings in adolescent patients parallel to some extent, similar findings in adult patients. But the parallel is not complete.
XI.E.5 IMPROVEMENT OF MEMORY IN PATIENTS FOLLOWING FRONTAL LOBE DAMAGE: A LONGITUDINAL FOLLOW-UP USING 3D MR-IMAGING
STUDY
H.E. H u l s h o f f P o l , R. Hijman, P. Meyer, C.A.F. Tulleken, L.M.P. R a m o s , M.A. Viergever, R.S. K a h n , a n d J.M. v a n Ree
Department of Psychiatry, UniversityHospital and Rudolf Magnus Institutefor Neurosciences, AO1.126, PO 85500, 3508GA Utrecht, The Netherlands To investigate the influence of time after frontal lobe damage on verbal and visual memory processing in humans, 11 patients with right-medial/dorsolateral, right medial, or left medial frontal lobe damage due to a tumor were assessed 3-5 weeks and 2-4 years post-neurosurgery, and compared to 11 age, and education matched controls also assessed at both time points. The damaged brain region was evaluated by 0.5T, T2-weighted MRI, or by CT. In addition, 3-dimensional computerreconstructions of 0.5T, Tl-weighted 3D-FFE MRI following Gadolinium-DTPA were acquired 2-4 years postsurgery. While initially verbal or visual memory deficits depended on the localization of the damage, with time, verbal and visual memory had improved to normal. Thus, shortly after damage there was a relation between site of the damage and memory deficits, while this was not present some years later, despite the persistence of the damage.
XI.E.6 A COMPARISON OF THE COGNITIVE CORRELATES OF BRAIN STRUCTURE VOLUMES IN PATIENTS WITH SCHIZOPHRENIA AND NORMAL CONTROLS T.M. Rushe, P.W.R. Woodruff, R.M. M u r r a y a n d R.G. Morris
Department of Psychology and Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, U.K. Previous studies have reported significant correlations between brain structure volume and measures of cognitive function in patients with schizophrenia. However in the absence of normal control data, interpretation of the pathological significance of these relationships is limited. Magnetic Resonance Imaging was used to assess brain structural volumes and measures of memory and executive function were derived from a comprehensive battery in 34 patients with schizophrenia and 42 matched normal controls. In the control sample, verbal memory was significantly correlated with volume of both the left and right hippocampus (r=.34,=.03, and r=.41, p<.01 respectively). The volume of the left parahippocampal gyrus was correlated with performance on the Tower of London planning task (r=.41, p = . 0 1 ) as well as performance on a conditional associative learning task (r=.35, p=.04). In the patient sample, the only significant correlations to emerge were between the volume of the right hippocampus and performance on a visuospatial memory task (r = .46, p = .02) as well as on a visuospatial learning task (r = .46, p = .02). The loss of 'normal' structure/function relationships, and the stronger than normal 'localization' of visuospatial function in patients with schizophrenia is consistent the view that schizophrenia is characterized by an altered pattern of structure function relationships.
XI.E.7 PREFRONTAL CORTICAL NEUROPSYCHOLOGICAL SCHIZOPHRENIA
VOLUMES DEFICITS
AND IN
P.B. Ward, C. Loneragan, E.L. Ganser, S. Chaturverdi, B. Liebert, R. L a n g d o n 1 a n d J. R e d e n b a c h
School of Psychiatry, Universityof New South Wales, Sydney, 2052, Biological Schizophrenia Research Team, Psychiatry Department, Prince of WalesHospital, XSchoolof Behavioural Sciences, Maequarie University, NSW 2109 Australia Previous studies have reported evidence of volume reductions in prefrontal cortical regions in schizophrenic patients. In some
MRI studies investigating frontal brain volume in schizophrenia are inconsistent. The fact that these studies did not measure frontal lobe subregions may have contributed to this inconsistency. MR imaging was performed with a 0.5 T magnet. Coronal Tl-weighted 3D gradient echo MRI scans (1 x 1 x 1.2 mm 3, TR=30 ms, T E = 13 ms) were obtained from 13 male schizophrenic patients and 14 age, sex, handedness, and parental SES matched healthy controls. Volume measurements were obtained from medial, dorsolateral and orbitofrontal subregions. Groups did not differ in absolute or relative (/total brain volume) volumes as evidenced by MANOVA. Patients performed significantly worse on several neuropsychological tests such as the Verbal Fluency Task and the Californian Verbal Learning Test. Impaired neuropsychological test performance significantly correlated with smaller frontal volumes. Furthermore, significant negative correlations between the total score of negative symptoms (SANS) and relative frontal volumes were found (rs = -.66; p < .01 for total orbitofrontal gray matter volume).
XI.E.2 STRUCTURE-FUNCTION RELATIONS FIRST EPISODE SCHIZOPHRENIA
IN
R.M. Bilder, H. Wu, B. Bogerts, G. Degreef, M. Chakos, J.A. Lieberman
Hillside Hospital--Research, 75-59 263rd Street, Glen Oaks, NYl1004, U.S.A. We report combined results of studies conducted in 94 first episode patients, examining relations between brain structures (measured on MR images), and functions (measured on a comprehensive neuropsychological [NP] battery). Structural indices include the volumes and asymmetries of the major cortical regions (prefrontal, premotor, sensorimotor, parietooccipital, and temporal), components of the ventricular system (frontal, body, occipital, and temporal horns of the lateral ventricle, and third ventricle), mesiotemporal regions (amygdala, anterior hippocampus, posterior hippocampus), caudate nucleus, superior temporal gyrus. NP indices include scales loading on language, memory, attentional, executive, motor, and visuospatial functions, along with an index of 'premorbid' ability. Larger cortical volume was moderately correlated with better NP function, especially among men. Ventricular enlargement was correlated with memory deficits, after controlling for 'premorbid' ability. Among the mesiotemporal measures, only anterior hippocampal volume reductions were associated with NP deficits, specifically with executive and motor functions usually attributed to the frontal lobes. Larger caudate volume was associated with nonspecifically poorer NP function. Superior temporal gyrus volume was not associated with any NP deficit, after controlling for overall cortical volume. The results are consistent with the hypothesis that NP deficits in schizophrenia reflect multiple dissociable cerebral risk factors, with some occurring earlier and others later in ontogeny.
XI.E.3 CORRELATION BETWEEN GREY MATTER VOLUME AND SYNDROME SCORES IN SCHIZOPHRENIA: A DATA-LED APPROACH S.E. Chua 1, P.K. McGuire 1'2, I.C. Wright 1, J.-B. Poline 2, P.F. Liddle 3, R.M. Murray 1, R.S.J. Frackowiak 2, K.J. Friston 2.
1Institute of Psychiatry, De Crespigny Park, London SEF 8AF, U.K. 2WellcomeDept. of Cognitive Neurology. 3Dept. of Psychiatry, University of British Columbia, Vancouver, Canada We examined the correlation between the relative volume of cerebral grey matter in structural magnetic resonance images (MRI) of schizophrenic subjects and ratings of the three syndromes of psychomotor poverty, disorganization and reality distortion. These subjects had previously had positron emission tomographic (PET) scans, which had demonstrated specific patterns of cerebral blood flow correlating with each syndrome. The magnetic resonance data revealed that there was a significant negative correlation between psychomotor poverty score and the volume of the left orbito-medial cortical grey matter (relative to whole brain volume), and a significant positive correlation between disorganization score and the relative volumes of the hippocampi and the parahippocampal gyri bilaterally. The correlation between left prefrontal grey matter volume and psychomotor poverty resembles that seen in these same subjects between this syndrome and prefrontal blood flow, suggesting that the functional resting abnormality may reflect underlying anatomical change.
XI.E.4 STRUCTURAL MRI AND NEUROPSYCHOLOGICAL ASSESSMENTS IN ADOLESCENT PATIENTS WITH EITHER SCHIZOPHRENIA OR AFFECTIVE DISORDERS L. Friedman, R.L. Findling, J. Buck, D.M. Cola, T.P. Swales, J.T. Kenny and S.C. Schulz
Department of Psychiatry, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, U.S..4. Adolescent schizophrenia is of interest because of proximity to illness onset. Also, adolescent schizophrenics may comprise a distinct subtype. We have assessed structural MRI and neuropsychological function in a group of 17 patients with schizophrenia during adolescence (mean 14.9 yrs, range=9 to 18) as well as 13 age-matched community controls. Eight adolescents with affective disorder (6 with bipolar and 2 with
190
unipolar disorder) have also been evaluated for comparison. MRI: We find no evidence for ventricular enlargement in the schizophrenics, but we do find statistically significant reductions in brain volume in this group when compared to controls. Patients with schizophrenia have a statistically significant reduction in the ratio of left to right hippocampal volume when compared to controls. Interestingly, there is a statistical trend (p = 0.0506) for adolescent patients with affective disorders to exhibit increased sulcal fluid spaces when compared to controls. NEUROPSYCHOLOGY: Both patient groups had reduced performance on one or more measures of attention, when compared to controls. In addition, the patients with schizophrenia had significant reductions in measures of short-term memory and recent long-term memory. Thus, our findings in adolescent patients parallel to some extent, similar findings in adult patients. But the parallel is not complete.
XI.E.5 IMPROVEMENT OF MEMORY IN PATIENTS FOLLOWING FRONTAL LOBE DAMAGE: A LONGITUDINAL FOLLOW-UP USING 3D MR-IMAGING
STUDY
H.E. H u l s h o f f P o l , R. Hijman, P. Meyer, C.A.F. Tulleken, L.M.P. R a m o s , M.A. Viergever, R.S. K a h n , a n d J.M. v a n Ree
Department of Psychiatry, UniversityHospital and Rudolf Magnus Institutefor Neurosciences, AO1.126, PO 85500, 3508GA Utrecht, The Netherlands To investigate the influence of time after frontal lobe damage on verbal and visual memory processing in humans, 11 patients with right-medial/dorsolateral, right medial, or left medial frontal lobe damage due to a tumor were assessed 3-5 weeks and 2-4 years post-neurosurgery, and compared to 11 age, and education matched controls also assessed at both time points. The damaged brain region was evaluated by 0.5T, T2-weighted MRI, or by CT. In addition, 3-dimensional computerreconstructions of 0.5T, Tl-weighted 3D-FFE MRI following Gadolinium-DTPA were acquired 2-4 years postsurgery. While initially verbal or visual memory deficits depended on the localization of the damage, with time, verbal and visual memory had improved to normal. Thus, shortly after damage there was a relation between site of the damage and memory deficits, while this was not present some years later, despite the persistence of the damage.
XI.E.6 A COMPARISON OF THE COGNITIVE CORRELATES OF BRAIN STRUCTURE VOLUMES IN PATIENTS WITH SCHIZOPHRENIA AND NORMAL CONTROLS T.M. Rushe, P.W.R. Woodruff, R.M. M u r r a y a n d R.G. Morris
Department of Psychology and Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, U.K. Previous studies have reported significant correlations between brain structure volume and measures of cognitive function in patients with schizophrenia. However in the absence of normal control data, interpretation of the pathological significance of these relationships is limited. Magnetic Resonance Imaging was used to assess brain structural volumes and measures of memory and executive function were derived from a comprehensive battery in 34 patients with schizophrenia and 42 matched normal controls. In the control sample, verbal memory was significantly correlated with volume of both the left and right hippocampus (r=.34,=.03, and r=.41, p<.01 respectively). The volume of the left parahippocampal gyrus was correlated with performance on the Tower of London planning task (r=.41, p = . 0 1 ) as well as performance on a conditional associative learning task (r=.35, p=.04). In the patient sample, the only significant correlations to emerge were between the volume of the right hippocampus and performance on a visuospatial memory task (r = .46, p = .02) as well as on a visuospatial learning task (r = .46, p = .02). The loss of 'normal' structure/function relationships, and the stronger than normal 'localization' of visuospatial function in patients with schizophrenia is consistent the view that schizophrenia is characterized by an altered pattern of structure function relationships.
XI.E.7 PREFRONTAL CORTICAL NEUROPSYCHOLOGICAL SCHIZOPHRENIA
VOLUMES DEFICITS
AND IN
P.B. Ward, C. Loneragan, E.L. Ganser, S. Chaturverdi, B. Liebert, R. L a n g d o n 1 a n d J. R e d e n b a c h
School of Psychiatry, Universityof New South Wales, Sydney, 2052, Biological Schizophrenia Research Team, Psychiatry Department, Prince of WalesHospital, XSchoolof Behavioural Sciences, Maequarie University, NSW 2109 Australia Previous studies have reported evidence of volume reductions in prefrontal cortical regions in schizophrenic patients. In some