- Email: [email protected]
Regional brain glucose metabolism in neuroleptic naive first episode and chronic schizophrenic patients and normal controls at rest and after dopamine agonist and antagonist drugs
401
These data suggest that these brain regions are involved in a neural circuit underlying the production of deficit symptoms; a circuit corresponding to the dorsolateral prefrontal basal ganglia-thalamocortical circuit of Delong et al. and distinct from circuit(s) implicated in the production of psychotic symptoms. To further examine the involvement of these brain regions and neural circuit in the production of deficit symptoms and to test the hypothesis that the functional impairments described above are related to structural changes in one or more components of the proposed circuit, we measured the volume of selected components of the proposed circuit and other non-circuit brain regions in 12 deficit and 15 non-deficit patients. Volume measurements were derived from 3 mm coronal MRI images analyzed using the LOATS Image Analysis System. There were no differences between the two groups in the volume of circuit brain regions, i.e., prefrontal cortex and caudate, or non-circuit regions, i.e., amygdala and hippocampus. These results suggest that either structural changes in other components of the circuit or other brain regions outside of the circuit are responsible for the observed functional impairments, or that gross structural changes are not responsible for the observed functional impairments.
Striatal-thalamic schizophrenics
disorder of cerebral metabolism
M.S. Buchsbaum*, R. Haier, C. Teng, S. Potkin, K. Nuechterlein, Jerabek, and W.E. Bunney, Jr.
in never-medicated
J. Lohr, J. Wu, S. Lottenberg,
P.A.
Universityof California, Irvine, Brain Imag’ng Center, Room 164, Whitby Research Center, Irvine, CA 92717, USA
We scanned 24 patients with schizophrenia who had never received neuroleptic medication with positron emission tomography (PET) and 18F-deoxyglucose (FDG) as a tracer of glucose metabolism. Patients performed a Continuous Performance Test (CPT) during FDG uptake. Twenty normal volunteers without a history of psychiatric disease in themselves or their 1st degree relatives served as controls. Scans were converted to metabolic rate. MRI scans were obtained using the same head holder and computer algorithms were used to outline the caudate, putamen, and thalamus at multiple dorsal/ventral levels. Diminished metabolism was found in the basal ganglia and in anterior but not posterior thalamus. The sizes and volumetric estimates of caudate and putamen were assessed and glucose metabolic rates calculated for the entire volume. Probability contours for the anatomic locations of the basal ganglia were obtained and will be illustrated. The correlations among cortical and subcortical structures selected on the basis of a theoretical model of schizophrenia were also examined. Significantly different patterns of intercorrelation between brain regions were found between schizophrenics and normals.
Regional brain glucose metabolism in neuroleptic naive first episode and chronic schizophrenic patients and normal controls at rest and after dopamine agonist and antagonist drugs J.M. Cleghorn*,
H. Szechtman,
E.S. Garnett,
C. Nahmias, R.D. Kaplan, G.M. Brown, S. Franc0
Schizophrenia Research Program, Clarke Institute of Psychiatry, 250 College Street, East, Room 526, Toronto, Ontario M5T lR& Canada, and McMaster UniversiQ, Faculty of Health Sciences, 1200 Main Street West, Hamilton, Ontario LBN 3Z5, Canada
We describe regional cerebral [“F]FDG metabolism with positron emission tomography in 18 neuroleptic naive, 10 drug-free for four months, 23 neuroleptic-treated DSM-III schizophrenic patients, and 30 normal controls. We have replicated our previously reported finding of relative hypermetabolism in dorsolateral prefrontal cortex. However, the variance in the patient groups is greater than in the controls so that, in fact, some patients are hypofrontal and some are normal. Relative frontal metabolism correlates positively and significantly with measures of recall of meaningful information. A similar trend is seen within the controls. Our previous report of relative hypometabolism inparietal cortex has been replicated and discriminates more powerfully between patients and controls than does frontal metabolism.
402 Neuroleptic-treated patients show relative hypermetabolism in the striatum and in focal areas of frontal and parietal cortex, when compared with drug-free patients and normal controls. A prior history of severe substance abuse, meeting DSM-III criteria in approximately half of our patients, is not associated with altered relative metabolism in any region. The dopamine agonist apomorphine 0.75 mg SCand normal saline, was administered on alternate days to 11 drug-naive patients and 8 normal controls, twenty minutes prior to the administration of [18F]FDG. A highly consistent reduction in striatal metabolism was observed in the patient group and not in the controls. The direction of the effect is opposite to the effect of neuroleptics. Consistent reductions in relative metabolism were also observed in superior temporal and parietal cortices. The above represents analyses of three tomographic slices. In order to determine the extent to which other regions may be involved, lateral reconstructions of the brain have been made. The AC-PC line can be identified, and this permits localization of brain structures from a neurosurgical atlas (Talairach and Tournaoux, 1988). An analysis of the data using this new method will be presented.
Temporal lobe asymmetries
as a clue to the aetiology of schizophrenia
T.J. Crow*, C.J. Bruton, C.D. Frith, E.C. Johnstone Division of Pgchiaty,
and D.G.C. Owens
Clinical Research Centre, Watford Road, Harrow, Middleseu, HA I SlJJ, U.K.
A series of radiological and post-mortem studies conducted within the Division cast new light on the problem of the morphological changes in the brain in schizophrenia. These studies suggest that the changes are asymmetrical, and that the asymmetry may be specific to this disease: - i) in a post-mortem study (Brown et al., 1986, Archives of General Psychiatry, 43:36 -42) the brains of patients with schizophrenia were found to be 6% lighter than those of patients with affective (manic-depressive) disorders dying in the same hospital, and the ventricles were found to be larger. This enlargement applied particularly to the temporal horns. Within the temporal lobes, the parahippocampal gyrus (a structure that relays information to the hippocampus and limbic system) was reduced in width and this reduction was significantly greater on the left side of the brain. ii) in a CT scan study (Crow et al., 1989, Psychiatry Research, 29:247-253) the width of the brain was found to be reduced in temporo-occipital segments on the left side in patients with an early onset of illness by comparison with those of late onset and with patients with other psychiatric diseases. Early onset was found to be predictor of poor outcome. iii) in an NMR study (Johnstone et al., 1989, Journal of Neurology, Neurosurgery and Psychiatry, 52:736 -741) temporal lobe area was reduced on the left side in patients with schizophrenia relative to those with affective disorder and normal controls. iv) in a post-mortem study (Crow et al., 1989, Archives of General Psychiatry, 46:1145 - 1150) lateral ventricular enlargement was again found to be greatest in the temporal horn. Temporal horn enlargement in patients with schizophrenia was selective to the left side whereas similar enlargement in patients with Alzheimer-type dementia was present on both sides (ANOVA p < 0.001). Histopathological examination (Bruton et al., 1990, Psychological Medicine, 20:285 -304) of these brains indicates that these changes are unrelated to the presence of gliosis such as might be expected if they were due to degeneration or exogenous insult. It seems likely that the changes in schizophrenia are at least in part developmental. They can be explained on the basis that in this disease there is an arrest of development of cerebral asymmetry that results in the temporal lobe on the left side being slightly smaller and the temporal horn slightly larger than would normally be the case.
Frontal and right-left differences in schizophrenic vs normal subjects: A magnetic resonance brain imaging (MRI) study M.K. DeMyer*,
W.E. DeMyer, H.C. Hendrie,
S. Babb, R. Smith, M. Edwards, J.M. Wright
Department of Psychiatry, Indiana University School of Medicine, Zndiauapolis, IN 46202, U.S.A.
Most investigators using computerized tomography (CT) and magnetic resonance imaging (MRI) techniques have found that schizophrenic patients (Sch) have enlarged ventricles in comparison to age and sex matched normal controls (Nr). Because MRI allows a better differentiation of brain structures, the search has com-
These data suggest that these brain regions are involved in a neural circuit underlying the production of deficit symptoms; a circuit corresponding to the dorsolateral prefrontal basal ganglia-thalamocortical circuit of Delong et al. and distinct from circuit(s) implicated in the production of psychotic symptoms. To further examine the involvement of these brain regions and neural circuit in the production of deficit symptoms and to test the hypothesis that the functional impairments described above are related to structural changes in one or more components of the proposed circuit, we measured the volume of selected components of the proposed circuit and other non-circuit brain regions in 12 deficit and 15 non-deficit patients. Volume measurements were derived from 3 mm coronal MRI images analyzed using the LOATS Image Analysis System. There were no differences between the two groups in the volume of circuit brain regions, i.e., prefrontal cortex and caudate, or non-circuit regions, i.e., amygdala and hippocampus. These results suggest that either structural changes in other components of the circuit or other brain regions outside of the circuit are responsible for the observed functional impairments, or that gross structural changes are not responsible for the observed functional impairments.
Striatal-thalamic schizophrenics
disorder of cerebral metabolism
M.S. Buchsbaum*, R. Haier, C. Teng, S. Potkin, K. Nuechterlein, Jerabek, and W.E. Bunney, Jr.
in never-medicated
J. Lohr, J. Wu, S. Lottenberg,
P.A.
Universityof California, Irvine, Brain Imag’ng Center, Room 164, Whitby Research Center, Irvine, CA 92717, USA
We scanned 24 patients with schizophrenia who had never received neuroleptic medication with positron emission tomography (PET) and 18F-deoxyglucose (FDG) as a tracer of glucose metabolism. Patients performed a Continuous Performance Test (CPT) during FDG uptake. Twenty normal volunteers without a history of psychiatric disease in themselves or their 1st degree relatives served as controls. Scans were converted to metabolic rate. MRI scans were obtained using the same head holder and computer algorithms were used to outline the caudate, putamen, and thalamus at multiple dorsal/ventral levels. Diminished metabolism was found in the basal ganglia and in anterior but not posterior thalamus. The sizes and volumetric estimates of caudate and putamen were assessed and glucose metabolic rates calculated for the entire volume. Probability contours for the anatomic locations of the basal ganglia were obtained and will be illustrated. The correlations among cortical and subcortical structures selected on the basis of a theoretical model of schizophrenia were also examined. Significantly different patterns of intercorrelation between brain regions were found between schizophrenics and normals.
Regional brain glucose metabolism in neuroleptic naive first episode and chronic schizophrenic patients and normal controls at rest and after dopamine agonist and antagonist drugs J.M. Cleghorn*,
H. Szechtman,
E.S. Garnett,
C. Nahmias, R.D. Kaplan, G.M. Brown, S. Franc0
Schizophrenia Research Program, Clarke Institute of Psychiatry, 250 College Street, East, Room 526, Toronto, Ontario M5T lR& Canada, and McMaster UniversiQ, Faculty of Health Sciences, 1200 Main Street West, Hamilton, Ontario LBN 3Z5, Canada
We describe regional cerebral [“F]FDG metabolism with positron emission tomography in 18 neuroleptic naive, 10 drug-free for four months, 23 neuroleptic-treated DSM-III schizophrenic patients, and 30 normal controls. We have replicated our previously reported finding of relative hypermetabolism in dorsolateral prefrontal cortex. However, the variance in the patient groups is greater than in the controls so that, in fact, some patients are hypofrontal and some are normal. Relative frontal metabolism correlates positively and significantly with measures of recall of meaningful information. A similar trend is seen within the controls. Our previous report of relative hypometabolism inparietal cortex has been replicated and discriminates more powerfully between patients and controls than does frontal metabolism.
402 Neuroleptic-treated patients show relative hypermetabolism in the striatum and in focal areas of frontal and parietal cortex, when compared with drug-free patients and normal controls. A prior history of severe substance abuse, meeting DSM-III criteria in approximately half of our patients, is not associated with altered relative metabolism in any region. The dopamine agonist apomorphine 0.75 mg SCand normal saline, was administered on alternate days to 11 drug-naive patients and 8 normal controls, twenty minutes prior to the administration of [18F]FDG. A highly consistent reduction in striatal metabolism was observed in the patient group and not in the controls. The direction of the effect is opposite to the effect of neuroleptics. Consistent reductions in relative metabolism were also observed in superior temporal and parietal cortices. The above represents analyses of three tomographic slices. In order to determine the extent to which other regions may be involved, lateral reconstructions of the brain have been made. The AC-PC line can be identified, and this permits localization of brain structures from a neurosurgical atlas (Talairach and Tournaoux, 1988). An analysis of the data using this new method will be presented.
Temporal lobe asymmetries
as a clue to the aetiology of schizophrenia
T.J. Crow*, C.J. Bruton, C.D. Frith, E.C. Johnstone Division of Pgchiaty,
and D.G.C. Owens
Clinical Research Centre, Watford Road, Harrow, Middleseu, HA I SlJJ, U.K.
A series of radiological and post-mortem studies conducted within the Division cast new light on the problem of the morphological changes in the brain in schizophrenia. These studies suggest that the changes are asymmetrical, and that the asymmetry may be specific to this disease: - i) in a post-mortem study (Brown et al., 1986, Archives of General Psychiatry, 43:36 -42) the brains of patients with schizophrenia were found to be 6% lighter than those of patients with affective (manic-depressive) disorders dying in the same hospital, and the ventricles were found to be larger. This enlargement applied particularly to the temporal horns. Within the temporal lobes, the parahippocampal gyrus (a structure that relays information to the hippocampus and limbic system) was reduced in width and this reduction was significantly greater on the left side of the brain. ii) in a CT scan study (Crow et al., 1989, Psychiatry Research, 29:247-253) the width of the brain was found to be reduced in temporo-occipital segments on the left side in patients with an early onset of illness by comparison with those of late onset and with patients with other psychiatric diseases. Early onset was found to be predictor of poor outcome. iii) in an NMR study (Johnstone et al., 1989, Journal of Neurology, Neurosurgery and Psychiatry, 52:736 -741) temporal lobe area was reduced on the left side in patients with schizophrenia relative to those with affective disorder and normal controls. iv) in a post-mortem study (Crow et al., 1989, Archives of General Psychiatry, 46:1145 - 1150) lateral ventricular enlargement was again found to be greatest in the temporal horn. Temporal horn enlargement in patients with schizophrenia was selective to the left side whereas similar enlargement in patients with Alzheimer-type dementia was present on both sides (ANOVA p < 0.001). Histopathological examination (Bruton et al., 1990, Psychological Medicine, 20:285 -304) of these brains indicates that these changes are unrelated to the presence of gliosis such as might be expected if they were due to degeneration or exogenous insult. It seems likely that the changes in schizophrenia are at least in part developmental. They can be explained on the basis that in this disease there is an arrest of development of cerebral asymmetry that results in the temporal lobe on the left side being slightly smaller and the temporal horn slightly larger than would normally be the case.
Frontal and right-left differences in schizophrenic vs normal subjects: A magnetic resonance brain imaging (MRI) study M.K. DeMyer*,
W.E. DeMyer, H.C. Hendrie,
S. Babb, R. Smith, M. Edwards, J.M. Wright
Department of Psychiatry, Indiana University School of Medicine, Zndiauapolis, IN 46202, U.S.A.
Most investigators using computerized tomography (CT) and magnetic resonance imaging (MRI) techniques have found that schizophrenic patients (Sch) have enlarged ventricles in comparison to age and sex matched normal controls (Nr). Because MRI allows a better differentiation of brain structures, the search has com-