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Pet study of the dopamine neurotransmitter dependent tracer 6-18F-DOPA in schizophrenia
198
at a mean age of 40 years) which, in turn, predicted infant emotional hyposensitivity. Infant hyposensitivity, delivery complications, and third ventricle widening all predicted flattened affect in adulthood. This study provides support for the theory that at least some forms of schizophrenia are lifetime, longitudinal syndromes.
PET STUDY OF THE DOPAMINE NEUROTRANSMITTER DEPENDENT 6-‘XF-DOPA IN SCHIZOPHRENIA Ahmed Richard
M. Elkashef*, J. Wyatt
Neuropsychiatry
Doris
Branch,
NIMH,
Doudet,
TRACER
Robert
Washington,
M. Cohen,
DC 20032,
USA
Dysfunction of the dopamine system has been the most widely accepted hypothesis of schizophrenia. Support for this hypothesis has been derived from indirect evidence. 6-‘XF-DOPA, an analogue of L-DOPA when used with PET allows in vivo visualization of dopamine and its metabolites in the brain. We studied 6 normal controls (5 males and 1 female, mean age 28.17f8.3) and 4 schizophrenics (1 female and 3 males, mean age 38.7k8.3) using ‘“F-DOPA PET. All schizophrenics were on constant doses of neuroleptics for at least 3 months prior to scanning (one on fluphenazine, 16 mg/day and the other 3 on varying doses of clozapine). All subjects received 150 mg of Carbidopa The scan lasted for 120 60 min before lXF-DOPA injection. min. Over the second hour the subjects received a continuous infusion of unlabelled large neutral amino acids solution (Travasol 5% 40 mg/kg). lXF-DOPA metabolites were analysed. ROIs were placed on multiple cortical and subcortical areas. A Patlak graphical analysis from 30-60 min yielded K (the rate constant for uptake of ‘XF-DOPA from blood to striatum). The ratios of specific to non-specific (occipital cortex) activity (RA) were obtained between 90-120 min. Unpaired t-tests comparing (RA) in schizophrenics vs. normal controls showed significant differences in the posterior putamen, the ventral tegmental/substantia nigra (VTA/SN), and the ventral striatum. K values showed a similar trend. Normals N=6 (meanfso)
Region
Schizophrenics (meanfso)
4.18kO.83 4.19w.73 2.56w.46
Post. Put. VentStr. VTA/SN
N=4
P value
0.04 0.048 0.004
5.3oti.43 5.1Ofl.28 3.57X1.26
P. FaIkai*,
Neurohistological
REDUCED
FRONTAL
ASYMMETRY SCHIZOPHRENIC AND
CLINICAL
ON
AND THE
OCCIPITAL
CT-SCANS
PATIENTS. SIGNIFICANCE
ITS
LOBE
OF SPECIFICITY
Th. Schneider,
Laboratory,
University of Diisseldorf, Diisseldorf
Department
Bergische
B. Greve of Psychiatry,
Lund~:m;fle 2, 4000
12, FRG
The CT-scans of 60% healthy right handed subjects show a relative increase of the right frontal and left occipital lobe in comparison to the contralateral side. This asymmetry seems to be disturbed in some brain disorders like dyslexia and autism. 9 out of 14 CT-scan studies found no disturbance of these laterality parameters in schizophrenia. One found inverse frontal and occipital inverse asymmetry and three detected inverse occipital asymmetry. One showed inverse occipital and reduced temporal asymmetry. On the level of the epiphysis of the CT scans of 135 schizophrenic patients (41 males and 94 females), 101 non-schizophrenic psychiatric controls (30 males and 71 females; including patients with major depression, personality disorder and schizoaffective psychosis) and 155 non-psychiatric control subjects (43 males and 112 females) the width of the frontal and occipital lobes were determined. The ratio between the left and right frontal and the left and right occipital width was calculated. The ratios were then correlated with the BPRS subscores for psychosis and anergia, drug response and psychopathological subgroup. Schizophrenics showed a numerically small but statistically significant reduction of frontal (6%, p<.OOOl) and occipital (3%, pc.03) lobe asymmetry compared to both control groups. There was no significant difference between the two control groups. There was no correlation between the ratios and the BPRS subscores or psychopathological subgroups, but a correlation between drug non-response and inverse cerebral asymmetry. In sum disturbed cerebral asymmetry is specific for schizophrenia in general and does not distinguish between subgroups of the disease.
SYMPTOM
DOMAINS
SUBSTRATES
MAGNETIC
OF
AND
NEURAL
SCHIZOPHRENIA:
RESONANCE
M.A. Flaum*, V.W. N.C. Andreasen Department
We will also present data on neuroleptic-free schizophrenics we have studied. This technique provides a very useful tool to examine the dopamine system in schizophrenia.
B. Bogetts,
Swayze,
of Psychiatry,
Drive, Iowa City, IA 52242,
A
IMAGING S. Gupta,
STUDY
D.S. O’Leary
and
Uni~~ersity of Iowa, 200 Hawkins USA
Introduction: The heterogeneity of symptoms in schizophrenia may reflect different underlying pathophysiology. Factor analytic studies have consistently identified three symptom factors, positive, negative and disorganized, as independent domains of psychopathology. This study examined the relationship of these three domains with volumes of specific brain regions. Methods: 165 schizophrenia spectrum patients were scanned with a 1.S Tesla MRI. Regions of interest (ROI’s) were
at a mean age of 40 years) which, in turn, predicted infant emotional hyposensitivity. Infant hyposensitivity, delivery complications, and third ventricle widening all predicted flattened affect in adulthood. This study provides support for the theory that at least some forms of schizophrenia are lifetime, longitudinal syndromes.
PET STUDY OF THE DOPAMINE NEUROTRANSMITTER DEPENDENT 6-‘XF-DOPA IN SCHIZOPHRENIA Ahmed Richard
M. Elkashef*, J. Wyatt
Neuropsychiatry
Doris
Branch,
NIMH,
Doudet,
TRACER
Robert
Washington,
M. Cohen,
DC 20032,
USA
Dysfunction of the dopamine system has been the most widely accepted hypothesis of schizophrenia. Support for this hypothesis has been derived from indirect evidence. 6-‘XF-DOPA, an analogue of L-DOPA when used with PET allows in vivo visualization of dopamine and its metabolites in the brain. We studied 6 normal controls (5 males and 1 female, mean age 28.17f8.3) and 4 schizophrenics (1 female and 3 males, mean age 38.7k8.3) using ‘“F-DOPA PET. All schizophrenics were on constant doses of neuroleptics for at least 3 months prior to scanning (one on fluphenazine, 16 mg/day and the other 3 on varying doses of clozapine). All subjects received 150 mg of Carbidopa The scan lasted for 120 60 min before lXF-DOPA injection. min. Over the second hour the subjects received a continuous infusion of unlabelled large neutral amino acids solution (Travasol 5% 40 mg/kg). lXF-DOPA metabolites were analysed. ROIs were placed on multiple cortical and subcortical areas. A Patlak graphical analysis from 30-60 min yielded K (the rate constant for uptake of ‘XF-DOPA from blood to striatum). The ratios of specific to non-specific (occipital cortex) activity (RA) were obtained between 90-120 min. Unpaired t-tests comparing (RA) in schizophrenics vs. normal controls showed significant differences in the posterior putamen, the ventral tegmental/substantia nigra (VTA/SN), and the ventral striatum. K values showed a similar trend. Normals N=6 (meanfso)
Region
Schizophrenics (meanfso)
4.18kO.83 4.19w.73 2.56w.46
Post. Put. VentStr. VTA/SN
N=4
P value
0.04 0.048 0.004
5.3oti.43 5.1Ofl.28 3.57X1.26
P. FaIkai*,
Neurohistological
REDUCED
FRONTAL
ASYMMETRY SCHIZOPHRENIC AND
CLINICAL
ON
AND THE
OCCIPITAL
CT-SCANS
PATIENTS. SIGNIFICANCE
ITS
LOBE
OF SPECIFICITY
Th. Schneider,
Laboratory,
University of Diisseldorf, Diisseldorf
Department
Bergische
B. Greve of Psychiatry,
Lund~:m;fle 2, 4000
12, FRG
The CT-scans of 60% healthy right handed subjects show a relative increase of the right frontal and left occipital lobe in comparison to the contralateral side. This asymmetry seems to be disturbed in some brain disorders like dyslexia and autism. 9 out of 14 CT-scan studies found no disturbance of these laterality parameters in schizophrenia. One found inverse frontal and occipital inverse asymmetry and three detected inverse occipital asymmetry. One showed inverse occipital and reduced temporal asymmetry. On the level of the epiphysis of the CT scans of 135 schizophrenic patients (41 males and 94 females), 101 non-schizophrenic psychiatric controls (30 males and 71 females; including patients with major depression, personality disorder and schizoaffective psychosis) and 155 non-psychiatric control subjects (43 males and 112 females) the width of the frontal and occipital lobes were determined. The ratio between the left and right frontal and the left and right occipital width was calculated. The ratios were then correlated with the BPRS subscores for psychosis and anergia, drug response and psychopathological subgroup. Schizophrenics showed a numerically small but statistically significant reduction of frontal (6%, p<.OOOl) and occipital (3%, pc.03) lobe asymmetry compared to both control groups. There was no significant difference between the two control groups. There was no correlation between the ratios and the BPRS subscores or psychopathological subgroups, but a correlation between drug non-response and inverse cerebral asymmetry. In sum disturbed cerebral asymmetry is specific for schizophrenia in general and does not distinguish between subgroups of the disease.
SYMPTOM
DOMAINS
SUBSTRATES
MAGNETIC
OF
AND
NEURAL
SCHIZOPHRENIA:
RESONANCE
M.A. Flaum*, V.W. N.C. Andreasen Department
We will also present data on neuroleptic-free schizophrenics we have studied. This technique provides a very useful tool to examine the dopamine system in schizophrenia.
B. Bogetts,
Swayze,
of Psychiatry,
Drive, Iowa City, IA 52242,
A
IMAGING S. Gupta,
STUDY
D.S. O’Leary
and
Uni~~ersity of Iowa, 200 Hawkins USA
Introduction: The heterogeneity of symptoms in schizophrenia may reflect different underlying pathophysiology. Factor analytic studies have consistently identified three symptom factors, positive, negative and disorganized, as independent domains of psychopathology. This study examined the relationship of these three domains with volumes of specific brain regions. Methods: 165 schizophrenia spectrum patients were scanned with a 1.S Tesla MRI. Regions of interest (ROI’s) were