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Activation in the frontal-temporal cortex in a word fluency task vs. a mental arithmetic task: a schizoprenia project
Abstracts / P~chiatr), ' Research: Ne,lroimaging 68 (1997) 155-184 subgroup of the children sufler from retardation and minor behavioral abnormalities, and some symptoms continue into early childhood. It is not known whether ISHs predispose to psychiatric disorders in adult life, because no catamnestic studies exist up to now. Several synonyms for ISH exist. Differentiation between 1SH and benign enlargement of the subarachnoid spaces (BESS) earlier was seldom done. The conditions can now easily be differentiated by MR1. In ISH minor head injuries are frequently reported and neurosurgery is recommended. The pericerebral collections (ISH and BESS) are typically bifrontal. At a psychotherapy ward we observed in recent years several cases suffering from personality disorders (including an atypical case of anorexia nervosa with 'nervous" symptoms in infancy) with a bifrontal widening of subarachnoid spaces resembling the shape seen in ISH or BESS. Infancy of our cases was in the pre-computer tomography era and no definite results can be given. We suggest that 1SH or BESS could be a risk factor for later psychiatric disorders and propose to perform catamnestic studies. Implication of functional imaging studies of neurotransmitter interactions in the living brain J.D. Brodie, S.L. Dewey, P. Simkowitz, G. Smith, R. Schloesser, A.P. Wolf Department of Psvchiat~, Nee" York UniversiO, Medical Center, USA and Chemist O, Department, Brookhaven Nat. Lab., USA
A fundamental tenet in chemical kinetics is that the rate of change in the concentration of a product of a biochemical system reflects activity of that system. This approach to assessing brain activity has a rich, if controversial role in psychiatry, c.g. prolactin, HVA, dexamcthasone suppression, behavioral change. Similarly, the notion of quantitating a difficult to measurc biochemical transformation by linking the reaction in vitro to a series of functionally linked enzymes to yield an easily measurable change in product concentration has a long tradition in biochemistry. Joining these constructs enables the detection of receptor activity with PET in the living human and non-human primate brain that can be visualized by measuring change,; in ligand binding at a synapse which is functionally coupled to the receptor of interest. Results will be presented from a series of PET and SPECT studies showing that ncurochemical plasticity and ncurotransmittcr variability arc normal components of the homeostatic state. Evidence from primate studies will bc presented which shows that perturbations of every major ncurotransmitter system we have examined to datc (dopammcrgic, cholincrgic, serotonergic, GABAcrgic, opiate) have propagated effects which can be mcasurcd by changes in binding of reccptor ligands to other. functionally linked neurotransmitter systems. Our data support two major points: (I) Responsivity of a system to challenge varies remarkably among normal subjects and may bc highly dependent on the state (tone) of the system at that time. (2) Chronic trealment of non-human primates with antipsychotic agents has effccts which go far beyond changes in dopaminergic activity. These data support our hypothesis that neurochemical plasticity is necessary for the normal state
157
and its maintenance is the target of therapeutic intervention in all neuropsychiatric disorders. If this is true, it suggests that longitudinal studies of neurotransmitter activity are greatly needed. Metabolic changes with age in schizophrenia M.S. Buchsbaum. E. Hazlett, L. Shihabuddin, T. Wet, M. Haznedar, D. Schnur, J. Machac, S. Vallabhajosula, K. Knesaurek, R.C. Mohs, K. Davis Department of Psvchiat~_ , Mount Sinai School of Medicine, New York. USA
A new analytic technique for visualizing correlations between metabolic rate and age in all brain areas has been applied in 62 normal subjects and 18 unmedicated patients with schizophrenia. Schizophrenic subjects (n = 18, 12 males, six females) were recruited from Mount Sinai Hospital and affiliates (mean age 38.5 years, range 18-65). All patients were assessed using the CASH (Comprehensive Assessment of Symptoms and History) structured interview, and diagnoses were assigned according to DSM IV criteria. Sixty-two healthy adults (mean age 48.6, S.D. 20.6, range 21-87) served as a comparison aging sample. PET scans were obtained with our GE 2048 head scanner with measured resolution of 4.5 mm in plane and 5.0 mm axially. We obtained 30 slices at 5 mm intervals in wobbled mode. MRI acquisition for image coregistration and morphometry used the GE Sigma 5x system with TR 24, TE 5, flip angle 40 °, for 1.2 mm thick slices. Images were coregistered following standard surface matching methods. The mean outline and nine midline landmark coordinates were computed and both PET and MRI images reformed to these standard coordinates. Correlations between age and metabolic rate for each pixel imaged. A computer simulation was used to assess statistical significance of observed areas of correlation. We observed a pattern of reduced frontal metabolism with age in norma[s. Patients with schizophrenia showed significantly reduced frontal metabolism when young and minimal change with age. This pattern is consistent with a neurodevelopmental process and is similar to the age patterns seen with ventricular enlargement when aging patterns arc comparcd in normal and patient populations. Activation in the frontal-temporal cortex in a word fluency task vs. a mental arithmetic ia~.k: a schizophrenia project A. Chen Rheumatic Diseases Centre, UniverxiO' of Manchester, UK
Schizophrenia patients of paranoia type (n = 15), cohorts (n = 15) and healthy controls (n = 15) are assessed with the PANSS (Positive and Negative Syndromes of Schizophrenia) befl~re E E G / E R P studies. EEG were recorded at pre- and post-baselines, as well as during the neuropsychological tests: listening to a short story, adjusting a geometric figure, performing mental arithmatics and the Word Fluency Test (50 letters according to the FAS test) to examine the language and memory processing in the brain of schizophrenia. The
158
Abstracts / PsychiatryResearch:Neurohnaging68 (1997) 155-184
initiation of speech (thinking and motor execution) in the brain is analyzed by ERP of the speech onset. Pilot results in the controls showed the first pre-frontal activation at - 8 5 0 ms, with a focal temporal activation at - 8 0 0 ms, reflecting cortical initiation of memory process. Immediately prior to speech onset, a parallel frontal SMA activation and temporal lobe activation followed by similar parallel activations immediately after speech onset were shown, reflecting execution of word fluency activation. Renewed pre-frontal activation at 420 ms was observed, which may reflect further thinking for the next new word fluency task. The results in the controls demonstrated a pre-frontal, temporal, and SMA network in memory, thinking, and motor execution during the word fluency task. Schizophrenia is hypothesized as a disruption in the links of this neural network. Loss of cerebral asymmetry as the key to the aetiology of schizophrenia T. Crow
University Depamnent of Psychiat~, WarnefordHospital, Oxford, UK The onset of psychotic illness, with constant incidence across populations, in the reproductive phase of life with a decrease in fecundity requires an evolutionary explanation: What is the survival value of the predisposing gene or genes? In morphological studies 3 findings - - (1) ventricular enlargement, (2) a decrease in cortical mass, and (3) loss of asymmetry - - each appear to apply to the group of patients with schizophrenia as a whole. The findings must be related - - schizophrenia is a disorder of brain size and shape. In developmental studies there is evidence that deficits in language and reading ability, and a failure of lateralisation for hand-skill precede the onset of psychosis by at least 15 years. It will be argued that schizophrenia represent a component of the variation generated in the evolution of language: the function that accounts for the great increase in brain size in homo sapiens. Thalamic pathology in schizophrenia - - a morphometric and immunocytochemical post-mortem study P. Danos, B. Baumann, P. Falkai, H. Henning, T. Schneider, B. Bogerts
Depa~rnent of Psychiatry, University of Magdeburg, Germany We determined quantitatively the volume of the thalamus in post-mortem brains of 26 schizophrenics who met DSM-III-R criteria (12 males, 14 females) and in 28 age- and sex-matched controls without neurological or psychiatric diseases (14 males, 14 females). The histological methods and volume measurements have been described previously. There was no significant difference ( P = 0.46) of brain weight in patients and controls. The volumes of the thalamus were significantly smaller (diff. = 8-18%; thalamus left/right: P = 0.004/0.016) in schizophrenics, both hemispheres being equally affected. There was no significant correlation between disease duration and thalamic volumes of both hemispheres (thalamus
left/right: r = 0.299,/0.021). We also investigated immunorcactivity for parvalbumin (PV) in the thalamus of schizophrenics and controls. Both in schizophrenics and controls parvalbumin-immunoreactivity showed a different distribution i~1 the thalamie nuclei. Numerous densely PV-positive cell bodies were found in the ventral lateral and ventral posterior nuclei and in the anterior thalamus nucleus. The mediodorsal nucleus contained a moderate number of parvalbumin palestained cell bodies. PV-positive cells in schizophrenics and controls were quantitatively estimated in the anterior nucleus. The results may be discussed in the framework of possible pathophysiological mechanisms of the thalamus in schizophrenia. Hippocampal atrophy: an early brain marker for Alzheimer's disease (AD) and a correlate of HPA axis dysfunction M.J. de Leon, S. De Santi, A. Convit, C. Tarshish. H. Rusinek, A.E. Georgc
Medical Center, New York University, USA Post-mortem studies have suggested that in AD, lesions in the hippocampus precede neocortical lesions and dementia. Recent MRI results are in agreement and expand these findings. Our cross-sectional results show that hippocampal formation atrophy (HA) diseriminates between normal elderly and nondemented elderly with memory impairments. Volumetric MRI data and PET-FDG data both show that after controlling for age, volume losses are specific to the hippocampus in the memory impaired but include the lateral temporal lobe in patients with dementia. The longitudinal data show that baseline HA is predictive of dementia within 4 years. Little evidence exists for a relationship between HPA axis functioning and HA in AD. We observed that the hypercortisolemia in AD that followed a glucose challenge was associated with HA. Moreover, the infusion of hydrocortisone (cortisol) had a differential effect on hippocampal glucose metabolism bctwccn elderly controls and AD. These results contribute to a hypothesized early endocrine-hippocampus pathology in AD. First experiences with positron emission tomography changes of the carbohydrate metabolism in the brain of dementia patients 1. DegrelP, A. Egerhazi a, T. Glaub a, L. Tron b, J. Kollar ~, J. Sikula ~', E. Ambrus c, L. Balkay b, M. Emri b, Z. K6szegi :~
aDepartment of Psychiatry, University. of Debrecen, Htmgao,. blnstitute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen, Hungary. CHospitalof Gyula Kene=y,Debreten, Hungary Of the current available functional imaging techniques PET is the most informative because of its accurate quantification of cerebral metabolism. We report our first experiences in PET investigations of 24 dementia patients versus seven healthy volunteers. A detailed routine clinical and laboratory examination was performed on the patients including Cq" scan, MMSE, and Luria-Nebraska Neuropsychological Test Battery.
A fundamental tenet in chemical kinetics is that the rate of change in the concentration of a product of a biochemical system reflects activity of that system. This approach to assessing brain activity has a rich, if controversial role in psychiatry, c.g. prolactin, HVA, dexamcthasone suppression, behavioral change. Similarly, the notion of quantitating a difficult to measurc biochemical transformation by linking the reaction in vitro to a series of functionally linked enzymes to yield an easily measurable change in product concentration has a long tradition in biochemistry. Joining these constructs enables the detection of receptor activity with PET in the living human and non-human primate brain that can be visualized by measuring change,; in ligand binding at a synapse which is functionally coupled to the receptor of interest. Results will be presented from a series of PET and SPECT studies showing that ncurochemical plasticity and ncurotransmittcr variability arc normal components of the homeostatic state. Evidence from primate studies will bc presented which shows that perturbations of every major ncurotransmitter system we have examined to datc (dopammcrgic, cholincrgic, serotonergic, GABAcrgic, opiate) have propagated effects which can be mcasurcd by changes in binding of reccptor ligands to other. functionally linked neurotransmitter systems. Our data support two major points: (I) Responsivity of a system to challenge varies remarkably among normal subjects and may bc highly dependent on the state (tone) of the system at that time. (2) Chronic trealment of non-human primates with antipsychotic agents has effccts which go far beyond changes in dopaminergic activity. These data support our hypothesis that neurochemical plasticity is necessary for the normal state
157
and its maintenance is the target of therapeutic intervention in all neuropsychiatric disorders. If this is true, it suggests that longitudinal studies of neurotransmitter activity are greatly needed. Metabolic changes with age in schizophrenia M.S. Buchsbaum. E. Hazlett, L. Shihabuddin, T. Wet, M. Haznedar, D. Schnur, J. Machac, S. Vallabhajosula, K. Knesaurek, R.C. Mohs, K. Davis Department of Psvchiat~_ , Mount Sinai School of Medicine, New York. USA
A new analytic technique for visualizing correlations between metabolic rate and age in all brain areas has been applied in 62 normal subjects and 18 unmedicated patients with schizophrenia. Schizophrenic subjects (n = 18, 12 males, six females) were recruited from Mount Sinai Hospital and affiliates (mean age 38.5 years, range 18-65). All patients were assessed using the CASH (Comprehensive Assessment of Symptoms and History) structured interview, and diagnoses were assigned according to DSM IV criteria. Sixty-two healthy adults (mean age 48.6, S.D. 20.6, range 21-87) served as a comparison aging sample. PET scans were obtained with our GE 2048 head scanner with measured resolution of 4.5 mm in plane and 5.0 mm axially. We obtained 30 slices at 5 mm intervals in wobbled mode. MRI acquisition for image coregistration and morphometry used the GE Sigma 5x system with TR 24, TE 5, flip angle 40 °, for 1.2 mm thick slices. Images were coregistered following standard surface matching methods. The mean outline and nine midline landmark coordinates were computed and both PET and MRI images reformed to these standard coordinates. Correlations between age and metabolic rate for each pixel imaged. A computer simulation was used to assess statistical significance of observed areas of correlation. We observed a pattern of reduced frontal metabolism with age in norma[s. Patients with schizophrenia showed significantly reduced frontal metabolism when young and minimal change with age. This pattern is consistent with a neurodevelopmental process and is similar to the age patterns seen with ventricular enlargement when aging patterns arc comparcd in normal and patient populations. Activation in the frontal-temporal cortex in a word fluency task vs. a mental arithmetic ia~.k: a schizophrenia project A. Chen Rheumatic Diseases Centre, UniverxiO' of Manchester, UK
Schizophrenia patients of paranoia type (n = 15), cohorts (n = 15) and healthy controls (n = 15) are assessed with the PANSS (Positive and Negative Syndromes of Schizophrenia) befl~re E E G / E R P studies. EEG were recorded at pre- and post-baselines, as well as during the neuropsychological tests: listening to a short story, adjusting a geometric figure, performing mental arithmatics and the Word Fluency Test (50 letters according to the FAS test) to examine the language and memory processing in the brain of schizophrenia. The
158
Abstracts / PsychiatryResearch:Neurohnaging68 (1997) 155-184
initiation of speech (thinking and motor execution) in the brain is analyzed by ERP of the speech onset. Pilot results in the controls showed the first pre-frontal activation at - 8 5 0 ms, with a focal temporal activation at - 8 0 0 ms, reflecting cortical initiation of memory process. Immediately prior to speech onset, a parallel frontal SMA activation and temporal lobe activation followed by similar parallel activations immediately after speech onset were shown, reflecting execution of word fluency activation. Renewed pre-frontal activation at 420 ms was observed, which may reflect further thinking for the next new word fluency task. The results in the controls demonstrated a pre-frontal, temporal, and SMA network in memory, thinking, and motor execution during the word fluency task. Schizophrenia is hypothesized as a disruption in the links of this neural network. Loss of cerebral asymmetry as the key to the aetiology of schizophrenia T. Crow
University Depamnent of Psychiat~, WarnefordHospital, Oxford, UK The onset of psychotic illness, with constant incidence across populations, in the reproductive phase of life with a decrease in fecundity requires an evolutionary explanation: What is the survival value of the predisposing gene or genes? In morphological studies 3 findings - - (1) ventricular enlargement, (2) a decrease in cortical mass, and (3) loss of asymmetry - - each appear to apply to the group of patients with schizophrenia as a whole. The findings must be related - - schizophrenia is a disorder of brain size and shape. In developmental studies there is evidence that deficits in language and reading ability, and a failure of lateralisation for hand-skill precede the onset of psychosis by at least 15 years. It will be argued that schizophrenia represent a component of the variation generated in the evolution of language: the function that accounts for the great increase in brain size in homo sapiens. Thalamic pathology in schizophrenia - - a morphometric and immunocytochemical post-mortem study P. Danos, B. Baumann, P. Falkai, H. Henning, T. Schneider, B. Bogerts
Depa~rnent of Psychiatry, University of Magdeburg, Germany We determined quantitatively the volume of the thalamus in post-mortem brains of 26 schizophrenics who met DSM-III-R criteria (12 males, 14 females) and in 28 age- and sex-matched controls without neurological or psychiatric diseases (14 males, 14 females). The histological methods and volume measurements have been described previously. There was no significant difference ( P = 0.46) of brain weight in patients and controls. The volumes of the thalamus were significantly smaller (diff. = 8-18%; thalamus left/right: P = 0.004/0.016) in schizophrenics, both hemispheres being equally affected. There was no significant correlation between disease duration and thalamic volumes of both hemispheres (thalamus
left/right: r = 0.299,/0.021). We also investigated immunorcactivity for parvalbumin (PV) in the thalamus of schizophrenics and controls. Both in schizophrenics and controls parvalbumin-immunoreactivity showed a different distribution i~1 the thalamie nuclei. Numerous densely PV-positive cell bodies were found in the ventral lateral and ventral posterior nuclei and in the anterior thalamus nucleus. The mediodorsal nucleus contained a moderate number of parvalbumin palestained cell bodies. PV-positive cells in schizophrenics and controls were quantitatively estimated in the anterior nucleus. The results may be discussed in the framework of possible pathophysiological mechanisms of the thalamus in schizophrenia. Hippocampal atrophy: an early brain marker for Alzheimer's disease (AD) and a correlate of HPA axis dysfunction M.J. de Leon, S. De Santi, A. Convit, C. Tarshish. H. Rusinek, A.E. Georgc
Medical Center, New York University, USA Post-mortem studies have suggested that in AD, lesions in the hippocampus precede neocortical lesions and dementia. Recent MRI results are in agreement and expand these findings. Our cross-sectional results show that hippocampal formation atrophy (HA) diseriminates between normal elderly and nondemented elderly with memory impairments. Volumetric MRI data and PET-FDG data both show that after controlling for age, volume losses are specific to the hippocampus in the memory impaired but include the lateral temporal lobe in patients with dementia. The longitudinal data show that baseline HA is predictive of dementia within 4 years. Little evidence exists for a relationship between HPA axis functioning and HA in AD. We observed that the hypercortisolemia in AD that followed a glucose challenge was associated with HA. Moreover, the infusion of hydrocortisone (cortisol) had a differential effect on hippocampal glucose metabolism bctwccn elderly controls and AD. These results contribute to a hypothesized early endocrine-hippocampus pathology in AD. First experiences with positron emission tomography changes of the carbohydrate metabolism in the brain of dementia patients 1. DegrelP, A. Egerhazi a, T. Glaub a, L. Tron b, J. Kollar ~, J. Sikula ~', E. Ambrus c, L. Balkay b, M. Emri b, Z. K6szegi :~
aDepartment of Psychiatry, University. of Debrecen, Htmgao,. blnstitute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen, Hungary. CHospitalof Gyula Kene=y,Debreten, Hungary Of the current available functional imaging techniques PET is the most informative because of its accurate quantification of cerebral metabolism. We report our first experiences in PET investigations of 24 dementia patients versus seven healthy volunteers. A detailed routine clinical and laboratory examination was performed on the patients including Cq" scan, MMSE, and Luria-Nebraska Neuropsychological Test Battery.