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Biomedical subjects

R E Gur

Publications and source records attributed to R E Gur.

At least 19 recordsLinked to original sources
PubMed1996

Assessing declarative memory in schizophrenia using Wisconsin Card Sorting Test stimuli: the Paired Associate Recognition Test.

The Paired Associate Recognition Test (PART) was developed to measure declarative memory using Wisconsin Card Sorting Test (WCST) stimuli, so that both tasks could be administered during functional neuroimaging to differentiate memory and executive function, and associated frontal and temporal lobe activation in schizophrenia. The current study was designed to compare PART and WCST performance in schizophrenic patients and to examine effects of medication and symptomatology. The PART, WCST, and standard declarative memory tasks were administered to 30 chronic schizophrenic patients and 30 matched healthy control subjects. Supporting task validity was the finding that patients were equally impaired on the PART and the WCST. Neuroleptics did not appear to affect performance. The effect of anticholinergic medication correlated negatively with WCST performance in a small subsample. Severity of schizophrenia-specific symptoms measured at intake on the Brief Psychiatric Rating Scale correlated negatively with performance on the WCST. These results support the application of the PART and WCST in future functional neuroimaging studies.

Adult↗
PubMed1996

Glial fibrillary acidic protein-immunoreactive astrocytosis in elderly patients with schizophrenia and dementia.

Clinical and neuropsychological studies of chronically institutionalized patients with schizophrenia indicate that severe cognitive impairment and functional disability in late life are very prevalent. The biological substrates for this dementia remain unknown. While subtle cytoarchitectural and morphometric abnormalities have been described in patients with schizophrenia and interpreted as reflecting aberrant neurodevelopment, postmaturational injury or neurodegeneration associated with gliosis remain as plausible explanations of at least some of the clinical manifestations of schizophrenia. We monitored astrocytosis and neurofibrillary tangle (NFT) formation in 21 elderly patients with schizophrenia (14 with concurrent dementia, 7 without), and in 12 normal and 5 Alzheimer's disease (AD) control cases. Astrocytes in ventromedial temporal, frontal, and calcarine cortices were immunohistochemically identified with monoclonal antibodies directed at glial fibrillary acidic protein (GFAP) and vimentin, and NFTs were labeled with an anti-tau antibody specific for paired helical filaments. There were no increases in GFAP- or vimentin-immunoreactive astrocyte counts, GFAP optical density, or NFT counts for the schizophrenic group as a whole compared to the non-neuropsychiatric group, while both groups differed from AD. When patients with schizophrenia were divided into demented and non-demented subtypes, those with dementia demonstrated significantly greater numbers of GFAP-positive astrocytes than those without dementia. These data may reflect an up-regulation of GFAP in normal astrocytes or the presence of reactive astrocytosis in a subgroup of schizophrenics. In the absence of any diagnostic neuropathological findings in this subgroup, the implications of these observations for the pathogenesis of schizophrenia remain to be determined.

Aged↗
PubMed1996

Schizophrenia throughout life: sex differences in severity and profile of symptoms.

BACKGROUND: The impact of aging and of gender has been examined in health and disease, but has received limited attention in schizophrenia. A lifespan perspective of gender differences can contribute to an understanding of clinical features and their underlying neurobiological processes. METHOD: A prospective sample of 272 patients with schizophrenia, divided into four age groups: < 35, 35-65, 65-80 and > 85, was assessed with standardized procedures to measure the composition and severity of symptoms. RESULTS: Aging was associated with increased severity of symptoms and gender differences were noted. Negative symptoms increased in severity, while some positive symptoms ameliorated with aging. Women were characterized by reduced negative symptoms, and this remained evident until the eighth decade. CONCLUSIONS: Aging and gender moderate the clinical features of schizophrenia in specific symptom clusters. These effects may give insight into neurobiological substrates of the illness.

Adult↗
PubMed1996

Cerebral blood flow changes in limbic regions induced by unsolvable anagram tasks.

OBJECTIVE: The study addressed the question of whether unsolvable as opposed to solvable cognitive problems activate discrete neuronal systems in the human brain. METHOD: Twelve healthy humans tried to solve unsolvable anagrams. Solvable anagrams and a resting baseline after each anagram task served as control conditions in a within-subject design. Activation was measured with the equilibrium infusion method by using 15O-labeled water and positron emission tomography, with absolute quantitation of anatomically defined regional cerebral blood flow (CBF). RESULTS: Compared to rest, both anagram tasks increased activity in frontal and temporal regions. The soluble task condition increased hippocampal activation and decreased mammillary bodies activity, while unsolvable anagrams were associated with increased CBF to the mamillary bodies and amygdala and decreased hippocampal activity. CONCLUSIONS: A limbic network integrating negative emotion and cognition seems reflected in reciprocal diencephalic and limbic activation with solvable and unsolvable anagrams. Since unsolvable anagrams have been used to induce learned helplessness in humans, this finding may provide an initial step toward clarifying its neural substrate.

Adult↗
PubMed1996

Course of treatment response in first-episode and chronic schizophrenia.

OBJECTIVE: The timing and clinical correlates of symptom change following antipsychotic treatment were examined in first-episode and chronic schizophrenia. METHOD: The subjects were 36 first-episode schizophrenic patients who had received minimal or no neuroleptics and 34 patients with chronic illness whose neuroleptics had been withdrawn. They were followed for 2 years and assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. Treatment decisions during follow-up were made clinically by the treating physicians. RESULTS: At 6-month follow-up, both the neuroleptic-naive and previously treated patients showed significant improvement in positive symptoms (52% and 44% reductions from baseline, respectively). The previously treated but not the neuroleptic-naive patients also showed a significant reduction in negative symptoms (19% from baseline). A longer duration of illness before baseline assessment and inconsistent treatment during follow-up were independently associated with poorer treatment outcome in terms of positive symptoms in both groups. There were no significant changes on the outcome measures in either group after the 6-month follow-up. CONCLUSIONS: The results suggest that maximum symptomatic improvement occurs within the first 6 months of treatment and that disease progression may blunt treatment efficacy in both first-episode and chronic schizophrenia.

Adult↗
PubMed1996

Sex differences in neuroanatomical and clinical correlations in schizophrenia.

OBJECTIVE: The purpose of this study was to investigate sex differences in relationships between brain and behavior in schizophrenia. METHOD: Frontal lobe, temporal lobe, and whole brain volumes were obtained from magnetic resonance images of 91 patients with schizophrenia (54 men and 37 women) and 114 healthy comparison subjects (62 men and 52 women). Four independent symptom scales, based on the following symptom clusters, were derived from clinical data: negative, disorganization, Schneiderian hallucinations-delusions, and suspicion-hostility. Regression analyses incorporating the four clinical scales and neuroanatomical volumes were performed to investigate possible interactions between brain region and sex. RESULTS: Significant interactive effects of sex and frontal lobe volume were found in regression analyses of the disorganization and suspicion-hostility symptom scales. In men, higher frontal lobe volume was associated with milder severity of disorganization but was not correlated with severity of suspicion-hostility. In women, higher frontal lobe volume was associated with more severe disorganization as well as more severe suspicion-hostility. No associations were found between brain volume and severity of negative or Schneiderian symptoms. CONCLUSIONS: Differences between male and female patients were observed in the relationships between frontal lobe volume and two of the four clinical dimensions examined. These findings suggest that aspects of the neuropathological basis for some symptoms of schizophrenia may be sexually dimorphic.

Adolescent↗
PubMed1995

Mood effects on limbic blood flow correlate with emotional self-rating: a PET study with oxygen-15 labeled water.

Positron emission tomography was used to study the effects of experimentally controlled mood states on cerebral blood flow (CBF), measured with the quantitative equilibrium infusion method and 15O-labeled water. Twenty-seven brain regions in each hemisphere were assessed in 16 normal subjects. CBF and heart rate were measured during happy and sad mood induction, and during two nonemotional control conditions: sex differentiation and resting baseline. Valence-specific effects of mood on CBF were obtained for subcortical, but not for frontal-temporal or control regions. CBF increased in left amygdala and decreased in right amygdala during sad mood relative to the averaged control conditions. These changes correlated with shifts toward negative affect. Correlations were opposite for subcortical (negative affect associated with lower left hemispheric CBF) compared with frontal-temporal cortical regions. Results support limbic involvement in regulating emotional states and suggest some reciprocity between subcortical and frontal-temporal regulation of emotional experience.

Adolescent↗
PubMed1995

Sex differences in regional cerebral glucose metabolism during a resting state.

Positron emission tomography was used to evaluate the regional distribution of cerebral glucose metabolism in 61 healthy adults at rest. Although the profile of metabolic activity was similar for men and women, some sex differences and hemispheric asymmetries were detectable. Men had relatively higher metabolism than women in temporal-limbic regions and cerebellum and relatively lower metabolism in cingulate regions. In both sexes, metabolism was relatively higher in left association cortices and the cingulate region and in right ventro-temporal limbic regions and their projections. These results are consistent with the hypothesis that differences in cognitive and emotional processing have biological substrates.

Adult↗
PubMed1995

Resting cerebral glucose metabolism in first-episode and previously treated patients with schizophrenia relates to clinical features.

BACKGROUND: Functional neuroimaging can elucidate brain dysfunction in schizophrenia. The frontal, temporolimbic, and diencephalic regions have been implicated. There is a lack of prospective samples of first-episode and previously treated patients followed up longitudinally. METHODS: Patients and controls (42 per group) were studied. Positron emission tomography with flurodeoxyglucose, cross-registered with magnetic resonance imaging, measured metabolism. Scales assessed clinical features, premorbid adjustment, and outcome. RESULTS: There were no differences between groups in whole-brain metabolism or regional ratios or in anterior-posterior gradients, but left midtemporal metabolism was relatively higher in patients. This was pronounced in the negative and Schneiderian and absent in the paranoid subtypes. Higher metabolism and lower relative left hemispheric values were associated with better premorbid adjustment and outcome. A higher subcortical-cortical gradient was noted in first-episode patients. CONCLUSIONS: There are no resting metabolic abnormalities in any brain region, but abnormal gradients are evident. These vary in subtypes, and laterality is associated with functioning. The results support the hypothesis of temporolimbic disturbance in schizophrenia that is all ready present at the onset of illness.

Adult↗
PubMed1995

Frontal and temporal lobe brain volumes in schizophrenia. Relationship to symptoms and clinical subtype.

BACKGROUND: Quantitative magnetic resonance imaging (MRI) studies demonstrate reduced brain volumes in schizophrenics, but specific structural abnormalities have not been clearly delineated. The structural abnormalities of this disorder are likely to be heterogeneous, consistent with its diverse clinical presentation. To investigate the relationship between structural abnormality and clinical symptoms, we examined regional brain and cerebral spinal fluid (CSF) volumes in a large sample of schizophrenic patients and controls, with patients aggregated into clinical subtypes. METHODS: Right and left hemisphere frontal and temporal lobe brain and CSF volumes were quantified from 5-mm axial spin-echo MRIs for 71 schizophrenic patients and 77 age- and sex-matched controls. The following four standardized rating scales were used to assess symptom severity: Negative Symptoms, Disorganization, Schneiderian Delusions and Hallucinations, and Suspicion-Hostility. Patients were also subtyped as either deficit or nondeficit on the basis of enduring negative symptoms. RESULTS: Schizophrenic patients overall exhibited abnormal brain asymmetry, with selective decrease in brain volume in the left temporal and right frontal regions. Left temporal lobe parenchymal volume reduction and CSF volume increase were correlated with the severity of negative symptoms. Consistent with this, the subtype analysis revealed abnormal temporal lobe asymmetry for the deficit subgroup only. Right frontal lobe volume reduction correlated with the duration of illness, independent of symptom severity or schizophrenic subtype. CONCLUSIONS: Abnormal lateral asymmetry suggests selective structural deficits in schizophrenia, rather than diffusely undifferentiated CNS abnormalities. The pattern of regional abnormalities is related to clinical symptoms, with negative symptoms being associated with left temporal lobe rather than frontal lobe abnormality. This is consistent with suggestions of a temporolimbic prefrontal network abnormality in schizophrenia. Further longitudinal studies are warranted, using higher-resolution MRI technology and gray matter-white matter segmentation to confirm and extend these findings.

Adolescent↗
PubMed1995

Emotional processing in schizophrenia: neurobehavioral probes in relation to psychopathology.

The application of neurobehavioral methods in functional neuroimaging can provide useful information on the neurobiology of schizophrenia. This process can be enhanced by using a standard set of procedures to construct 'neurobehavioral probes' which are suitable for functional imaging and provide reliable measures discriminating patients from healthy controls. While such probes are available for cognitive tasks, none has been applied to study emotional processing in schizophrenia. We examined emotional discrimination and experience probes and correlated performance with cognitive and clinical measures. Emotion discrimination tasks and mood induction procedures with happy, sad, and neutral facial expressions were administered to 40 patients with schizophrenia. Neuropsychological testing assessed intellectual, attention, abstraction-flexibility, memory, language, spatial, and sensory-motor functions. Emotional performance was compared to a group of 40 normal subjects. Performance for face discrimination was impaired in patients. There was specific impairment in discrimination of happy expressions. Mood induction was effective in both groups, but diminished in patients, especially for happiness. Poorer performance in emotion discrimination correlated with severity of negative symptoms and bizarre behavior. Hallucinations were associated with more pronounced mood induction effects. Emotion discrimination was also correlated with abstraction, memory, language and spatial tasks, while mood induction effects showed no such associations. Thus, the impairment in discriminating and experiencing valence-specific emotions in schizophrenia relates to symptomatology and neuropsychological functioning. The results encourage the use of the emotion discrimination task and the mood induction procedure as neurobehavioral probes in physiologic neuroimaging studies for investigating the neural substrates of emotion.

Adult↗
PubMed1995

Prospective clinicopathologic studies of schizophrenia: accrual and assessment of patients.

OBJECTIVE: The purpose of this study was to characterize the neuropsychiatric profile of elderly patients with schizophrenia and establish a patient registry for prospective ante-mortem and post-mortem studies. METHOD: Medical records of all chronically institutionalized patients in eight state hospitals who were over the age of 65 and had a chart diagnosis of schizophrenia (N = 528) were reviewed. Of the potential subjects, 192 were excluded because of clinical histories inconsistent with a diagnosis of schizophrenia, 56 because of insufficient information to establish a psychiatric diagnosis, and 122 because of family members' refusal to give consent for autopsy in the event of death. To date, 81 of the remaining 158 patients have undergone neuropsychiatric evaluation with standard assessment instruments. RESULTS: Mini-Mental State scores of the 81 patients indicated severe dementia, and Functional Assessment Scale scores showed that patients required assistance with activities of daily living. All patients were rated as severely ill on the Brief Psychiatric Rating Scale. Ratings on the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms indicated a predominance of negative symptoms over positive. Of 30 patients who have died to date, research autopsies have been conducted on 26. CONCLUSIONS: Establishing a well characterized, prospective patient registry for clinicopathologic studies of schizophrenia is feasible but labor intensive. Diagnosis of schizophrenia with a high degree of confidence can be achieved by means of detailed chart review and assessment of current neuropsychiatric functioning with standard rating instruments. These data provide a basis for correlations of clinicopathologic factors.

Activities of Daily Living↗
PubMed1995

Smaller neuron size in schizophrenia in hippocampal subfields that mediate cortical-hippocampal interactions.

OBJECTIVE: The goal of this study was to characterize the hippocampal formation in patients with schizophrenia by measuring neuron density, neuron size, and variability of neuronal axis orientation. METHOD: Brain tissue was obtained at autopsy from 14 prospectively accrued elderly patients with chronic schizophrenia and 10 age-compatible individuals without psychiatric disorder. Eight hippocampal regions of interest and two internal control regions (primary motor and visual cortices) were identified on Nissl-stained sections. Morphometric measurements were made without knowledge of diagnosis by means of a computer-based image analysis system. RESULTS: The patients exhibited smaller neuron size in the hippocampal regions relative to the control regions, which was significant only for the subiculum, CA1, and layer II of the entorhinal cortex. Neuron size in the control regions was nearly identical in the two groups. No significant differences in neuron density or in variability of neuronal axis orientation were identified for any region. There was no correlation between neuron size in any area and several potentially confounding variables (age, post-mortem interval, neuroleptic exposure, sex, brain hemisphere studied, duration of illness), with the exception of a negative correlation with age in layer II of the entorhinal cortex. Regression analyses indicated that the findings could not be attributed to these age effects. CONCLUSIONS: The subiculum, entorhinal cortex, and CA1 are the major subfields of the hippocampal region that maintain the afferent and efferent connections of the hippocampus with widespread cortical and subcortical targets. The smaller size of neurons in these subfields may reflect the presence of structural or functional impairments that disrupt these connections, which in turn could have important behavioral sequelae.

Age Factors↗
PubMed1995

Regional cerebral function determined by FDG-PET in healthy volunteers: normal patterns and changes with age.

UNLABELLED: The main objective of this study was to determine patterns of regional brain metabolic activity utilizing high-resolution PET in normal healthy volunteers and variations in different age groups. METHODS: High-resolution [18F]FDG PET images of the entire brain were obtained in 120 healthy normal volunteers (64 men, 56 women), age range from 19 to 79 yr. Each anatomic region was assessed using a qualitative rating scale with a score ranging from 1 to 6 (1 = definitely normal and 6 = definitely abnormal). Local metabolic activity was also estimated as showing increased (+) or decreased (-) compared to normal (0) states. RESULTS: The most consistent finding in normal aging was decreased cortical metabolism, particularly in the frontal lobes. Temporal, parietal and occipital lobe metabolism varied considerably among subjects within the same age group as well as over decades. Basal ganglia, hippocampal area, thalami, cerebellum, posterior cingulate gyrus and visual cortex remained metabolically unchanged with advancing age. CONCLUSION: These data indicate that qualitative interpretation of FDG-PET images allows accurate assessment of regional metabolic activity of the brain in normal subjects similar to those described with quantitative techniques. Adequate knowledge of normal variations and changes related to normal aging is necessary for optimal assessment of pathologic states.

Adult↗
PubMed1994

Cerebral blood flow in schizophrenia: effects of memory processing on regional activation.

Regional cerebral blood flow (rCBF) was measured with the 133Xenon clearance technique and a high resolution (254 detectors) scanner during the performance of a verbal and a facial memory task in 18 patients with schizophrenia and 18 sociodemographically matched controls. Patients and controls had comparable resting rCBF, but differed in global and hemispheric rCBF changes induced by the memory tasks. Patients had less global increase, which was relatively higher in the left hemisphere, and this was more pronounced for the verbal task. Although controls showed appropriate laterality changes (L > R for verbal and R > L for facial memory) in the midtemporal region, patients failed to show such a focal pattern. They did not show appropriate laterality change in the midtemporal region, but instead showed such changes in other regions. Patients showed greatest impairment in specificity of verbal recognition performance, and this correlated with severity of hallucinations and delusions. This supports a model of left temporal lobe dysfunction in schizophrenia.

Adult↗
PubMed1994

Neuropsychological deficits in neuroleptic naive patients with first-episode schizophrenia.

BACKGROUND: Medication and chronicity have complicated past attempts to characterize the neuropsychological performance of patients with schizophrenia. There have been inconsistencies regarding the pattern, selectivity, and sources of observed deficits. Our objective was to comprehensively examine neuropsychological function in patients with schizophrenia who had never been exposed to neuroleptic medication, and who were experiencing their first episode (FE) of psychosis. METHODS: Subjects were consecutive recruitments that included 37 patients with FE schizophrenia who were never exposed to neuroleptics. These subjects were compared with 65 unmedicated, previously treated (PT) patients and 131 healthy controls. RESULTS: The patients groups had nearly identical profiles showing generalized impairment, particularly in verbal memory and learning, attention-vigilance, and speeded visual-motor processing and attention. Verbal memory and learning accounted for most of the variance between patients and controls and removing this effect substantially attenuated all other differences. By contrast, both the FE group and PT group continued to show highly significant deficits in verbal memory and learning after controlling for attention, abstraction, and all other functions. Some functions not typically implicated in schizophrenia (spatial cognition, fine motor speed, and visual memory) were more impaired in the PT group than in the FE group. CONCLUSIONS: Verbal memory, as a primary neuropsychological deficit present early in the course of schizophrenia, implicates the left temporal-hippocampal system. Neuropsychological evaluations before treatment permit differentiation of primary deficits from changes secondary to medication or chronicity. This is essential for developing a neurobehavioral perspective on schizophrenia.

Adult↗
PubMed1994

Neuropsychological functioning in siblings discordant for schizophrenia and healthy volunteers.

OBJECTIVE: To determine whether schizophrenics and their nonschizophrenic siblings have a similar pattern of neuropsychological deficit when compared with normal controls. DESIGN AND PARTICIPANTS: Fifteen probands with schizophrenia, 16 of their nonschizophrenic siblings, and 31 unrelated, demographically balanced, normal individuals underwent evaluation with a comprehensive neuropsychological test battery. All subjects were screened for history of head injury, neurologic illness, major medical conditions, substance use, and axis I psychiatric disorders other than schizophrenia. Probands underwent evaluation twice: once at intake when half had never received neuroleptic medication and the other half had received none for a minimum of 2 weeks, and again at the 2- to 4-week follow-up, after stabilization with neuroleptic medications. RESULTS: Both schizophrenics and their nonschizophrenic siblings were impaired neuropsychologically compared with normal controls, with the nonschizophrenic siblings' performance intermediate between that of the schizophrenic siblings and the normal controls on all measures of functioning. The shapes of the deficit profiles of schizophrenic patients and their siblings were similar; in patients, verbal memory, abstraction, attention, and language functions were significantly more affected compared with spatial abilities, spatial memory, and sensory-motor functions, with a nonsignificant trend in the same direction in siblings. Cognitive functioning in patients was found to be stable across changes in medication status and clinical state. Four fifths of patients obtained more deviant scores than their nonschizophrenic siblings. Among the sibling group, those with probable and certain diagnoses of schizotypal personality disorder were more impaired compared with those without schizophrenia-spectrum symptoms. CONCLUSION: These results support the hypothesis that impaired information processing aggregates in the family members of schizophrenics and may serve as an indicator of genetic vulnerability to the disorder. Further work is needed to establish whether particular areas of functioning are selectively impaired in relatives and to determine whether the performance deficits are mediated by structural and/or metabolic disturbances in specific brain regions.

Adult↗