Biomedical subjects

R E Gur

Publications and source records attributed to R E Gur.

At least 55 records · Page 3Linked to original sources

PubMed1998

P50 abnormalities in schizophrenia: relationship to clinical and neuropsychological indices of attention.

While the P50 component (50-60-ms latency) of the auditory evoked potential has been reported as abnormal in schizophrenia, few studies have examined the relationship between this abnormality and clinical or neuropsychological measures. To examine these possible relationships, mid-latency auditory evoked potentials were recorded at the CZ recording site of 47 patients with schizophrenia in response to binaural clicks presented at three stimulus rates: 1, 5 and 10/sec. A sub-sample of patients were then divided into high- (n = 15) and low-P50 abnormality (n = 16) groups based on a median split of the P50 amplitude at a rate of 10/sec (a greater amplitude at this rate suggests a greater abnormality in recovery) of the entire sample. Only those patients with complete neuropsychological and clinical data and who were reasonably matched on demographic dimensions were included. A multivariate analysis of variance of 11 neuropsychological function profile scores showed a significant group x global score interaction (Hotelling t = 3.97, p < 0.005). The high-abnormality group had relatively greater deficits for attention profile scores than for the remaining neuropsychological measures. An analysis of global subscores for SAPS and SANS clinical measures revealed a significant difference only for the SANS attention subscale (p < 0.05). The high-abnormality group was rated as more severe on the attention measure. These convergent findings across both phenomenological and neuropsychological measures suggest that abnormalities in P50 recovery may be linked to deficits in attention processes in schizophrenia.

Adult↗

PubMed1998

Leukocyte differentials predict short-term clinical outcome following antipsychotic treatment in schizophrenia.

BACKGROUND: The majority of patients with schizophrenia and many of their unaffected siblings exhibit a relative granulocytosis and lymphopenia. To characterize these abnormalities better, we examined leukocyte differentials and organ nonspecific autoantibodies in relationship to intake phenomenology and short-term clinical outcome. METHODS: We studied patients with schizophrenia (n = 81) and their siblings (n = 18). At intake assessment, about one-half of the probands (n = 38) were neurolepticnaive first-episode patients; the remainder were medication-free for at least 2 weeks. Hematologic indices were obtained at intake assessment, and psychiatric symptomatology was assessed at baseline and following 6 months of clinically determined treatment. RESULTS: A relative granulocytosis and lymphopenia prospectively predicted poorer recovery in positive, but not negative, symptoms after 6 months of antipsychotic treatment. Abnormal leukocyte proportions were specific to patients who presented with clinically significant positive symptomatology at intake. In contrast, clinically significant negative symptoms were only evident in a small subgroup of patients who were positive for antinuclear autoantibodies and/or rheumatoid factor. CONCLUSIONS: Future research should further test the hypothesis that a relative granulocytosis and lymphopenia reflect genetic loading for the pathophysiologic determinants of positive symptoms. Future research also should determine the etiologic significance of organ nonspecific autoimmunity in predominantly negative symptom schizophrenia.

Adult↗

PubMed1998

Depression in schizophrenia: I. Association with neuropsychological deficits.

BACKGROUND: The presence of depression in schizophrenia has been well described with regard to stage and symptoms of illness; however, little is known about the possible etiology. METHODS: In an effort to advance the understanding of the neurobiology of depression in schizophrenia, we grouped patients with schizophrenia based on their ratings on the 21-item Hamilton Depression Rating Scale. There were 63 patients (35 men, 28 women) in the high (> or = 18) depression group and 81 patients (52 men, 29 women) in the low (< 18) depression group. The groups were compared in demographic, clinical, and eight neuropsychological domains. RESULTS: The two groups differed in age at onset of illness, severity of delusions, and performance in a single neuropsychological domain: attention. The specific component of impaired attention was vigilance, with poorest performance seen in women with higher depression scores. CONCLUSION: The presence of specific attentional impairment associated with depressive symptoms in schizophrenia is consistent with the hypothesis of frontal lobe dysfunction in depression, because these regions have been implicated in attentional processes.

Adult↗

PubMed1998

Depression in schizophrenia: II. MRI and PET findings.

BACKGROUND: Despite consistent descriptions of depressive symptoms in schizophrenia, little is known about their neurobiology. The purpose of this study was to examine the association of depression in schizophrenia with measures of brain anatomy and metabolism. METHODS: Seventy-nine patients were grouped according to their ratings on the Hamilton Depression Rating Scale (HDRS): > or = 18 was the cutoff between the "high" and "low" depression groups. All patients underwent clinical and magnetic resonance imaging (MRI) evaluation, and a subsample of 37 underwent 2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) measurements of cerebral glucose metabolism. RESULTS: The high depression group had larger bilateral temporal lobe volumes and decreased laterality (left minus right of metabolism in the anterior cingulate). CONCLUSIONS: The neurobiology of depression in schizophrenia thus seems to share features with major depression due to other disease states.

Adult↗

PubMed1998

P300 subcomponent abnormalities in schizophrenia: I. Physiological evidence for gender and subtype specific differences in regional pathology.

BACKGROUND: P300 event-related brain potential (ERP) amplitude is reduced in patients with schizophrenia. Little attention has been paid to gender differences underlying this abnormality, despite clinical differences between male and female schizophrenics. Studies have also largely ignored the fact that the P300 represents the activity of multiple neural generators and have not assessed the separate activity of different subcomponents. METHODS: Auditory P300 ERPs were recorded from 65 patients (42 male, 23 female) and 48 controls (30 male, 18 female). Positive and negative symptoms were assessed with standardized rating scales, and patients were subtyped as deficit or nondeficit. Five P300 subcomponents were identified using current source density measures: frontal (P3f), bilateral parietal (P3pL, P3pR), and bilateral temporal (P3tL, P3tR). RESULTS: Three subcomponents (P3tL, P3f, P3pR) were reduced in patients. The left temporal (P3tL) deficit was common across patient groups, but the overall profile of P300 abnormalities varied by gender and deficit/nondeficit status. Women had greater P3tL and P3f decrements; P3pR was abnormal in men. Deficit and nondeficit patients resembled men and women, respectively, independent of gender. P3f and P3tL amplitudes were correlated and unrelated to symptomatology. P3pR was related to Brief Psychiatric Rating Scale score. CONCLUSIONS: A left temporal abnormality exists in schizophrenia, along with two different profiles of regional pathology, which segregate by gender and deficit/nondeficit status. This supports the hypothesis of two distinct illness subtypes and suggests a physiological basis for phenotypic gender and deficit/nondeficit differences. P300 subcomponent abnormalities may serve as subtype markers. Correlated left temporal and frontal dysfunction is consistent with a frontotemporal neural network disturbance in some schizophrenics. Further investigation of the longitudinal stability and familial inheritance of these subcomponent abnormalities is warranted.

Adult↗

PubMed1998

P300 subcomponent abnormalities in schizophrenia: II. Longitudinal stability and relationship to symptom change.

BACKGROUND: Reduced amplitude of the P300 event-related brain potential (ERP) is a robust finding in schizophrenia. It remains unclear whether this represents a state or trait abnormality. We previously reported reductions of specific subcomponents of the auditory oddball P300 that were independent of acute symptomatology and were differentially associated with gender and deficit/nondeficit subtype. To clarify the state vs. trait nature of these abnormalities, we reassessed a subset of these patients after a minimum interval of 1 year following initial study. METHODS: Auditory P300 ERPs were obtained from 18 patients at two time points and compared to baseline normative data recorded from 48 controls. Five P300 subcomponents were identified using current source density measures: frontal (P3f), bilateral parietal (P3pL, P3pR), and bilateral temporal (P3tL, P3tR). RESULTS: Patients exhibited reduced P300 amplitudes at baseline, including specific reductions of left temporal and right parietal subcomponents. There were no significant changes in P300 amplitudes over time, despite significant improvement in symptomatology, and the parietal subcomponent exhibited persistent impairment. There was, however, a trend toward normalization of the left temporal subcomponent that correlated with change in Brief Psychiatric Rating Scale. There was also a highly significant inverse relationship between changes in frontal P300 subcomponent amplitude and severity of auditory hallucinations (r = -.76). CONCLUSIONS: The findings support the overall longitudinal stability of P300 deficits in schizophrenia, though there is some state-dependent modulation of these deficits. The relationship between the frontal P300 and hallucinations is consistent with both the cognitive orienting function of this subcomponent and the role of the anterior cingulate as a hypothesized generator of this ERP activity.

Adolescent↗

PubMed1998

Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls.

BACKGROUND: Cortical gray matter volume reductions and cerebrospinal fluid (CSF) volume increases are robust correlates of schizophrenia, but their sources have not been established conclusively. METHODS: Structured diagnostic interviews and magnetic resonance imaging scans of the brain were obtained on 75 psychotic probands (63 with schizophrenia and 12 with schizoaffective disorder), ascertained so as to be representative of all such probands in a Helsinki, Finland, birth cohort; 60 of their nonpsychotic full siblings; and 56 demographically similar control subjects without a personal or family history of treated psychiatric morbidity. RESULTS: Patients with schizophrenia and their siblings exhibited significant reductions in cortical gray matter volume and significant increases in sulcal CSF volume compared with controls. The patients, but not their siblings, also exhibited significant reductions in white matter volume and significant increases in ventricular CSF volume. Regional effects were most robust when component volumes were expressed as percentages of overall regional volumes; in this case, for patient and sibling groups, gray matter volume reductions and sulcal CSF volume increases were significantly more pronounced in the frontal and temporal lobes than in the remainder of the brain. None of the group differences varied significantly by sex or hemisphere. CONCLUSIONS: Structural alterations of the cerebral cortex, particularly in the frontal and temporal lobes, are present in patients with schizophrenia and in some of their siblings without schizophrenia; such changes are thus likely to reflect genetic (or shared environmental) effects. Ventricular enlargement is unique to the clinical phenotype and is thus likely to be affected primarily by nonshared causative factors.

Adult↗

PubMed1998

A follow-up magnetic resonance imaging study of schizophrenia. Relationship of neuroanatomical changes to clinical and neurobehavioral measures.

BACKGROUND: Cross-sectional neuroanatomical studies have reported abnormalities in schizophrenia that relate to disease variables. Longitudinal neuroimaging investigations that integrate anatomical, clinical, and neurobehavioral measures may help clarify the pathogenesis of schizophrenia. METHODS: Magnetic resonance brain imaging and neurobehavioral studies were conducted at baseline and after 30.63 +/- 12.92 months (mean +/- SD) in 40 patients with schizophrenia (23 men and 17 women) and 17 healthy controls (13 men and 4 women). The schizophrenia group included 20 first-episode and 20 previously treated subjects. Volumes of whole-brain, cerebrospinal fluid, and frontal and temporal lobes were measured. The severity of negative and positive symptoms was assessed, medications were monitored, and neurobehavioral functioning in 8 domains was evaluated. RESULTS: Both first-episode and previously treated patients had smaller brains and frontal and temporal lobes than controls at intake. Longitudinally, reduction in frontal lobe volume was found only in patients, whereas temporal lobe reduction was also seen in controls. The association between volume reduction and symptom changes differed between patient groups, but volume reduction was associated with decline in some neurobehavioral functions in both groups. Exploratory analysis suggested that neuroleptic dose is correlated with changes in all 3 domains. CONCLUSIONS: The existence of neuroanatomical and neurobehavioral abnormalities in patients with first-episode schizophrenia indicates that the brain dysfunction occurred before clinical presentation. However, there is also evidence of progression, in which anatomical changes may affect some clinical and neurobehavioral features of the illness in some patients.

Adult↗

PubMed1998

Absence of neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia.

BACKGROUND: The cognitive and functional deterioration that is observed in many "poor-outcome" patients with schizophrenia suggests a neurodegenerative process extending into late life. Previous diagnostic studies have excluded known neurodegenerative diseases as explanations for this dementia. However, we hypothesized that relatively small accumulations of age- or disease-related neurodegenerative lesions occurring in an otherwise abnormal brain could result in deterioration in schizophrenia. METHODS: Postmortem studies were conducted using 23 prospectively accrued elderly persons with chronic schizophrenia for whom clinical ratings had been determined before death, 14 elderly control patients with no neuropsychiatric disease, and 10 control patients with Alzheimer disease. Immunohistochemistry and unbiased stereological counting methods were used to quantify common neurodegenerative lesions (ie, neurofibrillary tangles, amyloid plaques, and Lewy bodies) and cellular reactions to a variety of noxious stimuli (ubiquitinated dystrophic neurites, astrocytosis, and microglial infiltrates) in the ventromedial temporal lobe and the frontal and the calcarine (primary visual) cortices. RESULTS: No statistically significant differences were found between the patients with schizophrenia and the control patients without neuropsychiatric disease for the densities of any of the markers, while both groups exhibited fewer lesions than did the control group with Alzheimer disease. Correlation analyses in the schizophrenia sample failed to identify significant correlations between cognitive and psychiatric ratings and densities of any of the neuropathologic markers. CONCLUSIONS: No significant evidence of neurodegeneration or ongoing neural injury in the cerebral cortex was found in this sample of elderly persons with schizophrenia. Furthermore, the behavioral and cognitive deterioration observed in late life did not correlate with age-related degenerative phenomena.

Age Factors↗

PubMed1998

Frontotemporal cerebral blood flow change during executive and declarative memory tasks in schizophrenia: a positron emission tomography study.

Schizophrenia affects prefrontal and temporal-limbic networks. These regions were examined by contrasting regional cerebral blood flow (rCBF) during executive (Wisconsin Card Sorting Test [WCST]), and declarative memory tasks (Paired Associate Recognition Test [PART]). The tasks, and a resting baseline, were administered to 15 patients with schizophrenia and 15 healthy controls during 10 min positron emission tomography 15O-water measures of rCBF. Patients were worse on both tasks. Controls activated inferior frontal, occipitotemporal, and temporal pole regions for both tasks. Similar results were obtained for controls matched to level of patient performance. Patients showed no activation of hypothesized regions during the WCST and activated the dorsolateral prefrontal cortex during the PART. On the PART, occipitotemporal activation correlated with better performance for controls only. Better WCST performance correlated with CBF increase in prefrontal regions for controls and in the parahippocampal gyrus for patients. Results suggest that schizophrenia may involve a breakdown in the integration of a frontotemporal network that is responsive to executive and declarative memory demands in healthy individuals.

Adult↗

PubMed1998

Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia.

OBJECTIVE: This study examined whether subcortical volumes of the basal ganglia and thalamus in schizophrenic patients are related to neuroleptic exposure and symptom severity. METHOD: Basal ganglia substructures and thalamic volumes were measured with magnetic resonance imaging in 96 patients with schizophrenia (50 men and 46 women) and 128 healthy comparison subjects (60 men and 68 women). Twenty-one of the patients were neuroleptic-naive; of the 75 previously treated patients, 48 had received typical neuroleptics only, and 27 had received typical and atypical neuroleptics. The relation of volume measures to treatment status, exposure to neuroleptics, and symptoms was examined. RESULTS: The neuroleptic-naive patients did not differ from the healthy comparison subjects in subcortical volumes except for lower thalamic volume. In the neuroleptic-naive group, volumes did not correlate with severity of negative symptoms, but higher volumes in both the thalamus and the putamen were associated with more severe positive symptoms. The previously treated group showed higher volumes in the putamen and globus pallidus than the healthy comparison subjects and the neuroleptic-naive patients. In the treated group, a higher dose of a typical neuroleptic was associated with higher caudate, putamen, and thalamus volumes, whereas a higher dose of an atypical neuroleptic was associated only with higher thalamic volume. Higher subcortical volumes were mildly associated with greater severity of both negative and positive symptoms. CONCLUSIONS: Increased subcortical volumes in treated schizophrenic patients seem to be medication-induced hypertrophy. This hypertrophy could reflect structural adaptation to receptor blockade and may moderate the effects of neuroleptic treatment.

Antipsychotic Agents↗

PubMed1998

MMPI-2 characteristics of adults diagnosed with attention deficit disorder.

Attention Deficit Disorder (ADD) has been increasingly recognized as extending into adulthood, affecting occupational, interpersonal, and psychological functioning. The Minnesota Multiphasic Personality Inventory (MMPI) and its revision (MMPI-2) have been widely used in the assessment of patients with psychiatric disorders, but few studies have attempted to characterize the personality profiles of individuals with ADD and none have used the MMPI-2. Thirty-three patients with ADD and 33 schizophrenia patients were compared to 46 healthy control subjects on the MMPI-2 validity, clinical and Harris-Lingoes scales. With the exception of significantly lower scores for general affective distress (F), thought disorder (Sc), and paranoia (Pa), ADD subjects demonstrated remarkably similar profiles to those seen in the schizophrenia group. Significant differences between the three groups were found on a majority of the clinical scales, with ADD subjects showing similar profile elevations as schizophrenic subjects on both clinical- and sub-scales. These results were consistent with previous research using the original MMPI in adults with ADD, and confirm that examination of MMPI-2 profiles may be a useful diagnostic aid for this disorder.

Adult↗

PubMed1997

Apolipoprotein E genotype in schizophrenia: frequency, age of onset, and neuropathologic features.

Apolipoprotein E (ApoE) genotype has been found to affect the expression of a variety of neuropsychiatric disorders. We determined ApoE genotype frequencies and their relationship to clinical and pathological features in a diverse cohort of individuals with schizophrenia. There were no differences in ApoE genotype frequencies between schizophrenics and controls. However, the ApoE epsilon 4 genotype was associated with a younger age of onset of schizophrenia, and in an elderly subsample, individuals with the epsilon 4 allele more frequently exhibited co-existent dementia and had more neurofibrillary pathology (although none of the cases met criteria for Alzheimer's disease). This examination of ApoE in relation to clinical and neurobiological features of schizophrenia suggests that it modifies the phenotypic expression of the disease.

Adult↗

PubMed1997

Neuropsychological evidence supporting a neurodevelopmental model of schizophrenia: a longitudinal study.

The stability of neuropsychological performance in schizophrenia and its relationship to clinical change was contrasted between 60 patients with schizophrenia (30 first-episode, 30 previously treated) and 38 healthy controls using a comprehensive neuropsychological battery and clinical scales administered at intake and at a 19-month follow-up. Consistent with the neurodevelopmental model of schizophrenia, patients demonstrated deficits in cognitive performance at initial testing and did not show decline at follow-up. There were no differences in neuropsychological performance over time between first-episode and previously treated patients, nor between male and female patients or controls. As expected, patients improved clinically with treatment with respect to both positive and negative symptoms. First-episode patients improved more on the positive symptoms of hallucination and delusion; male and female patients showed equivalent clinical improvement. Clinical improvement correlated positively with neuropsychological change, with improved negative symptomatology accounting for most of the significant correlations.

Adult↗

PubMed1997

Mesolimbic dopamine D3 receptors and use of antipsychotics in patients with schizophrenia. A postmortem study.

BACKGROUND: The pharmacological properties and distribution of a recently cloned member of the dopamine D2 receptor subfamily, the D3 receptor, has led directly to the hypothesis that it may be the target of antipsychotic action. METHODS: To quantify D3 receptors, we characterized the conditions for selective binding of the radioligand iodine 125-labeled (R)-trans-7-hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)-amino] tetralin ([125I]trans-7-OH-PIPAT) to the human D3 receptor. We then measured by quantitative autoradiography in postmortem tissue the concentration of D3 receptors in the caudal and rostral basal ganglia regions in patients with schizophrenia and control subjects. RESULTS: We found about 2-fold elevations in the number of D3 receptors in the basal ganglia and ventral forebrain of long-term hospitalized patients with schizophrenia who received no antipsychotic drugs for at least a month before death (n = 7) compared with matched control subjects (n = 15). Patients with schizophrenia receiving antipsychotic drugs less than 72 hours before death (n = 8) had levels similar to those of control subjects. There were no differences in the binding characteristics or affinity of [125I]trans-7-OH-PIPAT binding to D3 receptors between control subjects and patients with schizophrenia. CONCLUSION: In contrast to the previously detected elevation of D2 and D4 receptor levels in schizophrenia, elevation of D3 receptor levels in limbic striatum and its efferents observed in patients with schizophrenia may be reduced by antipsychotic drugs.

Adult↗

PubMed1997

Lateralized changes in regional cerebral blood flow during performance of verbal and facial recognition tasks: correlations with performance and "effort".

Functional neuroimaging has been used to investigate neural substrates of mnemonic processes, and cerebral blood flow (CBF) measures have been sensitive to activation with memory tasks. Studies of memory with two-dimensional 133Xenon clearance techniques found that word and face recognition tasks produced contralateral CBF changes in mid-temporal cortical regions. This study replicated the activation paradigm, expanding to the three-dimensional resolution of positron emission tomography (PET). Word and face recognition, and a control baseline task were administered to 19 healthy right-handed volunteers (11 men, 8 women) during successive 10 min PET 15O-water measures of CBF. Quantitative CBF rates were calculated with the arterial input function and the equilibrium model. Redistributions of blood flow were compared across tasks-using both absolute and relative (region/ whole brain) CBF. Replicating the 133Xenon clearance findings, CBF was "appropriately" lateralized during task performance (left-right for words > left-right for faces) in the mid-temporal region. Contrary to predictions, the recognition tasks did not activate expected mesolimbic or prefrontal areas. The task-induced CBF changes also correlated with performance. Bilateral CBF in mid-temporal and parahippocampal gyrus regions of interest correlated with the ability to correctly identify word targets (sensitivity). Left-lateralized CBF in the amygdala and hippocampus correlated with better word sensitivity as well as specificity (ability to correctly reject foils). Complementally, right-lateralized CBF in the parahippocampal gyrus correlated with better face specificity performance. In addition, left-lateralized CBF in the amygdala and right-lateralized CBF in the parahippocampal gyrus and hippocampus correlated with "mental effort" indices (task performance relative to basal ability) for word and face memory tasks, respectively. Thus, whereas this recognition task showed the expected lateralized increase in the mid-temporal region and not in frontal and limbic areas, lateralized activation in some of these areas was associated with better performance. Exploratory analyses on other regions showed lateralized changes in one additional temporal region, the occipital-temporal, and several limbic regions.

Adult↗

PubMed1997

Attentional dysfunctions in neuroleptic-naive and neuroleptic-withdrawn schizophrenic patients and their siblings.

This study examined attentional deficits in 44 schizophrenic patients (24 neuroleptic-naive and 20 neuroleptic-withdrawn patients) across changes in medication status and clinical state using a 1-9 continuous performance test (CPT) with distractors. Patients' attentional selectivity scores (A') were unchanged from the off-medication to on-medication testings (on average, 6 months later), despite significant improvement in both positive and negative symptoms. Both patient groups had significantly lower A' scores than 44 matched healthy controls at each testing. The nonschizophrenic siblings (n = 15) of these patients made significantly more errors of omission and commission than healthy controls. The results suggest that attentional deficits, as measured by this CPT, appear to measure stable markers of schizophrenia that may be associated with genetic vulnerability to the illness.

Adolescent↗

PubMed1997

PET regional cerebral blood flow change during working and declarative memory: relationship with task performance.

Functional and anatomical relationships between working and declarative memory were investigated by contrasting regional cerebral blood flow (rCBF) change during standard working (Wisconsin Card Sorting Test, WCST) and declarative memory (Paired Associate Recognition Test, PART) tasks using identical stimulus-response modalities. The tasks and a resting baseline were administered to 30 participants (16 men, 14 women) during successive 10-min positron emission tomography 15O-water measures of rCBF. For both tasks, rCBF increased over baseline in inferior frontal and occipitotemporal regions, with more consistent dorsolateral prefrontal activation for WCST than PART. Additional orbitofrontal increases and dorsomedial decreases were seen for the PART. Activation patterns diverged when performance was considered. For the WCST, high performers activated dorsolateral and inferior frontal regions, whereas top PART performers activated only the occipitotemporal region. These results suggest operation of a frontotemporal network subserving both types of memory function that becomes more focal as performance increases.

Adolescent↗