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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
PubMed2006

Olanzapine and haloperidol in first episode psychosis: two-year data.

Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic medications in patients within their first episode of psychosis. This study examined the effectiveness of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year treatment period. Two hundred and sixty-three patients were randomized to olanzapine or haloperidol in a doubleblind, multisite, international 2-year study. Clinical symptoms and side effects were assessed at baseline and longitudinally following randomization for the duration of the study. Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity (the primary outcome measure) over the course of the study. However, the treatment groups differed on two secondary efficacy measures. Patients were less likely to discontinue treatment with olanzapine than with haloperidol: mean time (in days) in the study was significantly greater for those treated with olanzapine compared to haloperidol (322.09 vs. 230.38, p<0.0085). Moreover, remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol (57.25% vs. 43.94%, p<0.036). While extrapyramidal side effects were greater in those treated with haloperidol, weight gain, cholesterol level and liver function values were greater in patients treated with olanzapine. The data from this study suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients, which must be weighed against those adverse effects that are more likely with olanzapine.

Adult↗
PubMed2006

Are neurologic examination abnormalities heritable? A preliminary study.

BACKGROUND: Neurologic examination abnormalities (NEA) are more prevalent among patients with schizophrenia as well as their unaffected relatives when compared with healthy controls, suggesting that NEA may be endophenotypes for schizophrenia. We estimated the heritability of NEA in moderately sized pedigrees. We also evaluated correlations between NEA and cognitive performance in order to examine their construct validity. METHODS: Members of eight extended families, each consisting of two first degree relatives with schizophrenia/schizoaffective disorders, as well as available first- to fifth-degree relatives were examined (n=96 participants). A modification of the Neurological Evaluation Scale (NES) was employed, augmented with localizing signs. Where feasible, we used untransformed data such as error counts and completion time, rather than ordinal measures. Heritability was estimated using the variance component method, implemented in SOLAR. RESULTS: Statistically significant heritability (h2) estimates were obtained for several measures (p<0.05, h2+/-standard error: rapid alternating movements, right-sided completion time, 0.99+/-0.19; alternating fist-palm test, completion time, 0.77+/-0.19 s, errors, 0.70+/-0.32; fist-ring test, right-sided completion time, 0.53+/-0.23 s, left-sided completion time, 0.70+/-0.21 s; go-no go task, correct responses, 0.93+/-0.33; audio-visual integration, correct responses, 0.79+/-0.54). For most items, heritability analysis was hampered by insufficient data variability (infrequent errors). Correlational analyses show some degree of divergence among types of NEA, repetitive motor tasks being associated with most domains of cognitive functioning other than executive functioning, and cognitive-perceptual tasks being associated with memory and executive functioning. CONCLUSIONS: Significant familial influences on certain aspects of neurologic performance were detected. These heritable measures were also correlated with heritable neurocognitive measures.

Adolescent↗
PubMed2005

Monoamine reuptake inhibition and nicotine receptor antagonism reduce amplitude and gating of auditory evoked potentials.

BACKGROUND: Sensory encoding deficits have been extensively studied as endophenotypic markers of schizophrenia using auditory evoked potentials. In order to increase understanding of the neurochemical basis of such deficits, we utilized an animal model to test whether monoamine reuptake inhibition and nicotine receptor antagonism reduce the amplitude and gating of the P20 and N40 auditory components. METHODS: C57BL/6J mice received 12 days of chronic vehicle, bupropion, haloperidol or bupropion plus haloperidol. Auditory evoked potentials were then recorded in alert mice to measure the amplitude and gating of evoked components during a paired click paradigm similar to tasks used to measure the P50 and N100 auditory potentials in schizophrenia. Evoked potentials were recorded prior to and following acute nicotine. RESULTS: Bupropion reduced the amplitude and gating of the N40 evoked potential in mice, similar to the P50 and N100 endophenotypes associated with sensory encoding deficits in schizophrenia. This deficit was fully reversed only by the combination of haloperidol and nicotine, suggesting that dopamine reuptake inhibition and nicotine antagonism both contribute to the observed phenotype. Furthermore, nicotine increased P20 amplitude across all groups supporting a role for nicotine agonists in pre-attentive sensory encoding deficits. CONCLUSIONS: We propose that the combination of monoamine inhibition and nicotine receptor antagonism may serve as a useful model for preclinical screening of pharmaceutical compounds aimed at treating sensory encoding deficits in schizophrenia.

Animals↗
PubMed2001

Comparison of the continuous performance test with and without working memory demands in healthy controls and patients with schizophrenia.

The Penn Continuous Performance Test (PCPT), a measure of sustained visual attention developed for use in functional neuroimaging studies, was compared with a standard CPT developed by Gordon Diagnostic Systems (GDS; Vigilance subtest). The PCPT and the GDS CPT were administered with a standard neuropsychological battery to 68 healthy adults to assess reliability and construct validity. The test had adequate internal consistency, and convergent validity was established through significant correlations between measures of efficiency on the PCPT and the GDS CPT. With the exception of a significant correlation between efficiency measures on the GDS CPT and a measure of auditory sustained attention, neither version of the CPT correlated significantly with other measures in the battery. Factor analysis showed that the PCPT loaded with the GDS CPT. In 39 patients with schizophrenia and 39 matched, healthy controls, equivalent impairment was evident on the two CPT tasks. Neither version correlated significantly with symptom measurements. These results support previous conclusions that sustained visual attention in schizophrenia is a core information processing deficit, not directly related to symptomatology.

Adult↗
PubMed2001

Dysregulation of olfactory receptor neuron lineage in schizophrenia.

BACKGROUND: Growing evidence implicates abnormal neurodevelopment in schizophrenia. While neuron birth and differentiation is largely completed by the end of gestation, the olfactory epithelium (OE) is a unique part of the central nervous system that undergoes regeneration throughout life, thus offering an opportunity to investigate cellular and molecular events of neurogenesis and development postmortem. We hypothesized that OE neurons exhibit deviant progress through neurodevelopment in schizophrenia characterized by an increase in immature neurons. METHODS: Olfactory epithelium was removed at autopsy from 13 prospectively assessed elderly subjects who had schizophrenia and 10 nonpsychiatric control subjects. Sections were immunolabeled with antibodies that distinguish OE neurons in different stages of development, including basal cells (low-affinity nerve growth factor receptor, p75NGFR), postmitotic immature neurons (growth-associated protein 43 [GAP43]), and mature olfactory receptor neurons (olfactory marker protein). Absolute and relative densities of each cell type were determined. RESULTS: We observed a significantly lower density of p75NGFR basal cells (37%) in schizophrenia and increases in GAP43 + postmitotic immature neurons (316%) and ratios of GAP43 + postmitotic immature neurons to p75NGFR + cells (665%) and olfactory marker protein + mature neurons to p75NGFR + basal cells (328%). Neuroleptic-free schizophrenia subjects exhibited the highest GAP43 + postmitotic immature neuron values. CONCLUSIONS: Abnormal densities and ratios of OE neurons at different stages of development indicate dysregulation of OE neuronal lineage in schizophrenia. This could be because of intrinsic factors controlling differentiation or an inability to gain trophic support from axonal targets in the olfactory bulb. While caution is necessary in extrapolating developmental findings in mature OE to early brain development, similarities in molecular events suggest that such studies may be instructive.

Aged↗
PubMed2001

Cognitive impairment and functional status in elderly institutionalized patients with schizophrenia.

OBJECTIVE: The relationship of cognitive impairment to functional status in older adults with schizophrenia was investigated. PATIENTS: Ninety-three psychiatric inpatients with schizophrenia between the ages of 65 and 88 years. Two subsets of this sample, consisting of 48 and 24 patients, were studied with a greater number of assessment instruments. MEASURES: The Mini-Mental State Examination (MMSE) was used for brief assessment of overall cognitive functioning, and the Psychogeriatric Dependency Rating Scale (PGDRS) was administered to assess functional status. The cognitive test battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and/or an expanded neuropsychological battery, was given to a subset of the patients. RESULTS: In the overall sample, patients with greater global cognitive impairment had higher levels of rated impairment on the individual items that comprised the Orientation and Physical, but not Behavior, subscales of the PGDRS. Furthermore, in the two subsamples, specific neuropsychological measures of problem-solving, word list learning, naming and constructional praxis were related to overall measures of outcome. CONCLUSIONS: Neuropsychological deficit and psychosocial outcome are multi-dimensional entities that relate to one another in complex ways.

Activities of Daily Living↗
PubMed2001

Computerized neurocognitive scanning: I. Methodology and validation in healthy people.

Neuropsychological testing batteries are applied in neurobehavioral evaluations of brain disorders, including neuropsychiatric populations. They are lengthy, require expert administrators and professional scorers, and are prone to data handling errors. We describe a brief computerized neurocognitive "scan" that assesses similar domains with adequate reliability. The scan and a traditional battery were administered to a sample of 92 healthy individuals (44 men, 48 women) in a counterbalanced order. Both approaches showed a significant "sex-typical" gradient, with women outperforming men in verbal memory relative to spatial tasks. Both methods also yielded similar profiles of sex differences, with the additional computerized measure of face memory showing better performance in women. Age effects were evident for both methods, but the computerized scan isolated the effects to speed rather than accuracy. Therefore, the computerized scan has favorable reliability and construct validity and can be applied efficiently to study healthy variability related to age and gender.

Adult↗
PubMed2001

Computerized neurocognitive scanning: II. The profile of schizophrenia.

Cognitive dysfunction in schizophrenia is well established with neuropsychological batteries, which have assessed multiple domains indicating diffuse deficits especially in processing related to frontotemporal systems. Two studies are reported examining the feasibility of the computerized neurocognitive scan to assess differential deficits in schizophrenia. In Study 1, we tested 53 patients and 71 controls with the traditional and computerized assessments counterbalanced in order. Both showed comparable generalized impairment in schizophrenia with differential deficits in executive functions and memory. The profile was replicated in Study 2 in a new sample of 68 patients and 37 controls, receiving only the computerized scan. The combined sample showed robust correlations between performance on both speed and accuracy measures of the neurocognitive scan and clinical variables, including premorbid adjustment, onset age, illness duration, quality of life, and severity of negative symptoms. These correlations were higher and more prevalent in women than men, who showed correlations predominantly for speed rather than accuracy. Neuroleptic exposure was associated with poorer performance only for speed of memory processing, and in men, this association was seen only for typical neuroleptics. We conclude that the computerized neurocognitive scan can be applied reliably in people with schizophrenia, yielding data that support its construct and criterion validity.

Adult↗
PubMed2001

Approaches to cognitive remediation of neuropsychological deficits in schizophrenia: a review and meta-analysis.

A review and critique of the literature pertaining to the use of cognitive remediation techniques in patients with schizophrenia is presented. The review is organized into three sections, according to the neuropsychological deficit targeted for remediation: 1) executive-function, 2) attention, and 3) memory. With regards to executive-function, despite an initial report suggesting that Wisconsin Card Sorting Test performance cannot be remediated, subsequent studies suggest that performance can be improved on a variety of dependent measures including perseverative errors, categories achieved, and conceptual level responses. These observations were confirmed by a meta-analytic investigation that revealed large mean effects sizes (d+ = 0.96) for these studies. Effect sizes were homogenous across discrepant remediation strategies and dependent measures. With regards to attention, serial scanning can be improved with instruction and reinforcement, whereas there is mixed evidence suggesting that practice-based attention drills can improve performance on measures of sustained attention in schizophrenia. With regards to memory, relatively simple semantic and affective elaborate encoding strategies elevates verbal list-learning memory in patients with schizophrenia to levels consistent with controls. A similar encoding procedure, combined with vigilance training, produces substantial improvement in social cue recognition. Avenues for future research are discussed.

Attention↗
PubMed2001

Effect of schizophrenia on frontotemporal activity during word encoding and recognition: a PET cerebral blood flow study.

OBJECTIVE: Neuropsychological studies have shown that deficits in verbal episodic memory in schizophrenia occur primarily during encoding and retrieval stages of information processing. The current study used positron emission tomography to examine the effect of schizophrenia on change in cerebral blood flow (CBF) during these memory stages. METHOD: CBF was measured in 23 healthy comparison subjects and 23 patients with schizophrenia during four conditions: resting baseline, motor baseline, word encoding, and word recognition. The motor baseline was used as a reference that was subtracted from encoding and recognition conditions by using statistical parametric mapping. RESULTS: Patients' performance was similar to that of healthy comparison subjects. During word encoding, patients showed reduced activation of left prefrontal and superior temporal regions. Reduced left prefrontal activation in patients was also seen during word recognition, and additional differences were found in the left anterior cingulate, left mesial temporal lobe, and right thalamus. Although patients' performance was similar to that of healthy comparison subjects, left inferior prefrontal activation was associated with better performance only in the comparison subjects. CONCLUSIONS: Left frontotemporal activation during episodic encoding and retrieval, which is associated with better recognition in healthy people, is disrupted in schizophrenia despite relatively intact recognition performance and right prefrontal function. This may reflect impaired strategic use of semantic information to organize encoding and facilitate retrieval.

Adult↗
PubMed2001

Striatal dopamine transporters and cognitive functioning in healthy men and women.

OBJECTIVE: There is growing interest in distinguishing the biological bases of sex differences in behavior from environmental influences. Sex hormone levels seem to be related to some cognitive abilities, particularly memory, and the dopaminergic system participates in the mediation of memory. The dopamine transporter is the primary indicator of dopaminergic tone. This study investigated the relationship between cognition and dopamine transporter availability in healthy men and women. METHOD: Dopamine transporter levels were measured with a technetium-99m radiolabeled analog of cocaine, TRODAT-1, in 66 healthy volunteers (30 men and 36 women). A neuropsychological battery designed to target functions associated with dopaminergic activity was administered during the uptake interval between the radiopharmaceutical injection and image acquisition. RESULTS: Women and younger participants had higher dopamine availability in the caudate nucleus, and these groups also performed better on verbal learning tasks. Furthermore, dopamine transporter availability was correlated with learning performance within groups. Relationships between dopamine availability in the caudate and putamen and executive and motor functioning were observed in women, but not in men. CONCLUSIONS: The results provide further evidence for age effects and sex differences in the neuromodulatory influences of dopamine on behavior in humans.

Adolescent↗
PubMed2001

Effectiveness of an attention- and memory-training program on neuropsychological deficits in schizophrenia.

The effect of two cognitive remediation procedures developed for closed head injury, Attention Process Training (APT) and Prospective Memory Training (PROMT), on neuropsychological deficits in schizophrenia was investigated. Six patients with schizophrenia, varying in baseline intellectual function and symptoms, were studied; three in a remediation condition and three in a nonremediated control condition. Results were evaluated individually for each of the three treated patients. Two of three remediation-treated subjects showed marked improvement on tests of sustained and divided attention. Untreated patients showed little evidence of change in neuropsychological test performance across a similar time interval, when tested on a subset of the measures administered to remediation-treated patients. The results of this study are discussed with a view toward future studies using larger sample sizes with homogeneous subject populations.

Adult↗
PubMed2001

Neuropsychological differences among empirically derived clinical subtypes of schizophrenia.

Neuropsychological profile differences between empirically derived clinical subtypes of schizophrenia were examined. Two hundred five patients and 209 demographically matched controls were administered a neuropsychological battery examining 8 domains. Subtypes included negative, disorganized, paranoid, Schneiderian, and mild. All subtypes displayed a neuropsychological profile of generalized impairment with greater deficits in learning, memory, and attention. Results were suggestive of diffuse cognitive dysfunction in schizophrenia with more severe deficits in learning and memory relative to executive skills. This pattern of greater learning and memory impairment was pronounced for disorganized patients. In contrast, paranoid patients outperformed disorganized and negative patients in several domains. These findings reflect bilateral frontal-temporal dysfunction, particularly in disorganized and negative patients. Subtype differences highlight the importance of conceptualizing schizophrenia as a multifocal disorder.

Adolescent↗
PubMed2001

Controlled and automatic processing during animal word list generation in schizophrenia.

Controlled and automatic aspects of semantic-associative functioning in schizophrenia were investigated by evaluating performance on animal word list generation (WLG). Responses from control (n = 47) and patient (n = 38) participants were subjected to multidimensional scaling (MDS), cluster analysis (CA), and indices on the basis of number of shared attributes (SA) between consecutive responses. Patient MDS results accounted for less variance and contained more error than control data. CA results yielded fewer and less clear animal-response subgroups among patients yet demonstrated intact associations among strongly related exemplars. The SA indices revealed better clustering and more effective switching among response clusters in controls than patients. Results suggest that animal WLG in schizophrenia is compromised both by aberrant automatic semantic-associative network activation and by controlled processes such as search, access, and selection. This pattern is consistent with prominent frontotemporal pathology evident in the disorder.

Adult↗
PubMed2000

Emotion recognition deficit in schizophrenia: association with symptomatology and cognition.

BACKGROUND: Previous investigations have found impaired recognition of facial affect in schizophrenia. Controversy exists as to whether this impairment represents a specific emotion recognition deficit when compared with other face recognition control tasks. Regardless of whether the emotion processing deficit is differential, it may uniquely influence other manifestations of schizophrenia. We compared patients and healthy control subjects on computerized tasks of emotion and age recognition. Performances on emotion and age recognition tasks were correlated with cognitive functioning and with symptomatology. METHODS: Thirty-five patients with schizophrenia and 45 healthy people underwent computerized testing for emotion and age recognition. Participants were assessed neuropsychologically, and patients were rated for positive and negative symptoms. RESULTS: The patients with schizophrenia performed worse than control subjects on emotion and age recognition without differential deficit. In both groups, we found higher error rates for identification of emotion in female faces and for identification of sad versus happy faces. In schizophrenic patients, emotion but not age recognition correlated with severity of negative and positive symptoms. In healthy control subjects, neither task correlated with cognitive functions. In schizophrenic patients, emotion but not age recognition correlated with attention, verbal and spatial memory, and language abilities. CONCLUSIONS: This study did not reveal a specific deficit for emotion recognition in schizophrenia; however, our findings lend support to the concept that emotion recognition is uniquely associated in schizophrenia with core symptomatology and cognitive domains.

Adult↗
PubMed2000

Emotional processing in schizophrenia across cultures: standardized measures of discrimination and experience.

Schizophrenia appears quite similar across a range of cultures. However, variability has been noted, and understanding the variant and invariant features of the disorder is necessary for elucidating its biological and environmental basis. Evidence of prominent emotion processing deficits in schizophrenia, including perceptual and experiential aspects, led us to extend the paradigm of standardized measures cross-culturally. We assessed performance of American, German, and Indian patients with schizophrenia and healthy controls on standardized emotion discrimination and experience (mood induction) procedures using happy, sad, and neutral facial expressions of Caucasian actors. Participants were 80 Americans (40 patients; 40 controls), 48 Germans (24 patients; 24 controls), and 58 Indians (29 patients; 29 controls). Face discrimination performance was impaired across patient groups, but was most impaired in those of Indian origin. Lower performance was also found in Indian controls, relative to their American and German counterparts. Mood induction produced weaker effects in all patient groups relative to their respective controls. The results supported the feasibility of cross-cultural comparisons and also emphasized the importance of poser ethnic background for facial affect identification, while poser ethnicity was less consequential for mood induction effects. Emotion processing deficits in schizophrenia may add to the clinical burden, and merit further examination.

Adult↗
PubMed2000

P300 subcomponent abnormalities in schizophrenia: III. Deficits In unaffected siblings of schizophrenic probands.

BACKGROUND: Reduced P300 amplitude is a robust finding in patients with schizophrenia. In previous investigations, we reported reductions of specific subcomponents of the auditory oddball P300 that were independent of acute symptomatology and persistent over time, consistent with a trait abnormality. To clarify whether these stable deficits represented genetic markers of vulnerability to schizophrenia, event-related brain potentials (ERPs) from patients were compared to those from their own healthy siblings and unrelated control subjects. METHODS: Auditory P300 ERPs were acquired from 11 schizophrenic patients, 12 healthy siblings and 23 matched control subjects. Five P300 subcomponents were identified using current source density measures: frontal, bilateral parietal, and bilateral temporal. RESULTS: Consistent with previous reports, patients had reduced parietal and frontal P300 amplitudes. The healthy siblings of the schizophrenic probands had an isolated reduction of the frontal P300. CONCLUSIONS: Frontal P300 amplitude is a potential endophenotypic marker of genetic vulnerability to schizophrenia in individuals who otherwise show no evidence of clinical symptomatology. Given the functional interpretation of the frontal P300 as a physiological correlate of cognitive orienting, this supports the hypothesis that impairments of the neural substrate underlying attentional mechanisms are selective indicators of genetic susceptibility to schizophrenia in high-risk individuals.

Adult↗