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Robert W Buchanan

Publications and source records attributed to Robert W Buchanan.

At least 19 recordsLinked to original sources
PubMed2007

Independent domains of inhibitory gating in schizophrenia and the effect of stimulus interval.

OBJECTIVE: Patients with schizophrenia are known to have inhibitory gating deficits in the suppression of evoked potential P50 response to repeated stimuli and the prepulse inhibition of the startle response. In the current study, the authors aimed to determine whether these two inhibitory gating measures are related in schizophrenia patients or whether abnormal P50 suppression and abnormal prepulse inhibition are independent neurophysiological characteristics of schizophrenia. The authors hypothesized that the relationship of the two measures may vary as a function of interstimulus intervals of stimulus presentations. METHOD: Fifty-nine schizophrenia patients and 17 healthy comparison subjects were tested on both P50 suppression and prepulse inhibition. P50 suppression was measured using paired clicks with 500-msec interstimulus intervals. Prepulse inhibition was measured by using a series of prepulse-pulse pairs with interstimulus intervals ranging from 30 to 500 msec. RESULTS: Patients showed reduced P50 suppression and prepulse inhibition in relation to healthy comparison subjects. Concordance analysis showed that abnormal P50 suppression and abnormal prepulse inhibition do not necessarily occur together. Prepulse inhibition was most prominent at the 120-msec interstimulus interval, which was not correlated to P50 suppression. At the 500-msec interstimulus interval, prepulse inhibition was significantly but negatively correlated to P50 suppression. Prepulse inhibition at the other interstimulus intervals was not correlated with P50 suppression. CONCLUSIONS: These neurophysiological measures lack robust and direct relationships and likely mark independent aspects of abnormal brain inhibitory functions in schizophrenia.

Acoustic Stimulation↗
PubMed2006

Lack of association between COMT gene and deficit/nondeficit schizophrenia.

BACKGROUND: The dopamine dysregulation hypothesis of schizophrenia posits that positive, negative and cognitive symptoms correlate with cortical/subcortical imbalances in dopaminergic transmission. A functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene is implicated in the pathophysiology of schizophrenia by its effect on prefrontal dopamine transmission, and its unique impact on prefrontal cognitive and behavioral phenotypes. Cognitive impairments and negative symptoms in schizophrenia have been hypothesized to be associated with hypodopaminergic states. Schizophrenia patients with the deficit syndrome are characterized by primary enduring negative symptoms, impairment on neurocognitive tasks sensitive to frontal and parietal cortical functioning, and poorer functional outcome compared to non-deficit patients. METHODS: Eighty-six schizophrenia cases that met DSM-IV criteria for schizophrenia were recruited. Additional categorization into deficit and nondeficit syndrome was performed using the Schedule for the Deficit Syndrome (SDS). A healthy comparison group (n = 50) matched to cases on age and ethnicity was recruited. Allele and genotype frequencies of the Val158Met polymorphism were compared among healthy controls, and schizophrenia cases with the deficit (n = 21), and nondeficit syndrome (n = 65). RESULTS: There was a significant difference in Val/Val genotype frequencies between schizophrenia cases (combined deficit/nondeficit) and healthy controls (p = 0.004). No significant differences in allele or genotype frequencies were observed between deficit and nondeficit cases. CONCLUSION: Results from this preliminary analysis failed to show an effect of COMT gene on deficit schizophrenia.

Journal Article↗
PubMed2006

Neuropsychology of the deficit syndrome: new data and meta-analysis of findings to date.

The deficit syndrome is thought to characterize a pathophysiologically distinct subgroup of patients with schizophrenia. Supporting this notion, prior research examining the neuropsychological correlates of the deficit syndrome has suggested the presence of a differential impairment in frontal and parietal functions. This article reports findings from 2 studies attempting to replicate and extend previous reports of a differential neuropsychological impairment in deficit schizophrenia. In the first study, we administered a comprehensive neuropsychological battery to 20 deficit and 25 nondeficit patients with schizophrenia and 25 normal healthy controls. In the second study, a meta-analysis was conducted of 13 separate studies examining the neuropsychology of the deficit syndrome. There was little evidence from either of the present studies that the deficit syndrome is associated with a selective impairment in frontal and parietal lobe functions. The first study failed to find significant differences in frontal or parietal abilities for deficit vs nondeficit patients. The meta-analytic findings revealed that deficit patients were globally more neuropsychologically impaired than nondeficit patients (effect size [ES] = 0.41). Relative to nondeficit patients, deficit patients performed poorest on tests of olfaction (ES = 1.11), social cognition (ES = 0.56), global cognition (ES = 0.52), and language (ES = 0.51). The neuropsychological impairments associated with the deficit form of schizophrenia do not follow an obvious anatomically defined pattern of impairment. The question of whether deficit patients exhibit a unique cognitive impairment profile will require a more sophisticated and rigorous examination of the neuropsychology of the deficit syndrome.

Adult↗
PubMed2006

Prefrontal cortex and insight in schizophrenia: a volumetric MRI study.

Previous studies have suggested a relationship between frontal lobe-based neuropsychological functions and insight in schizophrenia. There is some evidence linking both smaller whole brain volume and frontal cortical atrophy to poor insight in this population. We investigated the relationship between total as well as specific prefrontal regional volumes and insight in schizophrenia. Twenty-eight stable outpatients with schizophrenia underwent magnetic resonance imaging scanning and assessment for insight. Insight was measured using the Birchwood self-report Insight Scale and the Expanded Schedule of Assessment of Insight. The whole brain and prefrontal regional (superior frontal, middle frontal, inferior frontal and orbitofrontal) volumes were then manually measured using the Cavalieri method and established criteria. Twenty healthy subjects were also scanned to provide control data for volumetric assessments. Smaller total prefrontal grey matter volume was moderately associated with a lower level of insight into the presence of illness. At the prefrontal sub-regional level, volumes of the superior, inferior and orbitofrontal regions contributed to this relationship, especially in males. It is concluded that smaller prefrontal grey matter volume is associated with poor insight into the presence of illness in stable schizophrenia patients. Future research should examine the association of specific dimensions of insight with frontal as well as non-frontal regional brain volumes.

Adult↗
PubMed2006

Persistent negative symptoms in schizophrenia: an overview.

Persistent negative symptoms represent an alternative approach for assessing negative symptoms in the context of clinical trials. Persistent negative symptoms are designed to capture those symptoms that lead to functional impairment but are currently understudied and for which there are no currently available effective treatments. Persistent negative symptoms differ from the 2 most commonly used approaches: primary, enduring negative symptoms or deficit symptoms and negative symptoms broadly defined to include negative symptoms, regardless of their etiology or duration. In contrast to deficit symptoms, persistent negative symptoms may include secondary negative symptoms. However, in contrast to negative symptoms broadly defined, the secondary negative symptoms included in the assessment of persistent negative symptoms only include those that have failed to respond to usual treatments for secondary negative symptoms. In consequence, the presence of persistent negative symptoms identifies a patient population with clinically relevant symptomatology, which is larger than the one with the deficit syndrome but less heterogeneous than that captured through the use of a nonrestrictive definition of negative symptoms. This may facilitate the selection of subjects for inclusion into research and efforts to develop new pharmacological treatments and enhance our understanding of a relevant clinical problem. Ultimately, the investigation of the different entities characterized by negative symptoms, such as persistent negative symptoms, and the enhanced understanding of their biological and clinical characteristics may help to unravel the psychopathological and biological heterogeneity of schizophrenia.

Affect↗
PubMed2006

Review of clinical correlates of P50 sensory gating abnormalities in patients with schizophrenia.

A large percentage of patients with schizophrenia are characterized by an abnormality in P50 sensory gating. This abnormality has been shown to be genetically linked to the alpha-7 nicotinic receptor and is transiently reversed by acute nicotine administration. These observations have led to the development of pharmacological treatments designed to improve sensory gating. However, if normalization of P50 gating abnormalities is to guide drug development, then it becomes important to delineate the clinical correlates of enhanced P50 gating. We conducted a review of all available articles through March 2005 that have examined this issue. We found that, despite the prominent role that P50 abnormalities have played in our understanding of schizophrenia, there is a relative dearth of data examining P50 clinical correlates. There is evidence suggestive of an association between P50 and measures of attention, and multiple studies have failed to document a cross-sectional or longitudinal relationship between P50 and positive, negative, or other symptoms. These results suggest that considerably more work needs to be done to understand and validate the clinical significance of this impairment.

Acoustic Stimulation↗
PubMed2006

Genetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia.

CONTEXT: There is evidence of linkage to a schizophrenia susceptibility locus on chromosome 8p21-22 found by several family linkage studies. OBJECTIVES: To fine map and identify a susceptibility gene for schizophrenia on chromosome 8p22 and to investigate the effect of this genetic susceptibility on an endophenotype of abnormal brain structure using magnetic resonance imaging. DESIGN: Fine mapping and identification of a chromosome 8p22 susceptibility gene was carried out by finding linkage disequilibrium between genetic markers and schizophrenia in multiply affected families, a case-control sample, and a trio sample. Variation in brain morphology associated with pericentriolar material 1 (PCM1) alleles was examined using voxel-based morphometry and statistical parametric mapping with magnetic resonance imaging. Setting and Patients A family sample of 13 large families multiply affected with schizophrenia, 2 schizophrenia case-control samples from the United Kingdom and Scotland, and a sample of schizophrenic trios from the United States containing parents and 1 affected child with schizophrenia. MAIN OUTCOME MEASURES: Tests of transmission disequilibrium between PCM1 locus polymorphisms and schizophrenia using a family sample and tests of allelic association in case-control and trio samples. Voxel-based morphometry using statistical parametric mapping. RESULTS: The family and trio samples both showed significant transmission disequilibrium between marker D85261 in the PCM1 gene locus and schizophrenia. The case-control sample from the United Kingdom also found significant allelic association between PCM1 gene markers and schizophrenia. Voxel-based morphometry of cases who had inherited a PCM1 genetic susceptibility showed a significant relative reduction in the volume of orbitofrontal cortex gray matter in comparison with patients with non-PCM1-associated schizophrenia, who, by contrast, showed gray matter volume reduction in the temporal pole, hippocampus, and inferior temporal cortex. CONCLUSIONS: The PCM1 gene is implicated in susceptibility to schizophrenia and is associated with orbitofrontal gray matter volumetric deficits.

Adult↗
PubMed2005

Dihydropyrimidinase-related protein 2 (DRP-2) gene and association to deficit and nondeficit schizophrenia.

A previous study has shown an association between the *2236T > C allele polymorphism of the dihydropyrimidinase-related protein 2 (DRP-2) gene and schizophrenia in a Japanese sample [Nakata et al. (2003); Biological Psychiatry 53:571-576]. DRP-2 is an important molecule in guiding neuronal development and its gene is located in 8p21, a chromosomal region that was previously shown to have significant linkage to schizophrenia and to several deficit symptoms of schizophrenia. We compared the frequency of the DRP-2 *2236T > C polymorphism between subjects with (n = 117) and without (n = 72) schizophrenia, and then further evaluated whether the association was specific for the deficit (n = 24) and nondeficit (n = 93) forms of schizophrenia. In both Caucasians and African-Americans, the C allele occurred more frequently in schizophrenia cases than controls, with this difference achieving statistical significance in Caucasians (C allele frequency: 42.0% in cases vs. 25.0% in controls, P = 0.014) but not African Americans (52.6% in cases vs. 50.0% in controls, P = 0.93). In Caucasians, the frequency of the C allele was significantly higher in both the deficit (allele frequency 53.3%, P = 0.009) and nondeficit (39.2%, P =0.050) forms of schizophrenia compared to controls (allele frequency 25.0%). We conclude that the DRP-2 *2236 C allele may mark another polymorphism in DRP-2, or in a nearby gene, that may influence susceptibility to schizophrenia.

Adult↗
PubMed2005

Significance and meaning of neurological signs in schizophrenia: two decades later.

OBJECTIVE: Patients with schizophrenia are characterized by neurological abnormalities, which can be assessed by bedside clinical examination. These abnormalities have been argued to represent core features of the illness. We review studies published since our last review in 1988 that address the validity of neurological signs as a trait feature of schizophrenia. METHODS: We conducted a literature search in the following computer databases: MEDLINE, PSYCHLIT, EMBASE, and COCHRANE. The search was limited to articles published from January 1988 to May 2005. RESULTS: Neurological signs occur in the majority of patients with schizophrenia. Their occurrence is independent of demographic and most medication variables. Neurological signs are strongly associated with negative symptoms and cognitive impairments. There is also evidence to suggest that their occurrence is under genetic control. CONCLUSIONS: There is compelling evidence to suggest the hypothesis that neurological signs represent a trait feature of schizophrenia.

Antipsychotic Agents↗
PubMed2005

Voxel-based morphometry versus region of interest: a comparison of two methods for analyzing gray matter differences in schizophrenia.

Many previous studies exploring cortical gray matter (GM) differences in schizophrenia have used "region of interest" (ROI) measurements to manually delineate GM volumes. Recently, some investigators have instead employed voxel-based morphometry (VBM), an automated whole-brain magnetic resonance image measurement technique. The purpose of the current study was to compare the above methods in calculating GM distributions in schizophrenia patients relative to matched controls. Using ROIs, Buchanan et al. (Buchanan, R.W., Francis, A., Arango, C., Miller, K., Lefkowitz, D.M., McMahon, R.P., Barta, P.E. and Pearlson, G.D., 2004. Morphometric assessment of the heteromodal association cortex in schizophrenia. Am J Psychiatry. 161 (2), 322-331.) found decreased dorsolateral prefrontal GM volume and altered symmetry of inferior parietal GM in schizophrenia patients. We hypothesized that VBM analyses of the same data would complement the ROI findings. As predicted, VBM analyses replicated results of less left inferior and right superior frontal cortical GM in schizophrenia. Additionally, VBM uncovered a significantly lower concentration of GM in the middle and superior temporal gyri, sought but not detected using ROIs, but did not replicate the parietal changes. The principal explanation for these differences may be the methodological differences between voxel-averaged, landmark-based ROI analyses and the single, voxel-by-voxel whole brain VBM measurements. Although VBM is rapid and fully automated, it is not a replacement for manual ROI-based analyses. Both methods provide different types of information and should thus be used in tandem.

Adult↗
PubMed2005

A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia.

OBJECTIVE: On April 23, 2004, a joint meeting of the FDA, NIMH, MATRICS investigators, and experts from academia and the pharmaceutical industry was convened to develop guidelines for the design of clinical trials of cognitive-enhancing drugs for neurocognitive impairments in patients with schizophrenia. METHOD: Experts were asked to address specific questions relating to clinical trial design of adjunctive/co-treatment and broad spectrum agents. At the workshop, experts reviewed relevant evidence before offering the discussion panel proposed guidelines for a given subset of questions. The discussion panel, which consisted of presenters and representatives from FDA, NIMH, academia, and industry, deliberated to reach consensus on suggested guidelines. When evidence was insufficient, suggested guidelines represent the opinion of a cross-section of the presenters and discussion panel. RESULTS: Guidelines were developed for inclusion criteria, the use of co-primary outcome measures, and statistical approaches for study design. Consensus was achieved regarding diagnostic and concomitant medication inclusion criteria and on the use of cognitive screening measures. A key guideline was to limit the trial to patients in the residual phase of their illness, who have a predefined level of positive, negative, and affective symptoms. The most difficult issues were the feasibility of including a co-primary measure of functional improvement and the choice of comparator agent for a trial of a broad spectrum agent (with antipsychotic and cognitive-enhancing effects). CONCLUSIONS: The suggested guidelines represent reasonable starting points for trial design of cognitive-enhancing drugs, with the understanding that new data, subsequent findings, or other methodological considerations may lead to future modifications.

Antipsychotic Agents↗
PubMed2005

No, it is not possible to be schizophrenic yet neuropsychologically normal.

Cognitive impairment is well documented in schizophrenia, though some reports have been interpreted to suggest that it is possible to have schizophrenia without neuropsychological impairment. The authors tested this by comparing the neuropsychological profiles of closely matched patients with schizophrenia and healthy comparison participants. Sixty-four patients with schizophrenia and 64 healthy comparison cases, matched to within 3 Full-Scale IQ points, were tested using the Wechsler Adult Intelligence Scale (3rd ed.; D. Wechsler, 1997b) and the Wechsler Memory Scale (3rd ed.; D. Wechsler, 1997c). Neuropsychological profiles for these groups were markedly different, with the group of patients with schizophrenia exhibiting performance deficits in memory and speeded visual processing but superior verbal comprehension and perceptual organization relative to the group of healthy comparison participants matched on Full-Scale IQ. Thus, scoring in the normal range does not preclude neuropsychological abnormality in schizophrenia, confirming that neuropsychological impairment is a core feature of the illness.

Adult↗
PubMed2005

Olanzapine treatment of residual positive and negative symptoms.

OBJECTIVE: Olanzapine has been hypothesized to have superior efficacy in patients with treatment-resistant schizophrenia. The authors examined the comparative efficacy and safety of olanzapine and haloperidol in outpatients with partially responsive schizophrenia. METHOD: Sixty-three outpatients with schizophrenia who met retrospective and prospective criteria for either residual positive or residual negative symptoms entered a 16-week double-blind, parallel-groups comparison of olanzapine and haloperidol. RESULTS: There were no significant differences between the two drugs in their effect on positive or negative symptoms. There were no significant differences between the two treatment groups on measures of social and functional outcome. Olanzapine-treated patients had a significant reduction in extrapyramidal symptoms and subjective measures of stiffness and dry mouth, but the increases in systolic blood pressure and weight in olanzapine-treated patients were significantly greater than they were in haloperidol-treated patients. CONCLUSIONS: Olanzapine has limited differential benefit for either positive or negative symptoms in patients with treatment-resistant schizophrenia. Although olanzapine is associated with fewer extrapyramidal symptoms, other side effects may offset this benefit.

Adult↗
PubMed2004

Brief cognitive assessment in schizophrenia: normative data for the Repeatable Battery for the Assessment of Neuropsychological Status.

BACKGROUND: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a brief, standardized cognitive screening instrument that assesses several domains of interest and offers an efficient approach to screening for cognitive impairment in schizophrenia (SC). Prior studies have established the clinical validity and test-retest reliability of the RBANS in SC. AIMS: The purpose of the current study was to guide clinical interpretation by providing normative data for the use of the RBANS as a measure of cognitive impairment in SC. We also sought to evaluate the role of demographic factors and to present percentile data accordingly. METHODS: 575 patients (391 male, 184 female) meeting the diagnostic criteria for SC or schizoaffective disorder were recruited from 4 inpatient (n=117) and 6 outpatient (n=458) sites in 2 different mental health treatment systems. All participants were administered the RBANS according to standardized instructions and a subgroup of 242 patients were also administered the Wide Range Achievement Test (3rd Edition) (WRAT-3) Reading subtest. RESULTS: RBANS Total Scale score for patients with SC was approximately 2 standard deviations below the normal mean, was approximately 1 standard deviation below WRAT-3 Reading scores, and expected patterns of impairment were observed: measures of language and visuospatial ability were preserved relative to those of memory and attention. Aside from weak associations with Language (0.139) and Attention (0.112), age was not significantly associated with RBANS Index scores (which are age adjusted in healthy controls). Education was significantly associated with all RBANS scores and one-way ANOVA indicates that those with more than high school education scored consistently higher than the other two groups (less than and equal to a complete high school education). Normative tables with age and education based percentiles are presented. CONCLUSIONS: The RBANS is an efficient screening tool for assessing cognitive impairment in patients with SC thereby making it a useful instrument for clinical and research applications.

Adolescent↗
PubMed2004

Evoked gamma band synchronization and the liability for schizophrenia.

OBJECTIVE: Electroencephalographic (EEG) synchronization in the gamma band is thought to represent a neuronal mechanism by which the brain integrates information processed in different cortical areas to build a coherent internal representation. Previous studies have reported abnormal gamma range ( approximately 40 Hz) synchronization in schizophrenic patients. We tested a group of first-degree relatives of schizophrenic probands who have schizophrenia spectrum personality symptoms, and a group of schizophrenic patients, to examine whether individuals with increased liability for schizophrenia have reduced gamma synchronization. METHOD: A steady-state auditory evoked potential paradigm was used to evaluate the brain's capacity to sustain 20, 30, and 40 Hz EEG synchronization in 11 relatives, 24 schizophrenic patients (11 on conventional, 13 on new generation antipsychotic medications), and 17 normal controls. RESULTS: Relatives with schizophrenic spectrum personality symptoms had reduced power at 40 Hz synchronization compared to normal controls (p=0.022). Previous findings of reduced steady-state gamma band synchronization in schizophrenic patients were not directly replicated in this study. Patients as a group did not significantly differ from controls, but patients taking new generation antipsychotics had significantly enhanced 40 Hz synchronization compared to patients taking conventional antipsychotics (p<0.001). There were no group differences in 20 or 30 Hz synchronization. CONCLUSIONS: Gamma band synchronization was found to be reduced in first-degree relatives with schizophrenia spectrum personality symptoms. Patients on new generation antipsychotic medications may exhibit enhanced gamma band synchronization.

Adult↗