Search PubMed⌕ Search

Biomedical subjects

R W Buchanan

Publications and source records attributed to R W Buchanan.

At least 19 recordsLinked to original sources
PubMed1999

Diazepam treatment of early signs of exacerbation in schizophrenia.

OBJECTIVE: Therapeutic intervention at the earliest phase of symptom exacerbation in schizophrenia is an important clinical need, but specific pharmacotherapeutic interventions for this phase of illness have not been established. This study examined diazepam efficacy for this phase of treatment. METHOD: A double-blind, randomized clinical trial with 53 schizophrenic patients compared diazepam with placebo (with fluphenazine treatment for a comparison group). Treatment was initiated at the earliest signs of exacerbation, and symptom progression was the dependent measure used to evaluate efficacy. RESULTS: Diazepam was statistically superior to placebo in preventing symptom progression and was comparable to fluphenazine. CONCLUSIONS: Efficacy data support the use of diazepam in treating prodromal and early warning signs of symptom exacerbation in schizophrenia. This therapeutic strategy may be especially important for patients who refuse antipsychotic drugs or as a supplemental approach in a treatment plan that emphasizes low-dose antipsychotic therapy.

Acute Disease↗
PubMed1999

Comparative effectiveness of fluphenazine decanoate injections every 2 weeks versus every 6 weeks.

OBJECTIVE: Dose reduction strategies for the maintenance treatment of schizophrenia are designed to maintain the benefits of antipsychotic drug therapy while reducing risks. Previous strategies with decanoate preparations have been based on the use of lower doses per injection to achieve dose reduction; these strategies have achieved dose reduction but have resulted in some increase in symptoms. The authors tested a new dose reduction approach: increasing the interval between injections during intramuscular decanoate antipsychotic treatment. METHOD: Fifty outpatients with schizophrenia or schizoaffective disorder were randomly assigned to receive 25 mg of fluphenazine decanoate intramuscularly either every 2 weeks or every 6 weeks for 54 weeks in a double-blind design. RESULTS: The two dose regimens did not differ significantly in relapse, symptom, or side effect measures. The every-6-weeks regimen was associated with a significant reduction in total antipsychotic exposure. CONCLUSIONS: The use of injections every 6 weeks instead of every 2 weeks may increase compliance and improve patients' comfort as well as decrease cumulative antipsychotic exposure, without increasing relapse rates or symptoms.

Adult↗
PubMed1999

Gender differences in temporal lobe structures of patients with schizophrenia: a volumetric MRI study.

OBJECTIVE: The temporal lobe and associated structures have been previously implicated in the neuroanatomy of schizophrenia. This study was designed to assess the potential influence of gender on the morphology of temporal lobe structures, including the superior temporal gyrus and the amygdala/hippocampal complex, in patients with schizophrenia and to examine whether schizophrenic patients differ morphologically in these structures from comparison subjects. METHOD: Magnetic resonance imaging was used to measure the volume of temporal lobe structures, including the superior temporal gyrus, the amygdala/hippocampal complex, and the temporal lobe (excluding the volumes of the superior temporal gyrus and amygdala/hippocampal complex), and two comparison areas--the prefrontal cortex and caudate--in 36 male and 23 female patients with schizophrenia and 19 male and 18 female comparison subjects. RESULTS: There was a significant main effect of diagnosis in the superior temporal gyrus and the amygdala/hippocampal complex, with smaller volumes in patients than in comparison subjects. There was a significant gender-by-diagnosis-by-hemisphere interaction for temporal lobe volume. Temporal lobe volume on the left was significantly smaller in male patients than in male comparison subjects. Female patients and female comparison subjects demonstrated no significant difference in temporal lobe volume. There were no statistically significant gender interactions for the superior temporal gyrus, the amygdala/hippocampal complex, or the comparison regions. CONCLUSIONS: These findings suggest that there may be a unique interaction between gender and the pathophysiologic processes that lead to altered temporal lobe volume in patients with schizophrenia.

Adult↗
PubMed1999

Stability of the diagnosis of deficit syndrome in schizophrenia.

OBJECTIVE: Primary, enduring negative symptoms have been distinguished from negative symptoms more generally and are used to define the deficit syndrome of schizophrenia. Although the validity of the deficit syndrome has been demonstrated by using brain imaging, neuropsychological, illness outcome, and developmental history data, the stability of this diagnostic category has not been tested prospectively by using direct patient assessments. METHOD: Forty-three outpatients with schizophrenia and schizoaffective disorder were categorized into deficit and nondeficit groups an average of 3.8 years after having been previously categorized. RESULTS: There was 83% agreement between initial and blind follow-up designations of deficit status and 88% agreement on the nondeficit categorization. CONCLUSIONS: These results provide evidence for the long-term stability of the deficit syndrome in patients with schizophrenia and the reliability of the deficit/nondeficit categorization when diagnosed by those with appropriate training. Furthermore, they validate the method of categorizing deficit patients by using cross-sectional and retrospective data.

Adult↗
PubMed1998

The relationship between smooth pursuit eye movements and tardive dyskinesia in schizophrenia.

OBJECTIVE: To examine the relationship between smooth pursuit eye movements and tardive dyskinesia (TD) in schizophrenia. METHODS: Forty schizophrenic patients with TD and 25 non-TD patients had smooth pursuit eye movements tested with infrared oculography. In addition to the diagnosis of TD (present or absent), each patient had ratings of severity of TD. RESULTS: There was no significant or strong association between TD and poor smooth pursuit eye movements. CONCLUSION: The results stand in contrast to those of several previous studies, which were based on limited methodology. However, this study was not able to exclude definitively the possibility that TD is associated with poor smooth pursuit, perhaps with a small to moderate effect. Furthermore, these conclusions are limited to simple eye tracking protocols in which distractions are minimized. The question of whether or not TD is associated with poor smooth pursuit in schizophrenia needs to be resurrected.

Adult↗
PubMed1998

The dopamine D3 receptor (DRD3) Ser9Gly polymorphism and schizophrenia: a haplotype relative risk study and association with clozapine response.

Several lines of evidence suggest that the dopamine D3 receptor is involved in the pathophysiology of schizophrenia. The D3 receptor gene (DRD3) contains a polymorphism resulting in a serine-glycine substitution in the N-terminus of the receptor. Shaikh and colleagues have reported a significant association between the DRD3 Ser9 allele and the Ser9/Ser9 genotype with schizophrenia in 133 Caucasians. In a meta-analysis of previous studies, Ser9 and the Ser9/Ser9 genotype were found to be significantly associated with schizophrenia, although these investigators could not confirm reports of excess homozygosity at this locus in schizophrenia. These authors also report that, in an unblinded study, the Ser9/Ser9 genotype was more frequent in patients who did not respond to clozapine. These data represent the most comprehensive examination of DRD3 Ser9Gly in schizophrenia to date. We have therefore determined DRD3 Ser9Gly genotypes in 58 patients with schizophrenia and in their parents. Moreover, we have genotyped 68 schizophrenics participating in double-blind clozapine trials. We do not find that Ser9 is preferentially transmitted in schizophrenia, cannot confirm excess DRD3 homozygosity in schizophrenia, and do not replicate the association between DRD3 and clozapine response. These data suggest that allelic variation in DRD3 may not play a role in the pathophysiology of schizophrenia or in clozapine response.

Alleles↗
PubMed1998

Schizophrenia research: a biennium of progress. Proceedings from the Sixth International Congress on Schizophrenia Research. Colorado Springs, CO, April 12-16, 1997.

The Sixth International Congress on Schizophrenia Research (ICOSR) took place in Colorado Springs, Colorado, April 12-16, 1997, where over 1,000 scientists presented and listened to the latest developments in the search for the cause and treatment of schizophrenia. The ICOSR is sponsored by Maryland Psychiatric Research Center, Case Western Reserve University, and the William K. Warren Foundation. The National Institute of Mental Health and several pharmaceutical companies contributed generously to the meeting. The ICOSR is co-organized by Dr. Carol A. Tamminga, Maryland Psychiatric Research Center, University of Maryland at Baltimore, and Dr. S. Charles Schulz, Case Western Reserve University, Cleveland, Ohio. The William K. Warren Research Award is given to a senior investigator, who has made outstanding contributions to our understanding of schizophrenia. The fifth William K. Warren Research Award was presented to Dr. Philip S. Holzman in recognition of his contributions to the identification of eye-tracking abnormalities as a potential phenotypic marker of the illness and also in recognition of his work as a lifelong mentor for schizophrenia researchers. The ICOSR Young Investigator Awards are presented to junior investigators who have demonstrated the potential to make significant contributions to research on schizophrenia. These awards promote scientific development by enabling these young researchers to attend the meeting. There were 30 Young Investigator Award winners. The ICOSR meeting is organized into four sessions: (1) a morning plenary session; (2) a plenary lecture; (3) a poster session; and (4) concurrent afternoon oral sessions. The morning plenary sessions are comprised of a set of 30-minute lectures, which provide an overview of a particular topic area relevant to schizophrenia research. The plenary lecture is an invited lecture on a basic topic related to current research efforts in schizophrenia. The poster sessions provide a forum for the presentation of prepublication reports of basic and clinical science projects. The afternoon sessions are a collection of approximately 10 focused presentations on current research projects related to a specific topic area. The purpose of this report is to provide an account of the proceedings from the plenary and afternoon oral sessions.

Animals↗
PubMed1998

The role of negative symptoms and cognitive dysfunction in schizophrenia outcome.

Schizophrenia is a lifelong illness, with symptoms beginning in late adolescence/early adulthood and persisting throughout the rest of the patient's life. Positive psychotic symptoms may fluctuate during the course of the illness, but negative symptoms, especially primary negative symptoms, and cognitive dysfunction are relatively constant. The negative symptoms of schizophrenia are both primary (associated with the illness) and secondary (due to depression, neuroleptic-induced parkinsonism or acute psychosis). While secondary negative symptoms may be reduced by treating the causative agent, primary negative symptoms are viewed as enduring, persisting between psychotic episodes. Conventional antipsychotics treat the positive symptoms of schizophrenia, but they have little effect on primary negative and cognitive symptoms. Primary negative symptoms are often associated with poor premorbid function, the male sex, and low IQ (Intelligence Quotient). In addition, most studies find that negative symptoms are associated with a poor overall outcome. Several studies, including our own, have suggested that primary negative symptoms are functionally localized to the frontal and parietal cortices. These kinds of data raise the possibility that primary negative symptoms may have a pathophysiological basis distinct from positive psychosis. Cognitive impairment also appears to be a relatively independent aspect of schizophrenia. Impairment may be evident in a subtle form from early childhood, and often precedes the development of psychotic symptoms. Additional impairment accrues with the onset of psychotic illness with little evidence, in the vast majority of cases, of progression over the course of the illness. Cognitive impairment is only modestly related to psychotic symptom severity and type. However, the extent, and perhaps specific types of cognitive impairment, appear to be predictive of functional outcome.

Adolescent↗
PubMed1998

Association between eye tracking disorder in schizophrenia and poor sensory integration.

OBJECTIVE: The authors tested the hypothesis that eye tracking disorder in schizophrenia is associated with neurological signs. METHOD: The subjects were 93 normal comparison subjects and 59 schizophrenic patients. They were evaluated with the Neurological Evaluation Scale, a standardized rating instrument that assesses sensory integration, motor coordination, sequencing of complex motor acts, and other neurological signs. Also, the schizophrenic patients' smooth-pursuit eye movements were tested in response to a 0.3-Hz sinusoidal target by means of infrared oculography. They were divided into those with (N=18) and without (N=41) eye tracking disorder by using a previously described method, which was based on mixture analysis of the distribution of position root mean square error. RESULTS: The patients with eye tracking disorder had significantly worse performance than the patients without eye tracking disorder with respect to sensory integration, and the effect size was moderate to large. In comparison with the normal subjects, both patient subgroups had significantly worse performance on all of the Neurological Evaluation Scale subscales. CONCLUSIONS: Although neurological signs are present generally in schizophrenia, poor sensory integration is particularly pronounced in patients with eye tracking disorder. A review of the literature shows that the two abnormalities have strikingly similar patterns of validators, including 1) familial aggregation, 2) premorbid presence, 3) syndromal specificity, 4) trait status, and 5) association with the deficit syndrome. Poor sensory integration and eye tracking disorder in schizophrenia may be various manifestations of a common, underlying pathophysiological process.

Adult↗
PubMed1998

Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome.

OBJECTIVE: In a preliminary report, the authors observed that clozapine was superior to haloperidol in the treatment of positive and negative symptoms in stable outpatients with schizophrenia. In this final report, they examine the effects of clozapine on positive and negative symptoms in patients with and without the deficit syndrome to determine which patients receive the positive symptom advantage of clozapine and the extent of clozapine's therapeutic effects on negative symptoms. In addition, they examine the long-term effects of clozapine on positive, negative, and affective symptoms, social and occupational functioning, and quality of life. METHOD: Seventy-five outpatients with schizophrenia, who met retrospective and prospective criteria for residual positive or negative symptoms, were entered into a 10-week double-blind, parallel-groups comparison of clozapine and haloperidol. Patients who completed the double-blind study were then entered into a 1-year open-label clozapine study. RESULTS: For patients who completed the 10-week double-blind study, clozapine was superior to haloperidol in treating positive symptoms. This effect was not observed in the intent-to-treat analyses. There was no evidence of any superior efficacy or long-term effect of clozapine on primary or secondary negative symptoms. Long-term clozapine treatment was associated with significant improvements in social and occupational functioning but not in overall quality of life. CONCLUSIONS: For schizophrenic patients who are able to tolerate clozapine therapy, clozapine has superior efficacy for positive symptoms but not negative symptoms and is associated with long-term improvements in social and occupational functioning for patients with and without the deficit syndrome.

Adult↗
PubMed1998

Structural evaluation of the prefrontal cortex in schizophrenia.

OBJECTIVE: Altered prefrontal cortical function has been repeatedly implicated in the pathophysiology of schizophrenia. Attempts to determine whether this altered function is associated with structural changes in the prefrontal cortex have been hampered by the failure to examine more anatomically and functionally homogeneous regions. The authors have developed a reliable set of anatomical landmarks for subdividing the prefrontal cortex into superior, middle, inferior, and orbital regions, in order to determine whether patients with schizophrenia exhibit selective morphological abnormalities of the prefrontal cortex. METHOD: Magnetic resonance imaging (MRI) studies were obtained in 24 normal control subjects (14 men and 10 women) and 18 patients with schizophrenia (12 men and six women) by using a high-resolution thin spoiled-gradient recall acquisition in the steady-state protocol. The MRI images were used to determine prefrontal gray matter volumes for the four prefrontal regions and prefrontal total gray and white volumes. RESULTS: Patients with schizophrenia exhibited selective gray matter volume reductions in the right and left inferior prefrontal cortex. There were no significant group differences in the other prefrontal regions. Patients with schizophrenia also exhibited decreased prefrontal total white matter and total volumes; there was no significant difference in prefrontal total gray matter volume. CONCLUSIONS: Patients with schizophrenia are characterized by relatively selective reductions in inferior prefrontal cortex gray matter volumes.

Adult↗
PubMed1998

Summer birth and the deficit syndrome of schizophrenia.

OBJECTIVE: Patients with the deficit syndrome differ from other patients with schizophrenia relative to physiological correlates, course of illness, and response to treatment. Because of the abnormal seasonality of birth among persons with schizophrenia, the authors examined the relation between this risk factor and the deficit syndrome. METHOD: Findings in two clinical groups suggested an increase in summer births among deficit syndrome patients. The association between summer birth and the deficit syndrome was then examined in a catchment area study of first-admission patients with psychosis. RESULTS: In the catchment area sample, summer birth was also significantly associated with the deficit syndrome; negative symptoms broadly defined were not. CONCLUSIONS: These findings add to the increasing evidence that 1) patients with the deficit syndrome have a disease with an etiopathophysiology separate from that of other patients with what is now called schizophrenia and 2) the correlates of broadly defined negative symptoms are different from those for the deficit syndrome. The previously reported association between winter birth and schizophrenia appears to apply to nondeficit schizophrenia only.

Adult↗
PubMed1997

Eye tracking disorder in schizophrenia is characterized by specific ocular motor defects and is associated with the deficit syndrome.

The objective was to determine the relationships between eye tracking disorder (ETD) in schizophrenia, specific ocular motor measures, and the deficit syndrome. Twenty-five normal comparison subjects and 53 schizophrenic patients had eye movements tested with infrared oculography using a sinusoidal target. Patients were assessed with the Schedule for the Deficit Syndrome. For the patients, the distribution of position root mean square error (a global measure of pursuit) was best fit by a mixture of two normal distributions. This information was used to divide the patients into two subgroups, those with and those without ETD. ETD was almost completely accounted for by several specific ocular motor measures and was significantly associated with the deficit syndrome. The finding that ETD was almost completely accounted for by specific measures bridges a gap of interpretation in this field. ETD and the deficit syndrome of schizophrenia may share a common pathophysiology of cerebral cortical-subcortical circuits.

Adult↗
PubMed1997

Borna disease virus antibodies and the deficit syndrome of schizophrenia.

We detected anti-Borna disease virus (BDV) antibodies at a 14.4% rate in patients with schizophrenia. The hypothesis of a higher rate of BDV seropositivity in deficit syndrome was borne out in a subset of 64 patients categorized according to the Schedule for the Deficit Syndrome with 5/15 seropositive deficit and 4/49 seropositive nondeficit (p < 0.05). This suggests that the antibodies and possibly a BDV-like virus are pathogenetically linked to this form of schizophrenia.

Adult↗
PubMed1997

The neuroanatomies of schizophrenia.

Schizophrenia is a brain disease whose pathophysiology has escaped detection despite intensive investigation. The failure to delineate the neuroanatomy of schizophrenia is related in part to both the subtle nature of the neuropathological abnormalities and to the failure to address adequately the pathophysiological heterogeneity of schizophrenia. The symptoms of schizophrenia aggregate into relatively independent symptom complexes, which suggests that there may be a distinct neural substrate for each complex. If this is true, then the neuroanatomy of schizophrenia is better addressed as the separate neuroanatomies of symptom complexes. However, the use of symptom complexes to guide future neuroanatomical investigations raises crucial methodological issues, including the differentiation of primary versus secondary symptoms, trait versus state characteristics, and continuous versus categorical variables. Decisive hypothesis testing requires that these issues be addressed in study design.

Brain↗
PubMed1997

Evaluation of treatment-resistant schizophrenia.

A systematic approach to the evaluation and characterization of treatment resistance in schizophrenia has become increasingly important since the introduction of clozapine, risperidone, and olanzapine. The need for accurate evaluation will increase with the introduction of the next generation of antipsychotic medications. People with schizophrenia may manifest a poor response to therapy secondary to intolerance of medication, poor compliance, or inappropriate dosing, as well as true resistance of their illness to antipsychotic drug therapy. Clinicians facing the decision of when to change from one antipsychotic to another must clearly understand the appropriate length of a trial and what target symptoms respond to antipsychotics in order to maximize the response in patients with treatment-resistant schizophrenia.

Antipsychotic Agents↗