Specific measures account for most of the variance in qualitative ratings of smooth pursuit eye movements in schizophrenia.
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Family↗
Biomedical subjects
R W Buchanan
Publications and source records attributed to R W Buchanan.
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↗
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↗
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↗
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↗
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↗
Failure of fusion of the septum pellucidum and the heterogeneity of schizophrenia.
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Adult↗
Attentional impairments in deficit and nondeficit forms of schizophrenia.
OBJECTIVE: Previous studies of attention/information processing impairments in schizophrenia suggest that patients with the deficit syndrome should be characterized by impaired performance on measures of visual information processing. Therefore, the authors examined whether two measures of visual information processing, a degraded stimulus version of the continuous performance test and a forced choice span of apprehension task, were uniquely related to the deficit syndrome. METHOD: Performance on the continuous performance test and span of apprehension task was examined in 20 deficit and 56 nondeficit patients with schizophrenia and in 27 subjects in a normal comparison group. RESULTS: Deficit patients performed significantly less well than both nondeficit patients and the normal comparison group on the continuous performance test and span of apprehension task. There were no significant differences between the nondeficit patients and the normal group on the continuous performance test, but nondeficit patients performed significantly less well on the span of apprehension task than the normal group. Differences between the deficit and nondeficit patients in performance on the continuous performance test and span of apprehension task were not related to total scores on the Brief Psychiatric Rating Scale factor 1 or on the Thought, Language, and Communication scale or to neuroleptic level. CONCLUSIONS: The results suggest that deficit patients are uniquely characterized by impaired performance on the continuous performance test. The deficit patients' differential performance on the continuous performance test may be related to either an inability to activate and allocate attention or an impairment in the perceptual organization of visual information.
Adult↗
Visual information-processing impairments in deficit and nondeficit schizophrenia.
OBJECTIVE: Previous studies of covert visuospatial attention in schizophrenia suggest a subtle form of right hemispatial neglect in acutely ill patients but not in chronic, stable patients. Because of previous work documenting various visual information-processing abnormalities in deficit schizophrenia, the authors investigated whether the deficit/nondeficit categorization would help clarify the presence of visual attentional asymmetries in schizophrenia. METHOD: Performance on a covert visuospatial attention task was examined in clinically stable outpatients with schizophrenia (17 in a deficit subgroup and 28 in a nondeficit subgroup) and 25 normal subjects. Peripheral cue and central cue versions of the covert visuospatial attention task, at 100-, 200-, and 800-msec intervals between cue and target, were administered a week apart. RESULTS: The nondeficit patients exhibited a significant and abnormal asymmetry, with slower reaction time to targets presented in the right visual field than in the left visual field. This right visual field disadvantage was found with both versions of the task, but only at the 100-msec cue-target interval. The deficit patients were slowest in overall reaction time but, similar to the normal subjects, showed no asymmetry. CONCLUSIONS: The results are consistent with slower visual information processing in the left compared to the right cerebral hemisphere in nondeficit schizophrenia. This finding cannot be accounted for by differences between the deficit and nondeficit subgroups in demographic characteristics, chronicity, or medication effects, nor is it secondary to generalized cognitive impairment.
Adolescent↗
Clozapine response and the 5HT2C Cys23Ser polymorphism.
The presence of the 5HT2C receptor allele, Ser23, has recently been reported to predict favorable response to the antipsychotic drug, clozapine. This finding is of interest as Ser23, compared with the more abundant Cys23, alters pharmacological characteristics of the receptor and therefore may provide insights into the mechanism of action of antipsychotic drugs. We determined 5HT2C receptor genotype at the Cys23Ser locus in 66 subjects participating in double-blind studies of clozapine. There was no relationship between Ser23 and clozapine response (p = 0.30, Fisher's exact) nor was there any effect of Ser23 upon absolute levels of psychiatric symptoms after 10 weeks of clozapine treatment (t = -0.57, p = 0.57). These data suggest that this 5HT2C receptor polymorphism is not associated with clozapine response.
Alleles↗
Does pursuit abnormality in schizophrenia represent a deficit in the predictive mechanism?
Although an abnormality of smooth pursuit eye movement has been consistently noted in schizophrenia, the underlying ocular motor pathophysiology is unknown. It is unclear whether the abnormality represents deficits in processing of information provided by the moving target, generation of pursuit eye movements, or other ocular motor and related cognitive processes. To evaluate the ability to process information provided by a moving target, saccadic accuracies were studied in step-ramp and single step tasks. Schizophrenic (with and without tardive dyskinesia [TD]) and normal subjects made equally accurate initial corrective saccades to the moving target. Thus, when the target jumped and then smoothly moved (creating a position and a velocity error on the retina), the patients were able to process retinal motion information and generate a normally accurate saccadic response. After the initial corrective saccade, both groups followed the target with a combination of pursuit eye movements and occasional catch-up saccades. During this period, the retinal velocity error is minimal because the eye approximates the target motion, and the major source of target motion information both for the smooth pursuit and saccadic responses is extra-retinal (i.e., predictive mechanism). The accuracies of catch-up saccades were significantly lower in the schizophrenic patients than in the normal subjects. During this period, overall pursuit performance, measured by pursuit gain, was also significantly worse in the patients. Accuracies of subsequent catch-up saccades, but not initial corrective saccades, significantly predicted the pursuit gain. Low pursuit gain was associated with high numbers of saccades per time spent in pursuit, which were similar in both schizophrenic subgroups (i.e., with and without TD), but were only significantly higher in the patients with TD than in the normal subjects. These preliminary data suggest that schizophrenic patients are able to process retinal motion information but have difficulties in using extra-retinal motion information to generate an appropriate saccadic response.
Adult↗
Catching up on schizophrenia. The Fifth International Congress on Schizophrenia Research, Warm Springs, Va, April 8-12, 1995.
It is axiomatic that the diversity and ingenuity of strategies in the study of schizophrenia bear testimony to the complexity of this disorder. Accordingly, the opportunity for investigators of diverse interests to share their latest findings and be informed of developments in key areas of science is critical to advance our understanding of schizophrenia. Nearly 700 investigators from around the world gathered at Warm Springs, Va, to present their data at the Fifth International Congress on Schizophrenia Research (April 8-12, 1995). This 5-day conference, held every other year alternating with the European Winter Workshop on Schizophrenia, is co-organized by S. Charles Schulz, MD, Case Western Reserve University, Cleveland, Ohio, and Carol Tamminga, MD, Maryland Psychiatric Research Center, University of Maryland at Baltimore. Drs Schulz and Tamminga first held the Congress in 1987 in Clearwater, Fla, with 170 investigators presenting. The Congress has flourished since then and is now the largest research meeting devoted solely to schizophrenia. The Congress organizers, the program coordinator (Jeffrey Lieberman, MD, Hillside Hospital, Glen Oaks, NY), and the Congress coordinator (Susan Nusbaum, Maryland Psychiatric Research Center) are congratulated on the success of this event and its contribution to fostering initiatives and collaborations within schizophrenia research.
Female↗
The deficit syndrome in the DSM-IV Field Trial. Part II. Depressive episodes and persecutory beliefs.
Patients with the deficit syndrome are remarkable for their decrease in interest in social relationships, suggesting they have an abnormality in those brain regions controlling social behavior and social cognition. To further assess social behavior and social cognition in this group of patients, we examined the relationships among three aspects of the psychopathology: suspiciousness; major depressive episodes; and the deficit syndrome. These features of psychopathology were examined in two clinical samples: stable outpatients from a research clinic (the MPRC sample), and patients in the DSM-IV Field Trial. In both samples, patients with history of a depressive episode had more severe suspiciousness than those without such a history; other psychotic symptoms were not associated with depressive episodes. In the MPRC sample, patients with the deficit syndrome exhibited less severe suspiciousness than nondeficit patients; in the Field Trial sample, this same comparison had a nonsignificant trend in the same direction. In the Field Trial sample, patients with the deficit syndrome also had less severe delusions with a predominantly social content than did nondeficit patients. These findings suggest suspiciousness is a risk factor for major depression in schizophrenia, and that the decreased interests in social relationships exhibited by deficit syndrome patients is reflected in the content of their delusions.
Adult↗
Negative symptoms: diagnosis, treatment and prognosis.
The concept of negative symptoms is derived from Kraeplin's description of the dissolution of the personality in patients with schizophrenia. Negative symptoms may be either primary, or secondary to positive symptoms, antipsychotic side effects, dysphoric affect and environmental deprivation. Primary negative symptoms represent core features of the illness, and have been termed deficit symptoms. The differentiation of primary from secondary negative symptoms has important treatment implications, as treatment approaches vary greatly for the different types of negative symptoms. Specific pharamacological and psychosocial treatments are available for secondary negative symptoms. However, to date, there are no known effective treatments for primary negative symptoms. The importance of developing effective treatments for primary negative symptoms is underscored by the relationship of these symptoms to poor social, occupational, and global outcome.
Antipsychotic Agents↗
Clozapine conflict.
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Antipsychotic Agents↗
Fluoxetine augmentation of clozapine treatment in patients with schizophrenia.
OBJECTIVE: The authors examined the efficacy of fluoxetine augmentation of clozapine treatment response in schizophrenic outpatients who, despite adequate treatment with clozapine, continued to exhibit persistent positive or negative symptoms. METHOD: Thirty-three patients completed on 8-week, double-blind, parallel-groups comparison of adjunctive fluoxetine and placebo. RESULTS: There were no significant differences in positive, negative, depressive, or obsessive-compulsive symptoms between patients given adjunctive fluoxetine or placebo. CONCLUSIONS: These results suggest that fluoxetine is not effective in augmenting clozapine treatment response.
Adult↗
Differential effect of clozapine on weight: a controlled study.
OBJECTIVE: This study examined whether clozapine induces more weight gain than haloperidol and whether weight gain is related to clinical improvement. METHOD: The weight and symptoms of 39 outpatients with schizophrenia who were randomly assigned to double-blind treatment with either clozapine or haloperidol were assessed. The weight and symptoms of 33 of the patients who chose to take clozapine during a 1-year follow-up after the study ended were also assessed. RESULTS: The patients treated with clozapine gained significantly more weight over baseline (7%) than the haloperidol-treated patients (1%). Weight gain was not significantly correlated with improvements in either positive or negative symptoms. Fifty-eight percent of the patients followed for 1 year gained at least 10% over their baseline weight. CONCLUSIONS: Weight gain is an important side effect of clozapine and is unrelated to the drug's differential antipsychotic efficacy.
Ambulatory Care↗
Association of abnormal smooth pursuit eye movements with the deficit syndrome in schizophrenic patients.
OBJECTIVE: The authors' goal was to test the hypothesis that abnormal smooth pursuit eye movements in schizophrenic patients are associated with the deficit syndrome. METHOD: The eye movements of 24 normal comparison subjects, 32 patients with nondeficit schizophrenia, and 11 patients with deficit schizophrenia were tested with infrared oculography using foveapetal step-ramp targets. RESULTS: The group of schizophrenic patients had normal latency to pursuit onset, abnormally decreased open-loop acceleration and abnormally decreased velocity during the periods of closed-loop acceleration and steady-state pursuit. The subgroup of schizophrenic patients with the deficit syndrome had particularly poor performance during the periods of open- and closed-loop acceleration. CONCLUSIONS: Patients with schizophrenia have abnormal smooth pursuit eye movements in response to a step-ramp stimulus, and the defects are particularly pronounced in patients with the deficit syndrome. Abnormal smooth pursuit eye movements in schizophrenia and related disorders have been consistently linked with primary and enduring negative symptoms.
Adult↗