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Biomedical subjects

S R Marder

Publications and source records attributed to S R Marder.

At least 55 records · Page 3Linked to original sources
PubMed1997

Does risperidone improve verbal working memory in treatment-resistant schizophrenia?

OBJECTIVE: Treatment efficacy in schizophrenia is typically defined in terms of symptom reduction. However, new antipsychotic medications could potentially have an impact on aspects of disability, such as neurocognitive deficits. The authors evaluated the effects of risperidone on verbal working memory, a memory component of theoretical interest because of its link to prefrontal activity and of practical interest because of its link to psychosocial rehabilitation. METHOD: Verbal working memory of 59 treatment-resistant schizophrenic patients was assessed as part of a randomized, double-blind comparison of treatment with risperidone and haloperidol. Verbal working memory was measured under both distracting and nondistracting conditions at baseline and after 4 weeks of both fixed- and flexible-dose pharmacotherapy. RESULTS: Risperidone treatment had a greater beneficial effect on verbal working memory than haloperidol treatment across testing conditions (with and without distraction) and study phases (fixed and flexible dose). The treatment effect remained significant after the effects of benztropine cotreatment, change in psychotic symptoms, and change in negative symptoms were controlled. Neither benztropine status nor symptom changes were significantly related to memory performance. CONCLUSIONS: Treatment with risperidone appears to exert a more favorable effect on verbal working memory than treatment with a conventional neuroleptic. The beneficial effect appears to be due, at least partially, to a direct effect of the drug, possibly through antagonism of the 5-HT2A receptor. Results from this study suggest that pharmacotherapeutic efficacy in schizophrenia treatment could be broadened to include impact on neurocognitive abilities.

Adult↗
PubMed1997

The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials.

BACKGROUND: In two double-blind trials conducted in North America, 513 patients with chronic schizophrenia received risperidone, haloperidol, or placebo. In the present study, combined data from the two trials were analyzed. METHOD: Patients were randomly assigned to receive placebo, fixed doses of risperidone (2, 6, 10, and 16 mg/day) or 20 mg/day of haloperidol for 8 weeks. Factor analysis of scores on the Positive and Negative Syndrome Scale (PANSS) produced five dimensions (negative symptoms, positive symptoms, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression), similar to the five dimensions of previous factor-analytic studies of PANSS data. RESULTS: Mean changes (symptom reductions) in PANSS factor scores from baseline to treatment Weeks 6 and 8 were significantly greater in patients receiving 6-16 mg/day of risperidone than in patients receiving placebo or haloperidol. The advantages of risperidone were greatest for negative symptoms, uncontrolled hostility/excitement, and anxiety/depression. Even at the lowest dose, 2 mg/day, risperidone was significantly (p < or = .05) superior to haloperidol in reducing negative symptoms. The differences in outcomes between risperidone and haloperidol on PANSS scores were not related to extrapyramidal symptoms. CONCLUSION: Risperidone produced significantly (p < or = .05) greater improvements than haloperidol on all five dimensions. The large between-group differences on negative symptoms, hostility/excitement, and anxiety/depression suggest that risperidone and other serotonin/dopamine antagonists have qualitatively different effects from those of conventional antipsychotic agents.

Adolescent↗
PubMed1996

Age at illness onset and left temporal lobe length in males with schizophrenia.

Post-mortem data suggest that in schizophrenia, temporal lobe length may be associated with age at illness onset. We used sagittal magnetic resonance images standardly acquired in reference to a coronal pilot image to obtain linear measurements of the left hemisphere in 38 male schizophrenic patients early in the course of their illness and 21 matched normal controls. In addition to temporal lobe and anterior temporal lobe (anterior to the anterior commissure) lengths, measurements of maximal brain and skull lengths were also obtained. The data show that differences in temporal lobe length between patients and normal controls are primarily due to significant differences between the groups in the global measures of brain and skull lengths. However, within the patient group, a significant association between temporal lobe length and age at onset of psychosis was observed. The same association was observed when the anterior part of the temporal lobe was measured separately. These associations remained significant after controlling for multiple variables such as subject height and brain and skull lengths. Further statistical evaluations showed that the temporal lobe was significantly shorter among the subgroup of schizophrenics whose illness began before the age of 23. The data suggest that temporal lobe length may be a useful variable for investigating the biological heterogeneity of schizophrenia and highlight important technical issues regarding current efforts to measure the volumes of temporal lobe structures.

Adult↗
PubMed1996

Display visual angle and attentional scanpaths on the span of apprehension task in schizophrenia.

The effect of display visual angle on span of apprehension (SOA) task performance was investigated in patients with schizophrenia and nonpsychiatric individuals. Narrow and wide visual-angle presentations of 3- and 10-letter arrays were compared. Detection rates were significantly higher with narrow than wide visual angle for nonpsychiatric individuals; the performance of those with schizophrenia was stable across visual-angle conditions. Patients with schizophrenia were best discriminated from nonpsychiatric individuals in the narrow-angle, 10-letter condition. Scanpath analyses, which were based on the pattern of detection rates across different target quadrant locations, suggested that the patients with schizophrenia used a similar number and path of covert scan moves as did the controls. Hypotheses are discussed regarding which of the multiple cognitive processes tapped by the SOA task may be impaired in schizophrenia.

Adult↗
PubMed1996

Pharmacological treatment strategies in acute schizophrenia.

It may be helpful for clinicians to consider the management of schizophrenia as occurring in three different phases: an acute phase which lasts about 4-8 weeks, a resolving phase which lasts about 4-6 months and a stable phase which lasts as long as the patient remains in remission. During the acute phase, patients demonstrate active symptoms of schizophrenia. The goal of treatment during this phase is to reduce the most severe symptoms of the illness, particularly positive symptoms. Nearly all acute episodes should be treated with an antipsychotic medication. Moreover, drug treatment should occur as early in this phase as possible, Certain treatment principles should guide management: an antipsychotic drug and dose should be used that appropriately balances side effects and efficacy. Trial of the selected drug(s) should last at least 4-6 weeks before the medication is changed. Newer antipsychotics have clear advantages over older drugs in terms of side effects and efficacy. Greater use of these agents may improve the outcome in acute schizophrenia.

Acute Disease↗
PubMed1996

Two-year outcome of social skills training and group psychotherapy for outpatients with schizophrenia.

OBJECTIVE: The authors evaluated the effectiveness of behaviorally oriented social skills training and supportive group therapy for improving the social adjustment of schizophrenic patients living in the community and for protecting them against psychotic relapse. METHOD: Eighty male outpatients with schizophrenia were stabilized with a low dose of fluphenazine decanoate (5 to 10 mg every 14 days), which was supplemented with oral fluphenazine (5 mg twice daily) or a placebo when they first met criteria for a prodromal period. (Half of the patients did so at some time during the study.) Patients were randomly assigned to receive either social skills training or supportive group therapy twice weekly for 6 months and then weekly for the next 18 months. Rates of psychotic exacerbation were monitored, as were scores on the Social Adjustment Scale II. RESULTS: There were significant main effects favoring social skills training over supportive group therapy on two of the six Social Adjustment Scale II cluster totals examined (personal well-being and total) and significant interactions between psychosocial treatment and drug treatment for three items (external family, social and leisure activities, and total). In each case, these interactions indicated that the advantage of social skills training over supportive group therapy was greatest when it was combined with active drug supplementation. Social skills training did not significantly decrease the risk of psychotic exacerbation in the full group, but an advantage was observed (post hoc) among patients who received placebo supplementation. CONCLUSIONS: These findings suggest that social skills training resulted in greater improvement in certain measures of social adjustment than supportive group therapy. The greatest improvement in social outcomes occurred when social skills training was combined with a pharmacological strategy of active drug supplementation at the time prodromal worsening of psychotic symptoms was first observed. However, these improvements were modest in absolute terms and confined to certain subgroups of patients.

Adult↗
PubMed1996

Predictive value of eosinophilia for neutropenia during clozapine treatment.

BACKGROUND: Myelotoxicity continues to hinder the widespread use of clozapine in the United States. It has been theorized that eosinophilia predicts later agranulocytosis and that agranulocytosis occurs due to an immunologic mechanism. Our study compares the rates of these dyscrasias in clozapine-treated patients and a control group. METHOD: Forty-one patients taking clozapine and 29 patients taking haloperidol were monitored for a period of 6 months. Rates of eosinophilia and neutropenia were compared between the two treatment groups. RESULTS: Treatment-emergent eosinophilia occurred frequently in both haloperidol- and clozapine-treated patients. No significant difference was seen between groups in the incidence of eosinophilia and neutropenia. CONCLUSION: We find no statistical difference between the rates of eosinophilia or neutropenia in haloperidol- and clozapine-treated patients. This study does not support the use of eosinophilia as a reliable predictor of neutropenia.

Adult↗
PubMed1996

Management of schizophrenia.

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for diagnosing schizophrenia require the presence of characteristic symptoms and disabilities, as well as the specific exclusion of other disorders with similar symptomatology. Once schizophrenia is diagnosed, the classification of schizophrenic symptoms as psychotic, disorganized, or negative can help clinicians predict treatment outcomes and individualize both pharmacologic and psychosocial treatment. Three treatment phases (acute, resolving, and maintenance) have been described; each has different medication strategies and goals. The introduction of novel antipsychotic agents, such as clozapine and risperidone, has enhanced the clinicians' ability to manage schizophrenic patients. Nonetheless, psychosocial treatment remains an important component of overall patient management.

Antipsychotic Agents↗
PubMed1996

Clinical experience with risperidone.

Recent clinical experiences with risperidone including controlled trials, clinical observations, and reports of side effects are reviewed. The controlled trials indicate that risperidone is an effective anti-psychotic that may have advantages over conventional antipsychotics for treating both positive and negative symptoms of schizophrenia. A number of clinical reports indicate that risperidone is also effective for psychotic illnesses that result from other disorders. Risperidone has a relatively mild side effect profile when compared with conventional antipsychotics.

Clinical Trials as Topic↗
PubMed1996

Management of treatment-resistant patients with schizophrenia.

This review will focus on three categories of poor response of patients with schizophrenia to an antipsychotic medication. The first category includes patients who continue to demonstrate positive psychotic symptoms when they receive adequate trials of an antipsychotic. These individuals may improve when their drug doses are altered or when they receive other drugs such as lithium or benzodiazepines in addition to their antipsychotic. Clozapine has been shown to result in substantial improvement in a majority of these patients. Additional evidence suggests that risperidone will also be effective in these individuals. The second category of poor responders consists of patients who are unable to tolerate the side effects of antipsychotics. These individuals may respond when they are changed to a newer antipsychotic. The third category includes patients who have persistent negative symptoms while they are treated with an antipsychotic. There is substantial evidence that these patients will demonstrate improvement in negative symptoms when they receive clozapine and risperidone as well as newer antipsychotics including olanzapine, sertindole, and quetiapine.

Antipsychotic Agents↗
PubMed1995

Schizophrenic patients' perceptions of their relatives' attitudes.

Although the attitudes of family members as revealed by measures of expressed emotion (EE) have been shown to be associated with the course of schizophrenic illness, little is known about how the patients perceive these attitudes. A detailed interview was used to assess patients' perceptions of their family members' behaviors toward them. Family member's EE was assessed with the Five-Minute Speech Sample (FMSS). Overall, patients' perceptions of criticism were congruent with a component of the FMSS-EE that measures criticism. Results indicated that when family members had high EE/critical scores, patients perceived them as displaying more instances of critical behavior. All cases in which patients' perceptions of criticism were incongruent with measures of FMSS-EE occurred among ethnic minority group members. Although the FMSS-EE did not predict outcome in this study, patients who perceived their relatives as higher in criticism had more negative outcomes at 1 year. These findings suggest that when family environments are examined in patients from ethnic minority groups, the patients' perspective may be a more potent predictor of outcome than traditional measures of EE.

Adult↗
PubMed1995

Distribution of fluphenazine and its metabolites in brain regions and other tissues of the rat.

Rats were given 5, 10, or 20 mg/kg oral doses of fluphenazine (FLU) dihydrochloride daily for 15 days. FLU and its sulfoxide (FL-SO), 7-hydroxy (7-OH-FLU) and N4'-oxide (FLU-NO) metabolites were assayed in plasma, liver, kidney, fat, whole brain, and brain regions by specific and sensitive radioimmunoassays (RIA). All metabolites were detected in tissues at higher levels than in plasma, and the levels increased with dose. FLU was 10- to 27-fold higher in brain regions than in plasma. Brain vs plasma levels of FLU correlated more closely than levels of its metabolites. Liver contained the highest levels of all analytes at all doses. FLU-SO was the major metabolite in brain regions (24% to 96% of FLU) and accumulated in fat 43 to 75 times more than FLU. Levels of 7-OH-FLU and FLU-NO were very low in brain (1% to 20% of FLU). FLU-SO and FLU-NO had only 1% to 3% the affinity for D1 and D2 receptors, but 7-OH-FLU had 20% the D2 and 5% the D1 affinity of FLU. The low affinity for dopamine receptors and low brain-levels of metabolites of FLU indicate that they are not likely to contribute importantly to pharmacologic responses of FLU. Also, the estimated relative "activity factor" for these compounds in the brain indicated that the contribution to neuropharmacologic activity by metabolites is less than 1% of FLU. Consequently, clinical monitoring of plasma FLU alone may be sufficient.

Animals↗
PubMed1995

Positron-emission tomography in tardive dyskinesia.

Cerebral glucose metabolic rates were determined in normal control subjects (n = 26) and schizophrenic patients with tardive dyskinesia (n = 14). Globus pallidus and primary motor cortex (precentral gyrus) metabolic values divided by those of the cerebral hemispheres were significantly increased in the patient group. A similar metabolic pattern has not been reported for schizophrenic patients without tardive dyskinesia, and the abnormalities were demonstrated despite the normal appearance of the basal ganglia on X-ray CT. The findings differed markedly from the reduced metabolic rates of the basal ganglia previously identified in other choreiform disorders, including Huntington's and Wilson's diseases. The findings suggest that tardive dyskinesia is characterized by increased pallidal synaptic activity resulting from either altered striatopallidal input or increased pallidal interneuron firing.

Adult↗
PubMed1994

Simultaneous determination of plasma haloperidol and its metabolite reduced haloperidol by liquid chromatography with electrochemical detection. Plasma levels in schizophrenic patients treated with oral or intramuscular depot haloperidol.

A simple and highly sensitive liquid chromatographic method with electrochemical detection for the simultaneous determination of haloperidol and its metabolite reduced haloperidol in human plasma has been developed. The sample preparation for the analysis involves a simple one-step extraction procedure with 10% methylene chloride in pentane. The compounds were separated on a cyano column maintained at a temperature of 40 degrees C and were detected electrochemically by a flow-through analytical cell kept at +0.95 V. The standard curve is linear over the range of 0.1 to 15 ng/ml and the lower limit of quantitation is 0.1 ng/ml for haloperidol and 0.25 ng/ml for reduced haloperidol which is equivalent to approximately 40 pg on column when 1 ml of plasma was used for the analysis. The lower limit of quantitation for reduced haloperidol can be extended to 0.1 ng/ml if 2 ml of plasma is used in the analysis. The coefficient of variation of the determination of plasma levels by this method over the standard curve concentration range was less than 10%. Commonly co-administered drugs and other neuroleptics used in conjunction with haloperidol did not interfere in the determination of either haloperidol or reduced haloperidol. This method has been successfully used for the determination of haloperidol and reduced haloperidol in plasma and their levels in patients treated with various doses oral haloperidol or intramuscular haloperidol decanoate are reported.

Administration, Oral↗
PubMed1994

In vivo evaluation of brain iron in Alzheimer's disease and normal subjects using MRI.

Magnetic resonance imaging (MRI) can measure transverse relaxation rate (R2) of tissues. Although R2 is increased by tissue iron levels, R2 is not a specific measure of iron. A new method, based on the fact that ferritin (the primary tissue iron storage protein) affects R2 in a field-dependent manner, can quantify tissue iron with specificity by measuring the Field Dependent R2 Increase (FDRI). Using the FDRI method, we compared brain iron stores in frontal white matter, caudate nucleus, putamen, and globus pallidus of five male patients with Alzheimer disease (AD) and eight age and gender-matched normal controls. FDRI values were significantly higher among AD patients in the caudate and globus pallidus. The data suggest that AD may involve disturbances in brain iron metabolism and that the involvement of iron in the pathophysiology of age-related neurodegenerative disorders can be investigated in vivo using MRI.

Aged↗
PubMed1994

Fluphenazine vs placebo supplementation for prodromal signs of relapse in schizophrenia.

BACKGROUND: We studied the effectiveness of treating patients with low doses of fluphenazine decanoate and supplementing them with oral fluphenazine when there was evidence of prodromal symptoms of psychotic exacerbations. METHODS: Eighty schizophrenic patients who were receiving 5 to 10 mg of fluphenazine decanoate every 2 weeks were monitored for prodromal symptoms using an idiosyncratic prodromal rating scale. When patients met our criteria for a prodromal episode, they were randomly assigned to a double-blind comparison of oral fluphenazine hydrochloride (5 mg twice daily) or a placebo for the current and future prodromal episodes. We compared rates of psychotic exacerbations in the two treatment groups. RESULTS: Thirty-six patients (45%) met the criteria for a prodrome at some point during the trial and were randomized to drug or placebo. Using survival analysis during the entire 2 years, we did not find a significant difference between fluphenazine and placebo in the likelihood that a prodrome would continue to an exacerbation. Survival analysis beginning at the start of the second year of treatment did indicate a significant reduction in exacerbation risk for patients receiving drug supplementation (P = .032). Similarly, there was no difference between the two groups in the proportion of time at risk spent in exacerbation during the first year, but patients receiving active drug supplementation spent less time in an exacerbated state in the second year (P = .05). CONCLUSIONS: Our treatment strategy appeared to be effective for some patients, particularly those who were able to remain in the study beyond the first year. Although the occurrence of a prodrome was a fairly good marker that a patient was at high risk of ultimate exacerbation with our low-dose maintenance protocol, prodromes were not highly sensitive indicators of imminent exacerbation.

Acute Disease↗
PubMed1994

Persisting negative symptoms and information-processing deficits in schizophrenia: implications for subtyping.

To test the hypothesis that schizophrenic patients with persisting negative symptoms have stable information-processing impairments compared with schizophrenic patients without persisting negative symptoms, 20 chronic schizophrenic outpatients were trichotomously subgrouped on the basis of the level of negative symptoms that they displayed across multiple rating periods over a 1-year period. Brief Psychiatric Rating Scale assessments of negative symptoms were used to assign subjects into either an operationally defined persisting negative symptom (PNS), transient negative symptom (TNS), or no negative symptom (NNS) subgroup. The level and pattern of these subgroups' performance on a visual information-processing task, the Span of Apprehension Test (SPAN), were compared. Although the three groups did not differ statistically in level of SPAN performance during a drug-free baseline, the PNS group had significantly poorer SPAN performance than the other two groups at the 1-year followup assessment. The SPAN performance of the TNS and NNS groups improved while the SPAN performance of the PNS group did not improve over the 1-year followup period.

Adult↗