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Biomedical subjects

Donald C Goff

Publications and source records attributed to Donald C Goff.

At least 37 records · Page 2Linked to original sources
PubMed2005

A pilot study of functional Cognitive Behavioral Therapy (fCBT) for schizophrenia.

BACKGROUND: The feasibility and preliminary efficacy of a novel cognitive behavioral treatment for decreasing psychotic symptoms and improving social functioning was evaluated in a pilot study. This represents the first treatment outcome study of CBT for psychosis with a manualized, active comparison condition. METHODS: Thirty outpatients with schizophrenia or schizoaffective disorder, depressed type with residual psychotic symptoms were randomly assigned to either 16 weekly sessions of functional cognitive behavioral therapy (fCBT) or psychoeducation (PE) with assessments conducted at baseline and post-treatment by blind evaluators. RESULTS: Attrition was only 7% and did not differ between fCBT and PE, indicating good tolerability of both treatments. For this sample with persistent symptoms, between groups effects were not significantly different, but within group effect sizes indicated greater treatment benefit for fCBT on positive symptoms, particularly for the PSYRATS voices subscale. CONCLUSION: The results suggest that fCBT is well tolerated and holds promise for reducing persistent positive symptoms.

Adolescent↗
PubMed2005

Functional magnetic resonance imaging studies of schizophrenic patients during word production: effects of D-cycloserine.

The objective of the present study was to examine patterns of cortical activation underlying D-cycloserine's therapeutic efficacy in schizophrenic patients using functional magnetic resonance imaging (fMRI). We measured frontal and temporal lobe activation following a word fluency task in 12 subjects meeting DSM-IV criteria for schizophrenia at baseline and after 8 weeks of supervised treatment, using a double-blind, placebo-controlled design. Half of the patients received D-cycloserine (n = 6) as a supplement to their conventional neuroleptic treatment while the other half (n = 6) was augmented with placebo. Patients receiving D-cycloserine, but not placebo, demonstrated a significant increase in temporal lobe activation. This increased activation was significantly associated with a reduction in negative symptoms. These results suggest that the addition of D-cycloserine to conventional neuroleptics may improve negative symptoms through enhanced temporal lobe function.

Antipsychotic Agents↗
PubMed2005

Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis.

BACKGROUND: While the incidence of new-onset diabetes mellitus may be increasing in patients with schizophrenia treated with certain atypical antipsychotic agents, it remains unclear whether atypical agents are directly affecting glucose metabolism or simply increasing known risk factors for diabetes. OBJECTIVE: To study the 2 drugs most clearly implicated (clozapine and olanzapine) and risperidone using a frequently sampled intravenous glucose tolerance test. DESIGN: A cross-sectional design in stable, treated patients with schizophrenia evaluated using a frequently sampled intravenous glucose tolerance test and the Bergman minimal model analysis. SETTING: Subjects were recruited from an urban community mental health clinic and were studied at a general clinical research center. Patients Fifty subjects signed informed consent and 41 underwent the frequently sampled intravenous glucose tolerance test. Thirty-six nonobese subjects with schizophrenia or schizoaffective disorder, matched by body mass index and treated with either clozapine, olanzapine, or risperidone, were included in the analysis. MAIN OUTCOME MEASURES: Fasting plasma glucose and fasting serum insulin levels, insulin sensitivity index, homeostasis model assessment of insulin resistance, and glucose effectiveness. RESULTS: The mean +/- SD duration of treatment with the identified atypical antipsychotic agent was 68.3 +/- 28.9 months (clozapine), 29.5 +/- 17.5 months (olanzapine), and 40.9 +/- 33.7 (risperidone). Fasting serum insulin concentrations differed among groups (F(33) = 3.35; P = .047) (clozapine>olanzapine>risperidone) with significant differences between clozapine and risperidone (t(33) = 2.32; P = .03) and olanzapine and risperidone (t(33) = 2.15; P = .04). There was a significant difference in insulin sensitivity index among groups (F(33) = 10.66; P<.001) (clozapine olanzapine>risperidone) (clozapine vs risperidone, t(33) = 2.94; P = .006; olanzapine vs risperidone, t(33) = 2.42; P = .02). There was a significant difference among groups in glucose effectiveness (F(30) = 4.18; P = .02) (clozapine<olanzapine<risperidone) with significant differences between clozapine and risperidone (t(30) = -2.59; P = .02) and olanzapine and risperidone (t(30) = -2.34, P = .03). CONCLUSIONS: Both nonobese clozapine- and olanzapine-treated groups displayed significant insulin resistance and impairment of glucose effectiveness compared with risperidone-treated subjects. Patients taking clozapine and olanzapine must be examined for insulin resistance and its consequences.

Adult↗
PubMed2005

What is perseverated in schizophrenia? Evidence of abnormal response plasticity in the saccadic system.

Although perseveration is sometimes attributed to defective set switching, the authors have recently shown that set-switching is normal in schizophrenia. In this article, the authors tested for persistent states of the saccadic response system, rather than set perseveration. Schizophrenic and healthy subjects performed antisaccades and prosaccades. The authors analyzed for 3 carry-over effects. First, whereas the latency of the current saccade correlated with that of the prior saccade in both groups, the correlations under mixed-task conditions declined in healthy but not in schizophrenic subjects. Second, antisaccades in penultimate trials delayed upcoming saccades in schizophrenic but not in healthy subjects. Third, schizophrenic subjects were more likely to erroneously perseverate the direction of a prior antisaccade but not a prior prosaccade. The authors concluded that, in schizophrenia, the effects of correct antisaccades are persistent not weak. Saccades in schizophrenia are characterized by perseveration of antisaccade-induced changes in the saccadic response system rather than failures to switch task set.

Adult↗
PubMed2005

Adverse cardiac effects associated with clozapine.

OBJECTIVE: To review the published literature on serious adverse cardiac events associated with the atypical antipsychotic agent, clozapine, and to make recommendations for cardiac assessment of candidates for clozapine treatment and for monitoring of cardiac status after treatment is initiated. DATA SOURCES: We searched the PubMed and MEDLINE databases for articles published from 1970 to 2004 that contain the keywords "clozapine and myocarditis," "clozapine and cardiomyopathy," "clozapine and cardiotoxicity," "clozapine and sudden death" or "clozapine and mortality." We also manually searched the bibliographies of these articles for related sources. STUDY SELECTION: We reviewed the 30 case reports, case series, laboratory and clinical trials, data mining studies, and previous reviews identified by this search. DATA SYNTHESIS: Recent evidence suggests that clozapine is associated with a low (0.015% to 0.188%) risk of potentially fatal myocarditis or cardiomyopathy. The drug is not known to be independently associated with pathologic prolongation of the QTc interval, but it may contribute to pathologic QTc prolongation in patients with other risk factors for this condition. CONCLUSIONS: The low risk of a serious adverse cardiac event should be outweighed by a reduction in suicide risk for most patients taking clozapine. We provide recommendations for assessing and monitoring cardiac status in patients prior to and after initiation of treatment with clozapine.

Antipsychotic Agents↗
PubMed2005

A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia.

The objective of this study was to examine the efficacy of bupropion for smoking cessation in patients with schizophrenia. Adults with schizophrenia who smoked more than 10 cigarettes per day and wished to try to quit smoking were recruited from community mental health centers, enrolled in a 12-week group cognitive behavioral therapy intervention, and randomly assigned to receive either bupropion sustained-release 300 mg/d or identical placebo. Fifty-three adults, 25 on bupropion and 28 on placebo, were randomized, completed at least 1 postbaseline assessment and were included in the analysis. The primary outcome measures were 7-day point prevalence abstinence in the week after the quit date (week 4) and at the end of the intervention (week 12). Subjects in the bupropion group were significantly more likely to be abstinent for the week after the quit date (36% [9/25] vs. 7% [2/28], P = 0.016) and at end of the intervention (16% [4/25] vs. 0%, P = 0.043). Subjects in the bupropion group also had a higher rate of 4-week continuous abstinence (weeks 8-12) (16% [4/25] vs. 0%, P = 0.043) and a longer duration of abstinence (4.2 [3.2] weeks vs. 1.8 [0.96] weeks, t = 2.30, P = 0.037). The effect of bupropion did not persist after discontinuation of treatment. Subjects in the bupropion group had no worsening of clinical symptoms and had a trend toward improvement in depressive and negative symptoms. We conclude that bupropion does not worsen clinical symptoms of schizophrenia and is modestly effective for smoking cessation in patients with schizophrenia. The relapse rate is high after treatment discontinuation.

Adult↗
PubMed2005

A double-blind, placebo-controlled trial of sibutramine for olanzapine-associated weight gain.

OBJECTIVE: Weight gain is commonly observed with olanzapine treatment and can increase the risk for obesity, cardiovascular disease, hypertension, and diabetes mellitus. This study examined the effectiveness of sibutramine, an approved weight loss agent, in overweight and obese subjects taking olanzapine for schizophrenia or schizoaffective disorder. METHOD: Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, had been taking a stable dose of olanzapine for at least 4 months, and had a body mass index of >/=30 kg/m(2) or >/=27 kg/m(2) plus at least one cardiovascular risk factor. In a 12-week double-blind, randomized, placebo-controlled study, 37 subjects received placebo or sibutramine (up to 15 mg/day). For the first 8 weeks all subjects participated in weekly group sessions focused on nutrition and behavioral modification. RESULTS: The sibutramine and placebo groups had no significant baseline differences on age, gender, education, ethnicity, diagnosis, weight, body mass index, and blood pressure. At week 12 the sibutramine group had significantly greater losses than the placebo group in weight (mean=8.3 lb, SD=2.4, versus mean=1.8 lb, SD=1.6), waist circumference, body mass index, and hemoglobin A(1c). There were no significant differences on most side effects, although the sibutramine group exhibited a mean increase in systolic blood pressure of 2.1 mm Hg (SD=8.5), and anticholinergic side effects and sleep disturbances were at least twice as common in the sibutramine group. CONCLUSIONS: Sibutramine was an effective and well-tolerated adjunct to behavior modification for weight loss in patients with schizophrenia and schizoaffective disorder being treated with olanzapine.

Adult↗
PubMed2005

Medical morbidity and mortality in schizophrenia: guidelines for psychiatrists.

BACKGROUND: Medical morbidity and mortality rates remain elevated in schizophrenia patients compared with the general population, in part due to potentially reversible medical risk factors. Psychiatrists should address this problem by adopting established strategies for prevention and intervention. METHOD: The literature on modifiable medical risk factors relevant to individuals with schizophrenia and corresponding guidelines for prevention and treatment established by expert consensus panels were reviewed. RESULTS: Schizophrenia patients are at elevated risk for cardiovascular disease due to high rates of cigarette smoking and, increasingly, due to obesity, diabetes, and hypertriglyceridemia. Rates of human immunodeficiency virus infection and infectious hepatitis are also higher in schizophrenia patients. Interventions that have reduced medical morbidity in the general population can be adopted to reduce premature mortality in individuals with schizophrenia. CONCLUSIONS: Patients with schizophrenia have high rates of potentially reversible medical morbidity. Implementation of practice guidelines for identifying and modifying risk factors could substantially improve the health of patients with schizophrenia.

Adult↗
PubMed2005

Clozapine, diabetes mellitus, hyperlipidemia, and cardiovascular risks and mortality: results of a 10-year naturalistic study.

OBJECTIVE: The goal of this 10-year naturalistic study was to examine, in clozapine-treated patients, the change in cardiovascular risk factors following clozapine initiation and the mortality estimates from cardiovascular disease. METHOD: Data were collected from medical records from January 1992 to December 2003 and included age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation for clozapine-treated patients with schizophrenia or schizoaffective disorder (DSM-IV criteria). Clozapine dosage and laboratory results were recorded at 12-month intervals. RESULTS: At the time of clozapine initiation, the mean +/-?SD age of the 96 patients studied was 36.5 +/- 7.9 years; 28% (N = 27) were women. The Kaplan-Meier estimate for 10-year mortality from cardiovascular disease was 9%. African American and Hispanic American patients exhibited elevated risk of cardiovascular disease-related mortality (odds ratio [OR] = 7.2, p = .09; OR = 11.3, p = .04, respectively) compared to white patients. Body mass index (BMI) significantly increased the odds ratio of mortality (OR = 1.2, p < .01). The Kaplan-Meier estimate for new-onset diabetes mellitus was approximately 43%, and Hispanic American (OR = 4.3, p = .027) and African American (OR = 11.5, p = .0001) patients showed elevated risks of developing diabetes mellitus compared to white patients. Additionally, BMI (OR = 1.11, p = .0006), total cholesterol level (OR = 1.006, p = .04), and serum triglyceride level (OR = 1.002, p = .04) modestly increased the odds ratio for the development of diabetes mellitus. CONCLUSIONS: These results support the hypothesis that clozapine-treated patients appear to be at risk for death from cardiovascular disease secondary to clozapine-associated medical disorders such as obesity, diabetes, hypertension, and hyperlipidemia.

Adult↗
PubMed2005

Independent effects of tobacco abstinence and bupropion on cognitive function in schizophrenia.

OBJECTIVE: The objective of this study was to examine the effects of tobacco abstinence and bupropion treatment on cognitive functioning in adult smokers with schizophrenia in the setting of a randomized, double-blind, placebo-controlled clinical trial of bupropion for smoking cessation. METHOD: Fifty-three adults with schizophrenia (DSM-IV) took part in a trial of bupropion for smoking cessation. Subjects were enrolled in the study from August 1999 to March 2003. Forty-five subjects remained in the trial at week 4; 41 subjects, 19 taking bupropion and 22 taking placebo, completed the baseline and week 4 cognitive assessments and were included in the analysis of adjusted effects of abstinence and bupropion treatment on cognitive function. RESULTS: Controlling for bupropion treatment and baseline performance, 7 days of tobacco abstinence was associated with slowed motor speed (finger tapping) but was not associated with worsening of performance on tests of attention (AX Continuous Performance Test [AX-CPT]), verbal learning and memory (California Verbal Learning Test [CVLT]), working memory (digit span), or executive function/inhibition (Stroop) and was not associated with worsening of any clinical measures. Controlling for abstinence status, bupropion was associated with reduction (improvement) in reaction time variability on the AX-CPT and with reduction in perseverative errors on the CVLT. CONCLUSION: We conclude that 1 week of tobacco abstinence is associated with slowed motor speed but is not associated with detectable worsening in performance on a range of neuropsychological tests or clinical symptoms in the subset of patients who were able to quit smoking. We also conclude that bupropion treatment may be associated with improvement in variability of attention.

Adult↗
PubMed2004

A failure of sleep-dependent procedural learning in chronic, medicated schizophrenia.

BACKGROUND: Schizophrenia patients have difficulty mastering even rote procedural tasks in rehabilitation settings. Although most studies demonstrate intact procedural learning in schizophrenia, recent findings demonstrate that a critical component of procedural learning is dependent on sleep. This study tested the hypothesis that patients with schizophrenia have a deficit in sleep-dependent procedural learning. METHODS: Using a simple, well-characterized test of motor skill learning, the finger tapping motor sequence task (MST), 26 patients with chronic, medicated schizophrenia and 14 demographically matched healthy control subjects were tested on two occasions, 24 hours apart. The main outcome measures were learning of the MST on day 1 (practice-dependent learning) and overnight, sleep-dependent improvement in performance. RESULTS: Although schizophrenia patients and control subjects did not differ in practice-dependent learning, patients failed to show overnight improvement (4% deterioration) and differed significantly from control subjects who showed a significant 11% improvement. CONCLUSIONS: We present here the first demonstration of a failure of sleep-dependent consolidation of procedural learning in chronic, medicated schizophrenia. This deficit occurred in the context of normal practice-dependent learning within a training session. This behavioral dissociation is consistent with evidence that practice- and sleep-dependent motor learning reflect independent processes and suggests that they are differentially affected in schizophrenia.

Adult↗
PubMed2004

A six-month, placebo-controlled trial of D-cycloserine co-administered with conventional antipsychotics in schizophrenia patients.

RATIONALE: D-Cycloserine, a partial agonist at the glycine site of the N-methyl-D-aspartate receptor, has demonstrated inconsistent efficacy for negative and cognitive symptoms of schizophrenia. The strongest evidence for efficacy has come from studies using D-cycloserine at a dose of 50 mg/day added to conventional antipsychotics in trials of 8 weeks duration or less. OBJECTIVE: To assess the efficacy for negative symptoms and cognitive impairment of D-cycloserine augmentation of conventional antipsychotics in a 6-month trial. METHODS: Fifty-five schizophrenia patients with prominent negative symptoms, treated with conventional antipsychotics, were randomly assigned to treatment with D-cycloserine 50 mg/day or placebo for 6 months in a double-blind, parallel group design. RESULTS: Twenty-six subjects completed the 6-month trial; drop-out rates did not differ between treatment groups. D-Cycloserine treatment did not differ from placebo treatment on any primary outcome measure at 8 or 24 weeks, including response of negative symptoms and performance on a cognitive battery. Serum D-cycloserine concentrations did not correlate with response of negative symptoms. CONCLUSION: D-Cycloserine did not exhibit therapeutic effects in this trial, possibly reflecting the high drop-out rate, a narrow range of therapeutic serum concentrations, a modest magnitude of therapeutic effect for the selected outcome measures, or loss of efficacy over time. Because D-cycloserine is a partial agonist with relatively low affinity for the glycine site, the magnitude of potential therapeutic effect may be smaller than that achieved by the higher-affinity full agonists, glycine and D-serine.

Adult↗
PubMed2004

The relationship of saccadic peak velocity to latency: evidence for a new prosaccadic abnormality in schizophrenia.

Antisaccades have not only longer latencies but also lower peak velocities than prosaccades. It is not known whether these latency and velocity differences are related. Studies of non-human primates suggest that prosaccade peak velocity declines as latency from target appearance increases. We examined whether a similar relationship between peak velocity and latency existed in human saccades, whether it accounted for the difference in peak velocity between antisaccades and prosaccades, and whether it was affected by schizophrenia, a condition that affects antisaccade performance. Sixteen control and 21 schizophrenia subjects performed prosaccade and antisaccade trials in the same test session. In both groups antisaccades had lower peak velocities than prosaccades. Latency did not influence the peak velocities of antisaccades in either subject group. At short latencies, the peak velocities of prosaccades were also similar in the two groups. However, while prosaccade peak velocities declined minimally with increasing latency in control subjects, those in the schizophrenia group declined significantly until they reached a value similar to antisaccade peak velocities. We conclude that, in normal subjects, the effect of latency on prosaccade peak velocity is minimal and cannot account for the lower velocity of antisaccades. In schizophrenia, we hypothesize that the latency-related decline in prosaccade peak velocity may reflect either an increased rate of decay of the effect of the transient visual signal at the saccadic goal, or a failure of the continuing presence of the target to sustain neural activity in the saccadic system.

Adult↗
PubMed2004

Anterior cingulate cortex activation during cognitive interference in schizophrenia.

BACKGROUND: Previous studies have reported evidence of structural and functional abnormalities in the anterior cingulate cortex of patients with schizophrenia. METHOD: The authors studied 19 male patients with chronic schizophrenia and 15 healthy male comparison subjects with functional magnetic resonance imaging and the novel Multi-Source Interference Task, a task designed to elicit robust dorsal anterior cingulate cortex activation in individual subjects. Group averaged and individual (region-of-interest-based) brain activation patterns were compared during the performance of control and interference trials. RESULTS: Performance (reaction times and accuracy) did not differ between healthy subjects and patients with schizophrenia. Comparison of interference and neutral blocks revealed activation in the medial wall of the prefrontal cortex in 93% (N=14) of the healthy subjects and 84% (N=16) of the subjects with schizophrenia. Sixty-seven percent (N=10) of the healthy subjects but only 16% (N=3) of the subjects with schizophrenia displayed maximum medial wall activation within the dorsal anterior cingulate cortex. CONCLUSIONS: The Multi-Source Interference Task produced robust activation in the medial wall of the prefrontal cortex during cognitive interference. Analysis of individual activation patterns revealed medial wall abnormalities in schizophrenia patients.

Cognition Disorders↗
PubMed2004

Folate, homocysteine, and negative symptoms in schizophrenia.

OBJECTIVE: Because glutamate carboxypeptidase II (GCPII) regulates both folate absorption and activation of N-methyl-d-aspartic acid receptors, the authors examined relationships between serum folate concentrations and clinical symptoms in schizophrenia patients. METHOD: For 91 outpatients with schizophrenia, clinical assessments were performed and serum folate, homocysteine, B(12), glycine, and serine concentrations were measured. RESULTS: Serum folate concentrations were significantly lower than in a representative sample from the Framingham Offspring Study. Folate concentration correlated inversely with the Scale for Assessment of Negative Symptoms total score and was lower in patients with the deficit syndrome than in nondeficit patients. Homocysteine concentration correlated with the severity of extrapyramidal symptoms. CONCLUSIONS: These findings could reflect several possible mechanisms, including low dietary intake of folate, low GCPII activity, cigarette smoking, and the involvement of folate in the synthesis of neurotransmitters. Additional studies are needed to clarify these findings.

Adult↗
PubMed2004

Two-year follow-up of a smoking cessation trial in patients with schizophrenia: increased rates of smoking cessation and reduction.

BACKGROUND: Long-term success rates of smoking cessation programs for patients with schizophrenia are unknown. This study, conducted between June 2001 and November 2002, evaluated the rate of smoking cessation and reduction in patients with schizophrenia (DSM-IV) 2 years after they had participated in a smoking cessation study in order to determine whether subjects who significantly reduced smoking during the original trial resumed their previous level of smoking at 2 years. METHOD: Two years following a double-blind placebo-controlled trial of bupropion sustained release, 150 mg/day, added to cognitive-behavioral therapy for smoking cessation in patients with schizophrenia, subjects were interviewed, medical charts were reviewed, and carbon monoxide in expired air was measured. RESULTS: Seventeen of 18 subjects completed the follow-up assessment. More subjects were abstinent (22% [N = 4]) at the 2-year follow-up than were abstinent at the end of the trial (6% [N = 1]). Subjects who achieved significant smoking reduction during the trial were more likely to be abstinent at 2 years (4/7) than those who did not significantly reduce smoking during the trial (0/11) (chi(2) = 8.1, p <.005). Most subjects who achieved > or = 50% reduction in smoking at the end of the trial maintained at least that level of reduction at 2 years. Smoking reduction during the treatment intervention was correlated with smoking reduction at follow-up (r = 0.60, p =.01). CONCLUSION: The results from this naturalistic study suggest that behavior changes achieved in smoking cessation programs for patients with schizophrenia may be durable and may predict future smoking behavior. We conclude that further investigation into the relationship between smoking reduction and future smoking cessation in special populations is indicated.

Adult↗