Faculty Bibliography

OBJECTIVE: To determine the prevalence and clinical significance of obsessive-compulsive (OC) symptoms among a group of stable outpatients with schizophrenia. METHODS: We studied 118 patients with schizophrenia from an urban clinic, characterized using clinical symptoms scales, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and neuropsychological testing. We categorized patients into three groups according to severity of OC symptoms and used multivariate linear regression and chi-square tests to compare groups on variables of interest. RESULTS: Only 10 patients (8.8%) had Y-BOCS scores greater than 16, a standard criterion for OCD studies. The patient group with the most OC symptoms (Y-BOCS scores >11) scored higher on the Hamilton Depression Scale, the positive symptoms subscale of the Positive and Negative Syndromes Scale (PANSS) and its delusions item, but not on any of the neuropsychological tests compared to the other two groups. Patients with most severe compulsive symptoms (but not OC symptoms together, or obsessions alone) were more likely to be treated with olanzapine or clozapine, atypical antipsychotic medications previously reported to induce or worsen OC symptoms. CONCLUSIONS: Our results confirm previous findings that patients with schizophrenia and comorbid OC symptoms have more positive symptoms but not the suggestion that such patients are more cognitively impaired than their counterparts without OC symptoms. We suggest possible explanations for discrepancies in the literature, including differences in patient sampling and definition of comorbid OC symptoms. Finally, our data suggest that olanzapine and clozapine may produce or worsen compulsions in some patients; prospective studies need to address this possibility

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

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

BACKGROUND: In healthy individuals, the activity of the medial temporal lobe habituates rapidly with the repeated presentation of a stimulus. Using functional magnetic resonance imaging (fMRI), we tested the hypothesis that habituation of the medial temporal lobe is reduced in schizophrenia. METHODS: During fMRI scanning, fearful and happy faces were presented repeatedly to healthy control subjects (n =16) and patients with schizophrenia (n =18). Habituation of medial temporal lobe structures was measured by comparing the hemodynamic response occurring during the early and late portions of the presentation of each face. RESULTS: Control subjects demonstrated significant medial temporal lobe habituation to fearful but not to happy faces. In contrast, patients with schizophrenia did not demonstrate medial temporal lobe habituation in response to fearful or happy faces. In a direct, between-group comparison, right hippocampal habituation to fearful faces was significantly greater in control subjects than in the schizophrenia patients. Also, there were no significant differences between the patients and control subjects in the early medial temporal lobe response to fearful faces, suggesting that attenuated hippocampal habituation in schizophrenia is not associated with a reduction in initial activation. CONCLUSIONS: These findings suggest that there is abnormal modulation of hippocampal responses to fearful faces in schizophrenia

RATIONALE: Schizophrenia is a disorder with cognitive deficits that could stem from cholinergic dysfunction. OBJECTIVES: Our aim was to examine if donepezil administered to stable, medicated outpatients with schizophrenia improves cognition and psychopathology. METHODS: We conducted a double-blind placebo-controlled trial of donepezil up to 10 mg/day added for 8 weeks to ongoing antipsychotic treatment in 36 typical community-treated schizophrenia patients not selected for cognitive impairment. RESULTS: Donepezil did not improve measures of cognition or psychopathology. It was well tolerated. CONCLUSION: Consistent with other studies, addition of donepezil to stable patients with schizophrenia did not improve cognition or measures of psychopathology. This result does not support the hypothesis that residual symptoms and cognitive problems result from a cholinergic deficit that can be remedied by an acetylcholinesterase inhibitor. A donepezil add-on strategy might make sense in selected schizophrenia cases where a pathological process is known to affect cholinergic neurons (e.g., history of head injury or comorbid dementia)

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

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

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

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

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