Faculty Bibliography

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

BACKGROUND: Attitude toward medications is important for medication adherence. A patient's drug attitude probably reflects a weighing of benefits against experienced or anticipated side effects or risks associated with the medication. We predicted (1) that drug attitudes would be more positive among schizophrenia patients taking second-generation compared to first-generation antipsychotics because of their greater tolerability and efficacy; and (2) that greater insight into illness, fewer extrapyramidal symptoms, and better social functioning would be associated with better attitudes toward psychiatric medication. METHOD: In a cross-sectional study of 81 DSM-IV-diagnosed schizophrenia outpatients, we used multivariate analysis to determine clinical and demographic predictors of drug attitude. Drug attitude was assessed with the 10-item Drug Attitude Inventory (DAI). The relationship between the DAI and psychopathology, insight, extrapyramidal symptoms, level of functioning, and type of antipsychotic (first-generation versus second-generation versus clozapine) was examined. RESULTS: Less awareness of current symptoms, presence of deficit symptoms, and employment predicted a negative attitude toward psychiatric medications. Extrapyramidal symptoms did not predict drug attitude. Drug attitudes were no different between patients taking first- or second-generation antipsychotics or clozapine. CONCLUSION: Patients may not favor second-generation over first-generation antipsychotics, and extrapyramidal symptoms may not be a primary factor determining attitudes. While attitudes may be more positive in patients who recognize therapeutic drug effects, patients who work may view medications particularly negatively, possibly due to a sense of stigma. Because drug attitudes may reflect compliance and are difficult to predict, clinicians should inquire directly

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

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

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

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