Patients with schizophrenia show deficits of working memory maintenance components in circuit-specific tasks

Working memory (WM) deficits are a neuropsychological core finding in patients with schizophrenia and also supposed to be a potential endophenotype of schizophrenia. Yet, there is a large heterogeneity between different WM tasks which is partly due to the lack of process specificity of the tasks applied. Therefore, we investigated WM functioning in patients with schizophrenia using process- and circuit-specific tasks. Thirty-one patients with schizophrenia and 47 controls were tested with respect to different aspects of verbal and visuospatial working memory using modified Sternberg paradigms in a computer-based behavioural experiment. Total group analysis revealed significant impairment of patients with schizophrenia in each of the tested WM components. Furthermore, we were able to identify subgroups of patients showing different patterns of selective deficits. Patients with schizophrenia exhibit specific and, in part, selective WM deficits with indirect but conclusive evidence of dysfunctions of the underlying neural networks. These deficits are present in tasks requiring only maintenance of verbal or visuospatial information. In contrast to a seemingly global working memory deficit, individual analysis revealed differential patterns of working memory impairments in patients with schizophrenia

Zustandserfassung in Kiefernbestaenden mit Hilfe des Luftbildes

SIGLETIB: DP 146+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Cognitive benefits of quetiapine versus risperidone in schizophrenia

Objective: This randomized, double-blind study compared the effect of quetiapine and risperidone on cognitive function in patients with schizophrenia. Methods: Patients (n=44) with predominantly negative symptoms were randomized to quetiapine (400–800mg/day) or risperidone (4–8mg/day) for 12 weeks. Cognitive function (reaction time and quality; executive function; working, verbal and visual memory) was assessed at baseline and Week 6. Between-group differences at Week 6 were analyzed using MANCOVA. The incidence of extrapyramidal symptoms (EPS) was also assessed. Results: Patients had impaired cognition at baseline. Twenty-six patients completed the study. At Week 6, 19 patients in the quetiapine group and 15 in the risperidone group had cognitive data available for analysis. Mean doses at Week 6 were 570.6mg/day for quetiapine and 5.1mg/day for risperidone. Cognitive scores improved from baseline to Week 6 in both groups. However, the improvement in working memory was significantly greater with quetiapine (p<0.01 risperidone). EPS and anticholinergic medication requirement were significantly lower in the quetiapine group. Conclusions: Although both quetiapine and risperidone improved cognition, quetiapine produced significantly greater improvements in working memory, with fewer EPS

Risperidone plasma levels, clinical response and side–effects

Assessment of the relation between oral risperidone dose, serum drug levels and clinical response may provide important information for rational treatment decisions. Inter–individual differences in the liver cytochrome P450 system, especially in the CYP2D6 subsystem, which account for a significant portion of risperidone metabolism, may also influence plasma drug levels and alter clinical response parameters. We thus prospectively investigated risperidone serum concentrations in relation to clinical efficacy and side–effects and genotyped major CYP2D6 polymorphisms to determine their effect upon these parameters.Neuroleptic monotherapy with risperidone was administered to schizophrenia patients in a 6–week open dose clinical trial. Weekly assessments including CGI and PANSS ratings to assess psychopathology; SAS to assess medication side effects; and blood draws to quantify steady state plasma levels of risperidone and 9–OH–risperidone were carried out. In addition, major CYP2D6 polymorphisms including alleles *4, *6 and *14 were genotyped.Eighty–two patients were recruited. Mean oral dose of risperidone was 4.3 ± 0.9mg. Mean plasma level of both risperidone and 9–OH–risperidone together (“active moiety”) was 41.6 ± 26.6 ng/ml. Significant improvements in PANSS scales and the various subscales ensued. There was a positive linear correlation between active moiety plasma levels and dose (r = 0.291, p = 0.015) and between risperidone and 9–OH–risperidone levels (r = 0.262; p = 0.016). Nonresponders to pharmacotherapy (PANSS–Improvement < 30%) showed significantly higher active moiety plasma levels (49.9 ± 30.7 ng/ml) than responders (38.2 ± 17.0 ng/ml; p = 0.045) without significantly higher oral doses (p = 0.601). Patients with longer illness duration (≥ 3 years) had significantly higher plasma drug levels than those with a shorter course (< 3 years; p = 0.039). Extrapyramidal side effects (EPS) and plasma levels were not correlated (r = 0.028; p = 0.843), but higher plasma levels at week 2 predicted an incidence for EPS (p < 0.050). Accordingly, patients initially receiving higher oral doses of risperidone were significantly more likely to respond with EPS in the trial course. Eight patients (9.8%) were heterozygous carriers of the CYP2D6 allele *4. CYP2D6 polymorphisms did not predict clinical response, but predicted a tendential increase in the plasma risperidone to 9–OH–risperidone ratio (0.5 ± 0.6 vs. 1.9 ± 1.8; p = 0.120).The major finding was that responders to risperidone treatment had significantly lower blood levels of risperidone and 9–OH risperidone than patients who did not respond to the treatment despite administration of similar oral doses. The observed CYP2D6 polymorphisms did not contribute to altered clinical efficacy, but affected risperidone to 9–OH–risperidone ratios. Increased plasma levels of the active moiety in patients with longer illness may represent general aging effects. Conversely, the observed higher plasma levels in nonresponders may derive from unaccounted genetic metabolism abnormalities or Phase II metabolism disturbances. Patients initially receiving higher oral risperidone doses were more likely to respond with extrapyramidal side effects which reaffirms the need for careful titration. The high inter–individual variability in risperidone and 9–OH–risperidone metabolization and the relationship between clinical outcome and plasma levels warrants regular plasma level monitoring of both compounds to assess for the clinically relevant active moiety