Schizophrenia Bulletin Open最新文献

Despite its unique efficacy, clozapine remains underutilized in the United States. Perceptions about clozapine and barriers to its use have been examined among prescribers, but insufficiently studied among consumers. We surveyed 211 antipsychotic consumers (86 on clozapine and 125 on other antipsychotics) on their medication-related perspectives in a public hospital system in Atlanta, Georgia, USA. In contrast to their previous regimen, 72% of clozapine consumers reported they were more satisfied with clozapine. When compared with consumers taking other antipsychotics, clozapine consumers reported more side effects but did not differ on other measures of satisfaction or efficacy. We found Caucasians to be overrepresented among clozapine, as compared to other antipsychotic consumers. Side effects most strongly associated with poor safety ratings were sedation, limb jerking, and dizziness when standing. However, clozapine was only rated less safe by consumers who experienced more than one of these side effects. We used an unsupervised clustering approach to identify three major groups of clozapine consumers. Cluster A (19%) had the lowest safety ratings, aversion to blood work, and a high rate of side effects that associate with lower safety ratings. Cluster B (25%) experienced more hospitalizations and reported satisfaction with clozapine that correlated with efficacy ratings, irrespective of safety ratings. Cluster C (56%) experienced fewer hospitalizations, fewer previous drug trials, greater educational attainment, lower rates of smoking, and rated clozapine more highly. This work identifies common side effects that influence the subjective safety of clozapine and suggests that attitudes toward clozapine depend on context-specific factors.

[This corrects the article DOI: 10.1093/schizbullopen/sgaa033.].

The cognitive dysmetria theory of psychotic disorders posits that cerebellar circuit abnormalities give rise to difficulties coordinating motor and cognitive functions. However, brain activation during cerebellar-mediated tasks is understudied in schizophrenia. Accordingly, this study examined whether individuals with schizophrenia have diminished neural activation compared to controls in key regions of the delay eyeblink conditioning (dEBC) cerebellar circuit (eg, lobule VI) and cerebellar regions associated with cognition (eg, Crus I). Participants with schizophrenia-spectrum disorders (n = 31) and healthy controls (n = 43) underwent dEBC during functional magnetic resonance imaging (fMRI). Images were normalized using the Spatially Unbiased Infratentorial Template (SUIT) of the cerebellum and brainstem. Activation contrasts of interest were "early" and "late" stages of paired tone and air puff trials minus unpaired trials. Preliminary whole brain analyses were conducted, followed by cerebellar-specific SUIT and region of interest (ROI) analyses of lobule VI and Crus I. Correlation analyses were conducted between cerebellar activation, neuropsychological test scores, and psychotic symptom scores. In controls, the largest clusters of cerebellar activation peaked in lobule VI during early dEBC and Crus I during late dEBC. The schizophrenia group showed robust cortical activation to unpaired trials but no significant conditioning-related cerebellar activation. Crus I ROI activation during late dEBC was greater in the control than schizophrenia group. Greater Crus I activation correlated with higher working memory scores in the full sample and lower positive psychotic symptom severity in schizophrenia. Findings indicate functional cerebellar abnormalities in schizophrenia which relate to psychotic symptoms, lending direct support to the cognitive dysmetria framework.

Objective: In the current posthoc analyses, we evaluated the impact of markers of aberrant data variability on drug placebo separation and placebo and drug response in an acute schizophrenia clinical trial.

Methods: Positive and negative syndrome scale data were obtained from a phase 2, randomized, double-blind, placebo controlled trial in hospitalized adults with schizophrenia experiencing an acute exacerbation. We assessed the impact of a total of six markers of aberrant data variability: erratic ratings, unusually large postbaseline improvement, high and low mean square successive difference (MSSD), identical and nearly identical ratings and compared the drug placebo difference, drug and treatment response at last visit in affected subjects vs those not affected. All analyses were conducted using generalized linear models.

Results: In this posthoc analysis, drug placebo separation decreased with the presence of most markers of aberrant data variability. The only exception was high MSSD was associated with significant increase in the signal. In the affected subjects, the presence of indicators of increased data variability augmented the response to placebo, in the case of large postbaseline change and high MSSD, significantly. The presence of indicators of decreased variability numerically but not statistically decreased the response to placebo. Similar findings were observed in the drug treatment group with the exception of erratic ratings that numerically but not statistically decreased the response to the drug.

Discussion: The presence of most indicators of aberrant data variability had a detrimental effect on drug-placebo separation and showed different effects on placebo and treatment response.

People diagnosed with schizophrenia have been broadly observed to experience deficits in clinical and cognitive insight; however, less is understood about how these deficits are related. One possibility is that these deficits co-occur among people when other deficits in cognition are present, such as in executive function, social cognition, and metacognition, which may either promote the development of both forms of poor insight or allow one to negatively influence the other. To explore this possibility, we conducted a cluster analysis using assessments of clinical and cognitive insight among 95 adults with a schizophrenia spectrum disorder. As predicted, this analysis yielded a group with concurrently poor clinical and cognitive insight (n = 36). Additional groups were found with concurrently good clinical and cognitive insight (n = 28) and poor clinical insight and good cognitive insight (n = 31). Groups were then compared on assessments of executive function, social cognition, and metacognition. The group with concurrently lower levels of cognitive and clinical insight had significantly poorer metacognition relative to the other groups. In particular, they tended to form more fragmented and less integrated ideas about themselves and others. No differences were found for executive function or social cognition. The result may suggest that while clinical and cognitive insight is partially orthogonal phenomena, relatively lower levels of metacognition, or difficulties forming integrated ideas about oneself and others, maybe a condition leading to the confluence of lower clinical and cognitive insight. Interventions targeting metacognition may be of particular use for this group.

Processing speed (PS) impairment is one of the most severe and common cognitive deficits in schizophrenia. Previous studies have reported correlations between PS and white matter diffusion properties, including fractional anisotropy (FA), in several fiber bundles in schizophrenia, suggesting that white matter alterations could underpin decreased PS. In schizophrenia, white matter alterations are most prevalent within inter-hub connections of the rich club. However, the spatial and topological characteristics of this association between PS and FA have not been investigated in patients. In this context, we tested whether structural connections comprising the rich club network would underlie PS impairment in 298 patients with schizophrenia or schizoaffective disorder and 190 healthy controls from the Australian Schizophrenia Research Bank. PS, measured using the digit symbol coding task, was largely (Cohen's d = 1.33) and significantly (P < .001) reduced in the patient group when compared with healthy controls. Significant associations between PS and FA were widespread in the patient group, involving all cerebral lobes. FA was not associated with other cognitive measures of phonological fluency and verbal working memory in patients, suggesting specificity to PS. A topological analysis revealed that despite being spatially widespread, associations between PS and FA were over-represented among connections forming the rich club network. These findings highlight the need to consider brain network topology when investigating high-order cognitive functions that may be spatially distributed among several brain regions. They also reinforce the evidence that brain hubs and their interconnections may be particularly vulnerable parts of the brain in schizophrenia.

Introduction: Only a few studies have comprehensively characterized default mode network (DMN) pathology on a structural and functional level, and definite conclusions cannot be drawn due to antipsychotic medication exposure and illness chronicity. The objective of this study was to characterize DMN pathology in medication-naïve first episode psychosis (FEP) patients, and determine if DMN structural and functional connectivity (FC) have potential utility as a predictor for subsequent antipsychotic treatment response.

Methods: Diffusion imaging and resting state FC data from 42 controls and 52 FEP were analyzed. Patients then received 16 weeks of antipsychotic treatment. Using region of interest analyses, we quantified FC of the DMN and structural integrity of the white matter tracts supporting DMN function. We then did linear regressions between DMN structural and FC indices and antipsychotic treatment response.

Results: We detected reduced DMN fractional anisotropy and axial diffusivity in FEP compared to controls. No DMN FC abnormalities nor correlations between DMN structural and FC were found. Finally, DMN fractional anisotropy and radial diffusivity were associated with response to treatment.

Conclusion: Our study highlights the critical role of the DMN in the pathophysiology suggesting that axonal damage may already be present in FEP patients. We also demonstrated that DMN pathology is clinically relevant, as greater structural DMN alterations were associated with a less favorable clinical response to antipsychotic medications.