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"Enhancing QUality of Care In Psychosis" (EQUIP) was an eight-site clustered controlled trial of the implementation and effectiveness of patient-reported outcomes to support evidence-based practice and improve care for schizophrenia. Implementation sites chose to improve care for weight. Implementation included monitoring patient-reported outcomes using kiosks, patient and staff education, quality improvement teams, and phone care management. Qualitative and quantitative methods compared implementation and effectiveness between sites for 13 months. Eighty percent of 801 randomly selected patients were overweight. Two hundred one clinicians varied in competency. Baseline use of behavioral weight services was low. At implementation sites, patients became 2.3 times more likely to use weight services compared with control sites (95% CI, 1.5-3.6; χ 2  = 14.4; p < 0.01). There was no effect on the weight gain liability of medications prescribed. Controlling for baseline, patients' final weight at control sites was 5.9 ± 2.7 kg heavier than at implementation sites (F = 4.8, p = 0.03). Patient-reported outcomes can inform implementation of evidence-based practice and improvement in outcomes.

Background: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores., Methods: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance., Results: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning., Conclusions: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Importance: Neurophysiologic measures of early auditory information processing (EAP) are used as endophenotypes in genomic studies and biomarkers in clinical intervention studies. Research in schizophrenia has established correlations among measures of EAP, cognition, clinical symptoms, and functional outcome. Clarifying these associations by determining the pathways through which deficits in EAP affect functioning would suggest when and where to therapeutically intervene., Objectives: To characterize the pathways from EAP to outcome and to estimate the extent to which enhancement of basic information processing might improve cognition and psychosocial functioning in schizophrenia., Design, Setting, and Participants: Cross-sectional data were analyzed using structural equation modeling to examine the associations among EAP, cognition, negative symptoms, and functional outcome. Participants were recruited from the community at 5 geographically distributed laboratories as part of the Consortium on the Genetics of Schizophrenia 2 from July 1, 2010, through January 31, 2014. This well-characterized cohort of 1415 patients with schizophrenia underwent EAP, cognitive, and thorough clinical and functional assessment., Main Outcome and Measures: Mismatch negativity, P3a, and reorienting negativity were used to measure EAP. Cognition was measured by the Letter Number Span test and scales from the California Verbal Learning Test-Second Edition, the Wechsler Memory Scale-Third Edition, and the Penn Computerized Neurocognitive Battery. Negative symptoms were measured by the Scale for the Assessment of Negative Symptoms. Functional outcome was measured by the Role Functioning Scale., Results: Participants included 1415 unrelated outpatients diagnosed with schizophrenia or schizoaffective disorder (mean [SD] age, 46 [11] years; 979 males [69.2%] and 619 white [43.7%]). Early auditory information processing had a direct effect on cognition (β = 0.37, P < .001), cognition had a direct effect on negative symptoms (β = -0.16, P < .001), and both cognition (β = 0.26, P < .001) and experiential negative symptoms (β = -0.75, P < .001) had direct effects on functional outcome. The indirect effect of EAP on functional outcome was significant as well (β = 0.14, P < .001). Overall, EAP had a fully mediated effect on functional outcome, engaging general rather than modality-specific cognition, with separate pathways that involved or bypassed negative symptoms., Conclusions and Relevance: The data support a model in which EAP deficits lead to poor functional outcome via impaired cognition and increased negative symptoms. Results can be used to help guide mechanistically informed, personalized treatments and support the strategy of using EAP measures as surrogate end points in early-stage procognitive intervention studies.

Background: Numerous studies have reported links between theory of mind (ToM) deficits, neurocognition and negative symptoms with functional outcome in chronic schizophrenia patients. Although the ToM deficit has been observed in first-episode patients, fewer studies have addressed ToM as a possible trait marker, neurocognitive and symptom correlations longitudinally, and associations with later functioning., Method: Recent-onset schizophrenia patients (n = 77) were assessed at baseline after reaching medication stabilization, and again at 6 months (n = 48). Healthy controls (n = 21) were screened, and demographically comparable with the patients. ToM was assessed with a Social Animations Task (SAT), in which the participants' descriptions of scenes depicting abstract visual stimuli 'interacting' in three conditions (ToM, goal directed and random) were rated for degree of intentionality attributed to the figures and for appropriateness. Neurocognition, symptoms and role functioning were also assessed., Results: On the SAT, patients had lower scores than controls for both intentionality (p < 0.01) and appropriateness (p < 0.01) during the ToM condition, at baseline and 6 months. The ToM deficit was stable and present even in remitted patients. Analyses at baseline and 6 months indicated that for patients, ToM intentionality and appropriateness were significantly correlated with neurocognition, negative symptoms and role functioning. The relationship between ToM and role functioning was mediated by negative symptoms., Conclusions: The ToM deficit was found in recent-onset schizophrenia patients and appears to be moderately trait-like. ToM is also moderately correlated with neurocognition, negative and positive symptoms, and role functioning. ToM appears to influence negative symptoms which in turn makes an impact on role functioning.

In this preliminary study, we examined the effect of transcranial direct current stimulation (tDCS) on social cognition in 36 individuals with schizophrenia. Participants received a baseline assessment and one week later received either anodal, cathodal, or sham tDCS, with 12 participants randomized to each condition. A single 20-minute session tDCS was administered bilaterally over the dorsolateral prefrontal cortex (centered at positions Fp1 and Fp2) at 2 mA. Among the 4 social cognitive tasks, participants showed a significant improvement on one of them, emotion identification, following anodal stimulation. Findings demonstrate the safety of this procedure and suggest potential therapeutic effects on one aspect of social cognition in schizophrenia., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements., Methods: The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003 and 2008. For these analyses, participants included schizophrenia probands (n=83), their nonpsychotic siblings (n=151), and community comparison subjects (n=209) with complete data on a battery of 12 neurocognitive tests (assessing domains of working memory, declarative memory, vigilance, spatial ability, abstract reasoning, facial emotion processing, and motor speed) and 3 neurophysiological tasks reflecting inhibitory processing (P50 gating, prepulse inhibition and antisaccade tasks). Factor analyses were conducted on the measures for each subject group and across the entire sample. Heritability analyses of factors were performed using SOLAR., Results: Analyses yielded 5 distinct factors: 1) Episodic Memory, 2) Working Memory, 3) Perceptual Vigilance, 4) Visual Abstraction, and 5) Inhibitory Processing. Neurophysiological measures had low associations with these factors. The factor structure of endophenotypes was largely comparable across probands, siblings and controls. Significant heritability estimates for the factors ranged from 22% (Episodic Memory) to 39% (Visual Abstraction)., Conclusions: Neurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia. Composite endophenotype measures may inform our neurobiological and genetic understanding of schizophrenia., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The number of separable cognitive dimensions in schizophrenia has been debated. Guided by the extant factor analytic literature, the NIMH Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative selected seven cognitive domains relevant to treatment studies in schizophrenia: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. These domains are assessed in the MATRICS Consensus Cognitive Battery (MCCB). The aim of this study was to conduct a confirmatory factor analysis (CFA) of the beta battery of the MCCB to compare the fit of the MATRICS consensus seven-domain model to other models in the current literature on cognition in schizophrenia., Method: Using data from 281 schizophrenia outpatients, we compared the seven correlated factors model with alternative models. Specifically, we compared the 7-factor model to (a) a single-factor model, (b) a three correlated factors model including speed of processing, working memory, and general cognition, and (c) a hierarchical model in which seven first-order factors loaded onto a second-order general cognitive factor., Results: Multiple fit indices indicated the seven correlated factors model was the best fit for the data and provided significant improvement in model fit beyond the comparison models., Conclusions: These results support the assessment of these seven cognitive dimensions in clinical trials of interventions to improve cognition in schizophrenia. Because these cognitive factors are separable to some degree, it is plausible that specific interventions may have differential effects on the domains.

Background: Although many studies have assessed cognitive functioning in first-episode schizophrenia (FESz), the pattern and severity of impairment across cognitive domains remain unclear. Moreover, few studies have directly compared the pattern of cognitive performance between FESz and chronic schizophrenia (CSz). In this study we examined the cognitive impairment profile in FESz using a standardized neurocognitive battery (MATRICS Consensus Cognitive Battery; MCCB)., Methods: MCCB data were compared from 105 FESz patients, 176 CSz patients and 300 non-psychiatric (NP) participants. Mixed model analysis evaluated group differences in MCCB profiles and relative strengths and weaknesses in the MCCB profiles of patients. Clinical implications of MCCB performance were also examined; we compared the proportion of participants from each group who exhibited clinically-significant global cognitive impairment based on the MCCB Overall Composite score., Results: FESz and CSz showed impaired performance across all MCCB domains relative to NP. With the exception of relative preservation of working memory and social cognition in FESz, the MCCB domain scores were similar in FESz and CSz. The distribution of impairment on the Overall Composite score did not significantly differ between FESz and CSz; compared to NP, both patient groups were overrepresented in moderate and severe impairment categories., Conclusion: The pattern, magnitude, and distribution of severity of impairment in FESz were similar to that observed in CSz. However, early in the illness, there may be relative sparing of working memory and social cognition., (Copyright © 2014 Elsevier B.V. All rights reserved.)

When two visual targets are presented in a rapid serial visual presentation (RSVP) paradigm, the ability to identify the second target is reduced when it is presented 200-500ms after the initial target. This phenomenon is referred to as the "attentional blink (AB)." Previous behavioral studies have reported aberrant AB in schizophrenia. The underlying cause, however, of the AB deficit in schizophrenia remains ambiguous. Individuals with schizophrenia consistently demonstrate impairments in early visual processing stages and later attentionally-mediated stages, yet the stage of processing that is contributing to patient-control differences on AB is unknown. The current study attempted to resolve this ambiguity by applying electrophysiological methodology to an RSVP paradigm with 70 clinically stable outpatients with schizophrenia and 63 healthy controls. The task was simplified to reduce task demands, and a suppression ratio was employed to control for possible differences between groups in the ability to identify a single stimulus within a visual stream. Early perceptual processing was assessed using the steady-state visual evoked potential (ssVEP), and attentional processing was assessed using the P300 event-related potential. Relative to the healthy controls, patients showed the expected behavioral AB deficits. These deficits coincided with reduced P300 amplitude: both performance and P300 reductions extended beyond the traditional AB window. Mean ssVEP amplitude did not differ between the groups, and the differences in P300 remained after controlling for ssVEP. These results suggest that the observed AB deficits were due to attentional, not perceptual, processing deficits., (Published by Elsevier B.V.)

Social cognition, which includes emotional intelligence, is impaired in schizophrenia. The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) is a widely-used assessment of emotional intelligence, with a four-factor structure in healthy individual. However, a recent factor analysis in schizophrenia patients revealed a two-factor structure of the MSCEIT. The current study aimed to replicate this finding in a larger, more diverse, schizophrenia sample (n=194). Our findings revealed an identical two-factor structure as in the previously-reported study, indicating that emotional intelligence is organized in a different manner in schizophrenia than it is in healthy controls., (Published by Elsevier B.V.)