MATRICS Consensus Cognitive Battery Composite Score Research Articles

Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex

Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material.

Effect of Virtual Reality on Cognitive Impairment and Clinical Symptoms among Patients with Schizophrenia in the Remission Stage: A Randomized Controlled Trial.

Aims: This intervention study evaluates the effect of a virtual reality cognition training system (VRCTS) on improving cognitive function and clinical symptoms in Han Chinese patients with schizophrenia in the remission stage. Methods: Sixty-eight patients with schizophrenia in the remission stage were recruited for this study and were randomly allocated to either the virtual reality training (VRT) group or the treatment-as-usual (TAU) group. For the VRT group, patients received training with the VRCTS for two weeks and antipsychotic treatment as usual, while the TAU group only received antipsychotic treatment as usual. Cognitive function and clinical symptoms before and after the two-week treatment were assessed by the MATRICS consensus cognitive battery (MCCB), positive and negative syndrome scale (PANSS), and personal and social performance scale (PSP). Results: The results showed that (1) VRCTS could improve MCCB composite scores and scores on 2 out of 7 cognitive domains: visual learning as well as reasoning and problem solving. It was also observed that (2) VRCTS could alleviate general psychopathology symptoms of PANSS, but did not exert effects on positive and negative symptoms among patients with schizophrenia in the remission stage. Conclusions: A therapeutic effect of VRCTS was observed in patients with schizophrenia in the remission stage. This may improve cognitive function and general psychopathological symptoms. Trial registration: China Clinical Trial Registry, ChiVTR1800016121.

High-Dose Betahistine Improves Cognitive Function in Patients With Schizophrenia: A Randomized Double-Blind Placebo-Controlled Trial.

Background: There is currently no effective treatment for cognitive impairment associated with schizophrenia (CIAS). Recent studies have shown that increased histamine levels in the brain may help to improve CIAS symptoms. Betahistine is an H1-receptor agonist and H3-receptor antagonist. This study evaluated the effect of high-dose betahistine on cognitive function as well as its safety in Chinese Han patients with schizophrenia.Methods: This randomized double-blind, placebo-controlled trial enrolled 89 patients with schizophrenia who were randomly administered betahistine (72 mg/d) or placebo for 12 weeks. At baseline and at 4, 8, and 12 weeks after commencing the intervention, we measured changes in cognitive function and clinical symptoms using the MATRICS Consensus Cognitive Battery (MCCB) and Positive and Negative Syndrome Scale (PANSS), respectively. Furthermore, we used the Treatment Emergent Symptom Scale (TESS) to assess the adverse effects of the patients' medications.Results: Compared to the placebo group, the betahistine group showed significant improvements in the MCCB composite score after 12 weeks of treatment (p = 0.003) as well as improvements in MCCB verbal learning (p = 0.02) and visual learning (p = 0.001) domain scores. However, there were no significant improvements in the PANSS total scores or subscores (p > 0.05). Generally, high-dose betahistine treatment was considered safe in patients with schizophrenia.Conclusions: Additional use of high-dose betahistine can effectively improve cognitive function but not psychiatric symptoms in patients with schizophrenia. Betahistine (72 mg/d) is well tolerated by Chinese Han patients with schizophrenia.Trial Registration: chictr.org.cn, identifier: ChiCTR1900021078. http://www.chictr.org.cn/edit.aspx?pid=35484&htm=4

Virtual reality cognitive & functional assessment in psychosis

AimsTo compare the MATRICS Consensus Cognitive Battery (MCCB) and a novel Virtual Reality (VR) task, called VStore, in assessing cognition and functional capacity (FC) in schizophrenia. We hypothesise that VStore reliably discriminates between patients and controls, correlates with the MCCB, and is well-tolerated. Additionally, VStore is expected to strongly correlate with FC measures.BackgroundCognitive and functional deficits in schizophrenia have a major impact on everyday functioning of patients. The gold-standard cognitive assessment is the MCCB, while the USCD Performance-Based Skills Assessment (UPSA) is used to assess FC in this patient group. Neither of which are without limitations. For example, both take a long time to administer, and the MCCB alone cannot give clear indications of FC. We propose the use of a novel VR task to simultaneously measure cognition and FC in a single assessment. VStore is a shopping task, which involves a verbal learning task followed by buying items from a predetermined shopping list in a virtual minimarket.MethodTen patients with schizophrenia or schizoaffective disorder and ten age/gender-matched healthy controls recruited from South London, completed the following assessments: VStore, MCCB, UPSA & Global Assessment of Functioning (GAF), and VR-Symptom Questionnaire (VRSQ); while controls only completed the VR task. To test whether VStore can differentiate between patients and controls we employed unpaired t-test. To explore associations between VStore Total Time, MCCB composite score and FC measures Pearson's r was used. Finally, mean differences between pre/post-VR symptoms scores were tested using paired t-test.ResultThere was a significant difference between patients and controls on the verbal learning task (t16.38=−4.67,p < .001), and total time spent completing the VR task (t11.41 = 2.67, p = .023). In addition, VStore had a strong association with MCCB composite score (r=−.80,p = .010). While both VStore (r=−.82, p < 001) and MCCB (r = .77,p = .010) had significant correlation with the UPSA, only VStore had a significant association with the GAF (r=−.68,p = .030). Finally, VStore appears to be well-tolerated, causing no measurable side effects in the VRSQ (Pre-VR Mean =12.1[SD = 13.5], Post-VR Mean = 9.6[SD = 11.5],t9 = 0.49,p > .05).ConclusionResults suggest that VStore can discriminate between schizophrenia patients and healthy controls. In addition, VStore and MCCB seem to be strongly associated, suggesting that they tap into identical cognitive domains. VStore seems to be strongly correlated with FC, more so than the MCCB, and cause no measurable side effects. Taken together, this suggests that this novel VR task has the potential to reliably measure cognition and FC simultaneously.

Factor structure of cognitive performance and functional capacity in schizophrenia: Evidence for differences across functional capacity measures

BackgroundCognition and functional capacity predict functional outcomes in mental illness. Traditional approaches conceptualize cognition as comprised of domains, but many studies support a unifactorial structure. Some functional capacity measures may share a single-factor structure with cognition. In this study, we examined the factor structure of two measures of functional capacity, a conventional assessment and a newer computerized assessment, testing for a shared factor structure with cognition. MethodsPatients with schizophrenia and healthy controls were examined with the MATRICS Consensus Cognitive Battery (MCCB), the UCSD Performance Based Skills Assessment (UPSA), and the Virtual Reality Functional Capacity Assessment Tool (VRFCAT). Models of the factor structures of the MCCB, UPSA, and VRFCAT were calculated, as were correlations between MCCB scores and individual VRFCAT objectives. ResultsThe MCCB, VRFCAT, and UPSA all had unifactorial structures. The best fitting model of the correlations between MCCB and UPSA was a shared single factor, while the best fit for the relationship between MCCB and VRFCAT had two factors. Correlations between the MCCB domain and composite scores and the VRFCAT objectives suggested global rather than specific patterns of correlation. DiscussionThe relationship between cognitive performance and functional capacity was found to vary across functional capacity assessments. The UPSA and MCCB were not differentiated into separate factors, suggesting that the UPSA may overlap with neurocognitive performance. However, the VRFCAT appears to measure functional abilities that are separable from, yet correlated with, neurocognitive performance. It may provide a more distinctive assessment of the functional capacity construct.

Effects of an extrinsic motivator on the evaluation of cognitive and daily living functions in patients with schizophrenia

We investigated the effect of an extrinsic motivator on the MATRICS Consensus Cognitive Battery (MCCB) and UCSD Performance-Based Skills Assessment (UPSA) scores, which assess cognitive and daily living functions, in patients with schizophrenia. We enrolled 60 clinically stable patients with schizophrenia and allocated them to the motivator or control group. We conducted baseline assessments of cognitive function using the MCCB, daily living function using the UPSA, clinical symptoms, and psychosocial characteristics in both groups. In the retrial, we initially evaluated clinical symptoms. Next, we assigned an extrinsic motivator to the motivator group and again assessed cognitive function and daily living function using the MCCB and UPSA. Statistical analyses were performed using t-tests, Chi-square tests, Fisher's exact test, repeated measures analysis of variance, and logistic regression analysis. We found significant time × group interactions in processing speed, verbal learning, visual learning, and composite scores of MCCB. There were no significant interactions in UPSA scores. The meaningful change rates of social cognition and composite scores in MCCB were significantly higher in the motivator group than in the control group. After adjusting for additional variables, the extrinsic motivator had a significant effect on the meaningful MCCB composite score change. Conclusively, our findings suggest beneficial effects of extrinsic motivator on the MCCB score in patients with schizophrenia. In the future, the implementation and interpretation of the MCCB considering the motivation is necessary.

Profile of cognitive deficits in schizophrenia and factor structure of the Czech MATRICS Consensus Cognitive Battery

We aimed to validate the Czech version of the MATRICS Consensus Cognitive Battery (MCCB). The MCCB is a test battery designed to assess cognitive treatment effects in clinical trials of patients with schizophrenia. The valid, reliable and replicable measurement of cognition in schizophrenia is of substantial importance for such clinical trial studies. We performed a psychometric analysis of the MCCB composite and domain scores based on ROC analysis of 67 schizophrenia patients and 67 age- and education-matched healthy controls from a total sample of 220 controls. Also, we correlated MCCB variables with scales measuring psychosocial functioning (Personal and Social Performance scale; PSP). The internal consistency of all 10 tests in the MCCB battery was good (Cronbach's α = 0.85 (95% CI [0.83, 0.88])). The discriminative validity for the detection of neurocognitive dysfunction in schizophrenia based on the area under the curve of MCCB composite T-score was ≥90% (95% CI [0.85, 0.96]) and all MCCB domains showed ps < .001. The MCCB global composite and the Speed of Processing domain score significantly predicted the PSP ratings. A confirmatory factor analysis on the whole control sample (N = 220) showed an optimal fit for a 6-factor in comparison to 1-factor solution. In conclusion, we found high discriminative validity for the Czech MCCB version, similar to the differentiation of schizophrenia versus healthy control groups in the original MCCB studies. We also established the factorial validity of the MCCB and showed that the overall composite of the MCCB predicts psychosocial functioning in the patient group.

N400 event-related brain potential as an index of real-world and neurocognitive function in patients at clinical high risk for schizophrenia.

The N400 event-related potential is a neurophysiological index of cognitive processing of real-world knowledge. In healthy populations, N400 amplitude is smaller in response to stimuli that are more related to preceding context. This 'N400 semantic priming effect' is thought to reflect activation of contextually related information in semantic memory (SM). N400 semantic priming deficits have been found in schizophrenia, and in patients at clinical high risk (CHR) for this disorder. Because this abnormality in processing relationships between meaningful stimuli could affect ability to navigate everyday situations, we hypothesized it would be associated with real-world functional impairment in CHR patients. Second, we hypothesized it would correlate with global neurocognitive impairment in this group. We measured N400 semantic priming in 35 CHR patients who viewed prime words each followed by a related or unrelated target word, at stimulus-onset asynchrony (SOA) of 300 or 750 ms. We measured academic/occupational and social function with the global function (GF): Role and Social scales, and cognitive function with the MATRICS Consensus Cognitive Battery (MCCB). Decreased N400 semantic priming at the 300-ms SOA correlated with lower GF:Role scores. Decreased N400 semantic priming at the 750-ms SOA correlated with lower MCCB composite scores. Deficits in activating contextually related concepts in SM over short time intervals may contribute to functional impairment in CHR patients. Furthermore, N400 priming deficits over longer intervals may be a biomarker of global cognitive dysfunction in this population. Longitudinal studies are needed to determine whether these deficits are associated with schizophrenia risk within this population.

A randomized controlled trial of cognitive remediation for a national cohort of forensic patients with schizophrenia or schizoaffective disorder

BackgroundEvidence is accumulating that Cognitive Remediation Training (CRT) is effective for ameliorating cognitive deficits experienced by patients with schizophrenia and accompanying functional impairment. There has been no randomized controlled trial of CRT using a nationally representative population of forensic patients, despite the significant cognitive deficits frequently present within this group.MethodsSixty-five patients with schizophrenia or schizoaffective disorder were enrolled in a single blind randomized controlled trial of CRT versus treatment as usual (TAU); representing 94% of those eligible within a national forensic cohort. The primary outcome measure was the composite score of the MATRICS Consensus Cognitive Battery (MCCB). Secondary outcome measures included neurocognitive and social cognitive domains, symptoms, and ‘real world’ functioning. Patient satisfaction was examined using an exit interview. Participants were reassessed at 8 months follow up. All data were analyzed using an intention to treat design (ITT).ResultsFor the primary outcome measure, the MCCB composite score, there were significant differences between those who participated in CRT and those receiving TAU at both end of treatment and 8 months follow up (Cohen’s d = 0.34. Significant improvements were observed in visual and working memory. Mediation analysis found that those who cognitively benefited from CRT had corresponding improved functioning, and more net positive therapeutic moves i.e. moves to units with lower security within the hospital. Ninety-six percent believed their cognitive gains positively affected their daily lives.ConclusionsCRT may be an acceptable and efficacious intervention for forensic patients with schizophrenia or schizoaffective disorder.Trial registrationClinicalTrials.gov Identifier: NCT02360813. Trial registered Feb 4th 2015, last updated May 1st 2015.

The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial.

Preliminary evidence suggests that cannabidiol (CBD) may be effective in the treatment of neurodegenerative disorders; however, CBD has never been evaluated for the treatment of cognitive impairments associated with schizophrenia (CIAS). This study compared the cognitive, symptomatic, and side effects of CBD versus placebo in a clinical trial. This study was a 6-week, randomized, placebo-controlled, parallel group, fixed-dose study of oral CBD (600mg/day) or placebo augmentation in 36 stable antipsychotic-treated patients diagnosed with chronic schizophrenia. All subjects completed the MATRICS Consensus Cognitive Battery (MCCB) at baseline and at end of 6weeks of treatment. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and biweekly. There was no main effect of time or drug on MCCB Composite score, but a significant drug × time effect was observed (p = 0.02). Post hoc analyses revealed that only placebo-treated subjects improved over time (p = 0.03). There was a significant decrease in PANSS Total scores over time (p < 0. 0001) but there was no significant drug × time interaction (p = 0.18). Side effects were similar between CBD and placebo, with the one exception being sedation, which was more prevalent in the CBD group. At the dose studied, CBD augmentation was not associated with an improvement in MCCB or PANSS scores in stable antipsychotic-treated outpatients with schizophrenia. Overall, CBD was well tolerated with no worsening of mood, suicidality, or movement side effects. https://clinicaltrials.gov/ct2/show/NCT00588731.

Psychometric characteristics of the MATRICS Consensus Cognitive Battery in a large pooled cohort of stable schizophrenia patients

The MATRICS Consensus Cognitive Battery (MCCB) was developed to assess cognitive treatment effects in schizophrenia clinical trials, and is considered the FDA gold standard outcome measure for that purpose. The aim of the present study was to establish pre-treatment psychometric characteristics of the MCCB in a large pooled sample. The dataset included 2616 stable schizophrenia patients enrolled in 15 different clinical trials between 2007 and 2016 within the United States (94%) and Canada (6%). The MCCB was administered twice prior to the initiation of treatment in 1908 patients. Test-retest reliability and practice effects of the cognitive composite score, the neurocognitive composite score, which excludes the domain Social Cognition, and the subtests/domains were examined using Intra-Class Correlations (ICC) and Cohen's d. Simulated regression models explored which domains explained the greatest portion of variance in composite scores. Test-retest reliability was high (ICC=0.88) for both composite scores. Practice effects were small for the cognitive (d=0.15) and neurocognitive (d=0.17) composites. Simulated bootstrap regression analyses revealed that 3 of the 7 domains explained 86% of the variance for both composite scores. The domains that entered most frequently in the top 3 positions of the regression models were Speed of Processing, Working Memory, and Visual Learning. Findings provide definitive psychometric characteristics and a benchmark comparison for clinical trials using the MCCB. The test-retest reliability of the MCCB composite scores is considered excellent and the learning effects are small, fulfilling two of the key criteria for outcome measures in cognition clinical trials.

SU27. Cognitive Remediation, Cognitive Behavioral Therapy, and Occupational Outcome in Schizophrenia Spectrum Disorders: A 2-Year Follow-up Study

Background: Neurocognitive impairment is prominent in schizophrenia and significantly related to low occupational attainment and poor occupational outcomes (August et al, 2012). Vocational rehabilitation (VR) is frequently implemented to counteract high unemployment rates. Individuals with schizophrenia however face numerous challenges such as neurocognitive impairments and psychotic symptoms. Hence, augmenting VR to address illness-related factors may optimize occupational outcomes. The aim of this study was to examine the effects of Cognitive Remediation (CR)-augmented compared to Cognitive Behavioral Therapy (CBT)-augmented VR on neurocognition and occupational functioning over a 2-year period. Methods: One hundred and thirty-one participants underwent assessments at baseline, post-treatment (after 10 months), and follow-up (2 years after randomization). Performance on the MATRICS Consensus Cognitive Battery (MCCB), occupational status, and number of hours worked per week were recorded at all assessment points. Results: Both intervention groups improved on several neurocognitive domains, improvements were however in favor of the CR group with significant intervention-by-time interactions for working memory (P = .009) and the composite score (P = .03). There was a significant increase in number of participants working (79% vs 80% at post-treatment and 68% vs 58% at follow-up in CBT and CR, respectively) and hours worked throughout the project period, with no between-group differences. CBT participants were working 11.6 hours a week at post-treatment and 14 hours at follow-up, whereas CR participants worked 10.6 hours at post-treatment and 11.3 hours a week at follow-up. Separate multiple regression analyses with hours worked as criterion was not significant for CBT (P = .13), but for CR (P = .03) with education (P = .03) and positive change in Working Memory (P = .02) as significant predictors. Entering the composite change score as predictor instead of separate domains produced a significant model for CR (P = .02). Significant predictors were age (P = .04) and change in the composite score (P = .007). Conclusion: CR-augmented VR improved several neurocognitive domains, particularly Working Memory, which was central in the CR program as well as the MCCB Composite Score. Neurocognitive improvements may also be partially explained by additional strategy learning and bridging to work settings provided in the CR program perhaps reducing interference caused by neurocognitive impairments and leading to more sufficient allocation of neurocognitive resources in turn aiding in transfer of learning to vocational settings which consequently may have helped optimize occupational functioning. The major implication of these findings is that the combined effect of VR, organized collaboration between services and CBT/CR enabled a significant proportion of the participants to attain work and to increase the number of hours worked in the study.

Cognitive dysfunction correlates with elevated serum S100B concentration in drug-free acutely relapsed patients with schizophrenia.

S100B, a biomarker of glial dysfunction and blood-brain barrier (BBB) disruption, has been proposed to be involved in the pathophysiology of schizophrenia. In the present study, we aimed at exploring the association of serum S100B levels with cognitive deficits using MATRICS Consensus Cognitive Battery (MCCB) in schizophrenia, by excluding the impact of antipsychotics. Sixty-two unmedicated patients with schizophrenia during their acute phases were divided into a drug-naïve group (n=34) and a drug-free group (n=28). S100B serum concentrations were measured and MCCB was administered to all of the patients. Forty healthy controls donated their blood samples for S100B assessment. The results indicated that serum S100B was significantly elevated in the drug-naive/free acute-stage schizophrenic patients when compared to the healthy controls. In the drug-free group, the serum S100B level was an independent contributor to the global cognitive dysfunctions, particularly for the speed of processing, attention/vigilance, visual learning and reasoning/problem solving subscores. Nevertheless, no significant associations between S100B and MCCB composite score or any cognitive domain subscore were observed in the drug-naïve group. These findings support the hypothesis that glial dysfunction and associated marker protein S100B may contribute to the pathophysiologic development of neurocognitive deficits in the relapsed individuals with schizophrenia.

A Randomized Trial to Assess the Efficacy and Safety of ABT-126, a Selective α7 Nicotinic Acetylcholine Receptor Agonist, in the Treatment of Cognitive Impairment in Schizophrenia

The authors sought to evaluate the efficacy and safety of ABT-126, a selective α7 nicotinic receptor partial agonist, in stable patients with schizophrenia. A 12-week, double-blind, placebo-controlled, parallel-group phase 2 study was conducted in 22 centers in the United States. Clinically stable patients with schizophrenia were randomly assigned to receive once-daily dosing with 10 mg of ABT-126, 25 mg of ABT-126, or placebo. The primary efficacy measure was change from baseline to week 12 on the MATRICS Consensus Cognitive Battery (MCCB) composite score compared with placebo, tested by a one-sided t test. Secondary measures included MCCB domain scores and UCSD Performance-Based Skills Assessment total score, each tested by two-sided t tests. A total of 207 subjects were randomized, of whom 165 (81%) completed the study. ABT-126 showed an improvement that fell short of significance on the MCCB composite score at week 12 (least squares mean difference from placebo, 1.3 and 1.5 for the 10 mg and 25 mg groups, respectively). A significant treatment-by-smoking status interaction was observed on the mean change from baseline to final MCCB composite score: nonsmokers (N=69) demonstrated a difference from placebo of 2.9 (SE=1.4) in the 10 mg group and 5.2 (SE=1.6) in the 25 mg group, whereas no differences were observed in smokers (N=113). Among the nonsmokers in the ABT-126 25 mg group (N=19), significant improvements compared with placebo occurred at final assessment for verbal learning (least squares mean difference=5.5, SE=1.9), working memory (least squares mean difference=5.4, SE=2.0), and attention/vigilance (least squares mean difference=8.7, SE=2.5). The most frequently reported adverse events for ABT-126 were dizziness, diarrhea, and fatigue (all <8% incidence). ABT-126 demonstrated a procognitive effect in nonsmoking subjects, particularly in verbal learning, working memory, and attention.

Effects of transcranial direct current stimulation (tDCS) on cognition, symptoms, and smoking in schizophrenia: A randomized controlled study

Schizophrenia is characterized by cognitive deficits which persist after acute symptoms have been treated or resolved. Transcranial direct current stimulation (tDCS) has been reported to improve cognition and reduce smoking craving in healthy subjects but has not been as carefully evaluated in a randomized controlled study for these effects in schizophrenia. We conducted a randomized double-blind, sham-controlled study of the effects of 5 sessions of tDCS (2 milliamps for 20minutes) on cognition, psychiatric symptoms, and smoking and cigarette craving in 37 outpatients with schizophrenia or schizoaffective disorder who were current smokers. Thirty subjects provided evaluable data on the MATRICS Consensus Cognitive Battery (MCCB), with the primary outcome measure, the MCCB Composite score. Active compared to sham tDCS subjects showed significant improvements after the fifth tDCS session in MCCB Composite score (p=0.008) and on the MCCB Working Memory (p=0.002) and Attention-Vigilance (p=0.027) domain scores, with large effect sizes. MCCB Composite and Working Memory domain scores remained significant at Benjamini–Hochberg corrected significance levels (α=0.05). There were no statistically significant effects on secondary outcome measures of psychiatric symptoms (PANSS scores), hallucinations, cigarette craving, or cigarettes smoked. The positive effects of tDCS on cognitive performance suggest a potential efficacious treatment for cognitive deficits in partially recovered chronic schizophrenia outpatients that should be further investigated.

Examination of the validity of the Brief Neurocognitive Assessment (BNA) for schizophrenia

BackgroundAlthough many comprehensive batteries exist to evaluate the nature and degree of cognitive impairments in patients with schizophrenia, short batteries hold promise for rapidly screening and estimating deficits in global cognition. Recently, the Brief Neurocognitive Assessment (BNA) was established and has been shown to have similar validity and utility to a more comprehensive battery of cognitive tests in evaluating global cognitive impairments in patients with schizophrenia. The present study sought to further establish the validity of the BNA by comparing it with the MATRICS Consensus Cognitive Battery (MCCB). MethodsOne-hundred seventy-six patients with schizophrenia and 300 healthy volunteers participated in the present study. Global cognition was evaluated using the MCCB composite score and estimated using the BNA. To examine practice effects and test–retest reliability, patients were re-assessed after 4weeks. ResultsThe BNA was highly correlated with global cognition as evaluated by the MCCB in both the schizophrenia (r=0.82) and healthy control samples (r=0.75). Both instruments were similarly sensitive to deficits in global cognition in patients with schizophrenia relative to healthy controls. The BNA also demonstrated high test–retest reliability in patients with schizophrenia (r=0.87), comparable to the level observed with the MCCB (r=0.91). In addition, both the BNA and MCCB showed a similar level of practice effects (both Cohen's d=0.11), and both instruments demonstrated equivalent sensitivities to longitudinal change. Furthermore, scores from the BNA and MCCB were related to symptom severity and functional capacity to a similar degree. ConclusionsThe BNA provides clinicians and researchers with an efficient and reliable means by which to evaluate global neurocognitive impairments in patients with schizophrenia by allowing estimation of performance on a more comprehensive standardized battery.

The Effects of a Combined Intervention for Cognition in Schizophrenia On Cogstate Schizophrenia Battery

Background Cognitive impairment in schizophrenia is a strong predictor of the functional outcome and no effective treatments are available. MATRICS Consensus Cognitive Battery (MCCB) is approved by the FDA as outcome measure for trials of cognitive-enhancing drugs in schizophrenia. CogState Schizophrenia Battery (CSB) provides a briefer cognition assessment with minimal practice effects and a strong correlation between the CSB and MCCB composite scores. We tested the sensitivity of CSB as a cognitive outcome measure in a clinical trial in schizophrenia, where a cognitive-enhancing drug and cognitive training were combined. Methods 49 participants with schizophrenia were enrolled in a double-blind, placebo-controlled study. Participants were randomised to modafinil (200mg/day) or placebo and underwent a cognitive training program for 10 weekdays. CSB was administered twice at baseline to minimise practice effects, at the last day of the intervention and two weeks after the completion of the intervention. Results There was a significant time effect at the end of the intervention on the CSB composite score (p=0.042). There was no significant treatment effect on CSB composite score at the end of the intervention (p=0.686) or at follow up (p=0.120). Conclusions Multiple administrations of CSB were well tolerated by participants. The significant time effects on the composite score may suggest the operation of practice effects. Several factors could have contributed to the lack of treatment effects on CSB, such as the burden of multiple neuropsychological testing in a relatively brief study, the duration of modafinil treatment and also the intensive nature of cognitive training.

Limited practice effects and evaluation of expectation for change: MATRICS Consensus Cognitive Battery

Understanding of the impact of antipsychotic medications on cognition requires differentiating between treatment effects and practice effects. This prospective study examines expectations for change on neuropsychological assessments and possible differential practice effects in community dwelling schizophrenia patients (n=27) who are clinically stable and on a stable medication regimen when compared to demographically similar psychiatrically healthy controls (n=29). All participants were administered the MATRICS Consensus Cognitive Battery (MCCB) twice over a period of four weeks. The use of Regression Based Norms for Change (RBNC) and Reliable Change Index (RCI) was completed to anchor estimates of meaningful change to a demographically similar control group. A repeated measures ANOVA was used to examine the effects of time and diagnosis on MCCB composite scores. A repeated measures MANOVA was used to examine the effects of time and diagnosis, and their interaction for MCCB subtests. Estimates of meaningful change are provided. A significant main effect was observed for time; no significant interactions were observed. There was no support for differential practice effects. In the absence of any behavioral, cognitive, or pharmaceutical interventions, these findings suggest limited change in performance over time in either group.

Intrinsic hippocampal activity as a biomarker for cognition and symptoms in schizophrenia.

Identification of biomarkers for cognitive dysfunction in schizophrenia is a priority for psychiatry research. Functional imaging studies suggest that intrinsic "resting state" hippocampal hyperactivity is a characteristic feature of schizophrenia. The relationships between this phenotype and symptoms of the illness, however, are largely unexplored. The authors examined resting hippocampal activity in schizophrenia patients and healthy comparison subjects and analyzed the relationship between intrinsic hippocampal activity and cognitive function in patients as measured by the MATRICS Consensus Cognitive Battery (MCCB). Twenty-eight schizophrenia patients and 28 age-matched healthy comparison subjects underwent functional "resting state" 3-T MR scanning. Hippocampal activity was extracted by group independent component analysis. Correlation analyses were used to examine the relationship between hippocampal activity and MCCB composite and domain scores in patients, as well as between hippocampal activity and positive and negative symptoms. Greater activity of the right hippocampus at rest was observed in patients relative to comparison subjects. In patients, a significant negative correlation was observed between right hippocampal activity and composite MCCB T-score. The correlation was driven by the MCCB domains of attention/vigilance, working memory, and visual learning. Hippocampal activity was positively correlated with negative symptoms. MCCB scores were inversely correlated with negative symptoms. These findings suggest that greater intrinsic hippocampal activity is a characteristic feature of schizophrenia that is broadly associated with cognitive dysfunction, and they support hippocampal activity as a candidate biomarker for therapeutic development.

Virtual reality functional capacity assessment in schizophrenia: Preliminary data regarding feasibility and correlations with cognitive and functional capacity performance

IntroductionAssessment of functional capacity is an intrinsic part of determining the functional relevance of response to treatment of cognitive impairment in schizophrenia. Existing methods are highly and consistently correlated with performance on neuropsychological tests, but most current assessments of functional capacity are still paper and pencil simulations. We developed a computerized virtual reality assessment that contains all of the components of a shopping trip. MethodsWe administered the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) to 54 healthy controls and to 51 people with schizophrenia to test its feasibility. Dependent variables for the VRFCAT included time to completion and errors on 12 objectives and the number of times that an individual failed to complete an objective. The MATRICS Consensus Cognitive Battery (MCCB) and a standard functional capacity measure, the UCSD Performance-Based Skills Assessment-Brief (UPSA-B), were administered to the patients with schizophrenia. ResultsPatients with schizophrenia performed more poorly than healthy controls on 10/11 of the time variables, as well as 2/12 error scores and 2/12 failed objectives. Pearson correlations for 7 of 15 VRFCAT variables with MCCB composite scores were statistically significant. ConclusionThese results provide support for the possibility of computerized functional capacity assessment, but more substantial studies are required.