The latest developments in the MATRICS process

Dr. Harvey is Professor of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
Psychiatry 06/2010; 7(6):49-52.
Source: PubMed


The Measurement and Treatment Research to Improve Cognition in Schizophrenia Research process has led to several developments in the assessment of cognitive functioning for schizophrenia-treatment studies. The first development was the development of a consensus cognitive battery and a United States Food and Drug Administration-endorsed research design. Since the development of the cognitive battery, interest has been spurred in clinical trials in different countries and the development of co-primary functional outcomes measures for these. The MATRICS Consensus Cognitive Battery has been translated into 11 different languages and is being translated into even more. A study has been completed that compared the usefulness of multiple potential co-primary measures, suggesting that the University of California San Diego Performance-Based skills assessment, version II (UPSA-II) is the most suitable for studies conducted in English. These findings suggest that reliable performance-based measures that are easy to administer and highly correlated with cognitive functioning are now available for use in treatment studies.

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Available from: Keith H Nuechterlein, Feb 15, 2015
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    • "The unmet medical need to find new approaches for the pharmacotherapy of the cognitive deficit in schizophrenia facilitated the establishment of MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia , and CNTRICS (Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia) initiatives (Carter, 2005; Carter and Barch, 2007; Carter et al., 2008; Harvey et al., 2010). As a result of the MATRICS collaboration a consensus of opinion on the core cognitive deficits in schizophrenia patients has emerged. "
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    ABSTRACT: Classical antipsychotics, e.g. haloperidol, chlorpromazine, are potent at controlling the positive symptoms of schizophrenia but frequently elicit extrapyramidal motor side-effects. The introduction of atypical antipsychotics such as risperidone, olanzapine and clozapine has obviated this problem, but none of the current drugs seem to improve the cognitive deficits accompanying schizophrenia. Thus there is an unmet need for agents that not only suppress the psychotic symptoms but also ameliorate the impairment of cognition. Here, we report the preclinical properties of a candidate antipsychotic, Egis-11150, that shows marked pro-cognitive efficacy. Egis-11150 displayed high affinity for adrenergic α(1), α(2c), 5-HT(2A) 5-HT(7), moderate affinity for adrenergic α(2a) and D(2) receptors. It was a functional antagonist on all of the above receptors, with the exception of 5-HT(7) receptors, where it was an inverse agonist. Phencyclidine-induced hypermotility in mice and inhibition of conditioned avoidance response in rats were assessed to estimate efficacy against the positive and social withdrawal test in rats was used to predict efficacy against the negative symptoms of schizophrenia. Passive-avoidance learning, novel object recognition and radial maze tests in rats were used to assess pro-cognitive activity, while phencyclidine-induced disruption of prepulse inhibition in mice was examined to test for effects on attention. Egis-11150 (0.01-0.3 mg/kg, ip.) was effective in all of the preclinical models of schizophrenia examined. Moreover, a robust pro-cognitive profile was apparent. In summary, work in preclinical models indicates that Egis-11150 is a potential treatment for controlling the psychosis as well as the cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
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    • "Such large samples imply multi-site trials, which present investigators and sponsors with specific challenges (for review, see ref.54). For international clinical trials, it is also important to ensure the cross-cultural and linguistic adaptability of primary67 and coprimary outcome measures.68 Several large-scale multisite studies, including international trials, are currently underway, and upon their completion, it may be possible to determine whether specific recommendations for performing multisite trials with neurocognitive assessments have been successfully implemented, and how these recommendations may impact trial results. "
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    ABSTRACT: In light of the number of studies conducted to examine the treatment of cognitive impairment associated with schizophrenia (CIAS), we critically reviewed recent CIAS trials. Trials were identified through searches of the website "" using the terms "schizophrenia AND cognition," "schizophrenia AND neurocognition," "schizophrenia AND neurocognitive tests," "schizophrenia AND MATRICS," "schizophrenia AND MCCB," "schizophrenia AND BACS," "schizophrenia AND COGSTATE," and "schizophrenia AND CANTAB" and "first-episode schizophrenia AND cognition." The cutoff date was 20 April 2011. Included trials were conducted in people with schizophrenia, the effects on cognition were either a primary or secondary outcome, and the effect of a pharmacologically active substance was examined. Drug challenge, pharmacokinetic, pharmacodynamic, or prodrome of psychosis studies were excluded. We identified 118 trials, with 62% using an add-on parallel group design. The large majority of completed trials were underpowered to detect moderate effect sizes, had ≤8 weeks duration, and were performed in samples of participants with chronic stable schizophrenia. The ongoing add-on trials are longer, have larger sample sizes (with a number of them being adequately powered to detect moderate effect sizes), and are more likely to use a widely accepted standardized cognitive battery (eg, the MATRICS Consensus Cognitive Battery) and MATRICS guidelines. Ongoing studies performed in subjects with recent onset schizophrenia may help elucidate which subjects are most likely to show an effect in cognition. New insights into the demands of CIAS trial design and methodology may help increase the probability of identifying treatments with beneficial effect on cognitive impairment in schizophrenia.
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    • "The executive functioning measures in the consensus battery included tests of working memory (letter-number and spatial span tests), vigilance (continuous performance) and reasoning-problem solving (Neuropsychological Assessment Battery mazes test). MATRICS' purpose, in part, was to have a repeatable battery which could be used to assess interventions over a short course clinical trial (Buchanan, Keefe et al. 2010; Harvey, Green et al. 2010). As a result of this short term, global cognitive functioning assessment aim, MATRICS might best be considered a baseline battery, useful for cross-study comparison, but with a breadth and depth too narrow for the assessment of trajectories or able to meaningfully capture any one set of abilities completely. "
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    ABSTRACT: Executive dysfunction is a core feature of schizophrenia, but our understanding of the developmental course of this neuropsychological domain in the disease remains largely unexplored. A review of the research evidence points to a number of persistent debates about the course of executive functioning and its relation to illness course. A better understanding of the neurocognitive trajectories of executive functioning in schizophrenia could help identify the risk and modifying factors that influence the onset, severity and course of disease, and the chance to re-direct or re-shape that course and improve outcomes. To accomplish this requires assessment of the diverse and integrated nature of those abilities, and the changes over time in those abilities requires multiple instruments and techniques in order to improve the research methods and understanding of an important area of impairment in schizophrenia.
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