Green MF, Nuechterlein KH. The MATRICS initiative: developing a consensus cognitive battery for clinical trials. Schizophr Res 72: 1-3

Schizophrenia Research (Impact Factor: 3.92). 01/2005; 72(1):1-3. DOI: 10.1016/j.schres.2004.09.006
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    • "Cognitive Impairment in Schizophrenia (CIAS) is a major unmet medical need for this patient population; while psychosis can be readily managed by the current antipsychotic drug armentarium, cognitive and negative symptoms are hampering patients to return to a more normal professional life (Kitchen et al., 2012). This has prompted the major stakeholders from industry, regulatory agencies and academia to develop a regulatory path for cognitive enhancement, resulting in the development of the Matrics battery (Green and Nuechterlein, 2004). Over the last 15 years, many novel highly selective drugs have been tested for cognitive enhancement as augmentation therapy without much success (Dunlop and Brandon, 2015). "
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    ABSTRACT: While many drug discovery research programs aim to develop highly selective clinical candidates, their clinical success is limited because of the complex non-linear interactions of human brain neuronal circuits. Therefore, a rational approach for identifying appropriate synergistic multipharmacology and validating optimal target combinations is desperately needed. A mechanism-based Quantitative Systems Pharmacology (QSP) computer-based modeling platform that combines biophysically realistic preclinical neurophysiology and neuropharmacology with clinical information is a possible solution. This paper reports the application of such a model for Cognitive Impairment In Schizophrenia (CIAS), where the cholinomimetics galantamine and donepezil are combined with memantine and with different antipsychotics and smoking in a virtual human patient experiment. The results suggest that cholinomimetics added to antipsychotics have a modest effect on cognition in CIAS in non-smoking patients with haloperidol and risperidone and to a lesser extent with olanzapine and aripiprazole. Smoking reduces the effect of cholinomimetics with aripiprazole and olanzapine, but enhances the effect in haloperidol and risperidone. Adding memantine to antipsychotics improves cognition except with quetiapine, an effect enhanced with smoking. Combining cholinomimetics, antipsychotics and memantine in general shows an additive effect, except for a negative interaction with aripiprazole and quetiapine and a synergistic effect with olanzapine and haloperidol in non-smokers and haloperidol in smokers. The complex interaction of cholinomimetics with memantine, antipsychotics and smoking can be quantitatively studied using mechanism-based advanced computer modeling. QSP modeling of virtual human patients can possibly generate useful insights on the non-linear interactions of multipharmacology drugs and support complex CNS R&D projects in cognition in search of synergistic polypharmacy.
    Frontiers in Pharmacology 09/2015; 6. DOI:10.3389/fphar.2015.00198 · 3.80 Impact Factor
    • "Neuropsychological assessment A comprehensive neuropsychological test battery was administered to all participants. Cognitive tests scores were reduced to the following six cognitive domains of the MATRICS consensus battery (Green et al., 2004): speed of processing, working memory, verbal learning and memory, visual learning and memory, attention/vigilance , reasoning, and problem solving. The appropriateness of the six factor structures was validated in a previous study (Noh et al., 2010). "
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    ABSTRACT: The neuregulin 1 (NRG1) gene has been investigated as a candidate susceptibility gene for schizophrenia. A number of studies have also explored the genetic effect of NRG1 on cognitive deficits related to schizophrenia, and thus far generated inconsistent results. The current study aimed to determine whether genetic variations in NRG1 are associated with cognitive domains in schizophrenic patients and healthy individuals. Comprehensive neuropsychological tests composed of six cognitive domains were administered to 135 clinically stable patients with schizophrenia and 119 healthy individuals. On the basis of previous reports of positive association, a total of four single nucleotide polymorphisms were analyzed. In testing the genotype effect on cognitive domains, we used repeated-measure analysis for six cognitive domain scores of each individual as repeated measurements. An association of P-value less than 0.05 with at least one cognitive domain in patients and/or healthy individuals was observed for all of the single nucleotide polymorphisms. After applying the correction for multiple testing, the association remained statistically significant between rs6994992 and general cognitive ability (g) in the patient group and between rs2439272 and the 'working memory' domain in the group of healthy participants. This study suggests the involvement of NRG1 in the susceptibility for developing cognitive deficits in schizophrenic patients. For some cognitive domains, its genetic effect was also significant in generating interindividual variability within the normal functional range.
    Schizophrenia Research 04/2014; 153(4):S237. DOI:10.1016/S0920-9964(14)70680-2 · 3.92 Impact Factor
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    • "To support the development of pharmacological agents to improve neurocognitive deficits of schizophrenia, NIMH launched an initiative called “Measurement and Treatment Research to Improve Cognition in Schizophrenia” (MATRICS). As a result this initiative developed a consensus neurocognitive battery for use in clinical trials to study the pharmacological effects on neurocognition (Green and Nuechterlein, 2004). "
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    ABSTRACT: Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been related not only to neurodevelopment and neuroprotection, but also to synapse regulation, learning, and memory. Research focused on the neurobiology of schizophrenia has emphasized the relevance of neurodevelopmental and neurotoxicity-related elements in the pathogenesis of this disease. Research focused on the clinical features of schizophrenia in the past decades has emphasized the relevance of cognitive deficits of this illness, considered a core manifestation and an important predictor for functional outcome. Variations in neurotrophins such as BDNF may have a role as part of the molecular mechanisms underlying these processes, from the neurodevelopmental alterations to the molecular mechanisms of cognitive dysfunction in schizophrenia patients.
    Frontiers in Psychiatry 06/2013; 4:45. DOI:10.3389/fpsyt.2013.00045
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