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      The Core Deficit of Classical Schizophrenia: Implications for Predicting the Functional Outcome of Psychotic Illness and Developing Effective Treatments Translated title: Le déficit de base de la schizophrénie classique : implications pour prédire le résultat fonctionnel de la maladie psychotique et développer des traitements efficaces

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          Abstract

          Many people suffering from psychotic illnesses experience persisting impairment of occupational and social function. Evidence assembled since the classical description of schizophrenia over a century ago indicates that both disorganization and impoverishment of mental activity are associated with persisting impairment. Longitudinal studies of young people at risk of schizophrenia reveal that both mental impoverishment and disorganization predict poor long-term outcome. These clinical features are related to cognitive impairments. Evidence from brain imaging indicates overlap in the brain abnormalities implicated in these phenomena, including impaired function of long-range connections between sensory cortex and the salience network, a network engaged in recruiting cerebral systems for processing of information salient to current circumstances.

          The evidence suggests that the common features underlying these two groups of symptoms might reflect a core pathological process distinguishing nonaffective from affective psychosis. This pathological process might therefore justifiably be designated the “core deficit” of classical schizophrenia. To develop more effective treatments to prevent persisting disability, we require the ability to identify individuals at risk at an early stage. Recent studies provide pointers toward effective strategies for identifying cases at risk of poor outcome. Accumulating evidence confirms that appreciable potential for neuroplastic change in the brain persists into adult life. Furthermore, brain function can be enhanced by targeted neuromodulation treatments. We now have promising tools not only for investigating the psychological and neural mechanisms that underlie persisting functional impairment but also for identifying individuals at risk and for harnessing brain plasticity to improve treatment.

          Translated abstract

          De nombreuses personnes souffrant de maladies psychotiques éprouvent une déficience persistante de la fonction professionnelle et sociale. Les données probantes assemblées depuis la description classique de la schizophrénie il y a plus d’un siècle indiquent que la désorganisation et l’appauvrissement de l’activité mentale sont associés à une déficience persistante. Les études longitudinales de jeunes personnes à risque de schizophrénie révèlent que tant l’appauvrissement que la désorganisation mentale prédisent de mauvais résultats à long terme. Ces traits cliniques sont liés aux déficiences cognitives. Les données probantes de l’imagerie cérébrale indiquent un chevauchement dans les anomalies du cerveau impliquées dans ces phénomènes, notamment la fonction déficiente des connexions longue portée entre le cortex sensoriel et le réseau de saillance, qui s’occupe de recruter les systèmes cérébraux pour traiter l’information digne d’attention dans les circonstances actuelles.

          Les données probantes suggèrent que les traits communs sous-jacents de ces deux groupes de symptômes pourraient refléter un processus pathologique de base distinguant la psychose non affective de la psychose affective. Ce processus pathologique pourrait donc être désigné de façon justifiable « déficit de base » de la schizophrénie classique. Afin de développer des traitements plus efficaces et prévenir la déficience persistante, nous réclamons la capacité d’identifier les personnes à risque à un stade précoce. Des études récentes offrent des pistes de stratégies efficaces pour identifier les cas à risque de mauvais résultats. L’accumulation de données probantes confirme que le potentiel appréciable de changement neuroplastique dans le cerveau persiste dans la vie adulte. En outre, la fonction cérébrale peut être améliorée par des traitements de neuromodulation ciblés. Nous avons dorénavant des outils prometteurs non seulement pour rechercher les mécanismes psychologiques et neuronaux qui sous-tendent la déficience fonctionnelle persistante, mais également pour identifier les personnes à risque et exploiter la plasticité du cerveau afin d’améliorer le traitement.

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          Most cited references35

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          A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes.

          Cognitive remediation therapy for schizophrenia was developed to treat cognitive problems that affect functioning, but the treatment effects may depend on the type of trial methodology adopted. The present meta-analysis will determine the effects of treatment and whether study method or potential moderators influence the estimates. Electronic databases were searched up to June 2009 using variants of the key words "cognitive," "training," "remediation," "clinical trial," and "schizophrenia." Key researchers were contacted to ensure that all studies meeting the criteria were included. This produced 109 reports of 40 studies in which ≥70% of participants had a diagnosis of schizophrenia, all of whom received standard care. There was a comparison group and allocation procedure in these studies. Data were available to calculate effect sizes on cognition and/or functioning. Data were independently extracted by two reviewers with excellent reliability. Methodological moderators were extracted through the Clinical Trials Assessment Measure and verified by authors in 94% of cases. The meta-analysis (2,104 participants) yielded durable effects on global cognition and functioning. The symptom effect was small and disappeared at follow-up assessment. No treatment element (remediation approach, duration, computer use, etc.) was associated with cognitive outcome. Cognitive remediation therapy was more effective when patients were clinically stable. Significantly stronger effects on functioning were found when cognitive remediation therapy was provided together with other psychiatric rehabilitation, and a much larger effect was present when a strategic approach was adopted together with adjunctive rehabilitation. Despite variability in methodological rigor, this did not moderate any of the therapy effects, and even in the most rigorous studies there were similar small-to-moderate effects. Cognitive remediation benefits people with schizophrenia, and when combined with psychiatric rehabilitation, this benefit generalizes to functioning, relative to rehabilitation alone. These benefits cannot be attributed to poor study methods.
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            Digit Symbol Substitution Test

            Abstract Purpose/Background Development of the Digit Symbol Substitution Test (DSST) was initiated over a century ago as an experimental tool to understand human associative learning. Its clinical utility, owing to its brevity and high discriminant validity, was first recognized in the 1940s, and now the DSST is among the most commonly used tests in clinical neuropsychology. Methods Specific studies and articles were reviewed to illustrate what the test measures, to evaluate its sensitivity to change, and to discuss its use in clinical practice. Results The DSST is a valid and sensitive measure of cognitive dysfunction impacted by many domains. Performance on the DSST correlates with real-world functional outcomes (eg, the ability to accomplish everyday tasks) and recovery from functional disability in a range of psychiatric conditions including schizophrenia and major depressive disorder. Importantly, the DSST has been demonstrated to be sensitive to changes in cognitive functioning in patients with major depressive disorder and offers promise as a clinical decision-making tool for monitoring treatment effects in this and other disorders affecting cognition. Implications/Conclusions The DSST is sensitive to the presence of cognitive dysfunction as well as to change in cognitive function across a wide range of clinical populations but has low specificity to determine exactly which cognitive domain has been affected. However, the DSST offers a practical and effective method to monitor cognitive functions over time in clinical practice.
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              Overlooking the obvious: a meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia.

              In focusing on potentially localizable cognitive impairments, the schizophrenia meta-analytic literature has overlooked the largest single impairment: on digit symbol coding tasks. To compare the magnitude of the schizophrenia impairment on coding tasks with impairments on other traditional neuropsychological instruments. MEDLINE and PsycINFO electronic databases and reference lists from identified articles. English-language studies from 1990 to present, comparing performance of patients with schizophrenia and healthy controls on coding tasks and cognitive measures representing at least 2 other cognitive domains. Of 182 studies identified, 40 met all criteria for inclusion in the meta-analysis. Means, standard deviations, and sample sizes were extracted for digit symbol coding and 36 other cognitive variables. In addition, we recorded potential clinical moderator variables, including chronicity/severity, medication status, age, and education, and potential study design moderators, including coding task variant, matching, and study publication date. Main analyses synthesized data from 37 studies comprising 1961 patients with schizophrenia and 1444 comparison subjects. Combination of mean effect sizes across studies by means of a random effects model yielded a weighted mean effect for digit symbol coding of g = -1.57 (95% confidence interval, -1.66 to -1.48). This effect compared with a grand mean effect of g = -0.98 and was significantly larger than effects for widely used measures of episodic memory, executive functioning, and working memory. Moderator variable analyses indicated that clinical and study design differences between studies had little effect on the coding task effect. Comparison with previous meta-analyses suggested that current results were representative of the broader literature. Subsidiary analysis of data from relatives of patients with schizophrenia also suggested prominent coding task impairments in this group. The 5-minute digit symbol coding task, reliable and easy to administer, taps an information processing inefficiency that is a central feature of the cognitive deficit in schizophrenia and deserves systematic investigation.
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                Author and article information

                Journal
                Can J Psychiatry
                Can J Psychiatry
                CPA
                spcpa
                Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
                SAGE Publications (Sage CA: Los Angeles, CA )
                0706-7437
                1497-0015
                21 August 2019
                October 2019
                : 64
                : 10
                : 680-685
                Affiliations
                [1 ]Division of Psychiatry and Applied Psychology, Institute of Mental Health, University of Nottingham, Nottingham, United Kingdom
                Author notes
                [*]Peter F. Liddle, Division of Psychiatry and Applied Psychology, Institute of Mental Health, University of Nottingham, Triumph Rd, Nottingham NG7 2TU, United Kingdom. Email: peter.liddle@ 123456nottingham.ac.uk
                Author information
                https://orcid.org/0000-0001-6473-7640
                Article
                10.1177_0706743719870515
                10.1177/0706743719870515
                6783668
                31434513
                8e70a2a9-e489-4ca8-b8a3-06dfbb2934f6
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Funding
                Funded by: National Institute for Health Research, FundRef http://dx.doi.org/10.13039/501100000272;
                Award ID: G0901321
                Categories
                Perspective

                schizophrenia,psychosis,outcome,disorganization,psychomotor poverty,negative symptoms,core deficit,salience network,neuroplasticity,treatment

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