Remediation In Schizophrenia Research Articles

Integrative Neuro-social cognitive Strategy Programme for Instilling REcovery (INSPIRE): a community-based cognitive remediation trial-study procotol

BackgroundAdults with schizophrenia experience a range of neurocognitive problems that affect their daily functioning. Evidence for the efficacy of cognitive remediation in schizophrenia has been established, but its implementation in under-resourced community-based settings is less well-studied. In recent years, interventions have also focused on the strategy-learning approach in favor of drill-and-practice. Moreover, there is an increasing recognition to address social cognition and negative symptoms alongside neurocognition.This study attempts to carry out cognitive remediation in a community mental health setting. The Neuropsychological and Educational Approach to Remediation (NEAR) is used as the cognitive remediation intervention. Neurocognitive and social cognitive games will be introduced during the computer-assisted cognitive exercises sessions. In addition, the instructional technique will foster the use of metacognition and cognitive strategies. Moreover, metamotivation training will be the focus of some bridging sessions to enhance motivation to engage in goal-directed learning behaviors.The aims of the study are to 1) investigate the effects of cognitive remediation on neurocognition, social cognition and functional outcomes of participants with schizophrenia/schizoaffective disorders in community mental health settings; and 2) explore the mediators for change (eg: metamotivation, metacognition and negative symptoms) in cognitive performance and functional outcomes.MethodsThis randomized controlled trial will be conducted in three Singapore Anglican Community Services (SACS) centers, where standard psychiatric rehabilitation is delivered. Participants who are randomized to the experimental arm will receive cognitive remediation and psychiatric rehabilitation, while those randomized to the control arm will receive standard psychiatric rehabilitation only. Cognitive remediation is carried out three times a week for 12 weeks. It consists of computer-assisted cognitive exercises, as well as bridging groups to aid transfer of learning to daily living. Baseline, post-intervention and eight-week follow-up measurements will be collected. Group by time differences in cognitive performance, negative symptoms, metamotivation, metacognition, functioning and recovery will be analyzed across the three time points. Mediators for improvement in cognitive performance and functioning will also be explored.DiscussionFindings of this research will add to the body of knowledge about the key therapeutic ingredients within a strategy-based cognitive remediation program and improve its implementation within under-resourced community settings.Trial registrationThis study has been registered with ClinicalTrials.gov (ID: NCT06286202). Date of registration: 29 February 2024. Date of last update: 21 May 2024.

Moderators of functional improvement after integrative cognitive remediation in schizophrenia: Toward a personalized treatment approach

Cognitive remediation is an effective intervention for improving functional outcome in schizophrenia. However, the factors that moderate this improvement are still poorly understood. The study aimed to identify moderators of functional outcome improvement after integrative cognitive remediation (REHACOP) in schizophrenia. This was a secondary analysis of data from two randomized controlled trials, which included 182 patients (REHACOP group=94; active control group=88). Hierarchical regression analyses were conducted to identify moderators of functional outcome improvement. Two baseline level groups (low-level and high-level) were created to analyze the moderating role of this baseline level cluster using repeated measures ANCOVA. The REHACOP was effective regardless of participants’ baseline level, but regression analyses indicated that the effectiveness on functional outcome was higher among those who were older, had fewer years in education, lower scores in baseline cognition and functional outcome, and more negative symptoms. Repeated measures ANOVA showed that the baseline level cluster influenced the improvement in functional outcome, with the low-level group showing greater improvements. The results reinforced the need to implement cognitive remediation programs more broadly as a treatment for schizophrenia in healthcare services. Furthermore, they provided evidence for the development of personalized cognitive remediation plans to improve benefits in different schizophrenia profiles.

Feasibility of six-month outpatient cognitive remediation in schizophrenia: Experience from the randomized controlled integrated social cognition and social skills therapy study

Patients with schizophrenia often have cognitive impairments that contribute to diminished psychosocial functioning. Cognitive remediation therapy (CRT) has proven efficacy and is recommended by evidence-based treatment guidelines. Important moderators of efficacy include integration of CRT into a psychiatric rehabilitation concept and patient attendance at a sufficient number of therapy sessions. These conditions can probably best be met in an outpatient setting; however, outpatient treatment is prone to higher rates of treatment discontinuation and outpatient settings are not as well protected as inpatient ones and less closely supervised.The present study investigated the feasibility of outpatient CRT in schizophrenia over a six-month period. Adherence to scheduled sessions and safety parameters were assessed in 177 patients with schizophrenia randomly assigned to one of two matched CRT programs.Results showed that 58.8 % of participants completed the CRT (>80 % of scheduled sessions) and 72.9 % completed at least half the sessions. Predictor analysis revealed a high verbal intelligence quotient as favorable for good adherence, but this factor had only low general predictive power. During the six-month treatment phase, serious adverse events occurred in 15.8 % (28/177) of the patients, which is a comparable rate to that reported in the literature.Our findings support the feasibility of six-month outpatient CRT in schizophrenia in terms of adherence to scheduled sessions and safety. Trial registration numberNCT02678858, DRKS00010033.

Discussion on Assessment and Treatment of Cognitive Impairment and New Developments of Cognitive Remediation in Schizophrenia

Cognitive impairment is conceptualised in different ways and the discussion will highlight differences and similarities. The importance of these cognitive impairments for choosing specific or generic cognitive remediation therapies will be highlighted as well as the need to consider social cognition and metacognition as potentially more important ingredients for improving recovery.DisclosureNo significant relationships.

The Feasibility and Effectiveness of Home-based Cognitive Remediation in Clinically Stable Schizophrenia Patients Attending a North Indian Tertiary Care Institution

Background: Cognitive deficits are one of the core symptoms of Schizophrenia that compromises real-world functioning, adversely impacts rehabilitation, and negatively influence the quality of life. Studies evaluating interventions for cognitive remediation in Schizophrenia are scarce in India. This study aimed to evaluate the effectiveness of the add-on home-based cognitive remediation strategy in schizophrenia in comparison to the schizophrenic patients receiving treatment as usual. 
 Methods: The research was carried out in a North Indian tertiary care teaching hospital. Clinically stable patients diagnosed with schizophrenia were randomly assigned to study and control groups. The control group had received treatment as usual, whereas the study group had received 8 weeks of home-based manual-based cognitive remediation in addition to the treatment as usual. Assessment of psychopathology, cognitive functioning, disability, and quality of life was done at baseline, completion at 8 weeks and 16 weeks follow up.
 Results: A total of 186 patients with schizophrenia were screened based on selection criteria. 74 patients were included in the study. During the intervention, 17 patients were dropped out, making the sample size of the study group to be 28 and the control group to be 29. At the baseline, the socio-demographic, as well as clinical variables, were comparable. After cognitive remediation intervention, the study group had better cognitive functioning, less disability, and better quality of life in comparison to the control group. The benefits were sustained in the study group at the end of two-month follow-up period. The effect size of home-based cognitive remediation was found to be moderate (Cohen’s d 0.4 to 0.69) at the end of the intervention.
 Conclusion: Home-based cognitive remediation is a feasible and effective strategy of intervention in patients with schizophrenia which has at least a short-lasting effect and it is also useful in limiting the disability and improving the quality of life.

Cognitive remediation in schizophrenia: What happens after 10 years?

Cognitive Remediation Therapy (CRT) represents the gold standard treatment for cognitive impairment in schizophrenia, but the permanence of its effects over time have been poorly investigated. Our study aims to evaluate long lasting cognitive and functional effects of CRT together with standard rehabilitation interventions (SRT) in a group of patients diagnosed with schizophrenia, 10 years after the end of the treatment. Forty patients, previously included in a 5-year follow-up study evaluating the effects of CRT combined with SRT, were revalued 10 years after the complete of the intervention. Results revealed that cognitive and functional improvements of combined CRT/SRT interventions are still preserved 10 years after the end of the treatments, with the only exception of psychomotor speed and coordination cognitive subdomain. Moreover, investigating persistence of the influence of SRT, patients that underwent a shorter SRT following CRT (six months vs one year) showed worsened processing speed abilities.This is the first study confirming that cognitive and functional improvements of joint CRT/SRT interventions are still conserved 10 years after the end of the treatments. Preliminary datas suggest that a longer SRT following CRT may lead to significant benefits, in terms of cognitive gains, in patients affected by schizophrenia.

Effects of repetitive training on learning and memory performance of TLR2 KO mice

Current antipsychotics have limited effects on the cognitive deficits of schizophrenia patients, therefore, cognitive remediation has been applied to schizophrenia patients to ameliorate cognitive dysfunction. However, the neurobiological mechanisms of cognitive training programs have not been well studied because established animal models are not suitable or because repetitive training has not been introduced in such animal models. In the present study, we employed Toll-like receptor 2 knockout (TLR2 KO) mouse as a schizophrenia mouse model and evaluated the effects of repetitive training as cognitive remediation therapy for schizophrenia. TLR2 KO mice could fully learn the Barnes maze paradigm through repetitive training to improve memory retrieval and reversal learning ability, although the learning speed was slower than that of wild-type (WT) animals. In addition, highly repetitive training activated the neuronal cells in the prefrontal cortex, hippocampal CA3 and hippocampal DG regions of TLR2 KO mice, similar to WT mice. These results indicated that TLR2 KO mouse would be a useful tool for studying the neurobiological mechanisms of cognitive remediation in schizophrenia.

A Literatur Review of Common Outcome in Cognitive Remediation for Schizophrenia

Background: People with schizophrenia experience a change especially in the cognitive aspect, and therefore require immediate intervention to improve their cognitive and other aspects. Cognitive remediation is a program that has been developed with promising results. Objective: to review the literature on outcomes in general from the provision of cognitive remediation in people with schizophrenia.Method: Searching relevant literature on relevant databases, i.e., Pubmed, Ebsco, Cochrane, JSTOR, and the Google Scholar search engine, using keywords: cognitive remediation, schizophrenia, therapy.Result: Taken from reviewing 21 relevant articles. Cognitive remediation affects cognitive function, functional ability and problem-solving, social skill and cognition, clinical symptoms, neural outcome, quality of life, self-esteem, and cost-utility analysis.Conclusions: Common outcomes in CRT (Cognitive Remediation Therapy) administration in people with schizophrenia have been identified. Improvement of cognitive function was defined to be the most commonly measured outcome in the study.

Effectiveness of cognitive remediation in schizophrenia: What works and what does not work?

Introduction: Cognitive function in schizophrenia is one of the main elements related to functional outcomes. Although there is enough evidence that cognitive remediation (CR) is beneficial, there is still a limited understanding of how the active therapy ingredients contribute to brain changes and translate into improved real-world functioning. Objectives: Identify neurobiological, psychopathological, cognitive, and functional CR response or resistance predictors in schizophrenia, considering both cognitive and functional outcomes. Results: We still lack a precise understanding of how CR produce its effects with different programs, different numbers of sessions, with and without a therapist. CR exerts its maximal benefit when delivered in the context of psychiatric rehabilitation, but it is not yet clear what are the mechanisms of integrated treatment effectiveness. Only a few studies have looked for the relationship between CR response or resistance and the biological, socio-demographic, clinical and cognitive features in schizophrenia. The current knowledge on efficacy predictors of CR is sparse and include: age, illness duration, premorbid adjustment, baseline cognitive performance, intrinsic motivation, hostility, disorganized symptoms, neurobiological reserve, genetic polymorphisms, antipsychotics amount, the type of CR, etc. All of these limitations may have contributed to the poor implementation of CR in national and international guidelines, as well as in clinical practice. Conclusions: It is important that future research shift from studies of group efficacy to individual efficacy of treatments, in the perspective of precision medicine. Issues related to individual effectiveness predictors and interactions between specific pharmacologic, specific CR technique and individual patients’ characteristics should be further addressed.DisclosureNo significant relationships.

Computer-Assisted Cognitive Remediation in Schizophrenia: Efficacy of an Individualized vs. Generic Exercise Plan.

Computer-assisted cognitive remediation (CACR) is an economical, adjustable, and effective treatment for individuals with schizophrenia. The current randomized controlled study examined whether an individualized or generic exercise plan in CACR is superior in patients with multiple cognitive deficits compared to treatment-as-usual (TAU). Fifty-nine inpatients diagnosed with schizophrenia were randomly assigned to 1) TAU, 2) TAU plus an individualized exercise plan in CACR, or 3) TAU plus a generic exercise plan in CACR. Neuropsychological performance, psychopathology, and functional outcome were assessed at baseline and post-treatment. The results show a medium to large training effect for all neuropsychological performance measures. Contrary to our expectations the neuropsychological improvement over time did not differ between groups. Self-reported depression, global level of functioning, and activity and participation functioning showed a significant improvement from baseline to post-treatment. However no further group, time, or interaction effects for other psychopathology and functional outcome could be demonstrated. Possible implications for clinical use of CACR and future studies are discussed.

How Cognitive Remediation in Schizophrenia Brings Us Back to Systemic Therapies: a Viewpoint

Almost a decade has passed since (Wykes et al. 2011) released a famous meta-analysis of cognitive remediation for schizophrenia. They concluded that stronger effects of the functional outcome of cognitive training occur when the remediation is co-provided with psychiatric rehabilitation. By analysing six recent research papers, we re-evaluated this hypothesis by comparing cognitive-oriented and multidimensional strategies. Consistent with (Wykes et al. 2011), the latest studies have shown that benefits from cognitive remediation are increased when associated with psychosocial intervention and focused on daily life implementation, although we were not able to formally conclude on these improvements related to psychosocial rehabilitation because the reviewed studies were not uniform in their control experiments.

Cognitive remediation and brain connectivity: A resting-state fMRI study in patients with schizophrenia

Cognitive remediation is able to improve activation patterns in the frontal lobe but only few data on neuroconnectivity has been reported yet. Resting-state approach is a neuroimaging methodology with potentiality for testing neuroconnectivity in the context of cognitive remediation in schizophrenia. A resting-state fMRI data was acquired in part of the sample (n = 26 patients, n = 10 healthy controls) of a partner study (NCT 02341131) testing the effects of cognitive remediation. A data-driven approach using independent component analysis (ICA) was used to identify functional brain networks, which were compared between groups and group per time using a dual-regression approach. ICA results revealed reduced functional connectivity between patients and controls in sensorimotor, basal ganglia, default mode and visual networks at baseline (p<0.05 FWE-corrected). After treatment, time per group analyses evidenced increased connectivity in sensorimotor network. Furthermore, group comparison at follow-up showed similar connectivity patterns between patients and healthy controls in sensorimotor network, but also in default mode and basal ganglia networks. No differences between treatment groups were found. Our results add some evidence to the hypothesis of altered connectivity in schizophrenia, and the possibility to modify some aspects of brain connectivity networks after psychological interventions.

Modulation of frontal gamma oscillations improves working memory in schizophrenia

Schizophrenia is a debilitating mental disorder that is associated with cognitive deficits. Impairments in cognition occur early in the course of illness and are associated with poor functional outcome, but have been difficult to treat with conventional treatments. Recent studies have implicated abnormal neural network dynamics and impaired connectivity in frontal brain regions as possible causes of cognitive deficits. For example, high-frequency, dorsal-lateral prefrontal oscillatory activity in the gamma range (30–50 Hz) is associated with impaired working memory in individuals with schizophrenia.In light of these findings, it may be possible to use EEG neurofeedback (EEG-NFB) to train individuals with schizophrenia to enhance frontal gamma activity to improve working memory and cognition. In a single-group, proof-of-concept study, 31 individuals with schizophrenia received 12 weeks of twice weekly EEG-NFB to enhance frontal gamma band response. EEG-NFB was well-tolerated, associated with increased gamma training threshold, and significant increases in frontal gamma power during an n-back working memory task. Additionally, EEG-NFB was associated with significant improvements in n-back performance and working memory, speed of processing, and reasoning and problem solving on neuropsychological tests. Change in gamma power was associated with change in cognition. Significant improvements in psychiatric symptoms were also found. These encouraging findings suggest EEG-NFB targeting frontal gamma activity may provide a novel effective approach to cognitive remediation in schizophrenia, although placebo-controlled trials are needed to assess the effects of non-treatment related factors.

Cognitive Remediation for Schizophrenia: Effectiveness, Core Elements and Moderators of Response. A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cognitive Remediation for Schizophrenia: Effectiveness, Core Elements and Moderators of Response. A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cognitive remediation in schizophrenia: the earlier the better?

Impairments in neuro and social cognition are considered core features of schizophrenia (SCZ) since they affect patients' functioning and contribute to poor socio-occupational outcomes. Therefore, the improvement of cognitive performances has become a primary goal in the care of patients with SCZ, especially in the first phases of the disease, as early interventions may favour better long-term outcomes. Cognitive remediation (CR) is a behavioural training aimed at improving cognitive functions with the goal of durability and generalisation in everyday life. Neuroimaging studies suggest that CR leads to neuroplasticity in chronic SCZ, whereas only a few studies tested the neural effects of CR in the early phase of the disease. Thus, in this review, we aimed at summarising CR-induced structural and functional brain changes in early SCZ. Existing evidence showed a protective effect of CR on grey matter volume in selected medial-temporal (i.e. hippocampus, parahippocampus and amygdala) and thalamic regions whereas functional changes affected mostly dorsolateral prefrontal and insular cortices both associated with improvements in cognitive performance and emotion regulation. Overall, CR in early SCZ appears to be associated with neural adaptations mostly allocated in prefrontal and limbic regions, however future longitudinal studies are needed to clarify whether the positive effects of cognitive training persist over time. It may also be interesting to investigate whether the application of CR in the early v. the late stage of the disease may lead to incremental benefits.

Neurocognitive and Self-efficacy Benefits of Cognitive Remediation in Schizophrenia: A Randomized Controlled Trial - Corrigendum.

Neurocognitive and Self-efficacy Benefits of Cognitive Remediation in Schizophrenia: A Randomized Controlled Trial - Corrigendum.

Remediation of Visual Processing Impairments in Schizophrenia: Where We Are and Where We Need to Be

Visual perceptual deficits are well-established in schizophrenia and are related to poorer outcomes and functioning. Improvement in perceptual functioning with training has been reliably demonstrated in healthy populations, yet relatively few studies have examined approaches to targeting visual processing dysfunction in schizophrenia. This review summarizes recent literature investigating visual remediation in schizophrenia, identifies current limitations, and suggests directions for further research. Existing studies provide support for the remediation of visual processing impairments in schizophrenia and demonstrate that improvement occurs at low-level, mid-level, and higher-level stages of processing. These studies also suggest that improvements in visual processes may generalize to other visual perceptual and visual cognitive functions. These early findings are promising and demonstrate the effectiveness of visual remediation interventions in schizophrenia. However, more empirical research is needed to determine the effectiveness of current interventions, to develop new interventions, to isolate the relevant mechanisms of change, and to promote the generalization of gains to other functions.

The Relationship Between Cognitive Dysfunction and Symptom Dimensions Across Schizophrenia, Bipolar Disorder, and Major Depressive Disorder.

Background: Cognitive dysfunction is considered a core feature among schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Despite abundant literature comparing cognitive dysfunction among these disorders, the relationship between cognitive dysfunction and symptom dimensions remains unclear. The study aims are a) to identify the factor structure of the BPRS-18 and b) to examine the relationship between symptom domains and cognitive function across SZ, BD, and MDD. Methods: A total of 716 participants [262 with SZ, 104 with BD, 101 with MDD, and 249 healthy controls (HC)] were included in the study. One hundred eighty participants (59 with SZ, 23 with BD, 24 with MDD, and 74 HC) completed the MATRICS Consensus Cognitive Battery (MCCB), and 507 participants (85 with SZ, 89 with BD, 90 with MDD, and 243 HC) completed the Wisconsin Card Sorting Test (WCST). All patients completed the Brief Psychiatric Rating Scale (BPRS). Results: We identified five BPRS exploratory factor analysis (EFA) factors (“affective symptoms,” “psychosis,” “negative/disorganized symptoms,” “activation,” and “noncooperation”) and found cognitive dysfunction in all of the participant groups with psychiatric disorders. Negative/disorganized symptoms were the most strongly associated with cognitive dysfunctions across SZ, BD, and MDD. Conclusions: Our findings suggest that cognitive dysfunction severity relates to the negative/disorganized symptom domain across SZ, BD, and MDD, and negative/disorganized symptoms may be an important target for effective cognitive remediation in SZ, BD, and MDD.

11.4 TOWARDS A MODEL FOR PERSONALIZING COGNITIVE REMEDIATION ON THE BASIS OF GENETIC POLYMORPHISMS

Cognitive remediation (CR) for schizophrenia is an evidence-based intervention as it has been demonstrated in meta-analytic studies. However, little is known about how individual differences could be affecting responsiveness. Among other variables, genetic variability could help to understand some aspects of the underlying biological mechanisms of cognitive remediation in schizophrenia. Intuitively, genetic variability could be causing different responsivity to cognitive remediation and then, if that would be proved, variability in genetics could help to define new predictors of response and eventually they might allow us to personalize treatments in the near future. In this talk we will discuss the literature on genetic factors that may impact response to CR and the results of a systematic review will be presented. Moreover, an exploratory study testing the potential role of two different gene polymorphisms (COMT and BDNF gene) on cognition in a sample of n=110 participants with schizophrenia will be presented. Finally, a tentative model for predicting responsiveness to CR will be presented. Two different genes have been studied in the context of CR responsiveness. The brain-derived neurotrophic factor (BDNF) has been proposed as a specific marker of cognitive recovery. When samples were divided according to the resulting polymorphisms of the BDNF gene, the carriers of the Met allele behaved totally differently from the rest and no increase in serum BDNF levels was observed, while those without the Met allele did experience an increase in serum levels similar to previous studies. Those data could be potentially reflecting the presence of a negative response marker to cognitive remediation. On the other hand, some studies have shown that other gene polymorphisms, especially those that influence the release of dopamine, could act to influence the response to cognitive interventions in schizophrenia. The most studied is catechol-O-methyltransferase (COMT), which is an important enzyme for the degradation process of dopamine that regulates the availability of dopamine in the frontal cortex. Finally, in our own sample significant differences were found in different COMT polymorphisms in cognitive flexibility (t= 12.81; p = 0.001). In addition, significant differences were also found in measures of verbal learning (t= 11.87; p = 0.04) for different variants of the BDNF gene. Current data allow us to postulate a provisional model for predicting response to cognitive remediation including the BDNF Val66Met polymorphism and the COMT Val158Met polymorphisms. It seems like those polymorphisms could be accounting for different response to cognitive remediation in different cognitive domains: memory and cognitive flexibility. Eventually, if more new data about different genetic polymorphisms become available, we will able to enhance and improve that prediction model. The aforementioned model could contribute to the particularization and optimization of cognitive remediation interventions in schizophrenia.

Factors Associated With Response and Resistance to Cognitive Remediation in Schizophrenia: A Critical Review.

Cognitive impairment is a central feature of schizophrenia and has shown to play a crucial role in the psychosocial function of the disorder. Over the past few years, several cognitive remediation (CR) interventions have been developed for schizophrenia, whose effectiveness has also been widely demonstrated by systematic reviews and meta-analysis studies. Despite these evidences, many questions remain open. In particular, the identification of CR response predictors in patients with schizophrenia is still a topic with equivocal findings and only a few studies have looked for the relationship between CR response or resistance and the biological, socio-demographic, clinical and cognitive features in schizophrenia. The current knowledge on positive or negative response predictors to CR treatment in schizophrenia include: age, duration of illness, premorbid adjustment, baseline cognitive performance, intrinsic motivation, hostility, disorganized symptoms, neurobiological reserve, genetic polymorphisms, the amounts of antipsychotics, the type of CR, etc. The aim of this review is to identify neurobiological, psychopathological, cognitive, and functional predictors of CR response or resistance in schizophrenia, taking into account both cognitive and functional outcome measures. The information obtained could be very useful in planning integrated and personalized interventions, also with a better use of the available resources.