Do metacognitive therapies for schizophrenia-spectrum disorders work? A meta-analytic investigation.

Recent reviews and meta-analyses of metacognitive therapy for schizophrenia-spectrum disorder (SSD) have included uncontrolled studies, single-session interventions, and/or analyses limited to a single form of metacognitive therapy. We sought to evaluate the efficacy of metacognitive therapies more broadly based on controlled trials (CT) of sustained treatments. We conducted a pre-registered meta-analysis of controlled trials that investigated the effects of meta-cognitive therapies on primary positive symptom outcomes, and secondary symptom, function and/or insight measures. Electronic databases were searched up to March 2022 using variants of the keywords, 'metacognitive therapy', 'schizophrenia', and 'controlled trial'. Studies were identified and screened according to PRISMA guidelines. Outcomes were assessed with random effects models and sample, intervention, and study quality indices were investigated as potential moderators. Our search identified 44 unique CTs with usable data from 2423 participants. Data were extracted by four investigators with reliability >98%. Results revealed that metacognitive therapies produced significant small-to-moderate effects on delusions (g = 0.32), positive symptoms (g = 0.30) and psychosocial function (g = 0.31), and significant, small effects on cognitive bias (g = 0.25), negative symptoms (g = 0.24), clinical insight (g = 0.29), and social cognition (g = 0.27). Findings were robust in the face of sample differences in age, education, gender, antipsychotic dosage, and duration of illness. Except for social cognition and negative symptoms, effects were evident even in the most rigorous study designs. Thus, results suggest that metacognitive therapies for SSD benefit people, and these benefits transfer to function and illness insight. Future research should modify existing treatments to increase the magnitude of treatment benefits.

A meta-analysis of the effects of social-cognitive training in schizophrenia: The role of treatment characteristics and study quality.

OBJECTIVES: This meta-analysis was designed to assess the effects of social-cognitive training (SCT) and whether study quality, treatment approach, treatment context, and sample characteristics influence these effects. METHODS: Electronic databases were searched up to 5 August 2020 using variants of keywords: 'social cognition', 'training', 'rehabilitation', 'remediation', and 'schizophrenia'. Methodological moderators were extracted through the Clinical Trials Assessment Measure and verified by authors. This study was pre-registered on PROSPERO (CRD42020154026). RESULTS: Forty-two controlled trials with 1,868 participants were identified. The meta-analysis revealed moderate effects on emotion recognition, mental state attribution, and social perception. No significant effects were evident on psychiatric symptoms or social functioning. A small signal was evident for the generalization of treatment gains to executive function. Moderator analyses revealed that studies of lower methodological quality reported larger effects, and samples with lower mean years of education were associated with larger effects of SCT on mental state attribution. Treatment effects did not differ by other moderator variables such as treatment context and intervention types. CONCLUSIONS: SCT benefits people with schizophrenia on a variety of social-cognitive outcomes. Differences in baseline symptoms, gender distribution, antipsychotic medication dose, IQ, and other sample features did not create barriers to treatment benefits. Future studies should aim to enhance the generalization of training effects on broader clinical outcomes.

The effects of cognitive-focused interventions on cognition and psychological well-being in persons with multiple sclerosis: A meta-analysis.

Cognitive impairment affects more than half of persons with multiple sclerosis (PwMS), and it is associated with difficulties in multiple aspects of daily functioning. There is a growing body of literature that has explored the use of cognitive-focused interventions in PwMS, which aim to improve cognition-related function through drill and practice exercises, training in compensatory strategies, or a combination of the two. The current study aimed to expand upon previously published meta-analyses in this area, exploring the effects of cognitive-focused interventions on objective and subjective functioning in PwMS, as well as determining demographic and treatment-related factors that may influence intervention efficacy. Thirty-three studies, with a total of 1890 participants, were included in the meta-analysis. Outcome measures were categorised based on the domain they presumably assessed. For objective cognitive functioning, weighted effect-size analysis revealed small effects of cognitive-focused interventions on working memory (g = 0.31) and visual learning (g = 0.32). Small mean effect sizes were also noted on self-reported anxiety (g = -0.30) and depression (g = -0.23). Cognitive-focused interventions did not produce changes in subjective cognitive functioning. Moderating variables and clinical applications are also discussed.

Verbal Learning and Memory Enhancement Strategies in Schizophrenia: A Randomized, Controlled Investigation.

OBJECTIVES: Verbal episodic memory is a key domain of impairment in people with schizophrenia with close ties to a variety of aspects of functioning and therapeutic treatment response. A randomized, blinded trial of two mnemonic strategies for verbal episodic memory deficits for people with schizophrenia was conducted. METHODS: Sixty-one people with schizophrenia were assigned to one of three experimental conditions: training in a mnemonic strategy that included both visualization and narrative structure (Story Method), a condition in which participants were trained to visualize words interacting with one another (Imagery), or a non-trained control condition in which participants received equivalent exposure to training word lists and other verbal memory assessments administered in the other two conditions, but without provision of any compensatory mnemonic strategy. Participants were assessed on improvements in recall of the word list used as part of training, as well as two, standardized verbal memory assessments which included stimuli not used as part of strategy training. RESULTS: The Story Method produced improvements on a trained word list that generalized to a non-trained, prose memory task at a 1-week follow-up. In contrast, provision of a mnemonic strategy of simple visualization of words produced little improvement on word recall of trained words or on measures of generalization relative to the performance of participants in the control condition. CONCLUSIONS: These findings support the inclusion of enriched mnemonic strategies consisting of both visualization and narrative structure in sustained and comprehensive programs of CR for enhancement of verbal episodic memory in schizophrenia. (JINS, 2017, 23, 352-357).

Neuroplastic Changes Following Social Cognition Training in Schizophrenia: A Systematic Review.

Social cognitive impairment is a key feature of schizophrenia and social cognition training (SCT) is a promising tool to address these deficits. Neurobiological dysfunction in schizophrenia has been widely researched, but neuronal changes induced by SCT have been scarcely explored. This review aims to assess the neuroplastic effects of SCT in patients with schizophrenia spectrum disorders. PubMed and Web of Science databases were searched for clinical trials testing the effects of SCT in functional and structural brain measurements of adult patients with schizophrenia or schizoaffective disorders. A total of 11 studies were included: five used fMRI, two used EEG and ERP, one used ERP only, two used MEG and one study used MRI. Data extracting and processing regarding sociodemographic and clinical variables, intervention characteristics, neuroimaging procedures, neuroplastic findings, effect sizes and study quality criteria was completed by two raters. Results indicate a wide range of structural and functional changes in numerous regions and circuits of the social brain, including early perceptual areas, the limbic system and prefrontal regions. Despite the small number of trials currently available, evidence suggests that SCT is associated with neuroplastic changes in the social brain and concomitant improvements in social cognitive performance. There is a lack of extensive knowledge about the neural mechanisms that underlie social cognitive enhancement after treatment, but the reported findings may shed light on the neural substrates of social cognitive impairment in schizophrenia and how improved treatment procedures can be developed and applied.

Adjunctive pharmacotherapy for cognitive deficits in schizophrenia: meta-analytical investigation of efficacy.

BACKGROUND: A growing number of studies have investigated the efficacy of novel, adjunctive pharmacotherapies for treatment of cognitive deficits in schizophrenia with conflicting results. AIMS: To investigate the comparative efficacy of these agents on cognition and symptoms in schizophrenia, and to identify promising cognitive domains and candidate medications that can be incorporated in treatment trials combined with cognitive remediation to maximise treatment effects. METHOD: A total of 26 double-blind, placebo-controlled studies investigating medications targeted at cholinergic, glutamatergic or serotonergic receptor classes and with participants with schizophrenia or schizoaffective disorder were identified. RESULTS: Medications targeted at the cholinergic receptor class produced marginal improvements in verbal learning and memory (d = 0.23, P = 0.06), and donepezil, a specific type of cholinergic agonist, produced a moderate effect (d = 0.58) on spatial learning and memory. Cholinergic and glutamatergic agents produced moderate effect-size improvements on negative symptoms (d = 0.54 and d = 0.62 respectively), and small effect-size improvements on general symptoms (d = 0.46 and d = 0.41 respectively). Serotonergic agents produced small effect-size improvements in positive symptoms (d = 0.33). CONCLUSIONS: Cholinergic medications produced marginal improvement in verbal learning and memory and moderate improvements on spatial learning and memory, although there was no evidence to support the use of glutamatergic or serotonergic medications as a stand-alone treatment for improving cognitive function. Cholinergic and glutamatergic agents improved negative and general symptoms, whereas serotenergic medications improved positive symptoms.

A meta-analytic investigation of cognitive remediation for mood disorders: Efficacy and the role of study quality, sample and treatment factors.

BACKGROUND: The number of randomized, controlled studies of cognitive remediation (CR) for mood disorders (major depressive disorder [MDD] and bipolar illness [BD]), has grown substantially over the past 10 years. The role of study quality, participant characteristics, and intervention features in CR treatment effects remains largely unknown. METHODS: Electronic databases were searched up to February 2022 using variants of the key words: "cognitive remediation", "clinical trials", "major depressive disorder" and "bipolar disorder". This search produced 22 unique randomized, controlled trials that met all inclusion criteria for the study. Data were extracted by 3 authors with strong reliability (>90 %). Primary cognitive, and secondary symptom and functional outcomes were assessed with random effects models. RESULTS: The meta-analysis (993 participants) revealed that CR produced significant small-to-moderate size effects in attention, verbal learning and memory, working memory and executive function (Hedge's g = 0.29-0.45). CR produced a small-moderate effect on one secondary outcome: depressive symptoms (g = 0.33). CR programs that used an individualized approach produced larger effects on executive function. Samples with lower baseline IQ were more likely to benefit from CR on measures of working memory. Sample age, education, gender, or baseline depressive symptomatology did not serve as barriers to treatment gains, and observed effects were not epiphenomena of poorer design quality. LIMITATIONS: The number of RCTs remains low. CONCLUSIONS: CR produces small to moderate improvements in cognition and depressive symptoms in mood disorders. Future research should study how CR might be optimized to help generalize CR-related cognitive and symptom improvements to function.

A meta-analysis of social cognitive deficits in schizophrenia: Does world region matter?

Individuals with schizophrenia (SCZs) demonstrate social cognitive (SC) deficits across a variety of social cognitive tasks: affect recognition, social perception, Theory-of-Mind (ToM), and attributional style. These tasks all use socially-relevant words, social scenarios, clothing, faces and voices that may make their application to different cultural contexts problematic. However a paucity of research has investigated the cross-cultural validity of SC measures. We meta-analyzed the literature investigating differences in social cognitive skills SCZs and matched healthy controls (NCs) across different regions of the world using a group of expert-selected, standardized measures of social cognition. Studies of SC in SCZ using these measures published between January 1980 and August 2020 were evaluated. Data were extracted independently by 3 reviewers with excellent reliability; 156 unique studies of 10,235 SCZs and 9924 NCs across 34 countries were identified. Random effects models revealed SCZs demonstrated poorer performance in all domains of SC including emotion processing (g = -0.770), social perception (g = -0.880), ToM (g = -1.090), attributional style (hostility: g = -0.715, aggression: g = -0.209, blame: g = -0.322), as well as a measure of emotion regulation (g = -0.867). Hostile attributional style was more pronounced in European and North American samples (g = 1.054 and g = -0.605, respectively) compared to Asian samples (g = -0.284). Our results revealed that SCZs performed mildly-severely worse than HCs in all domains of SC. With the exception of hostile attributional style, the magnitude of deficits in social cognition was consistent across the globe.

Neuropsychological functioning in hoarding disorder.

Hoarding disorder (HD) is increasingly viewed as distinct from obsessive-compulsive disorder (OCD). In particular, some researchers have suggested that HD is characterized by substantial problems of neurocognitive function; however, HD patients have not yet been compared to OCD patients in this respect. The aim of the present study was to compare neuropsychological test performance in HD patients (n=27), OCD patients (n=12), and healthy controls (n=26). Consistent with previous research, HD patients showed an attenuated ability to sustain attention and poorer employment of adaptive memory strategies compared to healthy controls. HD and OCD patients did not differ significantly on these measures, although moderate effect sizes suggested that hoarders showed somewhat greater attenuation of attentional capacity. Rates of true impairment on any particular neuropsychological test were fairly low across all three groups, although 67% of HD patients (compared to 58% of OCD patients and 42% of healthy controls) scored in the impaired range on at least one measure (odds ratio=2.22). Results are discussed in terms of emerging conceptualizations of HD as a distinct illness.

Predictors of participation in community outpatient psychosocial rehabilitation in schizophrenia.

This study investigated demographic, clinical and neurocognitive factors predicting drop-out from an intensive, community outpatient psychosocial rehabilitation program for people with schizophrenia or schizoaffective disorder. One-hundred and twenty-seven outpatients with DSM-IV schizophrenia or schizoaffective disorder participated. Demographic variables of age, sex, education and race/ethnicity were recorded and formal symptom measures and a neurocognitive assessment consisting of measures of crystallized verbal ability, sustained visual vigilance, verbal learning, verbal fluency and problem-solving were administered at study entry. Thirty-seven percent of the sample dropped-out of the program. In a final multivariate model, younger age, and lower verbal fluency scores in clients with a history of a high number of hospitalizations predicted a greater likelihood of drop-out. The implications of these findings are discussed.

A Meta-analysis of Cognitive Remediation for Schizophrenia: Efficacy and the Role of Participant and Treatment Factors.

The number of randomized, controlled studies of cognitive remediation (CR) for schizophrenia, a therapeutic approach designed to improve cognitive skills and function, has grown substantially over the past 20 years. Active elements of CR treatment, however, remain unknown. The current meta-analysis investigated treatment, study, and participant factors in the size of observed treatment effects. Electronic databases were searched up to May 2020 using variants of the key words "cognitive remediation," "clinical trials," and "schizophrenia." This search produced 73 unique, randomized, controlled trials. Data were independently extracted by 3 reviewers with excellent reliability. Random-effects models were used to assess primary cognitive and secondary symptom and functional outcomes. Moderator analyses investigated the role of a variety of treatment, study, and participant factors. The meta-analysis (4594 participants) revealed that CR produced significant small-to-moderate size improvements in all domains of cognition studied (Hedge's gs = .19-.33). and a significant small improvement in function (Hedge's g = .21). CR programs that included a discussion ("bridging") group to help apply acquired cognitive skills to everyday life produced larger effects on global cognition and verbal memory. CR programs with strategy-coaching produced larger effects on episodic memory. Sample age, gender, positive, negative, and overall symptoms, and medication dose did not serve as barriers to treatment gains. CR produces small-to-moderate improvements in cognition and function in schizophrenia. Programs of CR that utilize bridging groups and strategy-coaching are more cognitively potent. Future research should focus on ways to modify CR to bolster generalization of cognitive improvements to function.

The alliance-outcome relationship in individual psychosocial treatment for schizophrenia and early psychosis: A meta-analysis.

The therapeutic alliance, or client-provider relationship, has been associated with better treatment engagement and outcomes for persons with schizophrenia-spectrum disorders (SSDs) and early psychosis in some studies, but not others. We conducted a meta-analysis of the research on alliance in SSDs and early psychosis across a range of interventions and outcomes. Parallel literature searches were conducted in PubMed and PsycINFO databases for articles between inception and 6/11/2020. English-language studies were included if they evaluated the relationship between alliance and a prospective outcome (treatment engagement, medication adherence, functioning, or total, positive, negative, or depressive symptoms) in an individual clinical treatment for SSDs/early psychosis and contained analyzable data. Correlations and partial correlations were meta-analyzed with random effects models to calculate mean across-study correlations and to carry out subsequent homogeneity and moderator variable analyses. Fourteen studies consisting of 2968 participants that assessed six outcomes across six psychosocial treatments were included. Results indicated that better client-rated (r = 0.20) and other-rated (i.e., provider- or observer-rated; r = 0.25) alliance were associated with better treatment engagement. Treatment type and sample race/ethnicity, but not age, gender, or timing of alliance rating moderated the association between other-rated alliance and engagement. Further, better other-rated alliance was related to improvements in positive (r = -0.14) and negative (r = -0.22) symptoms. A strong therapeutic alliance is important for both engaging clients with SSDs and early psychosis in treatment and facilitating improvements in positive and negative symptoms. Delivery and monitoring of treatments for this population should include assessment of the therapeutic alliance from multiple perspectives.

What variables predict cognitive remediation associated improvement in individuals with psychosis?

On average, cognitive remediation (CR) is effective in improving cognitive function in individuals with psychosis, though there is considerable variability in treatment response. No consensus has emerged to date about the potential influence of patient and illness characteristics on CR efficacy. In the current analyses, we examined baseline demographic, cognitive, clinical, and functional ability variables as potential moderators of cognitive improvements during a randomized, controlled trial of a hybrid drill-and-practice plus strategy training CR intervention. In an attempt to disentangle non-specific vs. CR specific treatment effects, we separately examined potential predictors of cognitive improvement in individuals who received CR versus those in the control condition. Cognitive gains were predicted by a large array of demographic, symptom and cognitive variables, however this was true both in the CR and the control condition. CR-specific cognitive improvement was associated with more severe course of illness as indexed by higher number of hospitalizations, with poorer baseline cognition, and with less severe baseline negative symptoms.

The synergistic benefits of physical and cognitive exercise in schizophrenia: Promoting motivation to enhance community effectiveness.

Emerging research highlights the potential cognitive benefits of physical exercise (PE) programs for schizophrenia (SCZ). The few recent efficacy studies that examined augmenting cognitive training (CT) with PE suggest superior effects of the combination. The next step is to consider strategies to enhance adherence in real-world settings if this type of combined treatment is going to be effective. We present the first community effectiveness data for PE and CT that included a motivationally-enhancing, self-determined approach to exercise, in lieu of participant payment. Eighty-five outpatients with schizophrenia attending an intensive outpatient program were randomized to 18 h of either (A) self-determined PE regimen with choice from a menu of different activities; (B) tablet-based neurofeedback CT focused on processing speed (PS) and working memory (WM), or (C) a time-matched combination of PE and CT. Assessments were conducted at baseline, post, and follow-up (2 mo). All groups improved in WM from baseline to post, with greatest gains in the PE only group. At follow-up, cognitive gains originally observed in the PE-only group disappeared, while the PE + CT group evidenced improvements in WM and psychotic symptoms. Notably, attrition for PE was only 7%. Our data shows that combining PE and CT leads to lasting effects that are superior to those of either intervention alone. The low PE drop-out rate suggests a self-determined approach to the exercise regimen was tolerable, and may be an important component of future community implementation efforts.

A comparison of remediation techniques on the Wisconsin Card Sorting Test in schizophrenia.

A wealth of evidence has revealed that deficits on a commonly used measure of executive-function, the Wisconsin Card Sorting Test (WCST), can be improved through a variety of methods of instruction in patients with schizophrenia. Relatively little is known however, which of these remediation methods produce strongest and most durable effects and whether these effects generalize to other, untrained executive-function measures. Two of the most commonly studied methods for remediation on the WCST, step-by-step didactic instruction on the task and utilization of self-monitoring strategies, have both been shown to improve WCST performance, yet have never been directly compared. Thirty-four participants with schizophrenia were randomly assigned to one of three experimental conditions: Condition A consisted of didactic training which incorporated a detailed account of changing sorting principles throughout the test; Condition B consisted of a self-monitoring strategy that required that participants verbalize their strategies out loud after each card sort; Condition C was a non-trained control group that received the same outcome assessments as the two training groups at identical time intervals without intervening training. Patients were assessed with the WCST and two other executive-function tests immediately prior to training, immediately after training and at a 1-month follow-up. Results revealed: (1) participants assigned to the didactic and self-monitoring conditions made significant gains on the WCST relative to a no-intervention control condition; (2) the effects of self-monitoring, but not didactic training, were evident at a one-month follow-up; and (3) only participants assigned to the self-monitoring condition showed generalization to a second, non-trained measure of executive-function. The significance of these results for implementation of strategies for comprehensive and sustained programs of remediation are discussed.

Elementary neurocognitive function, facial affect recognition and social-skills in schizophrenia.

Social-skill deficits are pervasive in schizophrenia and negatively impact many key aspects of functioning. Prior studies have found that measures of elementary neurocognition and social cognition are related to social-skills. In the present study we selected a range of neurocognitive measures and examined their relationship with identification of happy and sad faces and performance-based social-skills. Fifty-three patients with schizophrenia or schizoaffective disorder participated. Results revealed that: 1) visual vigilance, problem-solving and affect recognition were related to social-skill; 2) links between problem-solving and social-skill, but not visual vigilance and social-skill, remained significant when estimates of verbal intelligence were controlled; 3) affect recognition deficits explained unique variance in social-skill after neurocognitive variables were controlled; and 4) affect recognition deficits partially mediated the relationship of visual vigilance and social-skill. These results support the conclusion that facial affect recognition deficits are a crucial domain of impairment in schizophrenia that both contribute unique variance to social-skill deficits and may also mediate the relationship between some aspects of neurocognition and social-skill. These findings may help guide the development and refinement of cognitive and social-cognitive remediation methods for social-skill impairment.

Predictors of change in life skills in schizophrenia after cognitive remediation.

Few studies have investigated predictors of response to cognitive remediation interventions in patients with schizophrenia. Predictor studies to date have selected treatment outcome measures that were either part of the remediation intervention itself or closely linked to the intervention with few studies investigating factors that predict generalization to measures of everyday life-skills as an index of treatment-related improvement. In the current study we investigated the relationship between four measures of neurocognitive function, crystallized verbal ability, auditory sustained attention and working memory, verbal learning and memory, and problem-solving, two measures of symptoms, total positive and negative symptoms, and the process variables of treatment intensity and duration, to change on a performance-based measure of everyday life-skills after a year of computer-assisted cognitive remediation offered as part of intensive outpatient rehabilitation treatment. Thirty-six patients with schizophrenia or schizoaffective disorder were studied. Results of a linear regression model revealed that auditory attention and working memory predicted a significant amount of the variance in change in performance-based measures of everyday life skills after cognitive remediation, even when variance for all other neurocognitive variables in the model was controlled. Stepwise regression revealed that auditory attention and working memory predicted change in everyday life-skills across the trial even when baseline life-skill scores, symptoms and treatment process variables were controlled. These findings emphasize the importance of sustained auditory attention and working memory for benefiting from extended programs of cognitive remediation.

A meta-analytic investigation of neurocognitive deficits in bipolar illness: profile and effects of clinical state.

A meta-analysis of neuropsychological studies of patients with bipolar disorder comprised of 42 studies of 1,197 patients in euthymia, 13 studies consisting of 314 patients in a manic/mixed phase of illness, and 5 studies of 96 patients in a depressed state. Cohen d values were calculated for each study as the mean difference between patient and control group score on each neuropsychological measure, expressed in pooled SD units. For euthymia, results revealed impairment across all neuropsychological domains, with d values in the moderate-to-large range (d = .5 - .8) for the vast majority of measures. There was evidence of large effect-size impairment on measures of verbal learning (d = .81), and delayed verbal and nonverbal memory (d = .80 - .92), while effect-size impairment on measures of visuospatial function was small-to-moderate (d

Objective psychosocial function vs. subjective quality-of-life in schizophrenia within 5-years after diagnosis: A study from southern India.

There is increasing interest from treaters and patients alike in subjective quality-of-life (sQOL) and objective psychosocial function as indices of treatment outcome in studies of schizophrenia. With the emergence of evidence-based treatment protocols (e.g., NIMH-funded Recovery after Initial Schizophrenia Episode Initiative) these outcomes are of particular significance in treatment studies of samples early in the course of their illness. Few studies have investigated demographic, clinical and cognitive factors associated with sQOL in samples early in the course of their illness and compared these factors to objective measures. We administered measures of sQOL or satisfaction with life, and objective psychosocial function to 59 people with schizophrenia within 5-years of diagnosis, along with standardized measures of symptoms and cognition. Results revealed that symptoms, rather than cognitive or demographic variables, were the best independent predictors of both subjective QOL and objective functioning. Positive symptoms were independent predictors of sQOL, while positive and negative symptoms were independent predictors of objective psychosocial status. Depression and cognition were also linked to sQOL. These findings point to the importance of attending to residual positive symptoms early in the treatment of schizophrenia as a means of possibly enhancing both subjective and objective outcome in early course schizophrenia.