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-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.

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 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.

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 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.

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.

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 relationship between the therapeutic alliance and client variables in individual treatment for schizophrenia spectrum disorders and early psychosis: Narrative review.

Given the high rates of treatment disengagement and medication nonadherence in individuals with schizophrenia spectrum disorders and early psychosis, fostering a strong alliance in treatment is critical. Moreover, the role of the therapeutic alliance extends beyond that in traditional psychotherapy because of the multifaceted nature of treatment. Thus, this review provides a comprehensive discussion of the relationship between the alliance and client variables across various provider types and individual treatments. This review summarizes existing research on (a) client correlates/predictors of the therapeutic alliance and on (b) the relationship between the alliance and client treatment outcomes in individual treatment for schizophrenia spectrum disorders and early psychosis. Parallel literature searches were conducted using PubMed and PsycINFO databases, which yielded 1202 potential studies with 84 studies meeting inclusion criteria. With regard to correlates/predictors, the existing evidence suggests that better insight, medication adherence, social support, and recovery variables were related to better client-rated alliance. Better medication adherence and recovery variables as well as less severe symptoms were related to better provider-rated alliance. In terms of alliance-outcome relationships, evidence suggests that a strong provider-rated alliance was predictive of improved functioning and medication and treatment adherence. There was some limited evidence that better client-rated alliance was related to improved recovery outcomes. Despite mixed results and heterogeneity among studies, this review suggests that a strong alliance can be beneficial in individual schizophrenia treatment. Thus, training and supervision of providers should emphasize developing a positive alliance, particularly with clients for whom developing an alliance may be difficult.

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.

Cognition, social cognition and functional disability in early-stage schizophrenia: A study from southern India.

In high-income countries a wealth of studies has revealed cognitive and social cognitive deficits in schizophrenia and a close relationship of these deficits to psychosocial functioning. Studies examining these illness features in middle and low-income countries are rare, particularly in early-stage samples. Sixty adult participants within 5 years of diagnosis with schizophrenia and 53 matched, healthy control were assessed with the MATRICS Consensus Cognitive Battery and the PEAT emotion identification task at study entry, and the WHODAS functioning scale one year later. Deficits on cognitive instruments ranged from d = 0.64-1.04 and were consistent with those reported in Western samples. Negative symptoms were linked to function longitudinally. Deficits in social cognitive skills and longitudinal links between cognition and functioning were not evident. These findings suggest a highly consistent magnitude of neurocognitive deficits in people with schizophrenia across widely varying cultures, but with limited evidence of social cognitive skill deficits using Western-based instruments. There was little evidence of a relationship between cognition and psychosocial disability in people with early-stage schizophrenia in this sample.

Examining the durability of a hybrid, remote and computer-based cognitive remediation intervention for adolescents with 22q11.2 deletion syndrome.

AIM: Schizophrenia and 22q11.2 deletion syndrome (22q11DS) share similar patterns of cognitive deficits. Up to 30% of those with 22q11DS develop schizophrenia during early adulthood. As cognitive decline has recently been found to predict onset of psychosis in adolescents with 22q11DS, early interventions such as cognitive remediation (CR) during adolescence are warranted. This paper investigates the durability of a remote, computerized, CR programme for youth with 22q11DS. Our aim was to determine if the positive effects of CR persisted 6 months beyond intervention completion. METHODS: A longitudinal design with 21 participants serving as their own controls was used. Youth were seen for neurocognitive assessments at pre-treatment, after the targeted 8-month intervention, at post-treatment, and 6 months after for follow-up. During the intervention, cognitive coaches met remotely with participants for CR via video conferencing three times a week, and offered task-specific strategies. To determine if intervention improvements held across the 6-month follow-up period, neurocognitive measures were statistically examined with repeated measures analysis of variances from pre-treatment through follow-up. RESULTS: Our CR intervention proved durable. Post-treatment improvements comprising cognitive flexibility, executive function, reaction time and working memory were maintained over the follow-up period. CONCLUSIONS: Results confirm previous research regarding the durability of CR treatment and extend these findings to youth with 22q11DS. The present study may serve to inform early intervention efforts focused on cognitive and functionally relevant rehabilitation goals for youth with 22q11DS and suggests that 22q11DS can potentially serve as a suitable model for examining the trajectory preceding psychosis.

The Duration of Untreated Psychosis: A Phenomenological Study.

Mounting evidence has indicated that early intervention leads to improved clinical and functional outcomes for young persons experiencing recent onset psychosis. As part of a large early detection campaign, the present study aimed to investigate subjective experiences during the duration of untreated psychosis (DUP), or time between psychosis onset and treatment contact. Participants were 10 young adults participating in early intervention services for psychosis. After DUP was estimated during standardized baseline assessment, participants engaged in qualitative interviews focused on their life experiences prior to treatment and leading up to the present. Mixed methods data analyses compared standardized DUP estimates with participants' subjective narratives. Findings revealed that participants experienced and conceptualized a longer trajectory of subjective difficulties (TSD) beginning before and extending beyond standardized DUP estimates. Participants emphasized striving for independence and social belonging. The majority of participants reported benefiting from their current services and believed that earlier support of some kind would have been beneficial. These findings support previous research on subjective barriers to early detection and treatment seeking in young adults experiencing psychosis. Implications and future research directions include further efforts to differentiate the struggles unique to early psychosis from psychosocial risk factors and other challenges of young adulthood.

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).

Cognitive remediation for adults with schizophrenia: Does age matter?

Cognitive remediation (CR), a novel behavioral intervention designed to improve cognitive deficits through repeated task practice and/or strategy acquisition has gained increasing empirical support in people with schizophrenia, but substantial individual differences in treatment response remain (Wykes et al., 2011). The role of age on response to CR in schizophrenia remains understudied. We evaluated the role of three age ranges in treatment response to CR relative to a closely-matched computer skills control intervention in a blinded, randomized control trial (RCT) with 112 adults with schizophrenia divided into three groups: an early-stage group (ES; 25 years or younger, mean=3.4 years of illness; n=45), an early-chronic group (EC; 26-39, mean=7.6 years of illness; n=31) and a late-chronic group (LC; 40 and over, mean=18.2 years of illness; n=36). With respect to cognitive outcomes, early-stage and early-chronic individuals with schizophrenia showed greater improvement in response to CR on a working memory measure at a trend level, relative to late-chronic clients. These findings were confirmed in analyses of a subsample of clients who received an adequate dose of treatment. These findings emphasize the need for adaptations of currently-existing CR programs to more effectively address the needs of older client populations.

Can brain games help smokers quit?: Results of a randomized clinical trial.

BACKGROUND AND AIMS: Deficits in cognitive function are observed during nicotine withdrawal and present a challenge to successful smoking cessation. This clinical trial evaluated a cognitive exercise training (CT) program to improve smoking cessation rates. METHODS: Adult treatment-seeking smokers (n=213) were randomized to receive nicotine patch therapy and 12 weeks of either computerized CT or computerized relaxation (control) training. Smoking status was biochemically verified at the end of treatment and 6-month follow-up. RESULTS: Quit rates did not differ by treatment arm at either time-point, nor were there effects on withdrawal symptoms or smoking urges. Reaction time for emotion recognition and verbal interference tasks showed improvement in the CT group. When including only successful quitters, improvements in recognition memory, verbal interference accuracy, and attention switching error rate were also observed in the CT group, while commission errors on the continuous performance task decreased in the control group. CONCLUSIONS: Despite modest changes in cognitive performance, these results do not support the efficacy of computerized cognitive training as an adjunctive therapy for smoking cessation.

The relationship between change in cognition and change in functional ability in schizophrenia during cognitive and psychosocial rehabilitation.

While a wealth of studies have evaluated cross-sectional links between cognition and functioning in schizophrenia, few have investigated the relationship between change in cognition and change in functioning in the context of treatment trials targeted at cognition. Identifying cognitive skills that, when improved, predict improvement in functioning will guide the development of more targeted rehabilitation for this population. The present study identifies the relationship between change in specific cognitive skills and change in functional ability during one year of cognitive rehabilitation. Ninety-six individuals with schizophrenia were assessed with a battery of cognitive measures and a measure of performance-based functioning before and after cognitive training consisting of either drill-and-practice cognitive remediation or computer skills training. Results revealed that while working and episodic memory, problem-solving, and processing speed skills all improved during the trial, only improved working memory and processing speed skills predicted improvement in functional ability. Secondary analyses revealed these relationships were driven by individuals who showed a moderate level (SD≥0.5) of cognitive improvement during the trial. These findings suggest that while a variety of cognitive skills may improve during training targeted at cognition, only improvements in a subset of cognitive functions may translate into functional gains.

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.