Efficacy of cognitive training on cognition, symptoms and functioning: Impact of motivation and attendance.

While cognitive remediation therapy (CRT) and compensatory strategy training both have large literature bases supporting their efficacy on both proximal and distal outcomes, the research base on stand-alone cognitive training (CT) is smaller and less consistent, with little information about factors associated with better outcomes. In this study, we examined the efficacy of CT on training task, cognitive, symptom, and functional ability measures as well as the impact of motivational interviewing (MI), motivation level, and session attendance on treatment outcomes. Adults with psychotic spectrum disorders (n = 114) were randomized to MI or a sham control interview (CI), followed by 4 months of computerized CT. In whole sample analyses, participants improved on training tasks, cognitive performance, and psychiatric symptoms, but self-reported cognition, self-reported depression, and functional ability did not change. Compared to CI, MI was associated with greater reductions in self-reported depressive symptoms. Motivation level and session attendance did not significantly influence outcomes. Findings support the efficacy of CT on several key outcomes, and its simplicity may be advantageous in uptake in community clinics with limited staffing. The lack of functional gains underscores the need to incorporate treatment ingredients that promote generalization and real-world implementation of learned skills. We also speculate that engagement during course of training may be a better predictor of training success than baseline task-specific motivation.

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS.

AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSIONS: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.

Experimental Therapeutics: Opportunities and Challenges Stemming From the National Institute of Mental Health Workshop on Novel Target Discovery and Psychosocial Intervention Development.

There has been slow progress in the development of interventions that prevent and/or reduce mental-health morbidity and mortality. The National Institute of Mental Health (NIMH) launched an experimental-therapeutics initiative with the goal of accelerating the development of effective interventions. The emphasis is on interventions designed to engage a target mechanism. A target mechanism is a process (e.g., behavioral, neurobiological) proposed to underlie change in a defined clinical endpoint and through change in which an intervention exerts its effect. This article is based on discussions from an NIMH workshop conducted in February 2020 and subsequent conversations among researchers using this approach. We discuss the components of an experimental-therapeutics approach such as clinical-outcome selection, target definition and measurement, intervention design and selection, and implementation of a team-science strategy. We emphasize the important contributions of different constituencies (e.g., patients, caregivers, providers) in deriving hypotheses about novel target mechanisms. We highlight strategies for target-mechanism identification using published and hypothetical examples. We consider the decision-making dilemmas that arise with different patterns of results in purported mechanisms and clinical outcomes. We end with considerations of the practical challenges of this approach and the implications for future directions of this initiative.

Metacognitive Training to Improve Insight and Work Outcome in Schizophrenia.

ABSTRACT: Individuals with psychotic disorders have deficits in metacognition. Thirty-four adults with schizophrenia were randomized to 2 months of metacognitive training (MCT) or a healthy living skills control group. All participants were enrolled in a work therapy program, followed by a supported employment program. Assessments were conducted at baseline, at the end of the 2-month active intervention, and at 4- and 12-month follow-ups. At the end of active intervention, the MCT group demonstrated greater improvement and better work behavior relative to controls. At follow-up, the MCT group demonstrated significantly greater insight and fewer positive symptoms and a greater percentage were employed in the community. We speculate that being better able to think about one's thoughts, recognize biases in thinking, and correct those thoughts may aid in responding to workplace challenges and hence improve work outcomes.

Motivational interviewing to enhance psychosocial treatment attendance in people with SMI.

BACKGROUND: While there is increasing support for the efficacy of psychosocial interventions for people with SMI, the real-world effectiveness of such treatments is diminished by lack of motivation for treatment, leading to poor treatment engagement/dropout. We sought to evaluate the efficacy of motivational interviewing (MI) in improving attendance in a full course of cognitive training, examine motivation level as a potential mechanism of action, and examine variables associated with initial engagement in the training. METHODS: One hundred fourteen participants with SMI were randomized to MI or sham control interview (CI), both of which were followed by a 4-month active phase during which participants could attend up to 50 unpaid cognitive training sessions. RESULTS: Fidelity to the MI intervention was high, and MI condition was associated with increases in perceived value of training tasks and, to a lesser extent, how enjoyable/interesting they were rated. Twenty-nine percent of the full sample did not attend any training sessions. In ITT analyses, there was no significant between-group impact of MI on treatment attendance, though one emerged when participants who did not attend any sessions were excluded. Treatment attendance was predicted by the level of motivation achieved after the MI/CI intervention. Those who attended at least one training session (regardless of randomization) were more likely to believe they had cognitive impairments, had higher IQ and had less severe general psychiatric symptoms. CONCLUSIONS: MI showed some promise and may be a worthwhile addition to more comprehensive, robust efforts to promote initial treatment engagement and subsequent adherence.

Counterpoint. Early intervention for psychosis risk syndromes: Minimizing risk and maximizing benefit.

BACKGROUND: Malhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis. METHOD: Response to points of critique. RESULTS: We agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not "extremely difficult"; e) the pattern of progression, although heterogenous, is discernible; f) "psychosis-like symptoms" are common but are not used to identify CHR; and g) on the point described as 'the real risk,' CHR diagnosis does not frequently cause harmful stigma. DISCUSSION: Malhi et al.'s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the "real risk" of stigma associated with a CHR "label," however, our view is that avoiding words like "risk" and "psychosis" reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them.

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.

How Music Impacts Visual Attention Training in Schizophrenia: A Pilot Study.

Music has been demonstrated to improve cognitive test performance in neuropsychiatric populations. However, the impact of music on cognitive training effects, and the importance of music preference, has yet to be studied. This is an essential oversight because many cognitive training programs play music in the background. We sought to determine if participant-preferred or random music would increase the efficacy of computer-based attention training (AT). Forty-eight patients with schizophrenia were randomly assigned to 2 weeks of either: 1) AT with participants' choice of background music, 2) AT with random background music, 3) AT without music, or 4) a no training or music control-watching videos without AT or music. All groups except the no training/no music control group demonstrated improvement in reaction time and response accuracy after training, with those participating in AT with their choice of music exhibiting greater gains than either of the other two AT groups. These findings suggest that complimenting AT with music, and allowing participants to choose the music, may increase the efficacy of AT.

Improving treatment motivation in individuals with psychosis: Predictors of response to motivational enhancement.

We sought to evaluate the influence of demographic, symptom, functional and cognitive factors on task-specific motivation, as well as improvement in task-specific motivation that occurs in response to motivational interviewing. In the absence of any intervention, better task-specific motivation was associated with higher perceived competence and lower symptomatology. Post-motivational enhancement improvement in motivation was predicted by fewer hospitalizations and better cognitive insight, with baseline symptomatology no longer predictive. Findings suggest motivational enhancement is likely to benefit individuals with diverse clinical presentations, though may be particularly well suited to those with lesser disease severity and better cognitive insight.

Metacognition Is Necessary for the Emergence of Motivation in People With Schizophrenia Spectrum Disorders: A Necessary Condition Analysis.

Metacognition deficits are a putative cause of reduced motivation in people with schizophrenia spectrum disorders. However, it is unclear whether certain levels of metacognition are necessary for motivation to emerge. This study used a Necessary Condition Analysis to test whether metacognition was necessary for the presence of motivation and to identify the minimum level of metacognition necessary for high motivation to be possible in people with schizophrenia spectrum disorders (N = 175). Participants completed clinician-rated measures of metacognition and motivation. Necessary Condition Analysis revealed that metacognition is a necessary condition for motivation and that high levels of motivation were only possible, although not guaranteed, when at least a basic level of metacognition was present. The findings suggest that metacognition is a necessary building block for the development of motivation. Results suggest that targeting metacognition may be essential for improving motivation among people with schizophrenia spectrum disorders who do not meet this metacognition threshold.

Decisional Informatics for Psychosocial Rehabilitation: A Feasibility Pilot on Tailored and Fluid Treatment Algorithms for Serious Mental Illness.

This study introduces a computerized clinical decision-support tool, the Fluid Outpatient Rehabilitation Treatment (FORT), that incorporates individual and ever-evolving patient needs to guide clinicians in developing and updating treatment decisions in real-time. In this proof-of-concept feasibility pilot, FORT was compared against traditional treatment planning using similar behavioral therapies in 52 adults with severe mental illness attending community-based day treatment. At posttreatment and follow-up, group differences and moderate-to-large effect sizes favoring FORT were detected in social function, work readiness, self-esteem, working memory, processing speed, and mental flexibility. Of participants who identified obtaining a General Education Diploma as their goal, 73% in FORT passed the examination compared with 18% in traditional treatment planning. FORT was also associated with higher agency cost-effectiveness and a better average benefit-cost ratio, even when considering diagnosis, baseline symptoms, and education. Although the comparison groups were not completely equivalent, the findings suggest computerized decision support systems that collaborate with human decision-makers to personalize psychiatric rehabilitation and address critical decisions may have a role in improving treatment effectiveness and efficiency.

Cognitive training to improve memory in individuals undergoing electroconvulsive therapy: Negative findings.

Although electroconvulsive therapy (ECT) remains the most effective treatment for severe depression, some patients report persistent memory problems following ECT that impact their quality of life and their willingness to consent to further ECT. While cognitive training has been shown to improve memory performance in various conditions, this approach has never been applied to help patients regain their memory after ECT. In a double-blind study, we tested the efficacy of a new cognitive training program called Memory Training for ECT (Mem-ECT), specifically designed to target anterograde and retrograde memory that can be compromised following ECT. Fifty-nine patients with treatment-resistant depression scheduled to undergo ultra-brief right unilateral ECT were randomly assigned to either: (a) Mem-ECT, (b) active control comprised of nonspecific mental stimulation, or (c) treatment as usual. Participants were evaluated within one week prior to the start of ECT and then again within 2 weeks following the last ECT session. All three groups improved in global function, quality of life, depression, and self-reported memory abilities without significant group differences. While there was a decline in verbal delayed recall and mental status, there was no decline in general retrograde memory or autobiographical memory in any of the groups, with no significant memory or clinical benefit for the Mem-ECT or active control conditions compared to treatment as usual. While we report negative findings, these results continue to promote the much needed discussion on developing effective strategies to minimize the adverse memory side effects of ECT, in hopes it will make ECT a better and more easily tolerated treatment for patients with severe depression who need this therapeutic option.

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).

Optimism and well-being: a prospective multi-method and multi-dimensional examination of optimism as a resilience factor following the occurrence of stressful life events.

Optimism has been conceptualised variously as positive expectations (PE) for the future , optimistic attributions , illusion of control , and self-enhancing biases. Relatively little research has examined these multiple dimensions of optimism in relation to psychological and physical health. The current study assessed the multi-dimensional nature of optimism within a prospective vulnerability-stress framework. Initial principal component analyses revealed the following dimensions: PEs, Inferential Style (IS), Sense of Invulnerability (SI), and Overconfidence (O). Prospective follow-up analyses demonstrated that PE was associated with fewer depressive episodes and moderated the effect of stressful life events on depressive symptoms. SI also moderated the effect of life stress on anxiety symptoms. Generally, our findings indicated that optimism is a multifaceted construct and not all forms of optimism have the same effects on well-being. Specifically, our findings indicted that PE may be the most relevant to depression, whereas SI may be the most relevant to anxiety.

Understanding Social Situations (USS): A proof-of-concept social-cognitive intervention targeting theory of mind and attributional bias in individuals with psychosis.

OBJECTIVES: In this proof-of-concept trial, we examined the feasibility and preliminary efficacy of Understanding Social Situations (USS), a new social-cognitive intervention that targets higher level social-cognitive skills using methods common to neurocognitive remediation, including drill and practice and hierarchically structured training, which may compensate for the negative effects of cognitive impairment on learning. METHOD: Thirty-eight individuals with schizophrenia spectrum disorders completed the same baseline assessment of cognitive and social-cognitive functioning twice over a 1-month period to minimize later practice effects, then received 7-10 sessions of USS training, and then completed the same assessment again at posttreatment. RESULTS: USS training was well tolerated and received high treatment satisfaction ratings. Large improvements on the USS Skills Test, which contained items similar to but not identical to training stimuli, suggest that we were effective in teaching specific training content. Content gains generalized to improvements on some of the social-cognitive tasks, including select measures of attributional bias and theory of mind. Importantly, baseline neurocognition did not impact the amount of learning during USS (as indexed by the USS Skills Test) or the amount of improvement on social-cognitive measures. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: USS shows promise as a treatment for higher level social-cognitive skills. Given the lack of relationship between baseline cognition and treatment effects, it may be particularly appropriate for individuals with lower range cognitive function. (PsycINFO Database Record

Effects of the Indianapolis Vocational Intervention Program (IVIP) on defeatist beliefs, work motivation, and work outcomes in serious mental illness.

Defeatist beliefs and amotivation are prominent obstacles in vocational rehabilitation for people with serious mental illnesses (SMI). The CBT-based Indianapolis Vocational Intervention Program (IVIP) was specifically designed to reduce defeatist beliefs related to work functioning. In the current study, we examined the impact of IVIP on defeatist beliefs and motivation for work, hypothesizing that IVIP would be associated with a reduction in defeatist beliefs and greater motivation for work. We also examined the effects of IVIP on these variables as well as work outcomes during a 12-month follow-up. Participants with SMI (n=64) enrolled in a four-month work therapy program were randomized to IVIP or a support therapy group (SG). Assessments were conducted at baseline, post-treatment (4months), and follow-up (1year). Compared to those in SG condition, individuals randomized to IVIP condition reported greater reductions in defeatist beliefs and greater motivation for work at follow-up, along with greater supported employment retention rates. Specifically treating and targeting negative expectations for work therapy improves outcomes, even once active supports of the IVIP program and work therapy are withdrawn.

Pupillometer-based neurofeedback cognitive training to improve processing speed and social functioning in individuals at clinical high risk for psychosis.

OBJECTIVE: Among individuals at clinical high risk (CHR) for psychosis, processing speed (PS) has been related to social and role functioning regardless of conversion to schizophrenia. This information processing dysfunction is a gateway to broader behavioral deficits such as difficulty executing social behaviors. We examined the feasibility of improving information processing relevant to social situations in CHR, including its sustainability at 2-month follow-up, and its association with concurrent social function. METHOD: This was a double-blind RCT in which 62 CHR participants were randomized to Processing Speed Training (PST) or an active control matched for training format and the same dose and duration of treatment. PST is a tablet-based program that uses pupillometry-based neurofeedback to continually adjust training parameters for an optimal neurocognitive load and to improve visual scanning efficiency by inhibiting selection of nonessential targets and discriminating figure-ground details. RESULTS: The PST group showed faster motoric and nonmotoric PS at post training and 2-month follow-up. At 2 month follow-up, the PST group reported better overall social adjustment. Changes in PS from baseline to 2 months were correlated with overall social adjustment and social avoidance in the entire sample. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This is the first study to test focal neurofeedback-based cognitive training for PS deficits in the putatively prodromal phase of schizophrenia to address associated social morbidity. Targeting PS appears to be a promising pathway to decreasing comorbidity and mitigating a risk factor for psychosis. (PsycINFO Database Record