The Effects of Remote Cognitive Training Combined With a Mobile App Intervention on Psychosis: Double-Blind Randomized Controlled Trial.

BACKGROUND: Impairments in cognition and motivation are core features of psychosis and strong predictors of social and occupational functioning. Accumulating evidence indicates that cognitive deficits in psychosis can be improved by computer-based cognitive training programs; however, barriers include access and adherence to cognitive training exercises. Limited evidence-based methods have been established to enhance motivated behavior. In this study, we tested the effects of web-based targeted cognitive and social cognitive training (TCT) delivered in conjunction with an innovative digital smartphone app called Personalized Real-Time Intervention for Motivational Enhancement (PRIME). The PRIME app provides users with a motivational coach to set personalized goals and secure social networking for peer support. OBJECTIVE: This study investigated whether deficits in cognition and motivation in people with a psychosis spectrum disorder (N=100) can be successfully addressed with 30 hours of TCT+PRIME as compared with 30 hours of a computer games control condition (CG) plus PRIME (CG+PRIME). Here, we describe our study procedures, the feasibility and acceptability of the intervention, and the results on all primary outcomes. METHODS: In this double-blind randomized controlled trial, English-speaking participants completed all cognitive training, PRIME activities, and assessments remotely. Participants completed a diagnostic interview and remote cognitive, clinical, and self-report measures at baseline, posttraining, and at a 6-month follow-up. RESULTS: This study included participants from 27 states across the United States and 8 countries worldwide. The study population was 58% (58/100) female, with a mean age of 33.77 (SD 10.70) years. On average, participants completed more than half of the cognitive training regimen (mean 18.58, SD 12.47 hours of training), and logged into the PRIME app 4.71 (SD 1.58) times per week. The attrition rate of 22% (22/100) was lower than that reported in our previous studies on remote cognitive training. The total sample showed significant gains in global cognition (P=.03) and attention (P<.001). The TCT+PRIME participants showed significantly greater gains in emotion recognition (P<.001) and global cognition at the trend level (P=.09), although this was not statistically significant, relative to the CG+PRIME participants. The total sample also showed significant improvements on multiple indices of motivation (P=.02-0.05), in depression (P=.04), in positive symptoms (P=.04), and in negative symptoms at a trend level (P=.09), although this was not statistically significant. Satisfaction with the PRIME app was rated at 7.74 (SD 2.05) on a scale of 1 to 10, with higher values indicating more satisfaction. CONCLUSIONS: These results demonstrate the feasibility and acceptability of remote cognitive training combined with the PRIME app and that this intervention can improve cognition, motivation, and symptoms in individuals with psychosis. TCT+PRIME appeared more effective in improving emotion recognition and global cognition than CG+PRIME. Future analyses will test the relationship between hours of cognitive training completed; PRIME use; and changes in cognition, motivation, symptoms, and functioning. TRIAL REGISTRATION: ClinicalTrials.gov NCT02782442; https://clinicaltrials.gov/study/NCT02782442.

Psilocybin therapy for treatment resistant depression: prediction of clinical outcome by natural language processing.

RATIONALE: Therapeutic administration of psychedelics has shown significant potential in historical accounts and recent clinical trials in the treatment of depression and other mood disorders. A recent randomized double-blind phase-IIb study demonstrated the safety and efficacy of COMP360, COMPASS Pathways' proprietary synthetic formulation of psilocybin, in participants with treatment-resistant depression. OBJECTIVE: While the phase-IIb results are promising, the treatment works for a portion of the population and early prediction of outcome is a key objective as it would allow early identification of those likely to require alternative treatment. METHODS: Transcripts were made from audio recordings of the psychological support session between participant and therapist 1 day post COMP360 administration. A zero-shot machine learning classifier based on the BART large language model was used to compute two-dimensional sentiment (valence and arousal) for the participant and therapist from the transcript. These scores, combined with the Emotional Breakthrough Index (EBI) and treatment arm were used to predict treatment outcome as measured by MADRS scores. (Code and data are available at https://github.com/compasspathways/Sentiment2D .) RESULTS: Two multinomial logistic regression models were fit to predict responder status at week 3 and through week 12. Cross-validation of these models resulted in 85% and 88% accuracy and AUC values of 88% and 85%. CONCLUSIONS: A machine learning algorithm using NLP and EBI accurately predicts long-term patient response, allowing rapid prognostication of personalized response to psilocybin treatment and insight into therapeutic model optimization. Further research is required to understand if language data from earlier stages in the therapeutic process hold similar predictive power.

Optimizing outcomes in psilocybin therapy: Considerations in participant evaluation and preparation.

Recent studies have demonstrated the promise of psilocybin therapies in creating positive changes for those with poor mental health across multiple diagnostic categories, including major depressive disorder (MDD), end-of-life anxiety, and obsessive-compulsive disorder (OCD). While there may be a large population that is eligible to participate in psilocybin therapy based on psychiatric diagnosis and medical clearance, little attention has been given to intrapersonal and interpersonal factors that might influence patient's readiness (i.e., eligibility and capacity) for psychedelic interventions. This paper proposes that readiness assessment includes both intrapersonal and interpersonal factors in order to improve safety, patient care, and treatment outcomes. While at the present time a reliable and valid instrument has not been developed, we propose that three specific areas of focus - patient presentation, therapeutic alliance, and patient safety - may be used to establish a patient's readiness for psilocybin therapy, thus increasing therapy optimization and personalization.

Durable Cognitive Gains and Symptom Improvement Are Observed in Individuals With Recent-Onset Schizophrenia 6 Months After a Randomized Trial of Auditory Training Completed Remotely.

OBJECTIVE: Cognitive impairment in schizophrenia predicts functional outcomes and is largely unresponsive to pharmacology or psychotherapy; it is thus a critical unmet treatment need. This article presents the impact of remotely completed, intensive, targeted auditory training (AT) vs control condition computer games (CG) in a double-blind randomized trial in young adults with recent-onset schizophrenia. METHOD: Participants (N = 147) were assessed for cognition, symptoms, and functioning at baseline, post-intervention, and at 6-month follow-up. All participants were provided with laptop computers and were instructed to complete 40 hours remotely of training or computer games. An intent-to-treat analysis (N = 145) was performed using linear mixed models with time modeled as a continuous variable. Planned contrasts tested the change from baseline to post-training, baseline to 6-month follow-up, and post-training to 6-month follow-up. RESULTS: Global Cognition, which had improved in the AT group relative to the CG group at post-training, showed durable gains at 6-month follow-up in an omnibus group-by-time interaction test (F(1,179) = 4.80, P = .030), as did Problem-Solving (F(1,179) = 5.13, P = .025), and Speed of Processing improved at trend level significance (F(1,170) = 3.80, P = .053). Furthermore, the AT group showed significantly greater improvement than the CG group in positive symptoms (F(1,179) = 4.06, P = .045). CONCLUSIONS: These results provide the first evidence of durable cognitive gains and symptom improvement at follow-up of cognitive training (CT) in early schizophrenia completed independently and remotely. While functioning did not show significant improvement, these findings suggest that intensive targeted CT of auditory processing is a promising component of early intervention to promote recovery from psychosis.

Toward a Mobile Platform for Real-world Digital Measurement of Depression: User-Centered Design, Data Quality, and Behavioral and Clinical Modeling.

BACKGROUND: Although effective mental health treatments exist, the ability to match individuals to optimal treatments is poor, and timely assessment of response is difficult. One reason for these challenges is the lack of objective measurement of psychiatric symptoms. Sensors and active tasks recorded by smartphones provide a low-burden, low-cost, and scalable way to capture real-world data from patients that could augment clinical decision-making and move the field of mental health closer to measurement-based care. OBJECTIVE: This study tests the feasibility of a fully remote study on individuals with self-reported depression using an Android-based smartphone app to collect subjective and objective measures associated with depression severity. The goals of this pilot study are to develop an engaging user interface for high task adherence through user-centered design; test the quality of collected data from passive sensors; start building clinically relevant behavioral measures (features) from passive sensors and active inputs; and preliminarily explore connections between these features and depression severity. METHODS: A total of 600 participants were asked to download the study app to join this fully remote, observational 12-week study. The app passively collected 20 sensor data streams (eg, ambient audio level, location, and inertial measurement units), and participants were asked to complete daily survey tasks, weekly voice diaries, and the clinically validated Patient Health Questionnaire (PHQ-9) self-survey. Pairwise correlations between derived behavioral features (eg, weekly minutes spent at home) and PHQ-9 were computed. Using these behavioral features, we also constructed an elastic net penalized multivariate logistic regression model predicting depressed versus nondepressed PHQ-9 scores (ie, dichotomized PHQ-9). RESULTS: A total of 415 individuals logged into the app. Over the course of the 12-week study, these participants completed 83.35% (4151/4980) of the PHQ-9s. Applying data sufficiency rules for minimally necessary daily and weekly data resulted in 3779 participant-weeks of data across 384 participants. Using a subset of 34 behavioral features, we found that 11 features showed a significant (P<.001 Benjamini-Hochberg adjusted) Spearman correlation with weekly PHQ-9, including voice diary-derived word sentiment and ambient audio levels. Restricting the data to those cases in which all 34 behavioral features were present, we had available 1013 participant-weeks from 186 participants. The logistic regression model predicting depression status resulted in a 10-fold cross-validated mean area under the curve of 0.656 (SD 0.079). CONCLUSIONS: This study finds a strong proof of concept for the use of a smartphone-based assessment of depression outcomes. Behavioral features derived from passive sensors and active tasks show promising correlations with a validated clinical measure of depression (PHQ-9). Future work is needed to increase scale that may permit the construction of more complex (eg, nonlinear) predictive models and better handle data missingness.

Measuring The Lifetime Costs Of Serious Mental Illness And The Mitigating Effects Of Educational Attainment.

Serious mental illness (SMI) is a disabling condition that develops early in life and imposes substantial economic burden. There is a growing belief that early intervention for SMI has lifelong benefits for patients. However, assessing the cost-effectiveness of early intervention efforts is hampered by a lack of evidence on the long-term benefits. We addressed this by using a dynamic microsimulation model to estimate the lifetime burden of SMI for those diagnosed by age twenty-five. We estimated that the per patient lifetime burden of SMI is $1.85 million. We also found that a policy intervention focused on improving the educational attainment of people with SMI reduces the average per person burden of SMI by $73,600 (4.0 percent)-a change driven primarily by higher lifetime earnings-or over $8.9 billion in reduced burden per cohort of SMI patients. These findings provide a benchmark for the potential value of improving educational attainment for people with SMI.

Development and testing of a web-based battery to remotely assess cognitive health in individuals with schizophrenia.

Cognitive impairment in schizophrenia is often severe, enduring, and contributes significantly to chronic disability. A standardized platform for identifying cognitive impairments and measuring treatment effects in cognition is a critical aspect of comprehensive evaluation and treatment for individuals with schizophrenia. In this project, we developed and tested a suite of ten web-based, neuroscience-informed cognitive assessments that are designed to enable the interpretation of specific deficits that could signal that an individual is experiencing cognitive difficulties. The assessment suite assays speed of processing, sustained attention, executive functioning, learning and socio-affective processing in the auditory and visual modalities. We have obtained data from 283 healthy individuals who were recruited online and 104 individuals with schizophrenia who also completed formal neuropsychological testing. Our data show that the assessments 1) are acceptable and tolerable to users, with successful completion in an average of under 40 min; 2) reliably measure the distinct theoretical cognitive constructs they were designed to assess; 3) can discriminate schizophrenia patients from healthy controls with a fair degree of accuracy (AUROC > 0.70); and 4) have promising construct, convergent, and external validity. Further optimization and validation work is in progress to finalize the evaluation process prior to promoting the dissemination of these assessments in real-world settings.

Childhood trauma and clinical high risk for psychosis.

As a risk factor for psychosis, childhood trauma rates are elevated in the clinical-high-risk (CHR) syndrome compared to the general population. However, it is unknown whether trauma is typically experienced in childhood or adolescence/young adulthood, whether it occurred prior to CHR syndrome onset, and how severe trauma relates to presenting symptoms. In this study, we examined the relationship of trauma history to symptoms and functioning in individuals diagnosed with the CHR syndrome on the Structured Interview for Psychosis-Risk Syndromes (N = 103). Trauma, defined as meeting the DSM-IV A1 criterion of actual or threatened death or injury, was assessed by semi-structured interview. A large proportion of CHR participants (61%) reported trauma exposure, including interpersonal trauma, trauma prior to CHR onset, and childhood trauma prior to age 12. Those with a trauma history (versus those without trauma) were rated as having more severe perceptual disturbances, general/affective symptoms and more impairment on the Global Assessment of Functioning Scale. The number of traumatic events correlated with more severe ratings in those three domains. Additionally, the number of interpersonal traumas was correlated with ratings of suspiciousness. Trauma was unrelated to specific measures of social and role functioning. A small proportion of CHR participants were diagnosed with formal PTSD (14%), which was unrelated to symptom severity or functioning. Thus, we demonstrate that trauma exposure is often early in life (before age 12), occurs prior to the onset of the CHR syndrome, and is related to both positive and affective symptoms.

Efficacy of PRIME, a Mobile App Intervention Designed to Improve Motivation in Young People With Schizophrenia.

The onset of schizophrenia occurs during a period critical for development of social relationships and functional independence. As such, interventions that target the early course of illness have the potential to stave off functional decline and restore functioning to pre-illness levels. In this entirely remote study, people with recent-onset schizophrenia spectrum disorders (SSDs) participated in a 12-week randomized controlled trial to determine the efficacy of PRIME (personalized real-time intervention for motivational enhancement), a mobile-based digital health intervention designed to improve motivation and quality of life. Participants were randomized into the PRIME (n = 22) or treatment-as-usual/waitlist (TAU/WL) condition (n = 21) and completed assessments at baseline, post-trial (12 wk), and for people in the PRIME condition, 3 months after the end of the trial. After 12-weeks, WL participants received PRIME, resulting in a total sample of 38 participants completing PRIME. In PRIME, participants worked towards self-identified goals with the support of a virtual community of age-matched peers with schizophrenia-spectrum disorders as well as motivation coaches. Compared to the WL condition, people in the PRIME condition had significantly greater improvements in self-reported depression, defeatist beliefs, self-efficacy, and a trend towards motivation/pleasure negative symptoms post-trial, and these improvements were maintained 3 months after the end of trial. We also found that people in the PRIME condition had significantly greater improvements in components of social motivation post-trial (anticipated pleasure and effort expenditure). Our results suggest that PRIME has the potential to be an effective mobile-based intervention for improving aspects of mood and motivation in young people with SSDs.

Social motivation in people with recent-onset schizophrenia spectrum disorders.

People with schizophrenia-spectrum disorders (SSD) often experience impairments in non-social motivation. In this study, we extended this line of investigation by examining specific components of social motivation and the extent to which these components work together in people with and without a recent-onset SSD. Sixty-four people with a recent-onset SSD and 26 controls completed a task that allowed us to examine changes in anticipated pleasure, decisions to trust, and effort expenditure over the course of repeated interactions with positive or negative outcomes. Compared to controls, we found that people in the SSD group placed less trust, tended to anticipate less pleasure, and expended less effort to increase the likelihood of future interactions with positive outcomes. Further, in the SSD group, effort expenditure was not associated with either anticipated pleasure or decisions to trust. While there were no group differences in anticipated pleasure or trust placed during interactions with negative outcomes, people in the SSD group expended less effort to decrease to the likelihood of future interactions. Taken together, our findings suggest that people with a recent-onset SSD may experience both impairment and disconnection between various components of social motivation for interactions with positive outcomes. Implications for interventions for social engagement in people with SSD are discussed.

Summary of Key Issues Raised in the Technology for Early Awareness of Addiction and Mental Illness (TEAAM-I) Meeting.

Technology provides an unparalleled opportunity to remove barriers to earlier identification and engagement in services for mental and addictive disorders by reaching people earlier in the course of illness and providing links to just-in-time, cost-effective interventions. Achieving this opportunity, however, requires stakeholders to challenge underlying assumptions about traditional pathways to mental health care. In this Open Forum, the authors highlight key issues discussed in the Technology for Early Awareness of Addiction and Mental Illness (TEAAM-I) meeting-held October 13-14, 2016, in New York City-that are related to three identified areas in which technology provides important and unique opportunities to advance early identification, increase service engagement, and decrease the duration of untreated mental and addictive disorders.

Potential Benefits of Incorporating Peer-to-Peer Interactions Into Digital Interventions for Psychotic Disorders: A Systematic Review.

OBJECTIVE: Peer-to-peer interactions and support groups mitigate experiences of social isolation and loneliness often reported by individuals with psychotic disorders. Online peer-to-peer communication can promote broader use of this form of social support. Peer-to-peer interactions occur naturally on social media platforms, but they can negatively affect mental health. Recent digital interventions for persons with psychotic disorders have harnessed the principles of social media to incorporate peer-to-peer communication. This review examined the feasibility, acceptability, and preliminary efficacy of recent digital interventions in order to identify strategies to maximize benefits of online peer-to-peer communication for persons with psychotic disorders. METHODS: An electronic database search of PubMed, EMBASE, PsycINFO, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Health Technology Assessment Database was conducted in February 2017 and yielded a total of 1,015 results. Eight publications that reported data from six independent trials and five interventions were reviewed. RESULTS: The technology supporting peer-to-peer communication varied greatly across studies, from online forums to embedded social networking. When peer-to-peer interactions were moderated by facilitators, retention, engagement, acceptability, and efficacy were higher than for interventions with no facilitators. Individuals with psychotic disorders were actively engaged with moderated peer-to-peer communication and showed improvements in perceived social support. Studies involving service users in intervention design showed higher rates of acceptability. CONCLUSIONS: Individuals with psychotic disorders value and benefit from digital interventions that include moderated peer-to-peer interactions. Incorporating peer-to-peer communication into digital interventions for this population may increase compliance with other evidence-based therapies by producing more acceptable and engaging online environments.

The feasibility, acceptability, and outcomes of PRIME-D: A novel mobile intervention treatment for depression.

BACKGROUND: Despite decades of research and development, depression has risen from the fifth to the leading cause of disability in the United States. Barriers to progress in the field are (1) poor access to high-quality care; (2) limited mental health workforce; and (3) few providers trained in the delivery of evidence-based treatments (EBTs). Although mobile platforms are being developed to give consumers greater access to high-quality care, too often these tools do not have empirical support for their effectiveness. In this study, we evaluated PRIME-D, a mobile app intervention that uses social networking, goal setting, and a mental health coach to deliver text-based, EBT's to treat mood symptoms and functioning in adults with depression. METHODS: Thirty-six adults with depression remotely participated in PRIME-D over an 8-week period with a 4-week follow-up, with 83% retained over the 12-week course of thestudy. RESULTS: On average, participants logged into the app 5 days/week. Depression scores (PHQ-9) significantly improved over time (over 50% reduction), with coach interactions enhancing these effects. Mood-related disability (Sheehan Disability Scale (SDS)) also significantly decreased over time with participants no longer being impaired by their mood symptoms. Overall use of PRIME-D predicted greater gains in functioning. Improvements in mood and functioning were sustained over the 4-week follow-up. CONCLUSIONS: Results suggest that PRIME-D is a feasible, acceptable, and effective intervention for adults with depression and that a mobile service delivery model may address the serious public health problem of poor access to high-quality mental health care.

Creating Live Interactions to Mitigate Barriers (CLIMB): A Mobile Intervention to Improve Social Functioning in People With Chronic Psychotic Disorders.

BACKGROUND: Numerous psychosocial interventions for individuals with chronic psychotic disorders (CPD) have shown positive effects on social cognitive and functional outcome measures. However, access to and engagement with these interventions remains limited. This is partly because these interventions require specially trained therapists, are not available in all clinical settings, and have a high scheduling burden for participants, usually requiring a commitment of several weeks. Delivering interventions remotely via mobile devices may facilitate access, improve scheduling flexibility, and decrease participant burden, thus improving adherence to intervention requirements. To address these needs, we designed the Creating Live Interactions to Mitigate Barriers (CLIMB) digital intervention, which aims to enhance social functioning in people with CPD. CLIMB consists of two treatment components: a computerized social cognition training (SCT) program and optimized remote group therapy (ORGT). ORGT is an innovative treatment that combines remote group therapy with group texting (short message service, SMS). OBJECTIVES: The objectives of this single-arm study were to investigate the feasibility of delivering 6 weeks of CLIMB to people with CPD and explore the initial effects on outcomes. METHODS: Participants were recruited, screened and enrolled via the Internet, and delivered assessments and interventions remotely using provided tablets (iPads). Participants were asked to complete 18 hours of SCT and to attend 6 remote group therapy sessions. To assess feasibility, adherence to study procedures, attrition rates, engagement metrics, and acceptability of the intervention were evaluated. Changes on measures of social cognition, quality of life, and symptoms were also explored. RESULTS: In total, 27 participants were enrolled over 12 months. Remote assessments were completed successfully on 96% (26/27) of the enrolled participants. Retention in the 6-week trial was 78% (21/27). Of all the iPads used, 95% (22/23) were returned undamaged at the end of the intervention. Participants on average attended 84% of the group therapy sessions, completed a median of 9.5 hours of SCT, and posted a median of 5.2 messages per week on the group text chat. Participants rated CLIMB in the medium range in usability, acceptability, enjoyment, and perceived benefit. Participants showed significant improvements in emotion identification abilities for prosodic happiness (P=.001), prosodic happiness intensity (P=.04), and facial anger (P=.04), with large within-group effect sizes (d=.60 to d=.86). Trend-level improvements were observed on aspects of quality of life (P values less than .09). No improvements were observed for symptoms. CONCLUSIONS: It is feasible and acceptable to remotely deliver an intervention aimed at enhancing social functioning in people with CPD using mobile devices. This approach may represent a scalable method to increase treatment access and adherence. Our pilot data also demonstrate within-group gains in some aspects of social cognition after 6 weeks of CLIMB. Future randomized controlled studies in larger samples should evaluate the extent to which CLIMB significantly improves social cognition, symptoms, and quality of life in CPD.

Feasibility of PRIME: A Cognitive Neuroscience-Informed Mobile App Intervention to Enhance Motivated Behavior and Improve Quality of Life in Recent Onset Schizophrenia.

BACKGROUND: Despite improvements in treating psychosis, schizophrenia remains a chronic and debilitating disorder that affects approximately 1% of the US population and costs society more than depression, dementia, and other medical illnesses across most of the lifespan. Improving functioning early in the course of illness could have significant implications for long-term outcome of individuals with schizophrenia. Yet, current gold-standard treatments do not lead to clinically meaningful improvements in outcome, partly due to the inherent challenges of treating a population with significant cognitive and motivational impairments. The rise of technology presents an opportunity to develop novel treatments that may circumvent the motivational and cognitive challenges observed in schizophrenia. OBJECTIVE: The purpose of this study was two-fold: (1) to evaluate the feasibility and acceptability of implementing a Personalized Real-Time Intervention for Motivation Enhancement (PRIME), a mobile app intervention designed to target reward-processing impairments, enhance motivation, and thereby improve quality of life in recent onset schizophrenia, and (2) evaluate the empirical benefits of using an iterative, user-centered design (UCD) process. METHODS: We conducted two design workshops with 15 key stakeholders, followed by a series of in-depth interviews in collaboration with IDEO, a design and innovation firm. The UCD approach ultimately resulted in the first iteration of PRIME, which was evaluated by 10 RO participants. Results from the Stage 1 participants were then used to guide the next iteration that is currently being evaluated in an ongoing RCT. Participants in both phases were encouraged to use the app daily with a minimum frequency of 1/week over a 12-week period. RESULTS: The UCD process resulted in the following feature set: (1) delivery of text message (short message service, SMS)-based motivational coaching from trained therapists, (2) individualized goal setting in prognostically important psychosocial domains, (3) social networking via direct peer-to-peer messaging, and (4) community "moments feed" to capture and reinforce rewarding experiences and goal achievements. Users preferred an experience that highlighted several of the principles of self-determination theory, including the desire for more control of their future (autonomy and competence) and an approach that helps them improve existing relationships (relatedness). IDEO, also recommended an approach that was casual, friendly, and nonstigmatizing, which is in line with the recovery model of psychosis. After 12-weeks of using PRIME, participants used the app, on average, every other day, were actively engaged with its various features each time they logged in and retention and satisfaction was high (20/20, 100% retention, high satisfaction ratings). The iterative design process lead to a 2- to 3-fold increase in engagement from Stage 1 to Stage 2 in almost each aspect of the platform. CONCLUSIONS: These results indicate that the neuroscience-informed mobile app, PRIME, is a feasible and acceptable intervention for young people with schizophrenia.

Intensive Auditory Cognitive Training Improves Verbal Memory in Adolescents and Young Adults at Clinical High Risk for Psychosis.

OBJECTIVE: Individuals at clinical high risk (CHR) for psychosis demonstrate cognitive impairments that predict later psychotic transition and real-world functioning. Cognitive training has shown benefits in schizophrenia, but has not yet been adequately tested in the CHR population. METHODS: In this double-blind randomized controlled trial, CHR individuals (N = 83) were given laptop computers and trained at home on 40 hours of auditory processing-based exercises designed to target verbal learning and memory operations, or on computer games (CG). Participants were assessed with neurocognitive tests based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS) battery and rated on symptoms and functioning. Groups were compared before and after training using a mixed-effects model with restricted maximum likelihood estimation, given the high study attrition rate (42%). RESULTS: Participants in the targeted cognitive training group showed a significant improvement in Verbal Memory compared to CG participants (effect size = 0.61). Positive and Total symptoms improved in both groups over time. CONCLUSIONS: CHR individuals showed patterns of training-induced cognitive improvement in verbal memory consistent with prior observations in schizophrenia. This is a particularly vulnerable domain in individuals at-risk for psychosis that predicts later functioning and psychotic transition. Ongoing follow-up of this cohort will assess the durability of training effects in CHR individuals, as well as the potential impact on symptoms and functioning over time. Clinical Trials Number: NCT00655239. URL: https://clinicaltrials.gov/ct2/show/NCT00655239?term=vinogradov&rank=5.

Modeling the role of negative symptoms in determining social functioning in individuals at clinical high risk of psychosis.

A priority for improving outcome in individuals at clinical high risk (CHR) is enhancing our understanding of predictors of psychosis as well as psychosocial functioning. Social functioning, in particular, is a unique indicator of risk as well as an important outcome in itself. Negative symptoms are a significant determinant of social functioning in CHR individuals; yet, it is unclear which specific negative symptoms drive functional outcome and how these symptoms function relative to other predictors, such as neurocognition and mood/anxiety symptoms. In a sample of 85 CHR individuals, we examined whether a two-factor negative symptom structure that is found in schizophrenia (experiential vs expressive symptoms) would be replicated in a CHR sample; and tested the degree to which specific negative symptoms predict social functioning, relative to neurocognition and mood/anxiety symptoms, which are known to predict functioning. The two-factor negative symptom solution was replicated in this CHR sample. Negative symptom severity was found to be uniquely predictive of social functioning, above and beyond depression/anxiety and neurocognition. Experiential symptoms were more strongly associated with social functioning, relative to expression symptoms. In addition, experiential symptoms mediated the relationship between expressive negative symptoms and social functioning. These results suggest that experiences of motivational impairment are more important in determining social functioning, relative to affective flattening and alogia, in CHR individuals, thereby informing the development of more precise therapeutic targets. Developing novel interventions that stimulate goal-directed behavior and reinforce rewarding experiences in social contexts are recommended.

Neuroplasticity-based auditory training via laptop computer improves cognition in young individuals with recent onset schizophrenia.

OBJECTIVE: Cognitive deficits that characterize schizophrenia are present in the prodrome, worsen with illness onset, and predict functional outcome. Cognitive dysfunction is thus a critical target for early intervention in young individuals with recent onset schizophrenia. METHOD: This 2-site double-blind randomized controlled trial investigated cognitive training of auditory processing/verbal learning in 86 subjects with recent onset schizophrenia (mean age of 21 years). Subjects were given laptop computers to take home and were asked to perform 40 hours of training or 40 hours of commercial computer games over 8 weeks. We examined cognitive measures recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS), symptoms, and functioning. We also assessed baseline reward anticipation to index motivational system functioning and measured changes in auditory processing speed after 20 hours of training to assess target engagement. RESULTS: Auditory training subjects demonstrated significant improvements in global cognition, verbal memory, and problem solving compared with those of computer games control subjects. Both groups showed a slight but significant decrease in symptoms and no change in functional outcome measures. Training-induced cognitive gains at posttraining showed significant associations with reward anticipation at baseline and with improvement in auditory processing speed at 20 hours. CONCLUSION: Neuroscience-informed cognitive training via laptop computer represents a promising treatment approach for cognitive dysfunction in early schizophrenia. An individual's baseline motivational system functioning (reward anticipation), and ability to engage in auditory processing speed improvement, may represent important predictors of treatment outcome. Future studies must investigate whether cognitive training improves functioning and how best to integrate it into critical psychosocial interventions.

Family-focused treatment for adolescents and young adults at high risk for psychosis: results of a randomized trial.

OBJECTIVE: Longitudinal studies have begun to clarify the phenotypic characteristics of adolescents and young adults at clinical high risk for psychosis. This 8-site randomized trial examined whether a 6-month program of family psychoeducation was effective in reducing the severity of attenuated positive and negative psychotic symptoms and enhancing functioning among individuals at high risk. METHOD: Adolescents and young adults (mean age 17.4 ± 4.1 years) with attenuated positive psychotic symptoms, brief and intermittent psychosis, or genetic risk with functional deterioration were randomly assigned to 18 sessions of family-focused therapy for individuals at clinical high risk (FFT-CHR) in 6 months or 3 sessions of family psychoeducation (enhanced care [EC]). FFT-CHR included psychoeducation about early signs of psychosis, stress management, communication training, and problem-solving skills training, whereas EC focused on symptom prevention. Independent evaluators assessed participants at baseline and 6 months on positive and negative symptoms and social-role functioning. RESULTS: Of 129 participants, 102 (79.1%) were followed up at 6 months. Participants in FFT-CHR showed greater improvements in attenuated positive symptoms over 6 months than participants in EC (F1,97 = 5.49, p = .02). Negative symptoms improved independently of psychosocial treatments. Changes in psychosocial functioning depended on age: participants more than 19 years of age showed more role improvement in FFT-CHR, whereas participants between 16 and 19 years of age showed more role improvement in EC. The results were independent of concurrent pharmacotherapy. CONCLUSION: Interventions that focus on improving family relationships may have prophylactic efficacy in individuals at high risk for psychosis. Future studies should examine the specificity of effects of family intervention compared to individual therapy of the same duration and frequency. Clinical trial registration information-Prevention Trial of Family Focused Treatment in Youth at Risk for Psychosis; http://clinicaltrials.gov/; NCT01907282.

Motivational deficits in individuals at-risk for psychosis and across the course of schizophrenia.

Motivational impairment is a critical factor that contributes to functional disability in schizophrenia and undermines an individual's ability to engage in and adhere to effective treatment. However, little is known about the developmental trajectory of deficits in motivation and whether these deficits are present prior to the onset of psychosis. We assessed several components of motivation including anticipatory versus consummatory pleasure (using the Temporal Experience of Pleasure Scale (TEPS)), and behavioral drive, behavioral inhibition, and reward responsivity (using the Behavioral Inhibition Scale/Behavioral Activation Scale (BIS/BAS)). A total of 234 participants completed study measures, including 60 clinical high risk (CHR) participants, 60 recent-onset schizophrenia participants (RO), 78 chronic schizophrenia participants (SZ) and 29 healthy controls (HC) age matched to the CHR group. CHR participants endorsed greater deficits in anticipatory pleasure and reward responsivity, relative to HC comparison participants and individuals diagnosed with schizophrenia. Motivational deficits were not more pronounced over the course of illness. Depressed mood was uniquely associated with impairments in motivation in the CHR sample, but not the schizophrenia participants. The results suggest that CHR individuals experience multiple contributors to impaired motivation, and thus multiple leverage points for treatment.