Danielle A. Schlosser

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 individuals 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.

Cognitive Interventions Targeting Brain Plasticity in the Prodromal and Early Phases of Schizophrenia

Several important paradigm shifts have occurred in the field of schizophrenia treatment, including an increased focus on early detection, the development of preemptive interventions, and the view of schizophrenia as a neurodevelopmental disease characterized by decreased efficiency and abnormal connectivity in cortical and subcortical neural networks. In this review, we briefly describe some of the neural impairments that contribute to the development of schizophrenia, with an emphasis on the impact of stress and trauma on cognitively vulnerable neural systems. We then present current data on two behavioral interventions that target these critical risk factors and that aim to preempt the onset of schizophrenia in vulnerable individuals or improve the clinical course in recent-onset schizophrenia: cognitive therapy and computerized cognitive training.

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 individuals 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.

Predicting the longitudinal effects of the family environment on prodromal symptoms and functioning in patients at-risk for psychosis

The current study examined the relationship between the family environment and symptoms and functioning over time in a group of adolescents and young adults at clinical high risk for psychosis (N=63). The current study compared the ability of interview-based versus self-report ratings of the family environment to predict the severity of prodromal symptoms and functioning over time. The family environmental factors were measured by interviewer ratings of the Camberwell Family Interview (CFI), self-report questionnaires surveying the patients perceptions of criticism and warmth, and parent reported perceptions of their own level of criticism and warmth. Patients living in a critical family environment, as measured by the CFI at baseline, exhibited significantly worse positive symptoms at a 6-month follow-up, relative to patients living in a low-key family environment. In terms of protective effects, warmth and an optimal level of family involvement interacted such that the two jointly predicted improved functioning at the 6-month follow-up. Overall, both interview-based and self-report ratings of the family environment were predictive of symptoms and functioning at follow-up; however patients self-report ratings of criticism had stronger predictive power. These results suggest that the family environment should be a specific target of treatment for individuals at risk for psychosis.

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.

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.

A randomized trial of family focused treatment for adolescents and young adults at risk for psychosis: study rationale, design and methods.

Aim: This article outlines the rationale for a family‐focused psychoeducational intervention for individuals at risk for psychosis and explains the design of a randomized multisite trial to test its efficacy.

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.

Environmental Risk and Protective Factors and Their Influence on the Emergence of Psychosis

Environmental risk and protective factors in schizophrenia play a significant role in the development and course of the disorder. The following article reviews the current state of evidence linking a variety of environmental factors and their impact on the emergence of psychotic disorders. The environmental factors include pre- and perinatal insults, stress and trauma, family environment, and cannabis use. The review of evidence is followed by case examples and clinical applications to facilitate the integration of the evidence into clinical practice.

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

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, EBTs to treat mood symptoms and functioning in adults with depression.