Neurocognitive dysfunction is a hallmark of schizophrenia and represents a significant risk factor for the development of psychosis. Among individuals at clinical high risk (CHR), greater neurocognitive deficits prospectively predict quicker illness progression, higher probability of transition to psychosis, and worse functional outcome after the disorder has taken hold. Moreover, even among CHR individuals who do not develop psychosis, those with cognitive deficits continue to struggle with functional difficulties. Thus, CHR individuals with cognitive deficits are not only at elevated risk for psychosis but they are also at elevated risk for functional disability. This project is a randomized-controlled trial o test the effectiveness of targeted cognitive training (TCT) versus a computer-game placebo intervention in a subgroup of CHR individuals with cognitive deficits. TCT is designed to optimize learning-induced neuroplasticity in vulnerable neurocognitive systems. A main aim is to test the hypothesis that, among the subgroup of CHR with cognitive deficits, this neuroscience-guided TCT intervention will improve neurocognitive function, and that these neurocognitive improvements will ameliorate clinical symptoms, improve cognition, and enhance functional outcome. CHR participants will be randomly assigned to 30 hours of TCT or placebo computer-games. Neurocognitive function, clinical symptoms, and functional status will be assessed at baseline, after 15 hours of cognitive training (mid-intervention), and after 15 hours of social-cognitive training (post-intervention). Clinical symptoms, cognition, and functioning will also be assessed at a 6 month follow-up to test durability of intervention effects. Treatment delivery is designed to promote adherence and minimize stigma. Cognitive exercises are structured as modern and engaging computer-games and accessed through the internet from home or another preferred location. Training performance and compliance is monitored through internet sites, and, if proven effective, can be distributed easily in community settings. We predict that TCT will lead to improvements in neurocognitive function, symptom severity, and functional status. The results of this study will provide important information about a benign, non-pharmacological intervention for improving cognition and functional outcome in CHR individuals.

Public Health Relevance

Young people at clinical high risk for developing psychosis have distressing psychotic-like symptoms, cognitive deficits, and functional impairment, yet there are currently no established treatments available. This project investigates whether computer-based, targeted cognitive training (TCT) of attention, memory and other skills will remediate neurocognitive function and improve functional outcome. Ultimately, TCT could provide a low cost, non-invasive treatment for individuals at risk of severe mental illness.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZMH1)
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Pearson, Jane L
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Harvard University
Schools of Arts and Sciences
United States
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Woodberry, Kristen A; Shapiro, Daniel I; Bryant, Caitlin et al. (2016) Progress and Future Directions in Research on the Psychosis Prodrome: A Review for Clinicians. Harv Rev Psychiatry 24:87-103
Dodell-Feder, David; Tully, Laura M; Hooker, Christine I (2015) Social impairment in schizophrenia: new approaches for treating a persistent problem. Curr Opin Psychiatry 28:236-42