EPI-MINN: Targeting Cognition and Motivation - National

Cognitive dysfunction is a core pathophysiological feature of psychosis and one of the strongest predictors of functional outcomes. Several studies indicate that current early intervention programs may not significantly alter long-term clinical outcome, suggesting that critical treatment target(s), beyond symptoms and functional status, are not being addressed. Evidence strongly indicates that, along with cognitive dysfunction, impaired motivation is also a critical target and unmet therapeutic need.

The application of effective treatment to improve cognition in early phases of psychosis has a very high likelihood of significantly improving long-term community functioning. The investigators have demonstrated both behavioral gains and improved neural system functioning after neuroscience-informed cognitive training in schizophrenia, in both chronic and early phases of the illness. In young recent-onset individuals (average age of 21 years), the investigators' multi-site double-blind randomized controlled trial showed that 40 hours/ 10 weeks of cognitive training delivered at home over a laptop resulted in significant gains in global cognition, verbal memory, and problem solving compared to a computer games control condition. Cognitive gains were significantly correlated with enhanced thalamic volume and thalamo-cortical connectivity, as well as increased white matter integrity. A meta-analysis of 11 RCTs in early schizophrenia has also indicated the benefit of cognitive remediation approaches.

Impaired motivation is also a core feature and very strong predictor of functional outcome in early stages of psychosis. Some studies have shown positive effects in improving motivation immediately after the intervention, but treatments that induce enduring improvements in motivated behavior are scarce. Disturbances in motivated behavior reflect a range of factors, including diminished anticipatory pleasure, difficulty learning from rewarding outcomes, reduction in effort expended to obtain rewarding outcomes, and impairment and disconnection between components of social motivation. This makes it difficult to determine optimal therapeutic approaches. However, some headway is starting to appear in the literature. For instance, social cognition impairments appear to play a specific contributing role to dysfunctions in motivated behavior, and are amenable to intervention. We have found that ratings of motivated behavior improve after social cognition training, and are significantly greater in subjects who performed cognitive training combined with social cognition training, than in those who completed only cognitive training. The investigators have also demonstrated a significant relationship between 6-month social functioning and training-induced improvements in the neural correlates of a self-other reality monitoring task. These data, along with the literature on reward anticipation and on social engagement in psychosis, led this group to work with young clients in a user-centered design process, to develop a mobile app called Personalized Real-time Intervention for Motivational Enhancement (PRIME). The app has been extremely well received by users and published behavioral findings are highly promising. Thus, the investigators will combine a focused course of cognitive plus social cognitive training (delivered remotely) with PRIME, to address the cognitive dysfunction and impaired motivation.

Functional recovery lags behind symptom recovery in early intervention programs, is sometimes difficult for individuals to attain, and is closely aligned with cognitive and motivational deficits. How could outcomes for individuals with early psychosis to improved? The results from this study will provide data-driven knowledge on factors that contribute to 2-year treatment response trajectories in early psychosis. The knowledge gained from this clinical trial will deepen understanding of methods to optimize coordinated specialty care to improve clinical trajectories, using a well-defined scalable mobile program that addresses as-of-yet unmet therapeutic needs.

Inclusion criteria

• Aged 15-40 (inclusive)
• Is enrolled in an early psychosis coordinated specialty care clinic, or is receiving services by a mental health care professional.
• Symptoms of psychosis started within the last 5 years
• Is in good general physical health (e.g., not acutely ill or experiencing a sever/chronic illness that would impede their ability to complete study activities)
• Fluent in spoken and written English
• Estimated IQ at or above 70, as estimated by the Test My Brain matrices task
• Participants will show overall clinical stability as determined by interview measures. Generally, participants who have not been hospitalized within the last 30 days, who have not had significant changes to medications, and do not have active suicidal ideation will be considered stable.
• Has access to a smart phone or other mobile device to use the PRIME App
• Has access to a computer or tablet to complete cognitive training exercises and study assessments

Exclusion criteria

• Unable to provide informed consent (i.e., cannot pass UBACC assessment)
• Participant is under legal commitment to treatment or is under medical guardianship
• Participated in significant cognitive training programs within the last 3 years
• Diagnosed with a neurological disorder that may interfere with participation in the study
• Clinically significant substance abuse that is impeding the participant's ability to participate fully during enrollment, assessment, or training (i.e., is unable to remain sober)
• Risk of suicidal behavior