COGNITION AND FUNCTIONAL OUTCOMES IN SCHIZOPHRENIA Highlights • Meta-analysis of 166 studies (12,868 individuals) examining relationships between neurocognition and social cognition and functional outcomes. • Domains of neurocognition and social cognition demonstrate small to medium relationships with functional outcomes. • Neurocognition and social cognition did not demonstrate significantly different relationships with functional outcomes, however, social cognition domains explained more unique variance. • Social cognition is a partial mediator between neurocognition and functional outcomes.

Reliability of clinical diagnoses is often low. There are many algorithms that could improve diagnostic accuracy, and statistical learning is becoming popular. Using pediatric bipolar disorder as a clinically challenging example, we evaluated a series of increasingly complex models ranging from simple screening to a supervised LASSO regression in a large (=550) academic clinic sample. We then externally validated models in a community clinic (=511) with the same candidate predictors and semi-structured interview diagnoses, providing high methodological consistency; the clinics also had substantially different demography and referral patterns. Models performed well according to internal validation metrics. Complex models degraded rapidly when externally validated. Naïve Bayesian and logistic models concentrating on predictors identified in prior meta-analyses tied or bettered LASSO models when externally validated. Implementing these methods would improve clinical diagnostic performance. Statistical learning research should continue to invest in high quality indicators and diagnoses to supervise model training.

Understanding the mechanisms of change of digital therapeutics is a critical step to improve digital health outcomes and optimize their development. Access to and engagement with digital content is arguably a core mechanism of change of these interventions. However, the mediational role of app engagement has been largely unexamined. To evaluate the mediational effect of engaging with a digital therapeutic for smoking cessation designed for adults with psychiatric disorders. Secondary analysis of a pilot clinical trial of 62 adults with serious mental illness who were randomized to receive either a tailored digital therapeutic (Learn to Quit) or a digital therapeutic for the general public (NCI QuitGuide). Engagement was captured using background analytics of app utilization, including (a) number of interactions with app content, (b) minutes/day of app use, and (c) number of days used. The main outcome was reductions in cigarettes per day from baseline to the four-month endpoint. Mediational analysis followed the Preacher and Hayes bootstrap method. Number of application interactions fully mediated reductions in cigarettes per day in the Learn to Quit application but not in QuitGuide (Average Causal Mediation Effect = .31, p = .02). Minutes/day of app use played an uncertain role, and number of days used was not a significant mediator. Results suggest that one of the mechanisms of action of the Learn to Quit device, engagement with theory-based content, functioned as intended. Future research of digital therapeutics should emphasize granular approaches to evaluating apps’ mechanisms of action.

The effects of intranasal oxytocin, a neuropeptide involved in prosocial behavior and modulation of neural networks underlying social cognition and emotion regulation, have been studied in schizophrenia. We tested the hypothesis that twice-daily intranasal oxytocin administered for 12-weeks would improve tertiary and exploratory outcomes of self-reported social symptoms, empathy and introspective accuracy from the Jarskog et al. (2017) randomized controlled trial. Sixty-eight stable outpatients with schizophrenia or schizoaffective disorder were randomized to receive oxytocin (24 IU twice daily) or placebo. Introspective accuracy was assessed with the Specific Level of Functioning Scale and the Interpersonal Perception Task. Empathy was assessed with the Interpersonal Reactivity Index (IRI), and social symptoms were assessed with the Liebowitz Social Anxiety Scale and the Green et al. Paranoid Thoughts Scales. Outcomes were assessed at baseline, six, and twelve weeks. Results demonstrated limited effect of oxytocin with some improvement on the IRI Perspective-Taking Subscale. No additional between-group differences emerged on self-reported symptoms, empathy, or introspective accuracy.