Danielle Schlosser

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.

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.

Targeted disruption of the mouse Ftz-F1 gene, which encodes the orphan nuclear receptors steroidogenic factor 1 (SF-1) and embryonal long terminal repeat-binding protein (ELP), established that this gene is essential for development of the primary steroidogenic tissues and for male sexual differentiation. Associated with these dramatic developmental abnormalities, all Ftz-F1-disrupted mice died in the immediate postnatal period and had very low glucocorticoid levels. In this report, we show that treatment with corticosteroids markedly prolonged survival of the Ftz-F1-disrupted mice, proving that steroid hormone deficiency causes their death. We also generated SF-1-specific knockout mice with a targeting construct that specifically disrupted the SF-1 coding sequence without impairing the ELP protein. The phenotype of the SF-1-specific knockout mice was indistinguishable from that observed in Ftz-F1-disrupted mice that lack both SF-1 and ELP. Taken together, these results indicate that SF-1 is the Ftz-F1-encoded protein that is required for multiple aspects of endocrine development and for postnatal survival.