Characterizing the Clinical Trajectory and Predicting Persistence and Deterioration of Attenuated Psychotic Symptoms in Ultra-High-Risk Individuals

Background: Almost 40% of individuals at ultra-high risk (UHR) for psychosis experience persistent attenuated psychotic symptoms (APS) yet it is unclear (1) whether they share overlapping clinical and functional outcomes compared to individuals who transition to psychosis, (2) when symptom and functioning trajectories begin to diverge between UHR individuals with different clinical outcomes, and (3) whether non-remission (persistent APS or transition) can be predicted using baseline and/or longitudinal data. Study design: Participants were drawn from 2 randomized clinical trials: Neurapro (n = 220; discovery sample) and STEP (n = 180; external validation sample). First, 12-24 month symptoms and functioning were compared between UHR individuals with persistent APS, sustained remission, or transition to psychosis. Next, short-term changes in symptoms and functioning were compared between groups to determine timepoints at which trajectories began to diverge. Finally, we used support vector machines to predict non-remission (persistent APS or transition) vs sustained remission using data from baseline, 6-month follow-up, and combined baseline and 6-month follow-up. Results: Individuals with persistent APS had substantially poorer outcomes compared to those who remitted, and more closely resembled individuals who later transitioned to psychosis. Despite few baseline differences between groups, clinical and functional trajectories of the persistent APS and transition groups rapidly diverged from those who remitted. Prediction of non-remission was poor using baseline data but improved substantially when using 6-month follow-up or combined baseline-6-month data. Conclusions: Ultra-high-risk individuals with persistent APS display similar clinical and functional trajectories to transitioned cases, suggesting that more intensive and sustained intervention is required for this subgroup. However, prospective identification of individuals with poor clinical outcomes (ie, persistence or deterioration of attenuated psychotic symptoms) may require longitudinal monitoring of symptom and functioning trajectories for several months

Enabling FAIR data stewardship in complex international multi-site studies: Data Operations for the Accelerating Medicines Partnership® Schizophrenia Program.

Modern research management, particularly for publicly funded studies, assumes a data governance model in which grantees are considered stewards rather than owners of important data sets. Thus, there is an expectation that collected data are shared as widely as possible with the general research community. This presents problems in complex studies that involve sensitive health information. The latter requires balancing participant privacy with the needs of the research community. Here, we report on the data operation ecosystem crafted for the Accelerating Medicines Partnership® Schizophrenia project, an international observational study of young individuals at clinical high risk for developing a psychotic disorder. We review data capture systems, data dictionaries, organization principles, data flow, security, quality control protocols, data visualization, monitoring, and dissemination through the NIMH Data Archive platform. We focus on the interconnectedness of these steps, where our goal is to design a seamless data flow and an alignment with the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles while balancing local regulatory and ethical considerations. This process-oriented approach leverages automated pipelines for data flow to enhance data quality, speed, and collaboration, underscoring the projects contribution to advancing research practices involving multisite studies of sensitive mental health conditions. An important feature is the datas close-to-real-time quality assessment (QA) and quality control (QC). The focus on close-to-real-time QA/QC makes it possible for a subject to redo a testing session, as well as facilitate course corrections to prevent repeating errors in future data acquisition. Watch Dr. Sylvain Bouix discuss his work and this article: https://vimeo.com/1025555648

Cognitive assessment in the Accelerating Medicines Partnership® Schizophrenia Program:harmonization priorities and strategies in a diverse international sample

Cognitive impairment occurs at higher rates in individuals at clinical high risk (CHR) for psychosis relative to healthy peers, and it contributes unique variance to multivariate prediction models of transition to psychosis. Such impairment is considered a core biomarker of schizophrenia. Thus, cognition is a key domain measured in the Accelerating Medicines Partnership® program for Schizophrenia (AMP SCZ initiative). The aim of this paper is to describe the rationale, processes, considerations, and final harmonization of the cognitive battery used in AMP SCZ across the two data collection networks. This battery comprises tests of general intellect and specific cognitive domains. We estimate premorbid intelligence at baseline and measure current intelligence at baseline and 2 years. Eight tests from the Penn Computerized Neurocognitive Battery (PennCNB), which measure verbal learning and memory, sensorimotor ability, attention, emotion recognition, working memory, processing speed, verbal memory, visual memory, and motor speed are administered repeatedly at baseline, and four follow-up timepoints over 2 years.</p

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals

Beyond black and white: Reducing dichotomous thinking to foster intellectual humility

This study examines the causal influence of dichotomous thinking on intellectual humility, evaluated through treatments designed to both increase and decrease dichotomous thinking. Employing an experimental design with 445 participants, we exposed experimental groups to either a black and white thinking treatment (high dichotomous thinking condition) or a dialectical thinking treatment (low dichotomous thinking condition), and then compared their intellectual humility scores to a control group. As hypothesized, significant differences in intellectual humility emerged among the groups. The most substantial effects were observed in the group exposed to the dialectical thinking treatment (low dichotomous thinking condition), where participants exhibited significantly elevated intellectual humility scores. Using instrumental variable estimation for the purposes of causal inference, we also confirmed that the mechanism by which the dialectical thinking treatment increased intellectual humility was by decreasing dichotomous thinking. Our study provides insights into the factors that influence intellectual humility and offers a practical method to enhance it through fostering dialectical thinking.</p

Helix Health Research Data Dictionary Template

As part of Monash University (Helix) Health Research Data Governance strategy a working group was established in 2019 to develop a data dictionary template for use in Health Research. This is an excel version of the template that can be output into a word document. It contains all the metadata (characteristics) that should be included in a health research data dictionary in a standardised format.</p