Baseline Clinical Characterization of Participants in the Accelerating Medicines Partnership Schizophrenia Program.

Background: This paper focuses on the baseline clinical characterization of the participants in the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program. The AMP SCZ program is designed to investigate a wide array of clinical variables and biomarkers in a total of 2040 clinical high-risk (CHR) participants and 652 community control (CC) participants.

Methods: The dataset analyzed includes 1642 individuals at clinical high risk for psychosis and 519 CCs.

Sample Ascertainment and Recruitment Sources in the Accelerating Medicines Partnership Schizophrenia Program.

Background: This paper presents the recruitment sources of clinical high-risk (CHR) and community controls (CC) from the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program, which aims to study various clinical variables and biomarkers in 2040 CHR and 652 CC participants.

Methods: A total of 1640 CHR and 514 CC had recruitment source data. The Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the SIPS was utilized to assess CHR criteria and severity of attenuated psychotic symptoms (APSs), and the Global Functioning: Social Scale was used for social functioning.

Grip Strength as a Marker of Resting-State Network Integrity and Well-Being in Early Psychosis.

Objective: Psychomotor function is a critical marker of risk and outcome of psychosis. Grip strength is one aspect of psychomotor function that is known to be linked to structural neural integrity and well-being. This study sought to determine whether grip strength is a marker of alterations in resting-state connectivity and well-being in psychotic disorders in order to further clarify the mechanisms by which psychosis phenomenology is related to psychomotor processes.

Characterizing heterogeneity in motivational impairments in psychosis.

Introduction: Motivational impairments are a hallmark symptom of psychotic disorders. However, motivation is a multidimensional construct believed to be underpinned by different neural mechanisms and differentially impaired both between and within diagnostic groups. We used a data driven approach to identify different motivational profiles in people with psychosis.

Negative symptoms, cognition, and community functioning in early psychosis.

Introduction: Negative symptoms are associated with poorer cognitive functioning in psychosis, and both negative symptoms and cognition are associated with poorer community functioning, even in the early course of illness. Current conceptualizations of negative symptoms in psychosis have identified separate subdomains, not all of which may be affected in every patient; however, few studies have examined associations between specific negative symptom subdomains and cognition and functioning in early psychosis.

Methods: Participants with schizophrenia spectrum disorders (SSD; n = 26) or mood disorders with psychosis (MDP; n = 41) within the first 6.

Distinct cognitive trajectories in the early course of psychosis are associated with clinical and functional outcomes longitudinally.

Cognitive dysfunction is a core dimension in psychotic disorders and among the strongest predictors of disability and poor quality of life. Cognitive impairments are highly heterogeneous, and cross-sectional studies have consistently found evidence of distinct cognitive profiles both within diagnoses and transdiagnostically. Findings regarding the course of cognitive impairments over time have been mixed.

Bridging Science and Hope: integrating and Communicating Lived experience in Accelerating Medicines Partnership® Schizophrenia Program.

The Accelerating Medicines Partnership Schizophrenia (AMP® SCZ) program integrates lived experience into psychosis research, leveraging over three decades of foundational studies to improve research quality, promote community engagement, and ensure ethical implementation of precision psychiatry. Lived experience is embedded in the program’s governance, shaping study protocols, recruitment strategies, and digital tools such as the mindLAMP platform. Study sites also integrate lived experience through youth advisory boards, peer support specialists, and advisory committees, ensuring diverse perspectives inform research design and implementation.

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.

Sample ascertainment and clinical outcome measures in the Accelerating Medicines Partnership® Schizophrenia Program.

Clinical ascertainment and clinical outcome are key features of any large multisite study. In the ProNET and PRESCIENT research networks, the Accelerating Medicines Partnership Schizophrenia (AMPSCZ) Clinical Ascertainment and Outcome Measures Team aimed to establish a harmonized clinical assessment protocol across these two research networks and to define ascertainment criteria and primary and secondary endpoints. In addition to developing the assessment protocol, the goals of this aspect of the AMP SCZ project were: (1) to implement and monitor clinical training, ascertainment of participants, and clinical assessments; (2) to provide expert clinical input to the Psychosis Risk Evaluation, Data Integration and Computational Technologies: Data Processing, Analysis, and Coordination Center (PREDICT-DPACC) for data collection, quality control, and preparation of data for the analysis of the clinical measures; and (3) to provide ongoing support to the collection, analysis, and reporting of clinical data.

Data analysis strategies for the Accelerating Medicines Partnership® Schizophrenia Program.

The Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) project assesses a large sample of individuals at clinical high-risk for developing psychosis (CHR) and community controls. Subjects are enrolled in 43 sites across 5 continents. The assessments include domains similar to those acquired in previous CHR studies along with novel domains that are collected longitudinally across a period of 2 years.

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).

Psychosis-linked Symptoms and Structural Brain Patterns in Cognitive Subgroups among Familial High-Risk Children in the ABCD Study.

Objective: Children at familial high risk for psychosis (FHR) are at substantially increased risk for psychotic disorders and other serious mental illnesses. Identifying risk subgroups within FHR youth may enhance prediction models to identify children at greatest risk for potential intervention. This study investigated psychosis-linked symptoms and structural brain patterns in neurocognitive subgroups among FHR children in the Adolescent Brain Cognitive Development (ABCD) Study using baseline, 2-year, and 4-year follow-up data.

Comorbidity of anorexia nervosa and schizophrenia: A systematic review.

Research on the intersection between eating disorders and schizophrenia (SCZ) has mainly focused on binge eating, since increased appetite and metabolic side effects are common during antipsychotic use. However, the prevalence of restrictive eating and anorexia nervosa may be higher in people with SCZ than in the general population, and evidence suggests shared genetic liability for SCZ and anorexia nervosa (AN). The aim of this systematic review was to examine the prevalence, psychological and biological mechanisms, and theoretical underpinnings underlying the co-occurrence of AN and SCZ.

Cognitive Impairment in Psychotic Disorders Is Associated with Brain Reductive Stress and Impaired Energy Metabolism as Measured by 31P Magnetic Resonance Spectroscopy.

Background And Hypothesis: Convergent evidence shows the presence of brain metabolic abnormalities in psychotic disorders. This study examined brain reductive stress and energy metabolism in people with psychotic disorders with impaired or average range cognition. We hypothesized that global cognitive impairment would be associated with greater brain metabolic dysregulation.

Robust Brain Correlates of Cognitive Performance in Psychosis and Its Prodrome.

Background: Neurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state functional magnetic resonance imaging. We hypothesized that a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies.

Data-driven, connectome-wide analysis identifies psychosis-specific brain correlates of fear and anxiety.

Decades of psychosis research highlight the prevalence and the clinical significance of negative emotions, such as fear and anxiety. Translational evidence demonstrates the pivotal role of the amygdala in fear and anxiety. However, most of these approaches have used hypothesis-driven analyses with predefined regions of interest.

Using Computational Phenotyping to Identify Divergent Strategies for Effort Allocation Across the Psychosis Spectrum.

Background And Hypothesis: Disturbances in effort-cost decision-making have been highlighted as a potential transdiagnostic process underpinning negative symptoms in individuals with schizophrenia. However, recent studies using computational phenotyping show that individuals employ a range of strategies to allocate effort, and use of different strategies is associated with unique clinical and cognitive characteristics. Building on prior work in schizophrenia, this study evaluated whether effort allocation strategies differed in individuals with distinct psychotic disorders.

Isolation of Distinct Networks Driving Action and Cognition in Psychomotor Processes.

Background: Psychomotor disturbances are observed across psychiatric disorders and often manifest as psychomotor slowing, agitation, disorganized behavior, or catatonia. Psychomotor function includes both cognitive and motor components, but the neural circuits driving these subprocesses and how they relate to symptoms have remained elusive for centuries.

Methods: We analyzed data from the HCP-EP (Human Connectome Project for Early Psychosis), a multisite study of 125 participants with early psychosis and 58 healthy participants with resting-state functional magnetic resonance imaging and clinical characterization.

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.

Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.

Background: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD.

Methods: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures.