Attention Deficit Hyperactivity Disorder Among Youth at Clinical High Risk of Psychosis.

Background: Attention Deficit Hyperactivity Disorder (ADHD) affects a significant proportion of the population and is associated with numerous adverse outcomes including lower educational attainment, occupational challenges, increased substance use, and various mental health issues including psychosis. This study examined the demographic, clinical, cognitive, social cognitive, and functional differences between youth at clinical high-risk (CHR) for psychosis with and without comorbid ADHD.

Method: Data were drawn from the North American Prodrome Longitudinal Studies (NAPLS2 and NAPLS3), which included 764 and 710 CHR individuals, respectively.

Mismatch Negativity as an Index of Auditory Short-Term Plasticity: Associations with Cortisol, Inflammation, and Gray Matter Volume in Youth at Clinical High Risk for Psychosis.

Mismatch negativity (MMN) event-related potential (ERP) component reduction, indexing N-methyl-D-aspartate receptor (NMDAR)-dependent auditory echoic memory and short-term plasticity, is a well-established biomarker of schizophrenia that is sensitive to psychosis risk among individuals at clinical high-risk (CHR-P). Based on the NMDAR-hypofunction model of schizophrenia, NMDAR-dependent plasticity is predicted to contribute to aberrant neurodevelopmental processes involved in the pathogenesis of schizophrenia during late adolescence or young adulthood, including gray matter loss. Moreover, stress and inflammation disrupt plasticity.

Cognitive-Behavioural Social Skills Training: Mediation of Treatment Outcomes in a Randomized Controlled Trial for Youth at Risk of Psychosis: L'entraînement aux compétences sociales cognitivo-comportementales : variables médiatrices des résultats thérapeutiques dans le cadre d'un essai clinique randomisé pour les jeunes présentant un risque de psychose.

Objectives: Currently, there are no effective treatments for functional outcomes (i.e., role and social) and negative symptoms for youth at clinical high-risk (CHR) for psychosis.

Protective Factors Predict Resilient Outcomes in Clinical High-Risk Youth with the Highest Individualized Psychosis Risk Scores.

Background And Hypothesis: Studying individuals at Clinical High Risk (CHR) for psychosis provides an opportunity to examine protective factors that predict resilient outcomes. Here, we present a model for the study of protective factors in CHR participants at the very highest risk for psychotic conversion based on the Psychosis Risk Calculator.

Study Design: CHR participants (N = 572) from NAPLS3 were assessed on the Risk Calculator.

Impact of adverse childhood experiences on risk for internalizing psychiatric disorders in youth at clinical high-risk for psychosis.

Introduction: Research has established that adverse childhood experiences (ACEs) confer risk for psychiatric diagnoses, and that protective factors moderate this association. Investigation into the effect of protective factors in the relationship between ACEs and internalizing disorders (e.g.

Beyond the Descriptive: A Comprehensive, Multidomain Validation of Symptom Trajectories for Individuals at Clinical High Risk for Psychosis.

Background: Although the clinical high risk for psychosis (CHR-P) criteria are widely used to ascertain individuals at heightened risk for imminent onset of psychosis, it remains controversial whether CHR-P status defines a diagnostic construct in its own right. In a previous study, CHR-P nonconverters were observed to follow 3 distinct trajectories in symptoms and functioning: remission, partial remission, and maintenance of symptoms and functional impairments at subthreshold levels of intensity.

Methods: Here, we utilized the NAPLS3 (North American Prodrome Longitudinal Study phase 3) sample (N = 806) to determine whether 1) the same trajectory groups can be detected when assessing symptoms at 2-month intervals over an 8-month period and 2) the resulting trajectory groups differ from each other and from healthy control participants and converting CHR-P cases in terms of risk factors, comorbidities, and functional outcomes.

Fetal Gene Regulatory Gene Deletions are Associated with Poor Cognition and Altered Cortical Morphology in Schizophrenia and Community-Based Samples.

Schizophrenia spectrum disorders (SSDs) are characterized by substantial clinical and genetic heterogeneity. Multiple recurrent copy number variants (CNVs) increase risk for SSDs; however, how known risk CNVs and broader genome-wide CNVs influence clinical variability is unclear. The current study examined associations between borderline intellectual functioning or childhood-onset psychosis, known risk CNVs, and burden of deletions affecting genes in 18 previously validated neurodevelopmental gene-sets in 618 SSD individuals.

Cognitive subtypes in youth at clinical high risk for psychosis.

Introduction: Schizophrenia is a mental health condition that severely impacts well-being. Cognitive impairment is among its core features, often presenting well before the onset of overt psychosis, underscoring a critical need to study it in the psychosis proneness (clinical high risk; CHR) stage, to maximize the benefits of interventions and to improve clinical outcomes. However, given the heterogeneity of cognitive impairment in this population, a one-size-fits-all approach to therapeutic interventions would likely be insufficient.

Unique Functional Neuroimaging Signatures of Genetic Versus Clinical High Risk for Psychosis.

Background: 22q11.2 deletion syndrome (22qDel) is a copy number variant that is associated with psychosis and other neurodevelopmental disorders. Adolescents who are at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms.

Occasional cannabis use is associated with higher premorbid functioning and IQ in youth at clinical high-risk (CHR) for psychosis: Parallel findings to psychosis cohorts.

Background: Neurocognitive deficits have been widely reported in clinical high-risk for psychosis (CHR) populations. Additionally, rates of cannabis use are high among CHR youth and are associated with greater symptom severity. Cannabis use has been sometimes shown to be associated with better neurocognition in more progressed psychosis cohorts, therefore in this study we aimed to determine whether a similar pattern was present in CHR.

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.

Sex differences in clinical presentation in youth at high risk for psychosis who transition to psychosis.

Sex differences have been observed in individuals with schizophrenia and for those at clinical high risk (CHR) for psychosis. However, specific differences in CHR individuals who transition to psychosis remain inconsistent and understudied. This study aimed to investigate sex differences in 156 CHR individuals who made the transition to psychosis.

Neurocognition in adolescents and young adults at clinical high risk for psychosis: Predictive stability for social and role functioning.

The prodromal phase of schizophrenia provides an optimal opportunity to mitigate the profound functional disability that is often associated with fully expressed psychosis. Considerable evidence supports the importance of neurocognition in the development of interpersonal (social) and academic (role) skills. Further findings from adolescents and young adults at clinical high risk for developing psychosis (CHRP) suggest that treatment for functioning might be most effective when targeting early and specific neurocognitive deficits.

Improving processing speed in adolescents at clinical high risk for psychosis with the Specific COgnitive REmediation plus Surround (SCORES) intervention: Study protocol.

Aim: Recent preventative approaches with young people at clinical high risk for psychosis (CHR-P) have focused on the remediation of the cognitive deficits that are readily apparent and predictive of future illness. However, the small number of trials using cognitive remediation with CHR-P individuals have reported mixed results. The proposed 2-phased study will test an innovative internet-based and remotely-delivered Specific COgnitive REmediation plus Surround (or SCORES) intervention that targets early processing speed deficits in CHR-P adolescents aged 14-20 years old.

The Complex Latent Structure of Attenuated Psychotic Symptoms: Hierarchical and Bifactor Models of SIPS Symptoms Replicated in Two Large Samples at Clinical High Risk for Psychosis.

Background And Hypothesis: The Structured Interview for Psychosis-Risk Syndromes (SIPS) and other assessments of psychosis risk define clinical high risk for psychosis (CHR) by the presence of attenuated psychotic symptoms. Despite extensive research on attenuated psychotic symptoms, substantial questions remain about their internal psychometric structure and relationships to comorbid non-psychotic symptoms.

Study Design: Hierarchical and bifactor models were developed for the SIPS in a large CHR sample (NAPLS-3, N = 787) and confirmed through preregistered replication in an independent sample (NAPLS-2, N = 1043).

Longitudinal Trajectories of Premorbid Social and Academic Adjustment in Youth at Clinical High Risk for Psychosis: Implications for Conversion.

Background And Hypothesis: Social and academic adjustment deteriorate in the years preceding a psychotic disorder diagnosis. Analyses of premorbid adjustment have recently been extended into the clinical high risk for psychosis (CHR) syndrome to identify risk factors and developmental pathways toward psychotic disorders. Work so far has been at the between-person level, which has constrained analyses of premorbid adjustment, clinical covariates, and conversion to psychosis.

Plasma complement and coagulation proteins as prognostic factors of negative symptoms: An analysis of the NAPLS 2 and 3 studies.

Introduction: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised.

The hierarchical taxonomy of psychopathology in clinical high risk for psychosis: Validation and extension.

The Hierarchical Taxonomy of Psychopathology (HiTOP) consortium's transdiagnostic dimensional model of psychopathology has considerable support; however, this model has been underresearched in individuals at clinical high risk for psychosis (CHR-P), a population that may advance the model. CHR-P individuals not only have attenuated psychotic symptoms that vary in severity, but also have many comorbid diagnoses and varied clinical outcomes, including disorders with uncertain relations to HiTOP (e.g.

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.

Negative self-reference as a component of subthreshold psychotic symptoms in clinical high-risk youth.

Aim: Schizophrenia is a leading cause of disability worldwide; early detection and intervention are critical. Early in their illness, individuals at clinical high-risk (CHR) for psychosis have subthreshold psychotic symptoms that are often derogatory and self-directed. We hypothesized that CHR participants with negative self-reference (NSR) as a component of subthreshold psychosis would also have higher levels of social anxiety and depression, lower self-esteem and lower social/role/global functioning as compared with CHR participants without NSR.

Differential expression of haptoglobin in individuals at clinical high risk of psychosis and its association with global functioning and clinical symptoms.

Background: Immune dysregulation has been observed in patients with schizophrenia or first-episode psychosis, but few have examined dysregulation in those at clinical high-risk (CHR) for psychosis. The aim of this study was to examine whether the peripheral blood-based proteome was dysregulated in those with CHR. Secondly, we examined whether baseline dysregulation was related to current and future functioning and clinical symptoms.

Racial Disparities Among Clinical High-Risk and First-Episode Psychosis Multisite Research Participants: A Systematic Review.

Objective: The NIH has mandated equal representation of Black, Indigenous, and people of color (BIPOC) individuals in clinical research, but it is unclear whether such inclusion has been achieved in multisite research studies of individuals at clinical high risk for psychosis or with first-episode psychosis (FEP). An assessment of inclusion rates is important for understanding the social determinants of psychosis and psychosis risk that specifically affect BIPOC individuals.

Methods: The authors conducted a systematic review of the literature published between 1993 and 2022 of multisite research studies of clinical high risk for psychosis and FEP in North America to determine ethnoracial inclusion rates.