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.

Neurophysiological Models in Individuals at Clinical High Risk for Psychosis: Using Translational EEG Paradigms to Forecast Psychosis Risk and Resilience.

Over the last several decades, there have been major research efforts to improve the identification of youth and young adults at clinical high-risk for psychosis (CHR-P). Among individuals identified as CHR-P based on clinical criteria, approximately 20% progress to full-blown psychosis over 2-3 years and 30% achieve remission. In more recent years, neurophysiological measures with established sensitivity to schizophrenia have gained traction in the study of CHR-P and its range of clinical outcomes, with the goal of identifying specific biomarkers that precede psychosis onset that 7 chapter, we review studies examining several translational electroencephalography (EEG) and event-related potential (ERP) measures, which have known sensitivity to schizophrenia and reflect abnormal sensory, perceptual, and cognitive processing of task stimuli, as predictors of future clinical outcomes in CHR-P individuals.

A Method for Multimodal IVA Fusion Within a MISA Unified Model Reveals Markers of Age, Sex, Cognition, and Schizophrenia in Large Neuroimaging Studies.

With the increasing availability of large-scale multimodal neuroimaging datasets, it is necessary to develop data fusion methods which can extract cross-modal features. A general framework, multidataset independent subspace analysis (MISA), has been developed to encompass multiple blind source separation approaches and identify linked cross-modal sources in multiple datasets. In this work, we utilized the multimodal independent vector analysis (MMIVA) model in MISA to directly identify meaningful linked features across three neuroimaging modalities-structural magnetic resonance imaging (MRI), resting state functional MRI and diffusion MRI-in two large independent datasets, one comprising of control subjects and the other including patients with schizophrenia.

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.

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.

Bringing Imaging Biomarkers Into Clinical Reality in Psychiatry.

Importance: Advancing precision psychiatry, where treatments are based on an individual's biology rather than solely their clinical presentation, requires attention to several key attributes for any candidate biomarker. These include test-retest reliability, sensitivity to relevant neurophysiology, cost-effectiveness, and scalability. Unfortunately, these issues have not been systematically addressed by biomarker development efforts that use common neuroimaging tools like magnetic resonance imaging (MRI) and electroencephalography (EEG).

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.

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.

Static and Dynamic Cross-Network Functional Connectivity Shows Elevated Entropy in Schizophrenia Patients.

Schizophrenia (SZ) patients exhibit abnormal static and dynamic functional connectivity across various brain domains. We present a novel approach based on static and dynamic inter-network connectivity entropy (ICE), which represents the entropy of a given network's connectivity to all the other brain networks. This novel approach enables the investigation of how connectivity strength is heterogeneously distributed across available targets in both SZ patients and healthy controls.

Adjustment of Regional Cortical Thickness Measures for Global Cortical Thickness Obscures Deficits Across the Schizophrenia Spectrum: A Cautionary Note About Normative Modeling of Brain Imaging Data.

Recent neuroimaging studies and publicly disseminated analytic tools suggest that regional morphometric analyses covary for global thickness. We empirically demonstrated that this statistical approach severely underestimates regional thickness dysmorphology in psychiatric disorders. Study 1 included 90 healthy control participants, 51 participants at clinical high risk for psychosis, and 78 participants with early-illness schizophrenia.

Structural white matter abnormalities in Schizophrenia and associations with neurocognitive performance and symptom severity.

Schizophrenia is associated with robust white matter (WM) abnormalities but influences of potentially confounding variables and relationships with cognitive performance and symptom severity remain to be fully determined. This study was designed to evaluate WM abnormalities based on diffusion tensor imaging (DTI) in individuals with schizophrenia, and their relationships with cognitive performance and symptom severity. Data from individuals with schizophrenia (SZ; n=138, mean age±SD=39.

Brain Age Gap in Early Illness Schizophrenia and the Clinical High-Risk Syndrome: Associations With Experiential Negative Symptoms and Conversion to Psychosis.

Background And Hypothesis: Brain development/aging is not uniform across individuals, spawning efforts to characterize brain age from a biological perspective to model the effects of disease and maladaptive life processes on the brain. The brain age gap represents the discrepancy between estimated brain biological age and chronological age (in this case, based on structural magnetic resonance imaging, MRI). Structural MRI studies report an increased brain age gap (biological age > chronological age) in schizophrenia, with a greater brain age gap related to greater negative symptom severity.

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.

Spectral graph model for fMRI: a biophysical, connectivity-based generative model for the analysis of frequency-resolved resting state fMRI.

Resting state functional MRI (rs-fMRI) is a popular and widely used technique to explore the brain's functional organization and to examine if it is altered in neurological or mental disorders. The most common approach for its analysis targets the measurement of the synchronized fluctuations between brain regions, characterized as functional connectivity (FC), typically relying on pairwise correlations in activity across different brain regions. While hugely successful in exploring state- and disease-dependent network alterations, these statistical graph theory tools suffer from two key limitations.

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.