Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts
Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts
Abstract BackgroundEarly Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions. MethodsA data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP. The primary cohort included EP patients from the Human Connectome Project-Early Psychosis (n=124). The replication cohort included EP patients from the Feinstein Institute for Medical Research (n=78). Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders. ResultsIn both cohorts, a significant latent component (LC) corresponded to a symptom profile combining negative symptoms, primarily diminished expression, with specific somatic symptoms. Both LCs captured comprehensive features of WM disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the PLS model trained on the primary cohort accurately predicted microstructural features and symptoms in the replication cohort. Findings were not driven by diagnosis, medication, or substance use. ConclusionsThis data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural WM alterations in EP, across diagnoses and datasets, showing a strong covariance of these alterations with a unique profile of negative and somatic symptoms. This finding suggests the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.
Schleifer Charles H.、Liu Zhen-Qi、Hegarty Catherine E.、Leathem Logan、Boeck Thomas P.、Thies Melanie Blair、Wang Haley R.、McKinney Rachel A.、Misic Bratislav、Karlsgodt Katherine H.、Currin Danielle、Patel Pooja K.、Nakua Hajer、Bearden Carrie E.、DeRosse Pamela
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California||David Geffen School of Medicine, University of CaliforniaMontr¨|al Neurological Institute, McGill UniversityDepartment of Psychology, University of CaliforniaDepartment of Psychology, University of CaliforniaDepartment of Psychology, University of CaliforniaDepartment of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer CenterDepartment of Psychology, University of California||Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of CaliforniaDepartment of Psychology, University of CaliforniaMontr¨|al Neurological Institute, McGill UniversityDepartment of Psychology, University of California||Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of CaliforniaDepartment of Psychology, University of CaliforniaDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California||Desert Pacific Mental Illness Research, Education, and Clinical Center Greater Los Angeles VA Healthcare SystemCentre for Addiction and Mental Health||Institute of Medical Science, University of TorontoDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California||Department of Psychology, University of CaliforniaDepartment of Psychology, Stony Brook University
神经病学、精神病学医学研究方法基础医学
PsychopathologyWhite Matter microstructureDiffusion-weighted ImagingEarly PsychosisNegative SymptomsClinical heterogeneity
Schleifer Charles H.,Liu Zhen-Qi,Hegarty Catherine E.,Leathem Logan,Boeck Thomas P.,Thies Melanie Blair,Wang Haley R.,McKinney Rachel A.,Misic Bratislav,Karlsgodt Katherine H.,Currin Danielle,Patel Pooja K.,Nakua Hajer,Bearden Carrie E.,DeRosse Pamela.Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts[EB/OL].(2025-03-28)[2025-06-24].https://www.biorxiv.org/content/10.1101/2024.05.10.593636.点此复制
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