RESUMEN
Background: Early 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. Methods: A 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. Results: In 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. Conclusions: This 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.
RESUMEN
BACKGROUND: Patients with early psychosis (EP) (within 3 years after psychosis onset) show significant variability, which makes predicting outcomes challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, which limits the development of early interventions. METHODS: A data-driven approach, partial least squares correlation, was used across 2 independent datasets to examine multivariate relationships between white matter properties and symptomatology and to identify stable and generalizable signatures in EP. The primary cohort included patients with EP from the Human Connectome Project for Early Psychosis (n = 124). The replication cohort included patients with EP from the Feinstein Institute for Medical Research (n = 78) as part of the MEND (Multimodal Evaluation of Neural Disorders) Project. Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders. RESULTS: In both cohorts, a significant latent component corresponded to a symptom profile that combined negative symptoms, primarily diminished expression, with specific somatic symptoms. Both latent components captured comprehensive features of white matter disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the partial least squares 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. CONCLUSIONS: This data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural white matter alterations in EP across diagnoses and datasets, showing strong covariance of these alterations with a unique profile of negative and somatic symptoms. These findings suggest the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.