Medication and atypical brain maturation in psychosis associated with long-term cognitive decline and symptom progression

作者：Claudio Alemán-Morillo, Natalia García-San-Martín, Richard A. I. Bethlehem, Lena Dorfschmidt, María Alemany-Navarro, Patricia Segura, Alessia Pasquini, Manuel Muñoz‐Caracuel, Manuel Canal-Rivero, Jakob Seidlitz, Rosa Ayesa‐Arriola, Javier Vázquez-Bourgón, John Suckling, Miguel Ruíz-Veguilla, Benedicto Crespo‐Facorro, Rafael Romero-García · 发表于：The British Journal of Psychiatry · 年份：2025 · DOI：10.1192/bjp.2025.10482 · 被引用次数：2 · 研究领域：Functional Brain Connectivity Studies、Schizophrenia research and treatment、Epilepsy research and treatment

BACKGROUND: Clinical progression during psychosis has been closely associated with grey matter abnormalities resulting from atypical brain development. However, the complex interplay between psychopathology and heterogeneous maturational trajectories challenges the identification of neuroanatomical features that anticipate symptomatic decline. AIMS: To investigate cortical volume longitudinal deviations in first-episode psychosis (FEP) using normative modelling, exploring their relationship with long-term cognitive and symptomatic outcomes, as well as their cytoarchitectural and neurobiological underpinnings. METHOD: We collected magnetic resonance imaging (MRI), cognitive and symptomatic data from 195 healthy controls and 357 drug-naïve or minimally medicated FEP individuals that were followed up 1, 3, 5 and 10 years following the first episode (1209 MRI scans and assessments in total). Using normative modelling, we derived subject-specific centile scores for cortical volume to investigate atypical deviations in FEP and their relationship to long-term cognitive and symptomatic deterioration. The resulting centile association maps were further characterised by examining their cytoarchitectural and neurobiological attributes using normative atlases. RESULTS: FEP centiles demonstrated a widespread reduction at treatment initiation, with longitudinal analysis showing an increase during treatment time, indicating convergence towards normal maturation trajectories. Interestingly, ...