Age of onset and intrinsic neural timescales in first‐episode schizophrenia

AIM: To investigate abnormal patterns of intrinsic neural timescales (INT) in first-episode schizophrenia across different ages of onset, with a focus on differences in neural temporal-dynamic characteristics between early-onset and adult-onset patients. METHODS: We collected resting-state fMRI data from 231 first-episode schizophrenia patients (early-onset, n = 122; adult-onset, n = 109) and 153 healthy controls (younger controls, n = 61; older controls, n = 92). INT was computed from the autocorrelation function of the fMRI signal. A two-way ANOVA tested the Diagnosis × Age-of-onset interaction. Further analyses included between-group comparisons, correlation analyses, and imaging transcriptomic analysis. RESULTS: Fourteen region of interests (ROIs) showed significant interaction effects (P < 0.05/264), predominantly located within the default mode network (DMN, 9 ROIs), with additional involvement of sensorimotor, frontoparietal, memory retrieval, and dorsal attention networks. Group comparisons indicated that early-onset patients exhibited more widespread INT reductions across multiple regions relative to age-matched controls, whereas INT abnormalities in adult-onset patients were more restricted and primarily centered on the DMN. Interaction effects on INT were possibly associated with gene enrichment related to chemical synaptic transmission, glutamatergic signaling, and calcium/calmodulin-dependent kinase activity. CONCLUSION: INT abnormalities in first-episode schizophrenia are dependent on age of onset: the early-onset subtype shows widespread shortening of timescales across multiple brain networks, suggesting broad neurodevelopmental compromise, whereas the adult-onset subtype exhibits more focal abnormalities centered on the DMN. These findings suggested that INT may serve as a potential neuroimaging biomarker for distinguishing onset-age subtypes, aiding precise stratification and mechanistic studies of schizophrenia.