Frequency-specific alteration of functional connectivity density in antipsychotic-naive adolescents with early-onset schizophrenia

Early-onset schizophrenia (EOS) is a severe mental illness associated with dysconnectivity that widespread in the brain. However, the functional dysconnectivity in EOS are still mixed. Recently, studies have identified that functional connectivity (FC) arises from a band-limited slow rhythmic mechanism and suggested that the dysconnectivity at specific frequency bands may provide more robust biomarkers for schizophrenia. The frequency-specific changes of FC pattern in EOS remain unclear. To address this issue, resting-state functional magnetic resonance imaging data scans from 39 EOS patients (drug-naive) and 31 healthy controls (HCs) were used to assess the FC density (FCD) across slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz). Results revealed that a remarkable difference between the FCD of the two bands existed mainly in the default mode network (DMN) and subcortical areas. Compared with the HCs, EOS patients showed significantly altered FCD involved in audiovisual information processing, sensorimotor system, and social cognition. Importantly, a significant frequency-by-group interaction was observed in the left precuneus with significantly lower FCD in the slow-4 frequency band, but no significant effect in the slow-5 frequency band. In addition, decreased FC was found between the precuneus and other DMN regions in the slow-4 band. Furthermore, the change in FCD in precuneus was inversely proportional to the clinical symptom in slow-4 band, indicating the key role of precuneus in schizophrenia progress. Our findings demonstrated that the dysconnectivity pattern in EOS could be frequency-dependent.