Multimodal brain deficits shared in early‐onset and adult‐onset schizophrenia predict positive symptoms regardless of illness stage

Incidence of schizophrenia (SZ) has two predominant peaks, in adolescent and young adult. Early‐onset schizophrenia provides an opportunity to explore the neuropathology of SZ early in the disorder and without the confound of antipsychotic mediation. However, it remains unexplored what deficits are shared or differ between adolescent early‐onset (EOS) and adult‐onset schizophrenia (AOS) patients. Here, based on 529 participants recruited from three independent cohorts, we explored AOS and EOS common and unique co‐varying patterns by jointly analyzing three MRI features: fractional amplitude of low‐frequency fluctuations (fALFF), gray matter (GM), and functional network connectivity (FNC). Furthermore, a prediction model was built to evaluate whether the common deficits in drug‐naive SZ could be replicated in chronic patients. Results demonstrated that (1) both EOS and AOS patients showed decreased fALFF and GM in default mode network, increased fALFF and GM in the sub‐cortical network, and aberrant FNC primarily related to middle temporal gyrus; (2) the commonly identified regions in drug‐naive SZ correlate with PANSS positive significantly, which can also predict PANSS positive in chronic SZ with longer duration of illness. Collectively, results suggest that multimodal imaging signatures shared by two types of drug‐naive SZ are also associated with positive symptom severity in chronic SZ and may be vital for understanding the progressive schizophrenic brain structural and functional deficits.