Objective: Age of onset is one of the heterogeneous factors in schizophrenia, and an earlier onset of the disease indicated a worse prognosis. The left superior frontal gyrus (SFG) is involved in numerous cognitive and motor control tasks. Hence, we explored the relationship between abnormal changes in SFG resting-state functional connectivity (rsFC) and cognitive function in the peak age of incidence to understand better the pathophysiological mechanism in youth-onset drug-naïve schizophrenia to search for reliable biomarkers.

Methods: About 66 youth-onset drug-naïve schizophrenia patients and 59 healthy controls (HCs) were included in this study. Abnormal connectivity changes in the left SFG and whole brain were measured using the region of interest (ROI) rsFC analysis method. The cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB), and the severity of the clinical symptoms was evaluated by positive and negative syndrome scale (PANSS). Furthermore, we analyzed the relationships among abnormal FC values, cognition scores, and clinical symptoms.

Results: We found decreased FC between left SFG and bilateral precuneus (PCUN), right hippocampus, right parahippocampal gyrus, left thalamus, left caudate, insula, and right superior parietal lobule (SPL), whereas increased FC was seen between the left SFG and right middle frontal gyrus (MFG) in the youth-onset drug-naïve schizophrenia group, compared with HCs. Meanwhile, the T-scores were lower in each cognitive domain than HCs. Moreover, in the youth-onset drug-naive schizophrenia group, the insula was negatively correlated with processing speed. No significant correlations were found between the FC-value and PANSS score.

Conclusions: Our findings suggest widespread FC network abnormalities in the left SFG and widespread cognitive impairments in the early stages of schizophrenia. The dysfunctional connectivity of the left SFG may be a potential pathophysiological mechanism in youth-onset drug-naïve schizophrenia.