Accumulating evidence suggests that a disruption of early brain development,in which insulin-like growth factor-2(IGF-2)has a crucial role,may underlie the pathophysiology of schizophrenia.Our previous study has shown that decreased serum IGF-2 was correlated with the severity of psychopathology in patients with schizophrenia.Here we conducted a prospective observation trial to investigate the effects of atypical antipsychotics on serum IGF-2 level and its relationship with clinical improvements in schizophrenia patients.Thirty-one schizophrenia patients with acute exacerbation and 30 healthy individuals were recruited in this study.Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale(PANSS)and serum IGF-2 levels were determined using ELISA.We found that schizophrenia patients with acute exacerbation had lower serum IGF-2 levels than control individuals at baseline(P＜0.05).After 2 months of atypical antipsychotic treatment,a significant improvement in each PANSS subscore and total score was observed in patients(all P＜0.01),and the serum IGF-2 levels of patients were significantly increased compared with those at baseline(203.13±64.62 vs.426.99±124.26 ng/mL;t=-5.044,P＜0.001).Correlation analysis revealed that the changes of serum IGF-2 levels in patients were significantly correlated with the improvements of negative symptoms(r=-0.522,P=0.006).Collectively,our findings demonstrated changes of serum IGF-2 response to improvements of negative symptoms in schizophrenia patients treated with atypical antipsychotics,suggesting that serum IGF-2 might be a treatment biomarker for schizophrenia.