Decreased serum IGFBP-7 level is associated with cognitive impairment in first-episode drug-naïve adolescent-onset schizophrenia

Adolescent-onset schizophrenia (AOS) is characterized by severe cognitive impairment. Insulin-like growth factor binding protein-7 (IGFBP-7), a biomarker of vascular aging and neuroinflammation, and hepatocyte growth factor (HGF), involved in neurodevelopment, have been linked to cognitive decline, but their roles in AOS remain unexplored. This case–control study enrolled 91 first-episode drug-naïve AOS patients and 40 healthy controls. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and its five-factor model, and cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). AOS patients exhibited significantly lower serum IGFBP-7 levels compared to healthy controls (10.15 ± 3.62 vs. 11.75 ± 3.41 ng/mL, t = -2.377, P = 0.019), while HGF levels showed no significant difference (P > 0.05). IGFBP-7 levels were negatively correlated with PANSS cognitive factor scores (r = -0.308, P = 0.003) and positively correlated with RBANS total scores (r = 0.353, P = 0.001). IGFBP-7 was independently associated with RBANS total score (β = 0.284, P = 0.002) after controlling for confounding factors. Sex (β = 0.467, t = 5.325, P < 0.001) was identified as a confounder but did not moderate the IGFBP-7-cognition relationship (P > 0.05). Modified Poisson regression revealed that low IGFBP-7 levels independently predicted AOS risk (RR = 1.298, 95% CI: 1.037–1.624, P = 0.023), with attributable fractions of 23.0% in exposed individuals and 12.7% in the overall population. Decreased serum IGFBP-7 levels are associated with cognitive impairment in AOS and represent a significant risk factor, suggesting IGFBP-7 as a potential biomarker for cognitive dysfunction in AOS.