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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.