Abstract
Early-onset schizophrenia (EOS) patients are at greater risk of poor long-term outcomes compared to later-onset patients, so it is essential to identify unique pathomechanisms and prognostic biomarkers for this EOS patient group. Deficits in neurotrophic and oxidative stress resistance are implicated in EOS, so this study investigated associations of EOS risk with peripheral blood platelet-derived growth factor (PDGF) subtype concentrations and superoxide dismutase (SOD) isoenzyme activities. Serum PDGF subtype concentrations and plasma SOD isoenzyme activities were measured in 99 first-episode drug-naïve EOS patients (ages 12-18 years) and 40 matched healthy controls (HCs). Disease severity was assessed using the five-factor model of the Positive and Negative Syndrome Scale (positive, negative, cognitive, excitement/hostility, and anxiety/depression). Serum PDGF-AB and PDGF-BB concentrations, as well as plasma total (T)-SOD and Mn-SOD activities, were significantly lower in EOS patients than HCs (all, P < 0.001 except for T-SOD, where P = 0.003). Serum PDGF-AB concentration was positively correlated with plasma Mn-SOD activity (r = 0.267, P = 0.007), while serum PDGF-BB concentration was negatively correlated with cognitive symptom severity (r = -0.406, P < 0.001), and T-SOD activity was negatively correlated with excitement/hostility symptom severity (r = -0.354, P < 0.001). Multivariate analysis with dichotomized factors identified low PDGF-AB (RR = 1.788, 95% CI: 1.226-2.608, P = 0.003), low PDGF-BB (RR = 1.758, 95% CI: 1.208-2.558, P = 0.003), and a significant PDGF-AB × Mn-SOD interaction (RR = 1.460, 95% CI: 1.044-2.042, P = 0.027) as independent EOS risk factors, with 44.1%, 43.1%, and 31.5% attributable risk, respectively, and population attributable risk fractions of 34.5%, 33.7%, and 23.6%, respectively. Reduced PDGF and SOD levels may contribute to the earlier onset of schizophrenia symptoms and exacerbate symptom severity. Peripheral blood PDGF concentrations and SOD activities may thus be valuable biomarkers for EOS detection.