Dual immune dysregulation in adolescent-onset schizophrenia: attenuated B cell trophic support and elevated IL-23/Th17 inflammation are diagnostic and clinical biomarkers.

Abstract

Adolescent-onset schizophrenia (AOS) is marked by severe symptoms and cognitive impairments, yet its peripheral immune profile remains insufficiently characterized. This cross-sectional study aimed to develop composite immune pathway indices integrating serum B cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), interleukin (IL)-23, and IL-17 levels to reflect immune dysfunction. We examined 93 patients with first-episode, antipsychotic-naive AOS and 40 healthy controls. Five indices were constructed: immune homeostasis protection index (IHPI), BAFF-APRIL immune ratio (BAIR), immune drive-attenuation ratio (IDA), Th17 decoupling index (TDI), and full immune imbalance index (FIII). Serum BAFF (t = -3.324, P = 0.001) and APRIL (t = -3.687, P < 0.001) were significantly reduced and IL-23 was increased (Z = -2.777, P = 0.005), whereas IL-17 remained unchanged (P = 0.292) in patients with AOS. BAIR did not differ between groups (P = 0.741). IHPI was significantly reduced in patients with AOS (t = -5.203, P < 0.001), whereas IDA, TDI, and FIII were elevated (all P < 0.001). Serum IL-23 was independently associated with Positive and Negative Syndrome Scale total score (β = 0.321, P = 0.002) and general psychopathology subscale score (β = 0.320, P = 0.001). In healthy controls, serum BAFF predicted immediate memory (β = 0.408, P = 0.009) and Repeatable Battery for the Assessment of Neuropsychological Status total score (β = 0.444, P = 0.005), an association not observed in patients with AOS. Among composite indices, IHPI achieved the best discriminative performance (AUC = 0.751, sensitivity: 69.9%, and specificity: 72.5%), outperforming individual biomarkers. These findings indicated that dual peripheral immune dysregulation in AOS was characterized by attenuated B cell trophic support and upstream IL-23/Th17 activation, and suggested that composite immune indices may provide incremental diagnostic value over single cytokines.