Longitudinal investigation of the T helper (Th)1-Th2 balance and complement system in clinical high risk for psychosis cohort

The T Helper (Th)1-Th2 imbalance has been observed during the transition from the clinical high-risk (CHR) state to psychosis. However, it remains unclear whether the complement system influences this imbalance during psychosis onset. This study aimed to investigate the dynamic interplay between complement activation and the Th1-Th2 balance during the progression of psychosis. A prospective case-control study was conducted to evaluate the Th1-Th2 balance, as indicated by interleukin(IL)-1Beta and IL-6 levels, in 49 individuals at CHR for psychosis and 26 age- and sex-matched healthy controls(HC). Based on the Th1-Th2 balance, the samples were divided into two groups: Th1 > Th2 and Th1 < Th2. Additionally, the levels of thirteen complement proteins (C1q, C2, C3, C3b, C4, C4b, C5, C5a, factor B, D, I, H, and Mannose-Binding Lectin) were measured at baseline. Correlations between cytokines and complement factors were examined, and longitudinal changes were assessed through a 1-year follow-up period. At baseline, significant differences were observed in complement characteristics (C4, C4b, C5, and B) between Th1 > Th2 and Th1 < Th2 balance states, highlighting variations in complement factors between the CHR and HC groups. In the CHR group, a negative association was noted between Th1-Th2 balance and complement factors, with significant correlations observed for components C4b, C5, I, C3, C4, and B. However, no significant correlation was found in the HC group. At follow-up, the Th1 < Th2 group exhibited a higher proportion of CHR individuals who converted to psychosis compared to the Th1 > Th2 group, indicating a significant association between Th1-Th2 balance and the onset of psychosis (χ² = 12.09, p = 0.001). This shift in balance was notably linked to baseline complement C4b and C4 levels. Our study reveals a complex interplay between complement and inflammatory factor balance in psychosis onset, highlighting the potential role of complement, particularly associated with baseline C4b and C4 levels, in modulating Th1-Th2 balance and contributing to the pathogenesis of psychosis.