Interleukin-17 potentially links prolactin to positive symptoms in first-episode drug-naive schizophrenia: An exploratory cross-sectional study.

The immune-inflammation hypothesis of schizophrenia has gained considerable support, yet the role of endocrine-immune interplay remains unclear. Prolactin, a stress-responsive hormone with immunomodulatory properties, is elevated in first-episode drug-naive (FEDN) schizophrenia independently of antipsychotic exposure. We hypothesized that increased prolactin may contribute to symptom severity and cognitive dysfunction by modulating specific inflammatory cytokines, with potential implications for schizophrenia pathophysiology. This study examined prolactin and inflammatory cytokines in 50 FEDN schizophrenia patients and 52 healthy controls (HCs), and evaluated both between-group differences and within-patient associations with clinical features. Patients exhibited elevated prolactin levels and altered inflammatory profiles, including increased IFN-γ and relatively lower IL-8 and IL-12p70 levels. Although IL-17 was numerically lower in patients in the crude comparison, this between-group difference was attenuated after covariate adjustment. Within the patient group, lower IL-17 levels were nominally associated with higher prolactin levels and more severe positive symptoms. Mediation identified a significant indirect effect involving IL-17 in the association between prolactin and positive symptoms, indicating its possible involvement in linking endocrine dysregulation to symptom severity. These exploratory findings suggest that IL-17 may be relevant to within-patient symptom-related processes, and provide preliminary evidence for endocrine-immune interactions in schizophrenia that warrant replication in larger samples.