Immunological predictors in first-episode psychosis: findings from one-year prospective follow-up study

Emerging evidence suggests that immune dysregulation may play a key role in the pathophysiology of psychosis. However, longitudinal studies integrating both innate and adaptive immune components in the same sample remain scarce. This study aimed to examine a broad spectrum of immunological parameters in first-episode psychosis (FEP) patients, both at onset and after treatment, in comparison to healthy controls.

Thirty-two minimally treated FEP patients (no lifetime psychotropic exposure >1 month) and 26 healthy controls were assessed at baseline. 20 patients completed a follow-up approximately one year later. Immunological markers – including complete blood count (leukocyte, neutrophil, lymphocyte, monocyte), C-reactive protein (CRP), SAA, complement components (C3, C4), and immunoglobulins (IgG, IgA, IgM, IgE) – were measured at both time points. First-episode psychosis was confirmed using SCID (DSM-IV). Symptom severity was evaluated using PANSS and BPRS. ROC and logistic regression analyses were performed to assess predictive value.

Neutrophil, monocyte, C3, C4 levels and neutrophil-to-lymphocyte ratio (NLR) were significantly elevated in patients at both time points, with no change over time. CRP was elevated at T1 but normalised at follow-up. In contrast, immunoglobulin levels showed temporal and dimensional associations with symptom severity. NLR was correlated with negative symptoms during the acute phase, while IgG was associated with positive symptoms during remission. Elevated NLR and C4 predicted patient status in logistic regression analysis.

This longitudinal study provides a system-level immunological profile across illness phases in FEP. The findings underscore distinct and dynamic contributions of innate and adaptive immunity to the onset and progression of psychosis.