2026 ECNP Congress

PS04-4230

Cytokines in first-episode psychosis

t.b.a. — J. Petrovic, S. Tosic Golubovic, F. Petrovic, M. Stevanovic · University Clinical Center- Psychiatry Clinic, Psychiatry, Nis, Serbia

2026 ECNP Congress

Background

Immune dysregulation has been increasingly implicated in the pathophysiology of schizophrenia spectrum disorders, with growing evidence supporting the role of inflammatory processes in the onset and progression of psychosis. [1,2] This is particularly relevant in first-episode psychosis (FEP), a clinical stage that is less affected by confounding factors such as chronic illness, prolonged antipsychotic treatment, and lifestyle-related influences. Cytokines, as key regulators of immune and inflammatory responses, have been proposed as potential peripheral biomarkers that may reflect central neurobiological alterations. [3] Their investigation in drug-naïve patients may provide valuable insight into early pathophysiological mechanisms and help identify clinically relevant biological signatures.

Objectives

The primary aim of this study was to evaluate serum levels of interleukins IL-1β, IL-2, IL-6, and IL-10 in drug-naïve patients with FEP compared to healthy controls. A secondary aim was to examine the associations between cytokine levels and clinical dimensions, including positive and negative symptoms, general psychopathology, aggressive behavior, and overall functional status.

Methods

The study included 60 participants: 38 patients experiencing their first psychotic episode who had not received prior pharmacological treatment, and 22 age- and sex-matched healthy controls. Blood samples were collected prior to the initiation of antipsychotic therapy. Serum cytokine concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical assessment was performed using the Positive and Negative Syndrome Scale (PANSS) to evaluate symptom severity, the Modified Overt Aggression Scale (MOAS) for aggression, and the Global Assessment of Functioning (GAF) scale for overall functioning. Statistical analyses included between-group comparisons, correlation analyses to explore associations between biological and clinical variables, and receiver operating characteristic (ROC) analysis to assess the discriminative ability of cytokines.

Results

Patients with FEP exhibited significantly elevated serum levels of IL-1β, IL-2, and IL-10 compared to healthy controls (all p < 0.01), indicating the presence of a distinct inflammatory profile in early psychosis. No statistically significant difference was observed for IL-6 levels between the two groups. ROC analysis demonstrated that IL-2 had the highest discriminative capacity for distinguishing FEP patients from controls (AUC = 0.83), suggesting its potential utility as a biomarker. Higher IL-2 levels were significantly associated with increased severity of positive symptoms, while IL-10 levels were positively correlated with negative symptoms and general psychopathology scores. In addition, elevated IL-1β levels were associated with lower GAF scores, reflecting reduced global functioning. Cytokine levels also showed associations with aggressive behavior, supporting their broader clinical relevance across multiple symptom domains.

Conclusions

These findings indicate that drug-naïve FEP is characterized by a specific inflammatory signature, with IL-2 emerging as a particularly promising candidate biomarker. The observed relationships between cytokine levels and clinical symptom dimensions underscore the importance of immune dysregulation in the early stages of psychotic disorders. [4] Incorporating inflammatory markers into clinical assessment frameworks may enhance diagnostic precision, improve patient stratification, and support the development of targeted immunomodulatory treatment strategies [5] aimed at optimizing outcomes in early psychosis.

References

  1. Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. (2011). Meta-analysis of cytokine alterations in schizophrenia. Biological Psychiatry, 70(7):663–671.
  2. Upthegrove R, Manzanares-Teson N, Barnes NM. (2014). Cytokine function in medication-naïve first episode psychosis. Schizophrenia Research, 155(1–3):101–108.
  3. Khandaker GM, Dantzer R, Jones PB. (2017). Immunopsychiatry: important facts. Psychological Medicine, 47(13):2229–2237.
  4. Goldsmith DR, Rapaport MH, Miller BJ. (2016). A meta-analysis of blood cytokine network alterations in psychiatric patients. Molecular Psychiatry, 21(12):1696–1709.
  5. Mondelli V, Vernon AC, Turkheimer F, Dazzan P, Pariante CM. (2017). Brain microglia in psychiatric disorders. Lancet Psychiatry, 4(7):563–572.