2026 ECNP Congress

PS03-3119

Selective cytokine alterations in depression: reduced IL-8 and its association with chronic stress

Defne Ertuna — S. Karslıoğlu, B. Tekirdağlı, A. Ercan Doğan, E.C. Çiftçi Ertürk, S.S. Kırlıoğlu Balcıoğlu, Ö. Albayrak, H. Yapıcı Eser · Koc University, Neuroscience, Istanbul, Türkiye

2026 ECNP Congress

Objectives

Depression is a psychiatric disorder characterized by a persistently depressed mood and loss of interest in activities, along with and appetite changes, fatigue, cognitive impairments, and suicidal ideation [1]. It arises from multifaceted biological alterations involving the hypothalamic–pituitary–adrenal (HPA) axis, dysregulation of key neurotransmitter systems (serotonin, glutamate, dopamine, and γ-aminobutyric acid [GABA]), and disrupted functional connectivity within networks such as the default mode network (DMN) [2]. Converging evidence further implicates neuroinflammation in the pathophysiology of mood disorders, including depression, with findings of aberrant immune responses to pathogen-associated molecular patterns (PAMPs) and elevated pro-inflammatory cytokines [3]. A subset of patients exhibits low-grade systemic inflammation, reflected by increased interleukin-6 (IL-6) and C-reactive protein (CRP) levels [4]. However, this “inflamed” profile of depression remains inconsistent and heterogeneous across studies. Aim of the study was to compare peripheral cytokine levels and explore their association between measures of chronic stress and childhood life adversities in patients diagnosed with depression and matched controls.

Methods

32 individuals diagnosed with depression and 30 healthy, age, sex and body mass index (BMI) matched controls were recruited. Eligible participants were aged 18-55 years with a BMI between 18.5-40. Exclusion criteria were having an autoimmune, endocrine or neurological disorder, being diagnosed with schizophrenia or bipolar disorder, and using psychiatric medication or any psychotropic medication. A structural clinical interview (SCID-5) was conducted for a clinical diagnosis. Participants completed psychological assessment scales, and blood samples were taken between 9-11AM. Cytokines in the serum samples were quantified using a multiplex assay.

Results

Cytokine levels (IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33) did not show significant differences between the depression and control groups (p > .05), except for IL-8, which was significantly lower in the depression group (U = 237.50, Z =-3.591, p < .001). No statistically significant correlations of cytokine levels were found between measures of childhood life adversities and perceived stress scores (p>0.05 multiple comparison corrected). However, within the patient group, IL-8 levels were found to increase as Chronic Stress Scale (CSS) total scores increased (r =0.512, p =0.004).

Conclusions

These findings suggest that immune dysregulation in depression extends beyond a nonspecific pro-inflammatory state, instead reflecting selective, pathway-specific alterations that may be modulated by stress-related mechanisms. The observed decrease in IL-8 in our sample may indicate a compensatory downregulation of pro-inflammatory signaling over time, potentially serving to mitigate the detrimental effects of chronic inflammation. This interpretation is consistent with prior studies reporting variable IL-8 dynamics depending on clinical context, sex, and biological conditions [5]. Collectively, these results support a model of depression as a dynamically integrated condition, in which immune, stress-related, and neurobiological systems interact in a context-dependent manner, contributing to its heterogeneity and the emergence of distinct biological subtypes. Studies with larger sample size and follow up are needed.

References

  1. American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders (5th ed., DSM-5-TR). American Psychiatric Association https://doi.org/10.1176/appi.books.9780890425787
  2. Hassamal, S. (2023). Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories. Frontiers in Psychiatry, 14, 1130989. https://doi.org/10.3389/fpsyt.2023.1130989
  3. Milaneschi, Y., Kappelmann, N., Ye, Z., Lamers, F., Moser, S., Jones, P. B., Burgess, S., Penninx, B. W. J. H., & Khandaker, G. M. (2021). Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts. Molecular Psychiatry, 26(12), 7393–7402. https://doi.org/10.1038/s41380-021-01188-w
  4. Wieck, A., Grassi-Oliveira, R., Prado, C. H. D., Viola, T. W., Petersen, L. E., Porto, B., Teixeira, A. L., & Bauer, M. E. (2016). Toll-like receptor expression and function in type I bipolar disorder. Brain Behavior and Immunity, 54, 110–121. https://doi.org/10.1016/j.bbi.2016.01.011
  5. João, R.B., Toiansk de Azevedo, J.P.R.P., Pereira, D.A., Ragazzo, P.C. and de Oliveira, P.M. (2025) Immune-inflammatory, neuroplastic, and epigenetic effects of electroconvulsive therapy in mood disorders: an overview of recent studies.Frontiers in Psychiatry 16, 1577530. doi: 10.3389/fpsyt.2025.1577530