2026 ECNP Congress

PS01-1038

Peripheral inflammation in bipolar disorder: impact of childhood trauma and metabolic dysregulation

Estêvão Scotti-Muzzi — L. Mendes, F. Baptista, P. Fernandez, G. de Moraes Rodrigues, M. Bravo Gonçalves, F. Costa, L. Silva Rodrigues, E. Cheniaux · Rio de Janeiro State University UERJ, Unit of Psychiaty- Pedro Ernesto University Hospital, Rio de Janeiro, Brazil

2026 ECNP Congress

Background

Bipolar disorder (BD) is a severe and disabling psychiatric illness affecting 1–3% of the population and is associated with high rates of comorbidity with metabolic syndrome (e.g., diabetes, dyslipidaemia, hypertension, and obesity), contributing to reduced life expectancy [1]. Despite advances in understanding its neurobiology, the underlying mechanisms remain incompletely defined. Converging evidence implicates fronto-limbic dysfunction alongside a state of low-grade systemic inflammation [2]. Childhood trauma—including emotional, physical, and sexual abuse, as well as emotional and physical neglect—is highly prevalent in BD and may contribute to immune dysregulation. Both metabolic abnormalities and early-life stress are potential modulators of inflammatory processes [3]. This study aimed to evaluate peripheral inflammatory biomarkers in BD across different mood states compared to healthy controls (HC), and to examine the influence of childhood trauma and metabolic dysregulation on these markers.

Methods

Peripheral inflammatory biomarkers were assessed in patients with BD across different mood states (euthymia, depression, and mania) and compared with HC without psychiatric or major clinical conditions. A total of 40 participants were included (BD = 23; HC = 17). Serum cytokines (IL-6, IL-8, IL-10, IL-12) were measured using cytometric bead array. Clinical assessments in the BD group included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), body mass index (BMI), and waist circumference. Participants were stratified according to mood state, presence of metabolic syndrome, and history of childhood trauma. Group differences were analyzed using analysis of variance or Kruskal–Wallis tests with Tukey-corrected post hoc comparisons.

Results

Individuals with BD showed significantly higher levels of IL-6 (p < 0.001) and IL-8 (p < 0.001) compared to HC, while no differences were observed for IL-10 or IL-12. Within the BD group, those with a history of childhood trauma exhibited significantly elevated IL-8 levels (p < 0.001) compared to those without trauma exposure. No significant differences in inflammatory markers were found across mood states or according to metabolic syndrome status. Additionally, no significant correlations were observed between interleukin levels and YMRS or HDRS scores, BMI, or waist circumference.

Conclusions

These findings support the presence of a pro-inflammatory profile in BD, characterized by elevated IL-6 and IL-8, cytokines involved in immune regulation and systemic inflammation. The lack of variation across mood states suggests that low-grade inflammation may represent a trait marker of BD, independent of current clinical status. Notably, the association between childhood trauma and increased IL-8 levels highlights the potential role of early-life stress in shaping long-term immune dysregulation. In contrast, no association was observed between inflammatory markers and metabolic syndrome in this sample, suggesting a more prominent contribution of stress-related mechanisms. Overall, these results support inflammation as a potential biomarker and therapeutic target in BD, with implications for stratification and personalized interventions, particularly in individuals with a history of childhood trauma.

References

1- Gimenez-Palomo, A., Gomes-da-Costa, S., Dodd, S., Pachiarotti, I., Verdolini, N., Vieta, E., & Berk, M. (2022). Does metabolic syndrome or its component factors alter the course of bipolar disorder? A systematic review. Neuroscience & Biobehavioral Reviews, 132, 142-153. 2- Benedetti, F., Aggio, V., Pratesi, M. L., Greco, G., & Furlan, R. (2020). Neuroinflammation in bipolar depression. Frontiers in psychiatry, 11, 71. 3- Guillen-Burgos HF, Montero N, Orozco I, Gamba G, Vanegas V, Uribe A, Morelli A, Moreno-Lopez SM, Galvez-Florez JF, and McIntyre RS (2026). Metabolic markers in bipolar disorder with childhood trauma exposure: a systematic review. CNS Spectrums, 31(1), e8, 1–11. https://doi.org/10.1017/S1092852926100881