Increased interleukin 18 activity in adolescents with early-onset psychosis is associated with cortisol and depressive symptoms. (February 2020)

• Record Type: Journal Article
• Authors: Wedervang-Resell, Kirsten; Friis, Svein; Lonning, Vera; Smelror, Runar E.; Johannessen, Cecilie; Reponen, Elina J.; Lyngstad, Siv H.; Lekva, Tove; Aukrust, Pål; Ueland, Thor; Andreassen, Ole A.; Agartz, Ingrid; Myhre, Anne M.
• Is Part Of: Psychoneuroendocrinology. Volume 112(2020)
• Publication Date: 2020-02
• Subjects: Cortisol -- Immune system -- Cytokines -- Inflammation -- IL-18; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2019.104513
• Languages: English
• ISSNs: 0306-4530

Abstract

Highlights: Adolescents with early-onset psychosis (EOP) have elevated levels of circulating IL-18. Elevated IL-18/IL-18BP ratio suggest increased activity in the IL-18 system in patients with EOP. Cortisol and depressive symptoms contributed to the variance in the IL-18/IL-18BP ratio. Abstract: Objective: Evidence indicates that the pathophysiology of adult psychosis involves immune dysregulation, but its associations with stress are often not considered. The inflammatory cytokine interleukin (IL)-18, which is elevated in adult schizophrenia, is suggested to be sensitive to stress. We compared the associations of IL-18 with cortisol and clinical variables in adolescents with early-onset psychosis (EOP) aged 12–18 years and age-matched healthy controls (HC). Method: We measured serum IL-18, IL-18 binding protein (IL-18BP), IL-18 receptor accessory protein (IL-18RAP), IL-18 receptor 1 (IL-18R1) and cortisol, and calculated the IL-18/IL-18BP ratio in patients (n = 31) and HC (n = 60). Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale and depressive symptoms by the Mood and Feelings Questionnaire-Child version (MFQ-C). Bivariate correlation analysis was used to explore relationships between IL-18/IL-18BP ratio and cortisol, depression and other clinical characteristics. Hierarchical multiple linear regression analysis was used to assess their individual contributions to the variance of the IL-18/IL-18BP ratio. Results: Patients had significantly higher IL-18 levels and IL-18/IL-18BP ratios than HC, but similar IL-18BP, IL-18RAP and IL-18R1. Both cortisol (R 2 change = 0.05) and the MFQ-C score (R 2 change = 0.09) contributed significantly to the variance in IL-18/IL-18BP ratios after controlling for confounders. Conclusion: We found increased IL-18 system activity in adolescents with EOP. Cortisol and depressive symptoms each contributed to the variance in the IL-18/IL-18BP ratio. Our findings support activation of inflammatory pathways in adolescent psychosis and suggest interactions between stress, inflammation and depressive symptoms in EOP.