Increased interleukin 18 activity in adolescents with early-onset psychosis is associated with cortisol and depressive symptoms

Kirsten Wedervang-Resell; Svein Friis; Vera Lonning; Runar E Smelror; Cecilie Johannessen; Elina J Reponen; Siv H Lyngstad; Tove Lekva; Pål Aukrust; Thor Ueland; Ole A Andreassen; Ingrid Agartz; Anne M Myhre

doi:10.1016/j.psyneuen.2019.104513

Increased interleukin 18 activity in adolescents with early-onset psychosis is associated with cortisol and depressive symptoms

Psychoneuroendocrinology. 2020 Feb:112:104513. doi: 10.1016/j.psyneuen.2019.104513. Epub 2019 Nov 14.

Authors

Affiliations

¹ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Department of Psychiatric Research and Development, Oslo University Hospital, Oslo, Norway. Electronic address: kirsten.wedervang-resell@medisin.uio.no.
² Division of Mental Health and Addiction, Department of Psychiatric Research and Development, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
⁴ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
⁶ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁷ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁸ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁹ Division of Mental Health and Addiction, Department of Psychiatric Research and Development, Oslo University Hospital, Oslo, Norway; Child and Adolescent Psychiatry Unit, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Norway.

PMID: 31761332
DOI: 10.1016/j.psyneuen.2019.104513

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 (R² change = 0.05) and the MFQ-C score (R² 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.

Keywords: Cortisol; Cytokines; IL-18; Immune system; Inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Age of Onset
Case-Control Studies
Child
Depression* / blood
Depression* / immunology
Depression* / physiopathology
Humans
Hydrocortisone / blood*
Intercellular Signaling Peptides and Proteins / blood*
Interleukin-18 / blood*
Interleukin-18 Receptor alpha Subunit / blood
Interleukin-18 Receptor beta Subunit / blood
Longitudinal Studies
Male
Psychotic Disorders* / blood
Psychotic Disorders* / immunology
Psychotic Disorders* / physiopathology

Substances

IL18 protein, human
IL18R1 protein, human
IL18RAP protein, human
Intercellular Signaling Peptides and Proteins
Interleukin-18
Interleukin-18 Receptor alpha Subunit
Interleukin-18 Receptor beta Subunit
interleukin-18 binding protein
Hydrocortisone