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

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Increased interleukin 18 activity in adolescents with early-onset psychosis is associated with cortisol and depressive symptoms
Psychoneuroendocrinology ( IF 3.7 ) Pub Date : 2020-02-01 , DOI: 10.1016/j.psyneuen.2019.104513
Kirsten Wedervang-Resell ₁ , Svein Friis ₂ , Vera Lonning ₃ , Runar E Smelror ₃ , Cecilie Johannessen ₃ , Elina J Reponen ₄ , Siv H Lyngstad ₄ , Tove Lekva ₅ , Pål Aukrust ₆ , Thor Ueland ₇ , Ole A Andreassen ₄ , Ingrid Agartz ₈ , Anne M Myhre ₉

Affiliation

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.
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.
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.
NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
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.
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.
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.
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.

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.

中文翻译：

患有早发性精神病的青少年的白细胞介素 18 活性增加与皮质醇和抑郁症状有关

目的证据表明，成人精神病的病理生理学涉及免疫失调，但通常不考虑其与压力的关联。炎症细胞因子白细胞介素 (IL)-18 在成人精神分裂症中升高，被认为对压力敏感。我们比较了 12-18 岁早发性精神病 (EOP) 青少年和年龄匹配的健康对照 (HC) 中 IL-18 与皮质醇和临床变量的关联。方法测定血清IL-18、IL-18结合蛋白（IL-18BP）、IL-18受体辅助蛋白（IL-18RAP）、IL-18受体1（IL-18R1）和皮质醇，计算IL-18患者 (n = 31) 和 HC (n = 60) 中的 /IL-18BP 比率。使用阳性和阴性综合征量表评估精神病症状，并通过情绪和情绪问卷 - 儿童版 (MFQ-C) 评估抑郁症状。采用双变量相关分析探讨IL-18/IL-18BP比值与皮质醇、抑郁等临床特征的关系。使用分层多元线性回归分析来评估他们对 IL-18/IL-18BP 比率方差的个人贡献。结果患者的 IL-18 水平和 IL-18/IL-18BP 比值显着高于 HC，但 IL-18BP、IL-18RAP 和 IL-18R1 相似。控制混杂因素后，皮质醇（R2 变化 = 0.05）和 MFQ-C 评分（R2 变化 = 0.09）对 IL-18/IL-18BP 比率的变化有显着影响。结论我们发现 EOP 青少年的 IL-18 系统活性增加。皮质醇和抑郁症状各自导致 IL-18/IL-18BP 比率的变化。我们的研究结果支持青少年精神病中炎症通路的激活，并表明 EOP 中压力、炎症和抑郁症状之间的相互作用。

更新日期：2020-02-01

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