NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry & Department of Clinical Research, Østfold Hospital, Grålum, Norway.
NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Psychoneuroendocrinology. 2022 Jun;140:105721. doi: 10.1016/j.psyneuen.2022.105721. Epub 2022 Mar 12.
Agitation is a challenging clinical feature in severe mental disorders, but its biological correlates are largely unknown. Inflammasome-related abnormalities have been linked to severe mental disorders and implicated in animal models of agitation. We investigated if levels of circulating inflammasome-related immune markers were associated with agitation in severe mental disorders.
Individuals with a psychotic or affective disorder (N = 660) underwent blood sampling and clinical characterization. Plasma levels of interleukin (IL)-18, IL-18 binding protein (IL-18BP), IL-18 receptor 1 (IL-18R1), IL-18 receptor accessory protein (IL-18RAP), and IL-1 receptor antagonist (IL-1RA) were measured. Agitation levels were estimated with the Positive and Negative Syndrome Scale Excited Component. Multiple linear- and logistic regression were used to investigate the associations between agitation and the immune markers, while controlling for confounders. The influence of psychotic and affective symptoms was assessed in follow-up analyses.
Agitation was positively associated with IL-18BP (β = 0.13, t = 3.41, p = 0.0007) after controlling for multiple confounders, including BMI, smoking, medication, and substance use. Adjustment for psychotic, manic, and depressive symptoms did not affect the results. There were no significant associations between agitation and the other investigated immune markers (IL-1RA (β = 0.06, t = 1.27, p = 0.20), IL-18 (β = 0.05, t = 1.25, p = 0.21), IL-18R1 (β = 0.04, t = 1.01, p = 0.31), IL-18RAP (odds ratio = 0.96, p = 0.30)). In a subsample (N = 463), we also adjusted for cortisol levels, which yielded unaltered results.
Our findings add to the accumulating evidence of immune system disturbances in severe mental disorders and suggest the IL-18 system as a part of the biological correlate of agitation independent of affective and psychotic symptoms.
激越作为严重精神障碍的一种具有挑战性的临床特征，但与之相关的生物学特征在很大程度上尚未可知。炎性小体相关异常与严重精神障碍有关，并与激越的动物模型有关。我们研究了循环炎性小体相关免疫标志物的水平是否与严重精神障碍中的激越有关。
共纳入 660 名患有精神病或情感障碍的个体进行了采血和临床特征分析。测量了白细胞介素（IL）-18、IL-18 结合蛋白（IL-18BP）、IL-18 受体 1（IL-18R1）、IL-18 受体辅助蛋白（IL-18RAP）和 IL-1 受体拮抗剂（IL-1RA）的血浆水平。使用阳性和阴性症状量表兴奋分量表来评估激越程度。采用多元线性和逻辑回归分析，在控制混杂因素的同时，研究激越与免疫标志物之间的关系。在后续分析中评估了精神病和情感症状的影响。
在控制 BMI、吸烟、药物和物质使用等多种混杂因素后，激越与 IL-18BP 呈正相关（β=0.13，t=3.41，p=0.0007）。调整精神病、躁狂和抑郁症状并未影响结果。激越与其他研究的免疫标志物之间无显著相关性（IL-1RA（β=0.06，t=1.27，p=0.20）、IL-18（β=0.05，t=1.25，p=0.21）、IL-18R1（β=0.04，t=1.01，p=0.31）、IL-18RAP（比值比=0.96，p=0.30））。在一个亚样本（N=463）中，我们还调整了皮质醇水平，结果仍然不变。
我们的研究结果增加了免疫系统紊乱与严重精神障碍之间的证据，并表明 IL-18 系统是激越的生物学相关因素的一部分，独立于情感和精神病症状。
