Tsai Shang-Ying, Chung Kuo-Hsuan, Huang Shou-Hung, Chen Pao-Huan, Lee Hsin-Chien, Kuo Chian-Jue
Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
Bipolar Disord. 2014 Dec;16(8):800-8. doi: 10.1111/bdi.12240. Epub 2014 Aug 11.
A proinflammatory phase with various immunomodulatory mechanisms has been noted in bipolar mania and major depression. Weight gain and increased production of leptin may be associated with immunomodulation and insulin resistance in bipolar disorder. However, immunomodulation and its linkage with leptin and insulin in the depressive episode of bipolar disorder remain unclear. We investigated alterations in inflammatory markers and their relationship with leptin and insulin levels in patients with phases of bipolar disorder from acute depression to full remission.
Thirty-two physically healthy bipolar I depressed patients aged <45 years and age- and sex-matched healthy controls participated in this study. We measured their circulating levels of leptin, insulin, high-sensitivity C-reactive protein (hs-CRP), soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 1 (sTNF-R1), and interleukin-1 receptor antagonist (IL-1Ra) in three phases, i.e., acute depression, subsequent partial remission, and full remission.
In acute depression, subsequent partial remission, and full remission, patients with bipolar disorder had significantly higher mean levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R compared with control subjects. The IL-1Ra and sTNF-R1 levels in various affective phases were significantly correlated to body mass index, leptin level, circulating lipids, and medication status. The sIL-2R levels in the three affective phases were all independent of other inflammatory markers and clinical and laboratory variables. Patients showed no alteration of sIL-6R levels through the depressive episode.
Patients with bipolar disorder in depressive episodes may exhibit persistent inflammation with elevated levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R but not sIL-6R from the acute phases to full remission. Only sIL-2R production seems to be tightly linked with the pathophysiology of bipolar depression and is independent of insulin and leptin levels.
在双相躁狂症和重度抑郁症中已观察到存在具有多种免疫调节机制的促炎期。体重增加和瘦素分泌增加可能与双相情感障碍中的免疫调节和胰岛素抵抗有关。然而，双相情感障碍抑郁发作中的免疫调节及其与瘦素和胰岛素的联系仍不清楚。我们研究了双相情感障碍患者从急性抑郁到完全缓解各阶段炎症标志物的变化及其与瘦素和胰岛素水平的关系。
32名年龄小于45岁、身体健康的双相I型抑郁症患者以及年龄和性别匹配的健康对照者参与了本研究。我们在三个阶段测量了他们循环中的瘦素、胰岛素、高敏C反应蛋白（hs-CRP）、可溶性白细胞介素-2受体（sIL-2R）、可溶性白细胞介素-6受体（sIL-6R）、可溶性肿瘤坏死因子受体1（sTNF-R1）和白细胞介素-1受体拮抗剂（IL-1Ra）水平，即急性抑郁期、随后的部分缓解期和完全缓解期。
在急性抑郁期、随后的部分缓解期和完全缓解期，双相情感障碍患者的hs-CRP、IL-1Ra、sTNF-R1和sIL-2R平均水平显著高于对照受试者。不同情感阶段的IL-1Ra和sTNF-R1水平与体重指数、瘦素水平、循环脂质和用药情况显著相关。三个情感阶段的sIL-2R水平均独立于其他炎症标志物以及临床和实验室变量。患者在整个抑郁发作期sIL-6R水平无变化。
双相情感障碍抑郁发作期的患者可能表现出持续炎症，hs-CRP、IL-1Ra、sTNF-R1和sIL-2R水平升高，但从急性期到完全缓解期sIL-6R水平未升高。似乎只有sIL-2R的产生与双相抑郁的病理生理学紧密相关，且独立于胰岛素和瘦素水平。
