Cytokine-associated emotional and cognitive disturbances in humans
Cytokine-associated emotional and cognitive disturbances in humans
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DOI：
10.1001/archpsyc.58.5.445
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发表时间：
2001-05-01
影响因子：
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通讯作者：
Pollmächer, T
中科院分区：
文献类型：
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作者：
Reichenberg, A;Yirmiya, R;Pollmächer, T
背景：感染性、自身免疫性和神经退行性疾病与严重的心理障碍有关。在动物身上的研究清楚地表明，细胞因子调节与疾病相关的行为变化。然而，人类各自心理变化背后的机制还没有建立起来。因此，我们研究了小剂量内毒素血症对情绪、认知、免疫和内分泌参数的影响。小剂量内毒素血症是一种公认的安全的宿主防御激活模型。方法：采用双盲交叉研究方法，20名健康男性志愿者在静脉注射马流产沙门氏菌内毒素(0.8 ng/kg)或生理盐水后1、3、9h完成心理问卷和神经心理测试。每小时采血一次，持续监测直肠温度和心率。结果：内毒素对躯体不适症状、血液无明显影响。血压或心率。内毒素引起直肠温度轻度升高(0.5℃)，循环中肿瘤坏死因子(TNF-α)、可溶性肿瘤坏死因子受体、白介素6、白介素1受体拮抗剂和皮质醇水平升高。注射内毒素后，受试者的焦虑(效应值[ES]=0.55)和抑郁情绪(效应值[ES=0.66])水平出现一过性显著增加。言语和非言语记忆功能明显下降(ES=0.55~0.64)。细胞因子的分泌与内毒素诱导的焦虑(r=0.49~r=0.60)、抑郁情绪(r=0.40~r=0.75)、记忆成绩下降(r=0.46~r=0.68)呈显著正相关。结论：轻度刺激人的初级宿主防御系统对情绪和记忆功能有负面影响，其机制可能与细胞因子的释放有关。因此，细胞因子是神经心理药理学研究的新靶点。
Background: Infectious, autoimmune, and neurodegenerative diseases are associated with profound psychological disturbances. Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes. However, the mechanisms underlying the respective psychological alterations in humans have not been established yet. Therefore, we investigated the effects of low-dose endotoxemia, a well-established and safe model of host-defense activation, on emotional, cognitive, immunological, and Endocrine parameters.Methods: In a double-blind, crossover study, 20 healthy male volunteers completed psychological questionnaires and neuropsychological tests 1, 3, and 9 hours after intravenous injection of Salmonella abortus equi endotoxin (0.8 ng/kg) or saline in 2 experimental sessions. Blood samples were collected hourly, and rectal temperature and heart rate were monitored continuously.Results; Endotoxin had no effects on physical sickness symptoms, blood. pressure, or heart rate. Endotoxin caused a mild increase in rectal temperature (0.5 degreesC), and increased the circulating levels of tumor necrosis factor or (TNF-alpha), soluble TNF receptors, interleukin (IL)-6, IL-1 receptor antagonist, and cortisol. After endotoxin administration, the subjects showed a transient significant increase in the levels of anxiety (effect size [ES] = 0.55) and depressed mood (ES = 0.66). Verbal and nonverbal memory functions were significantly decreased (ES = 0.55 to 0.64). Significant positive correlations were found between cytokine secretion and endotoxin-induced anxiety (r = 0.49 to r = 0.60), depressed mood (r = 0.40 to r = 0.75), and decreases in memory performance (r = 0.46 to r = 0.68).Conclusions: In humans, a mild stimulation of the primary host defense has negative effects on emotional and memory functions, which are probably caused by cytokine release. Hence, cytokines represent a novel target for neuropsychopharmacological research.