Cutaneous glucocorticoid receptor sensitivity and pro-inflammatory cytokine levels in antidepressant-resistant depression
Cutaneous glucocorticoid receptor sensitivity and pro-inflammatory cytokine levels in antidepressant-resistant depression
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DOI：
10.1017/s003329170500632x
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发表时间：
2006-01-01
影响因子：
6.9
通讯作者：
Dinan, TG
中科院分区：
文献类型：
--
作者：
Fitzgerald, P;O'Brien, SM;Dinan, TG
背景有证据表明，外周糖皮质激素受体（GR）的功能降低，在抑郁症，这是一个可能的分子解释是提高促炎细胞因子的影响。局部类固醇血管收缩试验提供了一个方便的探针外周GR功能。本研究旨在评估抗抑郁药耐药的重度抑郁症患者外周GR的敏感性，并探讨GR敏感性与循环血浆细胞因子之间的关系。19名抗抑郁药耐药的抑郁症患者与年龄和性别匹配的健康对照者一起进行了类固醇血管收缩试验，使用三种市售皮质类固醇制剂，分别含有丙酸氯倍他索0.05%、戊酸倍他索0.1%和丁酸氯倍他索0.05%，分别对应于非常有效、有效和中等有效的类固醇乳膏。促炎细胞因子，肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的测定使用酶联免疫吸附测定。采用汉密尔顿抑郁量表（HAMD）评定抑郁发作的严重程度。抑郁受试者在所有三种类固醇强度下的血管收缩反应均显著降低。它们还具有显著更高浓度的TNF-α和IL-6。TNF-α浓度与血管收缩反应呈显著负相关，HAMD评分与血管收缩反应也呈显著负相关。这些结果表明，皮肤GR功能是异常的抗抑郁药耐药抑郁症，循环TNF-α可能在这种异常中发挥重要作用，抗抑郁药耐药抑郁症的局部类固醇的疗效降低。
Background. There is evidence to indicate that peripheral glucocorticoid receptor (GR) function is reduced in major depression, and a possible molecular explanation for this is the impact of raised pro-inflammatory cytokines. The topical steroid vasoconstriction assay provides a convenient probe of peripheral GR function. The present study sought to assess the sensitivity of peripheral GRs in antidepressant-resistant major depressives and investigate the association between GR sensitivity and circulating plasma cytokines.Method. Nineteen antidepressant-resistant depressives together with age- and sex-matched healthy controls underwent the steroid vasoconstriction assay using three commercial preparations of corticosteroids containing clobetasol propionate 0.05%, betamethasone valerate 0.1%, and clobetasone butyrate 0.05%, corresponding to very potent, potent, and moderately potent steroid creams respectively. The pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured using enzyme-linked immunosorbent assays. The severity of the depressive episode was assessed using the Hamilton Depression Scale (HAMD).Results. Depressed subjects had a significantly reduced vasoconstriction response across all three strengths of steroid. They also had significantly higher concentrations of TNF-a and IL-6. There was a significant inverse correlation between TNF-alpha concentration and vasoconstriction response and also between the HAMD score and vasoconstriction response.Conclusions. These findings suggest that Cutaneous GR function is abnormal in antidepressant-resistant depression, that circulating TNF-a may play a significant role in this abnormality and that the efficacy of topical steroids in antidepressant-resistant depressives is reduced.