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血液淋巴细胞中 5-羟色胺转运体聚集作为重度抑郁症治疗效果的潜在生物标志物。

Serotonin transporter clustering in blood lymphocytes as a putative biomarker of therapeutic efficacy in major depressive disorder.

机构信息

Department of Cell Biology, Faculty of Biology, University of Santiago de Compostela, Santiago de Compostela, Galicia, Spain.

出版信息

J Affect Disord. 2012 Mar;137(1-3):46-55. doi: 10.1016/j.jad.2011.12.041. Epub 2012 Jan 16.

Abstract

BACKGROUND

Serotonin transporter (SERT) binding is decreased in lymphocytes of depression patients and this decrease is partially reversed by antidepressant medication. However, recent evidence has shown that clustering of SERT on cell membranes is very important for receptor functionality. Alteration in SERT clustering on peripheral lymphocytes does not affect symptoms severity. At the most it is associated or predicts responsivity to treatment.

METHODS

We collected blood samples from 38 untreated and newly diagnosed depression patients at the time of diagnosis and after 8weeks of pharmacological treatment and of 38 control subjects. We used the Hamilton Scale to quantify the level of depression in patients both before and after pharmacological treatment. We then used immunocytochemistry to assess SERT protein clusters in lymphocyte blood samples.

RESULTS

We found an increase in SERT cluster size, but not the number of SERT clusters, in naïve depression patients compared to control subjects. Based on the distribution of SERT cluster size we differentiated the naïve depression patients into two groups (D-I and D-II). Naïve D-I and D-II patients initially showed similar Hamilton scores. However, after pharmacological treatment the D-II patients showed a greater decrease in Hamilton scores than did the D-I patients, and they had an increase in the number of SERT clusters.

LIMITATIONS

The data should be replicated in a larger cohort of patients and with a proper clinical trial.

CONCLUSIONS

We propose that SERT clustering in blood lymphocytes may be a putative biomarker for antidepressant efficacy in major depressive disorder.

摘要

背景

抑郁症患者的淋巴细胞中血清素转运蛋白(SERT)结合减少,这种减少部分可以通过抗抑郁药物逆转。然而,最近的证据表明,SERT 在细胞膜上的聚集对于受体功能非常重要。外周血淋巴细胞中 SERT 聚集的改变并不影响症状的严重程度。最多它与治疗反应性相关或可预测治疗反应性。

方法

我们在诊断时和药物治疗 8 周后收集了 38 名未经治疗和新诊断的抑郁症患者以及 38 名对照者的血液样本。我们使用汉密尔顿量表在药物治疗前后量化患者的抑郁程度。然后,我们使用免疫细胞化学评估淋巴细胞血液样本中的 SERT 蛋白簇。

结果

我们发现与对照组相比,未接受治疗的抑郁症患者的 SERT 簇大小增加,但 SERT 簇数量没有增加。基于 SERT 簇大小的分布,我们将未接受治疗的抑郁症患者分为两组(D-I 和 D-II)。未接受治疗的 D-I 和 D-II 患者最初表现出相似的汉密尔顿评分。然而,在药物治疗后,D-II 患者的汉密尔顿评分下降幅度大于 D-I 患者,且 SERT 簇数量增加。

局限性

应在更大的患者队列中并通过适当的临床试验复制该数据。

结论

我们提出,血液淋巴细胞中的 SERT 聚类可能是预测重度抑郁症抗抑郁疗效的潜在生物标志物。

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