Sackler Institute of Psychobiological Research, Institute of Health and Wellbeing, University of Glasgow, United Kingdom.
Institute of Neurological Sciences, Southern General Hospital, Glasgow, United Kingdom.
Brain Behav Immun. 2016 Jan;51:29-38. doi: 10.1016/j.bbi.2015.08.005. Epub 2015 Aug 6.
Preclinical studies demonstrate that pro-inflammatory cytokines increase serotonin transporter availability and function, leading to depressive symptoms in rodent models. Herein we investigate associations between circulating inflammatory markers and brainstem serotonin transporter (5-HTT) availability in humans. We hypothesised that higher circulating inflammatory cytokine concentrations, particularly of tumour necrosis factor (TNF-α), would be associated with greater 5-HTT availability, and that TNF-α inhibition with etanercept (sTNFR:Fc) would in turn reduce 5-HTT availability. In 13 neurologically healthy adult women, plasma TNF-α correlated significantly with 5-HTT availability (rho=0.6; p=0.03) determined by [(123)I]-beta-CIT SPECT scanning. This association was replicated in an independent sample of 12 patients with psoriasis/psoriatic arthritis (rho=0.76; p=0.003). Indirect effects analysis, showed that there was a significant overlap in the variance explained by 5-HTT availability and TNF-α concentrations on BDI scores. Treatment with etanercept for 6-8weeks was associated with a significant reduction in 5-HTT availability (Z=2.09; p=0.03; r=0.6) consistent with a functional link. Our findings confirm an association between TNF-α and 5-HTT in both the basal physiological and pathological condition. Modulation of both TNF-α and 5-HTT by etanercept indicate the presence of a mechanistic pathway whereby circulating inflammatory cytokines are related to central nervous system substrates underlying major depression.
临床前研究表明，促炎细胞因子可增加 5-羟色胺转运体的可及性和功能，导致啮齿动物模型出现抑郁症状。在此，我们研究了循环炎症标志物与人类脑干 5-羟色胺转运体（5-HTT）可及性之间的关联。我们假设，较高的循环炎症细胞因子浓度，特别是肿瘤坏死因子（TNF-α），与更高的 5-HTT 可及性相关，而依那西普（sTNFR：Fc）抑制 TNF-α 又会反过来降低 5-HTT 可及性。在 13 名神经健康的成年女性中，血浆 TNF-α与通过[(123)I]-β-CIT SPECT 扫描确定的 5-HTT 可及性呈显著正相关（rho=0.6；p=0.03）。该关联在 12 名银屑病/银屑病关节炎患者的独立样本中得到了复制（rho=0.76；p=0.003）。间接影响分析显示，5-HTT 可及性和 TNF-α 浓度对 BDI 评分的解释方差存在显著重叠。依那西普治疗 6-8 周与 5-HTT 可及性显著降低相关（Z=2.09；p=0.03；r=0.6），这与功能联系一致。我们的研究结果证实了 TNF-α和 5-HTT 在基础生理和病理条件下的关联。依那西普对 TNF-α和 5-HTT 的调节表明，存在一种机制途径，即循环炎症细胞因子与中枢神经系统中与重度抑郁症相关的底物有关。
