Peripheral immune cell reactivity and neural response to reward in patients with depression and anhedonia.
Peripheral immune cell reactivity and neural response to reward in patients with depression and anhedonia.
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DOI：
10.1038/s41398-021-01668-1
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发表时间：
2021-11-05
影响因子：
6.8
通讯作者：
Murrough JW
中科院分区：
文献类型：
--
作者：
Costi S;Morris LS;Collins A;Fernandez NF;Patel M;Xie H;Kim-Schulze S;Stern ER;Collins KA;Cathomas F;Parides MK;Whitton AE;Pizzagalli DA;Russo SJ;Murrough JW
在临床前和临床研究中，外周细胞因子水平的升高与抑郁症有关。尽管抑郁症患者外周免疫功能障碍的确切性质尚不清楚，但来自动物研究的证据表明，外周白细胞的异常反应是应激易感性的风险因素。这项研究检测了抑郁症患者外周血单个核细胞(PBMC)中炎性血液因子的动态释放，以及与神经和行为奖赏处理措施的相关性。符合单相抑郁障碍诊断标准的非药物治疗患者30例，健康对照志愿者21例。从全血中分离PBMCs，用脂多糖(LPS)体外刺激。Olink多重分析用于分析大量的炎性蛋白。参与者完成了功能性磁共振成像和激励侧翼任务，以探测神经对奖励预期的反应，以及快感缺失和快感的临床测量，包括快感时间体验量表(TEPs)和Snaith-Hamilton快乐量表(Shaps)。使用总免疫评分(T49 = 2.83，p = 0.007)，LP刺激显示抑郁症患者的免疫因子比健康受试者增加更多。更高的外周免疫分数与腹侧纹状体(VS)对奖励预期的神经反应减少(r = −0.39，p = 0.01)，以及用TEP预期分分数测量的快乐预期减少(r = −0.318，p = 0.023)。我们的研究提供了新的证据，表明抑郁症患者外周血白细胞的动态高反应性与大脑奖励系统的钝化激活和对快乐的主观预期降低有关。
Increased levels of peripheral cytokines have been previously associated with depression in preclinical and clinical research. Although the precise nature of peripheral immune dysfunction in depression remains unclear, evidence from animal studies points towards a dysregulated response of peripheral leukocytes as a risk factor for stress susceptibility. This study examined dynamic release of inflammatory blood factors from peripheral blood mononuclear cells (PBMC) in depressed patients and associations with neural and behavioral measures of reward processing. Thirty unmedicated patients meeting criteria for unipolar depressive disorder and 21 healthy control volunteers were enrolled. PBMCs were isolated from whole blood and stimulated ex vivo with lipopolysaccharide (LPS). Olink multiplex assay was used to analyze a large panel of inflammatory proteins. Participants completed functional magnetic resonance imaging with an incentive flanker task to probe neural responses to reward anticipation, as well as clinical measures of anhedonia and pleasure including the Temporal Experience of Pleasure Scale (TEPS) and the Snaith-Hamilton Pleasure Scale (SHAPS). LPS stimulation revealed larger increases in immune factors in depressed compared to healthy subjects using an aggregate immune score (t49 = 2.83, p = 0.007). Higher peripheral immune score was associated with reduced neural responses to reward anticipation within the ventral striatum (VS) (r = −0.39, p = 0.01), and with reduced anticipation of pleasure as measured with the TEPS anticipatory sub-score (r = −0.318, p = 0.023). Our study provides new evidence suggesting that dynamic hyper-reactivity of peripheral leukocytes in depressed patients is associated with blunted activation of the brain reward system and lower subjective anticipation of pleasure.
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影响因子：
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作者：
Boyle, Chloe C.;Kuhlman, Kate R.;Bower, Julienne E.
通讯作者：
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影响因子：
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Felger JC;Haroon E;Patel TA;Goldsmith DR;Wommack EC;Woolwine BJ;Le NA;Feinberg R;Tansey MG;Miller AH
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