Adversity in childhood and depression: linked through SIRT1.
Adversity in childhood and depression: linked through SIRT1.
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DOI：
10.1038/tp.2015.125
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发表时间：
2015-09-01
影响因子：
6.8
通讯作者：
Carola V
中科院分区：
文献类型：
--
作者：
Lo Iacono L;Visco-Comandini F;Valzania A;Viscomi MT;Coviello M;Giampà A;Roscini L;Bisicchia E;Siracusano A;Troisi A;Puglisi-Allegra S;Carola V
在成年人群中，经历不利的童年和父母的忽视是患抑郁症的一个危险因素。有童年创伤病史的患者会发展成一种亚类型的抑郁症，其特点是发病较早，治疗反应差，症状更严重。在早期创伤事件中参与并决定抑郁风险的长期分子机制还知之甚少。在这项研究中，我们通过施加幼年隔离应激改变了成年小鼠的抑郁样行为。我们发现，这种行为表型与大脑和外周血单核细胞中脱乙酰酶Sirtuin1(SIRT1)水平的降低有关。值得注意的是，SIRT1的外周血液mRNA表达只有在青少年而不是成人压力诱导抑郁样行为时才能预测行为绝望的程度，这表明SIRT1参与了早期成人行为的调节。与这一假设一致的是，SIRT1在幼年期间的药理调节改变了幼年小鼠的抑郁样行为。我们还在人类身上进行了一项初步研究，在该研究中，SIRT1的血液水平与重度抑郁症患者的症状严重程度显著相关，特别是那些在童年期间接受较少父母照顾的患者。在这些新发现的基础上，我们建议SIRT1参与不良童年经历的长期后果。
Experiencing an adverse childhood and parental neglect is a risk factor for depression in the adult population. Patients with a history of traumatic childhood develop a subtype of depression that is characterized by earlier onset, poor treatment response and more severe symptoms. The long-lasting molecular mechanisms that are engaged during early traumatic events and determine the risk for depression are poorly understood. In this study, we altered adult depression-like behavior in mice by applying juvenile isolation stress. We found that this behavioral phenotype was associated with a reduction in the levels of the deacetylase sirtuin1 (SIRT1) in the brain and in peripheral blood mononuclear cells. Notably, peripheral blood mRNA expression of SIRT1 predicted the extent of behavioral despair only when depression-like behavior was induced by juvenile—but not adult—stress, implicating SIRT1 in the regulation of adult behavior at early ages. Consistent with this hypothesis, pharmacological modulation of SIRT1 during juvenile age altered the depression-like behavior in naive mice. We also performed a pilot study in humans, in which the blood levels of SIRT1 correlated significantly with the severity of symptoms in major depression patients, especially in those who received less parental care during childhood. On the basis of these novel findings, we propose the involvement of SIRT1 in the long-term consequences of adverse childhood experiences.
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