Cross-species evidence for the role of interleukin-33 in depression risk.
Cross-species evidence for the role of interleukin-33 in depression risk.
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DOI：
10.1037/abn0000158
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发表时间：
2016-05
影响因子：
4.6
通讯作者：
Gibb BE
中科院分区：
文献类型：
--
作者：
Kudinova AY;Deak T;Hueston CM;McGeary JE;Knopik VS;Palmer RH;Gibb BE
大量证据强调了炎症过程在重度抑郁症 (MDD) 中的作用。然而，大多数研究都检查了一组一致的炎症细胞因子，并且有证据表明其他免疫衍生产品可能在 MDD 中发挥作用。在本文中，我们提供了三项补充研究的数据，这些研究支持新型细胞因子白细胞介素 33 (IL-33) 在抑郁风险中的作用。首先，我们发现IL-33基因中的两个SNP单倍型（rs11792633和rs7044343）调节了女性儿童期虐待史与其复发性MDD（rMDD）史之间的联系，因此在保护性IL-33 CT单倍型拷贝数较少的女性中，儿童期虐待与rMDD之间的联系更强。其次，将这些发现与循环细胞因子水平的差异联系起来，我们在一个单独的样本中显示，与单次 MDD 发作或无 MDD 病史的女性相比，有 rMDD 病史的女性外周血 IL-33 和 IL-1β 水平较高。第三，利用档案大鼠脑组织提供这些影响背后的大脑区域的初步证据，我们发现急性应激源增加了下丘脑室旁核中IL-33的表达，并在较小程度上增加了前额皮质、压力反应和情绪调节的关键大脑区域。这些发现为 IL-33 在 MDD 复发风险中的潜在作用提供了一致支持。
Extensive evidence highlights the role of inflammatory processes in Major Depressive Disorder (MDD). However, most studies have examined a consistent set of inflammatory cytokines and there is evidence that other immune-derived products may play a role in MDD. In this article, we present data from three complimentary studies that support the role of a novel cytokine, interleukin-33 (IL-33), in depression risk. First, we show that a two-SNP haplotype in the IL-33 gene (rs11792633 and rs7044343) moderated the link between women's history of childhood abuse and their history of recurrent MDD (rMDD), such that the link between childhood abuse and rMDD was stronger among women with fewer copies of the protective IL-33 CT haplotype. Second, linking these findings to differences in circulating cytokine levels, we show in a separate sample that those with a history of rMDD had higher peripheral levels of IL-33 and IL-1β compared to women with a single MDD episode or no history of MDD. Third, providing initial evidence of brain regions underlying these effects using archival rat brain tissue, we show that an acute stressor increased IL-33 expression in the paraventricular nucleus of the hypothalamus and, to a lesser extent, the prefrontal cortex, key brain regions underlying stress response and emotion regulation. These findings provide converging support for the potential role of IL-33 in risk for recurrent MDD.