Labile anger during interferon alfa treatment is associated with a polymorphism in tumor necrosis factor alpha.
Labile anger during interferon alfa treatment is associated with a polymorphism in tumor necrosis factor alpha.
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DOI：
10.1097/wnf.0b013e3181de8966
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发表时间：
2010-07
影响因子：
1
通讯作者：
Pollock BG
中科院分区：
文献类型：
--
作者：
Lotrich FE;Ferrell RE;Rabinovitz M;Pollock BG
炎症细胞因子可能会影响不稳定的愤怒和抑郁。这两种精神疾病都可能在基于干扰素-α (IFN-α) 的治疗期间发生。证据还表明 TNF-α 具有中枢神经系统作用，IFN-α 可能会增加其表达。 TNF-α 启动子区域的多态性与多种炎症性疾病有关。因此，我们假设这种 TNF-α 多态性会影响 IFN-α 治疗期间对精神症状的易感性。 105 名最初没有活动性重性抑郁 (MDD) 的丙型肝炎患者接受了 IFN-α 治疗，然后使用 DSM-IV 结构化临床访谈、贝克抑郁量表-II (BDI)、愤怒易怒和攻击问卷以及循环 TNF-α 水平进行前瞻性监测。使用 5'-核酸酶测定法测定 A-308G 多态性 (rs1800629)。重复测量混合效应分析比较了症状随时间的变化。 IFN-α 治疗期间 BDI 增加（F = 6.2；p<0.001），其中 27% 发展为 MDD。 TNF-α A 等位基因与治疗期间不稳定愤怒恶化（F = 2.5；p<0.05）和疲劳（F = 2.9；p<0.05）相关，但与重度抑郁症发生率（X2 = 0.0；p=0.99）或 BDI 增加（F = 1.2；p=0.31）无关。血清素转运蛋白多态性不能预测不稳定的愤怒（F = 0.8；p = 0.59）。在使用外源性细胞因子治疗期间，易受不稳定愤怒恶化的影响（与重度抑郁症不同）与 TNF-α 的遗传变异性有关。这对于接受 IFN-α 治疗的患者以及我们对不同亚型烦躁和情绪障碍的遗传脆弱性的理解都有影响。
Inflammatory cytokines may influence both labile anger and depression. Both psychiatric conditions can occur during interferon-alpha (IFN–α) based treatments. Evidence also indicates a central nervous system role for TNF-α, whose expression may be increased by IFN-α. A polymorphism in the promoter region of TNF-α has been associated with various inflammatory illnesses. We therefore hypothesized that this TNF-α polymorphism would influence susceptibility to psychiatric symptoms during IFN-α therapy. 105 patients with hepatitis C, initially without active major depression (MDD), were treated with IFN-α and then prospectively monitored using the Structured Clinical Interview for DSM-IV, the Beck Depression Inventory-II (BDI), the Anger Irritability and Assault Questionnaire, and circulating TNF-α levels. The A-308G polymorphism (rs1800629) was determined using the 5′-nuclease assay. Repeated-measure mixed-effect analyses compared changes in symptoms over time. BDI increased during IFN-α therapy (F = 6.2; p<0.001), with 27% developing MDD. The TNF-α A allele was associated with worsened labile anger (F = 2.5; p<0.05) and fatigue (F = 2.9; p<0.05) during treatment, but not with major depression incidence (X2 = 0.0; p=0.99) or increased BDI (F = 1.2; p=0.31). Labile anger was not predicted by the serotonin transporter polymorphism (F = 0.8; p=0.59). During treatment with an exogenous cytokine, vulnerability to worsening labile anger -- distinct from major depression -- is associated with genetic variability in TNF-α. This has implications both for patients being treated with IFN-α, as well as our understanding of genetic vulnerability for different subtypes of dysphoric and mood disorders.