干扰素α治疗期间的易激性愤怒与肿瘤坏死因子α的多态性有关。
Labile anger during interferon alfa treatment is associated with a polymorphism in tumor necrosis factor alpha.
作者信息
Lotrich Francis E, Ferrell Robert E, Rabinovitz Mordechai, Pollock Bruce G
机构信息
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
出版信息
Clin Neuropharmacol. 2010 Jul;33(4):191-7. doi: 10.1097/WNF.0b013e3181de8966.
OBJECTIVE
Inflammatory cytokines may influence both labile anger and depression. Both psychiatric conditions can occur during interferon alfa-based treatments. Evidence also indicates a central nervous system role for tumor necrosis factor alpha (TNF-alpha), whose expression may be increased by interferon alfa. A polymorphism in the promoter region of TNF-alpha has been associated with various inflammatory illnesses. We therefore hypothesized that this TNF-alpha polymorphism would influence susceptibility to psychiatric symptoms during interferon alfa therapy.
METHODS
One hundred five patients with hepatitis C, initially without active major depression (major depressive disorder), were treated with interferon alfa and then prospectively monitored using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the Beck Depression Inventory II, the Anger Irritability and Assault Questionnaire, and circulating TNF-alpha levels. The A-308G polymorphism (rs1800629) was determined using the 5'-nuclease assay. Repeated-measure mixed-effect analyses compared changes in symptoms over time.
RESULT
Beck Depression Inventory II score increased during interferon alfa therapy (F = 6.2; P < 0.001), with 27% developing MDD. The TNF-alpha 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 (chi = 0.0; P = 0.99) or increased Beck Depression Inventory II (F = 1.2; P = 0.31). Labile anger was not predicted by the serotonin transporter polymorphism (F = 0.8; P = 0.59).
DISCUSSION
During treatment with an exogenous cytokine, vulnerability to worsening labile anger-distinct from major depression-is associated with genetic variability in TNF-alpha. This has implications both for patients being treated with interferon alfa and our understanding of genetic vulnerability for different subtypes of dysphoric and mood disorders.
目的
炎性细胞因子可能会影响易激惹性愤怒和抑郁。这两种精神状况都可能在基于干扰素α的治疗过程中出现。有证据还表明肿瘤坏死因子α（TNF-α）在中枢神经系统中发挥作用，其表达可能会因干扰素α而增加。TNF-α启动子区域的一种多态性与多种炎性疾病有关。因此，我们推测这种TNF-α多态性会影响干扰素α治疗期间出现精神症状的易感性。
方法
105例丙型肝炎患者，最初无活动性重度抑郁症（重度抑郁障碍），接受干扰素α治疗，然后使用《精神障碍诊断与统计手册》第四版的结构化临床访谈、贝克抑郁量表第二版、愤怒易激惹与攻击问卷以及循环TNF-α水平进行前瞻性监测。使用5′-核酸酶测定法确定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。
结果
在干扰素α治疗期间，贝克抑郁量表第二版评分升高（F = 6.2；P < 0.001），27%的患者发展为重度抑郁障碍。TNF-α A等位基因与治疗期间易激惹性愤怒加重（F = 2.5；P < 0.05）和疲劳（F = 2.9；P < 0.05）相关，但与重度抑郁障碍发病率（χ = 0.0；P = 0.99）或贝克抑郁量表第二版评分升高（F = 1.2；P = 0.31）无关。血清素转运体多态性不能预测易激惹性愤怒（F = 0.8；P = 0.59）。
讨论
在用外源性细胞因子治疗期间，易激惹性愤怒加重（与重度抑郁不同）的易感性与TNF-α的基因变异性有关。这对接受干扰素α治疗的患者以及我们对烦躁和情绪障碍不同亚型的遗传易感性的理解都有影响。
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