Risk for depression during interferon-alpha treatment is affected by the serotonin transporter polymorphism.
Risk for depression during interferon-alpha treatment is affected by the serotonin transporter polymorphism.
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DOI：
10.1016/j.biopsych.2008.08.009
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发表时间：
2009-02-15
影响因子：
10.6
通讯作者：
Pollock, Bruce G.
中科院分区：
文献类型：
--
作者：
Lotrich, Francis E.;Ferrell, Robert E.;Rabinovitz, Mordechai;Pollock, Bruce G.
重度抑郁症（MDD）发生在接受干扰素-α治疗的一部分患者中，尽管许多人对这种副作用有弹性。5-羟色胺再摄取转运蛋白启动子（5-HTTLPR）的遗传差异可能与炎症系统相互作用，并可能影响抑郁症的风险。采用诊断性结构化临床访谈（SCID; DSM-IV）和自我报告问卷，前瞻性随访了71例即将接受干扰素-α治疗的非抑郁丙型肝炎患者。对患者进行5-HTTLPR（LG、LA和S）和第二个内含子中可变数量串联重复（VNTR）多态性的基因分型。Kaplan-Meier分析用于比较重度抑郁症的发生率。采用混合效应重复测量分析评估基因型对睡眠质量（匹兹堡睡眠质量指数）和贝克抑郁量表（BDI）的影响。LA等位基因与MDD发生率降低相关（Mantel-Cox对数秩检验p<0.05），其中LA/LA基因型最有弹性。该基因型也与较好的睡眠质量相关（F（61.2，2）= 3.3 p<0.05）。当模型中也包括基因型时，基线睡眠质量预测抑郁症发病率的能力消失了。相反，神经质与抑郁症发病率的关系（B=0.07 SE = 0.02 p<0.005）并没有减轻时，包括基因型。采用前瞻性设计，5-HTTLPR与α干扰素治疗期间MDD的发生率相关。初步证据表明，这种影响可以通过对睡眠质量的影响来介导。这些发现为炎症细胞因子（α-干扰素）暴露与MDD中5-HTTLPR变异性之间可能的相互作用提供了支持。
Major depression (MDD) occurs in a subset of patients receiving interferon-alpha treatment, although many are resilient to this side effect. Genetic differences in the serotonin reuptake transporter promoter (5-HTTLPR) may interact with the inflammatory system and may influence depression risk. A cohort of 71 non-depressed hepatitis C patients about to receive interferon-alpha was prospectively followed, employing a diagnostic structured clinical interview (SCID; DSM-IV) and self-report questionnaires. Patients were genotyped for the 5-HTTLPR (LG, LA, and S) and the variable number of tandem repeats (VNTR) polymorphism in the second intron. Kaplan-Meier analyses were used to compare major depression incidence. Genotype effects on sleep quality (Pittsburgh Sleep Quality Index) and Beck Depression Inventory (BDI) were assessed using mixed-effect repeated-measure analyses. The LA allele was associated with a decreased rate of developing MDD (Mantel-Cox Log Rank Test p<0.05) with the LA/LA genotype being the most resilient. This genotype was also associated with better sleep quality (F(61.2,2) = 3.3 p<0.05). The ability of baseline sleep quality to predict depression incidence disappeared when also including genotype in the model. Conversely, the relationship of neuroticism with depression incidence (B=0.07 SE = 0.02 p<0.005) was not mitigated when including genotype. Using a prospective design, 5-HTTLPR is associated with MDD incidence during interferon-alpha treatment. Preliminary evidence that this effect could be mediated by effects on sleep quality was observed. These findings provide support for a possible interaction between inflammatory cytokine (interferon-alpha) exposure and 5-HTTLPR variability in MDD.
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DOI：
10.1002/ajmg.10119
发表时间：
2002-04-08
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Kaiser, R;Müller-Oerlinghausen, B;Brockmöller, J
通讯作者：
Brockmöller, J
影响因子：
17.7
作者：
Kendler, KS;Kuhn, J;Prescott, CA
通讯作者：
Prescott, CA
影响因子：
3.3
作者：
Brummett, Beverly H.;Krystal, Andrew D.;Williams, Redford B.
通讯作者：
Williams, Redford B.
影响因子：
10.6
作者：
Capuron, L;Neurauter, G;Miller, AH
通讯作者：
Miller, AH
影响因子：
10.6
作者：
Capuron, L;Miller, AH
通讯作者：
Miller, AH