Lotrich Francis E, Ferrell Robert E, Rabinovitz Mordechai, Pollock Bruce G
Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Biol Psychiatry. 2009 Feb 15;65(4):344-8. doi: 10.1016/j.biopsych.2008.08.009. Epub 2008 Sep 18.
Major depressive disorder (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 influence depression risk.
A cohort of 71 nondepressed hepatitis C patients about to receive interferon-alpha was prospectively followed, employing a diagnostic structured clinical interview (Structured Clinical Interview for DSM-IV Axis I Disorders [SCID-I]) and self-report questionnaires. Patients were genotyped for the 5-HTTLPR (L(G), L(A), 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 L(A) allele was associated with a decreased rate of developing MDD (Mantel-Cox log rank test p < .05) with the L(A)/L(A) genotype being the most resilient. This genotype was also associated with better sleep quality [F(61.2,2) = 3.3, p < .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 = .07, SE = .02, p < .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.
尽管许多接受α干扰素治疗的患者对这种副作用具有耐受性，但仍有一部分患者会发生重度抑郁症（MDD）。血清素再摄取转运体启动子（5-HTTLPR）的基因差异可能与炎症系统相互作用，并影响抑郁症风险。
对71名即将接受α干扰素治疗的非抑郁丙型肝炎患者进行前瞻性随访，采用诊断性结构化临床访谈（《精神疾病诊断与统计手册》第四版轴I障碍结构化临床访谈[SCID-I]）和自我报告问卷。对患者进行5-HTTLPR（L(G)、L(A)和S）以及第二个内含子中串联重复序列（VNTR）多态性的基因分型。采用Kaplan-Meier分析比较重度抑郁症发病率。使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。
L(A)等位基因与MDD发病率降低相关（Mantel-Cox对数秩检验p < .05），L(A)/L(A)基因型耐受性最强。该基因型还与更好的睡眠质量相关[F(61.2,2) = 3.3，p < .05]。当模型中也纳入基因型时，基线睡眠质量预测抑郁症发病率的能力消失。相反，当纳入基因型时，神经质与抑郁症发病率的关系（B = .07，SE = .02，p < .005）并未减弱。
采用前瞻性设计，5-HTTLPR与α干扰素治疗期间的MDD发病率相关。观察到这种效应可能通过对睡眠质量的影响介导的初步证据。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。
