Lotrich Francis E, Pollock Bruce G, Kirshner Margaret, Ferrell Robert F, Reynolds Iii Charles F
NIMH Advanced Center in Interventions and Services Research for Late-Life Mood Disorders and the John A. Hartford Foundation Center of Excellence in Geriatric Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
J Psychiatry Neurosci. 2008 Mar;33(2):123-30.
To investigate whether variable antidepressant response may be influenced by an interaction between the serotonin transporter promoter polymorphism (5-HTTLPR) and antidepressant concentration.
Elderly subjects with depression treated with paroxetine (n = 110) were genotyped and assessed with the Hamilton Rating Scale for Depression (HAMD). A mixed-effect analysis of repeated measures was used.
There was an interaction between early paroxetine concentration and 5-HTTLPR genotype on symptomatic improvement over 12 weeks (F(18,59.5) = 1.8, p < 0.05), as well as main effects of both paroxetine concentration (F(68,55.3) = 2.4, p < 0.005) and genotype (F(2,74.2) = 5.7, p < 0.005). Paroxetine concentrations were correlated with change in HAMD scores after 2 weeks of treatment in subjects with the short (s) allele (r = 0.31, p < 0.05) but not in subjects homozygous for the long (l) allele.
The results demonstrate a concentration-response relation for paroxetine in late-life depression and support the hypothesis for both a direct main effect and a moderating influence of 5-HTTLPR alleles on this concentration-response relation.
研究血清素转运体启动子多态性（5-HTTLPR）与抗抑郁药浓度之间的相互作用是否会影响抗抑郁药反应的变异性。
对接受帕罗西汀治疗的老年抑郁症患者（n = 110）进行基因分型，并用汉密尔顿抑郁量表（HAMD）进行评估。采用重复测量的混合效应分析。
在12周内，早期帕罗西汀浓度与5-HTTLPR基因型在症状改善方面存在相互作用（F(18,59.5) = 1.8，p < 0.05），同时帕罗西汀浓度（F(68,55.3) = 2.4，p < 0.005）和基因型（F(2,74.2) = 5.7，p < 0.005）均有主效应。在携带短（s）等位基因的受试者中，治疗2周后帕罗西汀浓度与HAMD评分变化相关（r = 0.31，p < 0.05），而在纯合长（l）等位基因的受试者中则无相关性。
结果表明帕罗西汀在老年抑郁症中存在浓度-反应关系，并支持5-HTTLPR等位基因对该浓度-反应关系具有直接主效应和调节作用的假设。
