Laboratories of Medical Research, Center for Faculty Development and Education, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan; Department of Psychiatry, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
Department of Psychiatry, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Nursing, School of Nursing, Fooyin University, Kaohsiung, Taiwan.
J Affect Disord. 2018 Oct 1;238:597-608. doi: 10.1016/j.jad.2018.06.035. Epub 2018 Jun 20.
To investigate whether the serotonin transporter (5-HTT or SERT or SLC6A4) mRNA level could be used as a biomarker of treatment response in patients with major depression treated with different antidepressants while controlling related factors.
One hundred and nineteen patients with major depression were recruited; all genotyped for the 5-HTT polymorphism concerning 5-HTTLPR, rs25531, and STin2 VNTR, provided demographic data and completed relevant questionnaires. Duloxetine and paroxetine were administered over 32 weeks to these patients. The Hamilton depression rating scale (HDRS) and 5-HTT mRNA level were evaluated at baseline (Week 0), and at 8, 16, 24 and 32 weeks.
Improvement in depressive symptoms (HDRS score declined) and increasing in 5-HTT mRNA level were found with longer duration of antidepressant treatment in patients with major depression. Patients with more 5-HTTPR long-form alleles and STin2.12 alleles had poor antidepressant treatment response. Duloxetine may give a better treatment response than paroxetine. Using structural equation modeling (SEM), the 5-HTTLPR long-form had a direct positive association with the 5-HTT mRNA level and an indirect adverse relationship with the 5-HTT mRNA level through neuroticism and previous suicide attempts.
The 5-HTT mRNA level increased and correlated with the treatment response (HDRS score improvement) under 32-weeks antidepressants treatment clinical trial. We speculate that the 5-HTT mRNA level may be used as a potential biomarker of antidepressant treatment response.
在控制相关因素的情况下，探讨 5-羟色胺转运体（5-HTT 或 SERT 或 SLC6A4）mRNA 水平能否作为不同抗抑郁药治疗抑郁症患者反应的生物标志物。
共纳入 119 例抑郁症患者，均对 5-HTTLPR、rs25531 和 STin2 VNTR 5-HTT 多态性进行基因分型，提供人口统计学数据并完成相关问卷。这些患者接受度洛西汀和帕罗西汀治疗 32 周。在基线（第 0 周）、第 8、16、24 和 32 周时评估汉密尔顿抑郁评定量表（HDRS）和 5-HTT mRNA 水平。
随着抗抑郁治疗时间的延长，抑郁症患者的抑郁症状（HDRS 评分下降）改善和 5-HTT mRNA 水平升高。5-HTT 多态性长等位基因和 STin2.12 等位基因较多的患者抗抑郁治疗反应较差。度洛西汀的治疗反应可能优于帕罗西汀。采用结构方程模型（SEM），5-HTTLPR 长等位基因与 5-HTT mRNA 水平呈直接正相关，与神经质和既往自杀企图通过 5-HTT mRNA 水平呈间接负相关。
在为期 32 周的抗抑郁药物治疗临床试验中，5-HTT mRNA 水平升高并与治疗反应（HDRS 评分改善）相关。我们推测 5-HTT mRNA 水平可能作为抗抑郁治疗反应的潜在生物标志物。
