Identifying biomarkers of antidepressant response may advance personalized treatment of major depressive disorder (MDD). We aimed to identify longitudinal changes in gene expression associated with response to antidepressants in a sample of MDD patients treated with escitalopram. Patients (N = 153) from the CAN-BIND-1 cohort were treated for 8 weeks, and depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale at 0, 2, 4, 6, and 8 weeks. We identified three groups of patients according to response status: early responders (22.9%), later responders (32.0%), and nonresponders (45.1%). RNA sequencing was performed in blood obtained at weeks 0, 2, and 8. RNA expression was modeled using growth models, and differences in the longitudinal changes in expression according to response were investigated using multiple regression models. The expression of RNAs related to response was investigated in the brains of depressed individuals, as well as in neuronal cells in vitro. We identified four RNAs (CERCAM, DARS-AS1, FAM228B, HBEGF) whose change over time was independently associated with a response status. For all except HBEGF, responders showed higher expression over time, compared to nonresponders. While the change in all RNAs differentiated early responders from nonresponders, changes in DARS-AS1 and HBEGF also differentiated later responders from nonresponders. Additionally, HBEGF was downregulated in the brains of depressed individuals, and increased in response to escitalopram treatment in vitro. In conclusion, using longitudinal assessments of gene expression, we provide insights into biological processes involved in the intermediate stages of escitalopram response, highlighting several genes with potential utility as biomarkers of antidepressant response.

识别抗抑郁反应的生物标志物可能会推进重度抑郁症 (MDD) 的个性化治疗。我们的目的是在接受艾司西酞普兰治疗的 MDD 患者样本中确定与抗抑郁药反应相关的基因表达的纵向变化。患者 ( N = 153) 来自 CAN-BIND-1 队列的患者接受了 8 周的治疗，并在 0、2、4、6 和 8 周时使用 Montgomery-Åsberg 抑郁量表评估抑郁症状。我们根据反应状态确定了三组患者：早期反应者 (22.9%)、晚期反应者 (32.0%) 和无反应者 (45.1%)。在第 0、2 和 8 周获得的血液中进行 RNA 测序。使用生长模型对 RNA 表达进行建模，并使用多元回归模型研究根据响应的表达纵向变化的差异。在抑郁个体的大脑以及体外神经元细胞中研究了与反应相关的 RNA 的表达。我们鉴定了四种 RNA（CERCAM、DARS-AS1、FAM228B、HBEGF) 其随时间的变化与响应状态独立相关。对于除HBEGF之外的所有情况，与无反应者相比，反应者随着时间的推移表现出更高的表达。虽然所有 RNA 的变化区分了早期反应者和无反应者，但DARS-AS1和HBEGF 的变化也区分了晚期反应者和无反应者。此外，HBEGF在抑郁个体的大脑中下调，并在体外对依他普仑治疗的反应中增加。总之，使用基因表达的纵向评估，我们提供了对涉及依他普仑反应中间阶段的生物学过程的见解，突出了几个具有作为抗抑郁反应生物标志物的潜在用途的基因。