Centro de Investigação em Saúde e Ambiente (CISA), Escola Superior de Saúde, Instituto Politécnico do Porto, 4200-072 Porto, Portugal.
Molecular Oncology & Viral Pathology, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology, 4200-072 Porto, Portugal.
Int J Mol Sci. 2023 Apr 4;24(7):6758. doi: 10.3390/ijms24076758.
This study aimed to investigate the influence of genetic variants in neuroplasticity-related genes on antidepressant treatment phenotypes. The BDNF-TrkB signaling pathway, as well as the downstream kinases Akt and ERK and the mTOR pathway, have been implicated in depression and neuroplasticity. However, clinicians still struggle with the unpredictability of antidepressant responses in depressed patients. We genotyped 26 polymorphisms in , , , , , , , , , and in 80 patients with major depressive disorder treated according to the Texas Medical Algorithm for 27 months at Hospital Magalhães Lemos, Porto, Portugal. Our results showed that , , and SNP were associated with treatment-resistant depression (TRD). Additionally, and gene polymorphisms were associated with relapse. Moreover, we found a link between the polymorphism and time to relapse. These findings suggest that the , , and genes may play a role in the development of TRD, while and may be associated with relapse. GO analysis revealed enrichment in synaptic and trans-synaptic transmission pathways and glutamate receptor activity with TRD-associated genes. Genetic variants in these genes could potentially be incorporated into predictive models of antidepressant response.
这项研究旨在探讨神经可塑性相关基因的遗传变异对抗抑郁治疗表型的影响。BDNF-TrkB 信号通路以及下游激酶 Akt 和 ERK 和 mTOR 通路与抑郁和神经可塑性有关。然而，临床医生仍然难以预测抑郁症患者对抗抑郁药物的反应。我们对 80 名在葡萄牙波尔图马加良斯莱莫斯医院接受 27 个月德克萨斯医学算法治疗的重度抑郁症患者的 、 、 、 、 、 、 、 、 和 中的 26 个多态性进行了基因分型。我们的结果表明，SNP 与治疗抵抗性抑郁症（TRD）相关。此外，基因多态性与复发相关。此外，我们发现 多态性与复发时间之间存在关联。这些发现表明，、和基因可能在 TRD 的发展中起作用，而和可能与复发有关。GO 分析显示，与 TRD 相关的基因在突触和跨突触传递途径以及谷氨酸受体活性中富集。这些基因中的遗传变异可能被纳入抗抑郁反应的预测模型。
