Evaluation of the role of MAPK1 and CREB1 polymorphisms on treatment resistance, response and remission in mood disorder patients
Evaluation of the role of MAPK1 and CREB1 polymorphisms on treatment resistance, response and remission in mood disorder patients
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DOI：
10.1016/j.pnpbp.2013.03.005
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发表时间：
2013-07-01
影响因子：
5.6
通讯作者：
Mendlewicz, Julien
中科院分区：
文献类型：
--
作者：
Calati, Raffaella;Crisafulli, Concetta;Mendlewicz, Julien
难治性抑郁症(TRD)是一个重要的临床和公共卫生问题。其中，神经可塑性和炎症通路似乎在抗抑郁药疗效的病理机制中起着至关重要的作用。本研究的主要目的是研究与神经可塑性和炎症过程相关的两个基因（丝裂原活化蛋白激酶1，MAPK1 （rs3810608, rs6928， rs13515和rs8136867）和环AMP反应元件结合蛋白1，CREB1 (rs889895, rs6740584， rs2551922和rs2254137)）中的一组单核苷酸多态性（snp）是否与抗抑郁治疗耐药性相关（根据两种不同的定义）。285例重度抑郁障碍（MDD）患者。作为次要目的，我们研究了MDD患者和包括82名双相情感障碍（BD）患者在内的更大样本中相同snp对反应、缓解和其他临床特征的遗传调节。所有患者在欧洲多中心项目的背景下进行筛选。在MDD患者中，所研究的基因与治疗耐药和反应之间没有关联。然而，考虑到缓解，据报道，MDD患者中CREB1 rs889895 GG基因型的发生率更高。此外，MAPK1 rs8136867 AG基因型被发现与整个样本（MDD和BD）的缓解相关。目前的结果表明，grow和MAPK1的一些遗传多态性可能与治疗缓解有关。虽然需要进一步的研究来得出更明确的结论，但这些结果是有趣的，因为这表明抗抑郁治疗后症状缓解中涉及神经可塑性和炎症过程的两个基因的潜在作用。(C) 2013爱思唯尔公司版权所有。
Treatment resistant depression (TRD) is a significant clinical and public health problem. Among others, neuroplasticity and inflammatory pathways seem to play a crucial role in the pathomechanisms of antidepressant efficacy.The primary aim of this study was to investigate whether a set of single nucleotide polymorphisms (SNPs) within two genes implicated in neuroplasticity and inflammatory processes (the mitogen activated protein kinase 1, MAPK1 (rs3810608, rs6928, rs13515 and rs8136867), and the cyclic AMP responsive element binding protein 1, CREB1 (rs889895, rs6740584, rs2551922 and rs2254137)) was associated with antidepressant treatment resistance (according to two different definitions), in 285 Major Depressive Disorder (MDD) patients. As secondary aims, we investigated the genetic modulation of the same SNPs on response, remission and other clinical features both in MDD patients and in a larger sample including 82 Bipolar Disorder (BD) patients as well. All patients were screened in the context of a European multicenter project.No association between both the investigated genes and treatment resistance and response was found in MDD patients. However, considering remission, higher rates of CREB1 rs889895 GG genotype were reported in MDD patients. Moreover, MAPK1 rs8136867 AG genotype was found to be associated with remission in the whole sample (MDD and BD).Present results suggest that some genetic polymorphisms in both GREW and MAPK1 could be associated with treatment remission. Although further research is needed to draw more definitive conclusions, such results are intriguing since suggest a potential role of two genes implicated in neuroplasticity and inflammatory processes in symptom remission after antidepressant treatment. (C) 2013 Elsevier Inc. All rights reserved.