单相抑郁症的表观基因组DNA甲基化--抗抑郁治疗反应的预测性生物标志物?

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY International Journal of Neuropsychopharmacology Pub Date : 2024-11-01 DOI:10.1093/ijnp/pyae045
Miriam A Schiele, Oscar Crespo Salvador, Jan Lipovsek, Kathrin Schwarte, Pascal Schlosser, Peter Zwanzger, Volker Arolt, Bernhard T Baune, Anna Köttgen, Katharina Domschke
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引用次数: 0

摘要

背景:尽管抗抑郁药物治疗重度抑郁障碍(MDD)的疗效已得到充分证实,但初始治疗的无应答率却很高。近年来,为改进诊断和个体化治疗,对预测性生物标志物的研究不断增加。其中,DNA 甲基化等表观遗传机制是预测 MDD 抗抑郁治疗反应的有希望的候选标志物。本研究试图将整个表观基因组的DNA甲基化作为迄今为止最大样本的MDD患者抗抑郁治疗反应的预测指标:采用Infinium MethylationEPIC BeadChip分析了在自然住院环境中接受六周抗抑郁治疗的230名白种MDD患者外周血中的表观基因组DNA甲基化,以及主要接受SSRIs或SNRIs持续治疗的107名患者的子样本。治疗反应通过汉密尔顿抑郁量表(HAM-D)进行评估:结果:未观察到全基因组范围内的重大突变。提示性(pConclusions:本研究结果提供了 DNA 甲基化模式改变与 MDD 抗抑郁治疗反应相关的初步证据。如果能在独立的、更大的样本中进行重要的复制,本研究结果将来可能有助于临床决策,从而对 MDD 进行更个体化、更有效的治疗。
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Epigenome-Wide DNA Methylation in Unipolar Depression: Predictive Biomarker of Antidepressant Treatment Response?

Background: Despite the well-documented efficacy of antidepressant agents for the treatment of major depressive disorder (MDD), initial treatment nonresponse rates are high. Recent years have seen an increase in research into predictive biomarkers toward improving diagnosis and individualized treatment. Among those, epigenetic mechanisms such as DNA methylation constitute promising candidate markers in predicting antidepressant treatment response in MDD. The present study sought to address epigenome-wide DNA methylation as a predictor of antidepressant treatment response in the largest sample to date of patients with MDD.

Methods: Epigenome-wide DNA methylation was analyzed using the Infinium MethylationEPIC BeadChip in peripheral blood of n = 230 Caucasian patients with MDD receiving 6-week antidepressant treatment in a naturalistic in-patient setting as well as in a subsample of n = 107 patients primarily receiving continuous treatment with serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. Treatment response was assessed by means of the Hamilton Depression Scale.

Results: No genome-wide significant hits were observed. Suggestive (P < 1E-5) epigenome-wide evidence was discerned for altered DNA methylation at 6 CpG sites (LOC102724467, LOC100506023, RSPO2, SAG, IL16, PRKCI) to predict response to naturalistic antidepressant treatment. In patients treated with serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors, differential DNA methylation at 11 CpGs, for example, mapping to the TIMP2, VDAC1, or SORL1 genes, was suggestively associated with treatment response.

Conclusions: The present results provide preliminary evidence for altered DNA methylation patterns to be associated with antidepressant treatment response in MDD. Provided significant replication in independent and larger samples, the present findings might in the future aid in clinical decision-making toward more individualized and thus more efficacious treatments of MDD.

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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
期刊最新文献
Anhedonia is associated with a specific depression profile and poor antidepressant response. 17β-estradiol Ameliorates Postoperative Cognitive Dysfunction in Aged Mice via miR-138-5p/SIRT1/HMGB1 Pathway. Risk of cognitive decline among patients with dengue virus infection: A systematic review. Epigenome-Wide DNA Methylation in Unipolar Depression: Predictive Biomarker of Antidepressant Treatment Response? Behavioral and neurophysiological signatures of cognitive control in humans and rats.
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