Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels.
Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels.
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DOI：
10.1016/j.euroneuro.2012.08.010
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发表时间：
2013-07
影响因子：
5.6
通讯作者：
Lucae, Susanne
中科院分区：
文献类型：
--
作者：
Kloiber, Stefan;Ripke, Stephan;Kohli, Martin A.;Reppermund, Simone;Salyakina, Daria;Uher, Rudolf;McGuffin, Peter;Perlis, Roy H.;Hamilton, Steven P.;Puetz, Benno;Hennings, Johannes;Brueckl, Tanja;Klengel, Torsten;Bettecken, Thomas;Ising, Marcus;Uhr, Manfred;Dose, Tatjana;Unschuld, Paul G.;Zihl, Josef;Binder, Elisabeth;Mueller-Myhsok, Bertram;Holsboer, Florian;Lucae, Susanne
瘦素是一种来自脂肪组织的肽激素，在体重调节中发挥着关键作用，已被认为与睡眠和认知有关，并可能通过其对 HPA 轴和海马功能的作用发挥抗抑郁样作用。这促使我们研究瘦素基因的遗传变异、瘦素 mRNA 表达水平和瘦素血清浓度是否与抗抑郁治疗的反应相关。我们的样本由来自慕尼黑抗抑郁反应特征 (MARS) 项目的住院患者组成，每周进行汉密尔顿抑郁评级，分为两个子样本。在探索性样本 (n=251) 中，对覆盖瘦素基因区域的 17 个单核苷酸多态性 (SNP) 进行了基因分型。经过多次测试校正后，我们发现几个 SNP 与抗抑郁治疗结果受损和认知能力受损存在显着关联。在复制样本 (n=358) 中分析了显示与治疗反应最高关联性 (p=3.9 × 10−5) 的 SNP (rs10487506)，并且可以通过三环类抗抑郁药的反应来验证这种关联性 (p=0.021)。在另一项荟萃分析中，将 MARS 研究的结果与基于基因组的抑郁症治疗药物 (GENDEP) 和缓解抑郁症的测序替代治疗 (STAR*D) 研究的数据相结合，检测到 rs10487506 上游附近的几个多态性与治疗结果的名义关联 (p=0.001)。此外，我们还测定了 MARS 研究子样本中淋巴细胞中的瘦素 mRNA 表达和瘦素血清水平。不良的治疗结果伴随着瘦素 mRNA 和瘦素血清水平的降低。我们的研究结果表明，瘦素参与抑郁症的抗抑郁作用和认知功能，瘦素基因的遗传多态性、瘦素基因表达减少和血清中瘦素缺乏是抑郁症患者抗抑郁治疗的危险因素。
Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9 × 10−5) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies, nominal associations of several polymorphisms in the upstream vicinity of rs10487506 with treatment outcome were detected (p=0.001). In addition, we determined leptin mRNA expression in lymphocytes and leptin serum levels in subsamples of the MARS study. Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant therapy in depressed patients.
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影响因子：
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