Pharmacogenomics of Lithium Response in Bipolar Disorder.
Pharmacogenomics of Lithium Response in Bipolar Disorder.
复制标题
双相情感障碍锂反应的药物基因组学。
DOI：
10.3390/ph14040287
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发表时间：
2021-03-24
期刊：
影响因子：
--
通讯作者：
Machado-Vieira R
中科院分区：
文献类型：
--
作者：
Vecera CM;Fries GR;Shahani LR;Soares JC;Machado-Vieira R
尽管锂是研究最广泛的情绪稳定剂，但研究人员尚未证实锂在双相情感障碍（BD）中的治疗效果的机制。药物基因组学的应用可能是临床上有用的，在未来确定锂反应患者和促进个性化治疗。本文综述的六项全基因组关联研究（GWAS）提供了与锂反应性和副作用表达相关的遗传变异的证据。在调节谷氨酸系统的基因上发现了变异体，包括GAD样基因1（GADL1）和GRIA2基因，这是锂的相互调节靶点。此外，在SESTD 1上发现的单核苷酸多态性（SNP）可以解释锂渗透细胞膜并介导自身免疫和肾脏效应的特殊能力。研究还证实了表观遗传学和压力调节对锂反应的重要性，发现了长的非编码RNA基因的变体以及精神病合并症的反应和遗传负荷之间的关联。总的来说，基于表型对患者进行分层的精确医学模型似乎得到了锂反应性BD的单独临床亚型的基因型支持。结果尚待详细说明，因此应谨慎解释。
Despite being the most widely studied mood stabilizer, researchers have not confirmed a mechanism for lithium’s therapeutic efficacy in Bipolar Disorder (BD). Pharmacogenomic applications may be clinically useful in the future for identifying lithium-responsive patients and facilitating personalized treatment. Six genome-wide association studies (GWAS) reviewed here present evidence of genetic variations related to lithium responsivity and side effect expression. Variants were found on genes regulating the glutamate system, including GAD-like gene 1 (GADL1) and GRIA2 gene, a mutually-regulated target of lithium. In addition, single nucleotide polymorphisms (SNPs) discovered on SESTD1 may account for lithium’s exceptional ability to permeate cell membranes and mediate autoimmune and renal effects. Studies also corroborated the importance of epigenetics and stress regulation on lithium response, finding variants on long, non-coding RNA genes and associations between response and genetic loading for psychiatric comorbidities. Overall, the precision medicine model of stratifying patients based on phenotype seems to derive genotypic support of a separate clinical subtype of lithium-responsive BD. Results have yet to be expounded upon and should therefore be interpreted with caution.
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DOI：
10.1016/s0140-6736(16)00143-4
发表时间：
2016-03-12
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hou L;Heilbronner U;Degenhardt F;Adli M;Akiyama K;Akula N;Ardau R;Arias B;Backlund L;Banzato CEM;Benabarre A;Bengesser S;Bhattacharjee AK;Biernacka JM;Birner A;Brichant-Petitjean C;Bui ET;Cervantes P;Chen GB;Chen HC;Chillotti C;Cichon S;Clark SR;Colom F;Cousins DA;Cruceanu C;Czerski PM;Dantas CR;Dayer A;Étain B;Falkai P;Forstner AJ;Frisén L;Fullerton JM;Gard S;Garnham JS;Goes FS;Grof P;Gruber O;Hashimoto R;Hauser J;Herms S;Hoffmann P;Hofmann A;Jamain S;Jiménez E;Kahn JP;Kassem L;Kittel-Schneider S;Kliwicki S;König B;Kusumi I;Lackner N;Laje G;Landén M;Lavebratt C;Leboyer M;Leckband SG;Jaramillo CAL;MacQueen G;Manchia M;Martinsson L;Mattheisen M;McCarthy MJ;McElroy SL;Mitjans M;Mondimore FM;Monteleone P;Nievergelt CM;Nöthen MM;Ösby U;Ozaki N;Perlis RH;Pfennig A;Reich-Erkelenz D;Rouleau GA;Schofield PR;Schubert KO;Schweizer BW;Seemüller F;Severino G;Shekhtman T;Shilling PD;Shimoda K;Simhandl C;Slaney CM;Smoller JW;Squassina A;Stamm T;Stopkova P;Tighe SK;Tortorella A;Turecki G;Volkert J;Witt S;Wright A;Young LT;Zandi PP;Potash JB;DePaulo JR;Bauer M;Reininghaus EZ;Novák T;Aubry JM;Maj M;Baune BT;Mitchell PB;Vieta E;Frye MA;Rybakowski JK;Kuo PH;Kato T;Grigoroiu-Serbanescu M;Reif A;Del Zompo M;Bellivier F;Schalling M;Wray NR;Kelsoe JR;Alda M;Rietschel M;McMahon FJ;Schulze TG
通讯作者：
Schulze TG
影响因子：
4.8
作者：
de Sousa, Rafael T.;Busnello, Joao V.;Machado-Vieira, Rodrigo
通讯作者：
Machado-Vieira, Rodrigo
影响因子：
2.1
作者：
Dmitrzak-Weglarz, Monika;Rybakowski, Janusz K.;Hauser, Joanna
通讯作者：
Hauser, Joanna
两极疾病中锂长期治疗结果的社会人口统计学和临床预测因素：对当代文献的系统评价和ISBD/IGSLI锂治疗的建议。
影响因子：
4
作者：
Grillault Laroche D;Etain B;Severus E;Scott J;Bellivier F;ISBD-IGSLI Joint Task Force on Lithium Treatment
通讯作者：
ISBD-IGSLI Joint Task Force on Lithium Treatment
影响因子：
5.3
作者：
Grof, P;Duffy, A;Alda, M
通讯作者：
Alda, M