Molecular actions and clinical pharmacogenetics of lithium therapy.
Molecular actions and clinical pharmacogenetics of lithium therapy.
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DOI：
10.1016/j.pbb.2014.02.004
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发表时间：
2014-08
影响因子：
3.6
通讯作者：
Gould, Todd D.
中科院分区：
文献类型：
--
作者：
Can, Adem;Schulze, Thomas G.;Gould, Todd D.
情绪障碍，包括双相情感障碍和抑郁症，是相对常见的人类疾病，其药物治疗方案往往不是最佳的。在用于治疗情绪障碍的现有药物和情绪稳定剂中，锂具有独特的临床特征。锂通常可有效治疗双相情感障碍，特别是躁狂症，同时也可用于辅助治疗难治性抑郁症。除了抗躁狂和辅助抗抑郁功效外，锂还被证明可以有效减少自杀和自杀行为。然而，只有一小部分患者表现出对锂疗法的有益反应，并且反应的潜在遗传因素尚不清楚。在这里，我们讨论临床前研究，表明锂的治疗作用可能涉及的机制，包括直接靶向肌醇单磷酸酶和糖原合成酶激酶 3 (GSK-3) 等，以及间接作用，包括调节神经营养和神经递质系统以及昼夜节律功能。接下来，我们讨论了与此背景下患者有效锂疗法的药物遗传学基础相关的当前知识。阐明可能与人类对锂药理学反应有关的遗传因素的进展缓慢，并且关于特定遗传因素的作用的确凿证据仍然有限。然而，全基因组关联研究（GWAS）等新方法的发展，以及基因检测的增加和对情绪障碍患者亚组的识别的改进，将在未来更好地阐明相关遗传因素。
Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and in particular mania, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifests beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium’s therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future.
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影响因子：
4.8
作者：
Berry, GT;Wu, S;Greer, JJ
通讯作者：
Greer, JJ
影响因子：
3.7
作者：
Alexander, Nina;Kuepper, Yvonne;Hennig, Juergen
通讯作者：
Hennig, Juergen
DOI：
10.1038/newbio233267a0
发表时间：
1971-01-01
期刊：
NATURE-NEW BIOLOGY
影响因子：
--
作者：
ALLISON, JH;STEWART, MA
通讯作者：
STEWART, MA
影响因子：
2.5
作者：
Benedetti, F;Serretti, A;Smeraldi, B
通讯作者：
Smeraldi, B
影响因子：
11
作者：
Baum, A. E.;Akula, N.;McMahon, F. J.
通讯作者：
McMahon, F. J.