Convergent functional genomic studies of ω-3 fatty acids in stress reactivity, bipolar disorder and alcoholism.
Convergent functional genomic studies of ω-3 fatty acids in stress reactivity, bipolar disorder and alcoholism.
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DOI：
10.1038/tp.2011.1
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发表时间：
2011-04-26
影响因子：
6.8
通讯作者：
Niculescu AB
中科院分区：
文献类型：
--
作者：
Le-Niculescu H;Case NJ;Hulvershorn L;Patel SD;Bowker D;Gupta J;Bell R;Edenberg HJ;Tsuang MT;Kuczenski R;Geyer MA;Rodd ZA;Niculescu AB
Omega-3脂肪酸已被提议作为精神疾病的辅助治疗选择。考虑到它们的其他健康益处以及它们相对缺乏毒性、致畸性和副作用，它们可能对儿童和育龄女性特别有用，特别是在怀孕和产后期间。需要对它们的影响有一个全面的机制性理解。在这里，我们报告的翻译研究表明，在双相情感障碍和共病酒精中毒的应激反应性基因敲除小鼠模型中，饮食ω-3脂肪酸，特别是二十二碳六烯酸（DHA）的表型正常化和基因表达的影响，使用生物信息学会聚功能基因组学方法整合动物模型和人类数据，优先考虑疾病相关基因。此外，为了在行为水平上验证新观察到的减少酒精消耗的效果，我们还在独立的动物模型中测试了DHA的效果，即酒精偏好（P）大鼠，这是一种成熟的酒精中毒动物模型。我们的研究揭示了性别差异、大脑区域特异性效应和血液生物标志物，这些可能是DHA效果的基础。值得注意的是，DHA调节目前精神药物靶向的一些相同基因，以及增加髓鞘相关基因的表达。髓鞘相关基因表达减少是神经精神疾病的常见（尽管非特异性）分母。总之，我们的工作支持omega-3脂肪酸，特别是DHA，对一系列精神疾病如应激障碍，双相情感障碍，酒精中毒等的潜在效用。
Omega-3 fatty acids have been proposed as an adjuvant treatment option in psychiatric disorders. Given their other health benefits and their relative lack of toxicity, teratogenicity and side effects, they may be particularly useful in children and in females of child-bearing age, especially during pregnancy and postpartum. A comprehensive mechanistic understanding of their effects is needed. Here we report translational studies demonstrating the phenotypic normalization and gene expression effects of dietary omega-3 fatty acids, specifically docosahexaenoic acid (DHA), in a stress-reactive knockout mouse model of bipolar disorder and co-morbid alcoholism, using a bioinformatic convergent functional genomics approach integrating animal model and human data to prioritize disease-relevant genes. Additionally, to validate at a behavioral level the novel observed effects on decreasing alcohol consumption, we also tested the effects of DHA in an independent animal model, alcohol-preferring (P) rats, a well-established animal model of alcoholism. Our studies uncover sex differences, brain region-specific effects and blood biomarkers that may underpin the effects of DHA. Of note, DHA modulates some of the same genes targeted by current psychotropic medications, as well as increases myelin-related gene expression. Myelin-related gene expression decrease is a common, if nonspecific, denominator of neuropsychiatric disorders. In conclusion, our work supports the potential utility of omega-3 fatty acids, specifically DHA, for a spectrum of psychiatric disorders such as stress disorders, bipolar disorder, alcoholism and beyond.
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影响因子：
2.9
作者：
Bergen AW;Yang XR;Bai Y;Beerman MB;Goldstein AM;Goldin LR;Framingham Heart Study
通讯作者：
Framingham Heart Study
影响因子：
--
作者：
Amminger, G. Paul;Schafer, Miriam R.;Berger, Gregor E.
通讯作者：
Berger, Gregor E.
影响因子：
2.8
作者：
Benes, FM;Todtenkopf, MS;Williams, M
通讯作者：
Williams, M
DOI：
10.1002/ajmg.b.30524
发表时间：
2007-09-05
影响因子：
2.8
作者：
Cassidy, F.;Zhao, C.;McKeon, P.
通讯作者：
McKeon, P.
影响因子：
4.5
作者：
Barley, Kevin;Dracheva, Stella;Byne, William
通讯作者：
Byne, William