GABAergic neuroactive steroids: a new frontier in bipolar disorders?
GABAergic neuroactive steroids: a new frontier in bipolar disorders?
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DOI：
10.1186/1744-9081-8-61
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发表时间：
2012-12-19
期刊：
影响因子：
--
通讯作者：
Preti A
中科院分区：
文献类型：
--
作者：
Carta MG;Bhat KM;Preti A
神经类固醇在大脑中合成并调节大脑兴奋性。越来越多的证据表明，它们具有镇静、麻醉和抗癫痫特性，以及它们对情绪的影响。目前，神经类固醇被分类为甾烷类神经类固醇（别孕烯醇酮和别四氢脱氧皮质酮）、雄甾烷类神经类固醇（雄甾烷酮和乙胆甾酮）或硫酸化神经类固醇（硫酸双烯醇酮和硫酸脱氢表雄酮）。临床前和临床研究结果表明，孕激素衍生物神经甾体，如别孕烯醇酮和别四氢脱氧皮质酮在情绪障碍中发挥作用。氯氮平和奥氮平，这被证明是有效的稳定双相情感障碍，提高在大鼠海马，大脑皮层，和血清中的双烯醇酮水平。在锂处理的小鼠中，与对照水平相比，别孕烯醇酮和双烯醇酮的血液水平升高。诊断为双相情感障碍的女性通常表现出与月经周期相关的症状恶化，并且在分娩后立即表现出对情绪障碍发作或复发的脆弱性，此时孕酮的神经类固醇衍生物水平下降。而在从双相情感障碍中恢复的女性中，与健康对照组或经前期患有重度抑郁症的女性相比，别孕烯醇酮的血浆浓度升高。在抑郁发作期间，血液中的alopregnanolone水平很低。氟西汀治疗倾向于稳定抑郁症患者的神经类固醇水平。这些研究结果表明，这些类固醇具有显着的情绪稳定作用。这一假说与一些抗惊厥药是双相情感障碍有效治疗的观察结果一致，这一发现也与神经类固醇的抗癫痫特性一致。进一步探索神经活性类固醇的作用可能会在心境障碍，特别是双相情感障碍的病因学和治疗研究中开辟新的领域。
Neurosteroids are synthesized in the brain and modulate brain excitability. There is increasing evidence of their sedative, anesthetic and antiseizure properties, as well as their influence on mood. Currently neurosteroids are classified as pregnane neurosteroids (allopregnanolone and allotetrahydrodeoxycorticosterone), androstane neurosteroids (androstanediol and etiocholanone) or sulfated neurosteroids (pregnenolone sulfate and dehydroepiandrosterone sulfate). Both preclinical and clinical findings indicate that progesterone derivative neurosteroids such as allopregnanolone and allotetrahydrodeoxycorticosterone play a role in mood disorders. Clozapine and olanzapine, which were shown to be effective in stabilizing bipolar disorder, elevate pregnenolone levels in rat hippocampus, cerebral cortex, and serum. In lithium-treated mice, the blood levels of allopregnanolone and pregnenolone were elevated compared to control levels. Women diagnosed with bipolar disorder typically show symptomatic exacerbation in relation to the menstrual cycle, and show vulnerability to the onset or recurrence of mood disorders immediately after giving birth, when the levels of neurosteroid derivatives of progesterone drop. Whereas in women who had recovered from bipolar disorder, the plasma concentration of allopregnanolone was elevated compared to either healthy controls or women with major depressive disorder during the premenstrual period. During depressive episodes, blood level of allopregnanolone is low. Treatment with fluoxetine tends to stabilize the levels of neurosteroids in depression. These findings converge to suggest that these steroids have significant mood-stabilizing effect. This hypothesis is consistent with the observation that a number of anticonvulsants are effective therapies for bipolar disorder, a finding also consistent with the antiseizure properties of neurosteroids. Further exploration of action of neuroactive steroids is likely to open new frontiers in the investigation of the etiology and treatment of mood disorders, particularly bipolar disorders.
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