Neuroactive steroids as modulators of depression and anxiety
Neuroactive steroids as modulators of depression and anxiety
复制标题
DOI：
10.1016/j.neuroscience.2005.07.007
复制
发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Rupprecht, R
中科院分区：
文献类型：
--
作者：
Eser, D;Romeo, E;Rupprecht, R
某些神经活性类固醇通过非基因组机制调节配体门控离子通道。特别是3 α-还原型甾烷类是GABA A型受体的有效正变构调节剂。在重性抑郁症期间，存在3 α-还原型神经活性甾类的失衡，这可通过临床有效的药物治疗来纠正。为了研究这些改变是否是成功的抗抑郁治疗的一般原则，我们研究了非药物治疗选择对重度抑郁症期间神经活性类固醇浓度的影响。无论是部分睡眠剥夺，经颅磁刺激或电休克治疗影响神经活性类固醇水平无关的反应，这些治疗。这些研究表明，抗抑郁药物治疗后观察到的神经活性类固醇的变化更可能反映抗抑郁药的独特药理学特性，而不是临床反应。在惊恐障碍患者中，观察到神经活性类固醇成分的变化与抑郁症患者相反。这些变化可能是自发性惊恐发作的反调节机制。然而，在用胆囊收缩素-四肽或乳酸钠进行的实验性惊恐诱导期间，惊恐障碍患者的3a还原型神经活性类固醇的浓度明显下降，这可能导致GABA能紧张性降低。相比之下，在健康对照中未观察到神经活性类固醇浓度的变化，3 α，5 α-四氢脱氧皮质酮、别四氢脱氧皮质酮除外。GABA A型受体的神经活性类固醇的调制可能有助于抑郁症和焦虑症的病理生理学，并可能提供新的抗焦虑化合物的开发新的目标。(C)2005由Elsevier Ltd代表IBRO出版。
Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the GABA type A-receptor.During major depression there is a dysequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment we studied the impact of non-pharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroids observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder changes in neuroactive steroid composition have been observed opposite of those seen in depression. These changes may represent counterregulatory mechanisms against the occurrence of spontaneous panic attacks. However, during experimental panic induction with either cholecystokinin-tetrapeptide or sodium lactate there was a pronounced decline in the concentrations of 3a-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone, allotetrahydrodeoxycorticosterone. The modulation of GABA type A-receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds. (C) 2005 Published by Elsevier Ltd on behalf of IBRO.