Eser Daniela, Schüle Cornelius, Baghai Thomas C, Romeo Elena, Rupprecht Rainer
Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany.
Neuroendocrinology. 2006;84(4):244-54. doi: 10.1159/000097879. Epub 2006 Dec 8.
Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3alpha-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 nonpharmacological 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 steroid concentrations 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 to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3alpha-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 3alpha,5alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(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.
某些神经活性甾体通过非基因组机制调节配体门控离子通道。特别是3α-还原孕烷甾体是γ-氨基丁酸A型（GABA(A)）受体的强效正性变构调节剂。在重度抑郁症期间，3α-还原神经活性甾体存在失衡，而临床有效的药物治疗可纠正这种失衡。为了研究这些改变是否是成功抗抑郁治疗的普遍原则，我们研究了非药物治疗方法对重度抑郁症期间神经活性甾体浓度的影响。无论是部分睡眠剥夺、经颅磁刺激还是电惊厥治疗，均未影响神经活性甾体水平，无论对这些治疗的反应如何。这些研究表明，抗抑郁药物治疗后观察到的神经活性甾体浓度变化更可能反映了抗抑郁药独特的药理特性，而非临床反应。在惊恐障碍患者中，观察到神经活性甾体组成的变化与抑郁症患者相反。然而，在通过胆囊收缩素四肽或乳酸钠实验性诱发惊恐发作期间，惊恐障碍患者中3α-还原神经活性甾体的浓度显著下降，这可能导致GABA能张力降低。相比之下，除3α,5α-四氢脱氧皮质酮外，健康对照中未观察到神经活性甾体浓度的变化。神经活性甾体对GABA(A)受体的调节可能有助于抑郁症和焦虑症的病理生理学，并可能为新型抗焦虑化合物的开发提供新的靶点。
