Department of Psychiatry, College of Medicine, Psychiatric Institute, University of Illinois at Chicago Chicago, IL, USA.
Front Endocrinol (Lausanne). 2011 Nov 21;2:73. doi: 10.3389/fendo.2011.00073. eCollection 2011.
The pharmacological action of selective serotonin reuptake inhibitor antidepressants may include a normalization of the decreased brain levels of the brain-derived neurotrophic factor (BDNF) and of neurosteroids such as the progesterone metabolite allopregnanolone, which are decreased in patients with depression and posttraumatic stress disorders (PTSD). The allopregnanolone and BDNF level decrease in PTSD and depressed patients is associated with behavioral symptom severity. Antidepressant treatment upregulates both allopregnanolone levels and the expression of BDNF in a manner that significantly correlates with improved symptomatology, which suggests that neurosteroid biosynthesis and BDNF expression may be interrelated. Preclinical studies using the socially isolated mouse as an animal model of behavioral deficits, which resemble some of the symptoms observed in PTSD patients, have shown that fluoxetine and derivatives improve anxiety-like behavior, fear responses and aggressive behavior by elevating the corticolimbic levels of allopregnanolone and BDNF mRNA expression. These actions appeared to be independent and more selective than the action of these drugs on serotonin reuptake inhibition. Hence, this review addresses the hypothesis that in PTSD or depressed patients, brain allopregnanolone levels, and BDNF expression upregulation may be mechanisms at least partially involved in the beneficial actions of antidepressants or other selective brain steroidogenic stimulant molecules.
选择性 5-羟色胺再摄取抑制剂抗抑郁药的药理作用可能包括使大脑源性神经营养因子 (BDNF) 和神经甾体如孕酮代谢物孕烷醇酮的水平正常化，这些物质在抑郁症和创伤后应激障碍 (PTSD) 患者中减少。PTSD 和抑郁患者的孕烷醇酮和 BDNF 水平降低与行为症状严重程度有关。抗抑郁治疗以上调两种方式上调孕烷醇酮水平和 BDNF 的表达，与改善症状有显著相关性，这表明神经甾体生物合成和 BDNF 表达可能相互关联。使用社交隔离小鼠作为行为缺陷的动物模型的临床前研究，这些行为缺陷类似于 PTSD 患者观察到的一些症状，表明氟西汀及其衍生物通过提高皮质边缘的孕烷醇酮和 BDNF mRNA 表达水平来改善焦虑样行为、恐惧反应和攻击行为。这些作用似乎与这些药物对 5-羟色胺再摄取的抑制作用无关，而且更具选择性。因此，本综述提出了这样一种假设，即在 PTSD 或抑郁患者中，大脑孕烷醇酮水平和 BDNF 表达的上调可能是抗抑郁药或其他选择性脑甾体生成刺激分子的有益作用的至少部分机制。
