Instituto de Histologia e Embriologia, Faculdade de Medicina e IBMC, Universidade do Porto, 4200-319, Porto, Portugal.
Curr Neuropharmacol. 2011 Dec;9(4):530-52. doi: 10.2174/157015911798376262.
Depression is a neuropsychiatric disorder affecting a huge percentage of the active population especially in developed countries. Research has devoted much of its attention to this problematic and many drugs have been developed and are currently prescribed to treat this pathology. Yet, many patients are refractory to the available therapeutic drugs, which mainly act by increasing the levels of the monoamines serotonin and noradrenaline in the synaptic cleft. Even in the cases antidepressants are effective, it is usually observed a delay of a few weeks between the onset of treatment and remission of the clinical symptoms. Additionally, many of these patients who show remission with antidepressant therapy present a relapse of depression upon treatment cessation. Thus research has focused on other possible molecular targets, besides monoamines, underlying depression. Both basic and clinical evidence indicates that depression is associated with several structural and neurochemical changes where the levels of neurotrophins, particularly of brain-derived neurotrophic factor (BDNF), are altered. Antidepressants, as well as other therapeutic strategies, seem to restore these levels. Neuronal atrophy, mostly detected in limbic structures that regulate mood and cognition, like the hippocampus, is observed in depressed patients and in animal behavioural paradigms for depression. Moreover, chronic antidepressant treatment enhances adult hippocampal neurogenesis, supporting the notion that this event underlies antidepressants effects. Here we review some of the preclinical and clinical studies, aimed at disclosing the role of neurotrophins in the pathophysiological mechanisms of depression and the mode of action of antidepressants, which favour the neurotrophic/neurogenic hypothesis.
抑郁症是一种影响大量活跃人群的神经精神障碍，尤其是在发达国家。研究已经将大量注意力集中在这个问题上，开发了许多药物，并目前用于治疗这种疾病。然而，许多患者对现有的治疗药物有抗药性，这些药物主要通过增加突触间隙中单胺类物质 5-羟色胺和去甲肾上腺素的水平来发挥作用。即使抗抑郁药有效，通常也会在开始治疗和临床症状缓解之间观察到数周的延迟。此外，许多在接受抗抑郁治疗后症状缓解的患者在停药后会出现抑郁复发。因此，研究的重点已经放在了除单胺类物质以外的其他可能的分子靶点上，这些靶点可能是导致抑郁症的原因。基础和临床证据表明，抑郁症与几种结构和神经化学变化有关，其中神经生长因子的水平，特别是脑源性神经营养因子（BDNF），发生了改变。抗抑郁药以及其他治疗策略似乎可以恢复这些水平。在抑郁症患者和抑郁症动物行为模型中观察到神经元萎缩，主要发生在调节情绪和认知的边缘结构中，如海马体。此外，慢性抗抑郁治疗可增强成年海马神经发生，支持了这一观点，即这种事件是抗抑郁药作用的基础。在这里，我们回顾了一些旨在揭示神经生长因子在抑郁症的病理生理机制和抗抑郁药作用模式中的作用的临床前和临床研究，这些研究支持了神经营养/神经发生假说。
