Department of Neuroscience, Carleton University Ottawa, ON, Canada.
Front Cell Neurosci. 2013 Nov 20;7:218. doi: 10.3389/fncel.2013.00218.
Depression is a common chronic psychiatric disorder that is also often co-morbid with numerous neurological and immune diseases. Accumulating evidence indicates that disturbances of neuroplasticity occur with depression, including reductions of hippocampal neurogenesis and cortical synaptogenesis. Improper trophic support stemming from stressor-induced reductions of growth factors, most notably brain derived neurotrophic factor (BDNF), likely drives such aberrant neuroplasticity. We posit that psychological and immune stressors can interact upon a vulnerable genetic background to promote depression by disturbing BDNF and neuroplastic processes. Furthermore, the chronic and commonly relapsing nature of depression is suggested to stem from "faulty wiring" of emotional circuits driven by neuroplastic aberrations. The present review considers depression in such terms and attempts to integrate the available evidence indicating that the efficacy of current and "next wave" antidepressant treatments, whether used alone or in combination, is at least partially tied to their ability to modulate neuroplasticity. We particularly focus on the N-methyl-D-aspartate (NMDA) antagonist, ketamine, which already has well documented rapid antidepressant effects, and the trophic cytokine, erythropoietin (EPO), which we propose as a potential adjunctive antidepressant agent.
抑郁症是一种常见的慢性精神障碍，也常常与许多神经和免疫疾病同时存在。越来越多的证据表明，抑郁症存在神经可塑性障碍，包括海马神经发生和皮质突触发生减少。应激引起的生长因子减少，特别是脑源性神经营养因子（BDNF），可能导致这种异常的神经可塑性。我们假设心理和免疫应激可以在脆弱的遗传背景上相互作用，通过干扰 BDNF 和神经可塑性过程来促进抑郁症。此外，抑郁症的慢性和常复发性质被认为源于情绪回路的“错误连接”，这种连接是由神经可塑性异常驱动的。本综述从这些方面考虑抑郁症，并试图整合现有证据，表明当前和“下一波”抗抑郁治疗的疗效，无论是单独使用还是联合使用，至少部分与它们调节神经可塑性的能力有关。我们特别关注 N-甲基-D-天冬氨酸（NMDA）拮抗剂氯胺酮，它已经具有快速抗抑郁作用，以及细胞因子促红细胞生成素（EPO），我们将其作为一种潜在的辅助抗抑郁药物。
