Depression is an episodic form of mental illness characterized by mood state transitions with poorly understood neurobiological mechanisms. Antidepressants reverse the effects of stress and depression on synapse function, enhancing neurotransmission, increasing plasticity, and generating new synapses in stress-sensitive brain regions. These properties are shared to varying degrees by all known antidepressants, suggesting that synaptic remodeling could play a key role in depression pathophysiology and antidepressant function. Still, it is unclear whether and precisely how synaptogenesis contributes to mood state transitions. Here, we review evidence supporting an emerging model in which depression is defined by a distinct brain state distributed across multiple stress-sensitive circuits, with neurons assuming altered functional properties, synapse configurations, and, importantly, a reduced capacity for plasticity and adaptation. Antidepressants act initially by facilitating plasticity and enabling a functional reconfiguration of this brain state. Subsequently, synaptogenesis plays a specific role in sustaining these changes over time.

中文翻译：

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调节抑郁情绪状态转变的突触机制

抑郁症是一种突发性精神疾病，其特征是情绪状态转变，而神经生物学机制知之甚少。抗抑郁药可以逆转压力和抑郁对突触功能的影响，增强神经传递，增加可塑性，并在压力敏感的大脑区域产生新的突触。所有已知的抗抑郁药都不同程度地具有这些特性，这表明突触重塑可能在抑郁症病理生理学和抗抑郁功能中发挥关键作用。尽管如此，目前尚不清楚突触发生是否以及究竟如何促进情绪状态转变。在这里，我们回顾了支持一种新兴模型的证据，在该模型中，抑郁症是由分布在多个压力敏感回路中的独特大脑状态来定义的，神经元的功能特性、突触配置发生了改变，重要的是，可塑性和适应能力降低了。抗抑郁药最初的作用是促进可塑性并实现这种大脑状态的功能重新配置。随后，突触发生在维持这些变化方面发挥着特定的作用。