Lavergne Francis, Jay Therese M
Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Pathophysiology of Psychiatric Disorders, Paris, France.
Front Psychiatry. 2025 Mar 12;16:1340179. doi: 10.3389/fpsyt.2025.1340179. eCollection 2025.
A review of scientific literature suggests that the use of antidepressants can be broadly extended to address various forms of stress and inflammation as an adjunctive therapy that enhances host resistance. While the effects of antidepressants on mood are well-documented in terms of their emotional, cognitive, and behavioral impacts, these aspects do not fully explain their cellular mechanisms of action. At the cellular level, antidepressants exert trophic effects that promote neurogenesis and synaptic connectivity. Studies demonstrate that antidepressants improve cell survival, enhance stem cell proliferation, and reduce danger perception (mood effects) in depressed patients and animal models of depression. These trophic properties highlight a deeper biological mechanism beyond their mood-related benefits. The acid sphingomyelinase (ASM) theory of mood offers a more compelling explanation of the cellular effects of antidepressants compared to the monoamine hypothesis. Antidepressants functionally inhibit the ASM enzyme, thereby reducing the production of ceramide, which directs cells toward increased survival, cytoprotection, and reproduction, as well as improved mood. This review also highlights research demonstrating that antidepressants enhance host resistance to infections, immunological challenges, stress, and depression. These findings support the potential use of antidepressants to bolster host resilience in scenarios involving infections, vaccinations, cellular aggression, stress, depression, and even aging.
一项科学文献综述表明，抗抑郁药的使用可以广泛扩展，作为一种增强宿主抵抗力的辅助疗法，用于应对各种形式的压力和炎症。虽然抗抑郁药对情绪的影响在其情感、认知和行为影响方面已有充分记录，但这些方面并不能完全解释其细胞作用机制。在细胞水平上，抗抑郁药发挥营养作用，促进神经发生和突触连接。研究表明，抗抑郁药可改善抑郁症患者和抑郁症动物模型中的细胞存活、增强干细胞增殖并降低危险感知（情绪影响）。这些营养特性突出了其超出情绪相关益处的更深层次生物学机制。与单胺假说相比，情绪的酸性鞘磷脂酶（ASM）理论对抗抑郁药的细胞作用提供了更有说服力的解释。抗抑郁药在功能上抑制ASM酶，从而减少神经酰胺的产生，神经酰胺可引导细胞提高存活率、实现细胞保护和增殖，以及改善情绪。本综述还强调了一些研究，这些研究表明抗抑郁药可增强宿主对感染、免疫挑战、压力和抑郁症的抵抗力。这些发现支持了在涉及感染、疫苗接种、细胞侵袭、压力、抑郁症甚至衰老的情况下，使用抗抑郁药来增强宿主恢复力的可能性。
