Liao Clara, Dua Alisha N, Wojtasiewicz Cassandra, Liston Conor, Kwan Alex C
Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, USA.
Nat Rev Neurosci. 2025 Feb;26(2):101-114. doi: 10.1038/s41583-024-00876-0. Epub 2024 Nov 18.
A feature in the pathophysiology of major depressive disorder (MDD), a mood disorder, is the impairment of excitatory synapses in the prefrontal cortex. Intriguingly, different types of treatment with fairly rapid antidepressant effects (within days or a few weeks), such as ketamine, electroconvulsive therapy and non-invasive neurostimulation, seem to converge on enhancement of neural plasticity. However, the forms and mechanisms of plasticity that link antidepressant interventions to the restoration of excitatory synaptic function are still unknown. In this Review, we highlight preclinical research from the past 15 years showing that ketamine and psychedelic drugs can trigger the growth of dendritic spines in cortical pyramidal neurons. We compare the longitudinal effects of various psychoactive drugs on neuronal rewiring, and we highlight rapid onset and sustained time course as notable characteristics for putative rapid-acting antidepressant drugs. Furthermore, we consider gaps in the current understanding of drug-evoked in vivo structural plasticity. We also discuss the prospects of using synaptic remodelling to understand other antidepressant interventions, such as repetitive transcranial magnetic stimulation. Finally, we conclude that structural neural plasticity can provide unique insights into the neurobiological actions of psychoactive drugs and antidepressant interventions.
重度抑郁症（MDD）作为一种情绪障碍，其病理生理学特征是前额叶皮质兴奋性突触受损。有趣的是，不同类型的具有相当快速抗抑郁作用（数天或几周内）的治疗方法，如氯胺酮、电休克疗法和非侵入性神经刺激，似乎都集中于增强神经可塑性。然而，将抗抑郁干预与兴奋性突触功能恢复联系起来的可塑性形式和机制仍然未知。在本综述中，我们重点介绍过去15年的临床前研究，这些研究表明氯胺酮和致幻药物可触发皮质锥体细胞树突棘的生长。我们比较了各种精神活性药物对神经元重新布线的纵向影响，并强调快速起效和持续的时间过程是假定的速效抗抑郁药物的显著特征。此外，我们考虑了目前对药物诱发的体内结构可塑性理解上的差距。我们还讨论了利用突触重塑来理解其他抗抑郁干预措施（如重复经颅磁刺激）的前景。最后，我们得出结论，结构性神经可塑性可以为精神活性药物和抗抑郁干预措施的神经生物学作用提供独特的见解。
