Structural neural plasticity evoked by rapid-acting antidepressant interventions.
Clara Liao, Alisha N Dua, Cassandra Wojtasiewicz, Conor Liston, Alex C. Kwan
Nature Reviews Neuroscience February 1, 2025 DOI: 10.1038/s41583-024-00876-0 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Review Longitudinal Peer reviewed |
|---|---|
| Topics | Neuroplasticity |
| Keywords | Antidepressants Mental health Ketamine therapy |
| Citations | 60 |
| Key findings | Ketamine and psychedelic drugs can trigger the growth of dendritic spines in cortical pyramidal neurons, and structural neural plasticity offers insights into the neurobiological actions of psychoactive drugs and antidepressant interventions. |
Abstract
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.
Comparable studies
Other narrative reviews on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists | 2012 | Review | |
| Towards an understanding of psychedelic-induced neuroplasticity. Review of preclinical and clinical studies | 2023 | Review | |
| Buddha's Brain: Neuroplasticity and Meditation [In the Spotlight] | 2008 | Review | |
| Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics | 2021 | Review | |
| Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms | 2020 | Review |
Citations in the library
Cited by 32
- Classification of psychedelics and psychoactive drugs based on brain-wide imaging of cellular c-Fos expression Nature Communications February 12, 2025
- Psilocybin triggers an activity-dependent rewiring of large-scale cortical networks Cell December 5, 2025
- The science of psychedelic medicine. Nature Medicine February 6, 2026
- The ABCs of psychedelics: a preclinical roadmap for drug discovery. TIPS - Trends in Pharmacological Sciences August 28, 2025
- Synaptic priming: A framework for pharmacotherapy in depression. Neuron November 19, 2025
and 27 more in the library
Cites 28
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
and 23 more in the library