Immune-brain plasticity underpins stress and affective behaviors.
Jinsu Lee, Michael A. Wheeler
Neuron January 7, 2026 DOI: 10.1016/j.neuron.2025.11.020 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review or theoretical paper Peer reviewed |
|---|---|
| Topics | Neuroplasticity |
| Keywords | Immunotherapy Neuroimmunology Psychedelics Stress |
| Key findings | Argues that neuroimmune interactions are key regulators of brain plasticity and vulnerability to mood disorders, and that therapeutic interventions such as anti-inflammatory biologics and psychedelics may target these pathways. |
Abstract
The lifetime prevalence of mood disorders such as major depressive disorder (MDD) is thought to approach up to 50% of the world's population. Traditionally, research into the mechanisms of these disorders has focused on neurotransmission, but emerging evidence highlights neuroimmune interactions-the molecular signaling between immune and brain cells-as key regulators of brain plasticity, affective behavior, and potential vulnerability to mood disorders. Chronic stress models have unearthed how immune cell responses modify neural circuit activity, synaptic connectivity, and behaviors relevant for mood disorders by acting on brain-resident cell types. This perspective synthesizes basic principles of neuroimmune communication derived from animal studies relevant for mood disorders and assesses their relevance in MDD and post-traumatic stress disorder (PTSD). We describe cellular neuroimmune interactions important for behavior as well as the molecular mechanisms that govern immune-brain plasticity across different cell types. We also explore how therapeutic interventions, including anti-inflammatory biologics and psychedelics, can target these pathways. Finally, we chart how the field could dissect neuroimmune interactions across biological scales in the near future by highlighting the conceptual frontiers and emerging technologies. Understanding the modulation of neuroimmune interactions promises to inform next-generation treatments for mood disorders.
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
Cites 48
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
and 43 more in the library