Challenges and rewards of in vivo synaptic density imaging, and its application to the study of depression.
Ruth H Asch, Chadi G. Abdallah, Richard E. Carson, Irina Esterlis
Neuropsychopharmacology November 1, 2024 DOI: 10.1038/s41386-024-01913-3 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Depression Neuroplasticity |
| Keywords | Mental health Brain research |
| Citations | 11 |
| Key findings | Lower SV2A synaptic density is observed in people with significant depressive symptoms. |
Abstract
The development of novel radiotracers for Positron Emission Tomography (PET) imaging agents targeting the synaptic vesicle glycoprotein 2 A (SV2A), an integral glycoprotein present in the membrane of all synaptic vesicles throughout the central nervous system, provides a method for the in vivo quantification of synaptic density. This is of particular interest in neuropsychiatric disorders given that synaptic alterations appear to underlie disease progression and symptom severity. In this review, we briefly describe the development of these SV2A tracers and the evaluation of quantification methods. Next, we discuss application of SV2A PET imaging to the study of depression, including a review of our findings demonstrating lower SV2A synaptic density in people with significant depressive symptoms and the use of a ketamine drug challenge to examine synaptogenesis in vivo. We then highlight the importance of performing translational PET imaging in animal models in conjunction with clinical imaging. We consider the ongoing challenges, possible solutions, and present preliminary findings from our lab demonstrating the translational benefit and potential of in vivo SV2A imaging in animal models of chronic stress. Finally, we discuss methodological improvements and future directions for SV2A imaging, potentially in conjunction with other neural markers.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cited by 3
- Structural neural plasticity evoked by rapid-acting antidepressant interventions. Nature Reviews Neuroscience February 1, 2025
- Quantitative monitoring of ketamine's impact on synaptic density using 11C-UCB-J PET imaging in the corticosterone mouse model of anxiety/depression. Molecular Psychiatry November 18, 2025
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery. Biomedicines June 1, 2026
Cites 18
- 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
- A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists Philosophical transactions of the Royal Society of London. Series B, Biological sciences July 23, 2012
- NEUROBIOLOGY OF STRESS, DEPRESSION, AND RAPID ACTING ANTIDEPRESSANTS: REMODELING SYNAPTIC CONNECTIONS Depression and Anxiety March 10, 2014
- Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression The Journal of Clinical Psychiatry May 15, 2014
and 13 more in the library