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Imaging synaptic density in depression

Abstract

Major depressive disorder is a prevalent and heterogeneous disorder with treatment resistance in at least 50% of individuals. Most of the initial studies focused on the monoamine system; however, recently other mechanisms have come under investigation. Specific to the current issue, studies show synaptic involvement in depression. Other articles in this issue report on reductions in synaptic density, dendritic spines, boutons and glia associated with stress and depression. Importantly, it appears that some drugs (e.g., ketamine) may lead to rapid synaptic restoration or synaptogenesis. Direct evidence for this comes from preclinical work. However, neuroimaging studies, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), have become useful in assessing these changes in vivo. Here, we describe the use of neuroimaging techniques in the evaluation of synaptic alterations associated with depression in humans, as well as measurement of synaptic restoration after administration of ketamine. Although more research is desired, use of these techniques widen our understanding of depression and move us further along the path to targeted and effective treatment for depression.

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Fig. 1: Parametric VT images for baseline and 24 hr post-ketamine scans for a representative participant with MDD and low baseline synaptic density levels.

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Funding

Funding support was provided by the Veterans Affairs National Center for PTSD (IE), National Institute of Mental Health (NIMH) Grant R01MH104459 (IE).

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SH prepared PET imaging portions of the manuscript and contributed to the overall flow. CA prepared the MR imaging portions of the manuscript and contributed to the overall flow. IE designed the project and oversaw manuscript preparation.

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Correspondence to Irina Esterlis.

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Holmes, S.E., Abdallah, C. & Esterlis, I. Imaging synaptic density in depression. Neuropsychopharmacol. (2022). https://doi.org/10.1038/s41386-022-01368-4

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