Lower synaptic density is associated with depression severity and network alterations

Sophie E. Holmes, Dustin Scheinost, Sjoerd J. Finnema, Mika Naganawa, Margaret T. Davis, Nicole DellaGioia, Nabeel Nabulsi, David Matuskey, Gustavo A. Angarita, Robert H. Pietrzak, Ronald S. Duman, Gerard Sanacora, John H. Krystal, Richard E. Carson and Irina Esterlis ()
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Sophie E. Holmes: Yale School of Medicine
Dustin Scheinost: Radiology and Biomedical Imaging, Yale School of Medicine
Sjoerd J. Finnema: Yale School of Medicine
Mika Naganawa: Radiology and Biomedical Imaging, Yale School of Medicine
Margaret T. Davis: Yale School of Medicine
Nicole DellaGioia: Yale School of Medicine
Nabeel Nabulsi: Radiology and Biomedical Imaging, Yale School of Medicine
David Matuskey: Yale School of Medicine
Gustavo A. Angarita: Yale School of Medicine
Robert H. Pietrzak: Yale School of Medicine
Ronald S. Duman: Yale School of Medicine
Gerard Sanacora: Yale School of Medicine
John H. Krystal: Yale School of Medicine
Richard E. Carson: Radiology and Biomedical Imaging, Yale School of Medicine
Irina Esterlis: Yale School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Synaptic loss and deficits in functional connectivity are hypothesized to contribute to symptoms associated with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The synaptic vesicle glycoprotein 2A (SV2A) can be used to index the number of nerve terminals, an indirect estimate of synaptic density. Here, we used positron emission tomography (PET) with the SV2A radioligand [11C]UCB-J to examine synaptic density in n = 26 unmedicated individuals with MDD, PTSD, or comorbid MDD/PTSD. The severity of depressive symptoms was inversely correlated with SV2A density, and individuals with high levels of depression showing lower SV2A density compared to healthy controls (n = 21). SV2A density was also associated with aberrant network function, as measured by magnetic resonance imaging (MRI) functional connectivity. This is the first in vivo evidence linking lower synaptic density to network alterations and symptoms of depression. Our findings provide further incentive to evaluate interventions that restore synaptic connections to treat depression.

Date: 2019
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DOI: 10.1038/s41467-019-09562-7

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