Lower synaptic density is associated with depression severity and network alterations

• Published in: Nature communications 2019-04, Vol.10 (1), p.1529-1529, Article 1529
• Main Authors: Holmes, Sophie E., Scheinost, Dustin, Finnema, Sjoerd J., Naganawa, Mika, Davis, Margaret T., DellaGioia, Nicole, Nabulsi, Nabeel, Matuskey, David, Angarita, Gustavo A., Pietrzak, Robert H., Duman, Ronald S., Sanacora, Gerard, Krystal, John H., Carson, Richard E., Esterlis, Irina
• Format: Article
• Language: English
• Subjects: 631/378; 631/378/2591; 692/699/476/1414; 692/699/476/1830; Adult; Density; Depression - pathology; Depressive Disorder, Major - pathology; Female; Functional magnetic resonance imaging; Glycoproteins; Humanities and Social Sciences; Humans; Magnetic resonance imaging; Male; Membrane Glycoproteins - metabolism; Mental depression; Mental disorders; Middle Aged; multidisciplinary; Nerve endings; Nerve Tissue Proteins - metabolism; Neural networks; NMR; Nuclear magnetic resonance; Positron emission; Positron emission tomography; Post traumatic stress disorder; Psychological stress; Science; Science (multidisciplinary); Signs and symptoms; Stress Disorders, Post-Traumatic - pathology; Synapses; Synapses - pathology; Synaptic density; Tomography
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09562-7

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 [ 11 C]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. Lowered synaptic density is believed to occur in major depressive disorder and PTSD, possibly as an effect of stress. Here, the authors use positron emission tomography (PET) to measure levels of the synaptic marker SV2A and show that SV2A density is lower in those with more severe symptoms of depression.