Study data published in the Journal of Affective Disorders suggest an association between higher levels of certain neuron-derived exosomes (NDE) and major depressive disorder (MDD).

Researchers measured NDE-related blood biomarkers using peripheral blood samples from 34 patients with MDD and 34 age- and sex-matched healthy controls. Participants with an MDD diagnosis were not using any psychotropic medications and were experiencing an acute depressive episode at the time of the study. Depressive symptoms were assessed using the Beck Depression Inventory. A sandwich immunoassay was developed to capture NDE levels, using antineuron antibody and antibodies against CD81, an exosome marker, and similar proteins related to neuroinflammation. 

Researchers detected a moderate to strong correlation between CD81 levels and most neuron-related blood biomarkers in patients with MDD, including interleukin (IL)-1 beta, IL-6, IL-34, tumor necrosis factor (TNF) alpha, orexin receptors (all P <.001), and TNF receptor 1 (TNFR1) (P =.012). As such, all biomarkers were subsequently normalized by CD81 levels. Per this baseline adjustment, patients with MDD had significantly higher levels of IL-34/CD81 compared with healthy controls (P <.001). Additionally, higher synaptophysin (SYP), SYP/CD81, and TNFR1/CD81 levels were correlated with increased MDD severity. Specifically, SYP/CD81 levels were correlated with more severe affective (P =.046), motivational (P =.023), cognitive (P =.036), cognitive distortion (P =.036), behavioral (P =.013), and vegetative (P =.007) symptoms. TNFR1/CD81 levels were associated with worse behavioral symptoms (P =.004).

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These data substantiate claims that certain neuroinflammatory biomarkers may predict depression symptoms or severity and could be useful in developing diagnostic and treatment strategies. 


Kuwano N, Kato TA, Mitsuhashi M, et al. Neuron-related blood inflammatory markers as an objective evaluation tool for major depressive disorder: an exploratory pilot case-control study. J Affect Disord. 2018;240:88-98.