Association Between Five Serum Proteins Levels And White Matter Integrity And In First-episode,drug-na?ve Patients With Major Depressive Disorder

Objective(s):Although the structural abnormalities of white matter(WM)have been described in patients with major depressive disorder(MDD),the neuropathological changes remain unclear.Evidences have highlighted that the WM microstructure damage in MDD was associated with the destruction of myelin and axons,in which immune and inflammatory mechanisms may be involved.Based on the theory,we hypothesized that the injury of WM integrity in MDD patients might link to immune activation and neuroinflammation which lead to the impairment of blood-brain barrier(BBB)and myelin sheath and axon damages,further resulting in an increased serum level of related proteins.Therefore,the current study aimed toinvestigate five proteins serum levels that may be associated with WM destruction and their correlations with WM integrity in first-episode,drug-na?ve MDD patients.These five proteins were the myelin oligodendrocyte glycoprotein(MOG)and the myelin-associated glycoprotein(MAG)which are related to myelin damages;the neurofilament proteins(NF)which may reflect axon damages;the soluble intercellular adhesion molecule-1(s1CAM-1)and the soluble vascular cell adhesion molecule-1(sVCAM-1)which may be related to brain microvascular damages and endothelial dysfunction.We first measured the five proteins serum levels in all participants and then explored the association between these proteins serum levels and WM integrity.Methods:We obtained diffusion tensor images of 102 first-episode,drug-na?ve MDD patients and 81 age-and sex-matched controls.MOG and MAG serum levels of all participants were measured and their correlations with clinical measurements were compared between the two groups.The correlations between WM integrity which was reflected by four parameters and examined using voxel-based analysis(VBA)method and MOG and MAG serum levels were further explored on both local and whole-brain levels.On the basis of the above investigations,NF,sICAM-1 and sVCAM-1 serum levels of 82 MDD patients and 72 controls were further examined,and the correlation between the three proteins serum levels and clinical variables were analyzed.In order to further explore the pathological mechanism of WM microstructure changes,the relationship between abnormal integrity of WM traces and NF,sICAM-1 and sVCAM-1 serum levels were analyzed using tract-based spatial statistics(TBSS)method on both local and whole-brain levels.Results:MOG and MAG serum levels were significantly higher in MDD patients than in controls.Patients with MDD also showed decreased fractional anisotropy(FA)and axial diffusivity in the WM of the bilateral thalamus,right hippocampus,right temporal lobe,and left pulvinar.At the whole-brain level,negative correlations between MOG and MAGserum levels and the FA of the left middle frontal gyrus were demonstrated in MDD patients.Positive correlations between the MD of the same brain area and MOG and MAG levels were found.The MOG level was positively correlated with FA and MD of the right inferior parietal gyrus.The MOG and MAG levels were positively correlated with the FA of the right supplementary motor area.Moreover,in controls,no regions revealed a relationship between the DTI parameters and MOG or MAG levels.The Hamilton Anxiety Rating Scale score was negatively correlated with the FA of the left hippocampus but positively correlated with the FA of the right frontal lobe and left thalamus.A positive correlation between the FA of the bilateral fusiform gyrus and illness duration was also observed.Compared with controls,MDD patients showed significantly higher NF,sICAM-1 and sVCAM-1 serum levels.The FA values of the body and genu of the corpus callosum,left superior and posterior corona radiate,and bilateral anterior corona radiate in patients with MDD were identified to be lower than that in controls.The FA of the left anterior corona radiate was negatively correlated with the sVCAM-1 serum level in MDD patients.The FA of the body of the corpus callosum was negatively correlated with the sICAM-1 serum level in female MDD patients.Conclusion(s):Our findings represent the first evidence of a relationship between elevated serum levels of myelin-specific proteins and impaired WM integrity.A negative relationship between elevated serum levels of cell adhesion molecules and impaired WM integrity was also found,which may indicate the presence of inflammation,immunity activation and dysfunction of endothelial cells as a potential mechanism.The results suggested that the above serum proteins as peripheral blood biomarkers may reflect WM microstructural damages in MDD patients,which might expand the current scope of knowledge regarding the neuropathology of MDD.