A combination of neuroimaging and plasma metabolomic analysis suggests inflammation is associated with white matter structural connectivity in major depressive disorder

Major depressive disorder (MDD) is a common mental disorder with unknown pathophysiology. The abnormality of white matter structural connectivity and dysregulation of metabolome in MDD had been widely reported previously. Exploration of the relationship between white matter structural connectivity and plasma metabolites would be helpful for explanation of molecular mechanism for the findings from neuroimaging researches in MDD.The diffusion spectrum imaging data were collected for identification of difference of white matter structural connectivity between MDD (n = 49) and HC (n = 68). The plasma metabolite profiles were acquired by liquid chromatography-mass spectrometry analysis and clustered as co-expression modules. The correlation analysis was performed to identify structural connectivity associated metabolite.We identified two structural connectivity related metabolite modules. One module was correlated with fractional anisotropy (FA) value between left middle temporal gyrus and left inferior temporal gyrus, which were enriched in tryptophan metabolism pathway; another module was correlated with fiber numbers (FN) between right fusiform gyrus and right inferior temporal gyrus, which was enriched in lysophosphatidylcholine (LPC), lysophosphatidylinositol (LPI) and lysophosphatidylglycerol (LPG) lipid sets. l-Kynurenine in tryptophan metabolism pathway was negatively correlated with FN between right fusiform gyrus and right inferior temporal gyrus, and LPC was positively correlated with FA value between left middle temporal gyrus and left inferior temporal gyrus in MDD.First, the sample size was relatively small. Second, the long-term effects of antidepressants were not excluded.The results suggested inflammation-related mechanism was associated with white matter structural connectivity in MDD.