Dysregulated cerebral blood flow, rather than gray matter Volume, exhibits stronger correlations with blood inflammatory and lipid markers in depression.

Arterial spin labeling (ASL) can be used to detect differences in perfusion for multiple brain regions thought to be important in major depressive disorder (MDD). However, the potential of cerebral blood flow (CBF) to predict MDD and its correlations between the blood lipid levels and immune markers, which are closely related to MDD and brain function change, remain unclear. The 451 individuals - 298 with MDD and 133 healthy controls who underwent MRI at a single time point with arterial spin labelling and a high resolution T1-weighted structural scan. A proportion of MDD also provided blood samples for analysis of lipid and immune markers. We performed CBF case-control comparisons, random forest model construction, and exploratory correlation analyses. Moreover, we investigated the relationship between gray matter volume (GMV), blood lipids, and the immune system within the same sample to assess the differences in CBF and GMV. We found that the left inferior parietal but supramarginal and angular gyrus were significantly different between the MDD patients and HCs (voxel-wise P < 0.001, cluster-wise FWE correction). And bilateral inferior temporal (ITG), right middle temporal gyrus and left precentral gyrus CBF predict MDD (the area under the receiver operating characteristic curve of the random forest model is 0.717) and that CBF is a more sensitive predictor of MDD than GMV. The left ITG showed a positive correlation trend with immunoglobulin G (r = 0.260) and CD4 counts (r = 0.283). The right ITG showed a correlation trend with Total Cholesterol (r = -0.249) and tumour necrosis factor-alpha (r = -0.295). Immunity and lipids were closely related to CBF change, with the immunity relationship potentially playing a greater role. The interactions between CBF, plasma lipids and immune index could therefore represent an MDD pathophysiological mechanism. The current findings provide evidence for targeted regulation of CBF or immune properties in MDD.