An independent component analysis reveals brain structural networks related to TNF-α in drug-naïve, first-episode major depressive disorder: a source-based morphometric study

In a previous mouse study, social defeat stress-induced microglial activation released tumor necrosis factor-α (TNF-α), leading to neuronal changes in the prefrontal cortex (PFC) and behavioral changes (anxiety). We aimed to investigate the relationship between gray-matter (GM) structural networks and serum TNF-α in patients with major depression disorder (MDD) using multivariate source-based morphometry (SBM). Forty-five first-episode and drug-naïve MDD patients and 38 healthy subjects (HSs) were recruited. High-resolution T1-weighted imaging was performed and serum TNF-α levels were measured in all MDD patients and HSs. After acquiring GM structural networks using SBM, we compared the Z-transformed loading coefficients (Z-scores) between MDD patients and HSs, and investigated the relationship between the Z-scores and the serum TNF-α levels in MDD patients. The serum TNF-α levels in MDD patients were significantly higher than those in HSs. We extracted two independent GM structural networks (the prefrontal network and the insula-temporal network) with significant differences between MDD patients and HSs (−0.305 ± 0.85 and 0.253 ± 0.82; P = 0.03 in the prefrontal network, and −0.268 ± 0.86 and 0.467 ± 0.71; P < 0.01 in the insula-temporal network). The serum TNF-α levels were significantly correlated with the Z-scores in the prefrontal network after Bonferroni correction (r = −0.419, p < 0.01); however, the correlation in the insula-temporal network was not significant (r = −0.290, p = 0.11). Elevated serum TNF-α levels in the early stage of MDD were associated with alteration of the prefrontal network.