An independent component analysis reveals brain structural networks related to TNF-α in drug-naive, 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-alpha (TNF-alpha), 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-alpha in patients with major depression disorder (MDD) using multivariate source-based morphometry (SBM). Forty-five first-episode and drug-naive MDD patients and 38 healthy subjects (HSs) were recruited. High-resolution T1-weighted imaging was performed and serum TNF-alpha 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 theZ-scores and the serum TNF-alpha levels in MDD patients. The serum TNF-alpha 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-alpha levels were significantly correlated with theZ-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-alpha levels in the early stage of MDD were associated with alteration of the prefrontal network.