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.

Objective:Benzodiazepines are sometimes co-prescribed with antidepressants for patients with major depressive disorder (MDD) who have symptoms such as sleep disturbance, restlessness, or anxiety. The aim of the present study was to examine whether serum levels of brain-derived neurotrophic factor (BDNF) differed between patients with MDD treated with fluvoxamine alone and those treated with a fluvoxamine and benzodiazepine combination. Methods:Twenty-eight first-episode patients with MDD were enrolled in the present study. Thirteen patients were male, and 15 were female, with ages ranging from 29 to 70 (mean ± standard deviation [SD], 47.9 ± 11.6) years. All the patients met the DSM-5 criteria for MDD; were physically healthy; and were free of alcohol or drug abuse, comorbid anxiety, or personality disorders at the time of the study. The patients were administered fluvoxamine monotherapy for eight weeks at doses that varied among the patients and were not fixed for ethical reasons. In the benzodiazepine co-administration group, the dose of benzodiazepines was kept constant during the experimental period. Depression was assessed using the Structured Interview Guide for the 17-item Hamilton Depression Rating Scale (HAMD17). Serum BDNF and plasma fluvoxamine levels were measured. Results:The HAMD17 scores in all subjects were significantly decreased after treatment with fluvoxamine. No significant difference was found between the two groups (fluvoxamine versus fluvoxamine and benzodiazepines) regarding the reduction in HAMD17 scores. Serum BDNF levels in all subjects were significantly increased after treatment with fluvoxamine. No difference was observed between the groups regarding the increase in serum BDNF levels. Conclusion:These results suggest that benzodiazepine co-administration did not influence serum BDNF levels or clinical improvement in MDD patients. KeywordsBenzodiazepine, Brain-derived neurotrophic factor, Major depressive disorder, Fluvoxamine Neuropsychiatry (London) (2018) 8(1) 19