Regionally-specific changes in levels of tumour necrosis factor in the dorsolateral prefrontal cortex obtained postmortem from subjects with major depressive disorder

Background: From studies in the periphery, changed levels of tumour necrosis factor (TNF) have been implicated in the pathophysiology of major depressive disorders (MDD). Therefore we decided to determine whether TNF was altered in the frontal cortex (Brodmann's areas (BA) 24 and 46) from 10 subjects with MDD and 10 control subjects. Methods: Tissue homogenates were prepared from the left hemisphere and levels of TNF trans-membrane (tmTNF) and TNF soluble (sTNF) forms measured by Western blots. Results: tmTNF was significantly increased in BA 46 (mean ± SEM: 7.70 ± 0.92 vs. 3.18 ± 0.87 Ratio Internal Control, p < 0.001), but not BA 24, from subjects with MDD, there was no change in levels of sTNF in either CNS region. Limitations: As the report of tmTNF in postmortem CNS from subjects with MDD, our findings need to be replicated in another group of cases. Conclusions: Our data supports the hypothesis that changes in pro-inflammatory pathways may be involved in the pathophysiology of MDD. Targeting these pathways may be a new approach to treating the disorder.