Different changes in cortical tumor necrosis factor-α-related pathways in schizophrenia and mood disorders

The growing body of evidence implicating tumor necrosis factor-alpha (TNF alpha) in the pathophysiology of psychiatric disorders led us to measure levels of that protein in the cortex of subjects with major depressive disorders (MDD). Having reported an increase (458%) in the levels of the transmembrane (tmTNF alpha), but not the soluble (sTNF alpha), form of the protein in Brodmann's area (BA) 46, but not 24, in people with the disorder, we decided to examine additional components of TNF alpha-related pathways in the same regions in people with MDD and extend our studies to the same cortical regions of people with schizophrenia (Sz) and bipolar disorders (BD). Using postmortem tissue, western blots and quantitative PCR, we have now shown there is a significant increase (305%) in tmTNF alpha in Brodmann's area 24, but not 46, from subjects with BD, and that levels of the protein were not altered in Sz. Levels of sTNF alpha were not altered in BD or Sz. In addition, we have shown that levels of TNF receptor 1 (TNFR1) mRNA are increased in BA 24 (53%) and BA 46 (82%) in people with Sz, whereas levels of TNFR2 mRNA was decreased in BA 46 in people with mood disorders (MDD = -51%; BD = -67%). Levels of proteins frequently used as surrogate markers of neuronal, astrocytic and microglia numbers, as well as levels of the pro-inflammatory marker (interleukin 1 beta), were not changed in the cortex of people with mood disorders. Our data suggest there are differential changes in TNF alpha-related markers in the cortex of people with MDD, BD and Sz that may not be related to classical inflammation and may cause changes in different TNF alpha-related signaling pathways.