Changes in cortical gene expression in major depressive disorders: More evidence implicating inflammatory-related pathways in disease etiology

Abstract Major depressive disorders (MDD) are thought to manifest in people with a genetic predisposition after they encounter a deleterious environmental factor. Genetic mutations and environmental factors, which act through epigenetic mechanisms, can alter gene expression. It is, therefore, significant that extensive changes in gene expression are present in the cortex of people with MDD given that some cortical regions are known to function abnormally in people with that disorder. This review highlights there are regionally specific changes in gene expression in people with MDD suggesting region-specific changes in gene expression could be contributing to the dysfunction of the cortex in people with the disorder. Significantly, changes in gene expression in many cortical regions would be associated with changes in glutamatergic and GABAergic neurotransmission. In addition, an interactome of genes with changed levels of expression in Brodmann’s area (BA) 9 from people with MDD has been reported and it is suggested this interactome represents a biochemical pathway contributing to the pathophysiology of the disorder. This pathway would affect cytokine signaling in the BA 9 from people with MDD. In conclusion, growing understanding of changes in gene expression in people with MDD are helping define the pathophysiology of the disorder. One outcome from this increased understanding is that proteins encoded by genes with changed levels of expression in the cortex of people with MDD should be considered as potentially clinically useful drug targets.