Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression

Abstract

The etiology of major depression (MDD), a common and complex disorder, remains obscure. Gene expression profiling was conducted on post-mortem brain tissue samples from Brodmann Area 10 (BA10) in the prefrontal cortex from psychotropic drug-free persons with a history of MDD and age, gender, and post-mortem interval matched normal controls (n=14 pairs of subjects). Microarray analysis was conducted using the Affymetrix Exon 1.0 ST arrays. A list of differential expression changes were determined by dual fold change-probability criteria (|ALR|>0.585 [equivalent to a 1.5-fold difference in either direction], p<0.01), while molecular pathways of interest were evaluated using Gene Set Enrichment Analysis (GSEA) software. The results strongly implicate increased apoptotic stress in the samples from the MDD group. Three anti-apoptotic factors, Y-box binding protein 1 (YBX1), Caspase-1 dominant-negative inhibitor pseudo-ICE (COP1), and the putative apoptosis inhibitor FKGS2 were over-expressed. Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1α (IL1α), IL2, IL3, IL5, IL8, IL9, IL10, IL12A, IL13, IL15, IL18, interferon gamma (IFNγ), and lymphotoxin alpha (LTA; TNF super family member 1). The genes showing reduced expression included metallothionein 1M (MT1M), a zinc binding protein with a significant role in the modulation of oxidative stress. The results of this study suggest that post-mortem brain tissue samples from BA10, a region which is involved in reward-related behavior, show evidence of local inflammatory, apoptotic, and oxidative stress in MDD.