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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 set of differential expression changes was determined by dual-fold change-probability criteria (∣ average log ratios∣> 0.585 [equivalent to a 1.5-fold difference in either direction], P< 0.01), whereas molecular pathways of interest were evaluated using Gene Set Enrichment Analysis software. The results strongly implicate increased apoptotic stress in the samples from the MDD group. Three anti-apoptotic factors, Y-box-binding protein 1, caspase-1 dominant …