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

• Published in: Molecular psychiatry Vol. 16; no. 7; pp. 751 - 762
• Main Authors: Shelton, R C, Claiborne, J, Sidoryk-Wegrzynowicz, M, Reddy, R, Aschner, M, Lewis, D A, Mirnics, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2011; Nature Publishing Group
• Subjects: 631/208/191/2018; 631/80/82/23; 692/420/256; 692/699/476/1414; Adult; Adult and adolescent clinical studies; Aged; Amphetamines; Apoptosis; Apoptosis - physiology; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Brain; Brain research; Brodmann's area; Caspase-1; Cluster Analysis; Computer programs; Cortex (frontal); Cortex (prefrontal); Cytokines; Cytokines - genetics; Cytokines - metabolism; Depression; Depression, Mental; Depressive Disorder, Major - pathology; DNA microarrays; Etiology; Female; Frontal Lobe - metabolism; Frontal Lobe - physiopathology; gamma -Interferon; Gene expression; Gene Expression Profiling; Genetic aspects; Humans; Inflammation; Interleukin 10; Interleukin 13; Interleukin 15; Interleukin 18; Interleukin 2; Interleukin 3; Interleukin 5; Interleukin 8; Interleukin 9; Lymphotoxin; Male; Medical sciences; Medicine; Medicine & Public Health; Mental depression; Metallothionein; Middle Aged; Mood disorders; Neurosciences; Oligonucleotide Array Sequence Analysis; original-article; Oxidative stress; Pharmacotherapy; Physiological aspects; Prefrontal cortex; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychotropic drugs; Reinforcement; Review boards; software; Statistics as Topic; Tomography; Tumor necrosis factor; Zinc-binding protein; γ-Interferon; United States; United States > US; Nashville Tennessee; apoptosis; microarray; cytokines; inflammation; major depression; oxidative stress; Mood disorder; Oxidative stress; Central nervous system; Cytokine; Depression; Inflammation; Frontal cortex; Genetic determinism; Encephalon; Gene; Genetics; Apoptosis
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/mp.2010.52

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-negative inhibitor pseudo-ICE, 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 (IL-1α), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNγ), and lymphotoxin α (TNF superfamily member 1). The genes showing reduced expression included metallothionein 1M (MT1M), a zinc-binding protein with a significant function in the modulation of oxidative stress. The results of this study indicate that post-mortem brain tissue samples from BA10, a region that is involved in reward-related behavior, show evidence of local inflammatory, apoptotic, and oxidative stress in MDD.