Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression.
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.
Shelton
R C
RC
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37212, USA. richard.shelton@vanderbilt.edu
Claiborne
J
J
Sidoryk-Wegrzynowicz
M
M
Reddy
R
R
Aschner
M
M
Lewis
D A
DA
Mirnics
K
K
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000503:physiopathology*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D013223:Statistics as Topic
D016207:Cytokines