MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Shelton, 2011 PubMed
Full Info	Shelton, R.C., Claiborne, J., Sidoryk-Wegrzynowicz, M., Reddy, R., Aschner, M., Lewis, D.A. and Mirnics, K. (2011) Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression. Mol Psychiatry, 16, 751-762.

Study

Hypothesis or Background	The etiology of major depression (MDD), a common and complex disorder, remains obscure.
Sample Information	psychotropic drug-free persons with a history of MDD and age, gender, and post-mortem interval-matched normal controls (n=14 pairs of subjects)
Method Detail	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 (mid R:average log ratiosmid R:>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.
Method Keywords	microarray
Result	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 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (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.
Conclusions	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.

Relationships reported by Shelton, 2011

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
MDD	syndrome	YBX1 (Y-box-binding protein 1)	gene		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	Positive
MDD	syndrome	LTA (lymphotoxin alpha)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IL9 (IL-9)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IL8 (IL-8)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IL5 (IL-5)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IL3 (IL-3)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IL2 (Il-2)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IL1A (IL-1alpha)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IL15 (IL-15)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IL18 (IL-18)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IL12A (IL-12A)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IL13 (IL-13)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IFNG (IFNgamma)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	IL10 (IL-10)	gene		Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).	Positive
MDD	syndrome	CARD16 (caspase-1 dominant-negative inhibitor pseudo-ICE)	gene		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	Positive
MDD	syndrome	FKGS2 (FKGS2)	gene		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	Positive
MDD	syndrome	Hippocampus (hippocampus)	brain morphology and function	P-value < 0.05	The level of GSK-3beta mRNA expression in the hippocampus was significantly increased in the MDD group (n=8) compared with the control group (n=12, p<0.05).	Positive