MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Hughes MM, 2012 PubMed
Full Info	Hughes MM, Carballedo A, McLoughlin DM, Amico F, Harkin A, et al. (2012) Tryptophan depletion in depressed patients occurs independent of kynurenine pathway activation. Brain Behav Immun 26: 979-987.

Study

Hypothesis or Background	The kynurenine pathway (KP) and its rate-limiting tryptophan degrading enzyme indolamine 2,3-dioxygenase (IDO) have been implicated in the pathogenesis of depression. IDO expression is driven by inflammatory cytokines, and has been suggested as the link between inflammation and a serotonergic deficit in depression. Studies also indicate that inflammatory cytokines upregulate the serotonin transporter (SERT), representing another mechanism by which inflammation could influence serotonin availability.
Sample Information	patients with major depressive disorder (MDD) compared with age and sex-matched controls
Method Detail
Method Keywords
Result	Whilst no changes in TNF-alpha or IL-1beta were observed, plasma concentrations of IL-6, IFN-gamma and CRP were increased in the depressed cohort. Despite this inflammatory phenotype, IDO expression or plasma kynurenine were not significantly different between MDD patients and controls. In addition, there was no difference between controls and depressives in concentrations of KYNA and 3-HAA, or in expression of enzymes KAT, KMO or kynureninase that drive their production. Nonetheless, a depletion in tryptophan was evident in depressed patients and was correlated with HAM-D scores. In addition, we failed to observe any difference in SERT mRNA expression in the blood cells from patients with MDD relative to controls. These data support the idea that a mild inflammatory signature is evident in MDD and is accompanied by reduced circulating tryptophan concentrations. However, we found no indication of KP activation in the depressed cohort suggesting that an alternative mechanism mediates the depletion of tryptophan observed.
Conclusions	Taken together these data question the ability of the mild inflammatory phenotype observed in depression to induce molecules such as IDO and SERT that could negatively impact upon serotonergic functioning.

Relationships reported by Hughes MM, 2012

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	Single-stranded DNA-binding protein, mitochondrial (SERT)	protein		We failed to observe any difference in SERT mRNA expression in the blood cells from patients with MDD relative to controls.	Negative
MDD	syndrome	C-reactive protein (CRP)	protein		Whilst no changes in TNF-alpha or IL-1beta were observed, plasma concentrations of IL-6, IFN-gamma and CRP were increased in the depressed cohort.	Positive
MDD	syndrome	Indoleamine 2,3-dioxygenase 1 (IDO)	protein		Despite this inflammatory phenotype, IDO expression or plasma kynurenine were not significantly different between MDD patients and controls	Negative
MDD	syndrome	G-protein coupled receptor 35 (KYNA)	protein		There was no difference between controls and depressives in concentrations of KYNA and 3-HAA, or in expression of enzymes KAT, KMO or kynureninase that drive their production.	Negative
MDD	syndrome	3-Hydroxyanthranilic Acid (3-HAA)	molecule		There was no difference between controls and depressives in concentrations of KYNA and 3-HAA, or in expression of enzymes KAT, KMO or kynureninase that drive their production.	Negative
MDD	syndrome	Histone acetyltransferase type B catalytic subunit (KAT)	protein		There was no difference between controls and depressives in concentrations of KYNA and 3-HAA, or in expression of enzymes KAT, KMO or kynureninase that drive their production.	Negative
MDD	syndrome	Kynurenine 3-monooxygenase (kynurenine 3-monooxygenase)	protein		There was no difference between controls and depressives in concentrations of KYNA and 3-HAA, or in expression of enzymes KAT, KMO or kynureninase that drive their production.	Negative
MDD	syndrome	Kynureninase (kynureninase)	protein		There was no difference between controls and depressives in concentrations of KYNA and 3-HAA, or in expression of enzymes KAT, KMO or kynureninase that drive their production.	Negative
MDD	syndrome	Tryptophan (tryptophan)	molecule		A depletion in tryptophan was evident in depressed patients and was correlated with HAM-D scores	Positive
MDD	syndrome	Interferon gamma (IFN-gamma)	protein		Whilst no changes in TNF-alpha or IL-1beta were observed, plasma concentrations of IL-6, IFN-gamma and CRP were increased in the depressed cohort.	Positive
MDD	syndrome	Interleukin-6 (IL-6)	protein		Whilst no changes in TNF-alpha or IL-1beta were observed, plasma concentrations of IL-6, IFN-gamma and CRP were increased in the depressed cohort.	Positive
MDD	syndrome	Interleukin-1 beta (IL-1beta)	protein		Whilst no changes in TNF-alpha or IL-1beta were observed, plasma concentrations of IL-6, IFN-gamma and CRP were increased in the depressed cohort.	Negative
MDD	syndrome	Tumor necrosis factor (TNF-alpha)	protein		Whilst no changes in TNF-alpha or IL-1beta were observed, plasma concentrations of IL-6, IFN-gamma and CRP were increased in the depressed cohort.	Negative