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Activation of the kynurenine pathway is associated with striatal volume in major depressive disorder. Psychoneuroendocrinology 2015 Dec;62:54-8

Date

08/02/2015

Pubmed ID

26232650

Pubmed Central ID

PMC4637239

DOI

10.1016/j.psyneuen.2015.07.609

Scopus ID

2-s2.0-84945226640   31 Citations

Abstract

Inflammation, which may be present in a subgroup of individuals with major depressive disorder (MDD), activates the kynurenine metabolic pathway to produce kynurenine metabolites kynurenic acid (KynA) and quinolinic acid (QA). We have previously reported an association between the ratio of KynA to QA and hippocampal volume in MDD. In animals, inflammation leads to deficits in incentive motivation. Given the central role of the nucleus accumbens (NAcc) and other regions of the striatum in motivated behavior, reward processing, and anhedonia, we hypothesized that abnormalities in the concentrations of kynurenine pathway metabolites would be associated with striatal volumes. As previously reported, after controlling for relevant confounds, the KynA/QA ratio was reduced in the serum of unmedicated patients with MDD (n=53) versus healthy controls (HC, n=47) and there was a non-significant trend in the correlation between KynA/QA and severity of anhedonia (r=-0.27, p<0.1). There was no significant difference between the MDD and HC groups in any of the individual kynurenine metabolites or volume of the striatum defined as the sum of the volumes of the NAcc, caudate, and putamen. After regressing out the effects of sex, analysis batch, and supratentorial volume, the kynurenine concentration and the ratio of kynurenine to tryptophan were inversely associated with striatal volumes in the MDD sample (p<0.05, uncorrected). Further, striatal volume was correlated with the items, "concentration difficulties", "lassitude", and "pessimism" from the Montgomery-Asberg Depression Rating Scale. Our results raise the possibility that activation of the kynurenine pathway is a marker of an inflammatory process that leads to reductions in striatal volume. However, unlike the hippocampus, the association does not appear to be mediated by the relative balance between KynA and QA.

Author List

Savitz J, Dantzer R, Meier TB, Wurfel BE, Victor TA, McIntosh SA, Ford BN, Morris HM, Bodurka J, Teague TK, Drevets WC

Author

Timothy B. Meier PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Anhedonia
Biomarkers
Corpus Striatum
Depressive Disorder, Major
Female
Humans
Kynurenic Acid
Kynurenine
Magnetic Resonance Imaging
Male
Middle Aged
Organ Size
Quinolinic Acid
Young Adult
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc