Faculty, Staff and Student Publications
Publication Date
3-1-2022
Journal
Brain, Behavior, and Immunity
Abstract
Considerable data relate major depressive disorder (MDD) with aberrant immune system functioning. Pro-inflammatory cytokines facilitate metabolism of tryptophan along the kynurenine pathway (KP) putatively resulting in reduced neuroprotective and increased neurotoxic KP metabolites in MDD, in addition to modulating metabolic and immune function. This central nervous system hypothesis has, however, only been tested in the periphery. Here, we measured KP-metabolite levels in both plasma and cerebrospinal fluid (CSF) of depressed patients (n = 63/36 respectively) and healthy controls (n = 48/33). Further, we assessed the relation between KP abnormalities and brain-structure volumes, as well as body mass index (BMI), an index of metabolic disturbance associated with atypical depression. Plasma levels of picolinic acid (PIC), the kynurenic/quinolinic acid ratio (KYNA/QUIN), and PIC/QUIN were lower in MDD, but QUIN levels were increased. In the CSF, we found lower PIC in MDD. Confirming previous work, MDD patients had lower hippocampal, and amygdalar volumes. Hippocampal and amygdalar volumes were correlated positively with plasma KYNA/QUIN ratio in MDD patients. BMI was increased in the MDD group relative to the control group. Moreover, BMI was inversely correlated with plasma and CSF PIC and PIC/QUIN, and positively correlated with plasma QUIN levels in MDD. Our results partially confirm previous peripheral KP findings and extend them to the CSF in MDD. We present the novel finding that abnormalities in KP metabolites are related to metabolic disturbances in depression, but the relation between KP metabolites and depression-associated brain atrophy might not be as direct as previously hypothesized.
Keywords
Depression, Depressive Disorder, Major, Humans, Kynurenic Acid, Kynurenine, Quinolinic Acid, Major depressive disorder, kynurenine pathway, inflammation, central nervous system, brain volumetry, structural magnetic resonance imaging, cerebrospinal fluid
DOI
10.1016/j.bbi.2022.01.002
PMID
34999196
PMCID
PMC9045681
PubMedCentral® Posted Date
4-27-2022
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Included in
Bioinformatics Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Medical Immunology Commons, Oncology Commons