Associations among peripheral and central kynurenine pathway metabolites and inflammation in depression.

Kynurenine pathway (KP) metabolites are believed to be a link between inflammation and depression through effects on brain glutamate receptors. However, neither the relationship between plasma and cerebrospinal fluid (CSF) KP metabolites nor their association with inflammatory mediators is well-established in depression. Moreover, the clinical profile associated with combined activation of plasma inflammatory and kynurenine pathways is unknown. Accordingly, plasma and CSF-KP metabolites and inflammatory markers along with depressive symptoms and antidepressant treatment response were measured in 72 unmedicated depressed patients. Following bivariate analyses, component factors representing immune and kynurenine variables in the plasma and CSF were extracted and were used to examine directionality of associations in a path model. In addition, patients were clustered using individual markers that most accounted for the association between plasma immune and KP systems. Path analysis revealed a directional association extending from plasma inflammatory markers to plasma kynurenines, to CSF kynurenines. Among immune markers, plasma tumor necrosis factor (TNF) was robustly associated with plasma kynurenine (KYN) and KYN/tryptophan (TRP), which was in turn significantly associated with CSF KYN, kynurenic acid, and quinolinic acid. Clustering of patients based on plasma TNF and KYN/TRP yielded subgroups of high (N = 17) and low (N = 55) TNF-KYN/TRP groups. High TNF-KYN/TRP subjects exhibited greater depression severity, anhedonia, and treatment nonresponse. In conclusion, plasma-KP metabolites may mediate an inflammation-associated depressive symptom profile via CNS KP metabolites that can serve as a target for intervention at the level of inflammation, peripheral KYN metabolism, KYN transport to the brain, or effects of KP metabolites on glutamate receptors.

Atherosclerotic Disease and its Relationship to Lumbar Degenerative Disk Disease, Facet Arthritis, and Stenosis With Computed Tomography Angiography.

BACKGROUND: The intervertebral disk is the largest avascular structure in the body. It relies on passive diffusion from arteries at the periphery of the disk for nutrition. Previous studies have suggested a correlation between vascular disease and lumbar degenerative disk disease (DDD), but the association with facet arthritis and stenosis has not been evaluated. OBJECTIVE: To evaluate the degree of lumbar artery stenosis, aortic atherosclerosis on computed tomography angiography, and its relationship to lumbar DDD, facet arthritis, and spinal canal stenosis. DESIGN: Retrospective case review. SETTING: Academic tertiary care hospital. PARTICIPANTS: Not applicable. METHODS: A total of 300 lumbar arteries (150 lumbar artery pairs of the first to fifth lumbar arteries) were evaluated on consecutive computed tomography angiography scans. Severity of vascular disease of lumbar arteries was documented as normal, mild, moderate, severe, or occluded. Aortic vascular disease was documented along the posterior wall where the lumbar arteries originate. MAIN OUTCOME MEASUREMENTS: The relationship between vascular disease with DDD, facet arthritis, and spinal canal stenosis was examined and further evaluated controlling for age. RESULTS: Lumbar artery and aortic atherosclerosis had a positive relationship with DDD, facet arthritis, and spinal stenosis that was statistically significant (P < .05) even after controlling for age. The correlation coefficient was greatest in the younger age group when looking at lumbar artery vascular disease with DDD (0.73, confidence interval 0.50-0.96, P < .0001) and aortic vascular disease with DDD (0.72, confidence interval 0.49-0.94, P < .0001). The correlation of vascular disease with facet arthritis and stenosis was not strong in the older age group. CONCLUSION: Atherosclerotic disease of the lumbar arteries and aorta correlated with lumbar DDD, facet arthritis, and spinal canal stenosis after we adjusted for age, although the correlation with facet arthritis and spinal canal stenosis was not as strong in the older age group. LEVEL OF EVIDENCE: IV.