Systematic Review of the Kynurenine Pathway and Psychoneurological Symptoms Among Adult Cancer Survivors

Abstract

The co-occurrence of multiple psychoneurological symptoms, including pain, sleep disturbance, fatigue, depression, anxiety, and cognitive disturbance among adult cancer survivors led us to question which common biological mechanisms are shared among these conditions. Variances in tryptophan (Trp) levels and downstream metabolites of the kynurenine (Kyn) metabolic pathway are known to affect immune response and psychoneurological symptoms. The objective of this systematic review was to help us (a) better understand the role of the Kyn pathway in psychoneurological symptoms among adult cancer survivors and (b) identify common significant biomarkers across psychoneurological symptoms as a guide for future research. Some evidence has shown that decreased Trp levels and increased Kyn, Trp/Kyn ratio, and kynurenic acid/Trp ratio in parallel with immune activation are correlated with some psychoneurological symptoms among people undergoing cancer treatment, although discrepancies exist between studies. Kyn pathway activation could also be associated with psychoneurological symptoms among adult cancer survivors, but further research is needed to confirm its exact etiological role with respect to psychoneurological symptoms.

Metabolic Pathways Associated With Psychoneurological Symptoms in Children With Cancer Receiving Chemotherapy

“…Our study found that metabolic pathways of fatty acids, bile acids, and amino acids were associated with the PNS in children with chemotherapy. These results were consistent with previous work from adult cancers (Li et al, 2020; Lyon et al, 2018). Specifically, moderate-to-strong correlations were found between changes in pain and tryptophan concentration and kynurenine/tryptophan ratio, as well as between changes in depression and serotonin level in women with breast cancer (Lyon et al, 2018).…”

Patient-centred approaches for the management of unpleasant symptoms in kidney disease

“…As symptoms often occur in clusters, they may also share a common biological aetiology 1,19,30,34 . For example, a psychoneurological symptom cluster (for example, involving pain, fatigue, anxiety, depression, pain, sleep disturbance and cognitive dysfunction) has been consistently observed among patients with cancer -a population that has a similar level of symptom experience to that of patients with advanced CKD [57][58][59][60] .…”

“…Alternatively, between-patient differences in the gut microbiome and putative modulatory effects of micronutrients may have a role 77,78 . As an example, alterations in the metabolism of tryptophan -an essential amino acid that is derived from dietary sources and contributes to the synthesis and regulation of neurotransmittersmight contribute to symptoms relating to sleep, mood and pain 58,79,80 , as well as the increased risk of cardiovascular disease 81 among patients with CKD. Tryptophan is the precursor of a number of signalling molecules, including the neurotransmitter serotonin, the hormone melatonin and vitamin B3 (niacin), all of which have important roles in the regulation of depression and sleep 79 .…”

“…CKD is associated with increased activity of the indolamine 2,3-dioxygenases 1 and 2 (IDO-1 and IDO-2), which catalyse the rate-limiting step of l-tryptophan degradation along the kynurenine pathway 58,79 . Although physiological levels of the downstream metabolite kynurenic acid are generally considered to be neuroprotective through antagonism of the N-methyl-d-aspartate receptor and α-7-nicotinic acetylcholine receptor 58,61,82,84 , elevated levels of kynurenic acid have been linked to neurological disturbances, including spatial and working memory deficits associated with schizophrenia as a result of reduced dopaminergic and glutaminergic transmission 84 . Additional studies are needed to understand better how the enzymes and products of tryptophan metabolism might be leveraged as biomarkers to monitor disease progression, phenotype symptoms or as biological targets for pharmacological or patient-centred lifestyle interventions.…”

Anxiety and depression after breast cancer: The predictive role of monoamine levels

“…Despite the wide prevalence of anxiety and depression among breast cancer survivors, studies exploring the relationship between monoamine levels and such disorders in this population are scarce and inconclusive (Li et al, 2020). Pertl et al (2013) found no association between depression and KYN levels either during cancer treatment or six weeks after finishing chemotherapy or radiation therapy.…”