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

ABSTRACT

CONTEXT Children with cancer undergoing chemotherapy experience a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, and depressive symptoms. Metabolomics is promising to differentiate metabolic pathways associated with the PNS cluster. OBJECTIVES: Identify metabolic pathways associated with the PNS cluster in children with cancer before and after chemotherapy. METHODS: Pain, fatigue, anxiety, and depressive symptoms were assessed using the Pediatric PROMIS scales. T-scores were computed and divided dichotomously by a cutoff point of 50; the PNS cluster was a sum of the four symptoms ranging from 0 (all T-scores <50) to 4 (all T-scores ≥50). Serum metabolites were processed using liquid chromatography mass-spectrometry untargeted metabolomics approach. Linear regression models examined metabolites associated with the PNS cluster. Metabolic pathway enrichment analysis was performed. RESULTS: Participant demographics (n = 40) were 55% female, 60% white, 62.5% aged 13-19 years, and 62.5% diagnoses of Hodgkin's lymphoma and B-cell acute lymphocytic leukemia. Among 9276 unique metabolic features, 454 were associated with pain, 281 with fatigue, 596 with anxiety, 551 with depressive symptoms, and 300 with the PNS cluster across one chemotherapy cycle. Fatty acids pathways were associated with pain de novo fatty acid biosynthesis (p < .001), fatty acid metabolism (p = .001), fatty acid activation (p = .004), and omega-3 fatty acid metabolism (p = .009). Tryptophan amino acid pathway was associated with fatigue (p < .001), anxiety (p = .015), and the PNS cluster (p = .037). Carnitine shuttle was associated with the PNS cluster (p = .015). CONCLUSION: Fatty acids and amino acids pathways were associated with PNS in children undergoing chemotherapy. These findings require further investigation in a larger sample.