Tryptophan and Kynurenine Pathway Metabolites and Psychoneurological Symptoms Among Breast Cancer Survivors

Abstract

BackgroundAmong breast cancer survivors, pain, fatigue, depression, anxiety, and sleep disturbance are common psychoneurological symptoms that cluster together. Inflammation-induced activation of the tryptophan-kynurenine metabolomic pathway may play an important role in these symptoms. AimsThis study investigated the relationship between the metabolites involved in the tryptophan-kynurenine pathway and psychoneurological symptoms among breast cancer survivors. DesignCross-sectional study. SettingParticipants were recruited at the oncology clinic at the University of Illinois Hospital & Health Sciences System. Participants/Subjects: 79 breast cancer survivors after major cancer treatment. MethodsWe assessed psychoneurological symptoms with the PROMIS-29 and collected metabolites from fasting blood among breast cancer survivors after major cancer treatment, then analyzed four major metabolites involved in the tryptophankynurenine pathway (tryptophan, kynurenine, kynurenic acid, and quinolinic acid). Latent profile analysis identified subgroups based on the five psychoneurological symptoms. Mann-Whitney U tests and multivariable logistic regression compared targeted metabolites between subgroups. ResultsWe identified two distinct symptom subgroups (low, 81%; high, 19%). Compared with participants in the low symptom subgroup, patients in the high symptom subgroup had higher BMI (p = .024) and were currently using antidepressants (p = .008). Using multivariable analysis, lower tryptophan levels (p = .019) and higher kynurenine/tryptophan ratio (p = .028) were associated with increased risk of being in the high symptom subgroup after adjusting for BMI and antidepressant status. ConclusionThe tryptophan-kynurenine pathway and impaired tryptophan availability may contribute to the development of psychoneurological symptoms.