Abstract
The lack of effective treatments and a high rate of relapse in cocaine addiction constitute a major health problem. The present study was conducted to examine the expression of tryptophan-derived metabolites in the context of cocaine addiction and psychiatric comorbidity, which is common in addicted subjects. Abstinent patients with cocaine use disorder (CUD) and control subjects were recruited for a cross-sectional study. Participants were assessed with a semi-structured diagnostic interview (PRISM) based on DSM-IV-TR for substance and mental disorders. Plasma concentrations of tryptophan metabolites and their association with relevant CUD-related variables and psychiatric comorbidity were explored. We observed decreased plasma kynurenic acid concentrations in the cocaine group, however no associations between CUD-related variables and tryptophan-derived metabolites were found. In contrast, 5-HT concentrations were increased in CUD-patients and the diagnosis of different psychiatric disorders in the cocaine group was related to higher plasma 5-HT concentrations compared with non-comorbid patients. Therefore, while changes in plasma kynurenic acid concentrations appear to be directly associated with lifetime CUD, changes in 5-HT concentrations are associated with psychiatric comorbidity. These results emphasize the need to find potential biomarkers for a better stratification of cocaine-addicted patients in order to develop therapeutic approaches to prevent cocaine relapse.
Highlights
The lack of effective treatments and a high rate of relapse in cocaine addiction constitute a major health problem
In this study we evaluated TRP metabolism in the plasma of abstinent cocaine users diagnosed with cocaine use disorder (CUD) to identify metabolites linked to the cocaine addict phenotype
We report a decrease in the plasma concentration of kynurenic acid (KA), a neuroprotective metabolite of the KYN pathway, which is independent of comorbid mental disorders and attributable to CUD
Summary
The lack of effective treatments and a high rate of relapse in cocaine addiction constitute a major health problem. Plasma concentrations of tryptophan metabolites and their association with relevant CUD-related variables and psychiatric comorbidity were explored. We observed decreased plasma kynurenic acid concentrations in the cocaine group, no associations between CUD-related variables and tryptophan-derived metabolites were found. While changes in plasma kynurenic acid concentrations appear to be directly associated with lifetime CUD, changes in 5-HT concentrations are associated with psychiatric comorbidity. These results emphasize the need to find potential biomarkers for a better stratification of cocaine-addicted patients in order to develop therapeutic approaches to prevent cocaine relapse. Alterations of the KYN pathway might contribute to cocaine-induced changes in inflammatory responses that are linked to cocaine symptom severity
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