Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study.

Journal Article

BACKGROUND: Mapping metabolic "signatures" can provide new insights into addictive mechanisms and potentially identify biomarkers and therapeutic targets. OBJECTIVE: We examined the differences in metabolites related to the tyrosine, tryptophan, purine, and oxidative stress pathways between cocaine-dependent subjects and healthy controls. Several of these metabolites serve as biological indices underlying the mechanisms of reinforcement, toxicity, and oxidative stress. METHODS: Metabolomic analysis was performed in 18 DSM-IV-diagnosed cocaine-dependent individuals with at least 2 weeks of abstinence and ten drug-free controls. Plasma concentrations of 37 known metabolites were analyzed and compared using a liquid chromatography electrochemical array platform. Multivariate analyses were used to study the relationship between severity of drug use [Addiction Severity Index (ASI) scores] and biological measures. RESULTS: Cocaine subjects showed significantly higher levels of n-methylserotonin (p < 0.0017) and guanine (p < 0.0031) and lower concentrations of hypoxanthine (p < 0.0002), anthranilate (p < 0.0024), and xanthine (p < 0.012), compared to controls. Multivariate analyses showed that a combination of n-methylserotonin and xanthine contributed to 73% of the variance in predicting the ASI scores (p < 0.0001). Logistic regression showed that a model combining n-methylserotonin, xanthine, xanthosine, and guanine differentiated cocaine and control groups with no overlap. CONCLUSIONS: Alterations in the methylation processes in the serotonin pathways and purine metabolism seem to be associated with chronic exposure to cocaine. Given the preliminary nature and cross-sectional design of the study, the findings need to be confirmed in larger samples of cocaine-dependent subjects, preferably in a longitudinal design.

Full Text

Duke Authors

Cited Authors

  • Patkar, AA; Rozen, S; Mannelli, P; Matson, W; Pae, C-U; Krishnan, KR; Kaddurah-Daouk, R

Published Date

  • October 2009

Published In

Volume / Issue

  • 206 / 3

Start / End Page

  • 479 - 489

PubMed ID

  • 19649617

Electronic International Standard Serial Number (EISSN)

  • 1432-2072

Digital Object Identifier (DOI)

  • 10.1007/s00213-009-1625-1

Language

  • eng

Conference Location

  • Germany