Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia

Jeffrey K. Yao, George G. Dougherty, Ravinder D. Reddy, Matcheri S. Keshavan, Debra M. Montrose, Wayne R. Matson, Joseph Patrick McEvoy, Rima Kaddurah-Daouk

Research output: Contribution to journalArticle

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Abstract

Background: Purine catabolism may be an unappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. Accumulating evidence suggests a pivotal role of oxidative stress in schizophrenia pathology. Methodology/Principal Findings:Using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system, we compared 6 purine metabolites simultaneously in plasma between first-episode neuroleptic-naïve patients with schizophrenia (FENNS, n = 25) and healthy controls (HC, n = 30), as well as between FENNS at baseline (BL) and 4 weeks (4w) after antipsychotic treatment. Significantly higher levels of xanthosine (Xant) and lower levels of guanine (G) were seen in both patient groups compared to HC subjects. Moreover, the ratios of G/guanosine (Gr), uric acid (UA)/Gr, and UA/Xant were significantly lower, whereas the ratio of Xant/G was significantly higher in FENNS-BL than in HC. Such changes remained in FENNS-4w with exception that the ratio of UA/Gr was normalized. All 3 groups had significant correlations between G and UA, and Xan and hypoxanthine (Hx). By contrast, correlations of UA with each of Xan and Hx, and the correlation of Xan with Gr were all quite significant for the HC but not for the FENNS. Finally, correlations of Gr with each of UA and G were significant for both HC and FENNS-BL but not for the FENNS-4w. Conclusions/Significance: During purine catabolism, both conversions of Gr to G and of Xant to Xan are reversible. Decreased ratios of product to precursor suggested a shift favorable to Xant production from Xan, resulting in decreased UA levels in the FENNS. Specifically, the reduced UA/Gr ratio was nearly normalized after 4 weeks of antipsychotic treatment. In addition, there are tightly correlated precursor and product relationships within purine pathways; although some of these correlations persist across disease or medication status, others appear to be lost among FENNS. Taken together, these results suggest that the potential for steady formation of antioxidant UA from purine catabolism is altered early in the course of illness.

Original languageEnglish (US)
Article numbere9508
JournalPloS one
Volume5
Issue number3
DOIs
StatePublished - Mar 3 2010

Fingerprint

uric acid
purines
Uric Acid
Antipsychotic Agents
Schizophrenia
metabolism
hypoxanthine
Hypoxanthine
High pressure liquid chromatography
purine
schizophrenia
guanosine
Mitochondria
Oxidative stress
Guanosine
guanine
Guanine
Pathology
Metabolites
Oxidants

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Yao, J. K., Dougherty, G. G., Reddy, R. D., Keshavan, M. S., Montrose, D. M., Matson, W. R., ... Kaddurah-Daouk, R. (2010). Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia. PloS one, 5(3), [e9508]. https://doi.org/10.1371/journal.pone.0009508

Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia. / Yao, Jeffrey K.; Dougherty, George G.; Reddy, Ravinder D.; Keshavan, Matcheri S.; Montrose, Debra M.; Matson, Wayne R.; McEvoy, Joseph Patrick; Kaddurah-Daouk, Rima.

In: PloS one, Vol. 5, No. 3, e9508, 03.03.2010.

Research output: Contribution to journalArticle

Yao, JK, Dougherty, GG, Reddy, RD, Keshavan, MS, Montrose, DM, Matson, WR, McEvoy, JP & Kaddurah-Daouk, R 2010, 'Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia', PloS one, vol. 5, no. 3, e9508. https://doi.org/10.1371/journal.pone.0009508
Yao, Jeffrey K. ; Dougherty, George G. ; Reddy, Ravinder D. ; Keshavan, Matcheri S. ; Montrose, Debra M. ; Matson, Wayne R. ; McEvoy, Joseph Patrick ; Kaddurah-Daouk, Rima. / Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia. In: PloS one. 2010 ; Vol. 5, No. 3.
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