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

Publication ,  Journal Article
Yao, JK; Dougherty, GG; Reddy, RD; Keshavan, MS; Montrose, DM; Matson, WR; McEvoy, J; Kaddurah-Daouk, R
Published in: PLoS One
March 3, 2010

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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

March 3, 2010

Volume

5

Issue

3

Start / End Page

e9508

Location

United States

Related Subject Headings

  • Xanthines
  • Uric Acid
  • Smoking
  • Schizophrenia
  • Ribonucleosides
  • Purines
  • Oxidative Stress
  • Oxidation-Reduction
  • Metabolism
  • Male
 

Citation

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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
Yao, Jeffrey K., George G. Dougherty, Ravinder D. Reddy, Matcheri S. Keshavan, Debra M. Montrose, Wayne R. Matson, Joseph McEvoy, and Rima Kaddurah-Daouk. “Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia.PLoS One 5, no. 3 (March 3, 2010): e9508. https://doi.org/10.1371/journal.pone.0009508.
Yao JK, Dougherty GG, Reddy RD, Keshavan MS, Montrose DM, Matson WR, et al. Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia. PLoS One. 2010 Mar 3;5(3):e9508.
Yao, Jeffrey K., et al. “Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia.PLoS One, vol. 5, no. 3, Mar. 2010, p. e9508. Pubmed, doi:10.1371/journal.pone.0009508.
Yao JK, Dougherty GG, Reddy RD, Keshavan MS, Montrose DM, Matson WR, McEvoy J, Kaddurah-Daouk R. Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia. PLoS One. 2010 Mar 3;5(3):e9508.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

March 3, 2010

Volume

5

Issue

3

Start / End Page

e9508

Location

United States

Related Subject Headings

  • Xanthines
  • Uric Acid
  • Smoking
  • Schizophrenia
  • Ribonucleosides
  • Purines
  • Oxidative Stress
  • Oxidation-Reduction
  • Metabolism
  • Male