Yao, JK and Dougherty, GG and Reddy, RD and Keshavan, MS and Montrose, DM and Matson, WR and McEvoy, J and Kaddurah-Daouk, R
(2010)
Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia.
PLoS ONE, 5 (3).
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.
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Details
| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
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| Contributors: |
| Contribution | Contributors Name | Email | Pitt Username | ORCID  |
|---|
| Editor | Hashimoto, Kenji | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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| Date: |
3 March 2010 |
| Date Type: |
Publication |
| Journal or Publication Title: |
PLoS ONE |
| Volume: |
5 |
| Number: |
3 |
| DOI or Unique Handle: |
10.1371/journal.pone.0009508 |
| Refereed: |
Yes |
| MeSH Headings: |
Adolescent; Adult; Antipsychotic Agents--pharmacology; Case-Control Studies; Diet; Female; Guanosine--chemistry; Homeostasis; Humans; Hypoxanthine--chemistry; Male; Metabolism; Oxidation-Reduction; Oxidative Stress; Purines--chemistry; Ribonucleosides--chemistry; Schizophrenia--blood; Schizophrenia--metabolism; Smoking; Uric Acid--chemistry |
| Other ID: |
NLM PMC2831068 |
| PubMed Central ID: |
PMC2831068 |
| PubMed ID: |
20209081 |
| Date Deposited: |
03 Aug 2012 18:46 |
| Last Modified: |
03 Feb 2019 04:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/13333 |
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