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Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia.

Publication ,  Journal Article
Yao, JK; Dougherty, GG; Reddy, RD; Keshavan, MS; Montrose, DM; Matson, WR; Rozen, S; Krishnan, RR; McEvoy, J; Kaddurah-Daouk, R
Published in: Mol Psychiatry
September 2010

Schizophrenia is characterized by complex and dynamically interacting perturbations in multiple neurochemical systems. In the past, evidence for these alterations has been collected piecemeal, limiting our understanding of the interactions among relevant biological systems. Earlier, both hyper- and hyposerotonemia were variously associated with the longitudinal course of schizophrenia, suggesting a disturbance in the central serotonin (5-hydroxytryptamine (5-HT)) function. Using a targeted electrochemistry-based metabolomics platform, we compared metabolic signatures consisting of 13 plasma tryptophan (Trp) metabolites simultaneously between first-episode neuroleptic-naive patients with schizophrenia (FENNS, n=25) and healthy controls (HC, n=30). We also compared these metabolites between FENNS at baseline (BL) and 4 weeks (4w) after antipsychotic treatment. N-acetylserotonin was increased in FENNS-BL compared with HC (P=0.0077, which remained nearly significant after Bonferroni correction). N-acetylserotonin/Trp and melatonin (Mel)/serotonin ratios were higher, and Mel/N-acetylserotonin ratio was lower in FENNS-BL (all P-values<0.0029), but not after treatment, compared with HC volunteers. All three groups had highly significant correlations between Trp and its metabolites, Mel, kynurenine, 3-hydroxykynurenine and tryptamine. However, in the HC, but in neither of the FENNS groups, serotonin was highly correlated with Trp, Mel, kynurenine or tryptamine, and 5-hydroxyindoleacetic acid (5HIAA) was highly correlated with Trp, Mel, kynurenine or 3-hydroxykynurenine. A significant difference between HC and FENNS-BL was further shown only for the Trp-5HIAA correlation. Thus, some metabolite interactions within the Trp pathway seem to be altered in the FENNS-BL patients. Conversion of serotonin to N-acetylserotonin by serotonin N-acetyltransferase may be upregulated in FENNS patients, possibly related to the observed alteration in Trp-5HIAA correlation. Considering N-acetylserotonin as a potent antioxidant, such increases in N-acetylserotonin might be a compensatory response to increased oxidative stress, implicated in the pathogenesis of schizophrenia.

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Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

September 2010

Volume

15

Issue

9

Start / End Page

938 / 953

Location

England

Related Subject Headings

  • Young Adult
  • Tryptophan
  • Serotonin
  • Schizophrenia
  • Psychiatry
  • Oxidative Stress
  • Melatonin
  • Male
  • Kynurenine
  • Hydroxyindoleacetic Acid
 

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). Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia. Mol Psychiatry, 15(9), 938–953. https://doi.org/10.1038/mp.2009.33
Yao, J. K., G. G. Dougherty, R. D. Reddy, M. S. Keshavan, D. M. Montrose, W. R. Matson, S. Rozen, R. R. Krishnan, J. McEvoy, and R. Kaddurah-Daouk. “Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia.Mol Psychiatry 15, no. 9 (September 2010): 938–53. https://doi.org/10.1038/mp.2009.33.
Yao JK, Dougherty GG, Reddy RD, Keshavan MS, Montrose DM, Matson WR, et al. Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia. Mol Psychiatry. 2010 Sep;15(9):938–53.
Yao, J. K., et al. “Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia.Mol Psychiatry, vol. 15, no. 9, Sept. 2010, pp. 938–53. Pubmed, doi:10.1038/mp.2009.33.
Yao JK, Dougherty GG, Reddy RD, Keshavan MS, Montrose DM, Matson WR, Rozen S, Krishnan RR, McEvoy J, Kaddurah-Daouk R. Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia. Mol Psychiatry. 2010 Sep;15(9):938–953.

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

September 2010

Volume

15

Issue

9

Start / End Page

938 / 953

Location

England

Related Subject Headings

  • Young Adult
  • Tryptophan
  • Serotonin
  • Schizophrenia
  • Psychiatry
  • Oxidative Stress
  • Melatonin
  • Male
  • Kynurenine
  • Hydroxyindoleacetic Acid