Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia
Year: 2009
Type: article
Abstract: 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.
Source: Molecular Psychiatry
DOI: 10.1038/mp.2009.33
Institutions: VA Pittsburgh Healthcare System, University of Pittsburgh, University of Pittsburgh Medical Center, Beth Israel Deaconess Medical Center, Harvard University, Wayne State University, Edith Nourse Rogers Memorial Veterans Hospital, Whitehead Institute for Biomedical Research, Duke Medical Center
Language: English
Subfield: Biological Psychiatry
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,490
Funders: U.S. Department of Veterans Affairs, Office of Research and Development, Deutsches Krebsforschungszentrum, National Alliance for Research on Schizophrenia and Depression, National Institutes of Health, VA Pittsburgh Healthcare System, National Institute of Mental Health, National Institute of General Medical Sciences, National Center for Research Resources
Awards: G1242861987, G1521515033, G1544529638, G2328791590, G2519210884, G312247606, G3208529581, EEG SLEEP AND NEURODEVELOPMENT IN SCHIZOPHRENIA, University of Pittsburgh Clinical and Translational Science Institute, G4003309079, G429317626, G4668387028, G5139886712, G7467587095, G9000052321, G9000087328, G9000162959, G9000295902, G9000353347
OpenAlex ID: W1990208139