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  Uncovering associations between mental illness diagnosis, nitric oxide synthase gene variation, and peripheral nitric oxide concentration

McNeill, R. V., Kehrwald, C., Brum, M., Knopf, K., Brunkhorst-Kanaan, N., Etyemez, S., et al. (2022). Uncovering associations between mental illness diagnosis, nitric oxide synthase gene variation, and peripheral nitric oxide concentration. Brain, Behavior, and Immunity, 101, 275-283. doi:10.1016/j.bbi.2022.01.006.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000C-85E2-E Version Permalink: https://hdl.handle.net/21.11116/0000-000C-85E3-D
Genre: Journal Article

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McNeill_2022_UncoveringAssociations.pdf (Publisher version), 2MB
 
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2022
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Copyright © 2022 Elsevier Inc.
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https://www.sciencedirect.com/science/article/pii/S0889159122000095 (Publisher version)
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 Creators:
McNeill, Rhiannon V., Author
Kehrwald, Christopher, Author
Brum, Murielle, Author
Knopf, Katrin, Author
Brunkhorst-Kanaan, Nathalie, Author
Etyemez, Semra, Author
Koreny, Carolin, Author
Bittner, Robert A.1, 2, Author
Freudenberg, Florian, Author
Herterich, Sabine, Author
Reif, Andreas, Author
Kittel-Schneider, Sarah, Author
Affiliations:
1Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Max Planck Society, Deutschordenstr. 46, 60528 Frankfurt, DE, ou_2074314              
2Singer Lab, Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Max Planck Society, Deutschordenstraße 46, 60528 Frankfurt, DE, ou_3381220              

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Free keywords: Nitric oxide Genetics Major depressive disorder Bipolar disorder Schizophrenia
 Abstract: Nitric oxide (NO) signalling has been implicated in the pathogenesis of several mental illnesses; however, its specific contribution remains unclear. We investigated whether peripheral NO concentration is associated with specific diagnoses, and whether there is a correlation with genetic variation in NO synthase (NOS) genes. We included 185 participants in the study; 52 healthy controls, 43 major depressive disorder (MDD) patients, 41 bipolar disorder (BPD) patients, and 49 schizophrenia (SCZ) patients. Clinical, genetic, and biochemical data were collected at admission to a psychiatric hospital and at discharge. Serum was used to quantify concentration of the stable NO metabolites nitrite and nitrate. Individuals were genotyped for the NOS1 exon 1f variable number of tandem repeats 1 (VNTR1) polymorphism, and single nucleotide polymorphisms (SNPs) in the NOS1, NOS1AP and NOS3 genes. At admission, SCZ patients were found to have significantly higher peripheral NO metabolite (NOx-) concentrations compared to healthy controls, MDD and BPD patients. NOS1 exon 1f VNTR1 short allele carriers were found to have significantly increased NOx- concentration. Moreover, this result was still significant in patients even at discharge. The data also revealed that patients who did not remit in their depressive symptoms had significantly increased NOx- concentration compared to remitters at discharge, supported by the finding of a significant positive correlation between depression symptom severity and NOx- concentration. Taken together, it is possible that elevated peripheral NOx- concentration is associated with increased severity of psychopathology, potentially due to NOS1 exon1f VNTR1 genotype. Our results further implicate NO signalling in mental illness pathogenesis, supporting its possible use as a peripheral biomarker, and imply that NOS genotype may play a significant role in regulating peripheral NOx- concentration.

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 Dates: 2022-01-152022-03
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.bbi.2022.01.006
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Title: Brain, Behavior, and Immunity
Source Genre: Journal
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Pages: - Volume / Issue: 101 Sequence Number: - Start / End Page: 275 - 283 Identifier: ISSN: 08891591