Association between genetic variability of neuronal nitric oxide synthase and sensorimotor gating in humans
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30096361
DOI
10.1016/j.niox.2018.08.002
PII: S1089-8603(18)30026-0
Knihovny.cz E-resources
- Keywords
- Endophenotypes, NOS1, Nitric oxide, Prepulse inhibition, Schizophrenia, Startle,
- MeSH
- Adult MeSH
- Exons MeSH
- Polymorphism, Single Nucleotide * MeSH
- Humans MeSH
- Minisatellite Repeats MeSH
- Nitric Oxide physiology MeSH
- Prepulse Inhibition genetics MeSH
- Schizophrenia genetics MeSH
- Sensory Gating genetics MeSH
- Nitric Oxide Synthase Type I genetics MeSH
- Reflex, Startle genetics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- NOS1 protein, human MeSH Browser
- Nitric Oxide MeSH
- Nitric Oxide Synthase Type I MeSH
Research increasingly suggests that nitric oxide (NO) plays a role in the pathogenesis of schizophrenia. One important line of evidence comes from genetic studies, which have repeatedly detected an association between the neuronal isoform of nitric oxide synthase (nNOS or NOS1) and schizophrenia. However, the pathogenetic pathways linking nNOS, NO, and the disorder remain poorly understood. A deficit in sensorimotor gating is considered to importantly contribute to core schizophrenia symptoms such as psychotic disorganization and thought disturbance. We selected three candidate nNOS polymorphisms (Ex1f-VNTR, rs6490121 and rs41279104), associated with schizophrenia and cognition in previous studies, and tested their association with the efficiency of sensorimotor gating in healthy human adults. We found that risk variants of Ex1f-VNTR and rs6490121 (but not rs41279104) were associated with a weaker prepulse inhibition (PPI) of the acoustic startle reflex, a standard measure of sensorimotor gating. Furthermore, the effect of presence of risk variants in Ex1f-VNTR and rs6490121 was additive: PPI linearly decreased with increasing number of risk alleles, being highest in participants with no risk allele, while lowest in individuals who carry three risk alleles. Our findings indicate that NO is involved in the regulation of sensorimotor gating, and highlight one possible pathogenetic mechanism for NO playing a role in the development of schizophrenia psychosis.
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