Neuronal nitric oxide synthase (NOS1) and its adaptor, NOS1AP, as a genetic risk factors for psychiatric disorders. (January 2015)

• Record Type: Journal Article
• Authors: Freudenberg, F.; Alttoa, A.; Reif, A.
• Is Part Of: Genes, brain, and behavior. Volume 14:Number 1(2015:Feb.)
• Page Start: 46
• Page End: 63
• Publication Date: 2015-01
• Subjects: Behavior genetics -- Periodicals; Neurogenetics -- Periodicals; 616.8
• DOI: 10.1111/gbb.12193
• Languages: English
• ISSNs: 1601-1848

Abstract

<abstract abstract-type="main" id="gbb12193-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="gbb12193-para-0001">Nitric oxide (NO) is a gaseous transmitter produced by nitric oxide synthases (NOSs). The neuronal isoform (NOS‐I, encoded by <italic>NOS1</italic>) is the main source of NO in the central nervous system (CNS). Animal studies suggest that nitrinergic dysregulation may lead to behavioral abnormalities. Unfortunately, the large number of animal studies is not adequately reflected by publications concerning humans. These include post‐mortem studies, determination of biomarkers, and genetic association studies. Here, we review the evidence for the role of NO in psychiatric disorders by focusing on the human <italic>NOS1</italic> gene as well as biomarker studies. Owing to the complex regulation of <italic>NOS1</italic> and the varying function of NOS‐I in different brain regions, no simple, unidirectional association is expected. Rather, the 'where, when and how much' of NO formation is decisive. Present data, although still preliminary and partially conflicting, suggest that genetically driven reduced NO signaling in the prefrontal cortex is associated with schizophrenia and cognition. Both <italic>NOS1</italic> and its interaction partner <italic>NOS1AP</italic> have a role therein. Also, reduced <italic>NOS1</italic> expression in the striatum determined by a length polymorphism in a <italic>NOS1</italic> promoter (<italic>NOS1</italic> ex1f‐VNTR) goes along with a variety of impulsive behaviors. An association of <italic>NOS1</italic> with mood disorders, suggested by animal models, is less clear on the genetic level; however, NO metabolites in blood may serve as biomarkers for major depression and bipolar disorder. As the nitrinergic system comprises a relevant target for pharmacological interventions, further studies are warranted not only to elucidate the pathophysiology of mental disorders, but also to evaluate NO function as a biomarker.</p> </abstract>