We previously demonstrated that cyclic AMP-dependent protein kinase (PKA) phosphorylates neuronal nitric oxide synthase (nNOS) at Ser<sup>1412</sup> in the hippocampal dentate gyrus after forebrain ischemia; this phosphorylation event activates NOS activity and might contribute to depression after cerebral ischemia.
Evidence has shown that single nucleotide polymorphisms located in pre‑microRNA (miRNA) or mature miRNA may modify various biological processes and affect the process of carcinogenesis, and the downregulation of neuronal nitric oxide synthase 1 (NOS1) can induce depression.
In this study, we examined the association between single-nucleotide polymorphisms of the genes encoding SOD2 (superoxide dismutase 2), CAT (catalase), GPx4 (glutathione peroxidase 4), NOS1 (nitric oxide synthase 1), NOS2 (nitric oxide synthase 2), and the development of depressive disorders.
Having a first-degree relative with symptoms of bipolar disorder and having a loaded pedigree for diagnosis of depression each were associated with conversion from BD-NOS to BD-I or II (odds ratio range: 1.09-3.14; relative risk range: 1.06-2.34).
The diminished ACC-NOS1 expression and decreased CSF-NOx levels may be involved in the alterations of ACC activity in depression, possibly by affecting glutamatergic and GABAergic neurotransmission.
For previously investigated candidate genes, some support (at a nominal significance level of 0.05/0.01) was found for association between NOS1 and personality traits (especially extraversion), PSEN1 and depression/neuroticism, and GRIK3 and depression.