Abstract
Objectives: Methylation of the neuronal nitric oxide synthase (NOS1/nNOS) gene has recently been identified as a promising biomarker of psychiatric disorders. NOS1 plays an essential role in neurite outgrowth and may thus affect the microstructure development of white matter (WM) in the corpus callosum (CC), which is known to be altered in panic disorder (PD). We examined the relationship between NOS1 methylation, WM tracts in the CC, and symptoms based on this finding.Methods: Thirty-two patients with PD and 22 healthy controls (HCs) were recruited after age, gender, and the education level were matched. The cell type used was whole-blood DNA, and DNA methylation of NOS1 was measured at 20 CpG sites in the promoter region. Although 25 patients with PD were assessed with the Panic Disorder Severity Scale (PDSS), diffusion tensor imaging (DTI) scans were only collected from 16 participants with PD.Results: We observed that the PD group showed lower methylation than did the HCs group and positive correlations between the symptom severity of PD and methylation at CpG4 and CpG9. In addition, CpG9 methylation was significantly correlated with the fractional anisotropy (FA) and mean diffusivity (MD) values of the CC and its major components (the genu and the splenium) in the PD group. Furthermore, path analyses showed that CpG9 methylation offers a mediating effect for the association between the MD values of the genu of the CC and PD symptom severity (95% CI = −1.731 to −0.034).Conclusions: The results suggest that CpG9 methylation leads to atypical development of the genu of the CC, resulting in higher PD symptom severity, adding support for the methylation of NOS1 as a future prognostic indicator of PD.
Highlights
Panic disorder (PD) is a frequent anxiety disorder characterized by recurrent accidental panic attacks and unexpected anxiety
We examined the levels of NOS1 methylation between patients with PD and healthy controls (HCs) and how the levels of DNA methylation related to the white matter (WM) microstructure in the corpus callosum (CC)
DNA methylation data were available for all 54 participants, and neuroimaging data were available for 16 participants with PD
Summary
Panic disorder (PD) is a frequent anxiety disorder characterized by recurrent accidental panic attacks and unexpected anxiety. PD is considered to be a multifactorial disease resulting from the interactions of multiple genetic and environmental factors. The 12-month prevalence rate of PD is 0.3%, and the lifetime prevalence rate is estimated at about 0.5% in China [1, 2]. Extensive research has been performed to identify specific biomarkers of PD. Nitric oxide (NO) has been identified as a neuromodulator in the central nervous system (CNS). NO plays an important role in many behavioral domains, including aggression [7], anxiety [8], depression, and cognitive functioning [9]. Of note is that NO can regulate both the glutamatergic and dopaminergic systems, which are strongly implicated in the biochemical pathology of anxiety [10]
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