AUTHOR=Xu Huazhen , Zhong Yuan , Yuan Shiting , Wu Yun , Ma Zijuan , Hao Ziyu , Ding Huachen , Wu Huiqing , Liu Gang , Pang Manlong , Liu Na , Wang Chun , Zhang Ning 

TITLE=Nitric Oxide Synthase Type 1 Methylation Is Associated With White Matter Microstructure in the Corpus Callosum and Greater Panic Disorder Severity Among Panic Disorder Patients

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.755270

DOI=10.3389/fneur.2021.755270

ISSN=1664-2295

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 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 CC, and symptoms based on this finding. Methods: 32 patients with PD and 22 healthy controls (HCs) were recruited after age, gender and 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 the HCs group and positive correlations between PD symptom severity and CpG4,9 methylation. In addition, CpG 9 methylation was significantly correlated with the fractional anisotropy (FA) and mean diffusivity (MD) values of the CC and its major components (genu and splenium) in the PD group. Furthermore, path analyses showed that CpG 9 methylation offers a mediating effect for the association between the MD values of the genu of CC and PD symptom severity (95% confidence intervals, CI [-1.731 to -0.034]). Conclusions: It suggests that CpG 9 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.