DNA methylation of IL-4 gene and the association with childhood trauma in panic disorder.

Increasing evidence suggests that aberrations in the immune-inflammatory pathways contribute to the pathophysiology of panic disorder (PD). We aimed to investigate whether an aberrant DNA methylation of the inflammation-related genes in the development of PD, including CCL3, CRP, CSF2, CXCL8, IFNG, IL12B, IL1A, IL-4, IL-6, TNF. Then, the effect of childhood trauma(CT) on methylation levels of  inflammation-related genes and the severity of PD was also investigated. We compared the methylation levels of the inflammation-related genes between 113 patients with PD and 130 matched healthy controls using MethylTarget approach. In addition, the Hamilton Anxiety Rating Scale (HAMA), Panic Disorder Severity Scale (PDSS) and Childhood Trauma Questionnaire-28 item Short Form (CTQ-28) were respectively assessed to all subjects. The result found that the methylation levels of IL-4 gene was significantly higher in PD patients than controls. ROC results found that the IL-4 gene had a sensitivity of 52.3% and a specificity of 74.6%. The methylation levels of IL-4 gene was significantly positively related to the severity of panic and anxiety. Finally, the hypermethylation of CSF2, CXCL8 and IL-4 genes was significantly associated with higher CT.