Supplementary Material for: Altered DNA Methylation of the Serotonin Transporter Gene Associated with Early Life Stress and White Matter Microalterations in Korean Patients with Panic Disorder

Background: Changes in the DNA methylation of 5-HTTLPR are associated with the pathophysiology of panic disorder (PD). This study was conducted to investigate the association between stressful life events and the level of 5-HTTLPR methylation in patients with PD. We also examined whether these factors were associated with white matter alterations in psychological trauma-related regions. Methods: Participants were 232 patients with PD and 93 healthy adults of Korean descent. DNA methylation levels of five CpG sites in the 5-HTTLPR region were analyzed. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the trauma-related regions. Results: PD patients showed significantly lower levels of the DNA methylation at 5-HTTLPR 5 CpG sites than healthy controls. There were positive correlations between the DNA methylation level at 5-HTTLPR 5 CpG sites and parental separation-related psychological distress in patients with PD. Additionally, there were significant positive associations between the fractional anisotropy values in the superior longitudinal fasciculus (SLF), which might be related to trait anxiety. Conclusion: Early life stress was significantly associated with DNA methylation levels at 5-HTTLPR related to the decreased WM integrity in the SLF region in PD. Decreased WM connectivity in the SLF might be related to trait anxiety and are vital to the pathophysiology of PD.