Abstract
BackgroundMultiple studies have related psychiatric disorders and immune alterations. Panic disorder (PD) has been linked with changes in leukocytes distributions in several small studies using different methods for immune characterization. Additionally, alterations in the methylation of repetitive DNA elements, such as LINE-1, have been associated with mental disorders. Here, we use peripheral blood DNA methylation data from two studies and an updated DNA methylation deconvolution library to investigate the relation of leukocyte proportions and methylation status of repetitive elements in 133 patients with panic disorder compared with 118 controls.Methods and resultsWe used DNA methylation data to deconvolute leukocyte cell-type proportions and to infer LINE-1 element methylation comparing PD cases and controls. We also identified differentially methylated CpGs associated with PD using an epigenome-wide association study approach (EWAS), with models adjusting for sex, age, and cell-type proportions. Individuals with PD had a lower proportion of CD8T cells (OR: 0.86, 95% CI: 0.78–0.96, P-adj = 0.030) when adjusting for age, sex, and study compared with controls. Also, PD cases had significantly lower LINE-1 repetitive element methylation than controls (P < 0.001). The EWAS identified 61 differentially methylated CpGs (58 hypo- and 3 hypermethylated) in PD (Bonferroni adjusted P < 1.33 × 10–7).ConclusionsThese results suggest that those with panic disorder have changes to their immune system and dysregulation of repeat elements relative to controls.
Highlights
Multiple studies have related psychiatric disorders and immune alterations
In the combined analysis of immune cell proportions in cases and controls from both studies, we observed significantly lower proportions of CD8+ T-lymphocytes in Panic disorder (PD) cases compared with controls (− 0.97%, P = 0.0044, Fig. 1a)
We observed significantly higher neutrophil proportions in PD cases compared with controls (1.20%, P = 0.043, Fig. 1b)
Summary
Multiple studies have related psychiatric disorders and immune alterations. Panic disorder (PD) has been linked with changes in leukocytes distributions in several small studies using different methods for immune characterization. We use peripheral blood DNA methylation data from two studies and an updated DNA methylation deconvolution library to investigate the relation of leukocyte proportions and methylation status of repetitive elements in 133 patients with panic disorder compared with 118 controls. Panic disorder has been associated with other comorbidities like agoraphobia, clinical depression [2], hypertension [4], diabetes [5], and irritable bowel syndrome, along with higher utilization of health systems [6]. Together, these findings suggest a complex mechanism that is impacted through experience, environment, and biology
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