Altered immune phenotype and DNA methylation in panic disorder

Abstract

Background 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. 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 results We 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). Conclusions These results suggest that those with panic disorder have changes to their immune system and dysregulation of repeat elements relative to controls.

DNA-methylation dynamics across short-term, exposure-containing CBT in patients with panic disorder

“…While some findings in regard to platelet reactivity indicators and red cell distribution width in PD compared to healthy controls suggest their diagnostic and predictive capacity [ 33 , 34 ], investigations of immune markers in PD are still at the early stage. Petersen et al analyzed immune cell proportions from two previous case-control DNAm studies in PD and observed significantly lower proportions of CD8 + T-lymphocytes, higher proportion of neutrophil as well as increased neutrophil-to-lymphocyte ratio in PD cases, however, after adjustment for age and sex, only CD8 + reduction was still significant [ 17 ]. The authors suggest that reduced CD8 + T cells are consistent with lower levels of IFN-gamma previously detected in a case-control study in PD [ 35 ].…”

“…Few case-control epigenome-wide association studies (EWAS) are available for PD or PD-related symptomatology showing significant association of CpG sites in genes involved in cell-cycle regulation and immune system with overall small effect sizes [14][15][16]. A meta-analysis of two published EWAS [17] identified 61 significantly differentially methylated CpGs on epigenomewide level. Several of those CpGs were annotated to genes which play a role in immune system regulations, such as the Tlymphokine-activated killer cell-originated protein kinase (TOPK) or in brain development and stress-induced depressive behavior, such as SMARCA5.…”

A Systematic Review of LINE-1 Methylation Profile in Psychiatric Disorders

“…Petersen et al [29] investigated the leukocyte proportions and the methylation status of repetitive elements in PD patients. Authors found LINE-1 hypomethylation for PD cases in comparison to the control group (difference in mean beta value = 0.002, p < 0.001), remaining statistically significant after adjustments for sex, age, and years of study.…”

Hypophosphatemia, hypokalaemia and rhabdomyolysis associated with a panic attack

“… 1 2 The prevalence and clinical significance of this finding are not well established, but hypophosphatemia poses risk for numerous medical complications including myopathies resulting in dysphagia, cardiac dysfunction and respiratory failure, as well as seizures and coma. There are reports of acute complications from panic-related hypophosphatemia including lactate elevation 3 and episodic weakness, 4 as well as immune-mediated signalling associated with panic disorder, 5 6 but panic-related rhabdomyolysis has not been reported. This case demonstrates an uncommon instance of rhabdomyolysis deemed secondary to metabolic derangements during an acute panic attack.…”