Differential immune system DNA methylation and cytokine regulation in post‐traumatic stress disorder

Abstract

DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects matched by age and sex, and stratified into four groups by post-traumatic stress disorder (PTSD) diagnosis and history of child abuse. Total Life Stress (TLS) was also assessed in all subjects. We evaluated DNA extracted from peripheral blood using the HumanMethylation27 BeadChip and analyzed both global and site-specific methylation. Methylation levels were examined for association with PTSD, child abuse history, and TLS using a linear mixed model adjusted for age, sex, and chip effects. Global methylation was increased in subjects with PTSD. CpG sites in five genes (TPR, CLEC9A, APC5, ANXA2, and TLR8) were differentially methylated in subjects with PTSD. Additionally, a CpG site in NPFFR2 was associated with TLS after adjustment for multiple testing. Notably, many of these genes have been previously associated with inflammation. Given these results and reports of immune dysregulation associated with trauma history, we compared plasma cytokine levels in these subjects and found IL4, IL2, and TNFα levels associated with PTSD, child abuse, and TLS. Together, these results suggest that psychosocial stress may alter global and gene-specific DNA methylation patterns potentially associated with peripheral immune dysregulation. Our results suggest the need for further research on the role of DNA methylation in stress-related illnesses.

Epigenetic Mechanisms in Learned Fear: Implications for PTSD

“…To date, the hypothesis of a role for epigenetic mechanisms in PTSD and amygdala-dependent fear responses has only begun to be tested (Monsey et al, 2011;Roth et al, 2011;Smith et al, 2011). Thus, it is important to begin to assess the role of epigenetics in the amygdala and in PTSD, and the potential therapeutic efficacy of epigenetic drugs in alleviating PTSD.…”

“…Recent studies have implicated epigenetic mechanisms in the psychopathology of PTSD. For example, Kerry Ressler's lab has shown that PTSD patients manifest altered DNA methylation in peripheral blood immune cells and identified several immune system-relevant genes that exhibit persisting epigenetic modification (Smith et al, 2011).…”

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

“…Parental separation in early childhood is also associated with increased CRP in adulthood (Lacey et al, 2013;McDade et al, 2013). Concentrations of IL-6, IL-1β, and TNF-α are elevated with childhood maltreatment (Gouin et al, 2012;Hartwell et al, 2013;Kiecolt-Glaser et al, 2011;Smith et al, 2011;Tietjen et al, 2012). Importantly, exposure to trauma in childhood is associated with increased risk for developing PTSD and other psychiatric conditions (Edwards et al, 2003).…”

Methyl Donors Supplementation Attenuates the Adverse Effects of Maternal High Fructose Diet of Offspring Emotional and Cognitive Behaviors

“…It has been clearly shown that maternal diet with supplementation in methyl donor changes gene expression in central nervous system and global DNA hypomethylation in prefrontal cortex [41]. Epigenetic regulation through DNA methylation or histone acetylation is essential factors in the control of psychiatric disorders such as depression and anxiety [42] [43]. Besides, methyl donors components are involved in some neurotransmitters synthesis namely dopamine, adrenaline, serotonin or acetylcholine known to be involved in regulation of depression state [44], as reported reduction of depression state of juveniles of dams fed to HFD and a methyl donors dietary.…”