DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience.

Miller, Olivia; Shakespeare‐Finch, Jane; Bruenig, Dagmar

doi:10.1037/tra0000574

Cited by 32 publications

(17 citation statements)

References 39 publications

(60 reference statements)

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“…Interestingly, in our study FKBP5 bin 2 methylation correlated with symptom severity, especially anxiety, as well as inversely with empathic perspective taking. This is consistent with previous reports showing increased FKBP5 methylation being associated with high levels of anxiety, depression and PTSD symptoms [ 31 , 54 , 57 ] (for review see [ 49 ]). Our findings expand on this indicating that FKBP5 methylation is also linked to empathy, which is compatible with studies demonstrating that emotional empathy is negatively affected by the experience of acute stress [ 58 ].…”

Section: Discussionsupporting

confidence: 93%

Association between childhood maltreatment, psychopathology and DNA methylation of genes involved in stress regulation: Evidence from a study in Borderline Personality Disorder

Flasbeck

Brüne

2021

PLoS ONE

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Previous research suggests that childhood maltreatment is associated with epigenetic modification of genes involved in hypothalamic-pituitary-adrenal (HPA) functioning, which could cause dysregulation of the stress response system. If pervasive, this may be associated with the development of stress-related disorder in adults, including affective disorders, anxiety disorders, post-traumatic stress disorder (PTSD) or borderline-personality disorder (BPD). The majority of studies have focused on DNA methylation of the glucocorticoid receptor gene (NR3C1) and the FKBP5 encoding gene, which regulates the sensitivity of the glucocorticoid receptor (GR). How methylation of NR3C1 and FKBP5 interferes with childhood adversity and psychopathology as well as empathy is an under-researched issue. Here, we sought to investigate the association of childhood maltreatment in a sample of 89 individuals (44 healthy participants and 45 patients diagnosed with BPD) with the methylation of the 1F promoter region of NR3C1 and the intron 7 of FKBP5 as well as with different measures of psychopathology and empathy. Methylation of FKBP5 (bin 2) correlated with anxiety (SCL-90-R) and the global psychopathological symptom load index (GSI), as well as with lower empathic perspective-taking abilities. Psychopathology and empathy impairments correlated with the level of childhood maltreatment. No difference in FKBP5 methylation was observed between the clinical and the non-clinical group. Methylation of NR3C1 was lower in BPD patients compared to controls, yet with small differences. The results are discussed regarding their biological relevance, including possible evolutionary explanations. In short, the regulation of the GR sensitivity by methylation of FKBP5 correlated with psychopathology and empathy scores, while no correlation emerged with the severity of childhood adversity.

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Section: Discussionsupporting

confidence: 93%

Association between childhood maltreatment, psychopathology and DNA methylation of genes involved in stress regulation: Evidence from a study in Borderline Personality Disorder

Flasbeck

Brüne

2021

PLoS ONE

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“…However, there are now multiple sources of objective evidence for PTG as a construct including self-report, qualitative, and longitudinal studies (Tedeschi et al, 2018). Emerging research has also found evidence for epigenetic markers of PTG (Miller et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Testing theoretical predictors of posttraumatic growth and posttraumatic stress symptoms.

David¹,

Shakespeare‐Finch²,

Krosch³

2022

Psychological Trauma: Theory, Research, Practice, and Policy

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Objective: The current study aimed to assess the new theoretical model of PTG, alongside a measure of posttraumatic stress symptoms (PTSS) due to the ongoing distress that is often experienced by trauma survivors. The study examined the direct pathway to PTG and PTSS through previously identified predictors including core belief disruption, event centrality, and rumination, with the addition of self-disclosure as a predictor variable. Method: Participants (N = 231) who had experienced a traumatic event were recruited through online forums and completed an anonymous survey. Factor analysis revealed 2 distinct types of disclosure: helpful and unhelpful. Hypotheses were tested using hierarchical regressions. Results: The findings supported a combination of event centrality, core-belief disruption, deliberate rumination, and helpful disclosure significantly predicting PTG, with event centrality and unhelpful disclosure being significant predictors of PTSS. Conclusions: The current findings provide support for the direct pathway described in the model of PTG, and that PTSS and PTG share some similar predictors, as well as distinct differences. These findings have the potential to assist clinicians and researchers in recognizing factors that are likely promote the development of PTG. Clinical Impact StatementThis study includes clinically relevant findings in relation to the important role that predictor variables listed in the most recent theoretical model of PTG play in both PTG and PTSS. Further, it investigates a person's subjective experience of self-disclosure and whether this experience led to positive or negative posttrauma outcomes. Findings are applicable to all practitioners working with clients who have experienced trauma and suggest that solely focusing on symptom reduction may not be optimal in promoting positive posttrauma outcomes.

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“…Another SNP (rs3800374 T allele frequency~18%) is associated with an increased cortisol response in males following psychosocial stress (Mahon et al, 2013). A recent study identified epigenetic modifications in FKBP5 and NR3C1 that appear to impact PTSD severity (Miller et al, 2020). Polymorphisms within regulators of the HPA axis have also been identified, including the CRH receptor 1 (CRHR1 Gen-Bank NG_009902.1), that have roles in modulating sensitivity to GCs.…”

Section: The Hpa Axis: a Moderator Of Health And Diseasementioning

confidence: 99%

Chronic stress and Alzheimer's disease: the interplay between the hypothalamic–pituitary–adrenal axis, genetics and microglia

et al. 2021

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Chronic psychosocial stress is increasingly being recognised as a risk factor for sporadic Alzheimer's disease (AD). The hypothalamic-pituitary-adrenal axis (HPA axis) is the major stress response pathway in the body and tightly regulates the production of cortisol, a glucocorticoid hormone. Dysregulation of the HPA axis and increased levels of cortisol are commonly found in AD patients and make a major contribution to the disease process. The underlying mechanisms remain poorly understood. In addition, within the general population there are interindividual differences in sensitivities to glucocorticoid and stress responses, which are thought to be due to a combination of genetic and environmental factors. These differences could ultimately impact an individuals' risk of AD. The purpose of this review is first to summarise the literature describing environmental and genetic factors that can impact an individual's HPA axis reactivity and function and ultimately AD risk. Secondly, we propose a mechanism by which genetic factors that influence HPA axis reactivity may also impact inflammation, a key driver of neurodegeneration. We hypothesize that these factors can mediate glucocorticoid priming of the immune cells of the brain, microglia, to become pro-inflammatory and promote a neurotoxic environment resulting in neurodegeneration. Understanding the underlying molecular mechanisms and identifying these genetic factors has implications for evaluating stress-related risk/progression to neurodegeneration, informing the success of interventions based on stress management and potential risks associated with the common use of glucocorticoids.

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DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience.

Cited by 32 publications

References 39 publications

Association between childhood maltreatment, psychopathology and DNA methylation of genes involved in stress regulation: Evidence from a study in Borderline Personality Disorder

Association between childhood maltreatment, psychopathology and DNA methylation of genes involved in stress regulation: Evidence from a study in Borderline Personality Disorder

Testing theoretical predictors of posttraumatic growth and posttraumatic stress symptoms.

Chronic stress and Alzheimer's disease: the interplay between the hypothalamic–pituitary–adrenal axis, genetics and microglia

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