scholarly journals Methylation of the glucocorticoid receptor gene NR3C1: a summary for clinicians working with children and families

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S241-S241
Author(s):  
Victoria Brown
Keyword(s):  
Mental Illness ◽  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Glucocorticoid Receptor ◽  
Receptor Gene ◽  
Borderline Personality ◽  
Response To Treatment ◽  
Original Research ◽  
Mesh Terms ◽  
Glucocorticoid Receptor Gene

AimsIt has been shown that the glucocorticoid receptor NR3C1 gene can be methylated (“switched off”) in response to early adversity. Methylation has also been linked to physiological changes in the body's response to stress by changing the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis. In adults, associations have been made between NR3C1 methylation and borderline personality disorder, depression and post-traumatic stress disorder. Environmental and social co-variates increase with lifespan so establishing cause and effect is difficult. Studies in children, then, may illuminate patterns to inform current hypotheses.This paper reviews the literature on children and adolescents linking glucocorticoid gene receptor NR3C1 to the psychopathology of mental illness. Findings are presented in an accessible manner to engage people less familiar with genetics and to inform frontline clinicians of this quickly growing area of research.MethodMEDLINE and PsychINFO were searched for relevant peer-reviewed original research using the following keywords and associated mesh terms: NRC31, glucocorticoid receptor gene, methylation, epigenetics, child, adolescent, trauma, psychopathology, gene expression.Result14 studies were identified involving 5475 young people. Degree of NR3C1 methylation was associated with severity of early life adversity. Methylation was linked with psychopathology including borderline personality disorder, internalising symptoms and externalising symptoms with sex differences. The most consistent association was with depression. Methylation seems to modulate the interaction between environment and genetics with the suggestion that the effect may be protective in some cases. However, longitudinal genetic sampling was only conducted in one study.ConclusionHeterogeneity of studies in the epigenetics field are discussed but should not detract from future possibilities. The hope is to identify therapeutic targets or monitor response to treatment as we work to better understand the biology of developmental psychology, mental illness and resilience. There is a growing understanding that epigenetic modifications likely change over time and clinical significance is most likely dictated by changes at multiple gene locations. Thus future research may need to move away from single gene research typically employed in favour of longitudinal whole genome studies in larger population studies.It is time that clinicians integrate the concepts of “epigenetic adaptation to environmental stress” with “nature vs. nurture” in their psychoeducation with families. To understand that one's problems might be the symptom of environmental mismatch, and potentially reversible too, can bring validation and hope to families.

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

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248514
Author(s):  
Vera Flasbeck ◽  
Martin Brüne
Keyword(s):  
Dna Methylation ◽  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Glucocorticoid Receptor ◽  
Childhood Maltreatment ◽  
Childhood Adversity ◽  
Borderline Personality ◽  
Clinical Group ◽  
Related Disorder ◽  
Glucocorticoid Receptor Gene

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.

Childhood trauma and functional disability in psychosis, bipolar disorder and borderline personality disorder: a review of the literature

2014 ◽  
Vol 32 (1) ◽  
pp. 21-30 ◽  
Author(s):  
J. Cotter ◽  
M. Kaess ◽  
A. R. Yung
Keyword(s):  
Bipolar Disorder ◽  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Childhood Trauma ◽  
Psychotic Disorders ◽  
Functional Disability ◽  
Clinical Work ◽  
Borderline Personality ◽  
Response To Treatment ◽  
Neurocognitive Deficits

ObjectivesWe aimed to examine the association between childhood trauma and functional impairment in psychotic disorders, bipolar disorder and borderline personality disorder, to speculate on possible mechanisms that underlie this association and discuss the implications for clinical work.MethodsNarrative review of the peer-reviewed English language literature in the area.ResultsHigh rates of childhood trauma in psychotic disorders, bipolar disorder and borderline personality disorder were identified. This was associated with impaired social and occupational functioning in both the premorbid and established phases of each of these psychiatric disorders over and above the deficits typically observed in these populations. Possible mechanisms mediating this relationship include neurocognitive deficits, insecure attachment, higher rates of comorbidities and problems with adherence and response to treatment.ConclusionsRoutine clinical inquiry about childhood maltreatment should be adopted within mental health settings. This has potentially important treatment implications for identifying those individuals at elevated risk of functional disability. While there is no clear guidance currently available on how to target childhood trauma in the treatment of psychotic disorders, bipolar disorder or borderline personality disorder, there are several promising lines of enquiry and further research is warranted.

Personality problems and disorders

2017 ◽  
Author(s):  
Tom Burns ◽  
Mike Firn
Keyword(s):  
Mental Illness ◽  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Personality Disorders ◽  
Borderline Personality ◽  
Team Work ◽  
Dimensional Approach ◽  
Outreach Workers ◽  
Dsm V ◽  
Icd 10

This chapter deals with the controversial issue of personality disorder, whether these are meaningful diagnoses and, if so, how they affect management. The classification is entirely pragmatic: the definitions and classification in both ICD-10 and DSM-V are outlined along with proposals to abandon categories in favour of a dimensional approach. The issue of treatability is explored, but we conclude that ignoring personality and personality disorders is not a viable alternative for outreach workers. Most of the chapter deals with the management of dissocial personality disorder (usually in men) and borderline personality disorder (usually in women). Specific psychotherapies are not dealt with here; the focus is on how to use team work to manage individuals with severe mental illness and disorders of personality.

Clinical Phenomenology of Borderline Personality Disorder

2017 ◽  
Author(s):  
Larry Siever
Keyword(s):  
Mental Illness ◽  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Clinical Manifestations ◽  
Borderline Personality ◽  
The Core ◽  
Clinical Phenomenology ◽  
The Brain

This chapter takes an in-depth look at the clinical phenomenology of borderline personality disorder (BPD); the core, essential dimensions that are widely recognized as part of this personality disorder; and will essentially examine what an individual with BPD looks like. Although research on mental illness is moving toward a more neurobiological approach to understanding illness, as we learn more about the brain and the ways in which it affects us, clinicians must maintain awareness of clinical phenomenology. The importance of learning the biological components of mental illness cannot be underscored enough, but as we learn what parts of the brain are activated during various mental activities, we need to be able to understand patients’ clinical manifestations of a disorder and the ways in which it directly affects their lives and the lives of those around them.

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