Methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (<i>NR3C1</i>), in maltreated and nonmaltreated children: Associations with behavioral undercontrol, emotional lability/negativity, and externalizing and internalizing symptoms

Cicchetti, Dante; Handley, Elizabeth D.

doi:10.1017/s0954579417001407

Cited by 66 publications

(61 citation statements)

References 78 publications

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“…In two of these studies greater GR gene methylation and reduced GR gene expression was found in cells of the hippocampus—a brain region involved in stress regulation—in suicide victims exposed to childhood maltreatment (Labonte et al., 2012, McGowan et al., 2009). Moreover, an association has also been found between GR gene hypermethylation and both emotion regulation difficulties and externalizing behavior in children (Cicchetti & Handley, 2017). Most research has focused on the role of the primary caregiver, typically the mother; only very few studies included fathers.…”

Section: (Epi)genetics In Parenting Effects On Disruptive Behaviormentioning

confidence: 99%

When mummy and daddy get under your skin: A new look at how parenting affects children's DNA methylation, stress reactivity, and disruptive behavior

Overbeek

Creasey

Wesarg

et al. 2020

New Directions for Child and Adolescent Development

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Child maltreatment is a global phenomenon that affects the lives of millions of children. Worldwide, as many as one in three to six children encounter physical, sexual, or emotional abuse from their caregivers. Children who experience abuse often show alterations in stress reactivity. Although this alteration may reflect a physiological survival response, it can nevertheless be harmful in the long run-increasing children's disruptive behavior and jeopardizing their development in multiple domains. But can we undo this process in atrisk children? Based on several lines of pioneering research, we hypothesize that we indeed can. Specifically, we hypothesize that highly dysfunctional parenting leads to an epigenetic pattern in children's glucocorticoid genes that contributes to stress dysregulation and disruptive behavior. However, we also hypothesize that it is possible to "flip the methylation switch" by improving parenting with known-effective parenting interventions in atrisk families. We predict that improved parenting will change methylation in genes in the glucocorticoid pathway, leading to improved stress reactivity and decreased disruptive behavior in children. Future research testing this theory may transform developmental and intervention science, demonstrating how parents can get under their children's skins-and how this mechanism can be reversed.

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Section: (Epi)genetics In Parenting Effects On Disruptive Behaviormentioning

confidence: 99%

When mummy and daddy get under your skin: A new look at how parenting affects children's DNA methylation, stress reactivity, and disruptive behavior

Overbeek

Creasey

Wesarg

et al. 2020

New Directions for Child and Adolescent Development

View full text Add to dashboard Cite

show abstract

“… 12 Adversity in early life (maltreatment, in particular) modifies the neuronal and cognitive processes underlying the stress response via epigenetic mechanisms. 13 …”

Section: Introductionmentioning

confidence: 99%

Borderline personality disorder in adolescents: prevalence, diagnosis, and treatment strategies

Guilé¹,

Boissel²,

Alaux‐Cantin³

et al. 2018

AHMT

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Using the same Diagnostic and Statistical Manual of Mental Disorders, fifth version (DSM-V) criteria as in adults, borderline personality disorder (BPD) in adolescents is defined as a 1-year pattern of immature personality development with disturbances in at least five of the following domains: efforts to avoid abandonment, unstable interpersonal relationships, identity disturbance, impulsivity, suicidal and self-mutilating behaviors, affective instability, chronic feelings of emptiness, inappropriate intense anger, and stress-related paranoid ideation. BPD can be reliably diagnosed in adolescents as young as 11 years. The available epidemiological studies suggest that the prevalence of BPD in the general population of adolescents is around 3%. The clinical prevalence of BPD ranges from 11% in adolescents consulting at an outpatient clinic to 78% in suicidal adolescents attending an emergency department. The diagnostic procedure is based on a clinical assessment with respect to developmental milestones and the interpersonal context. The key diagnostic criterion is the 1-year duration of symptoms. Standardized, clinician-rated instruments are available for guiding this assessment (eg, the Diagnostic Interview for Borderlines-Revised and the Childhood Interview for DSM-IV-TR BPD). The assessment should include an evaluation of the suicidal risk. Differential diagnosis is a particular challenge, given the high frequency of mixed presentations and comorbidities. With respect to clinical and epidemiological studies, externalizing disorders in childhood constitute a risk factor for developing BPD in early adolescence, whereas adolescent depressive disorders are predictive of BPD in adulthood. The treatment of adolescents with BPD requires commitment from the parents, a cohesive medical team, and a coherent treatment schedule. With regard to evidence-based medicine, psychopharmacological treatment is not recommended and, if ultimately required, should be limited to second-generation antipsychotics. Supportive psychotherapy is the most commonly available first-line treatment. Randomized controlled trials have provided evidence in favor of the use of specific, manualized psychotherapies (dialectic-behavioral therapy, cognitive analytic therapy, and mentalization-based therapy).

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“…Existing evidence suggests that placental NR3C1 DNAm is associated with neonatal neurobehavioral status including quality of movement, attention, and self-regulation (Bromer et al, 2013; Paquette et al, 2015; Stroud et al, 2016). Similar associations may exist between NR3C1 DNAm in saliva specimens collected from preschool aged children and concurrent behavioral outcomes (Tyrka et al, 2015; Parade et al, 2016; Cicchetti and Handley, 2017). There is some support for using saliva/buccal tissue in epigenetic analyses as a surrogate for the target brain tissue (Smith et al, 2015).…”

Section: Introductionmentioning

confidence: 65%

Neonatal NR3C1 Methylation and Social-Emotional Development at 6 and 18 Months of Age

Folger

Ding

et al. 2019

Front. Behav. Neurosci.

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The variation in childhood social-emotional development within at-risk populations may be attributed in part to epigenetic mechanisms such as DNA methylation (DNAm) that respond to environmental stressors. These mechanisms may partially underlie the degree of vulnerability (and resilience) to negative social-emotional development within adverse psychosocial environments. Extensive research supports an association between maternal adversity and offspring DNAm of the NR3C1 gene, which encodes the glucocorticoid receptor (GR). A gap in knowledge remains regarding the relationship between NR3C1 DNAm, measured in neonatal (1-month of age) buccal cells, and subsequent social-emotional development during infancy and early childhood. We conducted a longitudinal cohort study of n = 53 mother-child dyads (n = 30 with developmental outcomes formed the basis of current study) who were enrolled in a home visiting (HV) program. Higher mean DNAm of the NR3C1 exon 1F promoter was significantly associated with lower 6-month Ages and Stages Questionnaire: Social-Emotional (ASQ:SE) scores—more positive infant social-emotional functioning. A similar trend was observed at 18-months of age in a smaller sample (n = 12). The findings of this pilot study indicate that in a diverse and disadvantaged population, the level of neonatal NR3C1 DNAm is related to later social-emotional development. Limitations and implications for future research are discussed.

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Methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), in maltreated and nonmaltreated children: Associations with behavioral undercontrol, emotional lability/negativity, and externalizing and internalizing symptoms

Cited by 66 publications

References 78 publications

When mummy and daddy get under your skin: A new look at how parenting affects children's DNA methylation, stress reactivity, and disruptive behavior

When mummy and daddy get under your skin: A new look at how parenting affects children's DNA methylation, stress reactivity, and disruptive behavior

Borderline personality disorder in adolescents: prevalence, diagnosis, and treatment strategies

Neonatal NR3C1 Methylation and Social-Emotional Development at 6 and 18 Months of Age

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