Dataset Information

Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma.

ABSTRACT: Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic-pituitary-adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1(F) NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10(-8), 5.18 × 10(-7) and 1.25 × 10(-9), respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology.

SUBMITTER: Perroud N

PROVIDER: S-EPMC3309499 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma.

Perroud N N Paoloni-Giacobino A A Prada P P Olié E E Salzmann A A Nicastro R R Guillaume S S Mouthon D D Stouder C C Dieben K K Huguelet P P Courtet P P Malafosse A A

Translational psychiatry 20111213

Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic-pituitary-adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1(F) NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid po ...[more]

PMID: 22832351

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Project description:BackgroundExisting survey measures of childhood trauma history generally fail to take into account the relational-socioecological environment in which childhood maltreatment occurs. Variables such as the relationship between the perpetrator and the victim, the emotional availability of caregivers, witnessing the abuse of others, and the respondent's own thoughts, feelings, and actions in response to maltreatment are rarely assessed by current measures.MethodsTo address these concerns, the current study further investigated the family dynamics of childhood maltreatment using the Childhood Attachment and Relational Trauma Screen (CARTS) in 1,782 persons assessed online.ResultsPaired differences in means between item-rated descriptiveness of self, mothers, and fathers suggested that respondents' relationship with their biological fathers was less positive and secure than their relationship with their biological mothers, and that biological fathers were more often the perpetrator of emotional, physical, and sexual abuse than biological mothers. However, results further suggested that ratings between self, mothers, and fathers were positively correlated such that, for example, reports of a mother's or a respondent's own abusive behavior were more likely in the presence of reports of a father's abusive behavior. In addition, analyses evaluating witnessing violence demonstrated that fathers were rated as more often violent toward mothers than the reverse, although intimate partner violence was also frequently bidirectional. Analyses of sibling ratings further demonstrated that older brothers were either as or more frequently abusive when compared with parents. Finally, results suggested that childhood emotional, physical, and sexual abuse were much more often perpetrated by family members than extra-familial and non-family members.ConclusionsIn so far as these findings are consistent with the prior childhood trauma and attachment literature, the current study further supports the utility of the CARTS as a means of assessing the family dynamics of childhood attachment and maltreatment within a relational-socioecological framework.

Project description:ImportanceSubstance use disorders (SUDs) are among the most common sequelae of childhood maltreatment, yet the independent contributions of SUDs and childhood maltreatment to neurobiological changes and the effect of the latter on relapse risk (a critical variable in addiction treatment) are relatively unknown.ObjectivesTo identify structural neural characteristics independently associated with childhood maltreatment (CM; a common type of childhood adversity), comparing a sample with SUD with a demographically comparable control sample, and to examine the relationship between CM-related structural brain changes and subsequent relapse.Design, setting, and participantsStructural magnetic resonance imaging study comparing 79 treatment-engaged participants with SUD in acute remission in inpatient treatment at a community mental health center vs 98 healthy control participants at an outpatient research center at an academic medical center. Both groups included individuals with a range of CM experiences. Participants with SUD were followed up prospectively for 90 days to assess relapse and relapse severity.InterventionStandard 12-step, recovery-based, inpatient addiction treatment for all participants with SUD.Main outcomes and measuresGray matter volume (GMV), subsequent substance use relapse, days to relapse, and severity of relapse.ResultsControlling for SUD and psychiatric comorbidity, CM (dichotomously classified) was uniquely associated with lower GMV across all participants in the left hippocampus (cornu ammonis 1-3, dentate gyrus), parahippocampus (presubiculum, parasubiculum, prosubiculum, subiculum, and entorhinal cortex), and anterior fusiform gyrus (corrected P < .05; uncorrected P = .001). Among the sample with SUD, CM prospectively predicted a shorter relapse to use of any drug (P = .048), while CM-related GMV reductions predicted severity of substance use relapse (P = .04).Conclusions and relevanceFindings indicate that CM was related to decreased GMV in limbic regions, which in turn predicted increased risk of relapse in SUD. These results suggest that CM may significantly affect the course of SUD treatment outcomes and that SUD treatment planning may benefit from identifying and addressing CM.

Project description:ImportanceChildhood maltreatment can have significant consequences on health through the life course, but its association with health care costs in later life is not widely known.ObjectiveTo assess whether a history of childhood maltreatment is associated with additional medical costs among older adults in Japan.Design, setting, and participantsThis population-based cross-sectional study used data from the Japan Gerontological Evaluation Study, 2013, linked with national health insurance claims data from April 2012 to March 2014 for 1 municipality that participated in the Japan Gerontological Evaluation Study, 2013. The municipality had more than 1.5 million residents, and 978 independent individuals aged 65 to 75 years were included in the analysis. Data were analyzed from October 2017 to February 2019.ExposuresChildhood maltreatment, including physical abuse, emotional neglect, emotional abuse, and witnessing intimate partner violence.Main outcomes and measuresMean annual medical costs between April 2012 and March 2013 and between April 2013 and March 2014.ResultsAmong 978 independent older adults (mean [SD] age, 70.6 [2.9] years; 426 [43.6%] men), 44 (4.5%) witnessed intimate partner violence, 19 (1.9%) were physically abused, 104 (10.6%) were emotionally neglected, and 56 (5.7%) were emotionally abused in childhood. In total, 176 older adults (18.0%) experienced at least 1 type of childhood maltreatment. Mean annual medical costs of those who experienced any childhood maltreatment were significantly higher than of those who did not (difference, ¥136 456 [US$1255]; 95% CI, ¥38 155-¥234 757 [US$351-US$2160]; P = .007). Those who experienced emotional neglect incurred more mean medical costs than those who did not (difference, ¥161 400 [US$1484]; 95% CI, ¥42 779-¥280 021 [US$394-US$2576]; P = .008). The association of any childhood maltreatment with medical costs remained significant after controlling for age and sex (average marginal effect, ¥116 098 [US$1068]; SE, ¥53 620 [US$493]; 95% CI, ¥11 004-¥221 192 [US$101-US$2034]; P = .03). The estimated additional costs associated with childhood maltreatment would be more than ¥333 billion (US$3.1 million) per year nationwide.Conclusions and relevanceIn this study, childhood maltreatment was associated with additional medical costs among older adults living in Japan. This finding underlines the importance of primary and secondary prevention of child maltreatment.

Project description:BACKGROUND:Childhood maltreatment is one of the most potent predictors of future psychopathology, including internalizing disorders. It remains unclear whether heightened amygdala reactivity to threat and elevated stress exposure may be implicated in the pathogenesis and maintenance of internalizing disorders among individuals with a history of childhood maltreatment. METHODS:Using data from a sample of 1,144 young adults, we investigated the contribution of baseline threat-related amygdala reactivity and prospective major stressful life events to internalizing symptoms severity 1 year later (on average) in individuals with a history of maltreatment (n = 100) and propensity score matched nonmaltreated peers (n = 96). RESULTS:Even after stringently matching for several potentially confounding variables - including baseline internalizing symptoms, socioeconomic status and IQ - childhood maltreatment status predicted increased amygdala reactivity at baseline, elevated post-baseline exposure to major stressful life events and internalizing symptoms at follow-up. We also showed, for the first time, that amygdala reactivity at baseline and also post-baseline exposure to major stressful life events mediated the association between a history of maltreatment and future internalizing symptoms. CONCLUSIONS:These findings provide support for the view that maltreatment is a potent developmental insult leading to long-lasting neurocognitive recalibrations of the threat processing system. It is possible that such alterations, over time, may impact mental health functioning by compromising the ability to effectively negotiate everyday challenges (stress susceptibility). These alterations were not, however, found to sensitize an individual to the impact of major stressful life events. The results of this study also lend compelling support to the view that increased psychiatric risk, in the context of childhood maltreatment, follows from an increased propensity to experience major stressful life events (stress generation).

Dataset Information

Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma.

Publications

Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma.

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