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DNA methylation changes following narrative exposure therapy in a randomized controlled trial with female former child soldiers.

ABSTRACT: The aftermath of traumatization lives on in the neural and epigenetic traces creating a momentum of affliction in the psychological and social realm. Can psychotherapy reorganise these memories through changes in DNA methylation signatures? Using a randomised controlled parallel group design, we examined methylome-wide changes in saliva samples of 84 female former child soldiers from Eastern DR Congo before and six months after Narrative Exposure Therapy. Treatment predicted differentially methylated positions (DMPs) related to ALCAM, RIPOR2, AFAP1 and MOCOS. In addition, treatment associations overlapped at gene level with baseline clinical and social outcomes. Treatment related DMPs are involved in memory formation-the key agent in trauma focused treatments-and enriched for molecular pathways commonly affected by trauma related disorders. Results were partially replicated in an independent sample of 53 female former child soldiers from Northern Uganda. Our results suggest a molecular impact of psychological treatment in women with war-related childhood trauma.Trial registration: Addressing Heightened Levels of Aggression in Traumatized Offenders With Psychotherapeutic Means (ClinicalTrials.gov Identifier: NCT02992561, 14/12/2016).

SUBMITTER: Carleial S

PROVIDER: S-EPMC8445994 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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DNA methylation changes following narrative exposure therapy in a randomized controlled trial with female former child soldiers.

Carleial Samuel S Nätt Daniel D Unternährer Eva E Elbert Thomas T Robjant Katy K Wilker Sarah S Vukojevic Vanja V Kolassa Iris-Tatjana IT Zeller Anja C AC Koebach Anke A

Scientific reports 20210916 1

The aftermath of traumatization lives on in the neural and epigenetic traces creating a momentum of affliction in the psychological and social realm. Can psychotherapy reorganise these memories through changes in DNA methylation signatures? Using a randomised controlled parallel group design, we examined methylome-wide changes in saliva samples of 84 female former child soldiers from Eastern DR Congo before and six months after Narrative Exposure Therapy. Treatment predicted differentially methy ...[more]

PMID: 34531495

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Project description:This article reviews the available quantitative research on psychosocial adjustment and mental health among children (age <18?years) associated with armed forces and armed groups (CAAFAG)--commonly referred to as child soldiers.PRISMA standards for systematic reviews were used to search PubMed, PsycInfo, JSTOR, and Sociological Abstracts in February 2012 for all articles on former child soldiers and CAAFAG. Twenty-one quantitative studies from 10 countries were analyzed for author, year of publication, journal, objectives, design, selection population, setting, instruments, prevalence estimates, and associations with war experiences. Opinion pieces, editorials, and qualitative studies were deemed beyond the scope of this study. Quality of evidence was rated according to the systematic assessment of quality in observational research (SAQOR).According to SAQOR criteria, among the available published studies, eight studies were of high quality, four were of moderate quality, and the remaining nine were of low quality. Common limitations were lack of validated mental health measures, unclear methodology including undefined sampling approaches, and failure to report missing data. Only five studies included a comparison group of youth not involved with armed forces/armed groups, and only five studies assessed mental health at more than one point in time. Across studies, a number of risk and protective factors were associated with postconflict psychosocial adjustment and social reintegration in CAAFAG. Abduction, age of conscription, exposure to violence, gender, and community stigma were associated with increased internalizing and externalizing mental health problems. Family acceptance, social support, and educational/economic opportunities were associated with improved psychosocial adjustment.Research on the social reintegration and psychosocial adjustment of former child soldiers is nascent. A number of gaps in the available literature warrant future study. Recommendations to bolster the evidence base on psychosocial adjustment in former child soldiers and other war-affected youth include more studies comprising longitudinal study designs, and validated cross-cultural instruments for assessing mental health, as well as more integrated community-based approaches to study design and research monitoring.

Project description:Alcohol use disorder (AUD) is a chronic mental illness in which patients often achieve protracted periods of abstinence prior to relapse. Epigenetic mechanisms may provide an explanation for the persisting gene expression changes that can be observed even after long periods of abstinence and may contribute to relapse. In this study, we examined two histone modifications, histone 3 lysine 4 tri-methylation (H3K4me3) and histone 3 lysine 27 tri-methylation (H3K27me3), in the prefrontal cortex of Withdrawal Seizure Resistant (WSR) mice 21 days after 72 h of ethanol vapor exposure. These histone modifications were selected because they are associated with active promoters (H3K4me3) and repressed gene expression in a euchromatic environment (H3K27me3). We performed a genome-wide analysis to identify differences in H3K4me3 and H3K27me3 levels in post-ethanol exposure vs. control mice by ChIP-seq. We detected a global reduction in H3K4me3 peaks and increase in H3K27me3 peaks in post-ethanol exposure mice compared to controls, these changes are consistent with persistent reductions in gene expression. Pathway analysis of genes displaying changes in H3K4me3 and H3K27me3 revealed enrichment for genes involved in proteoglycan and calcium signaling pathways, respectively. Microarray analysis of 7,683 genes and qPCR analysis identified eight genes displaying concordant regulation of gene expression and H3K4me3/H3K27me3. We also compared changes in H3K4me3 and/or H3K27me3 from our study with changes in gene expression in response to ethanol from published literature and we found that the expression of 52% of the genes with altered H3K4me3 binding and 40% of genes with H3K27me3 differences are altered by ethanol exposure. The chromatin changes associated with the 21-day post-exposure period suggest that this period is a unique state in the addiction cycle that differs from ethanol intoxication and acute withdrawal. These results provide insights into the enduring effects of ethanol on proteoglycan and calcium signaling genes in the brain.

Dataset Information

DNA methylation changes following narrative exposure therapy in a randomized controlled trial with female former child soldiers.

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DNA methylation changes following narrative exposure therapy in a randomized controlled trial with female former child soldiers.

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