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      BDNF Methylation and Maternal Brain Activity in a Violence-Related Sample

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          Abstract

          It is known that increased circulating glucocorticoids in the wake of excessive, chronic, repetitive stress increases anxiety and impairs Brain-Derived Neurotrophic Factor ( BDNF) signaling. Recent studies of BDNF gene methylation in relation to maternal care have linked high BDNF methylation levels in the blood of adults to lower quality of received maternal care measured via self-report. Yet the specific mechanisms by which these phenomena occur remain to be established. The present study examines the link between methylation of the BDNF gene promoter region and patterns of neural activity that are associated with maternal response to stressful versus non-stressful child stimuli within a sample that includes mothers with interpersonal violence-related PTSD (IPV-PTSD). 46 mothers underwent fMRI. The contrast of neural activity when watching children—including their own—was then correlated to BDNF methylation. Consistent with the existing literature, the present study found that maternal BDNF methylation was associated with higher levels of maternal anxiety and greater childhood exposure to domestic violence. fMRI results showed a positive correlation of BDNF methylation with maternal brain activity in the anterior cingulate (ACC), and ventromedial prefrontal cortex (vmPFC), regions generally credited with a regulatory function toward brain areas that are generating emotions. Furthermore we found a negative correlation of BDNF methylation with the activity of the right hippocampus. Since our stimuli focus on stressful parenting conditions, these data suggest that the correlation between vmPFC/ACC activity and BDNF methylation may be linked to mothers who are at a disadvantage with respect to emotion regulation when facing stressful parenting situations. Overall, this study provides evidence that epigenetic signatures of stress-related genes can be linked to functional brain regions regulating parenting stress, thus advancing our understanding of mothers at risk for stress-related psychopathology.

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          Most cited references41

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          Emotional processing in anterior cingulate and medial prefrontal cortex.

          Negative emotional stimuli activate a broad network of brain regions, including the medial prefrontal (mPFC) and anterior cingulate (ACC) cortices. An early influential view dichotomized these regions into dorsal-caudal cognitive and ventral-rostral affective subdivisions. In this review, we examine a wealth of recent research on negative emotions in animals and humans, using the example of fear or anxiety, and conclude that, contrary to the traditional dichotomy, both subdivisions make key contributions to emotional processing. Specifically, dorsal-caudal regions of the ACC and mPFC are involved in appraisal and expression of negative emotion, whereas ventral-rostral portions of the ACC and mPFC have a regulatory role with respect to limbic regions involved in generating emotional responses. Moreover, this new framework is broadly consistent with emerging data on other negative and positive emotions. Published by Elsevier Ltd.
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            The development of a Clinician-Administered PTSD Scale.

            Several interviews are available for assessing PTSD. These interviews vary in merit when compared on stringent psychometric and utility standards. Of all the interviews, the Clinician-Administered PTSD Scale (CAPS-1) appears to satisfy these standards most uniformly. The CAPS-1 is a structured interview for assessing core and associated symptoms of PTSD. It assesses the frequency and intensity of each symptom using standard prompt questions and explicit, behaviorally-anchored rating scales. The CAPS-1 yields both continuous and dichotomous scores for current and lifetime PTSD symptoms. Intended for use by experienced clinicians, it also can be administered by appropriately trained paraprofessionals. Data from a large scale psychometric study of the CAPS-1 have provided impressive evidence of its reliability and validity as a PTSD interview.
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              Development and preliminary validation of a brief broad-spectrum measure of trauma exposure: the Traumatic Life Events Questionnaire.

              This article describes the development and preliminary validation of a brief questionnaire that assesses exposure to a broad range of potentially traumatic events. Items were generated from multiple sources of information. Events were described in behaviorally descriptive terms, consistent with Diagnostic and Statistical Manual of Mental Disorders IV posttraumatic stress disorder stressor criterion A1. When events were endorsed, respondents were asked if they experienced intense fear, helplessness, or horror (stressor criterion A2). In separate studies with college students, Vietnam veterans, battered women, and residents of a substance abuse program, most items possessed adequate to excellent temporal stability. In a study comparing questionnaire and structured-interview inquiries of trauma history, the 2 formats yielded similar rates of disclosure. Preliminary data on positive predictive power are also presented.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                9 December 2015
                2015
                : 10
                : 12
                : e0143427
                Affiliations
                [1 ]Department of Child & Adolescent Psychiatry, University of Geneva Hospitals, Geneva, Switzerland
                [2 ]Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
                [3 ]Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva Hospitals, Geneva, Switzerland
                [4 ]Faculty of Health, Psychology and Social care, Manchester Metropolitan University, Manchester, United Kingdom
                Nathan Kline Institute and New York University School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SRS DSS DAM FS ASR FA AGD. Performed the experiments: DAM MIC WA APG ASR FS AM MV SRS. Analyzed the data: DAM DSS WA APG LS. Contributed reagents/materials/analysis tools: LS APG AGD DAM. Wrote the paper: DAM DSS MIC FS LS AGD APG.

                Article
                PONE-D-15-39665
                10.1371/journal.pone.0143427
                4674054
                26649946
                56dd00c6-43bc-40d0-b5b5-3e7b9d06865a
                © 2015 Moser et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 9 September 2015
                : 4 November 2015
                Page count
                Figures: 2, Tables: 1, Pages: 13
                Funding
                This research was supported by the National Center of Competence in Research (NCCR) “SYNAPSY—The Synaptic Bases of Mental Diseases” (nccr-synapsy.ch) financed by the Swiss National Science Foundation (n° 51AU40_125759), the Gertrude von Meissner Foundation, the Oak Foundation ( http://www.oakfnd.org) and la Fondation Prim’Enfance ( http://www.primenfance.ch). This work was further supported in part by the Center for Biomedical Imaging (CIBM) of the Geneva-Lausanne Universities, the EPFL and the Geneva-Lausanne University Hospitals ( http://www.cibm.ch). The authors report no conflict of interest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All the available data will be part of the paper or the Supporting Information. Group analysis data but not single subject data will be available on a whole brain level (but individual data will be available at for significant clusters in the attached SPSS database). This is primarily due to the space this would require, and the fact that this data cannot easily be prepared for third parties. The presented data should easily be sufficient for control (and some use) by third parties though.

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