Does Prenatal Stress Shape Postnatal Resilience? – An Epigenome-Wide Study on Violence and Mental Health in Humans

Stress during pregnancy widely associates with epigenetic changes and psychiatric problems during childhood. Animal studies, however, show that under specific postnatal conditions prenatal stress may have other, less detrimental consequences for the offspring. Here, we studied mental health and epigenome-wide DNA methylation in saliva following intimate partner violence (IPV) during pregnancy in São Gonçalo, a Brazilian city with high levels of violence. Not surprisingly, mothers exposed to pregnancy IPV expressed elevated depression, PTSD and anxiety symptoms. Children had similar psychiatric problems when they experienced maternal IPV after being born. More surprisingly, when maternal IPV occurred both during (prenatal) and after pregnancy these problems were absent. Following prenatal IPV, genomic sites in genes encoding the glucocorticoid receptor (NR3C1) and its repressor FKBP51 (FKBP5) were among the most differentially methylated and indicated an enhanced ability to terminate hormonal stress responses in prenatally stressed children. These children also showed more DNA methylation in heterochromatin-like regions, which previously has been associated with stress/disease resilience. A similar relationship was seen in prenatally stressed middle-eastern refugees of the same age as the São Gonçalo children but exposed to postnatal war-related violence. While our study is limited in location and sample size, it provides novel insights on how prenatal stress may epigenetically shape resilience in humans, possibly through interactions with the postnatal environment. This translates animal findings and emphasizes the importance to account for population differences when studying how early life gene–environment interactions affects mental health

Capacitação nacional emergencial em saúde mental e atenção psicossocial na COVID-19: um relato de experiência

In March 2020, the World Health Organization declared a pandemic, due to the rapid spread of the SARS-Cov-2 virus, triggering the global alert about the need for rapid expansion of the capacity for surveillance, prevention and implementation of assistance structures for the countries' health systems. In the day after the statement by the Brazilian Ministry of Health, that recognized community transmission in Brazil, a group of researchers was invited to gather scientific evidence and best practices for mental health and psychosocial care at COVID-19. 1,563 articles were selected that referred to mental health and / or psychosocial care in contexts of health emergencies. Researchers, teachers and volunteers from 25 institutions, recognized for their notorious knowledge, participated, totaling 117 volunteer professionals. It was decided to set up an online national course. Altogether 60,780 professionals joined the course in the first 30 days of enrollment. The online modeling, synchronous and asynchronous, enabled training during a period of social distance, and also allowed professionals from different states in the national territory to have access to updated information based on national and international research, seeking to guarantee the strengthening of actions within the scope health policies, and based on international protocols.Em março/2020, a Organização Mundial da Saúde emitiu a declaração de pandemia, em decorrência da disseminação do vírus SARS-Cov-2, disparando o alerta mundial sobre a necessidade de rápida expansão da capacidade de vigilância, prevenção e implementação das estruturas de assistência dos sistemas de saúde dos países. No dia seguinte a declaração do Ministério da Saúde que reconheceu a transmissão comunitária no Brasil, um grupo de pesquisadores foi convidado a reunir evidências científicas e melhores práticas de SMAPS na COVID-19. Foram selecionados 1.563 artigos que se referiam à saúde mental e/ou atenção psicossocial em contextos de emergências sanitárias. Participaram pesquisadores, docentes e voluntários de 25 instituições reconhecidas pelo notório saber, totalizando um montante de 117 profissionais voluntários. Optou-se por conformar um curso nacional na modalidade de Educação a distância. Ao todo 60.780 profissionais ingressaram no curso nos primeiros 30 dias de inscrição. A modelagem online, síncrona e assíncrona, possibilitou a formação durante período de distanciamento social, e também permitiu que profissionais de todos os estados, e do Distrito Federal, pudessem ter acesso a informações atualizadas e baseadas em pesquisas nacionais e internacionais, buscando garantir o fortalecimento das ações no âmbito das políticas de saúde, e com base nos protocolos internacionais

Interpersonal violence and epigenetic modifications : the impact of prenatal and lifetime stress across three generations

Exposure to interpersonal violence not only affects individual’s physical health and safety but also increases their risk of developing psychiatric disorders. Experiencing interpersonal violence during pregnancy may also impact subsequent generations, which is evidenced by an increased susceptibility to childhood and adulthood health problems in the children and grandchildren. Although the importance of the prenatal environment is well reported with regards to future physical, emotional and behavioral outcomes, little is known about the molecular mechanisms that mediate the long-term consequences of early stress across generations. Epigenetic modifications, such as DNA methylation, have been suggested to be an important mechanism that might translate pre- and postnatal experiences into biological correlates and ultimately into psychological outcomes. To what extent maternal psychosocial experiences of stress during pregnancy are associated with DNA methylation changes in a genome-wide level is still unclear. Furthermore, few studies have investigated the impact of psychosocial stress during pregnancy across several generations. Accordingly, whether psychosocial stress during pregnancy affects DNA methylation of the grandchildren is currently not known. The present thesis addresses these questions by studying the impact of interpersonal violence during pregnancy on the children and grandchildren in families living in a region with high levels of community and domestic violence. Associations of lifetime exposure to interpersonal violence and DNA methylation, as well as stress related-disorders were also investigated.publishe

Epigenetic Biomarkers of Prenatal Maternal Stress

Serpeloni F, Radtke KM, Hecker T, Elbert T. Epigenetic Biomarkers of Prenatal Maternal Stress. In: Spengler D, Wetzel E, eds. Epigenetics and Neuroendocrinology. Epigenetics and Human Health. Cham: Springer International Publishing; 2016: 177-196

Experiencing community and domestic violence is associated with epigenetic changes in DNA methylation of BDNF and CLPX in adolescents

Experiencing violence changes behavior, shapes personalities, and poses a risk factor for mental disorders. This association might be mediated through epigenetic modifications that affect gene expression, such as DNA methylation. The present study investigated the impact of community and domestic violence on DNA methylation measured in saliva collected from 375 individuals including three generations: grandmothers (n = 126), mothers (n = 125), and adolescents (n = 124, 53% female). Using the Infinium HumanMethylation450 BeadChip array, in adolescents, we detected two CpG sites that showed an association of DNA methylation and lifetime exposure to community and domestic violence even after FDR correction: BDNF_cg06260077 (logFC -0.454, p = 3.71E-07), and CLPX_cg01908660 (logFC = -0.372, p = 1.38E-07). Differential DNA methylation of the CpG BDNF_cg06260077 associated with exposure to violence was also observed in the maternal but not the grandmaternal generation. BDNF (brain-derived neurotrophic factor) and CLPX (caseinolytic mitochondrial matrix peptidase chaperone subunit) genes are involved in neural development. Our results thus reveal altered molecular mechanisms of developmental and intergenerational trajectories in survivors of repeated violent experiences.publishe

Narrative Exposure Therapy versus treatment as usual in a sample of trauma survivors who live under ongoing threat of violence in Rio de Janeiro, Brazil: study protocol for a randomised controlled trial

Background: One in three individuals who live in Rio de Janeiro experience a traumatic event within a period of 12 months. In the favelas particularly, trauma exposure is ongoing. Psychological sequalae include posttraumatic stress disorder (PTSD), depression and other mental disorders. Trauma-focused therapy approaches have emerged as the treatment of choice when the dangerous events are over, but symptoms have remained for an extended time period. Ideally, the victim is in a safe context during treatment. However, frequently, survivors cannot escape from situations characterised by ongoing threat and traumatic stress. The aim of this study is to research the effectiveness of Narrative Exposure Therapy in a sample of PTSD patients living under these conditions.Methods: Individuals fulfilling the criteria for PTSD and who live in conditions of ongoing community violence (i.e. in the favelas) in Rio de Janeiro will be randomly assigned to one of two treatments: Narrative Exposure Therapy (NET) or treatment as usual (TAU). Clinical endpoints will be primarily PTSD and secondarily symptoms of shutdown dissociation, depression, substance involvement and functionality.Discussion: Effective treatment for PTSD patients who live in unsafe conditions could substantially reduce suffering of individuals and their families in Brazil. Based on this result, the extent to which such interventions may be useful as a first step in tackling the consequences of violence on a global scale will be discussed.publishe

Community and domestic violence are associated with DNA methylation GrimAge acceleration and heart rate variability in adolescents

Background: Cumulative exposure to violence can change the regulation of epigenetic and physiological markers. Although violence has been associated with accelerated cellular aging, little is known about associations with cardiac autonomic activity. Objective: The current study aimed to investigate the relationship of exposure to community and domestic violence (CDV) with vagal activity and epigenetic aging acceleration. Methods: A total of 86 adolescents (57% female) were evaluated and interviewed at two time-points in São Gonçalo (2014–2019), a Brazilian city with high levels of violence. Exposure to CDV was assessed in both time-points. GrimAge acceleration was calculated from saliva DNA methylation using Infinium HumanMethylation450K (Illumina) collected in the first assessment. Heart rate variability (HRV) was collected during two stress tasks at the second assessment. Results: The exposure to violence witnessed or directly experienced at home and in the community increased significantly (t = 4.87, p < .01) across two-time points, and males had reported higher violence exposure (t = 2.06, p = .043). Violence at 1st assessment was significantly associated with GrimAge acceleration (B = .039, p value = .043). Violence at both assessments were associated with HRV measured during the narration of the worst trauma (traumaHRV) (B = .009, p value = .039, and B = .007, p value = .024, 1st and 2nd assessment respectively). GrimAge acceleration was significantly associated with traumaHRV (B = .043, p value = .049), and HRV measured during a 3D roller coaster video (B = .061, p value = .024). Conclusions: We found relevant evidence that experiencing violence during adolescence is associated with epigenetic aging and stress-related vagal activity. Understanding these factors during this period could contribute to the development of early interventions for health promotion. HIGHLIGHTS Higher exposure to Community and domestic violence is associated with increased GrimAge acceleration. Higher GrimAge acceleration is associated with increased stress-related vagal activity. Exposure to community and domestic violence increased significantly over time

Panorama da produção científica sobre a presença de transtornos mentais em população privada de liberdade em países do continente americano: uma revisão de escopo

Revisão de escopo orientada pelas diretrizes da ferramenta PRISMA ScR e pela metodologia do Joanna Briggs Institute – JBI para mapear o conhecimento científico sobre a presença de transtornos mentais em população privada de liberdade em países do continente americano. A busca pelos estudos será desenvolvida a partir de palavras-chave nas seguintes bases de dados: SCIELO, EMBASE, PUBMED/MEDLINE, WEB OF SCIENCE, SCOPUS, PSYCINFO, CINAHL (EBSCO). Os artigos encontrados serão incluídos no gerenciador bibliográfico Rayyan, de onde serão excluídos os duplicados e será feita a triagem dos artigos a serem considerados para esta revisão de escopo, com base nos critérios de inclusão e exclusão já definidos. A triagem dos artigos será feita de forma cega e independente por dois revisores, a partir da leitura dos títulos e resumos e a resolução de divergências ocorrerá por consenso, com o auxílio de um juiz. Os estudos selecionados serão lidos na íntegra e os dados selecionados serão: autores, instituição, ano de publicação, periódico científico onde o artigo foi publicado, tipo de metodologia empregada, país, faixa etária dos participantes da pesquisa, idade, gênero e tipos de transtornos mentais estudados. O processo de extração será realizado por dois revisores. A partir dos dados extraídos será feita uma análise bibliométrica descritiva das informações coletadas. Os resultados serão apresentados de forma descritiva e ilustrados com auxílio de imagens, gráficos e tabelas. Não será executada a avaliação da qualidade metodológica dos estudos identificados. A apresentação dos resultados seguirá as recomendações do PRISMA ScR