Stress during pregnancy may impact subsequent generations, which is demonstrated 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 and emotional outcomes, little is known about the molecular mechanisms that mediate the long-term consequences of early stress across generations. Recent studies have identified DNA methylation as a possible mediator of the impact of prenatal stress in the offspring. Whether psychosocial stress during pregnancy also affects DNA methylation of the grandchildren is still not known. In the present study we examined the multigenerational hypothesis, that is, grandmaternal exposure to psychosocial stress during pregnancy affecting DNA methylation of the grandchildren. We determined the genome-wide DNA methylation profile in 121 children (65 females and 56 males) and tested for associations with exposure to grandmaternal interpersonal violence during pregnancy. We observed methylation variations of five CpG sites significantly (FDR<0.05) associated with the grandmother’s report of exposure to violence while pregnant with the mothers of the children. The results revealed differential methylation of genes previously shown to be involved in circulatory system processes (FDR<0.05). This study provides support for DNA methylation as a biological mechanism involved in the transmission of stress across generations and motivates further investigations to examine prenatal-dependent DNA methylation as a potential biomarker for health problems.

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.

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.

Background The frequency of trauma and different types of violence exposure in urban areas and their effects on the mental health of adolescents in developing countries are poorly investigated. Most information about traumatized young people comes from war scenarios or disasters. This study aimed to determine the prevalence of PTSD in trauma-exposed students in a low-resource city of the state of Rio de Janeiro, Brazil. The effects of sociodemographic and individual and family factors in the development of PTSD were also investigated. Methods Through multi-stage cluster sampling, 862 adolescents (Mage = 15 years old, 65% female) from public and private schools in the city of São Gonçalo were selected for the study. Self-rating structured questionnaires were applied to assess sociodemographic profile, exposure to physical and psychological violence (family, school, community), sexual abuse, social support, social functional impairment, resilience, and posttraumatic stress disorder. The data were grouped in blocks regarding sociodemographic, individual, family, and community variables. For statistical analysis, chi-square, Fisher’s exact test, and logistic regression were performed. Results The PTSD prevalence was 7.8% among adolescents. Boys were exposed to significantly higher number of events of community violence, while girls to family violence. The adjusted odds ratio (OR) for PTSD were statistically significant for age (OR, 1.45, [95% CI, 1.043–2.007]), social functional impairment (OR, 4.82, [95% CI, 1.77–13.10]), severe maternal physical violence (OR, 2.79, [95% CI, 0.79–9.93]), psychological violence by significant people (OR, 3.96, [95% CI, 1.89–8.31]) and a high number of episodes of community violence (OR, 3.52, [95% CI, 1.47–8.40). Conclusions There was a high prevalence of PTSD within this population associated with exposure to violence. Not only physical, but also psychological violence contributed to PTSD. The results also raise awareness to the differences in life trajectories between boys and girls regarding violence. These differences need to be better understood in order to enable the development of effective preventative interventions. Treating and preventing mental health disorders presents a challenge for countries, especially those with a lower degree of social and economic development and high community violence.

O Brasil é um dos países com maior número de casos e óbitos na pandemia por COVID-19, e seus impactos representam múltiplos desafios para a saúde mental. Esta comunicação relata a experiência de conformação emergencial do Grupo de Trabalho (GT) voluntário e colaborativo em saúde mental e atenção psicossocial, com objetivo de fornecer respostas rápidas aos serviços de saúde no contexto da COVID-19. O trabalho envolveu a identificação e sistematização de evidências atualizadas da literatura científica sobre saúde mental e atenção psicossocial em situações de emergências em saúde pública e pandemias, a constituição de uma rede envolvendo 117 pesquisadores e 25 instituições, além da organização de temas para elaboração de materiais, tendo como referência as fases de resposta em emergências em saúde pública e pandemias. Em menos de 60 dias foram publicados 18 documentos técnicos norteadores, englobando desde a organização e gestão dos serviços voltados aos diferentes grupos vulneráveis, ações que se tornaram referência em instituições e serviços de saúde, tendo sido também lançado um curso nacional sobre saúde mental e atenção psicossocial na COVID-19, com mais de 60 mil inscritos. Da experiência, são destacados tópicos para reflexão e contribuição para futuras ações, envolvendo translação do conhecimento nesta e em próximas emergências em saúde pública e pandemias: (1) combinar o trabalho voluntário e colaborativo com o envolvimento de profissionais experientes na organização de serviços e atenção em eventos passados; (2) contar com o suporte e recursos institucionais; (3) envolver a constituição de redes de profissionais e instituições para atingir rapidez e credibilidade no trabalho; (4) para as respostas às necessidades urgentes, deve-se envolver também a capacidade de moldar caminhos para a atenção e os cuidados em saúde mental e atenção psicossocial.

RESUMO 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 à 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 Saúde Mental e Atenção Psicossocial (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 on-line, síncrona e assíncrona, possibilitou a formação durante o período de distanciamento social, assim como 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.

Growing evidence suggests that peritraumatic tonic immobility, an involuntary defensive response that involves extreme physical immobility and the perceived inability to escape, is a significant predictor of post-traumatic stress disorder (PTSD) symptomatology. However, this issue has not been specifically addressed in adolescents. Here, we investigated whether tonic immobility response experienced during the worst childhood or adolescent trauma is associated with PTSD symptom severity in a non-clinical student sample. Methods: The sample was composed of students in 9th grade who were attending public and private schools. Symptoms of post-traumatic stress and tonic immobility were assessed using questionnaires. We performed bivariate and multivariate negative binomial regressions to examine whether tonic immobility was associated with PTSD symptomatology after controlling for confounders (peritraumatic dissociation, peritraumatic panic reactions, gender, age and time since trauma). Results: We found an association between tonic immobility and PTSD symptom severity, even after controlling for confounders. Therefore, tonic immobility is associated with PTSD symptoms in trauma-exposed adolescents. Conclusion: These findings highlight tonic immobility as a possible risk factor that could be used to provide direction for more targeted trauma interventions for individuals, particularly those at risk for developing PTSD. Therefore, it contributes to preventing and reducing the psychiatric burden in adolescence and later in life.

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