A Mendelian randomization study of genetic liability to post-traumatic stress disorder and risk of ischemic stroke.

Observational studies have shown an association between post-traumatic stress disorder (PTSD) and ischemic stroke (IS) but given the susceptibility to confounding it is unclear if these associations represent causal effects. Mendelian randomization (MR) facilitates causal inference that is robust to the influence of confounding. Using two sample MR, we investigated the causal effect of genetic liability to PTSD on IS risk. Ancestry-specific genetic instruments of PTSD and four quantitative sub-phenotypes of PTSD, including hyperarousal, avoidance, re-experiencing, and total symptom severity score (PCL-Total) were obtained from the Million Veteran Programme (MVP) using a threshold P value (P) of <5 × 10-7, clumping distance of 1000 kilobase (Mb) and r2 < 0.01. Genetic association estimates for IS were obtained from the MEGASTROKE consortium (Ncases = 34,217, Ncontrols = 406,111) for European ancestry individuals and from the Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) (Ncases = 3734, Ncontrols = 18,317) for African ancestry individuals. We used the inverse-variance weighted (IVW) approach as the main analysis and performed MR-Egger and the weighted median methods as pleiotropy-robust sensitivity analyses. In European ancestry individuals, we found evidence of an association between genetic liability to PTSD avoidance, and PCL-Total and increased IS risk (odds ratio (OR)1.04, 95% Confidence Interval (CI) 1.007-1.077, P = 0.017 for avoidance and (OR 1.02, 95% CI 1.010-1.040, P = 7.6 × 10-4 for PCL total). In African ancestry individuals, we found evidence of an association between genetically liability to PCL-Total and reduced IS risk (OR 0.95 (95% CI 0.923-0.991, P = 0.01) and hyperarousal (OR 0.83 (95% CI 0.691-0.991, P = 0.039) but no association was observed for PTSD case-control, avoidance, or re-experiencing. Similar estimates were obtained with MR sensitivity analyses. Our findings suggest that specific sub-phenotypes of PTSD, such as hyperarousal, avoidance, PCL total, may have a causal effect on people of European and African ancestry's risk of IS. This shows that the molecular mechanisms behind the relationship between IS and PTSD may be connected to symptoms of hyperarousal and avoidance. To clarify the precise biological mechanisms involved and how they may vary between populations, more research is required.

Intergenerational transmission of trauma and its association with attitudes toward reconciliation.

OBJECTIVE: We aimed to investigate the link between mothers' posttraumatic stress disorder (PTSD) symptoms and their adult offspring's attitudes toward reconciliation and psychopathology among survivors of the 1994 genocide perpetrated against the Tutsi in Rwanda. We also sought to examine whether parenting styles mediate the relationship between mothers' PTSD symptoms and their adult offspring's psychopathology, if any. METHOD: Mother-child dyads (N = 181) were recruited in Rwanda and completed measures of trauma exposure, PTSD, depression, attitudes toward reconciliation, and parenting styles. RESULTS: Adult offspring of mothers who suffered from more severe PTSD symptoms had less favorable attitudes toward reconciliation, even after controlling for their own PTSD symptoms. Mothers' PTSD symptoms were not associated with their adult offspring's PTSD or depression symptoms. In addition, mothers' PTSD symptoms did not predict their parenting styles. CONCLUSIONS: These results suggest that the mental health of survivors of mass violence has repercussions on the intergroup attitudes of the following generation. This study has practical implications for sustainable peacebuilding in postconflict societies. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A clustered randomized controlled trial to assess whether Living Peace Intervention (LPint) reduces domestic violence and its consequences among families of targeted men in Eastern Democratic Republic of the Congo (DRC): Design and methods.

The aim of this study is to assess the effectiveness of Living Peace Intervention (LPint) in terms of reduction of domestic violence and a range of secondary outcomes, including violence against children, mental health wellbeing, and social/family relations. The study aims also to determine whether LPint reduces domestic violence due to mediating effects of reduction of psychopathology, improved positive masculinity attitudes, family and social life and psychological states. This study uses a Cluster Randomized Controlled Trial design, with person-level and cluster-level outcomes. The counterfactual is villages that are listed as being affected by the conflict in North and South Kivu of Democratic Republic of the Congo (DRC). Sixty villages with 1736 participants were included in the study. The primary analysis will use generalized estimating equations to compare treatments versus control groups on their mean change in domestic violence between baseline and endline one and two. The allocated group will be regarded as fixed effects whilst villages and time points are regarded as random effects in the model. This is a unique study in the context of a protracted violent humanitarian crisis notably the DRC. It uses a Cluster Randomized Controlled Trial (CRCT) to obtain hard empirical evidence to prove the scalability of the Living Peace intervention in close humanitarian contexts.

Community engagement in epigenomic and neurocognitive research on post-traumatic stress disorder in Rwandans exposed to the 1994 genocide against the Tutsi: lessons learned.

Epigenomic and neurocognitive studies have provided new perspectives on post-traumatic stress disorder and its intergenerational transmission. This article outlines the lessons learned from community engagement (CE) in such research on Rwandan genocide survivors. A strong trauma-related response was observed within the research project-targeted community (genocide survivors) during explanation of the project. CE also revealed privacy concerns, as community members worried that any leakage of genetic/(epi)genomic data could affect not only themselves but also their close relatives. Adopting a culture of CE in the process of research implementation enables the prioritization of targeted community needs and interests. Furthermore, CE has stimulated the development of mental healthcare interventions, which married couples can apply to protect their offspring and thus truly break the cycle of inherited vulnerability.

Studies of how human genes are affected by the environment (epigenomic studies) have provided new perspectives on post-traumatic stress disorder and its intergenerational transmission. This article describes the lessons learned from community engagement (CE) in this type of research in a Rwandan genocide-exposed population. A strong trauma-related response was observed within the community while explaining the project. CE also revealed the participants' privacy concerns related to leakage of genetic/(epi)genomic data that could also affect their close relatives. Adopting a culture of CE in the process of research implementation enables the prioritization of community needs and interests. CE has furthermore stimulated the development of preventive interventions for married couples to protect their offspring and thus truly break the cycle of inherited vulnerability.

Attitudes, perceptions, and barriers of community pharmacists in Rwanda towards health promotion: a cross sectional study.

BACKGROUND: The practice of Pharmacists has changed worldwide over the past years. Today, health promotion is better known as an important part of modern pharmacy practice. Involving Community Pharmacists in health promotion is thus considered a valuable option in addressing public health issues. However, the literature on this practice remains unsubstantiated in African countries. In Rwanda, Community Pharmacists are believed to be solely involved in dispensing and very little has been studied about their role in health promotion. Thus, this study aimed to evaluate attitudes, perceptions, and barriers of Community Pharmacists in Rwanda towards their involvement in health promotion. METHODS: A cross-sectional study was conducted among 236 licensed Community Pharmacists in Rwanda from 23rd January to 23rd June, 2021. A list of all respondents was obtained from Rwanda Food and Drugs Authority. All participants were randomly enrolled. Each community pharmacy was represented by one Pharmacist. We collected data from community pharmacy settings using a self-administered questionnaire made of close and open-ended questions. Statistical analyses were performed using Statistical Packages for Social Sciences (SPSS) version 25. RESULTS: Of the 236 respondents, (n = 149, 63.1%) were male and (n = 87,37%) were female. The average age was 38.1 years (SD = 4.3). More than half confirmed that professional curriculum is adequate for offering health promotion services (n = 152, 64.4%).Majority responded that health promotion is part of their responsibility, and they are willing to provide health promotion services (n = 233,98.7%).The statement that "Pharmacists should not be involved in public health activities "was opposed by many (n=174,73.7%).The most sought-after service provided was education to drug misuse (n=211, 89.4%).Three major barriers to provision of health promotion were: lack of coordination with other healthcare professionals(n=106,69%),structure of healthcare system (n=157,67%),and lack of equipment (n=144,61%).Most Pharmacists disagreed with the statement that "patients are not interested in getting health promotion services"(n = 134,57%). CONCLUSION: Though Community Pharmacists faced several challenges that hindered their participation in health promotion, they had positive attitudes towards promoting public health messages. There are several barriers like lack of structure to provide health promotion services that need to be addressed to boost more active participation of Pharmacists in health promotion.

Leukocyte methylomic imprints of exposure to the genocide against the Tutsi in Rwanda: a pilot epigenome-wide analysis.

Aim & methods: We conducted a pilot epigenome-wide association study of women from Tutsi ethnicity exposed to the genocide while pregnant and their resulting offspring, and a comparison group of women who were pregnant at the time of the genocide but living outside of Rwanda.Results: Fifty-nine leukocyte-derived DNA samples survived quality control: 33 mothers (20 exposed, 13 unexposed) and 26 offspring (16 exposed, 10 unexposed). Twenty-four significant differentially methylated regions (DMRs) were identified in mothers and 16 in children. Conclusions:In utero genocide exposure was associated with CpGs in three of the 24 DMRs: BCOR, PRDM8 and VWDE, with higher DNA methylation in exposed versus unexposed offspring. Of note, BCOR and VWDE show significant correlation between brain and blood DNA methylation within individuals, suggesting these peripherally derived signals of genocide exposure may have relevance to the brain.

Lay abstract The 1994 Rwandan genocide against ethnic Tutsi has been associated with adverse mental health outcomes in survivors decades later, but the molecular mechanisms that contribute to this association remain poorly characterized. Epigenetic mechanisms such as DNA methylation regulate gene function and change in response to life experiences. We identified differentially methylated regions (DMRs) in genocide-exposed versus unexposed mothers and children. In utero genocide exposure was linked with methylation differences in three maternal DMRs, with higher methylation in exposed offspring. Two of three DMRs show correlation between brain and blood methylation within individuals, suggesting that peripherally derived signals of genocide exposure may be relevant to the brain.

Societal Healing in Rwanda: Toward a Multisystemic Framework for Mental Health, Social Cohesion, and Sustainable Livelihoods among Survivors and Perpetrators of the Genocide against the Tutsi.

The genocide against the Tutsi in Rwanda left the country almost completely devastated, with tremendous consequences for mental health, social cohesion, and livelihoods. In the aftermath of such extreme circumstances and human rights violations, societal healing should be conceptualized and approached based on a multisystemic framework that considers these three sectors-mental health, social cohesion, and livelihoods-as well as their interactions. The aims of the present study are twofold: (1) to review evidence on multisystemic healing initiatives already applied in Rwanda using fieldwork notes from interviews and focus groups, alongside relevant scholarly and gray literature, and (2) to propose a scalable multisystemic framework for societal healing in Rwanda that builds on existing innovations. Within a participatory action research methodology, we used a grounded theory approach to synthesize fieldwork findings and compare them with literature to generate a set of principles for multisystemic recovery in Rwanda. Recognizing the strengths and limitations of the current mental health system and other initiatives, including sociotherapy and collaborative livelihood projects, we propose a scalable and rights-based multisystemic approach for recovery and resilience that would target mental health, social cohesion, and sustainable livelihoods within an integrative cross-sectoral framework, thus reducing the risk of post-genocide conflict.

Burden of post-traumatic stress disorder in postgenocide Rwandan population following exposure to 1994 genocide against the Tutsi: A meta-analysis.

BACKGROUND: The 1994 genocide against Tutsi resulted in a massive death toll that reached one million people. Despite the tremendous efforts made to mitigate the adverse effects of the genocide, a substantial burden of mental health disorders still exists including the notably high prevalence of post-traumatic stress disorder (PTSD) among genocide survivors. However, a synthesized model of PTSD vulnerability in this population is currently lacking. METHODS: A meta-analysis of 19 original research studies that reported PTSD prevalence (n = 12,610). Medline-PubMed and Science.gov were key search engines. Random-Effects Model (k = 19; tau^2 estimator: DL) was applied. Data extraction, synthesis, and meta-analysis were carried out using R. RESULTS: The total of 2957 out of 11,746 individuals suffered from PTSD. The summary proportion is 25% (95% CI=0.16,0.36). The tau^2 is 0.06 (95% CI=0.03,0.14) in the absence of subgroups, and the Q-statistic is 2827.65 (p<0.0001), all of which suggests high heterogeneity in the effect sizes. Year of data collection and Year of publication were significant moderators. PTSD pooled prevalence in the genocide survivor category was estimated at 37% (95% CI=0.21,0.56). CONCLUSION: The PTSD prevalence among genocide survivors is considerably higher compared to the general Rwandan population. The burden of PTSD in the general Rwandan population declined significantly over time, likely due to treatment of symptoms through strong national mental health programs, peace building and resolution of symptoms over time. To the best of our knowledge little evidence has reported the burden of PTSD prevalence in African post conflict zones particularly in Rwanda. LIMITATION: Limitations of our review include the use of retrospective studies and studies with very small sample sizes, as well as language criterion.

Validity, Reliability, and Diagnostic Cut-off of the Kinyarwandan Version of the Hamilton Depression Rating Scale in Rwanda.

Introduction: In Rwanda, major depressive disorder affects 11.9% of the population and up to 35% of genocide survivors. Mental health services remain underutilized due to stigma and lack of awareness. Increasing the ability and capacity to diagnose and treat mental disorders is considered important to close this gap. We describe the translation, validity, and reliability assessment of the Hamilton Depression Rating Scale (HDRS) as a diagnostic tool for moderate to severe depression in Rwanda. Methods: The HDRS-21 was translated by a multi-group taskforce. We validated the translation against expert assessment in a comparative study on a sample of patients living with depression and of healthy volunteers. Psychometric properties, namely internal structure, reliability, and external validity were assessed using confirmatory factor analysis, three reliability calculations, and correlation analysis, respectively. Maximized Youden's index was used for determining diagnostic cut-off. Results: The translated version demonstrated a kappa of 0.93. We enrolled 105 healthy volunteers and 105 patients with confirmed mild to severe depression. In the confirmatory factor analysis, HDRS had good factor loadings of 0.32-0.80. Reliability coefficients above 0.92 indicated strong internal consistency. External validity was shown by good sensitivity (0.95) and specificity (0.94) to differentiate depression from absence of depression. At a cut-off point of 17 for the diagnosis of depression, sensitivity and specificity were both 0.95 relative to gold standard. Conclusion: The validated HDRS in Kinyarwanda with diagnostic cut-off provides mental healthcare staff with an accurate tool to diagnose moderate to severe depression, enabling closure of the diagnosis and treatment gap.

Impact of Music on Working Memory in Rwanda.

Previous research shows that listening to pleasant, stimulating and familiar music is likely to improve working memory performance. The benefits of music on cognition have been widely studied in Western populations, but not in other cultures. The purpose of this study was to explore the impact of music on working memory in a non-Western sociocultural context: Rwanda. One hundred and nineteen participants were randomly assigned to a control group (short story) or one of four different musical conditions varying on two dimensions: arousal (relaxing, stimulating) and cultural origin (Western, Rwandan). Working memory was measured using a behavioral task, the n-back paradigm, before and after listening to music (or the short story in the control condition). Unlike in previous studies with Western samples, our results with this Rwandan sample did not show any positive effect of familiar, pleasant and stimulating music on working memory. Performance on the n-back task generally improved from pre to post, in all conditions, but this improvement was less important in participants who listened to familiar Rwandan music compared to those who listened to unfamiliar Western music or to a short story. The study highlights the importance of considering the sociocultural context in research examining the impact of music on cognition. Although different aspects of music are considered universal, there may be cultural differences that limit the generalization of certain effects of music on cognition or that modulate the characteristics that favor its beneficial impact.

The psychological correlates of transitional justice in Rwanda: A long-term assessment.

OBJECTIVE: We tested the psychological correlates of the Gacaca tribunals, a massive program of transitional justice put in place by the Rwandan government following the 1994 genocide perpetrated against the Tutsi. METHOD: The sample consisted of 679 Rwandese participants, among which 373 (55%) were survivors of the genocide. We contrasted three groups of participants: (1) those who had never attended the Gacaca (N = 229), the control group, (2) those who had attended without testifying (N = 275), the attendance group, and (3) those who had attended and testified (N = 120), the testimony group. In the analyses, we controlled for the level of genocide-related negative consequences that participants reported. RESULTS: The attendance group presented lower levels of PTSD and depression symptoms than both the control and testimony groups. Both attendance and testimony groups had more positive opinions of the Gacaca and higher openness to reconciliation than the control group. CONCLUSIONS: contrary to what has been reported in two previous studies, participation in the Gacaca was not, in our data, negatively related to mental health or to social cohesion. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Effects of Institutionalization and Parental Living Status on Children's Self-Esteem, and Externalizing and Internalizing Problems in Rwanda.

The negative effects of institutionalization on children's wellbeing and psychological adjustment have been extensively documented. Throughout the world, particularly in developing countries, many children in residential child care institutions known as orphanages have parents, and it is not clear how this situation affects the psychological adjustment of institutionalized children. This study aimed at investigating specifically whether institutionalization impacts negatively children's psychological adjustment defined in terms of externalizing and internalizing behavior problems and self-esteem and whether having living parents or not has an additional influence. Children were recruited in Rwanda from seven registered institutions and six primary schools. Ninety-six institutionalized children (48 orphans, who lost at least one parent, and 46 non-orphans, who had both parents living) and 84 non-institutionalized children, who lived in a family (28 orphans and 56 non-orphans) aged 9 to 16 participated. The caregivers or parents assessed externalizing and internalizing behavior problems using the Child Behavior Checklist. Children completed the Coopersmith Self-Esteem Inventory. Controlling for gender, age, and residential area, analyses of covariance revealed that institutionalized children had significantly more externalizing behavior problems than had non-institutionalized children. In addition, non-orphans had more externalizing behavior problems than had orphans, regardless of whether they lived in an institution or not. There were no group differences in internalizing behavior problems, but there was a significant main effect of the parental living status (orphans vs. non-orphans) and a significant interaction effect between parental living status and institutionalization on self-esteem. Self-esteem of non-orphans in families was significantly higher than self-esteem of the other groups. This should be considered when making the decision to place a child in an institution, especially when her or his parents are still living, and when developing supportive programs for children without adequate parental care.

Long-term cognitive correlates of exposure to trauma: Evidence from Rwanda.

Research increasingly shows links between trauma exposure, posttraumatic stress symptoms, and cognitive functioning. We know relatively little about the long-term cognitive correlates of exposure to trauma, especially in civilian populations exposed to war and political violence. OBJECTIVE: Our goal was to examined short-term memory (STM) and executive function 20 years after the 1994 genocide of the Tutsis in Rwanda. We hypothesized that performance on these tasks would be negatively related to trauma exposure and to posttraumatic stress disorder (PTSD) symptoms. METHOD: In two studies, 470 Rwandan participants answered questionnaires measuring the severity of experiences that occurred during the 1994 genocide and current levels of PTSD symptoms. In both studies, we tested STM using a forward digit span task. In the second study, we also measured executive function using a semantic fluency task. RESULTS: There were modest but significant negative links between the severity of experiences during the genocide and STM function more than 20 years after. Current levels of PTSD symptoms were also related to STM and executive function. CONCLUSIONS: This study reveals the important link between exposure to highly emotional events and cognitive function and highlights the need to attend not only to the mental health but also to the cognitive health of populations exposed to political violence. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Twenty years later, the cognitive portrait of openness to reconciliation in Rwanda.

With this work, we intended to draw a cognitive portrait of openness to reconciliation. No study had yet examined the potential contribution of high-level cognitive functioning, in addition to psychological health, to explaining attitudes towards reconciliation in societies exposed to major trauma such as post-genocide Rwanda. We measured the contribution of general cognitive capacity, analytical thinking, and subjective judgements. Our results show that higher cognitive capacity is not associated with greater openness to reconciliation. On the other hand, proneness to think analytically about the genocide predicts more favorable attitudes towards reconciliation. The latter effect is associated with more tempered judgements about retrospective facts (e.g., number of genocide perpetrators) and prospective events (e.g., risk of genocide reoccurrence). This work establishes the importance of cognitive functioning in the aftermath of political violence: A better understanding of the influence of information processing on openness to reconciliation may help improve reconciliation policies and contribute to reducing risks of conflict reoccurrence.

The Tutsi genocide and transgenerational transmission of maternal stress: epigenetics and biology of the HPA axis.

OBJECTIVES: Transmission of parental post-traumatic stress disorder (PTSD) to offspring might be explained by transmission of epigenetic processes such as methylation status of the glucocorticoid receptor (GR) gene (NR3C1). METHODS: We investigated PTSD and depression severity, plasma cortisol, GR and mineralocorticoid receptor (MR) levels, and methylation status of NR3C1 and NR3C2 promoter regions in 25 women exposed to the Tutsi genocide during pregnancy and their children, and 25 women from the same ethnicity, pregnant during the same period but not exposed to the genocide, and their children. RESULTS: Transmission of PTSD to the offspring was associated with transmission of biological alterations of the HPA axis. Mothers exposed to the genocide as well as their children had lower cortisol and GR levels and higher MR levels than non-exposed mothers and their children. Moreover, exposed mothers and their children had higher methylation of the NR3C1 exon 1F than non-exposed groups. Finally, exposed mothers showed higher methylation of CpGs located within the NR3C2 coding sequence than non-exposed mothers. CONCLUSIONS: PTSD was associated with NR3C1 epigenetic modifications that were similarly found in the mothers and their offspring, modifications that may underlie the possible transmission of biological alterations of the HPA axis.