Differential methylation of linoleic acid pathway genes is associated with PTSD symptoms - a longitudinal study with Burundian soldiers returning from a war zone.

Soldiers may be exposed to traumatic stress during combat deployment and thus are at risk for developing posttraumatic stress disorder (PTSD). Genetic and epigenetic evidence suggests that PTSD is linked to forming stress-related memories. In the current study, we investigated post-deployment associations of PTSD symptoms with differential DNA methylation in a sample of Burundian soldiers returning from the African Union Mission in Somalia's war zone. We used a matched longitudinal study design to explore epigenetic changes associated with PTSD symptoms in N = 191 participants. PTSD symptoms and saliva samples were collected at 1-3 (t1) and 9-14 months (t2) after the return of the soldiers to their home base. Individuals with either worsening or improving PTSD symptoms were matched for age, stressful, traumatic and self-perpetrated events prior to the post-assessment, traumatic and violent experiences between the post- and the follow-up assessment, and violence experienced during childhood. A mixed model analysis was conducted to identify top nominally significantly differentially methylated genes, which were then used to perform a gene enrichment analysis. The linoleic acid metabolism pathway was significantly associated with post-deployment PTSD symptoms, after accounting for multiple comparisons. Linoleic acid has been linked to memory and immune related processes in previous research. Our findings suggest that differential methylation of linoleic acid pathway genes is associated with PTSD and thus may merit closer inspection as a possible mediator of resilience.

Barriers and opportunities for implementation of a brief psychological intervention for post-ICU mental distress in the primary care setting - results from a qualitative sub-study of the PICTURE trial.

BACKGROUND: The results of critical illness and life-saving invasive measures during intensive care unit treatment can sometimes lead to lasting physical and psychological impairments. A multicentre randomized controlled trial from Germany (PICTURE) aims to test a brief psychological intervention, based on narrative exposure therapy, for post-traumatic stress disorder symptoms following intensive care unit treatment in the primary care setting. A qualitative analysis was conducted to understand feasibility and acceptance of the intervention beyond quantitative analysis of the main outcomes in the primary study. METHODS: Qualitative explorative sub-study of the main PICTURE trial, with eight patients from the intervention group recruited for semi-structured telephone interviews. Transcriptions were analysed according to Mayring's qualitative content analysis. Contents were coded and classified into emerging categories. RESULTS: The study population was 50% female and male, with a mean age of 60.9 years and transplantation surgery being the most frequent admission diagnosis. Four main factors were identified as conducive towards implementation of a short psychological intervention in a primary care setting: 1) long-term trustful relationship between patient and GP team; 2) intervention applied by a medical doctor; 3) professional emotional distance of the GP team; 4) brevity of the intervention. CONCLUSION: The primary setting has certain qualities such as a long-term doctor-patient relationship and low-threshold consultations that offer good opportunities for implementation of a brief psychological intervention for post-intensive care unit impairments. Structured follow-up guidelines for primary care following intensive care unit treatment are needed. Brief general practice-based interventions could be part of a stepped-care approach. TRIAL REGISTRATION: The main trial was registered at the DRKS (German Register of Clinical Trials: DRKS00012589) on 17/10/2017.

Epigenetics of traumatic stress: The association of NR3C1 methylation and posttraumatic stress disorder symptom changes in response to narrative exposure therapy.

Epigenetic processes allow plasticity in gene regulation in response to significant environmental events. Accumulating evidence suggests that effective psychotherapy is accompanied by epigenetic changes, rendering DNA methylation a potential biomarker of therapy success. Due to the central role of glucocorticoid dynamics in stress regulation and the alteration of aversive memories, glucocorticoid receptors are likely involved in the molecular processes that are required to successfully treat Posttraumatic Stress Disorder (PTSD). This study aimed to investigate the relationship between methylation at the glucocorticoid receptor gene (NR3C1) and PTSD treatment success of evidence-based psychotherapy. A sample of N = 153 conflict survivors from Northern Uganda (98 females and 55 males) with PTSD were treated with Narrative Exposure Therapy (NET). Diagnostic interviews and saliva sampling took place at pretreatment and 4 and 10 months after treatment completion. We investigated potential associations between PTSD symptom development and methylation changes at 38 CpG sites spanning NR3C1 over the three times of measurement using the repeated measures correlation. After accounting for multiple comparisons, DNA methylation at CpG site cg25535999 remained negatively associated with PTSD symptoms. These results were followed up by mixed models as well as structural equation modelling. These analyses revealed that treatment responders had a significant cg25535999 methylation increase after treatment with NET. Furthermore, lower methylation at cg25535999 pretreatment predicted a higher symptom improvement. Our results suggest different epigenetic profile dynamics at NR3C1 cg25535999 in therapy responders compared to non-responders and underscore the central role of glucocorticoid signaling in trauma-focused therapy.

Cumulative trauma predicts hair cortisol concentrations and symptoms of depression and anxiety in pregnant women-an investigation of community samples from Greece, Spain and Perú.

Exposure to traumatic experiences across lifespan shapes the functioning of the hypothalamic pituitary adrenal (HPA) axis and sets individuals at risk to develop symptoms of depression and anxiety. Particularly, HPA axis regulation and the psychological health of the expectant mother have been of interest, as the health of the unborn child may be affected through changes in gestational biology. The present study investigated the potential associations between lifetime trauma, current symptoms (depression and anxiety) and hair cortisol concentrations (HCC) in pregnant women. A total of 149 pregnant women were interviewed in public outpatient clinics with varying gestational age in Greece, Spain and Perú. Lifetime trauma exposure and current symptoms of depression and anxiety were assessed. HCC was measured in scalp-near hair segments (2 cm length) reflecting cumulative cortisol secretion of the past two months. Results showed that trauma load is negatively associated with HCC and higher symptoms of depression and anxiety. There was a negative association between HCC and symptoms. The present findings support the notion that cumulative trauma exposure exerts long-lasting effects on the expectant mother's HPA axis activity functioning and mental health and may thereby potentially create risk trajectories for the unborn child via changes in gestational biology.

Breaking the cycles of violence with narrative exposure: Development and feasibility of NETfacts, a community-based intervention for populations living under continuous threat.

BACKGROUND: Interpersonal violence damages mental health and frequently leads to aggressive defence strategies. If survivors are subsequently blamed for the events, both consequences worsen. Stigma flourishes, especially when survivors are silenced so that details of the trauma remain unknown. Breaking the secrecy both at the individual and collective level is key to enable the healing and reconciliation of individuals and communities living under continuous threat. METHOD: The NETfacts health system is a stepped care model with three components: (1) Narrative Exposure Therapy (NET), an evidence-based trauma therapy that includes survivor testimony (2) NET for Forensic Offender Rehabilitation (FORNET) acknowledges that perpetrators are frequently also victims and assists in reducing aggression and the attraction to violence, and (3) a community intervention disseminating and discussing Facts derived from NET treatment (NETfacts) to challenge the collective avoidance of atrocities and other traumatic material. The intervention was piloted in a community with 497 adult residents in Eastern Democratic Republic of Congo. The willingness of clients to consent to sharing their anonymised testimonies (with a focus on sexual violence survivors and ex-combatants) was investigated, together with other components of feasibility including security and clinical safety, extent of support of respected local authorities and participation rates. As secondary outcomes, clinical and social measures were assessed before and post NETfacts among 200 village residents of whom 160 self-enrolled and 40 had not participated in any form of treatment. RESULTS: Implementation was feasible with 248 clients from a partner project giving consent to use their testimonies and high support of respected local authorities and participation rates (56% of residents self-enrolled in NETfacts). Immediate beneficial effects were shown for posttraumatic stress and rejection of rape myths among NETfacts participants who experienced multiple traumatic events in their own past. Attitudes towards ex-combatants improved and the perceived lack of social acknowledgement after trauma increased independent from participation. No significant change was observed for depressive symptoms. CONCLUSION: NETfacts is a feasible and promising approach to challenge the culture of secrecy surrounding trauma, suppression and social exclusion. Long term effectiveness requires further evaluation.

NETfacts: An integrated intervention at the individual and collective level to treat communities affected by organized violence.

War and crises affect mental health, social attitudes, and cultural norms, which can exacerbate the state of long-term insecurity. With decades of armed conflict, the Democratic Republic of Congo is one example, and violence has become normalized in civilian settings. In this study, we tested the effectiveness of the NETfacts health system, an integrated model of evidence-based individual trauma treatment (Narrative Exposure Therapy [NET]) and a trauma-informed community-based intervention (NETfacts). Alongside changes in mental health outcomes (posttraumatic stress disorder, depression, social disapproval, and shame) we also investigated change in attitudes, including rape myth acceptance, stigmatization of survivors of sexual violence, and skepticism about the reintegration of former combatants. To test whether the additional community intervention is superior to individual NET alone, we implemented a randomized controlled design with six villages and interviewed a sample of 1,066 community members. Our results demonstrate that the NETfacts health system in comparison with NET alone more effectively reduced rape myth acceptance and with it ongoing victimization and perpetration. Community members of the NETfacts group also presented with less stigmatizing attitudes against survivors of sexual violence. Skepticism about the reintegration of former combatants declined in both groups. NETfacts appears to have increased motivation to engage in individual treatment. Synergizing the healing effects of individual and collective trauma exposure, the NETfacts health system appears to be an effective and scalable approach to correct degrading or ignominious norms and restore functioning and mental health in postconflict communities.

Associations between telomere length and symptoms of posttraumatic stress disorder and appetitive aggression in trauma-exposed men.

Exposure to community violence is common in South Africa and negatively impacts on biopsychosocial health. Posttraumatic stress disorder (PTSD) is characterised by symptoms of intrusion, avoidance, hypervigilance and negative alterations in cognition and mood, and can develop consequent to trauma exposure. Individuals who repeatedly experience and witness violence may also come to view it as appealing and rewarding. This appetitive aggression (AA) increases the likelihood of perpetrating violence. Telomeres are repetitive nucleotide sequences that protect the ends of chromosomes. Telomere length (TL) attrition is a stress-sensitive marker of biological aging that has been associated with a range of psychiatric disorders. This study investigated the cross-sectional relationship between TL and symptoms of PTSD and AA in South African men residing in areas with high community violence. PTSD and AA symptom severity was assessed in 290 men using the Posttraumatic Stress Disorder Symptom Scale - Interview (PSS-I) and Appetitive Aggression Scale (AAS), respectively. Quantitative polymerase chain reaction was performed on DNA extracted from saliva and used to calculate relative TL (rTL). Regression models were used to assess the relationships between rTL and PSS-I and AAS scores. Network analyses using EBIC glasso methods were performed using rTL and items from each of the AAS and PSS-I measures. Both PSS-I (p = 0.023) and AAS (p = 0.016) scores were positively associated with rTL. Network analyses indicated that rTL was weakly related to two PSS-I and five AAS items but performed poorly on indicators of centrality and was not strongly associated with measure items either directly or indirectly. The positive association between rTL and measures of AA and PTSD may be due to the induction of protective homeostatic mechanisms, which reduce TL attrition, following early life trauma exposure.

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

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).

Treating trauma and aggression with narrative exposure therapy in former child and adult soldiers: A randomized controlled trial in Eastern DR Congo.

OBJECTIVE: Individuals who return from armed groups present with a history of traumatic events including perpetration. Subsequent severe mental stress and heightened levels of reactive and appetitive aggression may persist and if left untreated, frequently impede peacebuilding and societal stability. In this study, we tested a revised adaptation of Narrative Exposure Therapy (NET; Schauer et al., 2011) for Forensic Offender Rehabilitation (FORNET) implemented in a sample of male former combatants in war-torn regions of the DR Congo. METHOD: We applied a longitudinal parallel-group randomized controlled design with treatment as usual (TAU) as control condition and 3-5 and 6-9 months follow-up assessments. The effect of treatment over time on clinical and social outcomes was tested with GLMMs; appetitive aggression and current violent behavior (CVB) were specified as primary and posttraumatic stress as secondary outcomes. RESULTS: FORNET decreased appetitive aggression (within group Cohen's dz = 2.00), CVB (dz = .90) and posttraumatic stress (dz = 1.48) significantly more than treatment as usual. Clinical significance was obtained for all outcomes. Remarkably, NET clients also reduced their substance abuse (dz = .68) even though this was not targeted within the intervention. Depression, perceived social acknowledgement and subjective solidarity with (para)military life decreased. CONCLUSION: FORNET is a compact and scalable psychotherapeutic intervention that effectively reduces current aggressive behavior including physical abuse against children, intimate partner violence (IPV), and community violence. FORNET further decreases appetitive aggression, posttraumatic stress symptoms, and other clinical and social problems that commonly hinder demobilization, reintegration, and post-conflict peacebuilding. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

To add insult to injury: Stigmatization reinforces the trauma of rape survivors - Findings from the DR Congo.

BACKGROUND: Survivors of sexual violence are frequently condemned and socially excluded. Myths about rape may translate into stigmatization, diminish disclosure, prevent help-seeking from support structures and worsen mental health. Areas of conflict or organized violence remain the evident hotspots of sexual victimization. However, little is known about prevalence and predictors of rape myths in these settings or their association with survivors' disclosure, stigmatization and psychopathology. METHOD: Between September 2018 and May 2019, we assessed in a representative sample of 1066 individuals from six communities in Eastern DRC traumatic exposure, sexual perpetration, threats to social integrity, perceived stigmatization (perceived lack of social acknowledgement, shame), stigmatizing attitudes towards survivors (negative attitudes and willingness to provide support, rape myths acceptance), and mental illness (PTSD, depression). RESULTS: Survivors of sexual violence (33%, n = 184 of women, 16%, n = 84 of men) reported more traumatic exposure, threats to social integrity, shame, perceived lack of social acknowledgement, PTSD symptoms and depression. Their social environment affirmed various stigmatizing attitudes (5-89% affirmations). Beliefs in rape myths were predicted by its average acceptance in the community, education, and witness of others' sexual victimization. The rates of cases whose history of sexual victimization was socially disclosed were higher in communities and among survivors with low rape myths acceptance and disclosure showed associations with perceived stigmatization. Rape myths acceptance among individuals without a history of sexual victimization was associated with survivors' recently experienced threats to social integrity which predicted their stigma perceptions and mental illness. CONCLUSION: Rape myths acceptance in the community is associated with stigma and trauma-related mental illness of sexual violence survivors. This adds up to the psychic burden of trauma.

DNA methylation and psychotherapy response in trauma-exposed men with appetitive aggression.

Exposure to violence can lead to appetitive aggression (AA), the positive feeling and fascination associated with violence, and posttraumatic stress disorder (PTSD), characterised by hyperarousal, reexperience and feelings of ongoing threat. Psychotherapeutic interventions may act via DNA methylation, an environmentally sensitive epigenetic mechanism that can influence gene expression. We investigated epigenetic signatures of psychotherapy for PTSD and AA symptoms in South African men with chronic trauma exposure. Participants were assigned to one of three groups: narrative exposure therapy for forensic offender rehabilitation (FORNET), cognitive behavioural therapy or waiting list control (n = 9-10/group). Participants provided saliva and completed the Appetitive Aggression Scale and PTSD Symptom Severity Index at baseline, 8-month and 16-month follow-up. The relationship, over time, between methylation in 22 gene promoter region sites, symptom scores, and treatment was assessed using linear mixed models. Compared to baseline, PTSD and AA symptom severity were significantly reduced at 8 and 16 months, respectively, in the FORNET group. Increased methylation of genes implicated in dopaminergic neurotransmission (NR4A2) and synaptic plasticity (AUTS2) was associated with reduced PTSD symptom severity in participants receiving FORNET. Analyses across participants revealed a proportional relationship between AA and methylation of TFAM, a gene involved in mitochondrial biosynthesis.

Trauma, Aggression, and Post Conflict Perpetration of Community Violence in Female Former Child Soldiers-A Study in Eastern DR Congo.

OBJECTIVE: Former combatants are exposed to multiple traumatic stressors during conflict situations and usually participate in perpetration of violence. Ongoing perpetration of violence in post conflict areas, linked to mental health problems and appetitive aggression, destabilises peace keeping efforts. The aim of this study is to investigate lifetime exposure to violence and the relationship between this exposure and mental health and current violent behaviour in a sample of female former child soldiers with a history of perpetration of violence in Eastern DR Congo. METHODS: 98 female former child soldiers who had been abducted and forcibly recruited during the M23 insurgency (2012-2014) were assessed for lifetime exposure to trauma including perpetration of violence, clinical outcomes (PTSD and appetitive aggression), and current violent behaviour. RESULTS: Female former child soldiers had been exposed to extremely high levels of trauma including perpetration of violence and presented with high levels of mental health problems. Linear regression models showed that current violent behaviour was predicted by both PTSD and appetitive aggression. CONCLUSIONS: Trauma exposure predicts ongoing perpetration of violence post conflict via the resulting mental health problems. The findings imply that if PTSD and appetitive aggression symptoms are successfully treated, ongoing violent behaviour in the community post conflict will also decrease.

Does cumulative exposure to traumatic stressors predict treatment outcome of community-implemented exposure-based therapy for PTSD?

Background: Posttraumatic Stress Disorder (PTSD) is associated with high levels of functional impairments such as difficulties in academic or occupational performance and in social relationships. With an increasing number of traumatic event types experienced (trauma load), PTSD risk increases in a dose-dependent manner. Accordingly, high rates of PTSD can impair the reconstruction process in post-conflict societies. In order to meet these high needs for mental health services in societies with little access to professional care, task shifting approaches and community-based interventions have been suggested. Narrative Exposure Therapy (NET) has been developed as a short and pragmatic exposure-based PTSD treatment that can be easily trained to lay personnel. Yet, it remains unclear whether NET can be effectively provided by trained lay counsellors even at high levels of trauma load. Objective: To investigate whether trauma load influences the treatment effectiveness of NET provided by trained and supervised local lay counsellors. Method: Linear mixed models were calculated to investigate the influence of trauma load on treatment effectiveness in a sample of N = 323 rebel war survivors from Northern Uganda with PTSD. Results: We found a strong reduction of PTSD symptoms following NET, which was not influenced by trauma load. However, individuals with higher levels of trauma load reported higher PTSD symptoms before therapy as well as 4 and 10 months following treatment completion compared to individuals with lower trauma load. Conclusions: Treatment with NET by lay counsellors is effective independent of trauma load. However, individuals with higher trauma load have a higher probability to show residual symptoms, which might require additional time, sessions or treatment modules.

Antecedentes: El trastorno de estrés traumático (TEPT) se asocia con altos niveles de discapacidad funcional, tales como dificultades en el desempeño académico uocupacional yen las relaciones sociales. Con un número creciente de los tipos de eventos traumáticos experimentados (carga traumática), el riesgo de TEPT aumenta en una forma dependiente de la dosis. De la misma forma, altas tasas de TEPT pueden afectar el proceso de reconstrucción en las sociedad post-conflicto. Para abordar estas crecientes necesidades por servicios de salud mental en sociedades con poco acceso acuidado profesional, se ha sugerido el enfoque de cambio de tareas ylas intervenciones basadas en la comunidad. La Terapia de Exposición Narrativa (NET en su sigla en inglés) ha sido desarrollada como un tratamiento de TEPT basado en la exposición, breve ypragmático que puede ser fácilmente entrenado al personal laico. Aun así, permanece incierto si la NET puede ser implementada efectivamente por consejeros laicos entrenados, incluso aaltos niveles de carga traumática.Objetivo: Investigar si la carga traumática influencia la efectividad del tratamiento de la NET proporcionado por consejeros laicos locales entrenados ysupervisados.Método: Los modelos mixtos lineales se calcularon para investigar la influencia de la carga traumática en la efectividad del tratamiento, en una muestra de N= 323 sobrevivientes de guerra rebelde desde Uganda del Norte con TEPT.Resultados: Encontramos una clara reducción de los síntomas TEPT luego de la NET, la cual no fue influenciada por la carga traumática. Sin embargo, los individuos con altos niveles de carga traumática reportaron altos niveles de síntomas TEPT antes de la terapia como también 4 y 10 meses luego del término del tratamiento comparado alos individuos con carga traumáticamás baja.Conclusiones: El tratamiento con la NET administrada por consejeros laicos es efectiva independiente de la carga traumática. Sin embargo, los individuos con carga traumáticamás alta tienen una probabilidadmás alta de mostrar síntomas residuales, los cuales podrían requerir tiempo, sesiones omódulos de tratamiento adicionales.

Corrigendum: The Contribution of Posttraumatic Stress Disorder and Depression to Insomnia in North Korean Refugee Youth.

[This corrects the article DOI: 10.3389/fpsyt.2019.00211.].

NTRK2 methylation is related to reduced PTSD risk in two African cohorts of trauma survivors.

Extensive pharmacologic, genetic, and epigenetic research has linked the glucocorticoid receptor (GR) to memory processes, and to risk and symptoms of posttraumatic stress disorder (PTSD). In the present study we investigated the epigenetic pattern of 12 genes involved in the regulation of GR signaling in two African populations of heavily traumatized individuals: Survivors of the rebel war in northern Uganda (n = 463) and survivors of the Rwandan genocide (n = 350). The strongest link between regional methylation and PTSD risk and symptoms was observed for NTRK2, which encodes the transmembrane receptor tropomyosin-related kinase B, binds the brain-derived neurotrophic factor, and has been shown to play an important role in memory formation. NTRK2 methylation was not related to trauma load, suggesting that methylation differences preexisted the trauma. Because NTRK2 methylation differences were predominantly associated with memory-related PTSD symptoms, and because they seem to precede traumatic events, we next investigated the relationship between NTRK2 methylation and memory in a sample of nontraumatized individuals (n = 568). We found that NTRK2 methylation was negatively associated with recognition memory performance. Furthermore, fMRI analyses revealed NTRK2 methylation-dependent differences in brain network activity related to recognition memory. The present study demonstrates that NTRK2 is epigenetically linked to memory functions in nontraumatized subjects and to PTSD risk and symptoms in traumatized populations.

A combination of combat experience, early abduction, and severe traumatization fuels appetitive aggression and violence among abductees of rebel war in Northern Uganda.

Individuals who perpetrate violence may likely perceive violence as appealing and infliction of violence to derive pleasure is termed as appetitive aggression. Individuals who were abducted as children into an armed group often experience a higher number of traumatic event types, that is traumatic load and are usually socialized in a violence-endorsing environment. This study aims to investigate the interaction between age at initial abduction with that of traumatic load, and their influence on appetitive aggression along with perpetration of violent acts by former members of an armed rebel group of both sexes. Semi-structured interviews were conducted among a target group of formerly abducted rebel-war survivors (including participants with and without combat experience) from Northern Uganda. Participants included 596 women and 570 men with N = 1,166 (Mage = 32.58, SDage = 9.76, range: 18-80 years). We conducted robust linear regression models to investigate the influence of age at initial abduction, traumatic load, combat experience, and biological sex on appetitive aggression as well as their perpetrated violent acts. Our study shows, appetitive aggression and the number of perpetrated violent acts were specifically increased in individuals who were abducted young, experienced several traumatic events in their lifetime, and with previous combat experience. For perpetrated violence men showed increased levels whereas for appetitive aggression the association was independent of biological sex. Therefore, early abducted individuals with a higher traumatic load, who have combat experience, need to be given special intervention to prevent any further violence.

Evolutionary conserved role of neural cell adhesion molecule-1 in memory.

The neural cell adhesion molecule 1 (NCAM-1) has been implicated in several brain-related biological processes, including neuronal migration, axonal branching, fasciculation, and synaptogenesis, with a pivotal role in synaptic plasticity. Here, we investigated the evolutionary conserved role of NCAM-1 in learning and memory. First, we investigated sustained changes in ncam-1 expression following aversive olfactory conditioning in C. elegans using molecular genetic methods. Furthermore, we examined the link between epigenetic signatures of the NCAM1 gene and memory in two human samples of healthy individuals (N = 568 and N = 319) and in two samples of traumatized individuals (N = 350 and N = 463). We found that olfactory conditioning in C. elegans induced ncam-1 expression and that loss of ncam-1 function selectively impaired associative long-term memory, without causing acquisition, sensory, or short-term memory deficits. Reintroduction of the C. elegans or human NCAM1 fully rescued memory impairment, suggesting a conserved role of NCAM1 for memory. In parallel, DNA methylation of the NCAM1 promoter in two independent healthy Swiss cohorts was associated with memory performance. In two independent Sub-Saharan populations of conflict zone survivors who had faced severe trauma, DNA methylation at an alternative promoter of the NCAM1 gene was associated with traumatic memories. Our results support a role of NCAM1 in associative memory in nematodes and humans, and might, ultimately, be helpful in elucidating diagnostic markers or suggest novel therapy targets for memory-related disorders, like PTSD.

Trajectories of posttraumatic stress symptoms during and after Narrative Exposure Therapy (NET) in refugees.

BACKGROUND: Trauma-focused therapy approaches are recommended as treatment for posttraumatic stress disorder (PTSD). This includes the treatment of trauma-related suffering in refugee populations. However, there is a lack of knowledge about symptom trajectories in refugees living in volatile conditions. This has led to fear of "retraumatisation" and general skepticism in clinicians concerning the use of exposure therapy. METHODS: To test the relevance of this concern, we investigated PTSD symptom trajectories and potentially influencing factors during the course of Narrative Exposure Therapy (NET) in a refugee sample living in Germany. Refugees filled out the PTSD Checklist prior to each treatment session and also during follow-up interviews. Therapists continuously documented positive and negative life events as well as the content of the treatment sessions. Additionally, structured clinical interviews were conducted pre-treatment and at follow-up time points. RESULTS: On average, clients presented with substantial decreases in PTSD symptoms already during and after NET. However, symptom trajectories differed and ranged from fast responders to slow responders to no immediate response during treatment. Importantly, a persistent worsening of symptoms was not observed, also not after exposure to the most distressing events. In contrast, stressful life experiences seemed to aggravate PTSD symptoms. CONCLUSIONS: Consistent with earlier studies, NET leads to clinically and behaviorally relevant reductions in PTSD symptoms both throughout and following treatment in refugees living in volatile conditions. Concerns about imaginal exposure in refugees were not substantiated. While stressful life events contributed to transient symptom increases, they weren't found to prevent the overall effectiveness of NET. TRIAL REGISTRATION: NCT02852616.

The cycle of violence as a function of PTSD and appetitive aggression: A longitudinal study with Burundian soldiers.

During deployment, soldiers face situations in which they are not only exposed to violence but also have to perpetrate it themselves. This study investigates the role of soldiers' levels of posttraumatic stress disorder (PTSD) symptoms and appetitive aggression, that is, a lust for violence, for their engaging in violence during deployment. Furthermore, factors during deployment influencing the level of PTSD symptoms and appetitive aggression after deployment were examined for a better comprehension of the maintenance of violence. Semi-structured interviews were conducted with 468 Burundian soldiers before and after a 1-year deployment to Somalia. To predict violent acts during deployment (perideployment) as well as appetitive aggression and PTSD symptom severity after deployment (postdeployment), structural equation modeling was utilized. Results showed that the number of violent acts perideployment was predicted by the level of appetitive aggression and by the severity of PTSD hyperarousal symptoms predeployment. In addition to its association with the predeployment level, appetitive aggression postdeployment was predicted by violent acts and trauma exposure perideployment as well as positively associated with unit support. PTSD symptom severity postdeployment was predicted by the severity of PTSD avoidance symptoms predeployment and trauma exposure perideployment, and negatively associated with unit support. This prospective study reveals the importance of appetitive aggression and PTSD hyperarousal symptoms for the engagement in violent acts during deployment, while simultaneously demonstrating how these phenomena may develop in mutually reinforcing cycles in a war setting.

Effects of Narrative Exposure Therapy on Posttraumatic Stress Disorder, Depression, and Insomnia in Traumatized North Korean Refugee Youth.

Refugees affected by multiple traumatic stressors are at high risk for developing trauma-related mental disorders, including posttraumatic stress disorder (PTSD), depression, and insomnia, which is sometimes overlooked. The present study examined the effectiveness of narrative exposure therapy (NET) on trauma-related symptoms in a sample of North Korean refugee youth. We focused on sleep patterns in addition to changes in symptom severity for PTSD, depression, and internalizing and externalizing symptoms. North Korean refugee youth (N = 20) with PTSD were assigned to either an NET-based treatment group or a control group, which consisted of treatment as usual (TAU). There were clinically significant reductions in PTSD, depression, and internalizing and externalizing symptoms for the NET group, Hedges' g = 3.6, but not the TAU group. The change in diagnostic status for PTSD was more notable for participants in the NET group compared to the TAU group. Of note, NET also produced a significant improvement in insomnia symptoms and sleep quality, Hedges' g = 2.1. The substantial recovery regarding overall posttraumatic symptoms in the NET group was observed 2 weeks after the end of treatment and remained stable at 6-month follow-up. The results of the present study suggest that NET may be a treatment option for traumatized North Korean refugee youth and may also be effective for the treatment of sleep problems that arise from traumatic experiences.