Family Therapy for Kosovar Mothers Who Experienced Conflict-Related Sexual Violence and Their Children in Postwar Times: A Pilot Randomised Waitlist-Controlled Trial.

Women who have experienced conflict-related sexual violence report significant long-term effects, including posttraumatic stress disorder (PTSD), depression and relationship difficulties. Research has demonstrated that maternal trauma is associated with children's behavioural difficulties and challenges in family functioning, such as impaired communication and harsh parenting. This pilot study is aimed at evaluating the preliminary effectiveness of family therapy for Kosovar mothers who experienced conflict-related sexual violence in 1998-1999 and later developed PTSD and their children in improving family functioning and reducing behavioural difficulties in postwar times. Sixty-four mothers were randomised to an intervention group or a waitlist control group. Data was collected during a screening phase, at baseline before intervention initiation, after the intervention group completed family therapy and once the waitlist control group received the intervention. Generalised linear mixed models were used to analyse group differences in family functioning and children's behaviours over time. At follow-up, mothers in the intervention group reported improved family functioning. However, mothers in the waitlist control group reported significantly fewer behavioural difficulties than mothers in the intervention group before the control group had started family therapy. There was no significant interaction between group condition and time for child-rated family functioning. Overall, this pilot study suggests that family therapy could be effective in reducing the effects of intergenerational trauma related to PTSD and conflict-related sexual violence. Future research should evaluate the long-term effects of family therapy to assess if immediate effects were maintained.

An epigenome-wide study of a needs-based family intervention for offspring of trauma-exposed mothers in Kosovo.

INTRODUCTION: Maternal stress and trauma during pregnancy have been shown to influence cortisol levels and epigenetic patterns, including DNA methylation, in the offspring. This study aimed to determine whether a tailor-made family intervention could help reduce cortisol levels in children born to traumatized mothers, and to determine whether it effected offspring DNA methylation. The secondary aim was to determine whether the family intervention influenced DNA methylation aging, a marker of biological aging. METHODS: A needs-based family intervention was designed to help address relational difficulties and family functioning, and included a focus on family strengths and problem-solving patterns. Women survivors of sexual violence during the Kosovar war in 1998-1999, and their families (children with or without partners) were randomly assigned to 10 sessions of a family therapy over a 3-5-month period, or to a waitlist control group. Both mothers and children completed assessments prior to and after the intervention phase. Children's blood samples collected at these two time points were used to measure cortisol and epigenome-wide DNA methylation patterns (Illumina EPIC array). Cortisol levels, and genome-wide DNA methylation changes pre-/postintervention were compared between children in the intervention and the waitlist groups. DNA methylation age and accelerated biological aging were calculated. RESULTS: Sixty-two women-child dyads completed the study, 30 were assigned first to the intervention group, and 32 to the waitlist control group. In adjusted linear regression, the family intervention was associated with a significant decline in cortisol levels compared to the waitlist control (ß = -124.72, 95% confidence interval [CI]: -197.4 to -52.1, p = .001). Children in the intervention group, compared to the waitlist control group, showed >1% differential methylation degree at 5819 CpG (5'-C-phosphate-G-3') sites across the genome (p < .01), with the largest methylation difference being 21%. However, none of these differences reached genome-wide significant levels. There was no significant difference in DNA methylation aging between the two groups. CONCLUSION: We find evidence that a tailored family-based intervention reduced stress levels in the children (based on cortisol levels), and modified DNA methylation levels at a number of sites across the genome. This study provides some preliminary evidence to suggest the potential for tailored interventions to help break the intergenerational transmission of trauma, however, large studies powered to detect associations at genome-wide significant levels are needed.

DNA methylation in blood cells is associated with cortisol levels in offspring of mothers who had prenatal post-traumatic stress disorder.

Maternal stress during pregnancy is associated with differential DNA methylation in offspring and disrupted cortisol secretion. This study aimed to determine methylation signatures of cortisol levels in children, and whether associations differ based on maternal post-traumatic stress disorder (PTSD). Blood epigenome-wide methylation and fasting cortisol levels were measured in 118 offspring of mothers recruited from the Kosovo Rehabilitation Centre for Torture Victims. Mothers underwent clinically administered assessment for PTSD using Diagnostic and Statistical Manual of Mental Disorders. Correlations between offspring methylation and cortisol levels were examined using epigenome-wide analysis, adjusting for covariates. Subsequent analysis focussed on a priori selected genes involved in the hypothalamic-pituitary-adrenal (HPA) axis stress signalling. Methylation at four sites were correlated with cortisol levels (cg15321696, r = -0.33, cg18105800, r = +0.33, cg00986889, r = -0.25, and cg15920527, r = -0.27). In adjusted multivariable regression, when stratifying based on prenatal PTSD status, significant associations were only found for children born to mothers with prenatal PTSD (p < 0.001). Several sites within HPA axis genes were also associated with cortisol levels in the maternal PTSD group specifically. There is evidence that methylation is associated with cortisol levels, particularly in offspring born to mothers with prenatal PTSD. However, larger studies need to be carried out to independently validate these findings.