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.

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.

Intergenerational effects of maternal post-traumatic stress disorder on offspring epigenetic patterns and cortisol levels.

Aim: To investigate the association between maternal post-traumatic stress disorder (PTSD) during pregnancy and offspring DNA methylation and cortisol levels. Materials & methods: Blood genome-wide DNA methylation and cortisol was measured in the youngest child of 117 women who experienced sexual violence/torture during the Kosovo war. Results: Seventy-two percent of women had PTSD symptoms during pregnancy. Their children had higher cortisol levels and differential methylation at candidate genes (NR3C1, HTR3A and BNDF). No methylation differences reached epigenome-wide corrected significance levels. Conclusion: Identifying the biological processes whereby the negative effects of trauma are passed across generations and defining groups at high risk is a key step to breaking the intergenerational transmission of the effects of mental disorders.