Adverse childhood experiences, posttraumatic stress, and FKBP5 methylation patterns in postpartum women and their newborn infants.
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ABSTRACT: Background
Genetic variation and epigenetic mechanisms involving the stress-related gene FKBP5 have been implicated in the intergenerational transmission of trauma-related effects in adult offspring of trauma-exposed caregivers, but these processes have not been fully explored in postpartum women and their newborn infants.Methods
Women recruited from a prenatal care clinic during their third trimester of pregnancy (N = 114) completed a battery of instruments assessing adverse childhood experiences (ACEs), adversity in adulthood, posttraumatic stress disorder (PTSD) symptoms, negative emotional state, and emotion dysregulation. FKBP5 rs1360780 genotype and intron 7 methylation were derived from saliva collected from postpartum mothers and their newborn infants within 24 h of delivery.Results
Allele-specific associations of methylation with maternal ACEs and prenatal trauma-related symptoms were evident; however, relations differed between mothers and newborns. In mothers carrying the stress sensitive T-allele (CT and TT genotypes), maternal FKBP5 methylation negatively correlated with threat-based ACEs and maternal PTSD symptoms during pregnancy, but not deprivation-based ACEs. In infants homozygous for the C allele (CC genotype), infant FKBP5 methylation positively correlated with maternal threat-based ACEs and prenatal PTSD symptom severity, but not deprivation-based ACEs or adversity in adulthood.Conclusions
Our results provide evidence that links maternal threat-based ACEs and trauma-related symptoms during pregnancy with allele-specific epigenetic patterns in postpartum women and their newborn infants. These findings provide mechanistic insight into the potential intergenerational impact of ACEs and the effect of maternal PTSD symptoms during pregnancy.
SUBMITTER: Grasso DJ
PROVIDER: S-EPMC7096279 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ContextIn addition to trauma exposure, other factors contribute to risk for development of posttraumatic stress disorder (PTSD) in adulthood. Both genetic and environmental factors are contributory, with child abuse providing significant risk liability.ObjectiveTo increase understanding of genetic and environmental risk factors as well as their interaction in the development of PTSD by gene x environment interactions of child abuse, level of non-child abuse trauma exposure, and genetic polymorphisms at the stress-related gene FKBP5.Design, setting, and participantsA cross-sectional study examining genetic and psychological risk factors in 900 nonpsychiatric clinic patients (762 included for all genotype studies) with significant levels of childhood abuse as well as non-child abuse trauma using a verbally presented survey combined with single-nucleotide polymorphism (SNP) genotyping. Participants were primarily urban, low-income, black (>95%) men and women seeking care in the general medical care and obstetrics-gynecology clinics of an urban public hospital in Atlanta, Georgia, between 2005 and 2007.Main outcome measuresSeverity of adult PTSD symptomatology, measured with the modified PTSD Symptom Scale, non-child abuse (primarily adult) trauma exposure and child abuse measured using the traumatic events inventory and 8 SNPs spanning the FKBP5 locus.ResultsLevel of child abuse and non-child abuse trauma each separately predicted level of adult PTSD symptomatology (mean [SD], PTSD Symptom Scale for no child abuse, 8.03 [10.48] vs > or =2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs > or =4 types, 16.74 [12.90]; P < .001). Although FKBP5 SNPs did not directly predict PTSD symptom outcome or interact with level of non-child abuse trauma to predict PTSD symptom severity, 4 SNPs in the FKBP5 locus significantly interacted (rs9296158, rs3800373, rs1360780, and rs9470080; minimum P = .0004) with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. This gene x environment interaction remained significant when controlling for depression severity scores, age, sex, levels of non-child abuse trauma exposure, and genetic ancestry. This genetic interaction was also paralleled by FKBP5 genotype-dependent and PTSD-dependent effects on glucocorticoid receptor sensitivity, measured by the dexamethasone suppression test.ConclusionsFour SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult PTSD symptoms. There were no main effects of the SNPs on PTSD symptoms and no significant genetic interactions with level of non-child abuse trauma as predictor of adult PTSD symptoms, suggesting a potential gene-childhood environment interaction for adult PTSD.
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Project description:ObjectivesMothers with a history of adverse childhood experiences (ACE) are at elevated risk for postpartum mental illness and impairment in the mother-infant relationship. Interventions attending to maternal-infant interactions may improve outcomes for these parents and their children, but barriers to accessing in-person postpartum care limit uptake. We adapted a postpartum psychotherapy group for mothers with mental illness (e.g., mood, anxiety, trauma-related disorders) and ACE for live video-based delivery, and evaluated feasibility, acceptability, and preliminary efficacy in an open-label pilot study.MethodsWe recruited adults with children (6-18 months) from a perinatal psychiatry program in Toronto, Canada. The intervention was a live video-based 12-week interactive psychotherapy group focused on maternal symptoms and maternal-infant relationships. The primary outcome was feasibility, including feasibility of recruitment and retention, fidelity of the intervention, and acceptability to patients and group providers. Maternal clinical outcomes were compared pre- to post-intervention, as secondary outcomes.ResultsWe recruited 31 participants (mean age 36.5 years (SD 3.9)) into 6 groups; 93.6% (n = 29) completed post-group questionnaires, and n = 20 completed an optional post-group acceptability interview. Mean weekly group attendance was 83% (IQR 80-87); one participant (3.2%) dropped out. All group components were implemented as planned, except for dyadic exercises where facilitator observation of dyads was replaced with unobserved mother-infant exercises followed by in-group reflection. Participant acceptability was high (100% indicated the virtual group was easy to access, beneficial, and reduced barriers to care). Mean maternal depressive [Edinburgh Postnatal Depression Scale: 14.6 (SD 4.2) vs. 11.8 (SD 4.2), paired t, p = 0.005] and post-traumatic stress [Posttraumatic Stress Disorder Checklist for DSM-5: 35.5 (SD 19.0) vs. 27.1 (SD 16.7)], paired t, p = 0.01] symptoms were significantly lower post vs. pre-group. No differences were observed on mean measures of anxiety, emotion regulation or parenting stress.ConclusionsRecruitment and retention met a priori feasibility criteria. There were significant pre- to post-group reductions in maternal depressive and post-traumatic symptoms, supporting proceeding to larger-scale implementation and evaluation of the intervention, with adaptation of dyadic exercises.
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