Dataset Information

Adverse childhood experiences, posttraumatic stress, and FKBP5 methylation patterns in postpartum women and their newborn infants.

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:ObjectiveAdverse childhood experiences (ACEs) are linked to worsening overall health outcomes and psychological diagnoses. Routine screening, particularly in patients with postpartum depression (PPD), would identify patients who could benefit from interventions to prevent the perpetuation of ACEs and establish a system of preventative care to mitigate the risks of adverse health outcomes associated with high ACE scores. The purpose of this study is to explore the link between ACEs and PPD to advocate for the use of the ACE questionnaire as a routine screening tool in all pregnant patients diagnosed with PPD. We hypothesize that a cohort of patients with PPD will be more likely to have high-risk ACE scores than the general female population.Study designOur IRB approved, retrospective cohort study identified all patients diagnosed with PPD at an academic medical center between January 2015 and December 2019. The subjects were identified using retrospective chart review. Subjects were recruited via telephone and asked to complete an ACE questionnaire. Questionnaires were sent via RedCap. ACE scores were calculated, categorized as 0, 1, 2, 3, or 4 or more ACEs, and compared to the prevalence in the original Kaiser-CDC ACE study female cohort using a chi-square goodness-of-fit test.ResultsThere were 132/251 surveys completed (53% response rate). In our PPD population, 19.3% had 0 ACEs, 17.0% had 1 ACE, 13.1% had 2 ACEs, 16.5% had 3 ACEs, and 34.1% had 4 or more ACEs. These percentages were significantly different from the Kaiser-CDC ACE Study percentages of 34.5, 24.5, 15.5, 10.3, and 15.2%, respectively (p < 0.001).ConclusionOur unique study showed that women with PPD are more likely to have high-risk ACE scores than the general female population. This finding has important implications in regards to counseling, intervening to prevent perpetual ACEs, and establishing important provider-patient relationships for life-long preventative care.Non-gendered language is used when possible throughout. However, the wording from studies cited in this paper was preserved.

Project description:BackgroundAdverse childhood experiences (ACEs) increase the risk of poor health outcomes later in life. Psychosocial stressors may also have intergenerational health effects by which parental ACEs are associated with mental and physical health of children. Epigenetic programming may be one mechanism linking parental ACEs to child health. This study aimed to investigate epigenome-wide associations of maternal preconception ACEs with DNA methylation patterns of children. In the Center for the Health Assessment of Mothers and Children of Salinas study, cord blood DNA methylation was measured using the Illumina HumanMethylation450 BeadChip. Preconception ACEs, which occurred during the mothers' childhoods, were collected using a standard ACE questionnaire including 10 ACE indicators. Maternal ACE exposures were defined in this study as (1) the total number of ACEs; (2) the total number of ACEs categorized as 0, 1-3, and > 4; and (3) individual ACEs. Associations of ACE exposures with differential methylated positions, regions, and CpG modules determined using weighted gene co-expression network analysis were evaluated adjusting for covariates.ResultsData on maternal ACEs and cord blood DNA methylation were available for 196 mother/newborn pairs. One differential methylated position was associated with maternal experience of emotional abuse (cg05486260/FAM135B gene; q value < 0.05). Five differential methylated regions were significantly associated with the total number of ACEs, and 36 unique differential methylated regions were associated with individual ACEs (Šidák p value < 0.05). Fifteen CpG modules were significantly correlated with the total number of ACEs or individual ACEs, of which 8 remained significant in fully adjusted models (p value < 0.05). Significant modules were enriched for pathways related to neurological and immune development and function.ConclusionsMaternal ACEs prior to conception were associated with cord blood DNA methylation of offspring at birth. Although there was limited overlap between differential methylated regions and CpGs in modules associated with ACE exposures, statistically significant regions and networks were related to genes involved in neurological and immune function. Findings may provide insights to pathways linking psychosocial stressors to health. Further research is needed to understand the relationship between changes in DNA methylation and child health.