Threat-based Adverse Childhood Experiences and FKBP5 Methylation Patterns in Postpartum Women and their Newborn Infants

• In Event: 2-073 - Early Adversity, Biology, and Behavior: Examining Biological Consequences and Contingencies of Early Life Stress

Integrative Statement

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 (e.g., Yehuda et al., 2016), 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 standardized self-report questionnaires including a comprehensive assessment of adversity and trauma, as well as DSM-5 based posttraumatic stress disorder (PTSD) symptoms. FKBP5 rs1360780 genotype and intron 7 methylation were derived from saliva collected from postpartum mothers and newborn infants within 24 hours of delivery. Aims were to examine associations between maternal threat- and deprivation-based adversity, maternal PTSD, and maternal and infant FKBP5 methylation. Threat- and deprivation-based adversity was examined using subscales from the Childhood Trauma Questionnaire (CTQ). In analyses, FKBP5 methylation reflected a principal components analysis of methylation data from four sites. PTSD qualifying trauma exposure and symptoms were assessed with the Structured Trauma-Related Experiences and Symptoms Screener.

RESULTS. Hispanic/Latino women represented the majority of the sample (72.8%), with 88.6% receiving public insurance and 91.2% reporting an annual household income < $20,000. Rates of adversity/trauma were high, with 97.4% reporting childhood exposure and 77.2% reporting adulthood exposure. Probable PTSD was identified in 28.9% of pregnant women. For maternal risk allele carriers (CT or TT genotypes), FKBP5 methylation was negatively correlated with childhood threat-based adversity, r = -.26, p = .035, but not deprivation. For infants homozygous for the non-risk allele (CC), infant FKBP5 methylation was positively correlated with maternal childhood threat-based adversity, r = .39, p = .033, but not deprivation. No associations were found between maternal or infant methylation and measures of adulthood adversity/trauma. For maternal risk allele carriers, but not non-risk allele carriers, FKBP5 methylation was negatively correlated with PTSD symptom severity, r = -.42, p < .001. For infant non-risk allele carriers only, FKBP5 methylation was positively correlated with maternal PTSD severity, r = .41, p = .024. Similarly, for infant non-risk allele carriers, there were significant positive correlations between infant FKBP5 methylation and other measures of maternal psychopathology and functioning during pregnancy.

DISCUSSION. Consistent with prior work in samples of adult women (e.g., Klengel et al., 2013), we found allele-specific associations between maternal adverse childhood experiences and FKBP5 demethylation in a sample of pregnant women. Our findings specified this effect to threat-based, and not deprivation-based, childhood adversity. Indeed, a growing body of work suggests differential mechanisms by adversity type (McLaughlin, Sheridan, & Lambert, 2014). Also aligned with prior work was an allele-specific association between maternal PTSD and demethylation. In contrast, positive associations between maternal threat-based childhood adversity, PTSD severity, other aspects of maternal impairment, and infant FKBP5 methylation, for non-risk allele carriers only, suggest a unique, intergenerational effect of maternal trauma and associated impairment on newborn infant epigenetic patterns. Ongoing prospective research on this sample may shed light on whether this developmentally-specific effect reflects a compensatory or risk mechanism.

Authors

• Damion Grasso, University of Connecticut School of Medicine
  Presenting Author

• Jonathan Covault, University of Connecticut School of Medicine
  Non-Presenting Author

• Amy Johnson, Hartford Hospital
  Non-Presenting Author

• Stacy Drury, Tulane University School of Medicine
  Non-Presenting Author

• Garry Lapidus, Connecticut Children’s Medical Center
  Non-Presenting Author

• Victoria Scranton, University of Connecticut School of Medicine
  Non-Presenting Author

• Meghan Clough, Connecticut Children’s Medical Center
  Non-Presenting Author