Mediated Effects of Trauma and Epigenetic Outcomes in Offspring

Background and Purpose:

Traumatic experiences can generate devastating outcomes for individuals and societies. Exposure to trauma causes the addition of methyl groups to DNA, reducing gene activity in parts of the brain that mediate the human stress system and damaging the stress response. Studies show DNA methylation differences are associated with psychosocial stress, childhood trauma, PTSD and clinical severity; these differences may mediate increased vulnerability to emotional and mental health disorders in those who have experienced trauma. Moreover, growing evidence suggests these effects may be passed to subsequent generations. 

Methods:

Data for this study are from a subset of the CANDLE longitudinal research study in Memphis Tennessee, which is designed to examine risks to early child development. The sample included 216 mothers (55.0% African-American, 49.5% married, 38% with high school diploma or GED; age 18-39 years, M = 27) with reported household annual income of $25,000-35,000. Validated standardized measures assessed mothers’ trauma experiences, mental health symptoms, and social support. Umbilical cord blood was processed with the 27K methylation array to measure DNA methylation.

Mother’s variables were investigated for the structure of relationships within the initial generation using the Process software add on to SPSS.  DNA methylation was analyzed with the clinical variables above, using mixed effects regressions to investigate relationships across the two generations. We controlled for known DNA methylation covariates such as child sex, child ethnicity, chip and batch effects, as well as the Bonferroni and False Discovery Rate for multiple comparisons.

Results:

Results identified a complete mediation relationship where complexity of maternal childhood trauma (CCA) predicted cumulative experienced fear and helplessness (CFH) (B = 1.93, p < .001), and CFH predicted clinical severity of mental health symptoms (GSI) (B = 1.01, p = .007), accounting for 9.55% of variance in GSI.  Findings also identified a statistically significant relationship between the type of trauma (interpersonal or non-interpersonal) where interpersonal trauma predicted CFH (B = .66, p = .047), and CFH predicted GSI (B = 1.21, p < .001), and it was a complete mediation accounting for 9.84% of variance in GSI.

Intergenerational results identified clinical severity of mental health in the mother was associated with DNA methylation changes on CpG 08614528 of gene CRELD1 in infant cord blood when controlling for mother’s perceived social support (T(202) = 25.286, p = 1.19E-06).  Specifically, increased clinical severity in the mother predicted increased DNA methylation on CRELD1 at the identified CpG site.

Conclusions and Implications: These preliminary results demonstrate potential for trauma experiences to indirectly influence gene expression in subsequent generations.  The identified gene, CRELD1, has been recognized in multiple studies to be associated with heart disease. Identifying the mechanisms of how these experiences can translate to the next generation can inform assessment and provide new avenues for intervention and prevention across generations.  Research and practice implications will be discussed.