Childhood maltreatment (CM) is associated with long-term physical and mental health impairments. One central question is, how such adversities “get under the skin”. Epigenetic processes such as DNA methylation offer a potential mechanism by which CM may impact the regulation of physiological systems endocrine, immune, metabolic and cardiovascular system and increase the risk of disease. While different types of CM have repeatedly been associated with differential risk profiles for psychopathology and associated neurobiological dysregulations, potential epigenetic signatures of these changes are less well understood.
In 2016, Cecil and colleagues provided evidence that different types of CM are linked to distinct, but also share common epigenetic signatures (cf. “Epigenetic signatures of childhood abuse and neglect: Implications for psychiatric vulnerability”, http://dx.doi.org/10.1016/j.jpsychires.2016.09.010). For example, while several CM types were associated with DNAm of genes related to neurotransmitter biosynthesis, physical abuse was distinctively linked to DNAm of genes related to the regulation of cardiovascular processes, wound healing, and the fear response. To date, it is unclear whether these associations are generalizable.
In a preregistered report, we aimed to replicate these findings in an independent high-risk sample of formerly out-of-home-placed young adults in Switzerland (N = 116), from which 78% reported at least moderate to severe experiences in at least one of the five CM types assessed (i.e., emotional neglect, physical neglect, emotional abuse, physical abuse, sexual abuse). DNA was extracted from whole blood and DNA methyltion was assayed using the Illumina Infinium MethylationEPIC BeadChip Microarray.
With the ENIGMA pipeline, we failed to replicate the findings of the original study. When using a pipeline that matched the original more closely, we could replicate that methylation of cg07032930 was linked to emotional neglect, but in the reverse direction as the original report. Even when we did not apply FDR correction, the replication rates were only modest. These findings highlight the importance and challenges of replication attempts in the field of behavioral epigenetics and call for further work to clarify the robustness and specificity of DNA methylation patterns linked to distinct types of CM.
The preprint can be retrieved here: https://osf.io/preprints/psyarxiv/9j2v7_v1 – if you have feedback or comments, don’t hesitate to reach out!