Childhood maltreatment exert powerful and lasting ill effects throughout life. It increases the risk of almost all mental disorders and contributes to treatment resistance and chronicity.
How does such early experience get engraved and later unfold in us so profoundly? Would epigenetics help us identify any markers of this process?
Epigenetics involves modifications to the genetic material without changing the DNA sequence and such changes influence the ways genes function.Most studied example is DNA methylation. Effect of methylation depend on location of the gene and the developmental stage at which it occurs.Methylation usually result in reduced gene expression. Animal studies (rats) show that reduced maternal nurturing during the first week of life is associated with increased methylation of a neuron-specific promoter of the glucocorticoid receptor gene.This result in reduction in glucocorticoid receptor number and a higher hormonal response to stress throughout their life. Human brain studies ( of suicide victims) also show similar changes among those who had experienced maltreatment during childhood.
Nader Perroud, Alexandre Dayer, Camille Piguet, Audrey Nallet, Sophie Favre, Alain Malafosse and Jean-Michel Aubry from University of Geneva examined whether peripheral blood will show any evidence of such epigenetic traces of childhood maltreatment. They studied methylation patterns in the promoter region of the human glucocorticoid receptor gene (NR3C1) in blood samples from adult patients with bipolar disorder who had significant abusive experiences in childhood. 92 adult bipolar patients (diagnosis by SCID-1) were studied.Childhood trauma was assessed using Childhood Trauma Questionnaire (CTQ). 48% reported emotional abuse and 30% reported sexual abuse. 56% had experienced emotional neglect.One third suffered from physical abuse. Quarter of patients did not report any such events, whereas 7% had experienced a combination of five different types of abuse. DNA samples were extracted from peripheral blood leucocytes .
Higher number of maltreatment were associated with higher percentage of NR3C1 methylation. Percentage of NR3C1 methylation was significantly associated with the severity of each type of maltreatment. Emotional abuse was seen to be most significantly associated with methylation.Percentage of NR3C1 methylation was also significantly associated with a history of alcohol use disorder.
The functional consequences of these specific epigenetic modifications are not clearly known. Large-scale methylation changes in numerous genomic regions are reported ie this particular methylation may not be unique. Over all methylation rate was low i.e. 7% methylation was seen in those who reported no childhood abuse also. Methylation reached 15% in those who reported 4 or more types of abuse.
Mapping all the large-scale epigenetic changes in patients exposed to childhood maltreatment and assessing how these correlate with changes in neural circuit structure and function would be key to advance our knowledge in this area.
Conclusion: Early-life adversity has a long-lasting effect on NR3C1 methylation, an effect that can be measured in the peripheral blood.
In the accompanying editorial Rudolf Uher and Ian C. G. Weaver highlight that the effect size reported in this study is extraordinarily large for a relationship between a molecular measure and reported historical exposure and that it could effectively become a blood test for abuse in childhood. It will be useful to know whether individuals with such changes are at different risk for suicide/ poor response to treatment .
Summary of the article:
Perroud N, Dayer A, Piguet C, Nallet A, Favre S, Malafosse A, Aubry JM. Br J Psychiatry. 2014 Jan;204:30-5.