Childhood maltreatment and trauma can do more than scar
psychological memory—they may leave enduring molecular signatures in our
cells, altering how genes are switched on or off. The study of epigenetics,
helps us to explain how our environment and life experiences can shape biology
beyond DNA code.
In the context of PTSD and trauma in general, there is
mounting evidence that some stress-response genes, such as NR3C1, FKBP5, and
BDNF, experience epigenetic modifications, such as alterations in chromatin
structure or DNA methylation, that may influence an individual's resilience or
susceptibility. By altering the hypothalamic-pituitary-adrenal (HPA) axis'
sensitivity, these modifications can affect how strongly a person reacts to
stress. However, research on animals supports these findings, showing that stress
and fear can cause stable epigenetic changes in brain regions such as the
amygdala and hippocampus, resulting in long-lasting changes in the connections
and communication between neurons that impact fear-related memory and emotional
reactions. Importantly, there is hope for therapeutic approaches because some
of these alterations can be reversed by therapies that target DNA methylation
or histone acetylation. The ability of the germline to transmit these
stress-induced epigenetic alterations across generations points to a mechanism
for the intergenerational or transgenerational transfer of trauma effects.
Recently a study on humans revealed that men with high
levels of childhood trauma had sperm epigenetic changes. Changes in small
noncoding RNAs, including decreased miR-34c-5p, which is important for
embryonic development, and DNA methylation modifications at particular genomic
locations, especially close to CRTC1, WFIKKN1, and GBX2, were among them. These
areas have strong connections to neurodevelopment and synaptic transmission,
suggesting that the molecular effects of early-life adversity may be passed
down to the following generation and endure into adulthood.
However, there is still much disagreement over the existence
of actual transgenerational epigenetic inheritance in humans. warns that most
epigenetic marks are erased before new developmental programs are created in
mammalian germlines due to two waves of epigenetic reprogramming that occur
during primordial germ cell development and again after conception. It is
biologically difficult for environmental-induced epigenetic modifications to be
accurately passed down through several generations as a result of this process.
He goes on to say that rather than being the result of true epigenetic
inheritance independent of DNA sequence, many reported familial epigenetic
patterns may be the result of common genetics, a shared environment, or
secondary effects of DNA mutations.
References:
1. https://www.nature.com/articles/s41380-024-02872-3#Abs1
2. https://www.nature.com/articles/s41467-018-05445-5
3. https://www.sciencedirect.com/science/article/abs/pii/S000632231500281
4. https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00361/full
.png)