This 2015 UK human review discussed:
Gene linkage studies for depression, as well as for other common complex disorders, have been perceived by some to be of only limited success; hence the focus on GWAS [genome-wide association studies]. However, even for simple traits, genetic variants identified by GWAS are rarely shown to account for more than 20% of the heritability.
Epigenetic changes are potentially reversible and therefore amenable to intervention, as has been seen in cancer, cardiovascular disease and neurological disorders.”
Five of the review’s references included FKBP5 (a gene that produces a protein that dampens glucocorticoid receptor sensitivity) in their titles, but it wasn’t mentioned in the review itself. A search on FKBP5 also showed human studies such as the 2014 Placental FKBP5 Genetic and Epigenetic Variation Is Associated with Infant Neurobehavioral Outcomes in the RICHS Cohort that found:
“Adverse maternal environments can lead to increased fetal exposure to maternal cortisol, which can cause infant neurobehavioral deficits. The placenta regulates fetal cortisol exposure and response, and placental DNA methylation can influence this function.
Placental FKBP5 methylation reduces expression in a genotype specific fashion, and genetic variation supersedes this effect. These genetic and epigenetic differences in expression may alter the placenta’s ability to modulate cortisol response and exposure, leading to altered neurobehavioral outcomes.”
The authors listed seven human studies conducted 2008-2015 “investigating interactions between methylation of NR3C1, depression and early adversity”:
“Newborn offspring exposed to maternal depression in utero had increased methylation at [a GR CpG site] as well as adverse neurobehavioural outcomes.
Unlike the majority of animal studies examining NR3C1 methylation, many types of potential stressors, sometimes at different developmental stages, have been used to represent early human adversity.
Substantial differences can be expected in the nature of stresses prenatally compared with postnatally, as well as their developmental consequences.”
Seven human studies over the past eight years was a very small number considering both the topic’s importance and the number of relevant animal studies during the period.
Is the topic too offensive for human studies? What makes people pretend that adverse prenatal and perinatal environments have no lasting consequences to the child?
“Many more studies will be needed before effects directly attributable to early life trauma can be separated from those relating to tissue type.
Although investigators have amassed a considerable amount of evidence for an association between differential methylation and HPA axis function in humans, a causal relationship still needs to be fully established.”
Factors that disrupt neurodevelopment may be the largest originators of epigenetic changes that are sustained throughout an individual’s entire lifespan.
Are the multitude of agendas that have resources thrown at them more important than ensuring the well-being of a human before and after they are born?
https://www.researchgate.net/publication/282048312_Early_life_trauma_depression_and_the_glucocorticoid_receptor_gene_-_an_epigenetic_perspective “Early life trauma, depression and the glucocorticoid receptor gene–an epigenetic perspective”