This 2018 German human study found:
“DNA methylation in a biologically relevant region of NR3C1-1F [the glucocorticoid receptor gene] moderates the specific direction of HPA-axis dysregulation (hypo- vs. hyperreactivity) in adults exposed to moderate-severe CT [childhood trauma].
In contrast, unexposed and mildly-moderately exposed individuals displayed moderately sized cortisol stress responses irrespective of NR3C1-1F DNA methylation. Contrary to some prior work, however, our data provides no evidence for a direct association of CT and NR3C1-1F DNA methylation status.”
1. Limited subject histories
A. Why weren’t the subjects asked for historical information about their parents, grandparents, and great-grandparents?
The researchers had no problem using animal studies to guide the study design, EXCEPT for animal studies of the etiologic bases of intergenerational and transgenerational transmission of biological and behavioral phenotypes. Just the approximate places and dates of three generations of the German subjects’ ancestors’ births, childhoods, adolescences, and early adulthoods may have provided relevant trauma indicators.
B. Why are studies still using the extremely constrained Childhood Trauma Questionnaire? Only one CTQ aspect was acknowledged as a study design limitation:
“Our findings rely on retrospective self-report measures of CT, which could be subject to bias.”
But bias was among the lesser limiting factors of the CTQ.
The study correlated epigenetic changes with what the subjects selectively remembered, beginning when their brains developed sufficient cognitive functionalities to put together the types of memories that could provide CTQ answers – around age four. The basic problem prohibiting the CTQ from discovering likely most of the subjects’ historical traumatic experiences that caused epigenetic changes is that these experiences predated the CTQ’s developmental starting point:
- A human’s conception through prenatal period is when both the largest and the largest number of epigenetic changes occur, and is when our susceptibility and sensitivity to our environment is greatest;
- Birth through infancy is the second-largest; and
- Early childhood through the age of three is the third largest.
CTQ self-reports were – at best – evidence of experiences after age three, distinct from the experience-dependent epigenetic changes since conception. If links existed between the subjects’ early-life DNA methylation and later-life conditions, they weren’t necessarily evidenced by CTQ answers about later life that can’t self-report relevant early-life experiences that may have caused DNA methylation.
2. Limited subject selection
The researchers narrowed down the initial 622 potential subjects to the eventual 200 subjects aged 18 to 30. An exclusion criteria that was justified as eliminating confounders led to this limitation statement:
“Our results might be based on a generally more resilient sample as we had explicitly excluded individuals with current or past psychopathology.”
Was it okay for the researchers to assert:
“Exposure to environmental adversity such as childhood trauma (CT) affects over 10% of the Western population and ranges among the best predictors for psychopathology later in life.”
but not develop evidence for the statement by letting people who may have been already affected by age 30 and received treatment participate in the study? Was the study design so fragile that it couldn’t adjust to the very people who may be helped by the research findings?
3. Limited consequential measurements
The current study design was very conformant to previous studies’ protocols. The researchers chose cortisol and specific DNA methylation measurements.
A. Here’s what Sex-specific impacts of childhood trauma had to say about cortisol:
“Findings are dependent upon variance in extenuating factors, including but not limited to, different measurements of:
- early adversity,
- age of onset,
- basal cortisol levels, as well as
- trauma forms and subtypes, and
- presence and severity of psychopathology symptomology.”
The researchers knew or should have known all of the above since this quotation came from a review.
B. What other consequential evidence for prenatal, infancy, and early childhood experience-dependent epigenetic changes can be measured? One overlooked area is including human emotions as evidence.
There are many animal studies from which to draw inferences about human emotions. There are many animal models of creating measurable behavioral and biological phenotypes of human emotion correlates, with many methods, including manipulating environmental variables during prenatal, infancy, and early childhood periods.
Studies that take detailed histories may arrive at current emotional evidence for human subjects’ earliest experience-dependent changes. It’s not too big a leap to correlate specific historical environments and events, stress measurements, and lasting human emotions expressed as “I’m all alone” and “No one can help me” to better understand causes and effects.
CTQ answers aren’t sufficiently detailed histories.
4. Limited effective treatments and therapies
The current study only addressed this area in the final sentence:
“Given their potential reversibility, uncovering epigenetic contributions to differential trajectories following childhood adversity may serve the long-term goal of delivering personalized prevention strategies.”
Researchers: if your paradigms demonstrate these characteristics, why are you spending your working life in efforts that can’t make a difference? Isn’t your working life more valuable than that? What else could you investigate that could make a difference in your field?
I hope that researchers will value their professions enough to make a difference with their expertise. And that sponsors won’t thwart researchers’ desires for difference-making science by putting them into endless funding queues.
http://www.psyneuen-journal.com/article/S0306-4530(17)31355-0/pdf “Glucocorticoid receptor gene methylation moderates the association of childhood trauma and cortisol stress reactivity” (not freely available)