It’s transgenerational epigenetic inheritance week!

Transgenerational epigenetic inheritance is a subject whose time has come. This week I sequentially curated two 2017 reviews and two 2016 studies of the subject, and ended with a meta-analysis of human preventive treatments:


It’s the opposite of advancing science for those in the funding chain to give lip service to the subject, and then create an atmosphere where proposals to extend experiments to subsequent generations to study possible transgenerational epigenetic effects are neither encouraged nor funded.

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Does living near a forest keep your amygdala healthier?

A thought-provoking post from A Paper a Day Keeps the Scientist Okay entitled “Living Near a Forest Keeps Your Amygdala Healthier” referenced a 2017 German human study which found:

“..a relationship between place of residence and brain health: those city dwellers living close to a forest were more likely to show indications of a physiologically healthy amygdala structure and were therefore presumably better able to cope with stress.”

The researchers accomplished the imperative of meeting the study’s stated objective:

“We set out to identify and characterize the geographical elements of a city that are associated with these brain structures following a suggestion by Kennedy and Adolph that studies should begin to derive recommendations for urban planning and architecture.

The results of our study may suggest that forests in and around the cities are a valuable resource that should be promoted. However future longitudinal studies are needed to investigate the causal directionality of the effect in order to disentangle whether more forest in ones habitat facilitates brain structural integrity or potentially those people with better brain structural integrity choose to live closer to forests. Moreover we need to investigate whether living close to the forest is associated with an absence of risk factors such as noise, air pollution or stress and thereby has beneficial effects or whether the forest itself constitutes a salutary factor that promotes well-being.”


A major limitation of the study’s methodology that wasn’t noted by the researchers was the intentional non-use of an available data source. Referring to Do we need to study the brain to understand the mind? posted earlier this week:

“Self-report is still the gold standard for assessing emotional experience and the contents of thought. Isn’t it easier just to ask?”

The researchers put the forest before the trees, and designed a study that didn’t ask the subjects important questions such as why they lived where they lived. The researchers inferred sketchy fMRI-geography associations because they didn’t solicit relevant primary information via individual self-reports.


I imagined myself as one of the study’s subjects. I don’t live in Berlin, and I’m not part of the selected cohort, but I otherwise generally meet the study’s subject parameters.

Something in my past causes me to actively select housing that isn’t in a noisy environment. If I were asked why I lived where I lived, my answer would have included:

  • A deciding factor in why I sold my second house was the traffic noise in wintertime;
  • A deciding factor in why I bought my fourth house was its location in the center of the housing development, away from street noise; and
  • A deciding factor in why I live where I now live is the house’s orientation away from both direct and reflective traffic noise sources.

Processing my hypothetical fMRI data with my self-reported historical housing choices may or may not have found:

“Geographical features in the proximal participants’ habitat are associated with brain integrity.”

Using the better-quality information of self-reports, though, it’s unlikely that an association this study would have found to be significant – the chance fact that I live within one kilometer of a forest – would have been deemed significant.

https://www.nature.com/articles/s41598-017-12046-7 “In search of features that constitute an “enriched environment” in humans: Associations between geographical properties and brain structure”

Review of The Honest Truth About Dishonesty: How We Lie to Everyone–Especially Ourselves

Here’s an Amazon book review I wrote six years ago when I regularly read 2-3 books a week while on the train to and from work. The book served as an example of how behavioral researchers couldn’t reach their stated goals by using standard scientific methods.

Review of The Honest Truth About Dishonesty: How We Lie to Everyone–Especially Ourselves by Dan Ariely

Everybody would benefit from reading this collection of experiments with human behavior.

It would be fair to compare the book’s accomplishments with its declared goals. The author stated the book’s primary goal early on when he wrote:

“We need to first figure out what forces really cause people to cheat and then apply this improved understanding to curb dishonesty. That’s exactly what this book is about.

Once we more clearly understand the forces that really drive us, we discover that we are not helpless in the face of our human follies (dishonesty included), that we can restructure our environment, and that by doing so we can achieve better behaviors and outcomes.”

I appreciated the author’s research that described and delineated what his experiments chose to observe. For example, in one series of experiments, people lied in order to get tokens that a few seconds later were exchanged into money. These subjects cheated to an extent that was almost twice the amount of people who lied in order to directly get money.

Another series of experiments showed that when people were tired or stressed, they were more likely to cheat. The amount that mentally exhausted subjects cheated was almost three times the amount of non-stressed subjects.

There was also a series of experiments that tested the “what the hell” effect. The researchers found that the amount of cheating was not linear. A point was frequently reached where the subjects apparently decided to abandon a little bit of cheating, and started to cheat at every opportunity.

The author proposed that a “fake it until you make it” approach doesn’t ultimately lead to honest behavior. He suggested that it would probably start a chain of events that proceeded through the “what the hell” context, where a little bit of cheating became a lot, and ended up with suffering when the truth was eventually revealed.


What these experiments examined wasn’t the origins of dishonest behavior, but rather the middle and ending parts of dishonest behaviors. As such, I didn’t see how the book’s primary goal could be achieved.

Without exploring the precedents to dishonest behavior, we’re also left with a patchwork approach to achieving the secondary goal of changing outcomes by influencing the salient aspects of behavior.

Understanding that I’m not an expert or a researcher, let me offer an approach that could be more conducive to achieving the primary and secondary goals of the book. The necessary but unexplored research area would be along the lines of “What do I feel just before I act dishonestly?”

The subjects’ probable answers to this unasked question would indicate that the person’s unfulfilled needs were in play. These needs are for the most part unconscious, and are the sources of automatic behavior that seeks to fulfill these needs. The outward manifestations of this automatic behavior will lead the subjects to symbolic fulfillment of their old needs.

The subjects in the experiments may not be able to make the connection between their behaviors of say, cheating on a pledge to quit smoking, and their driving forces. This is probably because the subjects weren’t consciously aware of the feelings they had just before they acted.

The researchers may be able to bridge this gap with information obtained from measurements done by fMRIs and other instruments. They can integrate these measurements with the subjects’ reports of their feelings.

To meet the goals of the book, it’s important that the researchers uncover the subjects’ underlying feelings. This is necessary because feelings are usually closer to the causes of a person’s behavior.

The subjects’ behaviors were symptoms of their problems, not the problems themselves. The researchers would be better served to study the entire situation as best they can.


All of us anticipate while we read a book that there will be prescriptions and answers to the circumstances and troubles presented. But because The (Honest) Truth About Dishonesty didn’t identify “what forces really cause people to cheat,” the primary goal, to “clearly understand the forces that really drive us” wasn’t attained.

Realization of the secondary goal is undecided. The author presented several examples of how environments affect people’s dishonesty, such as conflicts of interests. He showed how people’s rationalizations allow them to permit a level of dishonesty that doesn’t harm their ideas about their own morality.

But how can effective and enduring solutions arise “so we can achieve better behaviors and outcomes” when the roots of the behaviors aren’t examined?

Do we need to study the brain to understand the mind?

A coauthor of the studies referenced in:

offered an opinion piece in A Paper a Day Keeps the Scientist Okay entitled “Do We Need To Study The Brain To Understand The Mind?”:

“The emerging consensus appears to be that implementation is important. Interestingly, the inverse question is also being asked by neurobiologists—do we need consider the mind to understand the brain?—and answered largely and increasingly in the affirmative.

Is pain different from negative emotions such as sadness and anger, or are they variants on a common theme? Pain appears to be distinct from negative emotion, but commonalities suggest ways in which they may share underlying processes such as heightened attention.

One of the biggest pitfalls is the temptation to observe brain activity and make inferences about the psychological state—for example, to infer:

  • Episodic memory retrieval from hippocampal activity,
  • Fear from amygdala activity, or
  • Visual processing from activity in the ‘visual cortex.’

These inferences ignore the scope of processes which may activate each of these areas and involve a fallacy in reasoning: “if memory then hippocampus” is not the same thing as “if hippocampus then memory.”

The fact that few brain areas, including the ‘visual cortex,’ are dedicated to one process means that self-report is still the gold standard for assessing emotional experience and the contents of thought. This is a serious challenge for those who would like, for example, to assess your brand preferences or your political affiliation from a brain scan. (And isn’t it easier just to ask?)”

Epigenetic effects of early life stress exposure

This 2017 Netherlands review subject was the lasting epigenetic effects of early-life stress:

“Exposure to stress during critical periods in development can have severe long-term consequences.

One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis.

Early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood.

ELS is able to “imprint” or “program” an organism’s neuroendocrine, neural and behavioral responses to stress. Research focuses along two complementary lines:

  1. ELS during critical stages in brain maturation may disrupt specific developmental processes (by altered neurotransmitter exposure, gene transcription, or neuronal differentiation), leading to aberrant neural circuit function throughout life.
  2. ELS may induce modifications of the epigenome which lastingly affect brain function.

These epigenetic modifications are inducible, stable, and yet reversible, constituting an important emerging mechanism by which transient environmental stimuli can induce persistent changes in gene expression and ultimately behavior.”


In early life, the lower brain and limbic system brain structures are more developed and dominant, whereas the cerebrum is less developed (use the above rodent graphic as a rough guide). Stress and pain generally have a greater impact on a fetus than an infant, and on an infant than an adult.

The reviewers cited 50+ studies from years 2000-2015 in the “Early Life Stress Effects in a “Matching” Stressful Adult Environment” section to argue for the match/mismatch theory:

“Encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context.

Initial evidence for HPA-axis hypo-reactivity is observed for early social deprivation, potentially reflecting the abnormal HPA-axis function as observed in post-traumatic stress disorder.

Interestingly, experiencing additional (chronic) stress in adulthood seems to normalize these alterations in HPA-axis function, supporting the match/mismatch theory.”

Evidence for this theory was contrasted with the allostatic load theory presented in, for example, How one person’s paradigms regarding stress and epigenetics impedes relevant research.


The review mainly cited evidence from rodent studies that mismatched reactions in adulthood may be consequences of early-life events. These events:

“Imprint or program an organism’s neuroendocrine, neural and behavioral responses..leading to aberrant neural circuit function throughout life..which lastingly affect brain function.”

Taking this research to a personal level:

  • Have you had feelings that you were unsafe, although your environment was objectively safe?
  • Have you felt uneasy when people are nice to you?
  • Have you felt anxious when someone pays attention to you, even after you’ve acted to gain their attention?

Mismatched human feelings are one form of mismatched reactions. These may be consequences of early-life experiences, and indicators of personal truths.

If researchers can let go of their biases and Advance science by including emotion in research, they may find that human subjects’ feelings produce better evidence for what actually happened during the subjects’ early lives than do standard scientific methods of:

Incorporating feeling evidence may bring researchers and each individual closer to discovering the major insults that knocked their development processes out of normally robust pathways and/or induced “persistent changes in gene expression and ultimately behavior.”

https://www.frontiersin.org/articles/10.3389/fncel.2017.00087/full “Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure”


I came across this review as a result of it being cited in http://www.sciencedirect.com/science/article/pii/S1084952117302884 “Long-term effects of early environment on the brain: Lesson from rodent models” (not freely available)

Epigenetic similarities between placental and cancer cells

This 2017 New Zealand review compared and contrasted epigenetic evidence from placental and cancer research:

“Placental and cancer cells are globally hypomethylated and share an epigenetic phenomenon that is not well understood – they fail to silence repetitive DNA sequences (retrotransposons) that are silenced (methylated) in healthy somatic cells.

In the placenta, hypomethylation of retrotransposons has facilitated the evolution of new genes essential for placental function. In cancer, hypomethylation is thought to contribute to activation of oncogenes, genomic instability, and retrotransposon unsilencing; the latter, we postulate, is possibly the most important consequence.

Activation of placental retrotransposon-derived genes in cancer underpins our hypothesis that hypomethylation of these genes drives cancer cell invasion.”

http://onlinelibrary.wiley.com/doi/10.1002/bies.201700091/abstract “The Genes of Life and Death: A Potential Role for Placental-Specific Genes in Cancer” (not freely available)


The review cited a 2014 study from the same research group that covered some of the same points and is freely available:

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0095840 “Retrotransposon Hypomethylation in Melanoma and Expression of a Placenta-Specific Gene”

Epigenetic effects of THC differ between female adolescents and adults

This 2017 Italian rodent study found:

“THC [delta9-tetrahydrocannabinol, the psychoactive compound of cannabis] exposure affects histone modifications in the brain of female rats in a region- and age-specific manner. Specifically, THC acts on different targets depending on the considered brain area and, remarkably, the adolescent brain is generally more sensitive to THC than the adult brain.

Adolescent exposure to THC, or to synthetic cannabinoids, induced sex-dependent brain and behavioral alterations at adulthood. In female rats, the phenotype was more complex, as both depressive-like and psychotic-like signs were present..the development of the depressive/psychotic-like phenotype is restricted to adolescent THC exposure..not only the behavioral phenotype developed after adolescent, and not adult, exposure, but also changes in both histone modifications and gene expression were more widespread and intense after adolescent treatment, further confirming a specific adolescent susceptibility.

The primary effect in the adolescent brain was represented by changes leading to transcriptional repression, whereas the one observed after adult treatment led to transcriptional activation. Moreover, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the THC-induced repressive effect, except in the amygdala.”

The authors’ interpretation of the brain area results was:

“..the amygdala is more responsive in adult than adolescent animals..Since it has been established that the amygdala is activated during exposure to aversive stimuli, functioning as a “behavioral brake”, the different response between adult and adolescent animals could represent the biological bases of the adolescent propensity for risk-taking and novelty-seeking behaviors..also in adolescent humans, neuroimaging studies have shown a weaker involvement of the amygdala, and a greater contribution of the NAc [nucleus accumbens], in response to negative and positive stimuli compared to adults.”

http://www.mdpi.com/1422-0067/18/10/2094 “Chronic Δ9-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain”