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.

Firstly, 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..

Secondly, 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 and other brain structures are less developed (use the above graphic as a rough guide). Stress and pain generally have a greater impact on the fetus, then the infant, and then the 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 cites 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?

I assert that mismatched human feelings are one form of mismatched reactions. As such, they may be interpreted as 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 this evidence may bring researchers closer to backwardly predicting the major insults to an individual 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 discovered 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)

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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”

Remembering Dr. Arthur Janov

Here are some of the sites, other than the NYT, WP, and AP obituaries and their repetitions, where people remember Dr. Janov:

https://www.facebook.com/pg/DrArthurJanov/

https://www.facebook.com/photo.php?fbid=10155221889014118&set=a.65601639117.72499.674399117&type=3

https://www.thetimes.co.uk/edition/register/arthur-janov-obituary-n7zgws597

https://pessimisticshrink.blogspot.com/2017/10/janov.html

http://forward.com/culture/384164/arthur-janov-the-jewish-creator-of-primal-scream-therapy/

http://tributes.com/obituary/guestbook/105268227?pane=candle#guestbook_area


Here’s one that I had a reaction to. My comment is posted below, in case that site’s moderator deletes it:

https://www.smithsonianmag.com/smart-news/founder-primal-scream-therapy-has-died-what-exactly-180965126/

Poor job reporting. According to the NYT..according to Vice..according to the AP..

The last paragraph is especially horrible for misguided attempts to place Dr. Janov’s life in historical context: the unattributed “experts widely regard;” the “pseudoscience” assertion with no proof; the snide implication that his life only had value because John Lennon produced an album.

Why couldn’t the writer be bothered to gather first-hand information such as taking 10-15 minutes to look at the Primal Center’s website? Or look at Dr. Janov’s May 2016 book Beyond Belief, which was outstanding? Or Dr. Janov’s blog that he kept up throughout the years until 2017?

Does this hit piece on the occasion of a man’s death comply with Smithsonian Magazine’s journalism standards?

Dr. Arthur Janov passed away

Dr. Janov passed away October 1, 2017 at the age of 93.

I remember him as always helping others.

I’ll add more as time goes by. Today, I’ll repeat the last of his 10 comments he made on this blog:

Beyond Belief: What we do instead of getting well

“I do thank you over and over because who quote the essence of my work which pleases me a lot. art janov”


Dr. Janov’s comment on Beyond Belief: Symptoms of hopelessness was:

“i thank you for your help art”

and I replied:

“Thank you for giving me a lens to more clearly see!”


Dr. Janov’s comment on Beyond Belief: Why do we accept being propagandized? was:

“good good art janov”

but my post wasn’t really good. I worked on it, and replied the next day:

“Thanks for helping me improve this post!”


I remember and miss Dr. Janov when I read research and curate studies from what I interpret would be his viewpoint. For example, were he still alive and well, I feel that he would have provided favorable feedback on my Epigenetic effects of early life stress exposure post.

He often noted that aspects of Primal Therapy were proven by subsequent research – especially topics in epigenetics, where research didn’t really start in earnest until the 1980s.

http://cigognenews.blogspot.com/2017/10/the-passing-of-great-man.html

A study of perinatal malnutrition where the paradigm excluded epigenetic inheritance

This 2017 New York/Swedish rodent study subject was the epigenetic effects on the F1 generation of maternal low protein diet during pregnancy and lactation:

“Male, but not female, offspring of LPD [low protein diet] mothers consistently displayed anxiety- and depression-like behaviors under acute stress.

Our proposed pathway connecting early malnutrition, sex-independent regulatory changes in Egr1 [an Early growth response gene], and sex-specific epigenetic reprogramming of its effector gene, Npy1r [neuropeptide Y receptor Y1 gene], represents the first molecular evidence of how early life risk factors may generate sex-specific epigenetic effects relevant for mental disorders.”


The study was purposely incomplete regarding epigenetic effects that may be transmitted from the F1 generation to a F2 generation. Similar to How one person’s paradigms regarding stress and epigenetics impedes relevant research, the paradigm continued by one of this study’s coauthors restricted inquiry into epigenetic inheritance.

How can the other coauthors respond when a controller of funding publishes the paper referenced in What is epigenetic inheritance? and otherwise makes his narrow views regarding epigenetic inheritance well-known? If the controller’s restricted views won’t allow the funding scope to extend to study a F2 generation, the experiments end, and our understanding of epigenetic inheritance isn’t advanced.

This purposely incomplete study showed that the coauthor only gave lip service to advancing science when he made statements like:

“Further work is needed to understand whether and to what extent true epigenetic inheritance of stress vulnerability adds to the well-established and powerful influence of genetics and environmental exposures.”

https://www.nature.com/articles/s41598-017-10803-2 “Perinatal Malnutrition Leads to Sexually Dimorphic Behavioral Responses with Associated Epigenetic Changes in the Mouse Brain”

Prisoners of our childhoods

Same old shit – another failed relationship.

Coincident with the start of our relationship, I was struck by a phrase by Dr. Janov, posted in Beyond Belief: What we do instead of getting well:

“It doesn’t matter about the facts we know..if we cannot maintain a relationship with someone else.”

I kept that thought in the forefront.

Both of us are prisoners of our childhoods. I’ve tried to see and feel the walls and bars for what they are.

J hadn’t tried to process the reality of her childhood and life. For example, on her birthday, June 19, I asked her how she celebrated her birthdays when she was growing up. She provided a few details, then mentioned that her parents had skipped some of her birthdays. Although I had no immediate reaction, she quickly said that she had a happy childhood.

I was at fault, too, of course. I again asked a woman to marry me who hadn’t ever told me she loved me, except in jest.

I asked J to marry me around the six-month point of our relationship. I felt wonderful, in love with her that August morning after she slept with me at my house. I made an impromptu plan: in the middle of a four-mile walk, I asked her to marry me while kneeling before her as she sat on a bench outside a jewelry store. But she wouldn’t go in to choose a ring. She said she’d think about it.

A month later, after several dates, sleepovers at her house, and a four-day trip to Montreal, I again brought up marriage while we rested on her large couch in her nice sun room. The thing I felt would be wonderful brought about the end.

I tried to understand why she couldn’t accept me for the person who I intentionally showed her I am. She abstracted everything that she said. I tried to get her to identify why, after all the times we cared for each other, after all our shared experiences, she didn’t want me around anymore.

Didn’t happen. She didn’t tell me things that made sense as answers to my questions.

One thing she said without abstraction was that I was weak for showing my feelings. She told me I was clingy.

Another thing she communicated at the end shocked me. She somehow thought that I was going to dump her. I said that the thought never even crossed my mind.

I didn’t recognize it as projection at the time. Prompted by her underlying feelings, she attributed to me the actions and thoughts that only she herself had.


One thing I’ve felt after the end was that the need underlying my only stated relationship goal – to live with a woman I love who also loves me – is again ruining my life. My latest efforts towards that goal were rife with unconscious symbolic act outs of an unsatisfied need from my early life.

That unrelenting need is for a woman’s love, but it’s deviated in that somehow she’s always one who doesn’t accept me as I am, and doesn’t love me. My cell is what Dr. Janov calls the imprint that I – as an infant, boy, teenager, young man, middle-aged man, old man – retreat to after my futile attempts to change the past.

I’ve tried to put myself in J’s place. How horrible must it have been for her to be steadily intimate with a man and not feel that his touches, kisses, words, affection, expressed love? That he couldn’t really love me, and I therefore couldn’t love him? That he was actually after something else: sex, property, etc., because it was impossible that he loved me?

“Standing next to me in this lonely crowd
Is a man who swears he’s not to blame
All day long I hear him shout so loud
Crying out that he was framed
I see my light come shining
From the west unto the east
Any day now, any day now
I shall be released”