The future of your brain is in your gut right now

A 2020 paper by the author of Sulforaphane: Its “Coming of Age” as a Clinically Relevant Nutraceutical in the Prevention and Treatment of Chronic Disease:

“The gut and brain communicate bidirectionally via several pathways which include:

  1. Neural via the vagus nerve;
  2. Endocrine via the HPA axis;
  3. Neurotransmitters, some of which are synthesized by microbes;
  4. Immune via cytokines; and
  5. Metabolic via microbially generated short-chain fatty acids.

How does nature maintain the gut-microbiome-brain axis? Mechanisms to maintain homeostasis of intestinal epithelial cells and their underlying cells are a key consideration.

The symbiotic relationship that exists between microbiota and the human host is evident when considering nutrient requirements of each. The host provides food for microbes, which consume that food to produce metabolites necessary for health of the host.

Consider function of the human nervous system, not in isolation but in integration with the gastrointestinal ecosystem of the host, in expectation of a favorable impact on human health and behavior.”

https://www.sciencedirect.com/science/article/pii/B9780128205938000148 “Chapter 14 – The gut microbiome: its role in brain health” (not freely available)


Always more questions:

  • What did you put into your gut today?
  • What type of internal environment did it support?
  • What “favorable impact on human health and behavior” do you expect from today’s intake?
  • How will you feel?
  • Will you let evidence guide feeding your gut environment?

See Switch on your Nrf2 signaling pathway for an interview with the author.

Week 37 of Changing to a youthful phenotype with broccoli sprouts

1. Been wrong about a few things this past week:

A. I thought in Week 28 that extrapolating A rejuvenation therapy and sulforaphane results to humans would produce personal results by this week. An 8-day rat treatment period ≈ 258 human days, and 258 / 7 ≈ 37 weeks.

There are just too many unknowns to say why that didn’t happen. So I’ll patiently continue eating a clinically relevant 65.5 gram dose of microwaved broccoli sprouts twice every day.

PXL_20201015_105645362

The study’s lead researcher answered:

“Depends, it might take 37 weeks or more for some aspects of ‘youthening’ to become obvious. It might even take years for others.

Who really cares if you are growing younger every day?

For change at the epigenomic/cellular level to travel up the biological hierarchy from cells to organ systems seems to take time. But the process can be repeated indefinitely (so far as we know) so by the second rejuvenation you’re already starting at ‘young’. (That would be every eight to ten years I believe.)”

His framework is in An environmental signaling paradigm of aging.

B. I thought that adding 2% mustard seed powder to microwaved broccoli sprouts per Does sulforaphane reach the colon? would work. Maybe it would, maybe it wouldn’t, but my stomach and gut said that wasn’t for me.

C. I thought I could easily add Sprouting whole oats to my routine. I ran another trial Sprouting hulled oats using oat seeds from a different company and Degree of oat sprouting as a model.

2. Oat sprouts analysis paired studies were very informative, don’t you think? One study produced evidence over 18 germination-parameter combinations (hulled / dehulled seeds of two varieties, for 1-to-9 days, at 12-to-20°C).

Those researchers evaluated what mix of germination parameters would simultaneously maximize four parameters (β-glucan, free phenolic compounds, protease activity, and antioxidant capacity) while minimizing two (enzymes α-amylase and lipase). Then they followed with a study that characterized oat seeds sprouted under these optimal conditions.

I doubted PubMed’s “oat sprout” 20 search results for research 1977 to the present. Don’t know why they didn’t pick up both of these 2020 studies, but I’m sure that .gov obvious hindrances to obtaining relevant information like this won’t be fixed. What other search terms won’t return adequate PubMed results?

3. The blog post readers viewed this week that I made even better was Do delusions have therapeutic value? from May 2019. Sometimes I’ve done good posts describing why papers are poorly researched.

4. I’ve often changed my Week 4 recipe for an AGE-less Chicken Vegetable Soup dinner (half) then the next day for lunch. The biggest change brought about by 33 weeks of behavioral contagion is that I now care more about whether vegetables are available than whether or not they’re organic. Coincidentally, I’ve developed a Costco addiction that may require intervention.

  • 1/2 lemon
  • 4 Roma tomatoes
  • 4 large carrots
  • 6 stalks organic celery
  • 6 mushrooms
  • 6 cloves garlic
  • 6 oz. organic chicken breast fillet
  • 1 yellow squash, alternated with 1 zucchini
  • 1 cup sauvignon blanc
  • 32 oz. “unsalted” chicken broth, which still contains 24% of the sodium RDA

Pour wine into a 6-quart Instant Pot; cut and strain squeezed lemon; cut chicken into 1/4″ cubes and add; start mixture on Sauté. Wash and cut celery and stir in. Wash and cut carrots and stir in.

When pot boils around 8 minutes, add chicken broth and stir. Wash mushrooms, slicing into spoon sizes.

Wash and slice yellow squash / zucchini. Crush and peel garlic, tear but don’t slice. Turn off pot when it boils again around 15 minutes.

Wait 2-3 minutes for boiling to subside, then add yellow squash / zucchini, mushrooms, garlic, whole tomatoes. Let set for 20 minutes; stir bottom-to-top 5 and 15 minutes after turning off, and again before serving.

AGE-less Chicken Vegetable Soup is tasty enough to not need seasoning.

Week 34 of Changing to a youthful phenotype with broccoli sprouts

1. Thank you to readers of this blog who find the 650+ curations and other posts worth their time. I reread blog posts after you read them, and sometimes improve them for our mutual benefit.

One such post this week was Broccoli sprout compounds include sinapic acid derivatives. Although it was already fairly detailed, it received a half-dozen improvements.

  • Those researchers measured composition changes of 31 compounds (18 sinapic acid derivatives, 8 glucosinolates, and 5 flavonoids) identified in seed-2-4-6-day germination stages of one cultivar. They provided convertible dry weight and fresh weight measurements in mg / g.
  • It complemented the 3-day-old broccoli sprouts have the optimal yields study comparisons of six cultivated varieties’ seed-3-5-7-day germination stage weights and measurements with their origins using a milligram-per-gram-of-seeds scale:

    “To be comparable, the content of these bioactive compounds from 100 fresh sprouts was divided by the weight (g) of 100 seeds, and then this value was compared with their content from one gram seeds.”

  • The sinapic acid study discussed another study for:

    “In a study, diminishing amounts of total phenolic acids in sprouts of three broccoli cultivars was observed only between 3rd and 7th day of germination under photoperiod conditions and only when expressed on fresh weight basis. After recalculating results to dry weight, amounts were increasing during the whole 14-day observation period.”

All studies were scientifically informative. Still, results depended on researchers’ operative paradigms, and human behavior such as unconscious act-outs of unsatisfied needs to feel important.

2. Speaking of which, I viewed a 1:48 video with broccoli sprout experts who disparaged microwaving around the 1:10 mark. I’m not an expert, but I’ve eaten a clinically-relevant dose of microwaved broccoli sprouts every day for 34 weeks now.

Here are a few studies of microwaving’s effects on phenolic, glucosinolate, and flavonoid broccoli compounds. Just for those who value evidence more than opinion.

  • Microwaving broccoli sprouts may not affect phenolic levels found four of five test cases didn’t significantly diminish total phenolic fresh weight contents of whole broccoli. They blended 100 grams broccoli in 200 ml water, halved the purée, then microwaved half on 700W power for 30 seconds. No disclosure of what temperature was achieved, but it was probably < 60°C (140°F). Microwaving significantly increased the glucosinolate hydrolysis product indole-3-carbinol:

    “I3C in broccoli was increased by 3.1, 9.1 and 1.9 folds respectively using blenders 1, 2 and 5 with microwaving.”

  • Microwave broccoli to increase flavonoid levels study design was “Broccoli florets (150 g) were put in a microwave safe bowl with a 1 tablespoon [15 ml] of water” and a 1200W microwave on full power for one minute. Although this may have produced temperatures > 60°C, flavonoid fresh weight contents increased > 30%:

    Microwaving may increase extractability and/or release from binding to other compounds as a result of matrix softening.

  • Microwave broccoli to increase sulforaphane levels demonstrated significant differences for 475W (LL) and 950W (HL) power settings in glucoraphanin and sulforaphane dry weight amounts when broccoli florets were microwaved to the same temperatures. Compare white bar sulforaphane amounts for LL60 and HL60 (both 60°C), annotated as E and F:

    “Microwave treatment causes a sudden collapse of cell structure due to the increase in osmotic pressure difference over vacuole membrane. Microwave irradiation might help to release more conjugated forms of glucosinolates and then get hydrolyzed by released myrosinase.

  • Enhancing sulforaphane content confirmed the above 60°C finding with broccoli florets:

    “The best treatment temperature for maximizing sulforaphane yield was 60 °C. The slightly higher sulforaphane yield than would be predicted from the level of glucoraphanin in raw broccoli requires further investigation. Sulforaphane yield of broccoli after 5 min thermal treatment at 65 °C was even lower than the value obtained for raw broccoli.

3. I see socialistic animal behavior often during beach walks. If one seagull pecks a food morsel, a half-dozen others immediately position themselves to take it. It’s a race to the bottom of existence.

Too bad we humans don’t learn pertinent lessons from others’ experiences, much less our own. Today’s US Thanksgiving provides one example.

Richard Ebeling presented the factual Thanksgiving story a while back. Have you read about collectivism that arrived with the Mayflower in 1620? Do you think we’ve learned what we needed to learn about communism from four centuries ago through today?

4. Seagulls are also inspirational in their flock behavior of joie de vivre predawn flying.

Week 10 of Changing to a youthful phenotype with broccoli sprouts

To follow up Week 9 of Changing to a youthful phenotype with broccoli sprouts:

1. I increased three of eight upper body exercises by 50% through adding another set. I did it because I didn’t feel muscle exhaustion after two sets like I’d previously felt. 🙂

Cognitively, see A claim of improved cognitive function and its follow on Upgrade your brain’s switchboard with broccoli sprouts.

2. It’s been inspirational at times, and at other times, dull, duller, dullest, to do what’s necessary and keep on track. But efforts paid off when Week 9 was unlike any previous week!

I expressed appreciation in Our model clinical trial for Changing to a youthful phenotype with broccoli sprouts because scientific evidence provides great bases for intentional behavior. It’s still up to me to voluntarily carry out my part.

And why wouldn’t I act when my healthspan and lifespan are consequences? Except…

What if I’d been:

  • Tired of the hassle, or bored with self-imposed discipline, or lazy, and quit?
  • Projecting personal problems onto others, such that improving my present and future became less important than present act-outs?
  • Distracted by, or believed propaganda, or participated in Madness of Crowds behavioral contagion, and missed day after day of required actions?

I may not have ever experienced Week 9’s intermediate-term benefits!

If I keep going past ten weeks, what long-term benefits could be expected?

Our model clinical trial didn’t say how researchers decided on a ten-week period for subjects to consume broccoli sprouts every day. I asked a study coauthor about trial duration, but no answer yet.

A few of the same coauthors answered generally in Reviewing clinical trials of broccoli sprouts and their compounds:

Biomarkers of effect are early stage end-points, for instance modulation of phase 2 enzymes by glucosinolates. They need more time than biomarkers of exposure to be influenced by dietary treatment.

Hence, length or duration of the study must be defined according to the biomarker measured to be modified, that is, to define perfectly the time of exposure to observe changes in relevant parameters. Gene expression is one important target for glucosinolates, and it requires a sufficient period of exposure to (de)activate signaling pathways involved.

It is crucial to find appropriate biomarkers of effect that are linked to later disease outcomes, and more investigation is needed in this sense. Post-study follow-up can be of great value in assessing persistence of certain effects, or in discovering those that appear more long-term.

3. I’ll go into a clinic on Sunday for Day 70 truth tests. Here they are: Day 70 results from Changing to a youthful phenotype with broccoli sprouts!

Living beings – thousands of years old – growing together

We believe what we need to believe

While getting ready for bed tonight, I mused about how my younger brother had such an idealized postmortem view of our father. As he expressed six years ago in an obituary for our high school Literature teacher:

“I’ll remember my favorite teacher and how much he’s meant to my life. My father and Martin Obrentz were the two people who made me care about the things that make me the person I am today.”

Believe what you need to believe, David. But like I said five years ago in Reflections on my four-year anniversary of spine surgery:

“I don’t remember that my three siblings ever received a paddling or belting, although they were spanked. Even before he retired, 17 years before he died, the Miami-Dade County public school system stopped him and the rest of their employees from spanking, whipping, beating, and paddling children.”


It’s extremely important for a child to have a witness to their adverse childhood experiences. Otherwise, it’s crazy-making when these experiences aren’t acknowledged as truths by anyone else. Especially by those who saw but disavow what they saw.

It didn’t really drum into my conscious awareness until tonight that I had such a witness. It wasn’t my mother, of course, since she directed most of my being whipped with a belt, and beaten with a paddle that had holes in it to produce welts. She has denied and deflected my childhood experiences of her ever since then.

It wasn’t my siblings, regrettably for all of us. It wasn’t our Miami neighbors.

When I was twenty, I ran across a guy 300 miles north in Gainesville, Florida, named David Eisenberg, if I remember correctly. A couple of weeks after we met, he asked if my father was Fred Rice, Dean of Boys, West Miami Junior High School. He said he had been beaten by my father several times!

Those weren’t early childhood memories like mine. Those were experiences of a young man during grades 7-9 that he remembered more than a decade later.

I was shocked. It came at a time when I wasn’t ready to face facts about my life, though. I needed fantasies, beliefs to smother what I felt.


I don’t expect that the impacts of my childhood experiences will ever go away. After three years of Primal Therapy that ended a decade ago, at least mine don’t completely control my life anymore.

Dr. Arthur Janov put self-narratives of several patients’ experiences into his May 2016 book Beyond Belief which I partially curated in February 2017. It was partial because I couldn’t read much past Frank’s horrendous story in pages 89 – 105, “The Myth of a Happy Childhood.”

Forcing people to learn helplessness

Learned helplessness is a proven animal model. Its reliably-created phenotype is often the result of applying chronic unpredictable stress.

As we’re finding out worldwide, forcing humans to learn helplessness works in much the same way, with governments imposing what amounts to martial law. Never mind that related phenotypes and symptoms include:

  • “Social defeat
  • Social avoidance behavior
  • Irritable bowel syndrome
  • Depression
  • Anxiety
  • Anhedonia
  • Increased hypothalamic-pituitary-adrenal (HPA)-axis sensitivity
  • Visceral hypersensitivity” [1]

Helplessness is both a learned behavior and a cumulative set of experiences. Animal models demonstrate that these phenotypes usually continue on throughout the subjects’ entire lifespans.

Will the problems caused in humans by humans be treated by removing the causes? Or will the responses be approaches such as drugs to treat the symptoms?


A major difference between our current situation and the situation depicted below is that during communism, most people didn’t really trust or believe what the authorities, newspapers, television, and radio said:

Image from Prague’s Memorial to the Victims of Communism


[1] 2014 GABAB(1) receptor subunit isoforms differentially regulate stress resilience curated in If research provides evidence for the causes of stress-related disorders, why only focus on treating the symptoms?

Flatten the Panic Curve April 13-17, 2020

To better understand our internal origins of panic, here’s Dr. Arthur Janov’s interpretation of a 2013 Iowa study Fear and panic in humans with bilateral amygdala damage (not freely available):

“Justin Feinstein did a study with those who had a damaged amygdala, the hub of the emotional system. They did not have normal fear responses. But if oxygen supplies were lowered and carbon dioxide supplies were increased, mimicking suffocation (increasing acidity of the blood) there were panic attacks.

Where in the world did those attacks come from? Certainly not from the usual emotional structures.

They believe it includes the brainstem! Because the lowering of oxygen supplies and adding carbon dioxide provoked the lower structures to sense the danger and reacted appropriately.

Very much like what happens to a fetus when the mother smokes during pregnancy and produces those same effects.”


Since those of us who chronically experience panic aren’t going into therapy over this weekend, what else can we do?

1. Stop looking at the John Hopkins Panic map.

2. Search out realistic news such as: “Change in [New York state] ICU admissions is actually a negative number for the first time since we started this intense journey.”

3. Stop clicking sensational headline links.

4. Question your information, and investigate multiple views. Trust has been lost:

  • Dr. Scott Jensen, a Minnesota physician for 35 years and state senator, on the inappropriate CDC / WHO guidelines for reporting COVID-19 deaths:

    “It’s ridiculous. The determination of cause of death is a big deal. The idea that we’re going to allow people to massage and game the numbers is a real issue because we’re going to undermine trust.

    I would never put down influenza as the cause of death. Yet that’s what we’re being asked to do here.”

  • The same day, Dr. Fauci arrogantly grouped physicians in with conspiracy theorists if they didn’t conform to these bordering-on-fraudulent CDC / WHO guidelines:

    “Every time we have a crisis of any sort, there’s always this popping-up of conspiracy theories. I think the deaths that we’re seeing are coronavirus deaths, and the other deaths are not being counted as coronavirus deaths.”

    Telling people to trust him – a bureaucrat who hasn’t been in active practice for over three decades – because he had far superior medical judgment than did practicing doctors who for years continuously see patients?

  • Consider the evidence.
  • Don’t accept lies you feel uneasy about. Trust your internal BS detector.

Which herd will you choose to belong to?

https://nypost.com/video/bison-stampede-terrorizes-family-trapped-in-car/

or

Do early experiences of hunger affect our behavior, thoughts, and feelings today?

Reposted from five years ago.


A 2015 worldwide human study Hunger promotes acquisition of nonfood objects found that people’s current degree of hungriness affected their propensity to acquire nonfood items.

The researchers admitted that they didn’t demonstrate cause and effect with the five experiments they performed, although the findings had merit. News articles poked good-natured fun at the findings with headlines such as “Why Hungry People Want More Binder Clips.”

The research caught my eye with these statements:

“Hunger’s influence extends beyond food consumption to the acquisition of nonfood items that cannot satisfy the underlying need.

We conclude that a basic biologically based motivation can affect substantively unrelated behaviors that cannot satisfy the motivation.


The concept of the quotes relates to a principle of Dr. Arthur Janov’s Primal Therapy – symbolic satisfaction of needs. Two fundamentals of Primal Therapy:

  1. The physiological impacts of our early unmet needs drive our behavior, thoughts, and feelings.
  2. The painful impacts of our unfulfilled needs impel us to be constantly vigilant for some way to fulfill them.

Corollary principles of Primal Therapy:

  • Our present efforts to fulfill our early unmet needs will seldom be satisfying. It’s too late.
  • We acquire substitutes now for what we really needed back then.
  • Acquiring these symbols of our early unmet needs may – at best – temporarily satisfy derivative needs.

But the symbolic satisfaction of derived needs – the symptoms – never resolves the impacts of early unfulfilled needs – the motivating causes:

  • We repeat the acquisition behavior, and get caught in a circle of acting out our feelings and impulses driven by these conditions.
  • The unconscious act-outs become sources of misery both to us and to the people around us.

As this study’s findings showed, there’s every reason for us to want researchers to provide a factual blueprint of causes for our hunger sensation effects, such as “unrelated behaviors that cannot satisfy the motivation.

Hunger research objectives could include answering:

  • What enduring physiological changes occurred as a result of past hunger?
  • How do these changes affect the subjects’ present behaviors, thoughts, and feelings?

Hunger research causal evidence for the effect of why people acquire items that cannot satisfy the underlying needmay include studying where to start the timelines for the impacts of hunger. The impacts potentially go back at least to infancy when we were completely dependent on our caregivers.

Infants can’t get up to go to the refrigerator to satisfy their hunger. All a hungry infant can do is call attention to their need, and feel pain from the deprivation of their need.

Is infancy far back enough, though, to understand the beginnings of potential impacts of hunger?

Humans individually evolve by..?

This 2020 UK evolutionary biology article was part of a “Fifty years of the Price equation” issue:

“Genetic and non-genetic inheritance usually produce a phenotype [the composite of an organism’s characteristics, including its developmental, biophysical, and behavioral traits] through a highly complex developmental process that also relies on many features of the world over which the parents have little, if any, control. As a consequence, the relationship between the phenotypes of parents and offspring, the offspring–parent distribution, can take on many forms and vary from one place or time to another.

The extension of transmission and quantitative genetic models retain the assumption that the relationship between inheritance and phenotypic variation is such that it is sufficient to focus on the transmissibility of inherited variants or additive variance rather than phenotype development.

The concept of heredity as a developmental process is a more significant departure from traditional notions of inheritance. The mechanisms of non-genetic inheritance, such as parental behaviour, do not only affect the parent–offspring resemblance, but also the generation of variation and individual fitness.

Any feature of the parents, including their DNA sequence, physiology and behaviour can carry information about the conditions that the offspring will encounter. That this information content itself must be an evolving property is perhaps most evident when heredity is viewed as a developmental process; a developmental perspective is particularly useful when the aim is to study how the evolutionary process itself is evolving.”

https://royalsocietypublishing.org/doi/full/10.1098/rstb.2019.0366 “Different perspectives on non-genetic inheritance illustrate the versatile utility of the Price equation in evolutionary biology”


This article and the “Fifty years of the Price equation” issue’s other articles had numerous mentions of individual evolution and behavior. They acknowledged “a diversity of perspectives” but I didn’t see my 2015 page’s perspective that it’s up to each individual to mold their own phenotype. In it, the Price equation prompted the question:

“How does a phenotype influence its own change?”

which I applied to a person individually evolving.

The article and the issue’s other articles tinkered with equations, and cited plant, animal, and human studies with frameworks that didn’t include investigating causes for the observed effects. These often wasted resources by providing solutions that addressed symptoms instead of addressing the uninvestigated causes.

For example, I didn’t see any mentions of how an individual’s pain may drive their phenotype. Pain induced by threats to survival are common parts of animal experiments that create and investigate phenotypes of epigenetic responses to stressors.

Regarding possible human applicability, how can a person remedy their undesirable traits and acquire desirable traits without addressing a root cause?

Unlike animals, people can therapeutically resolve underlying causes without the timing, duration, and intensity of efforts being externally determined. A human’s efforts to change their phenotype don’t have to mimic animal studies’ forcible approaches with drugs, etc., directed on someone else’s schedule. Addressing pain may be required for such efforts.


The article also promoted an outdated paradigm of epigenetic transgenerational inheritance:

“The transgenerational stability of some epigenetic states may fall within the same range as the stability of behaviours that are learnt from parents. Quantifying the environmental sensitivity and transgenerational stability of epigenetic variation has emerged as a major research focus over the past decade.”

As explained in Transgenerational epigenetic inheritance of thyroid hormone sensitivity:

“Observing the same phenotype in each generation is NOT required for transgenerational epigenetic inheritance to exist. Animal transgenerational studies have shown that epigenetic inheritance mechanisms may both express different phenotypes for each generation, and entirely skip a phenotype in one or more generations.”

Considering only “transgenerational stability of epigenetic variation” as proof will misinterpret this supporting evidence.

Recover your sanity

Men, it has been well said:

  • Think in herds; it will be seen that
  • They go mad in herds, while
  • They only recover their senses slowly, one by one.

During the great plague, which ravaged all Europe between the years 1345 and 1350, it was generally considered that the end of the world was at hand.

‘But the facts, my dear fellow,’ said his friend, ‘the facts do not agree with your theory.’ ‘Don’t they?’ replied the philosopher, shrugging his shoulders, ‘then, tant pis pour les faits’ – so much the worse for the facts!”

Charles Mackay, 1841

https://www.gutenberg.org/ebooks/24518 “Memoirs of Extraordinary Popular Delusions and the Madness of Crowds”

Alfred Jacob Miller “Hunting buffalo” 1837

“Establishing the hidden communication networks in large self-organized groups facilitates a quantitative understanding of behavioral contagion.

An individual will be more likely to respond (is more susceptible) if it:

  • Is strongly connected to the initiator (short path length), and if it
  • Has neighbors which are strongly connected to each other.”

Why is it so difficult to live your own life?

Using oxytocin receptor gene methylation to pursue an agenda

A pair of 2019 Virginia studies involved human mother/infant subjects:

“We show that OXTRm [oxytocin receptor gene DNA methylation] in infancy and its change is predicted by maternal engagement and reflective of behavioral temperament.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795517 “Epigenetic dynamics in infancy and the impact of maternal engagement”

“Infants with higher OXTRm show enhanced responses to anger and fear and attenuated responses to happiness in right inferior frontal cortex, a region implicated in emotion processing through action-perception coupling.

Infant fNIRS [functional near-infrared spectroscopy] is limited to measuring responses from cerebral cortex. It is unknown whether OXTR is expressed in the cerebral cortex during prenatal and early postnatal human brain development.”

https://www.sciencedirect.com/science/article/pii/S187892931830207X “Epigenetic modification of the oxytocin receptor gene is associated with emotion processing in the infant brain”


Both studies had weak disclosures of limitations on their findings’ relevance and significance. The largest non-disclosed contrary finding was from the 2015 Early-life epigenetic regulation of the oxytocin receptor gene:

These results suggest that:

  • Blood Oxtr DNA methylation may reflect early experience of maternal care, and
  • Oxtr methylation across tissues is highly concordant for specific CpGs, but
  • Inferences across tissues are not supported for individual variation in Oxtr methylation.

That rat study found that blood OXTR methylation of 25 CpG sites couldn’t accurately predict the same 25 CpG sites’ OXTR methylation in each subject’s hippocampus, hypothalamus, and striatum (which includes the nucleus accumbens) brain areas. Without significant effects in these limbic system structures, there couldn’t be any associated behavioral effects.

But CpG site associations and correlations were deemed good in the two current studies because they cited:

“Recent work in prairie voles has found that both brain- and blood-derived OXTRm levels at these sites are negatively associated with gene expression in the brain and highly correlated with each other.”

https://www.sciencedirect.com/science/article/pii/S0306453018306103 “Early nurture epigenetically tunes the oxytocin receptor”

The 2018 prairie vole study – which included several of the same researchers as the two current studies – found four nucleus accumbens CpG sites that had high correlations to humans. Discarding one of these CpG sites allowed their statistics package to make a four-decimal place finding:

“The methylation state of the blood was also associated with the level of transcription in the brain at three of the four CpG sites..whole blood was capable of explaining 94.92% of the variance in Oxtr DNA methylation and 18.20% of the variance in Oxtr expression.”

Few limitations on the prairie vole study findings were disclosed. Like the two current studies, there wasn’t a limitation section that placed research findings into suitable contexts. So readers didn’t know researcher viewpoints on items such as:

  • What additional information showed that 3 of the 30+ million human CpGs accurately predicted specific brain OXTR methylation and expression from saliva OXTR methylation?
  • What additional information demonstrated how “measuring responses from cerebral cortex” although “it is unknown whether OXTR is expressed in the cerebral cortex” provided detailed and dependable estimates of limbic system CpG site OXTR methylation and expression?
  • Was the above 25-CpG study evidence considered?

Further contrast these three studies with a typical, four-point, 285-word limitation section of a study like Prenatal stress heightened adult chronic pain. The word “limit” appeared 6 times in that pain study, 3 times in the current fNIRS study, and 0 times in the current maternal engagement and cited prairie vole studies.

Frank interpretations of one’s own study findings to acknowledge limitations is one way researchers can address items upfront that will be questioned anyway. Such analyses also indicate a goal to advance science.

A drug that countered effects of a traumatizing mother

This 2019 US rodent study concerned transmitting poor maternal care to the next generation:

“The quality of parental care received during development profoundly influences an individual’s phenotype, including that of maternal behavior. Infant experiences with a caregiver have lifelong behavioral consequences.

Maternal behavior is a complex behavior requiring the recruitment of multiple brain regions including the nucleus accumbens, bed nucleus of the stria terminalis, ventral tegmental area, prefrontal cortex, amygdala, and medial preoptic area. Dysregulation within this circuitry can lead to altered or impaired maternal responsiveness.

We administered zebularine, a drug known to alter DNA methylation, to dams exposed during infancy to the scarcity-adversity model of low nesting resources, and then characterized the quality of their care towards their offspring.

  1. We replicate that dams with a history of maltreatment mistreat their own offspring.
  2. We show that maltreated-dams treated with zebularine exhibit lower levels of adverse care toward their offspring.
  3. We show that administration of zebularine in control dams (history of nurturing care) enhances levels of adverse care.
  4. We show altered methylation and gene expression in maltreated dams normalized by zebularine.

These findings lend support to the hypothesis that epigenetic alterations resulting from maltreatment causally relate to behavioral outcomes.”

“Maternal behavior is an intergenerational behavior. It is important to establish the neurobiological underpinnings of aberrant maternal behavior and explore treatments that can improve maternal behavior to prevent the perpetuation of poor maternal care across generations.”


The study authors demonstrated intergenerational epigenetic effects, and missed an opportunity to also investigate transgenerational epigenetically inherited effects. They cited reference 60 for the first part of the above quotation, but the cited reviewer misused the transgenerational term by applying it to grand-offspring instead of the great-grand-offspring.

There were resources available to replicate the study authors’ previous findings, which didn’t show anything new. Why not use such resources to uncover evidence even more applicable to humans by extending experiments to great-grand-offspring that would have no potential germline exposure to the initial damaging cause?

Could a study design similar to A limited study of parental transmission of anxiety/stress-reactive traits have been integrated? That study’s thorough removal of parental behavior would be an outstanding methodology to confirm by falsifiability whether parental behavior is both an intergenerational and a transgenerational epigenetic inheritance mechanism.

Rodent great-grand-offspring can be studied in < 9 months. It takes > 50 years for human studies to reach the great-grand-offspring transgenerational generation.

  • Why not attempt to “prevent the perpetuation of poor maternal care across generations?”
  • Isn’t it a plausible hypothesis that humans “with a history of maltreatment mistreat their own offspring?”
  • Isn’t it worth the extra effort to extend animal research to investigate this unfortunate chain?

https://www.nature.com/articles/s41598-019-46539-4 “Pharmacological manipulation of DNA methylation normalizes maternal behavior, DNA methylation, and gene expression in dams with a history of maltreatment”

Do delusions have therapeutic value?

This 2019 UK review discussed delusions, aka false beliefs about reality:

“Delusions are characterized by their behavioral manifestations and defined as irrational beliefs that compromise good functioning. In this overview paper, we ask whether delusions can be adaptive notwithstanding their negative features.

We consider different types of delusions and different ways in which they can be considered as adaptive: psychologically (e.g., by increasing wellbeing, purpose in life, intrapsychic coherence, or good functioning) and biologically (e.g., by enhancing genetic fitness).”

https://onlinelibrary.wiley.com/doi/full/10.1002/wcs.1502 “Are clinical delusions adaptive?”


A. Although section 4’s heading was Biological Adaptiveness of Delusions, the reviewers never got around to discussing evolved roles of brain areas and beliefs (delusions). One mention of evolutionary biology was:

“Delusions are biologically adaptive if, as a response to a crisis of some sort (anomalous perception or overwhelming distress), they enhance a person’s chances of reproductive success and survival by conferring systematic biological benefits.”

B. Although section 5’s heading was Psychological Adaptiveness of Delusions, the reviewers didn’t connect feelings and survival sensations as origins of beliefs (delusions) and behaviors. They had a few examples of feelings:

“Delusions of reference and delusions of grandeur can make the person feel important and worthy of admiration.”

and occasionally sniffed a clue:

“Some delusions (especially so‐called motivated delusions) play a defensive function, representing the world as the person would like it to be.”

where “motivated delusions” were later deemed in the Conclusion section to be a:

“Response to negative emotions that could otherwise become overwhelming.”

C. Feelings weren’t extensively discussed until section 6 Delusions in OCD and MDD, which gave readers an impression that feelings were best associated with those diseases.

D. In the Introduction, sections 4, 5, and 7 How Do We Establish and Measure Adaptiveness, the reviewers discussed feeling meaning in life, but without understanding:

  1. Feelings = meaning in life, as I quoted Dr. Arthur Janov in The pain societies instill into children:

    “Without feeling, life becomes empty and sterile. It, above all, loses its meaning.

  2. Beliefs (delusions) defend against feelings.
  3. Consequentially, the stronger and / or more numerous beliefs (delusions) a person has, the less they feel meaning in life.

E. Where, when, why, and how do beliefs (delusions) arise? Where, when, why, and how does a person sense and feel, and what are the connections with beliefs (delusions)?

F. The word “sense” was used 29 times in contexts such as “make sense” and “sense of [anxiety, coherence, control, meaning, purpose, rational agency, reality, self, uncertainty]” but no framework connected biological sensing to delusions. Papers from other fields have detailed cause-and-effect explanations and predecessor-successor diagrams for every step of a process. Not this one.


Regarding any therapeutic value of someone else’s opinion of a patient’s delusions:

I’ll reuse this quotation from the Scientific evidence page of Dr. Janov’s 2011 book “Life Before Birth: The Hidden Script that Rules Our Lives” p.166:

“Primal Therapy differs from other forms of treatment in that the patient is himself a therapist of sorts. Equipped with the insights of his history, he learns how to access himself and how to feel.

The therapist does not heal him; the therapist is only the catalyst allowing the healing forces to take place. The patient has the power to heal himself.

Another way Dr. Janov wrote this was on p.58 of his 2016 book Beyond Belief as quoted in Beyond Belief: The impact of merciless beatings on beliefs:

NO ONE HAS THE ANSWER TO LIFE’S QUESTIONS BUT YOU. How you should lead your life depends on you, not outside counsel.

We do not direct patients, nor dispense wisdom upon them. We have only to put them in touch with themselves; the rest is up to them.

Everything the patient has to learn already resides inside. The patient can make herself conscious. No one else can.”

Non-emotional memories

This 2019 US review covered memory mechanisms:

“With memory encoding reliant on persistent changes in the properties of synapses, a key question is how can memories be maintained from days to months or a lifetime given molecular turnover? It is likely that positive feedback loops are necessary to persistently maintain the strength of synapses that participate in encoding.

These levels are not isolated, but linked by shared components of feedback loops.”


Despite the review’s exhaustive discussion, the reviewers never came to the point. The word cloud I made of the review’s most frequent thirty words had little to do with why memory occurs:

  • Why do some stimuli evoke a memory in response?
  • Why are almost all of the stimuli an organism receives not remembered?

Much of the discussion was baseless because it excluded emotion. Many of the citations’ memory findings relied on emotion, though.

For example, in the subsection Roles of persistent epigenetic modifications for maintaining LTF [long-term facilitation], LTP [long-term potentiation], and LTM [long-term memory]:

  • Histone acetylation is increased after fear conditioning in the hippocampus and amygdala.
  • Correspondingly, inhibition of histone deacetylase enhances fear conditioning and LTP.
  • Following fear conditioning, histone phosphorylation is also increased.
  • DNA methylation is also up-regulated in the hippocampus and amygdala after fear conditioning, and inhibition of DNA methylation blocks fear LTM.”

http://learnmem.cshlp.org/content/26/5/133.full “How can memories last for days, years, or a lifetime? Proposed mechanisms for maintaining synaptic potentiation and memory”