The lack of oxygen’s epigenetic effects on a fetus

This 2018 Loma Linda review subject was gestational hypoxia:

“Of all the stresses to which the fetus and newborn infant are subjected, perhaps the most important and clinically relevant is that of hypoxia. This review explores the impact of gestational hypoxia on maternal health and fetal development, and epigenetic mechanisms of developmental plasticity with emphasis on the uteroplacental circulation, heart development, cerebral circulation, pulmonary development, and the hypothalamic-pituitary-adrenal axis and adipose tissue.

An understanding of the specific hypoxia-induced environmental and epigenetic adaptations linked to specific organ systems will enhance the development of target-specific inhibition of DNA methylation, histone modifications, and noncoding RNAs that underlie hypoxia-induced phenotypic programming of disease vulnerability later in life.

A potential stumbling block to these efforts, however, relates to timing of the intervention. The greatest potential effect would be accomplished at the critical period in development for which the genomic plasticity is at its peak, thus ameliorating the influence of hypoxia or other stressors.

With future developments, it may even become possible to intervene before conception, before the genetic determinants of the risk of developing programmed disease are established.”

Table 3 “Antenatal hypoxia and developmental plasticity” column titles were Species | Offspring Phenotypes of Disorders and Diseases | Reference Nos.

Hypoxia phenotypes


This review was really an ebook, with 94 pages and 1,172 citations in the pdf file. As I did with Faith-tainted epigenetics, I read it with caution toward recognizing the influence of the sponsor’s biases, and any directed narrative that ignored evidence contradicting the narrative, and any storytelling.

See if you can match the meaning of the review’s last sentence quoted above with the meaning of any sentence in its cited reference Developmental origins of noncommunicable disease: population and public health implications.

One review topic that was misconstrued was transgenerational epigenetic inheritance of hypoxic effects. The “transgenerational” term was used inappropriately by several of the citations, and no cited study provided evidence for gestational hypoxic effects through the  F2 grandchild and F3 great-grandchild generations.

One omitted topic was gestational hypoxic effects of caffeine. The first paper that came up for my PubMed search of “caffeine pregnancy hypoxia” was an outstanding 2017 Florida rodent review Long-term consequences of disrupting adenosine signaling during embryonic development that had this paragraph and figure:

“One substance that fetuses are frequently exposed to is caffeine, which is a non-selective adenosine receptor antagonist. We discovered that in utero alteration in adenosine action leads to adverse effects on embryonic and adult murine hearts. We find that cardiac A1ARs [a type of adenosine receptor] protect the embryo from in utero hypoxic stress, a condition that causes an increase in adenosine levels. 

After birth in mice, we observed that in utero caffeine exposure leads to abnormal cardiac function and morphology in adults, including an impaired response to β-adrenergic stimulation. Recently, we observed that in utero caffeine exposure induces transgenerational effects on cardiac morphology, function, and gene expression.”

The timing of in utero caffeine treatment leads to differences in adult cardiac function, gene expression, and phenotype. Exposure to caffeine from E6.5–9.5 leads the F1 generation to develop dilated cardiomyopathy with decrease % FS and increased Myh7 expression. In utero caffeine exposure from E10.5–13.5 leads to a hypertrophic cardiomyopathy in the F2 generation along with increased % FS and decreased Myh7 expression

Why was this review and its studies omitted? It was on target for both gestational hypoxia and transgenerational epigenetic inheritance of hypoxic effects!

It was alright to review smoking, cocaine, methamphetamine, etc., but the most prevalent drug addiction – caffeine – couldn’t be a review topic?


The Loma Linda review covered a lot, but I had a quick trigger due to the sponsor’s bias. I started to lose “faith” in the reviewers after reading the citation for the review’s last sentence that didn’t support the statement.

My “faith” disappeared after not understanding why a few topics were misconstrued and omitted. Why do researchers and sponsors ignore, misrepresent, and not continue experiments through the F3 generation to produce evidence for and against transgenerational epigenetic inheritance? Where was the will to follow evidence trails regardless of socially acceptable beverage norms?

The review acquired the taint of storytelling with the reviewers’ assertion:

“..timing of the intervention. The greatest potential effect would be accomplished at the critical period in development for which the genomic plasticity is at its peak, thus ameliorating the influence of hypoxia or other stressors.”

Contradictory evidence was in the omitted caffeine study’s graphic above which described two gestational periods where an “intervention” had opposite effects, all of which were harmful to the current fetus’ development and/or to following generations. Widening the PubMed link’s search parameters to “caffeine hypoxia” and “caffeine pregnancy” returned links to human early life studies that used caffeine in interventions, ignoring possible adverse effects on future generations.

This is my final curation of any paper sponsored by this institution.

https://www.physiology.org/doi/abs/10.1152/physrev.00043.2017 “Gestational Hypoxia and Developmental Plasticity” (not freely available) Thanks to coauthor Dr. Xiang-Qun Hu for providing a copy.

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Ideaesthesia!

This 2018 UK review subject was colored-hearing arising on hearing music:

“Music-colour synaesthesia has a broad scope encompassing not only tone-colour synaesthesia elicited on hearing individual tones, but a complex and idiosyncratic mixture of phenomenological experiences often mediated by timbre, tempo, emotion and differing musical style.

The possession of synaesthesia or absolute pitch was shown to have very little effect on the actual colours chosen for each of the musical excerpts, but it might be reasonable to expect that music that elicits a strong emotional response may be more likely to induce synaesthesia than music that does not.

The examination of eight neuroimaging studies were found to be largely inconclusive in respect of confirming the perceptual nature of music-colour synaesthesia. Neither the hyperconnectivity nor the disinhibited feedback theory currently holds as a single categorical explanation for synaesthesia.

Theories promoting the notion of ‘ideaesthesia’ have highlighted the importance of the role of concept and meaning in the understanding of synaesthesia..and a replacement definition: Synaesthesia is a phenomenon in which a mental activation of a certain concept or idea is associated consistently with a certain perception-like experience.”

Much of the review was philosophizing and casting around for clues. The review cited interesting studies and reviews, including The Merit of Synesthesia for Consciousness Research.


One relevant element missed by the underlying research and the review was critical periods of human development. A cited reference in How brains mature during critical periods was Sensitive periods in human development: Evidence from musical training (not freely available) which illuminated some aspects of the research:

“In contrast to a critical period, where a function cannot be acquired outside the specific developmental window, a sensitive period denotes a time where sensory experience has a relatively greater influence on behavioral and cortical development. Sensitive periods may also be times when exposure to specific stimuli stimulates plasticity, enhancing changes at the neuronal and behavioral levels.

The developmental window for absolute pitch may be more similar to a critical than a sensitive period.

The auditory cortex appears to have an unusually long period of developmental plasticity compared with other sensory systems; changes in its cellular organization and connectivity continue into late childhood.

The effects of musical training have been shown to impact auditory processing in the brainstem as well.”

Let’s say that a researcher wanted – as one cited study did – to examine absolute pitch, a rare trait, present in a subset of synesthetes – music-color, another rare trait. The study as designed would probably be underpowered due to an insufficient number of subjects, and it would subsequently find “very little effect.”

Let’s say another researcher focused on brain areas in the cerebrum, and like the eight cited studies, ignored the nuclei in the pons part of the brainstem which are the first brain recipients of sound and equilibrium information from the inner ear via the eighth cranial nerve. Like those studies, they were also biased against including limbic brain areas that would indicate “a strong emotional response.” A study design that combined leaving out important brain-area participants in the synesthesia process with a few number of synesthetes would be unlikely to find conclusive evidence.

The reviewer viewed the lack of evidence from “eight neuroimaging studies” as indicating something about the “perceptual nature of music-colour synaesthesia.” An alternative view is that the “inconclusive” evidence had more to do with study designs that:

  • Had a small number of subjects;
  • Omitted brain areas relevant to the music-color synesthesia process;
  • Didn’t investigate likely music-color synesthesia development periods; and
  • Didn’t investigate associations of music-color synesthesia with epigenetic states.

Consider the magnitude of omitting the thalamus from synesthesia studies as one “perceptual nature” example. Just the background information of Thalamus gating and control of the limbic system and cerebrum is a form of memory indicated its relevance to synesthesia:

Despite the fundamental differences between visual, auditory and somatosensory signals, the basic layouts of the thalamocortical systems for each modality are quite similar.

For a given stimulus, the output neural response will not be static, but will depend on recent stimulus and response history.

Sensory signals en route to the cortex undergo profound signal transformations in the thalamus. A key thalamic transformation is sensory adaptation in which neural output adjusts to the statistics and dynamics of past stimuli.”

One of this study’s researchers described ways that an individual’s “stimulus and response history” became unconscious memories with the thalamus. Including the thalamus in synesthesia studies may also have findings that involve reliving or re-experiencing a memory, possibly an emotional memory.

In such future research, it could be a design element to ask synesthetes before and after the experiment to identify feelings and memories accompanying synesthesia experiences.

It shouldn’t be a requirement, however, to insist that memories and emotions be consciously identified in order to be included in the findings. Human studies, for example, Unconscious stimuli have a pervasive effect on our brain function and behavior have found:

“Pain responses can be shaped by learning that takes place outside conscious awareness.

Our results support the notion that nonconscious stimuli have a pervasive effect on human brain function and behavior and may affect learning of complex cognitive processes such as psychologically mediated analgesic and hyperalgesic responses.”


Does an orangey twilight of fading sunflowers help you feel?

https://www.sciencedirect.com/science/article/pii/S1053810017305883 “Music-colour synaesthesia: Concept, context and qualia” (not freely available)

A dietary supplement that reversed age-related hearing problems in the brainstem

This 2018 Nevada rodent study was on acetyl-L-carnitine’s action in the brainstem:

“We examined age-related changes in the efficiency of synaptic transmission at the calyx of Held, from juvenile adults (1-month old) and late middle-age (18- to 21-month old) mice. The calyx of Held synapse has been exploited as a model for understanding excitation-secretion coupling in central glutamatergic neurons, and is specialized for high-frequency transmission as part of a timing circuit for sound localization.

Our observations suggest that during aging, there is neuronal cell loss in the MNTB [Medial nucleus of the trapezoid body, a collection of brainstem nuclei in an area that’s the first recipient of sound and equilibrium information], similar to previous reports. In remaining synapses of the MNTB, we observed severe impairments in transmission timing and SV [synaptic vesicle] recycling, resulting in timing errors and increased synaptic depression in the calyx of Held synapse. These defects reduce the efficacy of this synapse to encode temporally sensitive information and are likely to result in diminished sound localization.

We orally administered ALCAR for 1 month and found that it reversed transmission defects at the calyx of Held synapse in the older mice.

These results support the concept that facilitators of mitochondrial metabolism and antioxidants may be an extremely effective therapy to increase synaptic function and restore short-term plasticity in aged brains, and provide for the first time a clear mechanism of action for ALCAR on activity-dependent synaptic transmission.


Human brainstem research is neglected, as noted by Advance science by including emotion in research. Evidence from such research doesn’t play well with beliefs in the popular models and memes of human cerebral dominance.

Do you know any “late middle-age” people who have obvious auditory and synaptic deficits? What if some of the neurobiological causes of what’s wrong in their brains could be “reversed by ALCAR?”

Before using this study as a guide, however, I asked the study’s researchers to calculate the human-equivalent dosage. When I translated the “daily dose of ~2.9 g/kg/d” it worked out to several hundred times the 500 mg to 1 g dietary supplement dosage of acetyl-L-carnitine.

The study’s corresponding coauthor replied:

“This is indeed much larger than that normally consumed by humans via dietary supplementation. We are currently working to determine the effective ‘minimal’ dose of ALCAR and alpha lipoic acid, to better assist guidelines for human application of this supplement.”

https://www.researchgate.net/publication/323941877_Age-related_defects_in_short-term_plasticity_are_reversed_by_acetyl-L-carnitine_at_the_mouse_calyx_of_Held “Age-related defects in short-term plasticity are reversed by acetyl-L-carnitine at the mouse calyx of Held”

Resiliency in stress responses

This 2018 US Veterans Administration review subject was resiliency and stress responses:

Neurobiological and behavioral responses to stress are highly variable. Exposure to a similar stressor can lead to heterogeneous outcomes — manifesting psychopathology in one individual, but having minimal effect, or even enhancing resilience, in another.

We highlight aspects of stress response modulation related to early life development and epigenetics, selected neurobiological and neurochemical systems, and a number of emotional, cognitive, psychosocial, and behavioral factors important in resilience.”

The review cited studies I’ve previously curated:


There were two things I didn’t understand about this review. The first was why the paper isn’t freely available. It’s completely paid for by the US taxpayer, and no copyright is claimed. I recommend contacting the authors for a copy.

The second was why the VA hasn’t participated in either animal or human follow-on studies to the 2015 Northwestern University GABAergic mechanisms regulated by miR-33 encode state-dependent fear. That study’s relevance to PTSD, this review’s subject, and the VA’s mission is too important to ignore. For example:

“Fear-inducing memories can be state dependent, meaning that they can best be retrieved if the brain states at encoding and retrieval are similar.

“It’s difficult for therapists to help these patients,” Radulovic said, “because the patients themselves can’t remember their traumatic experiences that are the root cause of their symptoms.”

The findings imply that in response to traumatic stress, some individuals, instead of activating the glutamate system to store memories, activate the extra-synaptic GABA system and form inaccessible traumatic memories.”

I curated the research in A study that provided evidence for basic principles of Primal Therapy. These researchers have published several papers since then. Here are the abstracts from three of them:

Experimental Methods for Functional Studies of microRNAs in Animal Models of Psychiatric Disorders

“Pharmacological treatments for psychiatric illnesses are often unsuccessful. This is largely due to the poor understanding of the molecular mechanisms underlying these disorders. We are particularly interested in elucidating the mechanism of affective disorders rooted in traumatic experiences.

To date, the research of mental disorders in general has focused on the causal role of individual genes and proteins, an approach that is inconsistent with the proposed polygenetic nature of these disorders. We recently took an alternative direction, by establishing the role of miRNAs in the coding of stress-related, fear-provoking memories.

Here we describe in detail our work on the role of miR-33 in state-dependent learning, a process implicated in dissociative amnesia, wherein memories formed in a certain brain state can best be retrieved if the brain is in the same state. We present the specific experimental approaches we apply to study the role of miRNAs in this model and demonstrate that miR-33 regulates the susceptibility to state-dependent learning induced by inhibitory neurotransmission.”

Neurobiological mechanisms of state-dependent learning

“State-dependent learning (SDL) is a phenomenon relating to information storage and retrieval restricted to discrete states. While extensively studied using psychopharmacological approaches, SDL has not been subjected to rigorous neuroscientific study.

Here we present an overview of approaches historically used to induce SDL, and highlight some of the known neurobiological mechanisms, in particular those related to inhibitory neurotransmission and its regulation by microRNAs (miR).

We also propose novel cellular and circuit mechanisms as contributing factors. Lastly, we discuss the implications of advancing our knowledge on SDL, both for most fundamental processes of learning and memory as well as for development and maintenance of psychopathology.”

Neurobiological correlates of state-dependent context fear

“Retrieval of fear memories can be state-dependent, meaning that they are best retrieved if the brain states at encoding and retrieval are similar. Such states can be induced by activating extrasynaptic γ-aminobutyric acid type A receptors (GABAAR) with the broad α-subunit activator gaboxadol. However, the circuit mechanisms and specific subunits underlying gaboxadol’s effects are not well understood.

Here we show that gaboxadol induces profound changes of local and network oscillatory activity, indicative of discoordinated hippocampal-cortical activity, that were accompanied by robust and long-lasting state-dependent conditioned fear. Episodic memories typically are hippocampus-dependent for a limited period after learning, but become cortex-dependent with the passage of time.

In contrast, state-dependent memories continued to rely on hippocampal GABAergic mechanisms for memory retrieval. Pharmacological approaches with α- subunit-specific agonists targeting the hippocampus implicated the prototypic extrasynaptic subunits (α4) as the mediator of state-dependent conditioned fear.

Together, our findings suggest that continued dependence on hippocampal rather than cortical mechanisms could be an important feature of state-dependent memories that contributes to their conditional retrieval.”


Here’s an independent 2017 Netherlands/UC San Diego review that should bring these researchers’ efforts to the VA’s attention:

MicroRNAs in Post-traumatic Stress Disorder

“Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop following exposure to or witnessing of a (potentially) threatening event. A critical issue is to pinpoint the (neuro)biological mechanisms underlying the susceptibility to stress-related disorder such as PTSD, which develops in the minority of ~15% of individuals exposed to trauma.

Over the last few years, a first wave of epigenetic studies has been performed in an attempt to identify the molecular underpinnings of the long-lasting behavioral and mental effects of trauma exposure. The potential roles of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) in moderating or mediating the impact of severe stress and trauma are increasingly gaining attention. To date, most studies focusing on the roles of miRNAs in PTSD have, however, been completed in animals, using cross-sectional study designs and focusing almost exclusively on subjects with susceptible phenotypes.

Therefore, there is a strong need for new research comprising translational and cross-species approaches that use longitudinal designs for studying trajectories of change contrasting susceptible and resilient subjects. The present review offers a comprehensive overview of available studies of miRNAs in PTSD and discusses the current challenges, pitfalls, and future perspectives of this field.”

Here’s a 2017 Netherlands human study that similarly merits the US Veterans Administration’s attention:

Circulating miRNA associated with posttraumatic stress disorder in a cohort of military combat veterans

“Posttraumatic stress disorder (PTSD) affects many returning combat veterans, but underlying biological mechanisms remain unclear. In order to compare circulating micro RNA (miRNA) of combat veterans with and without PTSD, peripheral blood from 24 subjects was collected following deployment, and isolated miRNA was sequenced.

PTSD was associated with 8 differentially expressed miRNA. Pathway analysis shows that PTSD is related to the axon guidance and Wnt signaling pathways, which work together to support neuronal development through regulation of growth cones. PTSD is associated with miRNAs that regulate biological functions including neuronal activities, suggesting that they play a role in PTSD symptomatology.”


See the below comments for reasons why I downgraded this review’s rating.

https://link.springer.com/article/10.1007/s11920-018-0887-x “Stress Response Modulation Underlying the Psychobiology of Resilience” (not freely available)

How to cure the ultimate causes of migraines?

Most of the spam I get on this blog comes in as ersatz comments on The hypothalamus couples with the brainstem to cause migraines. I don’t know what it is about the post that attracts internet bots.

The unwanted attention is too bad because the post represents a good personal illustration of “changes in the neural response to painful stimuli.” Last year I experienced three three-day migraines in one month as did the study’s subject. This led to me cycling through a half-dozen medications in an effort to address the migraine causes.

None of the medications proved to be effective at treating the causes. I found one that interrupted the progress of migraines – sumatriptan, a serotonin receptor agonist. I’ve used it when symptoms start, and the medication has kept me from having a full-blown migraine episode in the past year.

1. It may be argued that migraine headache tendencies are genetically inherited. Supporting personal evidence is that both my mother and younger sister have migraine problems. My father, older sister, and younger brother didn’t have migraine problems. Familial genetic inheritance usually isn’t the whole story of diseases, though.

2. Migraine headaches may be an example of diseases that are results of how humans have evolved. From Genetic imprinting, sleep, and parent-offspring conflict:

“..evolutionary theory predicts: that which evolves is not necessarily that which is healthy.

Why should pregnancy not be more efficient and more robust than other physiological systems, rather than less? Crucial checks, balances and feedback controls are lacking in the shared physiology of the maternal–fetal unit.

Both migraine causes and effects may be traced back to natural lacks of feedback loops. These lacks demonstrate that such physiological feedback wasn’t evolutionarily necessary in order for humans to survive and reproduce.

3. Examples of other processes occurring during prenatal development that also lack feedback loops, and their subsequent diseases, are:

A. Hypoxic conditions per Lack of oxygen’s epigenetic effects are causes of the fetus later developing:

  • “age-related macular degeneration
  • cancer progression
  • chronic kidney disease
  • cardiomyopathies
  • adipose tissue fibrosis
  • inflammation
  • detrimental effects which are linked to epigenetic changes.”

B. Stressing pregnant dams per Treating prenatal stress-related disorders with an oxytocin receptor agonist caused fetuses to develop a:

  • “defect in glutamate release,
  • anxiety- and depressive-like behavior,

and abnormalities:

  • in social behavior,
  • in the HPA response to stress, and
  • in the expression of stress-related genes in the hippocampus and amygdala.”

1. What would be a treatment that could cure genetic causes for migraines?

I don’t know of any gene therapies.

2. What treatments could cure migraines caused by an evolved lack of feedback mechanisms?

We humans are who we have become, unless and until we can change original causes. Can we deal with “changes in the neural response to painful stimuli” without developing hopes for therapies or technologies per Differing approaches to a life wasted on beliefs?

3. What treatments could cure prenatal epigenetic causes for migraines?

The only effective solution I know of that’s been studied in humans is to prevent adverse conditions like hypoxia from taking place during pregnancy. The critical periods of our physical development are over once we’re adults, and we can’t unbake a cake.

Maybe science will offer other possibilities. Maybe it will be necessary for scientists to do more than their funding sponsors expect?

BTW, comments are turned off for the above-mentioned post. Readers can comment on this post instead.

Differing approaches to a life wasted on beliefs

Let’s start by observing that people structure their lives around beliefs. As time goes on, what actions would a person have taken to ward off non-confirming evidence?

One response may be that they would engage in ever-increasing efforts to develop new beliefs that justified how they spent their precious life’s time so far.

Such was my take on the embedded beliefs in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684598/pdf/PSYCHIATRY2017-5491812.pdf “Epigenetic and Neural Circuitry Landscape of Psychotherapeutic Interventions”:

“Animal models have shown the benefits of continued environmental enrichment (EE) on psychopathological phenotypes, which carries exciting translational value.

This paper posits that psychotherapy serves as a positive environmental input (something akin to EE).”

The author conveyed his belief that wonderful interventions were going to happen in the future, although, when scrutinized, most human studies have demonstrated null effects of psychotherapeutic interventions on causes. Without sound evidence that treatments affect causes, this belief seemed driven by something else.

The author saw the findings of research like A problematic study of oxytocin receptor gene methylation, childhood abuse, and psychiatric symptoms as supporting external interventions to tamp down symptoms of patients’ presenting problems. Did any of the paper’s 300+ citations concern treatments where patients instead therapeutically addressed their problems’ root causes?


For an analogous religious example, a person’s belief caused him to spend years of his life trying to convince men to act so that they could get their own planet after death, and trying to convince women to latch onto men who had this belief. A new and apparently newsworthy belief developed from his underlying causes:

“The founder and CEO of neuroscience company Kernel wants “to expand the bounds of human intelligence”. He is planning to do this with neuroprosthetics; brain augmentations that can improve mental function and treat disorders. Put simply, Kernel hopes to place a chip in your brain.

He was raised as a Mormon in Utah and it was while carrying out two years of missionary work in Ecuador that he was struck by what he describes as an “overwhelming desire to improve the lives of others.”

He suffered from chronic depression from the ages of 24 to 34, and has seen his father and stepfather face huge mental health struggles.”

https://www.theguardian.com/small-business-network/2017/dec/14/humans-20-meet-the-entrepreneur-who-wants-to-put-a-chip-in-your-brain “Humans 2.0: meet the entrepreneur who wants to put a chip in your brain”

The article stated that the subject had given up Mormonism. There was nothing to suggest, though, that he had therapeutically addressed any underlying causes for his misdirected thoughts, feelings, and behavior. So he developed other beliefs instead.


What can people do to keep their lives from being wasted on beliefs? As mentioned in What was not, is not, and will never be:

“The problem is that spending our time and efforts on these ideas, beliefs, and behaviors won’t ameliorate their motivating causes. Our efforts only push us further away from our truths, with real consequences: a wasted life.

The goal of the therapeutic approach advocated by Dr. Arthur Janov’s Primal Therapy is to remove the force of the presenting problems’ motivating causes. Success in reaching this goal is realized when patients become better able to live their own lives.


This post has somehow become a target for spammers, and I’ve disabled comments. Readers can comment on other posts and indicate that they want their comment to apply here, and I’ll re-enable comments.

Experience-induced transgenerational programming of neuronal structure and functions

The second paper of Transgenerational epigenetic inheritance week was a 2017 German/Israeli review focused on:

“The inter- and transgenerational effects of stress experience prior to and during gestation..the concept of stress-induced (re-)programming in more detail by highlighting epigenetic mechanisms and particularly those affecting the development of monoaminergic transmitter systems, which constitute the brain’s reward system..we offer some perspectives on the development of protective and therapeutic interventions in cognitive and emotional disturbances resulting from preconception and prenatal stress.”

The reviewers noted that human studies have difficulties predicting adult responses to stress that are based on gene expression and early life experience. Clinical studies that experimentally manipulate the type, level and timing of the stressful exposure aren’t possible. Clinical studies are also predicated on the symptoms being recognized as disorders and/or diseases.

The researchers noted difficulties in human interventions and treatments. Before and during pregnancy, and perinatal periods are where stress effects are largest, but current human research hasn’t gathered sufficient findings to develop practical guidelines for early intervention programs.


I’m not persuaded by arguments that cite the difficulties of performing human research on transgenerational epigenetic inheritance. There are overwhelming numbers of people who have obvious stress symptoms: these didn’t develop in a vacuum.

Researchers:

  • Design human studies to test what’s known from transgenerational epigenetic inheritance animal studies that will include documenting the subjects’ detailed histories with sufficient biometric samples and data obtained from their lineage.
  • Induce pregnant subjects to at least temporarily avoid what’s harmful for them and/or the offspring, in favor of what’s beneficial.
  • Document the subjects’ actions with history and samples.

I acknowledge that economic incentives may not be enough to get people to participate. I’m familiar with a juvenile sickle-cell study that didn’t get enough subjects despite offering free transportation and hundreds of dollars per visit. The main problem seemed to be that the additional income would be reported and threaten the caregivers’ welfare benefits.

Stop whining that your jobs are difficult, researchers. Society doesn’t owe you a job. Earn it – get yourself and the people in your organization motivated to advance science.

http://www.sciencedirect.com/science/article/pii/S014976341630731X “Experience-induced transgenerational (re-)programming of neuronal structure and functions: Impact of stress prior and during pregnancy” (not freely available)