On Primal Therapy with Drs. Art and France Janov

Experiential feeling therapy addressing the pain of the lack of love.

Contending with epigenetic consequences of violence to women

This 2016 UK review subject was the interplay of genomic imprinting and intergenerational epigenetic information transfer:

“A range of evolutionary adaptations associated with placentation transfers disproportionate control of this process to the matriline, a period unique in mammalian development in that there are three matrilineal genomes interacting in the same organism at the same time (maternal, foetal, and postmeiotic oocytes).

Genomic imprinting is absent in egg laying mammals and only around 6 imprinted genes have been detected in a range of marsupial species; this is in contrast to eutherian mammals where around 150 imprinted genes have been described.

The interactions between the maternal and developing foetal hypothalamus and placenta can provide a template by which a mother can transmit potentially adaptive information concerning potential future environmental conditions to the developing brain.

In circumstances either where the early environment provides inaccurate cues to the environmental conditions prevailing when adult due to rapid environmental change or when disruptions to normal neural development occur, the mismatch between the environmental predictions made during early development and subsequent reality may mean that an organism may have a poorly adapted phenotype to its adult environment. An appreciation of these underlying evolutionary salient processes may provide a novel perspective on the casual [causal] mechanisms of a range of health problems.

The concept of a brain that is not pathological in the classical sense but it is simply mismatched to its environment has been most extensively studied in the context of ancestral and early developmental nutrition. However, this concept can be extended to provide insights into the development of a range of alternative neural phenotypes.”

The review’s final sentence was:

“Examination of the adaptive potential of a range of neural and cognitive deficits in the context of evolutionary derived foetocentric brain and placental development, epigenetics and environmental adaptation may provide novel insights into the development and potential treatment of a range of health, neurological, and cognitive disorders.”

One of the reviewers was cited in Epigenetic DNA methylation and demethylation with the developing fetus, which the review cited along with Epigenetic changes in the developing brain change behavior.


Researchers who avoid hypotheses that can’t be proven wrong could certainly test the subject matter of this review if they investigated their subjects’ histories.

For example, let’s say a patient/subject had symptoms where the “150 imprinted genes” were implicated. What are the chances a clinician or researcher would be informed by this review’s material and investigate the mother’s and grandmother’s histories?

For clinicians or researchers who view histories as irrelevant busywork: how many tens of millions of people alive today have mothers who were fetuses when their grandmothers were adversely affected by violence? Wouldn’t it be appropriate to assess possible historical contributions of:

“The mismatch between the environmental predictions made during early development and subsequent reality”

to the patient’s/subject’s current symptoms?

http://www.hindawi.com/journals/np/2016/6827135/ “Placental, Matrilineal, and Epigenetic Mechanisms Promoting Environmentally Adaptive Development of the Mammalian Brain”

A human study of pain avoidance

This 2016 UK human study found:

“People differ in how they learn to avoid pain, with some individuals refraining from actions that resulted in painful outcomes, whereas others favor actions that helped prevent pain.

Learning in our task was best explained as driven by an outcome prediction error that reflects the difference between expected and actual outcomes. Consistent with the expression of such a teaching signal, blood-oxygen level-dependent (BOLD) responses to outcomes in the striatum were modulated by expectation.

Positive learners showed significant functional connectivity between the insula and striatal regions, whereas negative learners showed significant functional connectivity between the insula and amygdala regions.

The degree to which a participant tended to learn from success in avoiding than experiencing shocks was predicted by the structure of a participants’ striatum, specifically by higher gray matter density where the response to shocks was consistent with a prediction error signal. Higher gray matter density in the putamen (and lower gray matter density in the caudate) predicted better learning from shocks and poorer learning from success in avoiding shocks.”

The researchers termed the subjects’ pain responses “learning” instead of conditioning. The experiments presented no 100%-certain choices to avoid pain. The experiments were also rigged to force choices at similar rates among subjects because:

“Participants who learned more from painful outcomes developed a propensity to avoid gambling, whereas participants who learned more from success in preventing pain developed a propensity to gamble.”


Human responses to pain don’t arise out of nowhere. The subjects’ pain histories were clearly relevant, but weren’t investigated. The closest the study came to considering the subjects’ histories was:

“Before the experiment, participants completed an 80-item questionnaire composed of several measures of different mood and anxiety traits. Age, sex and mood and anxiety traits did not differ between participants later classified as positive and negative learners.”

Emotional content was neither included nor solicited. Emotions were inferred:

“Participants biased in favor of passive avoidance learning (i.e., learning what gambles should be avoided), striatal response to painful outcomes was consistent with an aversive prediction error, as seen in fear conditioning.”

As a result, there weren’t causal explanations for the subjects’ differing pain responses. How, when, and why did the behavioral, functional, and structural differences develop?


I didn’t see the level of detail needed to characterize striatal regions into the Empathy, value, pain, control: Psychological functions of the human striatum segments. I’d guess that the findings of “higher gray matter density in the putamen (and lower gray matter density in the caudate)” applied to the posterior putamen and the anterior caudate nucleus.

Two of the coauthors were also coauthors of If a study didn’t measure feelings, then its findings may not pertain to genuine empathy. The technique of Why do we cut short our decision-making process? was referenced.

http://www.pnas.org/content/early/2016/04/06/1519829113.full “Striatal structure and function predict individual biases in learning to avoid pain”

A one-sided review of stress

The subject of this 2016 Italian/New York review was the stress response:

“The stress response, involving the activation of the hypothalamic-pituitary-adrenocortical axis and the consequent release of corticosteroid hormones, is indeed aimed at promoting metabolic, functional, and behavioral adaptations. However, behavioral stress is also associated with fast and long-lasting neurochemical, structural, and behavioral changes, leading to long-term remodeling of glutamate transmission, and increased susceptibility to neuropsychiatric disorders. Of note, early-life events, both in utero and during the early postnatal life, trigger reprogramming of the stress response, which is often associated with loss of stress resilience and ensuing neurobehavioral (mal)adaptations.”


A key point in the review was the intentional dismissal of the role of GABA in favor of the role of glutamate:

“The changes in neuronal excitability and synaptic plasticity induced by stress are the result of an imbalance of excitatory (glutamatergic) and inhibitory (GABAergic) transmission, leading to long-lasting (mal)adaptive functional modifications. Although both glutamate and GABA transmission are critically associated with stress-induced alteration of neuronal excitability, the present review will focus on the modulation of glutamate release and transmission induced by stress and glucocorticoids.”

No particular reason was given for this bias. I inferred from the review’s final sentence that the review’s sponsors and funding prompted this decision:

“In-depth studies of changes in glutamate transmission and dendrite remodeling induced by stress in early and late life will help to elucidate the biological underpinnings of the (mal)adaptive strategies the brain adopts to cope with environmental challenges in one’s life.”

The bias led to ignoring evidence for areas the reviewers posed as needing further research. An example of relevant research the reviewers failed to consider was the 2015 Northwestern University study I curated in A study that provided evidence for basic principles of Primal Therapy that found:

“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.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812483/ “Stress Response and Perinatal Reprogramming: Unraveling (Mal)adaptive Strategies”

The cerebellum ages more slowly than other body and brain areas

This 2015 UCLA human study used the epigenetic clock to find:

“All brain regions have similar DNAm ages in subjects younger than 80, but brain region becomes an increasingly significant determinant of age acceleration in older subjects. The cerebellum has a lower epigenetic age than other brain regions in older subjects.

To study age acceleration effects in non-brain tissues as well, we profiled a total of 30 tissues of a 112 year old woman. The cerebellum exhibited the lowest (negative) age acceleration effect compared to the remaining 29 other regions. In contrast, bone, bone marrow, and blood exhibit relatively older DNAm ages.”

Limitations included:

  • “While the epigenetic age of blood has been shown to relate to biological age, the same cannot yet be said about brain tissue.
  • Cellular heterogeneity may confound these results since the cerebellum involves distinct cell types.
  • This cross-sectional analysis does not lend itself for dissecting cause and effect relationships.”

The study didn’t determine why the cerebellum was relatively younger. Some hypotheses are:

  • “Our findings suggest that cerebellar DNA is epigenetically more stable and requires less ‘maintenance work.’
  • The cerebellum has a lower metabolic rate than cortex.
  • It has far fewer mitochondrial DNA (mtDNA) deletions than cortex especially in older subjects, and it accumulates less oxidative damage to both mtDNA and nuclear DNA than does cortex.”

http://impactaging.com/papers/v7/n5/full/100742.html “The cerebellum ages slowly according to the epigenetic clock”

The current paradigm of child abuse limits pre-childhood causal research

As an adult, what would be your primary concern if you suspected that your early life had something to do with current problems? Would you be interested in effective treatments of causes of your symptoms?

Such information wasn’t available in this 2016 Miami review of the effects of child abuse. The review laid out the current paradigm mentioned in Grokking an Adverse Childhood Experiences (ACE) score, one that limits research into pre-childhood causes for later-life symptoms.


The review’s goal was to describe:

“How numerous clinical and basic studies have contributed to establish the now widely accepted idea that adverse early life experiences can elicit profound effects on the development and function of the nervous system.”

The hidden assumption of almost all of the cited references was that these distant causes can no longer be addressed. Aren’t such assumptions testable here in 2016?

As an example, the Discussion section posed the top nine “most pressing unanswered questions related to the neurobiological effects of early life trauma.” In line with the current paradigm, the reviewer assigned “Are the biological consequences of ELS [early life stress] reversible?” into the sixth position.

If the current paradigm encouraged research into treatment of causes, there would probably already be plenty of evidence to demonstrate that directly reducing the source of the damage would also reverse the damaging effects. There would have been enough studies done so that the generalized question of reversibility wouldn’t be asked.

Aren’t people interested in human treatments of originating causes so that their various symptoms don’t keep bubbling up? Why wouldn’t research paradigms be aligned accordingly?


The review also demonstrated how the current paradigm of child abuse misrepresents items like telomere length and oxytocin. Researchers on the bandwagon tend to forget about the principle Einstein expressed as:

“No amount of experimentation can ever prove me right; a single experiment can prove me wrong.”

That single experiment for telomere length arrived in 2016 with Using an epigenetic clock to distinguish cellular aging from senescence. The seven references the review cited for telomere length that had “is associated with” or “is linked to” child abuse findings should now be viewed in a different light.

The same light shone on oxytocin with Testing the null hypothesis of oxytocin’s effects in humans and Oxytocin research null findings come out of the file drawer. See their references, and decide for yourself whether or not:

“Claimed research findings may often be simply accurate measures of the prevailing bias.”

http://www.cell.com/neuron/fulltext/S0896-6273%2816%2900020-9 “Paradise Lost: The Neurobiological and Clinical Consequences of Child Abuse and Neglect”

Beneficial epigenetic effects of mild stress with social support during puberty

This 2016 Pennsylvania rodent study found:

“Stress in the context of social support experienced over the pubertal window can promote epigenetic reprogramming in the brain to increase the resilience to age-related cognitive decline in females.

These findings are actually consistent with previous studies showing that some amount of adversity, or adversity under more favorable circumstances such as social support or a protective gene polymorphism, provides a measure of ‘grit’ in coping with later life challenges.

Our findings provide a unique perspective on this relationship, as they highlight the important link between experience during the pubertal window and cognitive health during aging.”

The researchers made efforts to further investigate causes of unexpected results, such as:

“Peripubertal stress alone did not significantly alter Barnes maze performance in aging compared to aged Controls. Mice that had experienced stress with concurrent social support (CVS + SI) actually performed better than Control aged mice, specifically in learning the reversal task faster.

Peripubertal stress had no effect on corticosterone levels in response to an acute restraint stress or in sensorimotor gating and baseline startle reactivity.”

The investigations led to epigenetic findings:

“Consistent with our behavioral findings, stress in the context of social interaction resulted in long-term reprogramming of gene expression in the PFC [prefrontal cortex]. While there were no differentially expressed genes between Control and CVS females, there were 88 genes that were significantly different between Control and CVS + SI groups. Of the genes that were downregulated, a large portion (23 genes; 35%) were microRNAs.

We found that the PFC transcriptome of CVS + SI aged females was significantly enriched for predicted targets of the 23 microRNAs that were downregulated in the PFC in these mice. This suggests that microRNAs represent a mode of regulation capable of enacting far-reaching programmatic effects, and are a critical epigenetic gene expression regulatory mechanism.”

Applicability to humans was suggested by associations such as:

“A single microRNA can target more than a hundred different mRNA targets, and more than 45,000 conserved microRNA binding sites have been annotated in the 3′ UTR of 60% of human genes.”


A few limitations were noted:

“Given that mice at this age (1 year) are commonly compared to ‘late middle aged’ humans, later aging time points may yield differences in this group. Alternatively, it is possible that there was an effect of peripubertal stress that was not long-lasting due to the mild nature of our chronic stress model.

To include early neglect as a part of the stressor experience, CVS females were weaned one week earlier (PN21) than Control and CVS + SI mice. The addition of the stress of this earlier weaning likely poses a significant contribution to the programming of the PFC.”

One of the study coauthors was also a coauthor of:

http://press.endocrine.org/doi/pdf/10.1210/en.2015-1876 “Peripubertal stress with social support promotes resilience in the face of aging”