Cortisol

Inflexible behavior may be a byproduct of stress

gettingwell4 2-3 stars Required further work, Cortisol, Neurochemicals, Stress ,

This 2015 German human study found:

“15-mo-old infants exposed to stress thereafter kept performing a previously effective action, even after the action suddenly became ineffective.

Infants in a no-stress control group flexibly adjusted their behavior by disengaging from the newly ineffective action in favor of exploring an alternative action.

This finding demonstrates that stress impairs infants’ ability to adjust their behavior to changing circumstances.”

The primary measurement of stress levels was cortisol. Stressful conditions were:

  • A stranger sat down next to them;
  • A dancing robot played loud music and moved around;
  • The infant’s caregivers left the room for up to four minutes.

News coverage stated that the study’s design was an adaptation of experiments that produced the same findings in adults. But would adult humans be stressed by being left alone for four minutes?

It’s likely that animal studies were the basis for some of this study’s experiments, as in the If research provides evidence for the causes of stress-related disorders, why only focus on treating the symptoms? study:

“Maternal separation in rodents is a useful model of early-life stress that results in enduring physiological and behavioral changes that persist into adulthood.”

A study limitation was that it involved just 26 infants.

http://www.pnas.org/content/112/41/12882.full “Stress impairs cognitive flexibility in infants”

Leaky gates, anxiety, and grocery store trips without buying list items

gettingwell4 4-5 stars Advanced knowledge, Brain development, Brainstem, Cerebrum, Cortisol, Dopamine, Epigenetics, Limbic system, Lower brain, Memory, Neurochemicals, Oxytocin, Primal Therapy, Serotonin, Stress , , , , , , , ,

An interview with Jeff Link, the editor of Dr. Arthur Janov’s 2011 book “Life Before Birth: The Hidden Script that Rules Our Lives” with Ken Rose:

“Even further confirmation for some of the views of Janov, that maybe weren’t widely accepted for a time, it’s new research now being done into memory and what a lot of scientist are seeing, a lot of different studies is that memory reactivates the same neuroimpulses that were initially firing off when the event happened.

So a traumatic event when you remember it, the act of remembering it is actually creating a neuromirror of what went on initially.

In a lot of ways that is what Primal Therapy is attempting to do; is to go back to that place and reconnect, or as it’s sometimes referred to, reconsolidate the brain state so that real healing can take place.”

Transcript (part 4 of 6): http://cigognenews.blogspot.com/2015/09/ken-rose-on-life-before-birth-part-46.html

MP3: http://www.pantedmonkey.org/podcastgen/download.php?filename=2011-12-15_1300_what_now_jeff_link.mp3

Who’s responsible for your physical and emotional health?

gettingwell4 2-3 stars Required further work, Cortisol, Glutamate, Neurochemicals, Stress, Testosterone , ,

This 2015 Houston human study measured 575 metabolites in 72 biochemical pathways. The researchers used “nontargeted metabolomics” with next-generation gene sequencing to:

“Take account of human individuality in genes, environment, and lifestyle for early disease diagnosis and individualized therapy.”

The 80 subjects were 45 men and 35 women, average age of 54, in “normal health with complete medical records and three-generation pedigrees.” The subjects all had college degrees, and were members or spouses of members of an upper-level socioeconomic organization.

The study’s range of 575 metabolites certainly cast a shadow over studies such as Running a marathon, cortisol, depression, causes, effects, and agendas that singled out 1 metabolite and tortured its data until it confessed a relationship that supported the preferred agenda.

Limitations of this study that weren’t mentioned by the researchers included:

  1. There were no specific target levels for each metabolite, which could lead to a misinterpretation that a “healthy” blood plasma level of a metabolite would always be the norm of the 80 subjects. This interpretation of each metabolite’s ideal level could be reinforced by the study calculating z-scores and P values of each individual’s measurement’s position within the cohort. The researchers stated:

    “The identification of abnormal metabolic signatures was restricted by the relatively small number of subjects in the cohort.”

    but that limitation wasn’t the flip side of omitted optimal levels.

  2. The metabolite measurements were mainly a one-time event although a series of measurements may have been more appropriate. Many of these metabolite levels vary with the time of day, what each individual had recently eaten, what each individual’s recent stress levels were, etc. This limitation may have been one of the sources for what the researchers noted:

    “Statistical analysis revealed a considerable range of variation and potential metabolic abnormalities across the individuals in this cohort.”

  3. There was no assessment of the relative contributions of epigenetic and genetic factors when discussing possible genetic impacts.

Regarding 1. above:

  • It may be interesting to compare an individual to their peers and to other sources of information. However, when it comes time for “individualized therapy” because of a metabolic measurement that’s an outlier compared to these other sources, an individual’s history also matters.
  • Each individual’s history could be used as a guide for optimal levels of some metabolites. For example, an optimal goal for “individualized therapy” for low testosterone levels of each of the 54-year old male subjects could be each individual’s previous higher levels of three decades earlier. It wouldn’t make sense for a 54-year old male to start testosterone therapy with a goal of raising his low levels to the non-therapeutic, low-level norm of other 54-year old males.

Regarding 2. above:

Regarding 3. above:

  • As an example of unconsidered epigenetic factors, there was a discussion of acetaminophen metabolites because:

    “The identification of at-risk populations could improve therapeutic options for individual patients and prevent adverse clinical outcomes.”

    The researchers specifically compared and contrasted two subjects with the highest levels of acetaminophen metabolites, and concluded:

    “These observations may suggest that volunteer 3976 was sensitive to acetaminophen-induced liver injury, whereas volunteer 3958 could tolerate acetaminophen well. This difference may relate to their cellular capability to maintain GSH [reduced glutathione] levels in response to acetaminophen. We searched for a genetic basis of this variation in acetaminophen degradation/toxic metabolism without success.”

  • The researchers shouldn’t have left the discussion hanging at this point. There’s no reason in 2015 for researchers to not investigate the contribution of epigenetic factors to:

    “Take account of human individuality in genes, environment, and lifestyle.”

I was put off by the researchers statement:

“The volunteer’s cardiologist was informed of this observation to monitor possible drug interaction or toxicity.”

It appeared that the researchers bypassed one subject and informed the subject’s doctor directly when the subject was doing something the researchers considered detrimental to the subject’s health. I don’t know if the subject gave prior consent to be bypassed, though, because I didn’t see either study’s consent terms in the below linked material.

A few concluding questions:

  • If it’s alright for personal health information to be transmitted without the consent of highly-educated, upper-level socioeconomic subjects, what can the rest of the population expect?
  • Is “individualized therapy” best done through individual choices, or by forcing an individual to conform to expert opinion?
  • Who is responsible for an individual’s physical and emotional health?

http://www.pnas.org/content/112/35/E4901.full “Plasma metabolomic profiles enhance precision medicine for volunteers of normal health”

http://www.pnas.org/content/110/42/16957.full “Personalized genomic disease risk of volunteers” (2013 original study with the same subjects)

The effects of inescapable, uncontrollable, repeated stress on the hippocampus

gettingwell4 4-5 stars Advanced knowledge, Amygdala, Cerebrum, Cortisol, Epigenetics, Glutamate, Hippocampus, Limbic system, Neurochemicals, Stress , , ,

This 2015 MIT rodent study found:

“Behavioral stress impairs cognitive function via activation of a specific direct neural circuit from the basolateral amygdala to the dorsal hippocampus. Moreover, we delineate a molecular mechanism by which behavioral stress is translated to hippocampal dysfunction via a p25/Cdk5 (cyclin-dependent kinase 5)-dependent pathway and epigenetic alterations of neuroplasticity-related gene expression.”

The researchers made several intermediate findings to develop their main finding:

1. “Repeated stress is accompanied by

  • generation of p25,
  • up-regulation and phosphorylation of glucocorticoid receptors,
  • increased HDAC2 [the gene encoding the histone deacetylase 2 enzyme] expression, and
  • reduced expression of memory-related genes [most, but not all that were tested] in the hippocampus.”

2. “BLA [basolateral amygdala] activation is both necessary and sufficient for stress-associated molecular changes and memory impairments.”

3. “This effect [2. above] relies on direct glutamatergic projections from the BLA to the dorsal hippocampus.”

4. “p25 generation is necessary for the stress-induced memory dysfunction.”

From the Results section:

“Control mice showed a significant preference for the novel over the familiar object or location, whereas RFS [repetitive foot shock]-treated mice performed no better than chance.”

The subject adult mice underwent:

“Inescapable, uncontrollable repeated stress.”

Do humans also experience impaired “cognitive function” and “hippocampal dysfunction” and “epigenetic alterations of neuroplasticity-related gene expression” caused by “inescapable, uncontrollable repeated stress”?

And what are the real histories of people who aren’t curious, who don’t show “a significant preference for the novel over the familiar object or location”?

http://www.pnas.org/content/112/23/7291.full “Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway”

Stress in early life can alter physiology and behavior across the entire lifespan

gettingwell4 4-5 stars Advanced knowledge, Amygdala, Brain development, Cerebrum, Cortisol, Epigenetics, Hippocampus, Immune system, Limbic system, Memory, Neurochemicals, Stress, Testosterone , , , , , , , ,

I’ll quote a few sections of this 2014 summary of 111 studies concerning stress, including the authors’ research:

“The brain is the central organ of stress and adaptation to stressors because:

  • It not only perceives what is threatening or potentially threatening and initiates behavioral and physiological responses to those challenges,
  • But also is a target of the stressful experiences and the hormones and other mediators of the stress response.

The stress history of parents is a significant factor in the resilience of their offspring.

Environmental stress transduces its effects into lasting changes on physiology and behavior, which can vary even among genetically identical individuals.

Stress in early life can alter physiology and behavior across the entire lifespan.

Structural stress memory is even more apparent with regard to gene expression in stress-sensitive brain regions like the hippocampus.

Individual history is important and that there is a memory of stress history retained by neurons at the cellular level in regions like the hippocampus.

Stress has a number of known effects on epigenetic marks in the brain, producing alterations in DNA methylation and histone modifications in most of the stress-sensitive brain regions examined, including the hippocampus, amygdala, and prefrontal cortex.”

It seemed to be taboo to note that most of – and the largest of – detrimental effects of stress occurred during womb-life in the mother’s environment. The authors instead opted for a politically correct “the stress history of parents” phrase.

Referenced studies had findings relevant to the earliest periods of life, including Figure 1:

interactions

“Those organs that show the highest levels of retrotransposon [a repeat element (mobile DNA sequences often involved in mutations) type formed by copy-and-paste mechanisms] activity, such as the brain and placenta, also seem to be both steroidogenic and steroid-sensitive.”

However, Figure 1 was given a beneficial context, and other studies’ findings weren’t mentioned in their contexts of detrimental effects on fetuses of mothers who were stressed while pregnant.

http://www.pnas.org/content/112/22/6828.full “Stress and the dynamic genome: Steroids, epigenetics, and the transposome”

Running a marathon, cortisol, depression, causes, effects, and agendas

gettingwell4 < 0 Detracted from science, Cerebrum, Cortisol, Limbic system, Lower brain, Memory, Neurochemicals, Stress , ,

Let’s imagine that you decide you want to run a marathon. You haven’t run in six months, and you know you’ll have to train.

On the first day of training, as you run your first mile a friend pops out of nowhere and says, “You’re sweating! That means you’re going up to Mile 14 today! Good job, you’re on your way!”

You may appreciate the encouragement, but would a friend’s assessment have anything to do with your physical reality? Before you’ve run one mile, can an observer of your sweat say with certainty that you’ll run 14 miles on your first day of training?

Yeah. That’s how I felt when reading this 2014 UK study that found:

“Adolescent boys who have high levels of stress hormone ‘cortisol’ along with some symptoms of depression are at a 14 times higher risk of the condition than their peers.”

The researchers latched onto teenagers (12-16 years old, mean 13.7) to assess a psychiatric condition. They stated that a physical effect as common as visible sweat was a biomarker that predicted where some of the teenagers were going with their lives.

The study’s only physical measurements were cortisol from saliva samples at 8:00 a.m. on four consecutive days, then repeated a year later. For comparison, a standard lab test is to measure cortisol from saliva taken four times in one day at 9:00 a.m., 1:00 p.m., 5:00 p.m., and 9:00 p.m.

Cortisol is an effect of multiple potential causes, including stress, which itself is often an effect of multiple potential causes. One common cause of stress and its cortisol byproduct is diet, for example, when a person consumes caffeine.

“Mean time between waking and morning-cortisol collection was 50 min.”

I found it hard to believe that teenagers who:

  • woke up at 7:10 a.m.,
  • gulped down who knows what for breakfast,
  • got ready for, and then
  • went to school for an 8:00 a.m. cortisol test

wouldn’t have relatively “elevated morning cortisol” from the resultant stress.

Subjects self-reported depressive symptoms via a 33-item questionnaire initially and again every four months. They were interviewed for psychiatric diagnoses.

The largest separator used for stratification within subjects was an autobiographic memory test. Without this test, the study wouldn’t have made its main finding, so let’s look at the test’s details:

“Anxious and depressed adolescent patients report significantly elevated levels of over-general categoric memories compared with well controls. Six positive and six negative words are presented on flashcards in pseudorandom order, and participants are instructed to recall a particular memory of an event in their life after each word. Sixty seconds were allowed for each response.

Responses were categorized as specific if they referred to an event with a specific time and place, lasting no longer than 1 d[ay]. Responses were considered overgeneral if they formed a general class of repeated events.”

We can see that the autobiographical memory test only considered the subjects’ verbal expressions – within a short time period – of their recalls of emotionally triggered memories. As informed by the principles described in Agenda-driven research on emotional memories, the recall of an emotional memory is a product of the cerebrum responding to input from limbic system and lower brain areas. When someone describes their recall of an emotionally triggered memory, it’s yet another level further removed from the brain areas that store emotional memories.

We can also see that test scores of the subjects’ verbal expressions aren’t capable of providing any etiologic evidence for an effect of high cortisol. A correlation is the best that could ever be shown by an autobiographic memory test. Again, the study’s main finding hinged on this third-order observational method of trying to figure out what’s going on inside subjects’ brains.

The researchers developed a control group, and made only a token attempt to trace the control group teenagers’ histories:

“The primary caregiver was interviewed about the quality of the family environment in three epochs (0–5, 6–11, and 12–14 y of age).

Four classes were found: optimal class, aberrant parenting, discordant, and hazardous.”

Were we supposed to believe that any primary caregiver would tell the truth about anything in a teenager’s history that indicated they had damaged their child? Good luck with that.

Anyway, the researchers didn’t act as though teenagers’ histories had any significant relationships with any present or future conditions. Their ahistoric biases showed by subsequently processing the entire history of each of the control group teenagers into a 1 or a 0 for the model.

The researchers then modeled this binary assessment to be relevant to the study’s main subjects!

The researchers’ agenda led to predetermined findings. Was the reviewer onboard with this agenda?

  • By disregarding the main subjects’ histories, it couldn’t provide etiologic evidence for any present or future effects.
  • By measuring only early morning cortisol, are we surprised that model numbers could be processed into some correlation?
  • Comparing this sole measurement to 325 measurements taken of subjects in Assessing a mountain climber’s condition without noticing their empty backpack made me wonder about the study designers’ real intentions.

News coverage of the study jumped on its flimsy finding to demand that something must be done. What did researchers offer teenagers who needed help?

  • After citing research that:

    “Showed null effects for two active treatments [cognitive behavioral therapy (CBT) and attentional training, respectively]”

    they recommended some unspecific:

    “New models of public mental health education and intervention in the youth population.”

  • After citing research that found:

    “Current diagnostic classifications [e.g., the Diagnostic and Statistical Manual for Mental Disorders (DSM) and the International Classification of Diseases (ICD)] have proved to have low diagnostic validity for investigations on the etiology, prevention, or treatment of MD [major depression]“

    the study relied on these diagnoses anyway, and then disclaimed:

    “It may also be the case that current classifications, as used in this study, such as DSM and ICD are simply not optimally specified.”

They didn’t make their case that “elevated morning cortisol” effect was an adequate biomarker for teenagers who needed help. They did a disservice to their subjects by neither investigating nor providing any etiologic evidence for observed effects.

Who really benefited from this underlying agenda? I didn’t see that it was teenagers who may have actually needed assistance.

Did the study’s funders know that these efforts had enormous lacks? And what did:

“New models of public mental health education and intervention in the youth population”

really mean?

http://www.pnas.org/content/111/9/3638.full “Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms”

A possible link between stress responses and human cancers?

gettingwell4 4-5 stars Advanced knowledge, Brain development, Cortisol, Epigenetics, Neurochemicals, Primal Therapy, Stress ,

This 2015 UK rodent study found:

“An unexpected role for the GR [glucocorticoid receptor] in promoting accurate chromosome segregation during mitosis.

We also identify reduced GR expression in several common human cancers, thereby implicating GR as a novel tumor suppressor gene.”

One of the researchers said:

“Cancer is caused by cell division going wrong, but no one has previously looked at the role GR has to play in this process. It’s now clear that it is vital.”

From the study:

“Our findings now show that GR function regulates accurate mitotic progression, with clear implications for human health.

Add a previously unidentified perspective to GR action in cell division, affecting mitotic spindle function.

It may be that this action can be targeted by specific ligands, potentially opening up new therapeutic approaches to treat common cancers.”

The Translating PTSD research findings from animals to humans study also found reduced expression of glucocorticoid receptor genes, which appeared in some rodents after stress. Unfortunately, those researchers’ priorities weren’t to research the causes of this reduced expression.

One relevant hypothesis of Primal Therapy is that trauma in the earliest parts of human life epigenetically impairs the proper functioning of human development processes. A follow-on hypothesis is that the arrival of diseases in later life may be traceable back to the damage done during early-life development processes.

An example of this would be that a developing fetus adapts to being constantly stressed by an anxious and stressed mother. When the changes persist after birth, they may present as maladaptations of the infant to a non-stressful environment. These enduring changes may be among the causes of symptoms decades later such as over- and/or under-reactions to stress.

It seems possible that further research in these areas may find links among human stress responses and human cancers. The current study suggested that the glucocorticoid receptor may play a part in these links.

http://www.pnas.org/content/112/17/5479.full “Glucocorticoid receptor regulates accurate chromosome segregation and is associated with malignancy”

Translating PTSD research findings from animals to humans

gettingwell4 0-1 star Wasted resources, Amygdala, Cortisol, Hippocampus, Limbic system, Neurochemicals, Stress

This 2014 rodent study stressed the animals, measured their stress responses, then killed them and sampled genes in their amygdala, hippocampus, and blood. The researchers found that glucocorticoid receptor signaling genes were the primary pathway associated with “exposure-related individual differences“ in stress responses for the amygdala and blood. This pathway also placed first for the hippocampus in female rats (glucocorticoid receptor was second in male rats and prostate cancer signaling was first).

I’ll quote one press article’s coverage to show where the researchers wanted to go with the study’s findings:

“We found that most of the genes and pathways that are different in PTSD [post-traumatic stress disorder]-like animals compared to resilient animals are related to the glucocorticoid receptor, which suggests we might have identified a therapeutic target for treatment of PTSD.”

How about this lead sentence:

“There may some day be a blood test to determine whether someone suffers from Post-Traumatic Stress Disorder or is at risk for the psychiatric condition.”

Here’s another article’s paraphrase of a different researcher:

“Those are genes that become activated in the presence of stress. Like a key fitting into a lock, the hormone corticosterone, produced naturally by the body, connects to the receptor and has a calming effect.

In some rodents, and apparently in some people, the pathway appears to be defective, and this puts them at higher risk for PTSD.”

Also, from the study’s abstract:

“Corticosterone treatment 1 h[our] after PSS [predator-scent-stress]-exposure prevented anxiety and hyperarousal 7 d[ays] later in both sexes, confirming the GR [glucocorticoid receptor] involvement in the PSS behavioral response.”

Like other researchers continue to do, they stopped this study short of finding causes for the effects:

  1. What were the causes for genes in the glucocorticoid receptor signaling pathway being differentially expressed? “Exposure-related individual differences” isn’t a causal finding.
  2. If this pathway is “defective,” what exactly happened to make it that way?
  3. Did dampening the effects of stress with a shot of cortisol one hour after the stress treat the cause such that the rats were cured? Since the readers of the study and associated articles were led to infer that this treatment was a cure, why destroy the treated animals afterwards before the proofs of long-term efficacy were thoroughly documented and tested?

When studies like this are carried forward with humans, researchers should try to find the causes for these effects. It isn’t sufficient to pretend that there aren’t early-life causes for these effects. Such a pretense leads to the follow-on pretense that later-life consequences are mysteries such as “exposure-related individual differences” and not effects.

Researchers should act like the subjects are feeling human beings who can participate in treatments of both the causes and effects. They should remember that humans are not lab rats who need to be fixed.

http://www.pnas.org/content/111/37/13529.full “Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes”

Can a Romanian orphan give informed consent to be an experimental subject?

gettingwell4 < 0 Detracted from science, Amygdala, Brain development, Cerebrum, Cortisol, Hypothalamus, Limbic system, Neurochemicals, Stress , ,

This 2015 study used Romanian orphans as lab rats for findings of which I failed to see the value. The world didn’t really need any further research to demonstrate that foster care would be better for a child than staying in an orphanage.

The researchers placed the orphans in five separate stressful situations, and measured their cortisol and DHEA-S levels, along with their electrocardiograph and impedance cardiograph activity. The findings were:

“Children who were removed from the Romanian institutions and placed with foster parents before the age of 24 months had stress system responses similar to those of children being raised by families in the community.

The children raised in institutions showed blunted responses in the sympathetic nervous system, associated with the flight or fight response, and in the HPA axis, which regulates cortisol.”

One unsupported assertion from the researchers was:

“We provide evidence for a causal link between the early caregiving environment and stress response system reactivity in humans with effects that differ markedly from those observed in rodent models.”

The researchers stated that rodent studies have converged to find:

“Early-life adversity results in hyperreactivity of the sympathetic nervous system (SNS) and hypothalamic–pituitary–adrenal (HPA) axis.”

It’s baloney that the same results from early life adversity in rodents haven’t also been present in humans. Even the lead researcher herself said in a news article:

“More significantly, McLaughlin said, their [the orphans] stress response systems might have been initially hyperactive at earlier points in development, then adapted to high levels of stress hormones.”

The difference was that the rodents were monitored 24/7 until researchers killed and dissected them. The children’s periods of adversity likely started while in the womb, and their lives had been monitored for research purposes sporadically after their births.

Everybody knows that just because adverse events and effects in these children’s lives weren’t recorded by researchers didn’t mean these effects weren’t present at some point.

Particularly irksome was another unsupported assertion from the lead reviewer:

“The children involved in the study are now about 16 years old, and researchers next plan to investigate whether puberty has an impact on their stress responses. It could have a positive effect, McLaughlin said, since puberty might represent another sensitive period when stress response systems are particularly tuned to environmental inputs. “It’s possible that the environment during that period could reverse the impacts of early adversity on the system,” she said.”

No, this is NOT possible. We may as well expect an apple to fall upward.

The impacts of early adversity persist with enduring physiological changes as shown in experimental studies. Studies have NOT provided evidence that the subjects’ environment can cause the effects of complete reversal of all these changes, no matter the stage of life of the subjects.

This point was addressed in The effects of early-life stress are permanent alterations in the child’s brain circuitry and function rodent study:

“The current study manipulates the type and timing of a stressor and the specific task and age of testing to parallel early-life stress in humans reared in orphanages.

The results provide evidence of both early and persistent alterations in amygdala circuitry and function following early-life stress.

These effects are not reversed when the stressor is removed nor diminished with the development of prefrontal regulation regions.”

That study had the same reviewer as the current study. The current study’s lead researcher knew or should have known of this and other relevant research. She knew or should have known of the irreversibility of critical periods, during which developments either occurred or were forever missed.

Did the lead researcher make assertions not supported by the study or relevant research – assertions made counter to her scientific knowledge – show her unease about treating the orphans as lab rats? Was there was some other agenda in play?

The larger problem was the study’s informed consent with this group of Romanian orphans. If you were in contact with a damaged person, and implicitly gave them hope that you would improve their life, then who are you as a feeling human being when you don’t personally carry through? Does the legal documentation matter?

Also, I’ve noticed problems with several studies that had this particular reviewer:

Add the current study to the list.

http://www.pnas.org/content/112/18/5637.full “Causal effects of the early caregiving environment on development of stress response systems in children”

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Assessing a mountain climber’s condition without noticing their empty backpack

gettingwell4 2-3 stars Required further work, Acetylcholine, Cortisol, Neurochemicals, Stress

A metaphor: for a mountain climber, which point has the most influence on their condition during the climb?

  • The path ahead?
  • The current situation?
  • The recent past?
  • The starting point?
  • The preparations?

Hard to say? Once the climb has started and until it’s finished, though, are there any points at which the preparations have no influence?

Let’s imagine that factors beyond the climber’s control ruined their preparations, leaving them with no reserves and a limited capability to adapt to environmental changes.

Let’s imagine further that researchers take initial physical and psychological measurements of the climber’s condition at an arbitrary point of the ascent or descent. Due to the design of their measurement system, however, they don’t discover that this climber has an empty backpack.

When the researchers interpret the results, will they understand how the climber’s measurements were influenced by the ruined preparations?  end metaphor

A 2014 Israeli study primary finding was of:

“Fear of terror-induced annual increases in resting heart rate.”

The researchers took 325 measurements each “of 17,380 apparently healthy volunteers” who had “consistent exposure to terror threats.”

The study was opaque in some areas. For example, what was the content and handling of a 4-item anxiety questionnaire?

The supplementary material showed that the headlined “fear of terror” term involved three disparate factors:

  • feeling unsafe;
  • fear of crowds; and
  • anxiety about future harm.

I’d like to understand the bases of why the researchers and the reviewer felt it was appropriate that:

“The scores on these items were averaged to yield a continuous FOT [fear-of-terror] score.”

The researchers probably had sufficient measurements of the subjects’ current conditions. They didn’t have a frame of reference that incorporated the present data with contextual information from each individual’s history back to the earliest parts of their life.

Lacking the links provided by such a framework, the researchers likely misassessed measurements that were influenced by how the subjects’ backpacks were packed.

http://www.pnas.org/content/112/5/E467.full “Fear and C-reactive protein cosynergize annual pulse increases in healthy adults”

Epigenetic DNA methylation and demethylation with the developing fetus

gettingwell4 5+ stars Premium, Brain development, Cortisol, Epigenetics, Hypothalamus, Limbic system, Neurochemicals, Oxytocin, Serotonin , ,

This extremely dense and informative 2014 UK summary study provided details about genomic imprinting:

“An unusual epigenetic process in that it is heritable and results in autosomal gene expression according to parent of origin.”

Several notes of interest:

  • Figure 3 had a fascinating sketch of how the fetus caused the mother’s hypothalamus to:

    “Determine forward maternal planning by directing/orchestrating maternal physiology and postnatal maternalism to synchronize with development of the fetus.”

  • Figure 4 followed up with a flowchart of how – with a female fetus – coexistence of three matrilineal generations in the pregnant female (her, the fetus, and the grandmother’s influence on the developing fetus’ ovarian oocytes) enabled intergenerational forward planning.
  • The study briefly noted significance of genomic imprinting on male sexual behavior, where, if processes didn’t proceed normally at this early stage of a male fetus’ development, could result in suboptimal adult behavior that didn’t change with experience.

F4.large

I’ll quote a few other unrelated passages that caught my eye.

“Reproductive success of mammals also places a considerable burden on matrilineal time and energy, with some 95% of mammalian female adult life committed to pregnancy, lactation, and maternal care.

Offspring that receive optimal nourishment and improved maternal care will be predisposed to develop a hypothalamus that is both genetically and epigenetically predisposed to this same type of good mothering.

The fetus controls its own destiny in times of acute starvation, especially in the last trimester of pregnancy, by short-term sacrifice of its placenta to preserve resources critical for brain development.”

http://www.pnas.org/content/112/22/6834.full “Genomic imprinting, action, and interaction of maternal and fetal genomes”

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Pulling on the chain of causes and effects with insulin resistance

gettingwell4 0-1 star Wasted resources, Cortisol, Dopamine, Neurochemicals, Stress , , ,

This 2015 Harvard rodent study found multiple undesirable symptoms and attributed the cause to insulin resistance, which is itself a symptom.

Humans most often develop the symptom of insulin resistance due to causes other than genetics, such as a result of abnormal eating behaviors, which are symptoms of other causes.

Use of insulin-resistant-due-to-genetics mice may have misdirected the researchers to lose focus that their ultimate task was to find ways that their research can help humans. If helping humans was the researchers’ focus, it may have occurred to them to develop evidence for how “something” caused symptoms such as abnormal eating behaviors, that in turn caused a symptom of insulin resistance.

The study’s unexamined causes included why genetically insulin-resistant mice developed symptoms of anxiety and depressive-like behaviors between early adulthood and late middle age. Examples of undesirable symptoms described in the supplementary material included:

  • Higher body weight in late middle age, especially in females;
  • Depressive-like behavior in both sexes by late middle age;
  • Higher corticosterone levels in both sexes by late middle age, even when unstressed; and
  • Higher corticosterone levels in late middle age when stressed, especially in males.

It’s remarkable how researchers consistently get caught in a loop of studying only symptoms, paying little attention to studying causes, then suggesting various medications and treatments to suppress the studied symptoms.

It’s not surprising then that there’s no explanation of why and how symptoms develop. The study designs seldom include trying to show causes for the effects in the first place!

http://www.pnas.org/content/112/11/3463.full “Insulin resistance in brain alters dopamine turnover and causes behavioral disorders”

Dr. Arthur Janov interview on his 2011 book Life Before Birth: The hidden script that rules our lives

gettingwell4 4-5 stars Advanced knowledge, Brain development, Cerebrum, Cortisol, Epigenetics, Limbic system, Lower brain, Neurochemicals, Primal Therapy, Stress, Telomeres , , , , , ,

Dr. Arthur Janov’s 2011 book “Life Before Birth: The hidden script that rules our lives” describes problems that start in the earliest parts of our lives, when epigenetic changes due to trauma in the womb affect our development.

“The science has changed. When I first started out 44 years ago, there was nobody who could understand it, or agree, especially the professionals. Now all, or a great deal of the current research, is backing up everything I say.

I’m saying that this therapy is really a matter of life and death now. I should probably start at the beginning and say that there’s trauma in the womb. We need to set back the clock so that we take account of trauma that occurs while our mother is carrying that has lifelong consequences for how long we live, for example. There’s a current research study that shows that as you get more traumatized in the womb, your life expectancy is much shorter.

When you get rid of the childhood pain that happened way back when – and there are ways to do it – you will live much longer. So truly, a proper therapy now is a matter of life and death. Not only because your life expectancy is shorter when you have trauma, but you get sick earlier, you have diabetes, Alzheimer’s, all kinds of diseases on your way to your death, which makes life very uncomfortable.

But that’s just part of what we do. The idea is that we found a way to take the pain out of the system, going all the way back. And what we’re finding is that pain starts way, way earlier than we thought.

I used to think that the greatest point was the birth trauma. Well that’s no longer true. Way before the birth trauma there are traumas from the smoking mothers, the anxious mothers, the depressed mothers, that have lifelong effects on the baby, the offspring.”

“https://www.youtube.com/watch?v=dbUhjZhpEyct”

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.

Problematic research on stress that will never make a contribution toward advancing science

gettingwell4 < 0 Detracted from science, Cortisol, Neurochemicals, Stress

This 2014 UK human study found:

“Type 2 diabetes is characterized by disruption of stress-related processes across multiple biological systems and increased exposure to life stress.”

HOWEVER, the stress effects weren’t conclusively shown to be either a cause or consequence of type 2 diabetes. Correlation wasn’t causation.

Looking around for clues as to what went wrong, I found this data sample of cortisol in a small table that comprised the total amount of information in the supplementary material:

“Geometric means, adjusted for education, marital status, BMI, smoking status, use of statins, and time of day.”

It’s hubris for the researchers to state that they improved data measurements by averaging them after adjusting for all of the above six factors.

Maybe the problem was elsewhere, maybe in the study design. Wherever the problems were, they guaranteed that the researchers would NEVER find cause and effect.

But maybe that’s the point?

There appeared to be other agendas that ensured studies like these failed to make a contribution toward advancing science. The researchers inevitably used buzzwords such as “allostatic load” and cited the need for further studies (money). Everybody was okay with that, including the reviewer, and everybody kept their safe jobs.

Such studies also had limiting effects on how we “do something” about real problems because the researchers wouldn’t produce findings that weren’t politically correct.

http://www.pnas.org/content/111/44/15693.full “Disruption of multisystem responses to stress in type 2 diabetes: Investigating the dynamics of allostatic load”

If research provides evidence for the causes of stress-related disorders, why only focus on treating the symptoms?

gettingwell4 0-1 star Wasted resources, Brainstem, Cortisol, Hippocampus, Hypothalamus, Limbic system, Locus coeruleus, Lower brain, Memory, Neurochemicals, Stress , , ,

This 2014 rodent research reliably induced many disorders common to humans. Here are some post-birth problems the researchers caused, primarily by applying different types of stress, as detailed in the study’s supplementary material:

Yet the researchers’ goal was to identify a brain receptor for:

“Novel therapeutic targets for stress-related disorders.”

In other words, develop new drugs to treat the symptoms.

Where are the studies that have goals to prevent these common problems being caused in humans by humans?

Where is the research on treatments to reverse the enduring physiological impacts to stress by treating the causes?

What do you think of this excerpt?

“Accumulating evidence suggests that traumatic events particularly during early life (e.g., parental loss or neglect) coupled with genetic factors are important risk factors for the development of depression and anxiety disorders.

Moreover, the brain is particularly vulnerable to the effects of stress during this period.

Maternal separation in rodents is a useful model of early-life stress that results in enduring physiological and behavioral changes that persist into adulthood, including increased hypothalamic–pituitary–adrenal (HPA)–axis sensitivity, increased anxiety, and visceral hypersensitivity.”

http://www.pnas.org/content/111/42/15232.full “GABAB(1) receptor subunit isoforms differentially regulate stress resilience”