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Fat made rats fat with dysfunctional brains

gettingwell4 2-3 stars Required further work, Anterior cingulate cortex, Cerebrum, Cortisol, Epigenetics, Hippocampus, Limbic system, Neurochemicals, Stress, Testosterone , , ,

This 2015 New York rodent study found:

“Early stage [diet-induced] obesity, before the onset of diabetes or metabolic syndrome, produced deficits on cognitive tasks that require the prefrontal cortex.

These results strongly suggest that obesity must be considered as a contributing factor to brain dysfunction.”

The difference in the diets of the adult male subjects was that the control group ate 10% fat (20% protein, 70% carbohydrates) whereas the obese group ate 45% fat (20% protein, 35% carbohydrates). Significant changes in body weight were present after the first two weeks on the diets, but testing didn’t begin until after eight weeks.

I thought the study design prematurely terminated the experiments. The study didn’t justify the ultimate purpose of conducting rodent experiments, which is to find possible human applicability.

One study design possibility would have been to continue through old age to find how the conditions progressed. Another possibility would have been to reverse the high-fat diet to find whether the conditions reversed.

http://www.pnas.org/content/112/51/15731.full “Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function”

Testing the null hypothesis of psychological therapy

gettingwell4 2-3 stars Required further work, Primal Therapy , , ,

What forms of medicine don’t require an etiological approach, other than psychology and psychiatry?

This 2015 UK human study found:

“Supported cCBT [computerised cognitive behaviour therapy] does not substantially improve depression outcomes compared with usual GP [general practitioner] care alone.

In this study, neither a commercially available nor free to use computerised CBT intervention was superior to usual GP care.”

Subjects had concurrent access to most of the relevant UK health system:

“We imposed no constraints on usual GP care in the control or intervention groups, and participants were therefore free during the trial to access any treatment usually available in primary care, including the use of antidepressants, counselling, psychological services (including Improving Access to Psychological Therapy services, which were present in most sites during the course of the trial), or secondary care mental health services.”

The study’s null hypothesis was developed as follows:

“We based our sample size calculation on the usual care arm of primary care depression trials, where the proportion of patients responding to usual care was in the region of 0.6. This proportion is similar to that found in a UK Health Technology Assessment trial of antidepressants in primary care.

We regarded a figure of not more than 0.15 below this proportion as being acceptable, given the additional care options that are available to patients who do not initially respond to cCBT within a stepped care framework. In our original calculation, to detect non-inferiority with the percentage success in both groups as 60% and a non-inferiority margin of 15% with over 80% power and assuming 25% attrition, we required 200 participants in each of the three arms.”

The study’s null hypothesis was: the two cCBT methods wouldn’t improve on the “60%” “success” of both “the usual care arm” and “antidepressants in primary care.”

What outcome does a person desire when they seek out psychological care? I’d guess that their first need would be to stop their current suffering.

From a patient’s short-term perspective, the null hypothesis – any form of psychological therapy in the UK healthcare system wouldn’t improve their short-term condition – is likely to be initially disproved.

So, what accounts for the 40% failure rate? Or, as phrased in Psychological therapy and DNA methylation:

“Although CBT has been established as an efficacious treatment, roughly 40% of children retain their disorder after treatment.”

The treatments’ methods aren’t capable of anything more than temporarily suppressing symptoms. But the symptoms return, and require further interventions in order to stay suppressed.

From a patient’s long-term perspective, what would it take to disprove the null hypothesis – any form of psychological therapy in the UK healthcare system wouldn’t improve their long-term condition?

To effectively treat patients in the long term, and to prevent future suffering, the originating causes need to be addressed. IAW, hold psychological therapy to the same standard of care expected in other medical treatments.

http://www.bmj.com/content/351/bmj.h5627 “Computerised cognitive behaviour therapy (cCBT) as treatment for depression in primary care (REEACT trial): large scale pragmatic randomised controlled trial”

Beliefs about medical treatments affected perceived stress

gettingwell4 2-3 stars Required further work, Beliefs, Cerebrum, Neurochemicals, Oxytocin, Serotonin, Stress

This 2015 New Zealand human study found:

“Placebo effects can be translated to a real-life setting in the short-term reduction of stress, anxiety and symptoms of depression in a non-patient population.

In treating psychological distress, placebos may be useful addition to the treatment repertoire.“

The researchers provided a self-administered 3-day course of fake “anti-stress treatment spray” and told the participants the spray was either “oxytocin” or “serotonin” with these results:

“Both the ‘serotonin’ and ‘oxytocin’ treatment sprays were effective in reducing symptoms of depression; however, only those in the ‘oxytocin’ group reported less stress and anxiety as compared with controls. Overall, the ‘oxytocin’ was perceived as more effective.”

Will this study of non-patients be used to try to justify manipulating patients’ perceptions of their stress, anxiety, and depression?

http://anp.sagepub.com/content/early/2015/12/16/0004867415621390 “A take-home placebo treatment can reduce stress, anxiety and symptoms of depression in a non-patient population”

It is known: Are a study’s agendas more important than its evidence?

gettingwell4 < 0 Detracted from science, Amygdala, Anterior cingulate cortex, Brain hemispheres, Cerebrum, Cortisol, Epigenetics, Glutamate, Hippocampus, Hypothalamus, Limbic system, Memory, Neurochemicals, Stress , , , , ,

This 2015 Swiss human study’s Abstract began:

“It is known that increased circulating glucocorticoids in the wake of excessive, chronic, repetitive stress increases anxiety and impairs Brain-Derived Neurotrophic Factor (BDNF) signaling.”

The study had several statements that were unconvincingly supported by the study’s findings. One such statement in the Conclusions section was:

“This study supports the view that early-life adversity may induce long-lasting epigenetic changes in stress-related genes, thus offering clues as to how intergenerational transmission of anxiety and trauma could occur.”

However, the study’s evidence for “intergenerational transmission of anxiety and trauma” as summarized in the Limitations section was:

“This study did not directly associate child behavior or biology to maternal behavior and biology.”

In another example, the Discussion section began with:

“The severity of maternal anxiety was significantly correlated with mean overall methylation of 4 CpG sites located in exon IV of the BDNF promoter region as measured from DNA extracted from mothers’ saliva.

In addition, methylation at CpG3 was also significantly associated with maternal exposure to domestic violence during childhood, suggesting that BDNF gene methylation levels are modulated by early adverse experiences.”

The researchers assessed five DNA methylation values (four individual sites and the overall average). The CpG3 site was “significantly associated with maternal exposure to domestic violence during childhood” and the three other CpG sites’ methylation values were not.

IAW, the researchers found only one of four sites’ methylation values significantly associated to only one of many studied early adverse experiences. This finding didn’t provide sufficient evidence to support the overarching statement:

“BDNF gene methylation levels are modulated by early adverse experiences.”

To make such a generally applicable statement – more than one BDNF gene’s methylation levels could be directly altered by more than one early adverse experience – the researchers would, AT A MINIMUM, need to provide evidence that:

  1. The one category of significantly associated early adverse experience directly altered the one significantly associated CpG site’s DNA methylation level
  2. Other categories of early adverse experiences were fairly represented by the one significantly associated experience category
  3. Other categories of early adverse experiences could directly alter other BDNF genes’ DNA methylation levels
  4. The significantly associated DNA methylation level of only one out of four CpG sites was fairly represented by the overall average of the four sites
  5. Other BDNF gene’s methylation levels were fairly represented by the overall average of the four sites

If researchers and sponsors must have agendas, a worthwhile, evidence-supported one would be to investigate prenatal and perinatal epigenetic causes for later-life adverse effects.

As Grokking an Adverse Childhood Experiences (ACE) score pointed out, environmental factors that disrupt neurodevelopment may be the largest originators of epigenetic changes that are sustained throughout an individual’s entire lifespan.

What’s the downside of conducting studies that may “directly associate child behavior or biology to maternal behavior and biology” during time periods when a child’s environment has the greatest impact on their development?

When prenatal and perinatal periods aren’t addressed, researchers and sponsors neglect the times during which many harmful epigenetic consequences may be prevented. It is known.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143427 “BDNF Methylation and Maternal Brain Activity in a Violence-Related Sample”

Emotional memories create long-term epigenetic changes

gettingwell4 2-3 stars Required further work, Anterior cingulate cortex, Brain development, Epigenetics, Hippocampus, Limbic system, Memory, Stress , , , , , ,

This 2015 German rodent study found:

“Histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression.

Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning.”

Chromatin modifications in two limbic system brain areas were studied – the hippocampus (CA1 region) for short-term memories and the anterior cingulate cortex for short-and long-term memory formation and maintenance. The memories were induced by context (C) and context shock (CS) exposure:

“Overall, the data provides very strong and robust evidence for the establishment of long-term memory upon CS exposure, whereas C exposure alone did not induce the formation of long-term memory.”

So, without long-term shock/emotional memories, there would be no positive long-term findings for the researchers to report. There would be no lasting:

  • “Histone modifications
  • DNA methylation changes
  • Changes in gene expression”

The subjects were young adults at age 3 months. The CA1 and ACC studied brain areas are fully developed before this age.

It seemed feasible that if the study were performed with younger subjects, the results may have been different. For example:

“Context exposure alone did not induce the formation of long-term memory”

may not have been the finding for early learning situations.

The researchers qualified their results several times with the phrase “changes are limited to actively expressed genes.” A similar qualifier in A study of DNA methylation and age was a reminder that unexpressed genes may have also been important:

“The textbook case of DNA methylation regulating gene expression (the methylation of a promoter and silencing of a gene) remains undetected in many cases because in an array analysis, an unexpressed gene shows no signal that can be distinguished from background and is therefore typically omitted from the analysis.”

This general qualifier may not have necessarily applied to the current study, though, because the study’s design included an unexposed control group.

http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.4194.html “DNA methylation changes in plasticity genes accompany the formation and maintenance of memory”

Brain-region-specific energy metabolism affected the social competitiveness of highly-anxious rats

gettingwell4 4-5 stars Advanced knowledge, Acetylcholine, Amygdala, Cerebrum, Cortisol, Dopamine, Epigenetics, Limbic system, Memory, Neurochemicals, Stress , ,

This 2015 Swiss rodent study found:

“Mitochondrial function in the nucleus accumbens, a brain region relevant for motivation and depression, is a critical mediating factor in the subordinate status displayed by high-anxious rats.

Treatment with nicotinamide, an amide form of vitamin B3 that boosts mitochondrial respiration, into the NAc [nucleus accumbens] of high-anxious rats at a time point before the social encounter and at a dose that increased accumbal mitochondrial respiration, abolished the disadvantage of high-anxious animals to become dominant against low-anxious animals.

Our findings highlight a key role for brain energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for anxiety-related social disorders.”

The researchers handled individual differences of the outbred subjects by separating them into high-, intermediate-, and low-anxiety categories according to their responses on two tests. The high- and low-anxiety subjects were matched by weight, age, and social experience.

Here are a few examples of the researchers thoroughly ruling out confounding factors:

“Differences in social competitiveness are not related to overall differences in social motivation or sociability.

Although social competition did significantly increase corticosterone compared with baseline levels, there were no significant differences between anxiety groups at either time point.

Microinfusion of either ROT, MA, or 3NP [mitochondrial respiration inhibitors] reduced the success of treated animals to win the social contest.

Importantly, these treatments did not induce side effects on social investigation or auto-grooming during social competition, or alter locomotor activity, anxiety, or sociability in additional experiments.

Furthermore, these inhibitor treatments did not produce neurotoxic effects, as the drugs were infused at low doses and we confirmed the absence of lesion and neuronal death.

The effects of complex I or complex II inhibition on social competition were specific for the NAc, as infusions of the same inhibitors into the BLA [basolateral amygdala] had no effect on social dominance and did not affect general locomotor activity.

We further showed that, unlike infusion of muscimol [a GABA receptor agonist] in the BLA that interferes with BLA-dependent auditory fear conditioning, 3NP did not affect conditioning in this task, discarding that neuronal inactivation could be a general mechanism whereby impairing mitochondrial function would affect putative functions from the affected brain region.

The impact of mitochondrial function in social competition described here is not mediated by oxidative stress.”

http://www.pnas.org/content/112/50/15486.full “Mitochondrial function in the brain links anxiety with social subordination”

A study of stress factors and neuroplasticity during infancy/early childhood

gettingwell4 2-3 stars Required further work, Cerebrum, Cortisol, Epigenetics, Hippocampus, Hypothalamus, Limbic system, Neurochemicals, Stress , , , , ,

This 2015 French rodent study found:

“The coordinated actions of BDNF and glucocorticoids promote neuronal plasticity and that disruption in either pathway could set the stage for the development of stress-induced psychiatric diseases.

Genetic strategies that disrupted GR [glucocorticoid receptor] phosphorylation or TrkB [the BDNF receptor] signaling in vivo impaired the neuroplasticity to chronic stress and the effects of the antidepressant fluoxetine.

We demonstrate that fluoxetine prevented the neuroplasticity of chronic stress by priming GR phosphorylation at BDNF-sensitive sites.”

It wasn’t too difficult to see how many of the stressors had human equivalents during infancy/early childhood:

“To determine the plasticity of GR phosphorylation upon changes in the endogenous levels of BDNF and glucocorticoids, mice were exposed to a chronic unpredictable stress that included one daily random stressor for 10 consecutive days from P21 [immediately after weaning] to 1 mo of age.

Chronic unpredictable stress includes one of the following daily random stressors (wet bedding, no bedding, food deprivation, crowded cage, 2 h or 6 h restraining, forced swim, tail suspension).”

But who would give fluoxetine – Prozac – to a human infant or young child to prevent “the neuroplasticity of chronic stress” from having adverse effects?

http://www.pnas.org/content/112/51/15737.full “Neurotrophic-priming of glucocorticoid receptor signaling is essential for neuronal plasticity to stress and antidepressant treatment”

Improved methodology in studying epigenetic DNA methylation

gettingwell4 2-3 stars Required further work, Brain development, Cerebrum, Epigenetics, Glutamate, Neurochemicals , , , , ,

This 2015 New York human study was of:

“The two major populations of human prefrontal cortex neurons..the excitatory glutamatergic projection neurons and the inhibitory GABAergic interneurons which constitute about 80% and 20% of all cortical neurons, respectively.

Major differences between the neuronal subtypes were revealed in CpG, non-CpG and hydroxymethylation (hCpG).

A dramatically greater number of undermethylated CpG sites in GLU versus GABA neurons were identified. These differences did not directly translate into differences in gene expression and did not stem from the differences in hCpG methylation, as more hCpG methylation was detected in GLU versus GABA neurons.

Notably, a comparable number of undermethylated non-CpG sites were identified in GLU and GABA neurons, and non-CpG methylation was a better predictor of subtype-specific gene expression compared to CpG methylation.”

The researchers performed numerous cross checks to test the results of their methodologies. This was necessary because, for example, studies such as A human study of changes in gene expression point out that current technologies such as the 450K array:

“Queries only 1.6% of all CpGs in the genome and the CpG selection is biased towards CpG islands.”

From the Discussion section:

“The higher abundance of hmCpG sites in GLU versus GABA neurons appears indicative of a difference in transcriptional potential between the neuronal subtypes. The increased hydroxymethylation could enable certain genes (e.g. activity-dependent genes) to be more readily induced in GLU versus GABA neurons.

These findings emphasize the importance of even subtle differences in the promoter CpG methylation for neuron subtype-specific gene expression. They also suggest that differences in CpG methylation within gene bodies and distal regulatory elements are not always directly reflected in differences in gene expression between neuronal subtypes.

The functional relevance of the association between gene expression and distal non-CpG methylation remains to be characterized.

Our data suggest that, compared to GABA interneurons, GLU projection neurons are characterized by more permissive chromatin state that is less constrained by repressive DNA methylation marks and is instead controlled by more dynamic means of transcription inhibition, such as non-coding RNAs and/or histone modifications.”

This study was similar to A problematic study of DNA methylation in frontal cortex development and schizophrenia in examining:

“If common risk variants determined by the recent genome wide associated studies (GWAS) for several neuropsychiatric diseases including schizophrenia (SCZ), autism spectrum disorder (ASD), major depressive disorder (MDD), and Alzheimer’s disease (AD) significantly overlap.

These findings strongly suggest an association between the epigenetic specification of both GABA and GLU neurons and SCZ. Risk variants associates with ASD, MD, or AD were not enriched.

An alternative explanation of our negative results could be the involvement of different developmental stages and/or brain regions in different diseases.”

The current study performed more detailed analyses, but on fewer subjects. The emphasis was on demonstrating an improved methodology.

Both studies’ findings regarding disease were of effects, not causes. That both study designs were limited to the postmortem prefrontal cortex reminded me of the old joke about looking for lost keys under the street light because the light was better there. At least the current study acknowledged the existence of other areas to search.

http://nar.oxfordjournals.org/content/early/2015/11/25/nar.gkv1304.full “Substantial DNA methylation differences between two major neuronal subtypes in human brain”

Where do our beliefs about our children come from? An autism example

gettingwell4 < 0 Detracted from science, Beliefs, Brain development, Cerebrum, Epigenetics, Glutamate, Limbic system, Neurochemicals, Primal Therapy , , , ,

A 2015 case study by Ohio physicians highlighted:

“Although only a small minority of patients with autism have a mitochondrial disease, many patients with mitochondrial myopathies have autism spectrum disorder symptoms.

These symptoms may be the presenting symptoms, which presents a diagnostic challenge for clinicians.

The case of a 15-year-old boy with a history of autism spectrum disorder and neurocardiogenic syncope, admitted to the inpatient unit for self-injury, whose young mother, age 35, was discovered to suffer from mitochondrial myopathy, dysautonomia, neurocardiogenic syncope, Ehler-Danlos syndrome, and other uncommon multisystem pathologies likely related to mitochondrial dysfunction.”

I was somewhat taken aback by the Abstract and Introduction statements:

“All autism spectrum disorders are known to be heritable, via genetic and/or epigenetic mechanisms, but specific modes of inheritance are not well characterized.

This form of ASD is known to be heritable, as are all forms of ASD, despite the previous belief to the contrary, though the mechanisms of inheritance, both genetic and epigenetic, are not well characterized.”

The definition of heritable as used was “able to be passed from parent to child before birth.” The reference provided was a 2014 French review Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms.

I didn’t see the “known to be heritable” phrase mentioned in the referenced review. However, I also didn’t see anything stated in the review or cited from its 217 references that disproved this phrase.

I shouldn’t have been surprised by “despite the previous belief to the contrary” in the above quotation. I’d guess that the physicians frequently encountered parents who needed such beliefs when faced with their child’s condition.

A relevant hypothesis of Dr. Arthur Janov’s Primal Therapy is: a major function that our cerebrums have evolutionarily adapted is to use ideas and beliefs to repress pain and make us more comfortable.

I value this inference as an empathetic method of interpreting people’s behaviors and expressions of thoughts and feelings.

When a “known to be heritable” phrase can unleash pain, it likely won’t be understood in its appropriate context. Among the physicians’ challenges was a barrier that kept the parent’s pain from being felt – the belief.

http://innovationscns.com/autism-in-the-son-of-a-woman-with-mitochondrial-myopathy-and-dysautonomia-a-case-report/ “Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report”

2023 update – After all the medical gaslighting on display this decade, I don’t what it would take for me to trust a medical professional anymore. These doctors ‘knew’ somehow that autism was heritable, yet couldn’t describe mechanisms of inheritance? Please. Why were medical professionals trusted in the first place?

Epigenetics is gnarly and dynamic

gettingwell4 2-3 stars Required further work, Beliefs, Cerebrum, Epigenetics ,

From one of the articles in a freely-available Genome editing publication:

“Genomic studies frequently point to the important role that the full collection of epigenetic patterns in a cell nucleus has in complex diseases such as diabetes or schizophrenia, notes Tim Reddy, a genomics researcher also at Duke University. “In a lot of these cases, it really seems to be not a DNA mutation that impacts the protein sequence, but a change in how genes are regulated.”

Reddy says that he was surprised at the extent to which the expression of a target gene increased when a histone in an enhancer region was acetylated. “That result started to convince me that the acetylation of histones may be a direct cause of gene activation.”

Because of its simplicity and versatility, CRISPR–Cas9 opens up an opportunity. “If we want to target a region in the genome, we can have that targeting molecule here tomorrow for five dollars,” says Reddy.”

Reading this article and several of the publication’s other articles revealed the widespread belief that the goal of research should be to explain human conditions by explaining the actions of molecules.

One problem caused by this preconception is that it leads to study designs and models that omit relevant etiologic evidence embedded in each of the subjects’ historical experiences.

http://www.nature.com/nature/journal/v528/n7580_supp/full/528S12a.html “Epigenetics: The genome unwrapped”

Increased epigenetic brain capacity is an evolved human characteristic

gettingwell4 4-5 stars Advanced knowledge, Brain development, Cerebrum, Epigenetics, Limbic system , ,

This 2015 George Washington study compared human and chimpanzee brain attributes to find:

“The morphology of the human cerebral cortex is substantially less genetically heritable than in chimpanzees and therefore is more responsive to molding by environmental influences.”

From the news coverage:

“We found that the anatomy of the chimpanzee brain is more strongly controlled by genes than that of human brains, suggesting that the human brain is extensively shaped by its environment no matter its genetics.

Though our findings suggest that the increased plasticity found in human brains has many benefits for adaptation, it is also possible that it makes our brain more vulnerable to many human-specific neurodegenerative and neurodevelopment disorders.”

The study demonstrated an aspect of how natural selection of species leading to Homo sapiens – after humans and chimpanzees shared a common ancestor – favored our increased capacity to adapt to our environments.

http://www.pnas.org/content/112/48/14799.full “Relaxed genetic control of cortical organization in human brains compared with chimpanzees”

A problematic study of DNA methylation in frontal cortex development and schizophrenia

gettingwell4 < 0 Detracted from science, Amygdala, Brain development, Cerebrum, Epigenetics, Hippocampus, Limbic system, Lower brain , , , , , ,

This 2015 Baltimore human study found:

“CpGs that differ between schizophrenia patients and controls that were enriched for genes related to development and neurodifferentiation.

The schizophrenia-associated CpGs strongly correlate with changes related to the prenatal-postnatal transition and show slight enrichment for GWAS [genome-wide association study] risk loci while not corresponding to CpGs differentiating adolescence from later adult life.

Only a fraction of the illness-associated CpGs, 4.6%, showed association to nearby genetic variants in the meQTL [methylation quantitative trait loci] analysis, further suggesting that these findings may be more related to the epiphenomena of the illness state than to the genetic causes of the disorder.

These data implicate an epigenetic component to the developmental origins of this disorder.”

It wasn’t surprising in 2015 to find “an epigenetic component to the developmental origins of this disorder.” From the supplementary material:

“Diverse chromatin states suggest vastly different epigenetic landscapes of the prenatal versus postnatal human brain.

Approximately half of the CpGs had DNAm [DNA methylation] levels positively correlated with expression across the lifespan, and half had DNAm levels negatively correlated.

These results suggest that many of the epigenetic changes occurring between prenatal and postnatal life in prefrontal cortex manifest in the transcriptome, and that the directionality of association is not strictly linked to the location of the CpG or DMR [differentially methylated region] with respect to an annotated gene.

Diagnosis-associated CpGs were relatively small compared with those differentially methylated between fetal and postnatal samples.”

The studied brain area was limited to the dorsolateral portion of the prefrontal cortex, which isn’t mature in humans until we’re in our late teens/early twenties.

The researchers ignored brain areas that were fully developed or further along in development – such as the limbic system – during “the prenatal-postnatal transition.”

The researchers intentionally blinded themselves from discovering “many of the epigenetic changes occurring between prenatal and postnatal life” possibly associated with schizophrenia and these more-developed brain areas.

Where’s the evidence that the developmental origins of schizophrenia have no associations with brain structures whose development closely approximates their lifelong functionalities at birth?

The study’s limitations didn’t hamper researcher hubris in a press release for a site that touts business news, such as:

“This conclusion, while perhaps not the final verdict on the subject, is hard to resist given this remarkable evidence”

Did the spokesperson really understand GWAS? Or was he trying to exploit public ignorance of GWAS?

There’s a scientist’s view of GWAS at What do GWAS signals mean? that better puts this study’s findings into perspective. When understanding GWAS at an individual level, it should also be acknowledged that Genetic statistics don’t necessarily predict the effects of an individual’s genes.

http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.4181.html “Mapping DNA methylation across development, genotype and schizophrenia in the human frontal cortex” (not freely available). Use the full study link from the above-mentioned press release.

Trapped, suffocating, unable to move – a Primal imprint

gettingwell4 5+ stars Premium, Brain development, Brainstem, Epigenetics, Limbic system, Lower brain, Memory, Neurochemicals, Primal Therapy, Serotonin , , , , , , ,

“The malady of needing to move constantly: organizing trips, making reasons to go here and there, and in general, keeping on the move..below all that movement is a giant, silent scream.

The price we pay is never knowing our feelings or where they come from.

We have the mechanism for our own liberation inside of us, if we only knew it.

When we see constant motion we understand, but we never see the agony. Why no agony? Because it is busy being acted-out to relieve the agony before it is fully felt.”

http://cigognenews.blogspot.com/2015/11/epigenetics-and-primal-therapy-cure-for_30.html “The Miracle of Memory – Epigenetics and Primal Therapy: The Cure for Neurosis (Part 13/20)”

The emotional power of environmental sounds affects our sensory experiences

gettingwell4 5+ stars Premium, Amygdala, Hypothalamus, Limbic system, Neurochemicals

This 2015 Chinese/Australian study found:

“Human emotions systematically track changes in the acoustic environment, affecting not only how we experience those sounds but also how we perceive facial expressions in other people.

Three changes in acoustic attributes known to signal emotional states in speech and music [frequency spectrum, intensity, and rate] were imposed upon 24 environmental sounds.

Evolution promotes development in the direction toward selective advantage. Thus, it is reasonable to suggest that the capacity to track changes in the acoustic environment evolved before the development of a vocalization system for emotional communication.

Regardless of the evolutionary implications of the effect, the findings illustrate the emotional power of environmental sounds on both our experience of sounds and our evaluations of accompanying visual stimuli.”

Here are the sounds used in the study:

“Human actions (breathing, chatting, chewing, clapping, stepping, typing), animal sounds (bird, cat, cricket, horse, mosquito, rooster), machine noise (car engine, electrical drill, helicopter, jet plane, screeching tires, train), and sounds in nature (dripping water, rain, river, thunder, waves, wind)”

Does this emotional communication’s frequency spectrum, intensity, and rate affect your perception of her face?

http://www.pnas.org/content/112/47/14563.full “Human emotions track changes in the acoustic environment”

Who chooses whether research is important enough to be funded?

gettingwell4 0-1 star Wasted resources

This 2015 Chicago study of biomedical research published over a 30-year period found:

“Biomedical scientists pursue conservative research strategies exploring the local neighborhood of central, important molecules.

Although such strategies probably serve scientific careers, we show that they slow scientific advance, especially in mature fields, where more risk and less redundant experimentation would accelerate discovery of the network.”

“Importance” was determined as an objective variable in the study, then simultaneously emphasized and disavowed by the lead researcher in an interview:

“The trick is to find something really important, and not being attacked by thousands of other people around the globe.

One protein and all its connections is surely important, but what is the objective measure of importance?

You need to think about networks and interacting parts, not one protein.”

and in the study’s Discussion section:

“Efficient discovery of radically new knowledge in a mature field, including many areas of biomedicine, requires abandoning the current focus on important, nearby chemicals.”

A researcher who wasn’t involved in the study commented:

“Greater synthesis, and step-wise progress may sometimes be more important than disruptive innovation.”

Rationale that it was important for “scientific advance” to abandon studies in areas closely related to important chemicals disregarded researchers’ individual interests. It was implausible that the study’s recommendation to publish all research failures would be implemented without being forced, which would again disregard individual interests.

The researchers made recommendations as if these could be carried out by people who hypothetically acted independently of their personal histories and interests when making decisions important for “scientific advance.”

Who are these people? Just one example would suffice.

If these recommendations would be enforced by systems without people, who gets the funding to design and put such systems into place? Would scientists’ participation be voluntary, or essentially mandatory in order to work in covered areas?

There are many influences on which research proposal receives funding, of course. I didn’t see any coverage in the study or in the accompanying news articles of the influences discussed in How do we assess “importance” in our lives? An example from scientists’ research choices. That study was referenced, but only for its data distribution characteristics.

The current study assessed the importance of research choices as if each individual scientist had no motivating personal history. The researchers may have achieved actionable findings if the study’s design and methodology better incorporated the hypothesis that scientists’ career and personal choices were influenced by whether or not the work made them feel important.

http://www.pnas.org/content/112/47/14569.full “Choosing experiments to accelerate collective discovery”