Neurochemicals

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”

How to make a child less capable even before they are born: stress the pregnant mother-to-be

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

This 2014 rodent study showed how to make a less-capable pup by stressing the mother early in gestation. The study centered on a placental enzyme (OGT) that translates a mother’s stress into neuroprogramming of her developing fetus.

One finding was that this enzyme was less plentiful when the fetus was male compared with female.

Another finding was that the enzyme was less plentiful when the mother was stressed early in gestation, compared with unstressed mothers.

Informed by the first two findings, the researchers studied the placentae of male pups where the mother was stressed early in gestation. They found that these placentae had lower levels of an enzyme (Hsd17b3) that converts the precursor androstenedione into testosterone.

The resultant finding was that the male pups of stressed mothers had lower levels of testosterone than the control group of male pups.

A fourth finding was that offspring of both sexes born with a placenta where the OGT enzyme was less plentiful had 10-20% less body weight, a condition that developed after weaning. The researchers attributed this finding to reduced mitochondrial function in the hypothalamus compared with normal mice.

http://www.pnas.org/content/111/26/9639.full “Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction”

Are stress-induced epigenetic changes to DNA inherited across generations?

gettingwell4 0-1 star Wasted resources, Amygdala, Brain development, Cortisol, Epigenetics, Limbic system, Memory, Neurochemicals, Stress , , , , ,

This 2014 Geneva/Cambridge plant study ended by stating:

“The unequivocal demonstration of transgenerational transmission of environmentally-induced epigenetic traits remains a significant challenge.

One of the critical activities erasing stress memories is conserved between plants and mammals.”

However, the researchers didn’t demonstrate that their findings were broadly applicable for mammals or organisms other than the specific plant variety they studied. Possible reasons for these limited findings were given in a 2015 Australian study referenced by Mechanisms of stress memories in plants:

“The majority of DNA methylation analyses performed in plants to date have focused on Arabidopsis, despite being relatively depleted of TEs [transposable elements] (15–20% of the genome) and being poorly methylated compared to other plant genomes.

These studies have lacked the resolution to provide the specific context and genomic location of the changes in DNA methylation.”

There are also significant differences in how epigenetic inheritance across generations may operate among different species per Epigenetic reprogramming in plant and animal development.

Neither the current study nor the above review addressed the behavioral aspect of stress-induced epigenetic inheritance across generations. For example, the behavior of a mother whose DNA was epigenetically changed by stress can induce the same epigenetic changes to her child’s DNA when her child is stressed per One way that mothers cause fear and emotional trauma in their infants:

“Our results provide clues to understanding transmission of specific fears across generations and its dependence upon maternal induction of pups’ stress response paired with the cue to induce amygdala-dependent learning plasticity.”

http://www.pnas.org/content/111/23/8547.full “Identification of genes preventing transgenerational transmission of stress-induced epigenetic states”

Hypothalamic oxytocin and vasopressin have sex-specific effects on pair bonding, gregariousness, and aggression

gettingwell4 4-5 stars Advanced knowledge, Hypothalamus, Limbic system, Neurochemicals, Oxytocin, Stress, Vasopressin

This 2014 bird study showed the complementary effects of neurochemicals vasopressin and oxytocin in the hypothalamus.

Oxytocin neurons in the hypothalamus promote pair bonding and gregariousness in females.

Vasopressin neurons in the hypothalamus promote maternal care, social recognition, and gregariousness in both males and females, and aggression in males toward females.

Vasopressin and oxytocin released generally and in other parts of the brain have different effects. For example:

“Central administration of oxytocin also attenuates stress-induced effects on the brain and reverses stress-induced social avoidance.”

http://www.pnas.org/content/111/16/6069.full “Hypothalamic oxytocin and vasopressin neurons exert sex-specific effects on pair bonding, gregariousness, and aggression in finches”

Flooding the hypothalamus with neurochemicals affects reward-seeking, motivated, and depressive behavior

gettingwell4 4-5 stars Advanced knowledge, Hypothalamus, Limbic system, Lower brain, Neurochemicals

This 2014 rodent study showed the opposing effects of neurochemicals orexin (excitator) and dynorphin (inhibitor) in the hypothalamus.

The hypothalamus plays a role in behaviors such as addiction and impulsiveness. Food and cocaine self-administration were the main techniques used.

Flooding the hypothalamus with orexin produced reward-seeking and motivated behavior. That was greatly reduced when dynorphin levels were increased, and depressive behavior set in.

http://www.pnas.org/content/111/16/E1648.full “Hypocretin (orexin) facilitates reward by attenuating the antireward effects of its cotransmitter dynorphin in ventral tegmental area”

Do researchers have to be cruel to our fellow primates to adequately research oxytocin?

gettingwell4 < 0 Detracted from science, Brain development, Cortisol, Limbic system, Neurochemicals, Oxytocin, Primal Therapy , ,

This 2014 primate study found:

“Oxytocin increased infants’ affiliative communicative gestures and decreased salivary cortisol, and higher oxytocin levels were associated with greater social interest.”

One would have to take an anti-evolutionist stance and believe that primates do not feel what humans feel to consider this process to NOT be cruel:

“To test these macaques, we took advantage of ongoing experiments requiring infants to be separated from their mother on the day of birth. Infants were nursery-reared, housed individually, with a cloth surrogate mother. They could see and hear other infants, but could not touch them.”

We know that primate infants, like humans, need “nourishment, transportation, warmth, protection, and socialization” from their mothers. What level of findings about oxytocin can a research study make that would justify this deprivation?

It surely wasn’t the findings this study made. We knew without doing the study that getting oxytocin from a nebulizer would be nowhere near an acceptable substitute for a mother’s touch and care.

http://www.pnas.org/content/111/19/6922.full “Inhaled oxytocin increases positive social behaviors in newborn macaques”

Problematic research on oxytocin: If the study design excludes women, its findings cannot include women

gettingwell4 < 0 Detracted from science, Cerebrum, Limbic system, Neurochemicals, Oxytocin , ,

This 2014 study’s findings that “the hormone oxytocin promotes group-serving dishonesty” can’t apply generally to humans because its subjects were ALL men.

Regarding oxytocin, the researchers certainly knew or should have known previous studies’ findings about sex differences, as did Is oxytocin why more women than men like horror movies? which cited:

“Oxytocin modulates brain activity differently in male and female subjects.”

Regarding differing reciprocal behaviors, the researchers also knew or should have been better informed about associated brain areas through studies such as Reciprocity behaviors differ as to whether we seek cerebral vs. limbic system rewards and its references.

And how could the study produce reliable, replicable evidence of:

“Dishonesty to be plastic and rooted in evolved neurobiological circuitries”

when the researchers performed NO measurements of “neurobiological circuitries” that supported that finding?

What was the agenda in play here? What did the female Princeton reviewer see in this study that advanced science?

http://www.pnas.org/content/111/15/5503.full “Oxytocin promotes group-serving dishonesty”

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.

Is oxytocin why more women than men like horror movies?

gettingwell4 2-3 stars Required further work, Amygdala, Brain hemispheres, Limbic system, Neurochemicals, Oxytocin, Serotonin

This 2014 human study showed how oxytocin regulates serotonin with the involvement of the right part of the amygdala.

The following passage caught my eye as a possible explanation of why more women than men prefer horror movies: oxytocin?

“We have chosen to enroll male subjects only to avoid the confounding effects linked to sex and a possible interaction with gonadal steroids. Indeed, as shown by previous studies, oxytocin modulates brain activity differently in male and female subjects.

For instance, oxytocin suppresses amygdala response to emotionally threatening stimuli in males but enhances the same response in females.“

http://www.pnas.org/content/111/23/8637.full “Switching brain serotonin with oxytocin”

Maternal depression and antidepressants epigenetically change infant language development

gettingwell4 4-5 stars Advanced knowledge, Brain development, Epigenetics, Neurochemicals, Serotonin , , , , ,

This 2012 human study found that infant language development accelerated when the depressed mother-to-be took antidepressants:

“Language acquisition reflects a complex interplay between biology and early experience.

Psychotropic medication exposure has been shown to alter neural plasticity and shift sensitive periods in perceptual development.”

Infant language development was delayed when the depressed mother-to-be didn’t take serotonin reuptake inhibitor medication:

“Prenatal depressed maternal mood and (S)SRI exposure were found to shift developmental milestones bidirectionally on infant speech perception tasks.”

Contrast this study with Problematic research with telomere length, which pretended that maternal depression had negligible epigenetic effects on the developing fetus, infant, and child.

http://www.pnas.org/content/109/Supplement_2/17221.full “Prenatal exposure to antidepressants and depressed maternal mood alter trajectory of infant speech perception”

Chronic stress changes the architecture of the hippocampus, leading to depression and cognitive impairment

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

This 2014 rodent study gave further details that:

“Chronic stress, which can precipitate depression, induces changes in the architecture and plasticity of apical dendrites that are particularly evident in the CA3 region of the hippocampus.”

Other studies on the hippocampus CA3 region include:

http://www.pnas.org/content/111/45/16130.full “Role for NUP62 depletion and PYK2 redistribution in dendritic retraction resulting from chronic stress”

Activation of brainstem neurons induces REM sleep

gettingwell4 4-5 stars Advanced knowledge, Acetylcholine, Brainstem, Lower brain, Neurochemicals

This 2014 MIT/Harvard rodent study provided evidence that specific brainstem neurons (cholinergic, or containing acetylcholine) regulated dream sleep.

The researchers used a more exact technique that selectively activated just one neuron. They made the neurons in this study sensitive to light using an algae protein that responded to a specific light frequency. Once expressed in the neuron, the protein activated the neuron when that specific frequency of light was shown onto it.

“Interestingly, both manipulations resulted in a change in the number of REM [rapid eye movement] sleep episodes and did not change REM sleep episode duration, suggesting that the PPT [pedunculopontine tegmentumis part of the brainstem] involved in REM sleep initiation but not REM sleep maintenance.”

http://www.pnas.org/content/112/2/584.full “Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep”

The brainstem nucleus locus coeruleus is the primary source of norepinephrine

gettingwell4 4-5 stars Advanced knowledge, Brainstem, Cerebrum, Cortisol, Locus coeruleus, Lower brain, Neurochemicals

This 2014 rodent study provided further information on the locus coeruleus segment of the brainstem:

“The brainstem nucleus locus coeruleus is the primary source of norepinephrine to the mammalian neocortex.

Neurons in the locus coeruleus maintain segregated connections to brain regions with distinctly different functions. Specifically, cells that communicate with the prefrontal cortex, a region involved in cognition and executive function, are characterized by properties that allow for independent and asynchronous modulation of operations in this area, compared with those that project to the motor cortex and regulate movement generation.”

http://www.pnas.org/content/111/18/6816.full “Heterogeneous organization of the locus coeruleus projections to prefrontal and motor cortices”

Stress impairs the normal matching of neuronal activity to increased blood flow in the amygdala

gettingwell4 4-5 stars Advanced knowledge, Amygdala, Cortisol, Limbic system, Neurochemicals, Stress

This 2014 rodent study showed one aspect of how stress changed the amygdala. Stress didn’t allow normal matching of neuronal activity to increased blood flow:

“Chronic stress — which is a contributing factor for many diseases — impairs neurovascular coupling in the amygdala..

Neurovascular coupling (is) the process that matches neuronal activity with increased local blood flow.”

http://www.pnas.org/content/111/20/7462.full “Stress-induced glucocorticoid signaling remodels neurovascular coupling through impairment of cerebrovascular inwardly rectifying K+ channel function”

Active areas of the brain when making decisions in stressful conditions

gettingwell4 2-3 stars Required further work, Cerebrum, Cortisol, Limbic system, Lower brain, Memory, Neurochemicals, Stress

This 2013 human study was of decision making under stressful conditions.

Acute stress (ice water immersion) evoked habitual behavior rather than deliberative behavior. In my view, the subjects’ behaviors when under stress were driven more by their limbic system and lower brain areas than their cerebrum.

This finding wasn’t a big surprise. However, the researchers went on to state:

“Subjects with more executive resources to spare find themselves less susceptible to the behavioral changes brought about by stress response.”

I interpreted this statement to mean that when stressed, the more-capable subjects didn’t act out as much as the less-capable subjects acted out their respective feelings, instincts and impulses.

I felt that to understand this statement called for more investigation into the individual histories of the subjects:

  • What happened in their lives that enabled each person to acquire “more executive resources” or not?
  • What happened in their lives that made each person more or less sensitive to stress?
  • How are these two avenues of investigation related?

http://www.pnas.org/content/110/52/20941.full “Working-memory capacity protects model-based learning from stress”

How oxytocin and vasopressin were repurposed through evolution to serve social functions

gettingwell4 4-5 stars Advanced knowledge, Neurochemicals, Oxytocin, Vasopressin

This 2013 primate summary study showed how nonsocial behaviors, neurology and neurochemicals were repurposed through evolution to serve social functions.

Oxytocin and vasopressin retained their:

  • water regulation,
  • reproduction, and
  • anxiety relief

functionalities while they also evolved to become instrumental in:

  • pair-bonding,
  • parental care,
  • selective aggression,
  • social prominence,
  • generosity, and
  • trust.

http://www.pnas.org/content/110/Supplement_2/10387.full “Neuroethology of primate social behavior”