Month: August 2015

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)

A missed opportunity to study image-evoked emotional memories

gettingwell4 0-1 star Wasted resources, Hippocampus, Limbic system, Memory

This 2015 Ohio human study found that the:

“Hippocampus integrates distinct experiences, thereby providing a scaffold for encoding and retrieval of autobiographical memories.”

The researchers ignored the hippocampus’ role in emotional memories, although studies such as Emotional memories and out-of-body–induced hippocampal amnesia have shown emotional involvement to be desirable in order to properly study the hippocampus with human subjects.

The researchers missed quite a few good opportunities to advance science. Consider these opportunities:

  • All subjects were instructed during fMRI scans (here’s a video of one subject) to:

    “Try to remember the event depicted in each picture and relive the experience in their mind while viewing the photo for eight seconds.”

    The photos were taken during each subject’s day-to-day life by a smartphone hung around their neck. Following these instructions created an ideal situation for engaging the subjects’ emotions when they successfully remembered and relived. Although the experiment probably engaged the subjects’ emotions;

  • None of the subjects were asked anything that would lead the researchers to discover WHY the subjects remembered! The researchers had a perfect setup to make even a bare-bones inquiry, or to ask the subjects to immediately rate the emotional impact of each remembered event/relived experience, or to have them identify what emotions were evoked. But the researchers didn’t use any emotional measures to help understand how and why events were remembered or not.
  • Wouldn’t it also have potentially helped the subjects to become somewhat aware of how they processed memories, of how they felt with each remembered event/relived experience? They probably wouldn’t have remembered personally unimportant events, or forgotten personally significant ones.

  • “One subject recalled all of the items presented” and another had “very few unrecalled items.”

    Why? Weren’t the researcher interested in what was potentially the same between these two and different from the other subjects?

The researchers instead focused on rodent studies with statements such as:

“Validating the relevance of decades of rodent studies for human memory.”

They lost track of the reason rodent studies exist: to help humans.

In order for the research to help humans, move forward on the evolutionary scale, not backward! A rat or mouse can’t define and describe the emotional impact of an image of their life that evokes a memory.

http://www.pnas.org/content/112/35/11078.full “Human hippocampus represents space and time during retrieval of real-world memories”

Reflections on my four-year anniversary of spine surgery

gettingwell4 5+ stars Premium, Beliefs, Brain development, Cerebrum, Epigenetics, Limbic system, Lower brain, Memory, Primal Therapy, Stress , , , , ,

At age 55, I found out that I’d suffered for maybe 45 to 50 years from a childhood injury, and I didn’t know anything about it. It still seems unbelievable to me that I was physically ill for decades before I received a diagnosis.

As explained to me by two surgeons, the cause of my spondylolisthesis between L5 and S1 was a sudden injury sometime between ages 5 and 10. Here’s a further explanation:

“In children, spondylolisthesis usually occurs between the fifth bone in the lower back (lumbar vertebra) and the first bone in the sacrum (pelvis) area. It is often due to a birth defect in that area of the spine or sudden injury (acute trauma).

Other causes of spondylolisthesis include bone diseases, traumatic fractures, and stress fractures (commonly seen in gymnasts). Certain sport activities, such as gymnastics, weight lifting, and football, put a great deal of stress on the bones in the lower back. They also require that the athlete constantly overstretch (hyperextend) the spine.”

I played a lot of baseball when I was a kid growing up in Miami. I didn’t suffer from a birth defect or bone disease, play football before I was a teenager, do gymnastics, or lift weights.

I don’t remember a specific “sudden injury (acute trauma)” per the above explanation. Maybe I incurred the acute trauma that started my spondylolisthesis sliding into bases playing baseball. Maybe I incurred it playing in the other rough-and-tumble activities that I did as a boy.

Please stop at the first hint of any pain that you feel while reading the rest of this post. I don’t want to cause you pain.

I re-experienced while in Primal Therapy a day when I was seven or eight years old. A most exhilarating day, one that filled me with light and joy.

What brought on my elevated mood? It was the day I finally ran faster than my father did, and he couldn’t catch me to give me a beating as I ran out of the house.

My father never beat me on the sidewalk, the street, or the front yard anyway. That would make the abuse public.

My father’s job was assistant principal/dean of boys at West Miami Junior High School. He whipped boys with a thick belt or paddled them daily as part of his job requirements.

My father kept a wooden paddle with holes in it at home. For me.

I don’t remember that my three siblings ever received a paddling or belting, although they were spanked. I’ve remembered while in Primal Therapy that my younger sister and brother were spanked for crying.

I re-experienced the dread of waiting (in an exact place with visual details), waiting for my father to come home to administer a spanking or belting or paddling to me for some “transgression” my mother observed. She had dozens of rules of conduct for her children.

I re-experienced my early childhood feelings that my father’s punishments depended more on my mother’s mood than on what I did.

I re-experienced my early childhood feelings that I didn’t deserve the beatings. I didn’t deserve any beatings, not one!

My father continued, though, until I was around age 11 or so. I’m sure that the beatings were a factor in how I felt at age 12:

Suicidal. Needing to escape from my life.

When I was a child, I needed my parents’ love.

I re-experienced many times while in Primal Therapy the overwhelming hopelessness, helplessness, worthlessness, and betrayal when the people I needed to love me were cruel to me instead.

My parents knew what they did was wrong. Neither one of them ever told me that, though.

My father never apologized for beating me so much before he died 19 years ago. Even before he retired, 17 years before he died, the Miami-Dade County public school system stopped him and the rest of their employees from spanking, whipping, beating, and paddling children.

What could he even tell me to take away those experiences?

  • That he beat me as a child because he himself was beaten as a child?
  • That he couldn’t help it?
  • That how he and my mother frequently went out of their way to help me along in life after my childhood somehow made up for the beatings?

I’m certain that my father was beaten as a child. I bring this up not as a defense for what he did, but as part of my history, too.

It wasn’t enough for my father’s mother to beat me while she was babysitting my siblings and me at our parents’ house. I re-experienced crying as a five-year old when I was required to go cut off palm fronds from the tree in front of our house for her to use as a switch, and bring them to her.

It was a mark of my grandmother’s cruelty that she threatened to beat me with a broom handle when I tried to not participate in my own torment. I re-experienced exact places of my legs where she switched me with the palm fronds, giving me even more when I cried during the punishment.

These wounds left scars that haven’t gone away.

Run your hand down your spine until you reach the top of your sacrum. That’s the area on which I had surgery four years ago, where I now have a titanium cage, replacement disc, and two rods to keep the area stable.

I received a lot of beatings pretty close to that area. Maybe my boyhood activities didn’t cause the “sudden injury (acute trauma).”

I write frankly about my parents because that’s my history: the realities of who they were.

And the realities of who I needed them to be.

I express it because getting well has to address reality.

From Dr. Arthur Janov’s book, Primal Healing, page 133:

“Another cognitive technique is to help the patient understand and forgive his parents. ‘After all, your parents did the best they could. They had a pretty tough childhood too.’ ‘Oh yes, I understand. They did have it tough and I do forgive’ comes forth from the left side. Still, of course, the right side is crying out its needs and its pain, and will go on with its silent scream for the rest of our lives.

There is no way around need.

‘Forgiveness’ is an idea that has no place in therapy.

We are not here to pardon parents; we are here to address the needs of patients, and what the lack of fulfillment did to them.

I regret to say that much of current therapy and particularly cognitive therapy is about a moral position; well hidden, couched in psychological jargon, but, at bottom, moralizing. The therapist becomes the arbiter of correct behavior.

After all, the therapist is trying to change the patient’s behavior toward some preconceived goal. That goal has a sequestered moral position.”

Words are neither the problem nor the solution

gettingwell4 4-5 stars Advanced knowledge, Cerebrum, Limbic system, Lower brain, Primal Therapy , , , , , ,

“Words are neither the problem nor the solution. They are the last evolutionary step in processing the feeling or sensation. They are the companions of feelings.

We cannot make progress on the third-line cognitive level alone. We can become aware of why we act the way we do but nothing changes biologically; it is like being aware of a virus and expecting the awareness alone to kill it. Our biology has been left out of the therapeutic equation.”

Janov’s Reflections on the Human Condition: On the Difference Between Abreaction and Feeling (Part 6/9).

DNA damage to fat cells may cause obesity and insulin resistance

gettingwell4 2-3 stars Required further work, Epigenetics, Stress ,

This 2015 Indiana rodent study found:

“DNA damage is a root cause of adipocyte senescence [fat cells that can no longer replicate], which plays a determining role in the development of obesity and insulin resistance.”

The researchers removed the capability for the subject mice to produce a protein that “plays an essential role in preventing cutaneous cancer caused by UV radiation-induced DNA damage.” They showed that this genetic deficiency:

“Causes obesity with visceral fat accumulation, hepatic steatosis, hyperleptinemia, hyperinsulinemia, and glucose intolerance.”

These researchers – in contrast with the Pulling on the chain of causes and effects with insulin resistance study – investigated causes for the various effects that included insulin resistance. However, the study’s applicability to humans wasn’t clear, since we most often develop symptoms such as insulin resistance due to causes other than genetics.

The study also demonstrated that treatment with a common dietary supplement – N-acetyl cysteine (NAC) – or metformin (Met):

“Reduce[d] adipose DNA damage.

Ameliorated cellular senescence and metabolic abnormalities.”

Body fat

High-fat and high-fructose diets caused the opposite effects in the subject genetic-deficient mice.

http://www.pnas.org/content/112/33/E4556.full “Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities”

A study of how “age” itself wasn’t a causal factor for wound-healing differences

gettingwell4 < 0 Detracted from science, Stress

This 2015 California rodent study found:

“A surprising beneficial effect of mitochondrial dysfunction at young age (accelerated wound closure), and a potential mechanism for the reduced epidermal regeneration at older ages (stem cell depletion).”

The researchers generated mitochondrial oxidative stress by deleting:

“A nuclear gene that encodes the mitochondrial antioxidant enzyme superoxide dismutase 2 (Sod2). Epidermal Sod2 loss induced cellular senescence, which irreversibly arrested proliferation in a fraction of keratinocytes.

Surprisingly, in young mice, Sod2 deficiency accelerated wound closure, increasing epidermal differentiation and reepithelialization, despite the reduced proliferation.

In contrast, at older ages, Sod2 deficiency delayed wound closure and reduced epidermal thickness, accompanied by epidermal stem cell exhaustion.”

The term “cellular senescence” used above is defined as: a cell can no longer replicate. Although the word “senescence” implies that chronological age is a factor, “cellular senescence” by definition isn’t about age.

This study’s etiologic findings weren’t “age” itself, but:

  1. Sod2 deficiency – the subjects’ genetic condition – which increased free radicals;
  2. The interplay of Sod2 deficiency with varying keratinocyte and epidermal stem cell levels; and
  3. Sod2 deficiency’s influence on other items shown in the supplementary material, to include varying “mRNA levels of wound healing-related growth factors.”

I guess the “age was the cause” meme is hard to stop repeating, though. The researchers said they could “identify a previously unidentified age-dependent role for mitochondria in quality and wound closure,” and repeated the “age-dependent” phrase in the study title.

Is pitching this meme an organizational imperative for the Buck Institute for Research on Aging, no matter what their researchers find?

http://www.pnas.org/content/112/33/10407.full “Pleiotropic age-dependent effects of mitochondrial dysfunction on epidermal stem cells”

Another factor in producing new brain neurons in the adult hippocampus

gettingwell4 4-5 stars Advanced knowledge, Glutamate, Hippocampus, Limbic system, Neurochemicals

This 2015 New York rodent study provided further details on the production of new neurons in the adult hippocampus. The researchers found that a protein that regulated a glutamate receptor also:

“Significantly influences hippocampal neurogenesis and that both the proliferation and survival of newborn neurons are impaired in the absence.”

The study showed:

“The effect of Norbin [the protein] on neurogenesis is likely caused by a nonautonomous niche effect.

These results show that Norbin is a regulator of adult hippocampal neurogenesis and that its deletion causes depressive-like behaviors.”

http://www.pnas.org/content/112/31/9745.full “Norbin ablation results in defective adult hippocampal neurogenesis and depressive-like behavior in mice”