Posts Tagged ‘Parkinson’s disease’

Suggestible You 5

March 21, 2017

“Suggestible You” is the title of a book by Erik Vance.  The subtitle is “The Curious Science of Your Brain’s Ability to Deceive, Transform, and Heal.  This book is about the placebo response and related phenomena.   This is the fifth post on this book.

Vance describes the story of a man diagnosed ten years ago being severely debilitated in late stage Parkinson.  He volunteered for an experiment in which the medication was directly injected into a critical part of the brain.  To control for the placebo effect, these experiments require sham surgery that copies everything about the surgery except for the critical drug injected into the brain.  The study involved 51 participants.  Twenty-four people got the real surgery and 27 got the sham surgery.  The drug proved to be a failure.  However, the participant of interest did show a remarkable recovery.  However, he was one of those who had received sham surgery.

This dramatic example makes the point that there are large individual differences in the response to placebos.  Kathryn Hall of Harvard University was interested in studying possible genetic bases for this enhanced responsively.  She discovered the COMT gene.  The COMT genes codes for an enzyme in the brain, also called COMT, or catechol-O-methyltransferase.  Vance writes that this is one of the best-studied brain pathways in the world, and may be the most fascinating link he has discovered as a science writer.

Here’s how it works.  Dopamine has enormous power and is important for body movement and good moods.  However, it is possible to have too much of a good thing.  A mechanism is need to sweep up the bits we don’t need—the extra dopamine molecules floating around our skull that aren’t doing anything useful.  COMT gets rid of the excess dopamine molecules.  COMT is an extremely long and complicated enzyyme.  Fortunately, it is one within its machinery that defines how well it works.  Depending upon an individual’s genetics there are two types of this crucial portion of the enzyme:  valine (val) or methionine (met).  If one’s brain has val in that one spot, the enzyme performs its job of removing excess dopamine.  However, if the enzyme has met in that one spot, it is much less effective.  The brain is left with lots of excessive dopamine.

Remember that each trait in the body is a combination from each of the parents.  COMT works in a similar manner.  So we have val/met, but also val/vals and met/mets.  So 25% of the population are val/vals,and 25% are met/mets, 50% of the population are val/mets.

Hall conducted an experiment pairing COMT genes with placebos.  She enrolled 262 patients with irritable bowel syndrome (IBS) into an experimental treatment involving acupuncture.  She selected patients with either moderate or severe cases of IBS and then divided them into three groups. One group, the true control group, was put on a waiting list and given nothing.  The other two groups were told that they would get acupuncture, but they were unknowingly given fake acupuncture.  Half of the participants got treatment from a comforting, caring acupuncturist while the others got treatment from a cold, uncaring acupuncturist.

Here are the results.  People on the waiting list stayed the same regardless of their genes.

Met/mets with the uncaring acupuncturist  did better than the val/vals, but just barely.

Val/vals with the caring acupuncturist did about as well as the val/vals with the uncaring acupuncturist and all the people on the waiting list. In short, no placebo effect.

The val/mets who got the caring acupuncturist did about five times better.

The results of the met/mets who got the caring doctor went through the roof.

Clearly the kind words  meant something totally different to one genotype than it did with the others.  Hall had divided the placebo responders into measurable groups.Met/mets—those people who were born with lazy enzymes and a little too much dopamine in their responses were more prone to placebo responses.

Although the COMT gene plays a large role in the creation of the COMT enzyme, it’s not the only gene that does so.  Other genes help build the enzyme that can boost or cripple its performance, as well as all the other genes in you body that affect dopamine.    COMT also goes after epinephrine and norepinephrine, neurotransmitters that are key to regulating adrenaline, cardiac, function, and our response to stress.

So, in summary, the interactions are complex.  But different factors that contribute to the immune response are being identified.  Genes, the administrator of the placebo, and our fellow human beings are factors.

Humans as Superorganisms

July 31, 2015

This is the first part of a title, “Humans as Superorganisms:  How Microbes, Viruses, Imprinted Genes and Other Selfish Entities Shape Our Behavior” by Peter Kramer and Paola Bressan of the Department of General Psychology, University of Padua, Italy.  It was published in Perspectives on Psychological Science, 10, 2015, 464-481.  The only other article in this general area in the healthy memory blog is “You Have Two Brains.”  That blog barely touched this topic.  The authors note that psychologists and psychiatrists tend to be little aware of the science in this area, although they should be.  I believe that the general public is even less aware.  The objective of this blog post is to increase awareness somewhat.  As you will see, it is definitely relevant.

Let us begin with brain microbes, the most instructive of the lot is Toxoplasma gondii.   Sooner or later this brain microbe will infect about half or even most of us with potentially serious consequences for our mental health.  Eating meat undercooked is by far the most typical, though not the only way of contracting this parasite.  The infection rate is about 10% to countries with religions that promote vegetarianism, to 50% in some developed European countries, and over 70% in some parts of Africa and Latin America.  The adverse consequences of this microbe are potentially reckless behavior, depression, bipolar and obsessive-compulsive disorders.  It raises the probability of developing schizophrenia 2.7 times and is the largest known single risk factor, larger than any of the currently known genetic and environmental ones.

Gut microbes are for the most part beneficial.  This is fortunate as there are so many of them.  The human gastrointestinal tract houses up to 100 trillion microorganisms, belonging to more than 7,000 strains:  collectively, these contain 10 times the number of human cells and 100 times as many genes as our genome.  Each of us harbors at least 160 bacterial species, many of which are shared among us but in different proportions.  It is estimated that the gastrointestinal tract contains at least 500 million neurons, it is not surprising that gut microbiota and the brain communicate to each other.  Research has found that ingesting probiotics (microorganisms whose consumption provides health benefits, typically bifidobacteria and lactobacilli) that can mitigate some mood disturbances.  One recent study went beyond self reports showed that probiotics modify healthy women’s brain activity in regions that control processing emotion and sensation, dampening reactions to facial  expressions of anger and fear.  These same brain regions are involved in anxiety disorders.  When more research is done in this area, it is likely that more benefits will be found.

Brain viruses work both ways.  Some viruses exploit humans, but humans are also able to exploit some viruses.  Viruses exploit humans via our genes. For example, cytomegalovirus is a herpes virus that infects a majority of the world’s population.  The infection is usually benign, but not always.  It one large study this was not the case for 15% of the subjects who carried a particular variant of a gene involved in the stabilization of neuronal connections and in synaptic plasticity essential to learning and memory.  In the carriers of this gene variant, maternal cytomegalovirus infection increased fivefold the probability of developing schizophrenia.
We humans have begun to parasitize our parasites.  Some viruses are modified in the laboratory and then used to infect people to treat various genetic conditions, including those that affect the brain.  In one study 16 patients with Parkinson’s disease had a modified virus, containing genes that modulate the neurotransmitter GABA, injected into their brain. Relative to a control group of 21 patients who had received a sham injection, the motor ability of the experimental group improved by about 10%—a modest, but promising start.  In another study, patients with Alzheimer’s were treated with the help of a modified leukemia retrovirus that reduced degeneration.  The retrovirus contained genes that induced infected cells to produce nerve growth factor; cells infected in vitro were then implanted into the patient’s brain, in a specific area  that promotes cortical plasticity and memory.

Evidence is mounting that cells can be modified by the invasion of selfish entities that are not microorganisms or viruses.  These foreign cells come from another human person.  This topic becomes fairly technical, which will preclude further elaboration in this post.  This is also the case with the topic of imprinted genes. Just be aware that all of us carry genes originally designed to produce viruses.

So there is much to be learned.  Although there is much to be worried about, there is room for optimism and hope of new means of treatment,

The Latest Discoveries in Neuroplasticity

April 26, 2015

These can be found in the book, The Brain’s Way of Healing:  Remarkable Discoveries and Recoveries from the Frontiers of Neuroplasticity by Norman Dodge, M.D.  This is the sequel to his earlier book, The Brain That Changes Itself. I am especially impressed as when I was a graduate student, there was no such thing as neuroplasticity.  Once damage was done to the nervous system, it could neither be treated nor repaired.  The nervous system was fixed and not amenable to change.  So The Brain That Changes Itself was eye opening and overwhelming.  The Brain’s Way of Healing does not disappoint.

Doidge is a Canadian psychiatrist who has received research funding from both the National Institute of Mental Health in the United States and the National Health Research and Development Program of Health Canada.  And obviously he is an accomplished writer who knows this topic intimately.  You can visit his webpage http://www.normandoidge.com.

He relates case histories, explains the underlying  science, and documents this research with references and notes in the back of the book.

The first chapter discusses a physician who specialized in the treating pain discovering how Chronic Pain can be unlearned.   He discovered this in learning how to cope with his personal chronic pain and then formulated a course of treatment using this method.

The next chapter presented the case history of a Parkinson’s sufferer who learned how to walk off his Parkinsonian symptoms.  This showed how physical exercise helps fend off degenerative disorders and can defer dementia.

The third chapter discusses the stages of neuroplastic healing explaining how and why it works.

Chapter four explains how the brain can be rewired with light by using light to reawaken dormant neural circuits.

Chapter 5 introduces us to Moshe FeldenKrais, a physicist who had a Black Belt in Judo and who developed a means of healing serious brain problems through mental awareness of movement.

Chapter 6 explains how a blind mind learned to see using the method of Feldenkraus, Buddhist and other Neuroplastic Methods.

The seventh Chapter discusses a strange device called the PoNS that stands for Portable Neuromodulation Simulator because when it stimulates the brain, it modifies and corrects how the neurons are firing.  It stimulates modulation to reverse symptoms.  It has been successful in treating traumatic Brain Injury, Parkinson’s, Stroke, and Multiple Sclerosis.

The eighth chapter discusses how sound can be used and the special connection between music and the brain.  It has been successful in treating dyslexia, autism, attention deficit, and sensory process disorder.s

There are three appendices.  The first presents a general approach to Traumatic Brain Injury (TBI) and brain problems.  The second appendix discusses matrix repatterning for  TBI that has been developed by Canadian clinical Dr. George Bush.  Appendix 3 discusses neurofeedback for Attention Deficit Disorder (ADD), Attention Deficit Hyperactive Disorder (ADHD), Anxiety, and TBI.

After reading all this, it is understandable that you might conclude that this is bunk, it is simply too outlandish.  Please accept my assurances that this is not the case, and that this is genuine research at the forefront of knowledge.  I hope the Veterans Hospitals are applying this research to veterans suffering from trauma.  And I would like to encourage sufferers of these maladies to read about these treatments.  However, I am reluctant to do so, because there is little information on where information can be found to pursue these treatments.  Perhaps if it were, the limited resources available would be overwhelmed.  It will take time for this research to trickle down with resultant treatment centers employing and furthering the research.

How Placebos Could Change Research and Practice

March 29, 2015

The title was on the cover of the April 2015 Monitor on Psychology of the American Psychological Association.  Inside the issue was an article by Stacy Lu, “Great expectations:  New research is leading to an understanding of how placebos work—findings that may lead to more effective treatments and better drug research.  Our understanding and attitudes towards placebos is advancing.

In one study neuroscience researcher Shaffer and his colleagues asked participants to apply a “powerful analgesic” on their hands and arms.  Then the researchers administered small bursts of heat where the cream had been applied.  The cream was actually petroleum jelly, but participants reported that the s-called powerful cream protected them from feeling as much of a burn  as a control cream.  Even after the researchers showed them that the active cream was just petroleum jelly, it made little difference.  The participants still reported less pain from the heat when they were re-tested versus the control cream (The Journal of Pain, 2015).

Today scientists are studying  placebos as a psychobiological  phenomenon and the placebo response as a potentially important part of the success of many medical treatments.  Psychological assessments, brain scans, and genotyping are used  to understand better how placebo responses work and to identify who may be most likely to respond to them.  Placebos are similar to cognitive therapies in that they tap into people’s beliefs that there’s hope and that they will get better.

A meta-analysis of 25 neuroimaging studies of pain and placebos conducted by Wager and Atlas of the National Center for Complementary and Integrative Health (NCCIH) found that people who took placebos and expected have reduced pain had less activity in brain regions associated with pain processing, including the dorsal anterior cingulate, thamalus, and insula (Handbook of Experimental Pharmacology, 2014).

Research suggests that placebos have the greater effect in neural systems involved with processing reward seeking, motivation, and emotion.  Placebos seem to work especially well in patients with depression, Parkinson’s disease, and pain.  All three conditions involve the neurotransmitter dopamine.  These are also areas where people can consciously monitor their own treatment results.

In a study of patients with Parkinson’s disease Wager and colleagues found that simply expecting medication altered brain activity in the striatum and ventromedial prefrontal cortex in brain areas associated with reward learning in ways similar to actual dopaminergic medication (Nature Neuroscience, 2014).

In another study of people with migraines, placebos elicited a response without any verbal cue to effectiveness,   Slavenka Kam-Hansen and colleagues openly labeled placebo pills for some patients who reported as much pain relief as those who also got a placebo but had been told that they’d received real medication. (Science Translational Medicine, 2014).

Genetics research has found that participants with a specific genotype related to having more dopamine in the prefrontal cortex reported having a larger effect from a placebo  treatment  than participants with a genotype that produces less dopamine in the prefrontal cortex (PLOS ONE, 2012).

Children seem to respond especially well to placebos.  In one study their placebo response was 5.6 that of adults (The Journal of Pain, 2014).

Patients are interested and enthusiastic about placebo  treatments.  They are pleased to discover that they can contribute to their own healing.

You Have Two Brains

December 26, 2012

As do I. It was described by Byron Robinson in The Abdominal and Pelvic Brain in 1907 and named the enteric nervous system (ENS) by Johannis Langley.1 About the same time it was found that the ENS can act autonomously. When its main connection with the brain, the vagus nerve, is severed the ENS still is capable of coordinating digestion. Interest in this gut brain dropped until the field of neurogastroenterology was born in the 1990’s. It has since been learned that about 90% of the signals passing along the vagus nerve come not from the brain above, but from the ENS.2

How do these two brains compare? Both have barriers restricting blood flows to their respective brains and are supported by glial cells. The first brain consists of about 85 billion neurons; the second brain has about 500,000 neurons. 100 neurotransmitters have been identified for the first brain; 40 neurotransmitters have been identified for the second brain. Each brain produces about half of the body’s dopamine. The first brain produces 5% of all serotonin. The second brain produces 95% of all serotonin. This final comparison is quite telling. Serotonin is best known as the “feel-good” molecule. It is involved in preventing depression and in regulating sleep, appetite, and body temperature. Serotonin produced in the gut gets into the bloodstream, where it plays a role in repairing damaged cells in the liver and lungs. Moreover, it is important for the normal development of the heart, as well as in the regulation of bone density by inhibiting bone formation.

Serotonin produced in the ENS affects mood by stimulating the vagus nerve. Research has shown that stimulation of the vagus nerve can be an effective treatment for chronic depression that has failed to respond to other treatments.3 These gut to brain signals via the vagus nerve might also explain why fatty foods make us feel good. Brain scans of volunteers given a dose of fatty acids directly into the gut had a lower response to pictures and music designed to make them feel sad that a control group given saline. The fatty acid group also reported being only about half as sad as the control group.4

Stress leads the gut to increase its production of ghrelin. Ghrehlin is a hormone that makes you feel hungrier as well as reducing anxiety and depression. It stimulates the release of dopamine in the brain both directly, by directly triggering pleasure and reward pathways, and indirectly by signals triggered via the vagus nerve. At one time during our evolutionary past, the stress-busting effect of ghrelin might have been useful, but today the result of chronic stress or depression can be chronically elevated ghrelin leading to obesity.

The second brain has also been implicated in a variety of first brain disorders. In Parkinson’s disease the problems with movement and muscle control are caused not only by loss of dopamine producing cells in the first brain, but also by dopamine producing cells in the second brain due to Lewy bodies. It is even suspected that the disease starts in the second brain as the result of some trigger such as a virus, and then spreads to the brain via the vagus nerve. Similarly the characteristic plaques and tangles found in the first brains of people with Alzheimer’s are present in their second brains also.

Cells in the second brain could be used as the basis for treatments. One experimental intervention for neurodegenerative diseases involves transplanting neural stem cells into the first brain to replenish lost neurons. Harvesting these cells from the brain or spinal cord is difficult. Neural stem cells have been found in the second brain of human adults.5 These cells could be harvested using a simple endoscopic gut biopsy. This could provide a ready source of neural stem cells. One research team is planning toed them to treat diseases including Parkinson’s.

1Young, E. (2012). Alimentary thinking. New Scientist, 15 December, 39-42.

2American Journal of Gastrointestinal and Liver Physiology, vol 283, p G217.

3The British Journal of Psychiatry, vol 189, p.282.

4The Journal of Clinical Investigation, vol 121, p. 3094.

5Cell Tissue Research, vol 344, p.217.

A Treatable Condition Misdiagnosed as Alzheimer’s

November 14, 2012

I came across an article1 in Parade magazine that motivated this post. There is a condition, Normal Pressure Hydrocephalus (NPH), that is frequently misdiagnosed as Alzheimer’s, Parkinson’s, or Creutzfeldt-Jakob disease. Worse yet, sometimes it is attributable to aging. This is a tragedy because NPH is treatable. The most distinguishing feature of NPH is a disturbed gait while walking. Memory losses and a loss of bladder control are other symptoms. These symptoms occur gradually. NPH occurs when the cerebrospinal fluid (CSF) surrounding the brain fails to be reabsorbed. Treatment for NPH involves the surgical implantation of a shunt in the brain to drain excess CSF into the abdomen where it can be reabsorbed.

Although this disease can occur at any age, it is more prevalent in the elderly. The Hydrocephalus Association estimates that at least 350,000 Americans, and 5 percent of people with dementia, have the condition. Mark Luciano, M.D., the director at Cleveland Clinic says that about 30 percent of his NPH patients were originally told that they had Alzheimer’s or Parkinson’s.

In the case of Jimmy Nowell that was discussed in the Parade article, one specialist diagnosed his condition as Parkinson’s. Another specialist diagnosed it as Alzheimer’s. Had Nowell and his wife stopped at this point, his conditioned would have worsened until he died. Unless an autopsy had been taken, everyone would have thought he had died of Alzheimer’s. If an autopsy had been done they would have discovered that the distinctive plaque and neurofibril tangles were missing and would have been pondering as to what killed him. Fortunately they found a neurologist who correctly diagnosed the condition when he took an MRI and compared it to an MRI taken several years earlier. His treatment was successful.

I confess my ignorance of NPH until reading the Parade article. I had mistakenly thought that I was fairly familiar with the literature in the Alzheimer’s area. Unfortunately, I am not alone in my ignorance as it is apparently shared by too many in the medical community. Please spread the word regarding NPH, so that people suffering from the condition mistakenly think they have or are misdiagnosed with another condition. NPH is a condition that can be successfully treated.

 

1Chen, J. (2012). What If Grandpa Doesn’t Really Have Alzheimer’s? Parade, November 11, p.22

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