Dr Mariano on Dr Goldstein and CFS

[heapsreal]

Thank you for bringing up Jay Goldstein, M.D. Unfortunately, he retired before I ever got a chance to talk with him or learn directly from him. But his books are some of my favorites. And notably, Jay Goldstein, M.D. was also a psychiatrist before he left psychiatry to go into primary care, specializing in the assessment and treatment of chronic fatigue syndrome. When I read his books, I thought he was far ahead of his time - too far, actually, for most people to understand him. He is exceedingly bright. However, I believe he also burned out, retiring too early. Which is a loss to all of us. I would have loved to hob-knob and talk shop with him.

There are problems, however, in Jay Goldstein's ideas. First of all, he overly focused on the central nervous system to the exclusion of the endocrine system and immune system, metabolism and nutritional factors, in his search for causes of chronic fatigue syndrome. Perhaps because he was a psychiatrist he did this. But as a result, he missed the huge set of interactions that are possible when one considers the nervous system, endocrine system, and immune system as one system, as I do. He still separated mind from body - which I believe is an arbitrary delineation.

Second, he did not do lab tests. Rather, he gave patients various medications to elicit their reaction to them. Then by knowing the mechanisms of action of the medications and their reactions to the medications, he extrapolated the presumed pathophysiology underlying chronic fatigue syndrome. This style of logic is called the pharmacological bridge. This is the same logic that allowed psychiatrists to come up with the biogenic amine hypothesis for depression. There are flaws in using this type of logic. First of all, how does one know, for example, that the reactions reflect secondary, tertiary, etc. responses to the initial medication? Using the pharmacological bridge can lead one astray if it is one's only tool. If he did lab testing also, he would have had a better chance to determine what is going on.

Thus, I believe he missed a lot and did not see the whole body causes of chronic fatigue syndrome. But he did get in right in that overactivity in certain areas of the brain can lead to chronic fatigue and to fibromyalgia.

In any case, I greatly enjoy his books, the enormous research he did (which gives me large numbers of references, thank you, Jay) and the thought processed he employed.

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The two primary catecholamines in the brain are Dopamine and Norepinephrine. A few neurons employ Epinephrine, but so far, they don't have a large role in brain function.

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Generally, I do not see low brain norepinephrine (noradrenaline) levels in chronic fatigue syndrome. It may be low in patients who want to sleep all the time. But generally, the patients I see have insomnia instead. Insomnia is condition caused by excessive norepinephrine production.

When cortisol is low, norepinephrine generally goes too high since cortisol can no longer control norepinephrine signaling well.

Loss of well being may reflect low dopamine with high norepinephrine levels. Dopamine is the reward signal, the signal that one feels well, whatever the norepinephrine level is - high or low. But the levels of dopamine and norepinephrine may also be a secondary reflection of immune system pro-inflammatory vs. antiinflammatory balance, current endocrine status, current nutritional status, etc.

Loss of motivation my reflect low dopamine and/or low norepinephrine, but also may reflect high pro-inflammatory cytokine signaling, low cortisol signaling, low estrogen signaling, suboptimal nutritional status supporting these signals, etc. etc.

Loss of creativity may reflect the sum of multiple signaling and metabolic problems not just low dopamine or low norepinephrine.

 

[heapsreal]

Quote:
Originally Posted by hardasnails1973
What can one do to identify the imbalance in cytokines? Are there any specific blood tests which would go beyond the normal scope of LP-PLA2, CRP, CBC, ect?

It would be nice to be able to measure the interleukins, tumor necrosis factors, interferons, etc. But medical technology has not advanced to the point we can measure and monitor specific cytokines on a regular basis yet. It hasn't even advanced to the point of regularly monitoring nutritional status past amino acids yet. From my point of view, if it isn't available from major laboratories, it isn't available as a standard test yet.



Quote:
If one has low dopamine and high norephipherine in an adrenal related illness what modalities could be applied to help rectify this case.

1. MEDICATIONS: I address excessive norepinephrine signaling using one or more of the many psychiatric and non-psychiatric medications. If anything, the vast majority of psychiatric medications have as an endpoint, reduction of norepinephrine signaling. Sometimes, dopamine agonists or reuptake inhibitors are useful.

2. SIGNALS: Improving anti-stress signaling is important to help balance excessive norepinephrine/stress signaling.

3. METABOLISM-NUTRITION: Improving nutritional status would help improve non-stress related energy production and would help anti-stress signaling.

4. BEHAVIOR-PSYCHOLOGY: Reduction in environmental stress, psychological stresses, improving skills to adapt to stresses.


Quote:
Will quest diagnostics catecholamine test provide enough information to see what part of the adrenals are over or under active?

No.

The adrenal gland has two parts: the medulla and the cortex.

The fractionated catecholamine test gives one an idea of adrenal medullary function - e.g. production of norepinephrine and epinephrine.

Other tests are necessary to help monitor adrenal cortex function.


Quote:
If one has low dopamine, adrenaline, norepinepherine, low serotonin, would one look towards potential intestinal issues or factors that could be altered amino acid metabolism.

Low central nervous system dopamine, norepinephrine and serotonin would be an unusual case. For example, dopamine production and serotonin production are generally inverse to each other. Both dopamine and serotonin are control signals to the locus ceruleus, which produces norepinephrine. Thus having all three low is unusual. Epinephrine in the central nervous system is produced in miniscule amounts compared to the other catecholeamines. Thus stating it is low begs the question: by what criteria?

When it comes to measurements from the body, as opposed to the central nervous system: low dopamine has no clear meaning since dopamine in the body comes mostly from dopamine leakage from norepinephrine neurons. Dopamine production would reflect primarily norepinephrine production.

When body epinephrine and norepinephrine measurements are low, then I would think about factors that can disconnect the sympathetic nervous system from the adrenal medulla, such as diabetes.

When it comes to intestinal issues, the primary concerns wold be:
1. Is there adequate protein and fat intake - since fat is necessary for adequate absorption of many amino acids.
2. Are there factors which impair nutrient absorption, such as mineral deficiencies, inflammatory bowel disease, gastric bypass surgery, concurrent nutrients (e.g. tryptophan being more easily absorbed if there are carbohydrates available), etc. etc.?


Quote:
What factors would alter amino acid metabolism?

Amino Acid metabolism is a huge subject which cannot be discussed fully. One would have to be more specific since the subject encompasses everything from enzyme synthesis, protein synthesis, DNA, RNA synthesis, creation of structures such as receptors, various peptide signals, myelin chain formation, formation of cellular organelles, etc. etc. etc. etc. etc. etc.

If you mean amino acid absorption, then factors that affect absorption and thus availability to cells of specific amino acids for purposes of cellular metabolism would be considered as discussed above

 

[zzz]

I'd like to respond to a few points made in the first post.

Dr. Goldstein did not burn out. His retirement was forced, not voluntary. Despite the fact that he was curing 95% of his CFS patients of their symptoms, a group of doctors who did not approve of his methods got together and convinced the California medical board to revoke his license. The grounds, ironically enough, were that he did not know how to treat CFS properly, despite the fact that he has been the most successful CFS clinician in history. Dr. Goldstein details the whole story in his book "Tuning the Brain".

As for the statement that "he overly focused on the central nervous system to the exclusion of the endocrine system and immune system", I don't see this at all. He was well aware of the connection of all of these systems, and basically detailed how problems in the brain (such as the hypothalamus) could cascade into problems with these other systems. It's clear that these other systems are intimately involved in ME/CFS; Dr. Goldstein could not have achieved his 95% success rate if his methods did not address these symptoms. So I don't see that he separated mind and body at all - hence his coining of the term "neurosomatic medicine".

As far as low norepinephrine levels go, this really rang a bell with me when I read about it. When last measured, my cortisol was high, so I would not expect that to cause high norepinephrine levels. And I do have fairly severe insomnia. But insomnia can be caused by a huge number of factors. In my case, I discovered a while ago that the fast-acting TCA desipramine, which mainly boosts norepinephrine levels, was very effective at relieving my insomnia, as well as getting rid of a "wired" feeling during the day. So Dr. Goldstein's statements about norepinephrine correlate completely with my own experience.

 

[Helen]

Thanks @heapsreal and @zzz.
The book is rather expensive but you can read excerpts from it here
http://www.amazon.com/Tuning-Brain-Principles-Practice-Neurosomatic/dp/078902246X/ref=sr_1_1?ie=UTF8&qid=1401105003&sr=8-1&keywords=Tuning the Brain
I found some interesting and promising pages about gamaglobulin therapy on page 26-27.

It would be fantastic if it would be possible to get an interview with Dr. Goldstein. He is surely experienced.

To my pleasure I could also read glutathion and methyl groups in the index. @zzz did you read his thoughts on this?
( Rich Van Konynenburgs hypothesis is still possibly true).