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. ------------- 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. ------------- 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.