Blocking glucocorticoid receptor in GWI (Klimas at #MECFSConf18)

[adambeyoncelowe]

Interesting. I see there's already some published info on this.

Achieving Remission in Gulf War Illness: A Simulation-Based Approach to Treatment Design
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508058/

A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness.
https://www.ncbi.nlm.nih.gov/m/pubmed/26600007/

 

[Amw66]

Interesting. I see there's already some published info on this.

Achieving Remission in Gulf War Illness: A Simulation-Based Approach to Treatment Design
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508058/

A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness.
https://www.ncbi.nlm.nih.gov/m/pubmed/26600007/

I have not seen a paper published, but Dr Amalok Bansal had suggested in LiME conference in Sweden 2014, that glucocorticoid B receptor was affected in ME.

 

[Sly Saint]

"
Veterans told: there is no Gulf syndrome
By Michael Evans, Defence Editor


March 25 2006, 12:00am, The Times

GULF WAR veterans suffering from illnesses since the 1991 conflict were told yesterday that, after 15 years’ research, no single cause had been found for their health problems.

The final judgment on “Gulf War syndrome”, dismissing it as a recognisable disease, was delivered by scientists from the Royal Society, the leading science academy in Britain.

In a study of all the work carried out into the syndrome since the conflict, the Royal Society said that it was time to call a halt. “I believe there is little value in conducting further research into the causes,” Simon Wessely, the co-director of King’s College Centre for Military Health Research, said.

Professor Wessely co-edited a special journal documenting the research findings that was published by the Royal Society…"


anyone told the Times/Simon Wessely? and the people who gave him a knighthood for his 'work' on this subject?

 

[Helen]

As professor Wessely is a psychiatrist he surely won´t find the cause of the Gulf Syndrome. I wished the Royal Society would listen to Dr. Garth Nicholson a.o. instead, but it is surely cheaper for the well-fare systeme not to. It would be interesting to read the list of references to his claim.

 

[Helen]

I have not seen a paper published, but Dr Amalok Bansal had suggested in LiME conference in Sweden 2014, that glucocorticoid B receptor was affected in ME.

Interesting. Here is the video from his talk at the Swedish RME conference in Stockholm, 2014

 

[Hutan]

Hmm. I am a bit dubious of these mouse models. How do you make a mouse model when you don't know what caused a physiological problem or what that physiological problem is? (Remember that CFS model produced by having the mice/rats? swim until exhaustion?)

And while the mathematical modelling of biological systems and stable disease states is very interesting and may one day be useful for ME/CFS, I suspect we don't know nearly enough about how the body works yet. Or for that matter, how to define the perturbed start point in ME/CFS.

There seems to be a big emphasis on high cortisol in GWI, or low cortisol in ME, or, well you know, something wrong with cortisol and, stress... and HPA axis, and PTSD, and, did I say, stress. I'm probably being too harsh with respect to Klimas' work, but that publication in the first post doesn't sound terribly different to the BPS crowd (e.g. that recent hair cortisol paper) apart from the fact that the BPS crowd are certain that the right kind of talking therapy will fix things whereas Klimas and Broderick et al think that medicines are needed.

Given the lack of evidence for levels of cortisol being abnormal in ME (maybe for some individuals, but not overall), I'm not getting excited about a report of work on blocking the glucocorticoid receptor in ME/CFS, or of success in fixing a GWI mouse model with, presumably, high cortisol and low testosterone.

Hopefully I'm wrong and they come up with something great.

 

[adambeyoncelowe]

Hmm. I am a bit dubious of these mouse models. How do you make a mouse model when you don't know what caused a physiological problem or what that physiological problem is? (Remember that CFS model produced by having the mice/rats? swim until exhaustion?)

And while the mathematical modelling of biological systems and stable disease states is very interesting and may one day be useful for ME/CFS, I suspect we don't know nearly enough about how the body works yet. Or for that matter, how to define the perturbed start point in ME/CFS.

There seems to be a big emphasis on high cortisol in GWI, or low cortisol in ME, or, well you know, something wrong with cortisol and, stress... and HPA axis, and PTSD, and, did I say, stress. I'm probably being too harsh with respect to Klimas' work, but that publication in the first post doesn't sound terribly different to the BPS crowd (e.g. that recent hair cortisol paper) apart from the fact that the BPS crowd are certain that the right kind of talking therapy will fix things whereas Klimas and Broderick et al think that medicines are needed.

Given the lack of evidence for levels of cortisol being abnormal in ME (maybe for some individuals, but not overall), I'm not getting excited about a report of work on blocking the glucocorticoid receptor in ME/CFS, or of success in fixing a GWI mouse model with, presumably, high cortisol and low testosterone.

Hopefully I'm wrong and they come up with something great.

To be clear: she claims the glucocorticocoid problem is in GWI, not necessarily ME. She doesn't yet have a mouse model for our illness, which appears distinct from GWI. I didn't read it as 'stress causes GWI', but even if she is saying that, it doesn't mean ME follows suit. GWI occurs in the context of major conflict (war, not interpersonal conflict) while ME doesn't.

Also, the BPS model specifically focuses on psychological and behavioural interventions. Klimas' model involves a biomedical switch to turn something off. Psychological illnesses don't usually get resolved that easily. That an illness involves dysfunctional neurotransmitters does not in itself mean that illness is psychological. Take Parkinson's, where there's a depletion of dopamine (not the only problem, I know, but treatment often involves replenishing neurotransmitters).

I can see that superficially the two things may look similar, but it's what the researchers conclude from their results. The BPS crowd always twists any finding to support a psychosocial aetiology. I think Klimas is more realistic (and scientific) than that.

 

[Hutan]

To be clear: she claims the glucocorticocoid problem is in GWI, not necessarily ME.

Well, the tweet says

Work to block receptor in #mecfs now in Phase I.

Why would they be working to block the glucocorticoid receptor if there wasn't at least a suspicion that it was a problem in people with ME/CFS?

She doesn't yet have a mouse model for our illness, which appears distinct from GWI.

True. But my doubt about a mouse model extends to GWI for the same reasons - you have to have the right biological mechanism before that is of use. The tweet says that ME/CFS has no mouse model yet, but that they are in phase 1 of trying to block the glucocorticoid receptor in ME/CFS. That implies that there will be a mouse model at some time later.

I didn't read it as 'stress causes GWI'

The paper says

a leading hypothesis points to the involvement of a neuroinflammatory cascade triggered by exposure to a neurotoxin and exacerbated by the stress of a combat environment

Indeed veterans with GWI have been shown to have significantly higher rates of PTSD, supporting the idea that GWI symptoms are exacerbated by stress.

To be fair, the paper suggests that it is a multifactorial process. And yes, stress may be a factor in GWI.

From the paper;

From our previous investigation of normal HPA-HPG-Immune regulation in male subjects (Fig 2) we found that the endocrine-immune profile experimentally measured in male GWI subjects most closely aligned with an AHM characterized by hypercortisolism, low levels of testosterone and a shift towards Th1 immune activation.

The answer they propose includes blocking the glucocorticoid receptor.

That's the same answer they are proposing for people with ME, even though, to me, the ME/CFS question is different. There is no good evidence that we have, on average, that same group of signs.

It's the focus on cortisol and glucocorticoid receptors in people with ME that I have the biggest problem with. Leaping to work on glucocorticoid receptors on the basis of assumed abnormal cortisol levels and HPA axis problems is premature. I don't think that there is evidence to support abnormal cortisol levels being a widespread or diagnostically important problem in people with ME.

 

[Hutan]

Here are the results from the hair cortisol study in women with CFS I gave a link to above. Does it look like women with CFS have a problem with raised cortisol like the men with GWI are supposed to have? Or indeed anything really odd with our cortisol that can't be explained by a global hypometabolism? If not, then why would the same approach of blocking the glucocorticoid receptors be helpful?

I'm just saying, this doesn't seem to me to be the type of work that is likely to bear fruit. I'd be putting more work into defining a problem in cortisol or some other problem relevant to glucocorticoid receptors in ME/CFS before fiddling with the glucocorticoid receptors. But on the other hand, who knows what intervention will find the answer to ME/CFS and I don't know much about what else this team has done. At least they are trying something I guess.

 

[adambeyoncelowe]

I asked #MEAN what Klimas is blocking but they didn't answer, so maybe she didn't say. I don't think it's the same receptor as in GWI. I think the tweet is just ambiguously worded.

My take away from it was that she's trying to block a different receptor for us, after identifying the GCR in GWI. I may have misunderstood, though.

 

[Fungi]

I am not sure I follow all of the previous messages but it sounds a little like what I was thinking.
The symptoms for PTSD are similar to chronic fatigue. According to an article I read in Psychology today,

https://www.psychologytoday.com/us/blog/the-aftermath-trauma/201606/cortisol-and-ptsd-part-1

a lot of PTSD patients have lower cortisol levels (or levels that the body cannot regulate) which are often dismissed by doctors as they are not significantly lower and are still within the acceptable range yet it has very significant effects on PTSD patients. In this article, it discussed various studies which showed that if pregnant women experience a trauma, they can ‘programme’ the foetus with the result that when their children grow up, they are much more likely to develop PTSD. This is true even if other people experience the exact same trauma as them but with no effects. In utero babies are particularly sensitive to hormone fluctuations and this then predisposes their babies to be more susceptible to stress i.e. to lack resilience. So I wonder if ME patients have a biological marker whereby if they experience stress/work in high demanding areas and therefore higher levels of cortisol, the body (PTA) as a system then fails and is unable to produce even sufficient cortisol required for daily life or is unable to manage the normal daily pattern which cortisol should follow. These individuals lack the physiological resilience to cope with stress/high performance which would not affect the vast majority of the population. Many of the symptoms of chronic fatigue could be explained by even a little lower cortisol levels which medical professionals would not even register as important. What does anyone think?

BTW what does GCR and GWI mean?

 

[Andy]

BTW what does GCR and GWI mean?

Welcome @Fungi . I'd assume GCR means glucocorticoid receptor, GWI definitely means Gulf War Illness.

 

[Hutan]

The symptoms for PTSD are similar to chronic fatigue.

I can't see the resemblance between PTSD and ME/CFS myself (or even between PTSD and chronic fatigue - that latter presumably just being fatigue that is chronic). Here's one list of PTSD symptoms:

The disorder is characterized by three main types of symptoms:

• Re-experiencing the trauma through intrusive distressing recollections of the event, flashbacks, and nightmares.
• Emotional numbness and avoidance of places, people, and activities that are reminders of the trauma.
• Increased arousal such as difficulty sleeping and concentrating, feeling jumpy, and being easily irritated and angered.

Are you familiar with the symptoms of ME yourself Fungi? May I ask what your interest is in ME?

So I wonder if ME patients have a biological marker whereby if they experience stress/work in high demanding areas and therefore higher levels of cortisol, the body (PTA) as a system then fails and is unable to produce even sufficient cortisol required for daily life or is unable to manage the normal daily pattern which cortisol should follow.

Regarding your idea that people with ME might have a biological marker caused by their mothers experiencing trauma while they (the people with ME) were in utero:
My mother was happy and calm when she was pregnant with me. I was happy and calm when I was pregnant with my two children. All three of us developed ME at the same time.

Regarding your idea that people with ME might not be able to produce sufficient cortisol required for daily life:
I don't believe that there is any good evidence for that. Do you know of some?

These individuals lack the physiological resilience to cope with stress/high performance which would not affect the vast majority of the population.

So, I think you are saying that people are predisposed to ME in utero and then become ill when exposed to stress? I routinely dealt well with challenging work for many years before becoming ill. My children had normal childhoods and were not dealing with high levels of stress prior to becoming ill. If your theory was correct, then we would expect to see massive rates of ME in civilian populations exposed to long-running wars. I don't think we have evidence of that.

 

[Fungi]

Apologies for the long post. Here are some of my meandering ideas based on the article referred to above - links here:
An interview with Dr. Rachel Yehuda in
https://www.psychologytoday.com/us/blog/the-aftermath-trauma/201606/cortisol-and-ptsd-part-1
https://www.psychologytoday.com/us/blog/the-aftermath-trauma/201606/cortisol-and-ptsd-part-2
https://www.psychologytoday.com/us/blog/the-aftermath-trauma/201606/cortisol-and-ptsd-part-3

First of all, although I am not a scientist, I have been trying very hard to understand CFS for the last two years since my son has been affected by it, so please bear with me.

Patients with PTSD do not show lower levels of cortisol when discharged from psychiatric wards unlike other patients. In fact patients with PTSD have significantly lower levels of cortisol at admission and discharge compared to other patients with psychiatric diagnosis. This seems counter intuitive as you would expect cortisol levels to be high in patients with stress disorders. So Dr Yehuda and Mason replicated the study and found the same lower levels of cortisol. They also observed elevated catecholamines. Apparently this is to be expected, that people who are aroused and under stress have high levels of catecholamines, like norepinephrine but lower cortisol levels were harder for people to accept. The prevailing concept was that PTSD always occurred following trauma exposure.

But once there was a body of literature that showed that a lot of people are trauma exposed and only a smaller subset of those people get PTSD, the field could start speculating that perhaps low cortisol signals an abnormality that helps explain why recovery has not occurred. It turns out that one of the things that cortisol does in response to stress is that it helps contain the catecholamine system—it helps bring down the high levels of adrenaline that are released during fight or flight. Since we all know that adrenaline and norepinephrine are responsible for memory formation and arousal, not having enough cortisol to completely bring down the sympathetic nervous system, at the time when it is very important for a person to calm down, may partially explain the formation of traumatic memory or generalized triggers.

At this moment, we cannot use cortisol levels to aid in diagnoses. They are too variable, and although there is a mean difference between PTSD and other groups, in every study that has been performed to date, there are a lot of overlapping data. Furthermore, even the low cortisol levels in PTSD are well within the normal endocrinological range. Then it took us into the dynamics of the way that the hypothalamic–pituitary–adrenal (HPA) axis works and is regulated by the brain. Cortisol levels show natural variation during the day, and are affected by environmental perturbations. It is adaptive that cortisol levels vary, because cortisol helps regulate many bodily functions when we are stressed, and when we are not stressed. What we have been doing for the last 25 years is studying the underlying dynamics of cortisol levels. We have examined circadian rhythm changes that may determine how the brain regulates the release of cortisol over a diurnal cycle. We have looked at cortisol metabolism, to try to understand how cortisol is broken down into its various metabolites in the brain, liver, and kidney.

But most of our studies have involved the glucocorticoid receptor and all of the genes and proteins that are involved in regulating the activity and sensitivity of that receptor. These studies have begun to give us an understanding that there is something really different about the stress system in PTSD, or in specific subtypes of people with PTSD,, but it is not going to be cortisol levels per se that are going to be useful to a clinician.

In PTSD, cortisol levels are not lower than normal range. They are significantly lower on average compared to persons without PTSD, but the levels themselves are not abnormal. The cortisol levels in PTSD do not suggest that the adrenal gland is broken in any way or not releasing cortisol, but rather, given the normal range of cortisol, which is large—between 20 to 90 micrograms per 24 hours of urine—the means we would get in PTSD were in the 40s. Whereas, a straight mean would be more like in the 50s and 60s. We are not talking about an endocrine problem. We are talking about a tendency to be at the lower end which is within normal variability. Why this was newsworthy, again, was that we were expecting that it would be higher in a stress disorder, because cortisol is associated with stress. I personally would not use cortisol levels, not even 24-hour urinary cortisol levels, as a diagnostic marker.

I would want to know a lot more about how the glucocorticoid receptor works. Is it more sensitive? What is the circadian rhythm like? What about cortisol metabolism? What about the genes that control cortisol and glucocorticoid functioning? So there is a potential to find biomarkers that relate to cortisol that may be clinically applicable—we have not given up on that idea at all. It’s just important to understand what kind of neuroendocrine or molecular neuroendocrine information is most relevant.

But you offer a very important clarification: the pattern in PTSD is of lowER cortisol levels, not low cortisol.

Furthermore, the effect size of cortisol differences is small, too. In the Boscarino study (1995), he reported that cortisol was lower in PTSD, but there was a very small effect size. So it is not a diagnostic test. It is just a clue, and we used it exactly as a clue to unravel a deeper mystery.

I see at least three or four ways that we could think about cortisol-based interventions. The first one might be prevention. That is the Zohar study, which is a study being conducted in Tel Hashomer hospital in Israel, headed by Dr. Joseph Zohar. When I first heard his idea of using cortisol in the ER to prevent PTSD, I have to admit I was sceptical, even though we are the ones that published that cortisol levels are lower in the immediate aftermath in persons who are more likely to develop PTSD. What Dr. Zohar said was, if that is true then we should be able to give cortisol during the “golden hours.” But I was nervous. Why? Because I think that hormonal response is something that you want to be very careful about changing, because the body has a wisdom. That is my general view of the world, but he convinced me that if you give a single really high dose of glucocorticoids within a 4-hour window of a trauma, then the effect that that might have would be to recalibrate the HPA axis in a way that provides enough cortisol to quiet down the sympathetic nervous system in a very organic and permanent way. Also, Dr. Hagit Cohen’s in Ben Gurion Medical School in Beer Sheva work with animal studies had shown that this might actually work to prevent PTSD if given during the “golden hours.”

Another way to effect changes in the HPA axis might actually be to block the glucocorticoid receptor. There is a trial that is ongoing now using a drug called mifepristone, which is a glucocorticoid receptor antagonist. You might know this drug by a different name. This study is being run by my colleague Dr. Julia Golier. You might know mifepristone as RU-486, or the abortion pill. RU-486 obviously has effects on the progesterone receptor, which is why it is an effective treatment to prevent pregnancy, but it also has effects on the glucocorticoid receptor. There is a trial that is ongoing now, ending August. The pilot study showed some benefit. What happens with that treatment is that you can block the glucocorticoid receptor and really recalibrate the ratio of peripheral to central cortisol. The beauty of that treatment is again you give it once or you give it for a very short period of time, and you look for recalibration effects. People like to take medications that way as opposed to every single day.

There is this whole issue regarding lower cortisol levels being a pre-traumatic trait, like, somebody already has this and then they are trauma exposed and have a higher chance of developing PTSD. What are the implications of this for screening and resiliency programs in clinical settings?

In our studies, we found that lower cortisol levels were present in rape victims who had had a prior assault. They are more likely to develop PTSD, but was their cortisol level already low? Is that why it did not climb up higher than it could have?

I think that these are important issues. Now, there was a fascinating study that was published by Mirjam van Zuiden and her group in the Netherlands that basically took a thousand soldiers, before they went into combat, and looked at cortisol and glucocorticoids receptor measures and markers, as well as genes and epigenetic markers of the glucocorticoid receptor. They found that low cortisol and enhanced GR sensitivity were predictors of people that had PTSD a few months later.

At least we are getting closer to understanding that not all the action occurs at the time of the trauma. That the stage might be set in advance, we are actually an accumulation of our experiences, and we hold biologic changes and then use them to respond differently to traumatic events as they emerge in our lives.

There are a lot of people that are studying the effects of child abuse and early trauma even in the absence of PTSD. Their work is also supporting lower cortisol levels. It may be that low cortisol will impact whether someone gets PTSD to a later trauma. The problem can be that when you study someone at one point in time and they have low cortisol but they don’t have PTSD, that does not mean that they will not develop PTSD if exposed to a trauma in the future. We do not know whether low cortisol measures are markers or predictors of the future, but I would suspect that there is a genetic component as well as an early environmental component that would make these markers predictors.

So, you might be resilient following the first three events, and then the fourth one occurs and then you develop PTSD.

Dr Yehuda talks about the idea that epigenetic changes in traumatised parents that occur as a result of their trauma exposure can be passed on to children. She gives the examples of effects in the children of holocaust survivors and in babies born to women who survived 9/11.

So by the time I was involved, some of the women had already given birth, but there had been a lot of information about what trimester they were in, about any pregnancy complications, exposure to toxins, etc. etc. So we added to that an evaluation of PTSD. Then when they came in for their 7 month to 1 year wellness baby evaluation, we were able to get salivary samples from the mother and the child. By then it did not surprise us to see that mothers with PTSD had lower cortisol levels than mothers without PTSD. But what did fascinate us was that in the mothers that had lower cortisol, the babies also had lower cortisol, but that this was a trimester dependent effect and that it seemed to split out in the second and third trimester in mothers who had been exposed in the middle of the second trimester or exposed in the third trimester.

When we had those findings, a lot of possibilities opened up in terms of how cortisol levels might be transmitted from parents to child or from mother to child. We were not the first people to make this observation. There has been a literature that that has demonstrated that mothers who are exposed to under feeding before puberty have children and grandchildren that have metabolic problems. Since we knew that the women exposed to starvation during pregnancy also tend to give birth to children who were more prone to hypertension as adults, we knew that there was the possibility of in utero effects.

But what seemed to happen here was an example of glucocorticoid programming. In the middle of the second trimester of pregnancy, there is an enzyme that becomes expressed in the placenta. It is an enzyme that blocks the conversion of cortisol to its inactive metabolite, cortisone. The induction of this enzyme really helps protect the foetus from detrimental effects of maternal glucocorticoids, because the cortisol is broken down into its inactive metabolite, cortisone. The enzyme is called 11β-Hydroxysteroid dehydrogenase type 2. We had already been interested in studying this enzyme just because we were interested in cortisol metabolism. But it turns out that in mothers who are under stress, it is very possible that their enzyme levels and the amount of glucocorticoids they have could overwhelm the body’s ability to metabolize cortisol into cortisone and affect the foetus. That was one idea that we had, that there might be a transmission based on offspring response in utero to maternal levels of stress hormones.

The message is straightforward: mothers who are stressed during pregnancy can program the stress response of their offspring, in utero, and the offspring accommodates somehow to the level of stress hormone. That has become a very important issue also in our intergenerational studies. It has become one viable mechanism through which mothers may “transmit” different vulnerabilities (or resilience) to their offspring. One does not need to have actual trauma experiences post-natally in order to have some of the neuroendocrine features associated with PTSD and PTSD risk. And this means that pregnancy is an important time with great social implications for our society. I do not think that we think about pregnancy as the very important developmental event that it really is. Otherwise, we would be really taking much better care of traumatized pregnant women than we do.

So my interpretation idea is as follows:

Working mothers may experience more stress with higher cortisol levels which the body is unable to break down into cortisone. In utero babies are particularly sensitive to hormone fluctuations and this then predisposes their babies to be more susceptible to stress or hormonal fluctuations i.e. to lack hormonal resilience. As more women have entered the labour market, many work in demanding and stressful jobs, they pass on a physiological predisposition to their offspring which means their child is physically unable to cope with stress or hormonal fluctuations i.e. they lack physiological resilience.

This could then possibly explain the rise in mental health in young people in Britain in recent decades, what some people refer to as an epidemic of mental health. The government talks about helping to make children more resilient but that could be something built into their very DNA which external individuals would find hard to mitigate.

 

[Fungi]

This could then perhaps explain why some individuals are susceptible to CFS while others who experience the same events are not.

The other thing that I think is really important is this idea that the designation of PTSD is a static one, or that it is binary or not dynamic. We have to rethink that. Now that I have the perspective of having years in the field and seeing the same trauma survivors over a period of many years, even decades, I understand that the same person can at sometimes meet diagnostic criteria for PTSD while at other times, that person may not. Do we view the person as always at risk after s/he has recovered? Especially when you have recovered from something and you are asked about having had it in the past, your memory is not so good for how much you have suffered in the past when you are feeling good right now.

Many CFS patients have improved only to find that they relapse again. Also, many patients when they have been ill for a number of years with chronic fatigue readjust to their new norm and may say their health is good when in fact it is just that they have adjusted to a life with a severe disability e.g. not working, living in a bubble etc . I view the person as always at risk even after they have recovered they may relapse as they have biomarkers that predispose them to trauma.

Finally, I think we have been paying a lot of attention to the psychological aspect of trauma and not enough to the physical illness part—the fact that people who are exposed to combat may die at an earlier age, make poor behavioral health choices, and are more prone to hypertension, metabolic syndrome, inflammatory illness, cardiovascular disease, and cancer. These cannot be coincidences, but may either be part of the trauma effects, or part of the PTSD effects. Why are we not more focused on the biomarkers that might help explain and reverse some of these illnesses? When will we start seeing PTSD and trauma exposure as the multisystem condition that it is and really try to integrate care plans that not only assess for nightmares, hyper vigilance, and concentration, but diet and exercise and hemoglobin A1c? These are markers for trauma survivors because they are at greater risk for all these issues, not to mention cognitive decline.

Dr. Yehuda: It does not make sense. Many veterans that come for care do not take such good care of themselves. It is not a priority for them. They do not maybe eat as well as they could or they have really disrupted sleep. I would like us to think about trauma as something that really does affect the whole body and our behavioral health choices.

Dr. Jain: Yes, and enhance overall quality of life, too.

Dr. Yehuda: I think patients talk about what we (as healthcare professionals) want to talk about, and we lead the conversation in a symptom focused way. The symptoms of PTSD are impairing, don’t get me wrong, I am just saying there is a greater range of problems than are contained in the PTSD diagnosis.

Dr. Jain: I could not agree with you more. I feel like it is in the air. We are on the verge of embracing it that way. We are just not quite there yet.

Dr. Yehuda: I completely agree with you, and I think that the reason for that is that as we do our research on a genome wide level, we identify that so many of the biomarker pathways that seem to be altered relate to inflammatory immune functions. The pathways that are being identified in people with PTSD are not just those that associate with psychiatric symptoms, but really affect much more bodily functioning. I think that is also a lesson, just to close the loop on this that has been learned from the glucocorticoid story in PTSD. Cortisol is not just about mental health. There are GRs in almost every cell in the body. Cortisol has a myriad of different functions in different target tissues, mostly in the metabolic systems promoting fuel and energy. It is silly to just think about cortisol's role in traumatic memory when cortisol is a ubiquitous hormone that has so many different roles.

 

[Fungi]

Following on from my last post, I just wonder if ME/CFC is due to the inability of the body to regulate cortisol levels a bit like diabetes is due to the body's inability to produce/regulate insulin. This could be due to an autoimmune destruction of the cortisol producing cells in the cortex of the adrenal glands. It affects lots of areas in the body such as metabolism and immune response. This would be different than Addison’s or Cushing’s disease as cortisol levels may fluctuate i.e. be too high at some point and too low at others leading to inconsistent findings or perhaps the irregular levels may not be significant enough to merit medical interventions.

 

[Seven]

Hmm. I am a bit dubious of these mouse models.

She explained it, everytime she gave the neurotoxins ( I think it was or pesticide?)then stress them. Did that a few time and bang they have GWS (

 

[Fungi]

I can't see the resemblance between PTSD and ME/CFS myself (or even between PTSD and chronic fatigue - that latter presumably just being fatigue that is chronic). Here's one list of PTSD symptoms:


Are you familiar with the symptoms of ME yourself Fungi? May I ask what your interest is in ME?


Regarding your idea that people with ME might have a biological marker caused by their mothers experiencing trauma while they (the people with ME) were in utero:
My mother was happy and calm when she was pregnant with me. I was happy and calm when I was pregnant with my two children. All three of us developed ME at the same time.

Regarding your idea that people with ME might not be able to produce sufficient cortisol required for daily life:
I don't believe that there is any good evidence for that. Do you know of some?


So, I think you are saying that people are predisposed to ME in utero and then become ill when exposed to stress? I routinely dealt well with challenging work for many years before becoming ill. My children had normal childhoods and were not dealing with high levels of stress prior to becoming ill. If your theory was correct, then we would expect to see massive rates of ME in civilian populations exposed to long-running wars. I don't think we have evidence of that.

I see in this article that GWI has similar symptoms to CFS. 'GWI symptoms span several of the body’s principal regulatory systems and include debilitating fatigue, severe musculoskeletal pain, cognitive and neurological problems.'

 

[Fungi]

A few years ago I watched a bee 'staggering' around my garden as if it was blind or blind drunk. Some time after that I heard about the negative impact of pesticides on bees that can lead to Colony Collapse Disorder and it was like a Eureka moment as it made total sense. Reading this article here explains the effects of neonicotinoid pesticides as resulting in less movement and activity from queen bees and worker bees. However, if dosage of neonicotinoid was increased there wasn't a proportional response from different honey bee colonies i.e. even less activity. In other words, some colonies were better at detoxifying than others. I wonder if something similar is going on with CFS patients; that somehow their environment is toxic to them. Do they have biological markers that make them more susceptible and less able to detoxify? I mentioned it to my son's osteopath and she said that the ME patients she treats who live near farm land are worse during spraying season. I realise this is anecdotal but interesting nonetheless.

This links in with something else I was thinking about. There was a tragic death some time ago of a teenager who had a severe allergic reaction to sesame seeds and died while on a flight to France. Discussing allergies, they mentioned that there is often a link between childhood asthma and eczema and developing severe allergies later on. There has also been a dramatic increase in the number of people with severe allergies with around 2% of the population (if I remember correctly) having such an allergy. Again I just wondered how many CFC patients have similar issues in childhood i.e. asthma/eczema/food allergies and whether their bodies are programmed to react as if poisoned leading to systemic failure? Some can detoxify/repair themselves very slowly over a long period of time.