Blocking glucocorticoid receptor in GWI (Klimas at #MECFSConf18)

https://twitter.com/user/status/992518926310535169


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.

 

"
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?

 

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.

 

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

https://www.youtube.com/watch?v=VUDhI0gXbbE

 

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.

 

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.

 

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?

 

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

 

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.

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 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.

 

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

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.

 

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.

 

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 (

 

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.'

 

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.