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XMRV AND ANXIETY DEPRESSION THE anxious Amygdala

alex3619

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Hi Gerwyn,

This is an interesting hypothesis. CREB has been commented on before in connection with CFS, so this is something that should be investigated.

Bye
Alex

Take home message

XMRV inserts into CREB genes causing insertional mutagenesis.

In simple terms that means that it can change the activity of the gene and a change in the nature and function of the proteins made.
 

alex3619

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Hi Gerwyn

Apparently at the recent Invest in ME conference the issue of osteoporosis was raised, and we are at risk. The pathophysiology of CFS gives us several risk factors which should have been recognized long ago. I know I have written on this elsewhere some years ago.

Bye
Alex

This is what was worrying me if XMRV downregulates creb then osteoporosis is a real possibility

REB induces BMP2 transcription in osteoblasts and CREB knockout reduces bone mass in mic
 

alex3619

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Hi Gerwyn

I think your analysis is very likely. The brain is highly plastic up till about the age of six or seven, when plasticity decreases. Does anyone know if many cases of autism occur after age seven? I don't recall reading that it does.

bye
Alex
it looks as though the functional organisation of neurons into representations networks and circuits is disrupted leading to increased neural redundancy which would lead to an increase in overall volume but reduced density
 

alex3619

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Hi Recovery Soon

I have commented on this on another thread. You are not alone. This only occurs in me with brain fog or mental fatigue so intense that I lose the ability to speak - and barely have the strength to stand. It also requires a trigger, usually verbal abuse, but it can also be something as simple as a friendly pat on the back.

Bye
Alex
When my symptoms are bad I often feel a Rage so intense I have to avoid other people, for fear of violence.

I don't know how common this is, but it almost feels like insanity when it strikes, and it's directly correlated with bad symptoms.

This is something different than being irritable because I feel crappy- it completely unbalances my mental equilibrium.

Anyone else get this?
 

alex3619

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Hi Kurt,

My understanding is that the key to this arguement is brain plasticity. If intense damage occurs to the brain, young children have a huge capacity to compensate. If the brain merely senses damage, which may be more functional than structural, then there is a real chance the brain will overcompensate. This will result in increased hypersensitity in the amygdala and other regions of the brain. Under this model it is to be expected that we are sensitive to light, sounds, smells, voices, and other people.

A complicating factor is that in brain damage other areas of the brain can be co-opted for functions in the damaged region. This will result in deficits in all areas that have neuronal connections to the damaged area and are co-opted (neuronal remodelling).

I haven't touched this topic much for fifteen years, but neuronal modelling (computer models anyway) was a key part of my Ph.D. candidature.

Adults also retain some brain plasticity, at all ages. This could be why we get many ME and CFS symptoms, but also have symptoms resembling autism. It would be interesting to study if the symptom profile changes with age of onset of ME and CFS.

Remodelling is competitively driven if the old science I read in the 90s is correct. So it isn't precise or specific, only adaptive, and could cause different problems in different people.

The damage may also not be restricted to the amygdala region.

Bye
Alex

Anyway, I think your idea that XMRV is damaging the amygdala is very interesting. However, if that were happening in a way that lead to neuron damage or death, such as compromise of the CREB production, then would not the logical outcome be that the amygdala would have lower function?
 

natasa778

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Does anyone know if many cases of autism occur after age seven? I don't recall reading that it does.
it does, but very rarely. there are documented, published cases of previously healthy persons becoming autistic at the ages of 7, 11 and 14. Also one published case of a 30-something-year-old. All these cases were in persons hospitalised for viral encephalitis, I think it was herpes in all cases... autism followed acute encephalitis.



There is also a misterious pick's 'something' disease, happens in early 20s and later, the symptoms are absolutely identical to autism but probably not called that for 'political' reasons. Cannot find links now, sorry.



Alex do you have links or do you remember what CREB was discussed previously in relation to, what aspect of CFS?
 

wciarci

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Good thread Gerwyn

I wonder about the connection between CFS, anxiety disorder and bipolar disorder. My family is loaded with all three and rage is the norm with many of them. I posted a thread recently on bi-polar being linked to mitochondrial dysfunction, of course we know about this with CFS/ME. I was out of control with rage for a while, my husband took the brunt of it. It always happened on a Friday or Saturday the end of my work week when I was exhausted. I am much better with b12 shots, methylation support. I was just recently reading about lactoferrin and its effect on immune function, mitochondria (per removal of lactate that builds up in the brain when ATP energy conversion goes awry) and reduced inflamation. It is present in mother's milk and whey protein. I wasn't breast fed, nor were any of my siblings, cousins or nieces or nephews. I am wondering now why Immuplex (whey protein) isn't advised for CFS? It appears that we need the lactoferrin and glutathione. Oh yes, CoQ10 and other supplements are being used for people with bi-polar with better effectiveness than pharmaceuticals. I can drink red wine without a problem at all, but not other alcohol products. Just a thought.

Wendy
 

HopingSince88

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Good thread Gerwyn

I was just recently reading about lactoferrin and its effect on immune function, mitochondria (per removal of lactate that builds up in the brain when ATP energy conversion goes awry) and reduced inflamation. It is present in mother's milk and whey protein. I wasn't breast fed, nor were any of my siblings, cousins or nieces or nephews. I am wondering now why Immuplex (whey protein) isn't advised for CFS? It appears that we need the lactoferrin and glutathione. Oh yes, CoQ10 and other supplements are being used for people with bi-polar with better effectiveness than pharmaceuticals. I can drink red wine without a problem at all, but not other alcohol products. Just a thought.

Wendy
Hi Wendy,
Your comment on whey protein is interesting to me. I was on a doctor-prescribed diet in the late '90's that was a liquid protein diet to help me lose weight. (very low calorie and low carb shakes that were whey-based protein). I felt my best during the 18 months I was on this stuff (been sick 22 yrs). And I lost 70 lbs to boot. Unfortunately, that product is now made with soy instead of whey. So I can't make any recommendation for it here. But now I am wondering if I can pick up another whey-based product at Whole Foods that will provide a similar benefit.
 

alex3619

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CFS CREB links?

Hi Natasa778

The comment on encephalitis is interesting, I think I developed CFS at the age of seven after measles encephalitis.

it does, but very rarely. there are documented, published cases of previously healthy persons becoming autistic at the ages of 7, 11 and 14. Also one published case of a 30-something-year-old. All these cases were in persons hospitalised for viral encephalitis, I think it was herpes in all cases... autism followed acute encephalitis.

There is also a misterious pick's 'something' disease, happens in early 20s and later, the symptoms are absolutely identical to autism but probably not called that for 'political' reasons. Cannot find links now, sorry.

Alex do you have links or do you remember what CREB was discussed previously in relation to, what aspect of CFS?

I want to state, as I do periodically, that I have episodic (event) memory problems, which is why I rarely try to create models of CFS any more like I did in the past (that and a lack of resources such as energy, cash and transport). When I try to recall WHERE I read something, the fastest way is usually for me to run a search, since I never remember where unless I am very lucky. So, I ran a few searches and have sent an emailed question to a few likely sources, places where I may have discussed this in the past. Here is what I got from searching:


Gerwyn has talked about CREB before, in connection with gut permiability:

http://www.forums.aboutmecfs.org/showthread.php?4579-XMRV-CREB-and-LEAKY-GUT


This study talks about omega 3 and CFS:
http://www.ncbi.nlm.nih.gov/sites/pubmed, run a search on CFS and CREB for:

Altern Med Rev. 2003 Nov;8(4):410-25.

Neurobehavioral aspects of omega-3 fatty acids: possible mechanisms and therapeutic value in major depression.
Logan AC.

I am currently reading this paper. If it proves relevant, then high dose omega-3 therapy may help.


This next multiple-line link connects to a section in a book on the brain, which describes a patients with CFS treated with forskolin. I considered forskolin for myself many years ago but decided it was potentially too toxic and didn't try it. Maybe I was wrong. I cannot copy this text, it is protected and part of some PR for a book.

http://books.google.com.au/books?id...ed=0CD0Q6AEwCTge#v=onepage&q=CREB CFS&f=false


The following paper is about CREB and memory formation:
http://www.medicalnewstoday.com/articles/68404.php

Given that I have very poor episodic memory (events) and have to rely on semantic memory (ideas), this whole arguement is looking more and more interesting. Many of the neurocognitive deficits in CFS might be implicated here.


Be carefull of links on CFS and the amygdala. Some papers talk about Conditioned Fear Stress, which is also CFS, a technique often used to study amygdala responses.

Given that CREB responds to cAMP, and so is linked to the cAMP/Ca++ axis, there may be connections to other aspects of CFS pathophysiology that we haven't discussed yet. Forskolin is again implicated here, and this is why I considered forskolin as a treament in 1998.

CREB is also important to the hippocampus, and probably other regions of the brain.

My best guess is that this is related to Kerrs epigenetic study of CFS subtypes, and is where I read it, or found reference to it (it is actually about CREB binding protein, but it is only a guess:

Gene Expression Subtypes in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Table 2. Characteristics of differentially expressed genes in chronic fatigue syndrome/myalgic encephalomyelitis.
------------------------------------------------------------------------------------------------------------------
Gene Gene name GenBank TaqMan assay Microarray Real-time PCR
symbol accession identification no.a fold Fold 2-tailed P
no. difference difference
------------------------------------------------------------------------------------------------------------------
CREBBP CREB binding protein (Rubinstein- NM_004380 Hs00231733_m1 2.37 1.43 .016
Taybi syndrome)

Here is the link for better formatting:

http://www.cfids-cab.org/cfs-inform/Genes/kerr.etal08.tab2.txt

The paper is here:

http://www.cfids-cab.org/MESA/Kerr-5.pdf


The following paper might link CREB to parvovirus B19, but I haven't had time to read it yet:

http://jvi.asm.org/cgi/reprint/72/1/609


Here is a link to a forum discussion of XMRV and apparently mentions CREB, but I haven't read it yet:
http://www.forums.aboutmecfs.org/archive/index.php/t-4285.html

There are so many connections on search that I could spend the next several weeks checking them down, but I don't have the time or energy. I would also have posted more detail, but that would have blown this posting to multiple pages. The point is that there are both direct and indirect links, so there is cause for consideration of the XMRV CREB brain hypothesis, both for memory formation and sensory issues.

Bye
Alex
 

alex3619

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HI

Regarding the forskolin treatment, the lady in question reponded in 30 minutes on 10mg. She continued to respond. Forskolin is the active ingredient of the herb coleus (from memory, spelling could be wrong). Be warned, there are many potential risks with this, do check this out thoroughly if you are thinking of trying it.

Bye
Alex
 

natasa778

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Your comment on whey protein is interesting to me. I was on a doctor-prescribed diet in the late '90's that was a liquid protein diet to help me lose weight. (very low calorie and low carb shakes that were whey-based protein). I felt my best during the 18 months I was on this stuff (been sick 22 yrs). And I lost 70 lbs to boot. Unfortunately, that product is now made with soy instead of whey. So I can't make any recommendation for it here. But now I am wondering if I can pick up another whey-based product at Whole Foods that will provide a similar benefit.
Wondering if it could be for its IgG component?
 

natasa778

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Thanks alex, I will check the links... (I am aware of most from this forum, posted many myself, but would be great to see if someone discussed in the past, esp Kerr study...)
 

wciarci

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Hi hoping, I was taking Immuplex from prohealth but read somewhere (can't remember, you know) that it wasn't good for us so stopped it. I am thinking of going back on it. It is whey protein from cow's milk as I remember but don't count on my memory. I have been doing fairly well on a variety of supplements but will start the whey again, I think, if I can remember to do it.

Wendy
 

JT1024

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I knew I had read something about Immuplex..

I haven't had time to real all of this thread but Dr. Mikovits specifically mentioned it and it was posted on this thread: http://www.forums.aboutmecfs.org/sh...ritional-Supplements-to-Support-XMRV-Patients

ImmunoPro RX or ImmunPlex Both of these products contain whey protein, which has exceptional amounts of cysteine and glutamine, the precursors required for the production of intracellular glutathione. Regarding whey protein concentrate, the journal Immunology reports, "The bioactivity occurs through the ability of the protein concentrate to help replenish Glutathione levels via continuous dietary provision of Glutathione precursors, especially Cysteine, during lymphocyte proliferation, thus supporting an optimal immune response. This process seems to not only increase intercellular levels of Glutathione and precursors at the time of ingestion, but also builds up stores of these substances within the cells that lasts for a substantial post-ingestion time interval."(4)
 

gracenote

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I knew I had read something about Immuplex..

I haven't had time to real all of this thread but Dr. Mikovits specifically mentioned it and it was posted on this thread: http://www.forums.aboutmecfs.org/sh...ritional-Supplements-to-Support-XMRV-Patients
My understanding of that post is that it was written by ProHealth based on the minimal suggestions of Dr. Mikovitz. She did not specifically refer to these supplements.

Although Dr. Mikovits was quick to note that she is not a physician, she mentioned five areas of concern for people with XMRV and suggested that nutritional supplementation to strengthen those areas could be helpful.

Based on her insights, ProHealth suggests a number of options known to be helpful for these concerns, as outlined below. Please note, however, that Dr. Mikovits has made no specific product recommendations, nor does she endorse these products in any way.
Regarding whey protein (and sorry, I may just be adding more confusion here), I believe Cheney used to recommend it, and then changed his mind and no longer recommends it. I don't know where or how to find this information, but I'm pretty sure it's correct.
 

wciarci

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I found this statement on an older post

To stabilize an overactive immune system, Dr. Paul Cheney advocates the use of undenatured whey protein (as in Pro Health's ImmunPlex). Whey protein is useful because of its ability to replenish proper glutathione levels that are low in some with CFS.

Dr. Cheney believes that deficient glutathione coupled with excessive cytokines is what promotes activation of harmful microbes like EBV [Epstein-Barr Virus], HHV-6 [Human Herpes Virus-6] as well as chlamydia pneumonia, candida and other mycoplasmas.





In a small study on CFS patients, Cheney found whey protein to be very effective in wiping out these harmful microorganisms. Thus, by raising glutathione levels, undenatured whey protein apparently counteracts some of the damaging effects of excessive cytokines.


If I remember correctly Cheney doesn't advocate its' use anymore because of detox problems. Pulsing the supplement might be a good idea.

Wendy
 

wciarci

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Hi Hoping,

Pulsing could be one day on, one day off or one week on, one week off. It gives your body a chance to clear the dead organisms out, since we don't do that very well. When I was on anti-biotics and anti-virals I was told to pulse until my body could handle the die off. Hope this helps.

Wendy
 

JillBohr

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Hi Hoping,

Pulsing could be one day on, one day off or one week on, one week off. It gives your body a chance to clear the dead organisms out, since we don't do that very well. When I was on anti-biotics and anti-virals I was told to pulse until my body could handle the die off. Hope this helps.

Wendy
Hi Wendy, my soon has horrible yeast and my doctor said to use probiotics first before starting the anti-fungals because the die-off is going to be really bad. I have been giving him probiotics but the die-off is already really bad and I am wondering if I should do this every other day (and work slowly). The poor kid has dark circles underneath is eyes and his behaviours are off the chart. He has autism and he is doing the hysterical giggling (for mothers of ASD kids, we know this is a really bad sign). What do you think? Thank you, Jill