XMRV AND ANXIETY DEPRESSION THE anxious Amygdala

[Rosemary]

i will have a good look is it just the am that is bigger

Thanks Gerwyn,

In post mortem studies of patients with autism this is what they found in the brain, abnormal structures of the amygdala, limbic system, prefrontal lobes, basal forebrain, brainstem and cerebellum

Quote below is from Dr Peter Julu [Specialist Autonomic Neurophysiologist] Breakspear Hospital UK

Autism is a complex neurodevelopmental disorder affecting multiple organs and systems of the body. In the brain, abnormal structures of the amygdala, limbic system, prefrontal lobes,basal forebrain, brainstem and cerebellum have been found in post mortem studies of patients with autism. Abnormal levels of neurotransmitters, including norepinephrine, dopamine, acetylcholine, serotonin and neuropeptides, have also been found in children with autism. Animals with altered neurotransmission of serotonin, oxytocin and gamma-aminobutyric acid [ GABA ] exhibit behavioural disorders resembling autism in some features. All the brain structures and neurotransmitters mentioned above affect activation-inactivation balance of autonomic function.

 

[Gerwyn]

Thanks Gerwyn,

In post mortem studies of patients with autism this is what they found in the brain, abnormal structures of the amygdala, limbic system, prefrontal lobes, basal forebrain, brainstem and cerebellum

Quote below is from Dr Peter Julu [Specialist Autonomic Neurophysiologist] Breakspear Hospital UK

Autism is a complex neurodevelopmental disorder affecting multiple organs and systems of the body. In the brain, abnormal structures of the amygdala, limbic system, prefrontal lobes,basal forebrain, brainstem and cerebellum have been found in post mortem studies of patients with autism. Abnormal levels of neurotransmitters, including norepinephrine, dopamine, acetylcholine, serotonin and neuropeptides, have also been found in children with autism. Animals with altered neurotransmission of serotonin, oxytocin and gamma-aminobutyric acid [ GABA ] exhibit behavioural disorders resembling autism in some features. All the brain structures and neurotransmitters mentioned above affect activation-inactivation balance of autonomic function.

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

 

[Gerwyn]

http://www.springerlink.com/content/1561320617x48156/

Reduced bone thickness in autistic boys, p < 0.001.

thank you very much

 

[Recovery Soon]

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?

 

[gu3vara]

Yup, happened to me this very day, I know exactly what you mean, it correlated with worse than usual headaches for me, I hate it... I feel like I'm losing it and it comes and goes without reason.

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?

 

[kurt]

http://www.cnn.com/2009/HEALTH/05/04/autism.brain.amygdala/index.html

Any thoughts on why the amygdala in toddlers with autism is 13 percent larger than unaffected kids ?

CNN) -- The size of a specific part of the brain may help experts pinpoint when autism could first develop, University of North Carolina researchers report.

The amygdala helps individuals process faces and emotions.
Using MRI brain scans, researchers found that the area of the brain called the amygdala was, on average, 13 percent larger in young children with autism, compared with control group of children without autism. In the study, published in the latest Archives of General Psychiatry, researchers scanned 50 toddlers with autism and 33 children without autism at age 2 and again at age 4. The study adjusted for age, sex and IQ.

"We believe that children with autism have normal-sized brains at birth but at some point, in the latter part of the first year of life, it [the amygdala] begins to grow in kids with autism. And this study gives us insight inside the underlying brain mechanism so we can design more rational interventions," said lead study author Dr. Joseph Piven.

"Many studies have observed the brain grows too big in kids with autism, but this study finds that by age 2, the amygdala is already bigger and stops growing," said Kosofsky. "So it tells us the critical difference has already developed. It now poses the question: Are children born with autism or does it develop in the first two years of life?"

A woman posted on a forum I read a few years ago that she recovered from her CFS when one of her amygdala was removed due to its proximity to a cyst that had to be removed surgically. So since we have two amygdala that means one half of her amygdala function was removed. I did not think to ask her whether it was the right or left amygdala, that might have been interesting to learn. Anyway, just an anecdote but maybe supports the idea that over-activity of amygdala is involved and reducing that can help some CFS cases.

 

[subtr4ct]

Recovery Soon and gu3vara:

If you don't mind sharing, have you been tested for XMRV?

 

[gu3vara]

No, I don't want to end up with a false negative because of lab problems, other strains of XMRV not identified yet or anything else (assuming XMRV is the real deal).

@Recovery Soon and @gu3vara:

If you don't mind sharing, have you been tested for XMRV?

 

[natasa778]

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?

This is very interesting and similar to what many parents of ASD kids report - not usual irritability but sudden violence/rage attacks. This is especially frequent in puberty. Would you be able to explain what other bad symptoms would be there at the time - physical or cognitive.

Btw not sure if relevant but mostly those episodes happen in spring so have been hypothesised to be linked to allergies somehow. Also quite a few reports of those behaviours calming down after antihistamines are given!

 

[Gerwyn]

A woman posted on a forum I read a few years ago that she recovered from her CFS when one of her amygdala was removed due to its proximity to a cyst that had to be removed surgically. So since we have two amygdala that means one half of her amygdala function was removed. I did not think to ask her whether it was the right or left amygdala, that might have been interesting to learn. Anyway, just an anecdote but maybe supports the idea that over-activity of amygdala is involved and reducing that can help some CFS cases.

The amygdala is trilobar Kurt and does span the hemispheres.Is that what you mean?There is only one amygdla

 

[Rosemary]

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

Thanks for your response Gerwyn, how much of this damage in the brain would therefore be the direct result of neuronal apoptosis [neuronal cell death] ? and if you compared the damage that they found in the post mortem studies in the brain of children with autism to the neurodegeneration that is seen in HIV/AIDS dementia [which is also associated with neuronal apoptosis] what would the difference be ?

 

[Rosemary]

http://www.springerlink.com/content/1561320617x48156/

Reduced bone thickness in autistic boys, p < 0.001.

Thanks for this .....Further information here:-

Thin Bones Seen In Boys With Autism And Autism Spectrum Disorder
http://www.sciencedaily.com/releases/2008/02/080206204948.htm

The investigators found that the bones of the boys with autism were growing longer but were not thickening at a normal rate. During normal bone development, material from inside the bone is transferred to the outside of the bone, increasing thickness, while at the same time, the bones are also growing longer.

At 5 or 6 years of age, the bones of the autistic boys were significantly thinner than the bones of boys without autism and the difference in bone thickness became even greater at ages 7 and 8.

The bone thinning was particularly notable because the boys with autism and ASD were heavier than average and would therefore be expected to have thicker bones.

The researchers do not know for certain why the boys had thinner than normal bones. A possible explanation is lack of calcium and vitamin D in their diets. Dr. Hediger explained that a deficiency of these important nutrients in the boys diets could result from a variety of causes. Many children with autism, she said, have aversions to certain foods. Some will insist on eating the same foods nearly every day, to the exclusion of other foods. So while they may consume enough calories to meet their needsor even more calories than they needthey may lack certain nutrients, like calcium and vitamin D.

Other children with autism may have digestive problems which interfere with the absorption of nutrients. Moreover, many children with autism remain indoors because they require supervision during outdoor activity. Lack of exercise hinders proper bone development, she said. Similarly, if children remain indoors and are not exposed to sunlight, they may not make enough vitamin D, which is needed to process calcium into bones. The boys in the study who were on a casein-free diet had the thinnest bones. In fact, the 9 boys who were on a casein-free diet had bones that were 20 percent thinner than normal for children their age. Boys who were not on a casein-free diet showed a 10 percent decrease in bone thickness when compared to boys with normal bone development.

 

[Cort]

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.

CREB protects neurons within the amgydala.Down regulation can cause excessive neural death in the Amgydala(this is the responsible for regulating levels of anxiety ).

Excessive cell death causes hyperanxiety states and paradoxically depression.

So could XMRV cause anxiety and depression hypothetically yes

Clin Invest. 2005 October 1; 115(10): 26972699.
doi: 10.1172/JCI26436.

PMCID: PMC1236699
Copyright 2005, American Society for Clinical Investigation
The anxious amygdala: CREB signaling and predisposition to anxiety and alcoholism
Gary Wand
Department of Medicine and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Address correspondence to: Gary S. Wand, Johns Hopkins University School of Medicine, Ross Research Building, Room 863, 720 Rutland Avenue, Baltimore, Maryland 21205, USA. Phone: (410) 955-7225; Fax: (410) 955-0841; E-mail: gwand@jhmi.edu.
Small right arrow pointing to: See the article "Deficits in amygdaloid cAMP-responsive elementbinding protein signaling play a role in genetic predisposition to anxiety and alcoholism" on page 2762.

Small right arrow pointing to: This article has been cited by other articles in PMC.

* Other Sections▼
o Abstract
o Alcohol-abuse disorders
o Alcohol and the nucleus accumbens
o Alcohol and the amygdala
o Selectively bred rodent lines
o References

Abstract
The amygdala is believed to play a key role in assigning emotional significance to specific sensory input, and conditions such as anxiety, autism, stress, and phobias are thought to be linked to its abnormal function. Growing evidence has also implicated the amygdala in mediation of the stress-dampening properties of alcohol. In this issue of the JCI, Pandey and colleagues identify a central amygdaloid signaling pathway involved in anxiety-like and alcohol-drinking behaviors in rats. They report that decreased phosphorylation of cAMP responsive elementbinding protein (CREB) resulted in decreased neuropeptide Y (NPY) expression in the central amygdala of alcohol-preferring rats, causing high anxiety-like behavior. Alcohol intake by these animals was shown to increase PKA-dependent CREB phosphorylation and thereby NPY expression, subsequently ameliorating anxiety-like behavior. These provocative data suggest that a CREB-dependent neuromechanism underlies high anxiety-like and excessive alcohol-drinking behavior.

Very interesting Gerwyn - thanks. It is my fervent belief that my 'arousal' is mediated by some physiological pathway. fascinating stuff!

 

[Cort]

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?

I get that when I do too much exercise; my muscle feel hot and constricted and boy am I on edge. At one point I really wondered if somebody was to make the wrong move I'd be up for manslaughter because I don't know if I would've stopped. Almost all my outbursts occur in the aftermath period of too much exercise.

 

[strawberry]

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?

Yes. When I first got sick I suffered from serious rage. It was way off the scale of anything I had experience in normal health. The severity has lessened as my disease improved. I wonder how common it is because I've never noticed it discussed as a symptom. I also had weeping episodes that started and stopped without rhyme or reason.

I've heard of rage occuring in Lyme Disease ("Lyme Rage"), and people suffering from organophosphate poisoning (who swing between tearful depression and extreme irritibility). Both these illnesses are very similar to ME/CFS.

 

[Recovery Soon]

@Recovery Soon and @gu3vara:

If you don't mind sharing, have you been tested for XMRV?

I was tested as part of the Kerr study (at Dr. Enlander's office) but never received my individual results- although we learned that EVERYONE was negative in that study- whatever. Like gu3vara, I'm waiting til there's a valid test and a proven CFS correlation before I waste my time, money and hope.

This is very interesting and similar to what many parents of ASD kids report - not usual irritability but sudden violence/rage attacks. This is especially frequent in puberty. Would you be able to explain what other bad symptoms would be there at the time - physical or cognitive.

It is usually at lower points during fatigue, headache, brain foggy periods. Almost feels like something is gnawing at my brain. It could last for days. Not fun. And I agree with Cort - Post Exertional Malaise can set this off.

Man, I'm hoping XMRV is it. No one should live like this.

 

[kurt]

The amygdala is trilobar Kurt and does span the hemispheres.Is that what you mean?There is only one amygdla

I have always read there are two amygdala, what do you mean by trilobar? Perhaps you refer to the hypocampus that connects the two amygdala? I supposed that might be considered a third lobe if there is substantial amygdala tissue running through the hypocampus. Here is a 3D image:

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? I believe CFS is more consistent with hyperactivity in the amygdala, or a regulation failure, which suggests that if viral brain damage is involved, that damage is more likely in the pre-frontal cortex, particularly in the projections into the amygdala that ordinarily act as calming controllers of the amygdala... and that is very consistent also with other CFS problems that involve the pre-frontal cortex, such as a decrease in executive function and sudden problems with social skills. But then a virus in that region might alter all the tissues in the area, so I suppose there could be problems in both the pre-frontal and amygdala areas.

 

[gu3vara]

Man, I'm hoping XMRV is it. No one should live like this.

I hope too, and seeing ladybugmandy responded quite quickly to RAL (with some weird problems showing up though), saying her brain fog vanished in a couple days and energy improving makes me think this is it. Without a retrovirus present, it shouldn't do much taking it. And the placebo effect is certainly not something we are susceptible to, we tried so many things thinking that was the solution and still it did nothing. I believe in this more than ever.

 

[Gerwyn]

I have always read there are two amygdala, what do you mean by trilobar? Perhaps you refer to the hypocampus that connects the two amygdala? I supposed that might be considered a third lobe if there is substantial amygdala tissue running through the hypocampus. Here is a 3D image:

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? I believe CFS is more consistent with hyperactivity in the amygdala, or a regulation failure, which suggests that if viral brain damage is involved, that damage is more likely in the pre-frontal cortex, particularly in the projections into the amygdala that ordinarily act as calming controllers of the amygdala... and that is very consistent also with other CFS problems that involve the pre-frontal cortex, such as a decrease in executive function and sudden problems with social skills. But then a virus in that region might alter all the tissues in the area, so I suppose there could be problems in both the pre-frontal and amygdala areas.

Thanks for your input

The problem i have with amygdala hyperactivity is the concomitant release of cortisol.Cortisol as you know is neurotoxic .This hyperactivity scenario is central to PTDS and results in the dissociation between the amygdala and the hippocampus.

This of course leads to a dissociation between the elements of explicit and implicit memory and the destruction of the ascending and descending neural pathways linking the limbic system to the neocortex.This destroys the ability of any feedback mechanisms to "calm" the amygdala.This kind of hyperactivity results in a disruption of the normal integrative function of the brain.Our neurocognitive pattern,according to drs Klimas et al, is more akin to a functional encephalopathy.Their view is confirmed by spect scans pet scans and MRI.Persuasively there have never been any reports of hyperactive amygdala hyperactivity on these scans or indeed in any of the scientific journals.Gupta produced some work which he claimed was peer reviewed but on further investigation his paper was published in Medical Hypothesis which does not use any kind of peer review system.I thought it would be useful to mention this fact as people often get confused.Finally, the patterns of HPA activity are not consistent with over-activity of the amygdala.

P.S I forgot to mention that appears to be a misconception that the neural feedback type interventions function by feedback patterns between the neocortex and the limbic system.They actually work on relationships between the left and right hemisphere.They can be very effective palliative interventions for people suffereing from categorical anxiety but thus far there is no evidence of effectiveness on people having problems with primal anxiety

 

[fabiola7386]

Anti depressant treatments does a fine job in treating depression and stress.

Drug Rehab