Receptors in brain linked to schizophrenia, autism

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crzxn
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Receptors in brain linked to schizophrenia, autism

Postby crzxn » Wed Aug 12, 2015 12:07 am

And so far it seems right on. The SNP is present in all the genomes I have for Autistic children. The great news is that it is tweakable by changing the environment. It is a glutamate receptor gene. GRM5 is the gene name.

http://www.sciencedaily.com/releases/20 ... 171458.htm

Receptors in brain linked to schizophrenia, autism

Mice lacking a set of receptors in one type of neuron in the brain developed compulsive, anti-social behaviors, scientists have found. The importance of the receptor, called mGluR5, in other areas of the brain had been previously established. Until now, however, no one had studied their specific role in a cell type known as parvalbumin-positive interneurons, thought to be important in general cognition and generating certain types of oscillatory wave patterns in the brain.

Santosg
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Re: Receptors in brain linked to schizophrenia, autism

Postby Santosg » Wed Aug 12, 2015 1:35 am

Interesting article. Thanks for sharing. The problem with this approach, in my mind, is that it takes the end result of a neurological process and identifies it as causal as opposed to simply being a symptom. The single and striking similarity between the brain of people with autism and schizophrenia is precisely the fact that they have brains that are not correctly and completely connected. We have distinct parts of our brain, each assigned with distinct tasks. These parts of the brain, however, only truly work when they are able to work with the entire brain.

For instance, we all have an 'inner voice.' We have spoken to ourselves, scolded ourselves, had an internal dialogue and even shouted out-loud 'I can't believe you did that.' In sense, we are both processing the behavior as well as having distinct parts of the brain weight our actions. Even so, we recognize this as entirely 'ourselves.' Schizophrenia is a condition in which that 'inner voice' is not recognized as parts of the self, but instead belonging to someone else. One part of the brain is talking but the other part of the brain cannot recognize it as simply an element of its own production. Is this the result of a specific receptor gene. Not really.

Certainly, there is a genetic link to schizophrenia. There is also one with autism. But to treat either as strictly genetic is mistaken. In the case of both autism and schizophrenia, all of the science is pointing towards the increasingly role of environment as playing a very significant role. There are plenty of people with GRM5 receptor genes that are not schizophrenic. Hell, I'd say that almost 90 percent of the people with the mutation don't have anything resembling autism or schizophrenia.

Most of these studies don't reveal anything useful or significant. Genetics is a statistical discipline, and as such, almost all of what it reveals are correlations. From these, a few important causal variables will be identified. However, even then the conclusions that are drawn are often tentative and based on a number of caveats.

FatherOf2
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Re: Receptors in brain linked to schizophrenia, autism

Postby FatherOf2 » Wed Aug 12, 2015 5:02 pm

mGluR5 is also affected in Fragile X, only it is overexpressed, not lacking. And Fragile X has symptoms similar to autism. That is why it is so hard to find a treatment for autism: a very active receptor can cause it or a same but very weak receptor can also cause it. So, the conclusion is that everything has to be balanced, different types of receptors, neurotransmitters, etc.

crzxn
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Re: Receptors in brain linked to schizophrenia, autism

Postby crzxn » Wed Aug 12, 2015 6:35 pm

FatherOf2 wrote:mGluR5 is also affected in Fragile X, only it is overexpressed, not lacking. And Fragile X has symptoms similar to autism. That is why it is so hard to find a treatment for autism: a very active receptor can cause it or a same but very weak receptor can also cause it. So, the conclusion is that everything has to be balanced, different types of receptors, neurotransmitters, etc.


@Fatherof2,

While Fragile X and Autism might share similarities we cannot look at them as the same.
https://fragilex.org/fragile-x-associat ... different/

You are blaming the receptor as the only cause of reduced plasticity, I am not. It could be that they have extremely bad mGlur5 receptors or bad FMRP, or maybe both might need to only be slightly bad. There are also eight mGlur recpetors and I see SNPs in mGlur1 as well in ASD.

Since 23andme does not show an abundance of FMR1 SNPs it is hard to say which of my samples has the issue, but one SNP, rs25704, stands out, The males without Autism are T and the males with Autism are C. I do not know what this means but it might be that the FRM1 protein is slightly bad but that is just a guess.

The very fact that they have similarities and both share some dysfunction of mGlur5 is important. Synaptic plasticity can be shut sown either by FMRP SNPs or GRM5 SNPs.
http://www.nature.com/nm/journal/v14/n3 ... 49_F1.html

But every child with Autism whose genes I have have these GRM5 SNPs and people who do not have Autism do not have them. Yes, my sample sizes is small but at 100% I say it is interesting.

The way to treating autism and increasing plasticity might be very different for a child who has one combination of SNPs or another, yet they can express almost similar symptoms. This is the reason we should not only be interested in genetic, we need to be interested in the PERSON's genetics.

This all leads me to an interesting conclusion however, that since these mGlur5 receptors are few, wouldn't that call for the need for more glutamate in the cerebral cortex? And since mercury increases the release of glutamate in the cerebral cortex, wouldn't that mean that autistic children might NEED MORE mercury? Could that have adapted to high mercury levels after a few generations of mercury poisoning and now they are dependent on it?

Ans since serotonin is also implicated in autism, and mercury increases serotonin....
http://www.ncbi.nlm.nih.gov/pubmed/7715848

In all the children with Autism I have SNPs for they have TPH2 SNPs (turns tryptophan into serotonin more quickly) and MAOA SNPs that make the enzyme that breaks down serotonin slowly, exactly the same.

TPH2 and Autism
http://www.ncbi.nlm.nih.gov/pubmed/15768392
MAOA and Autism
http://www.ncbi.nlm.nih.gov/pubmed/12919132

I think what we are seeing in Autism is a genetic adaptation to mercury. And I think reducing mercury in the environment is great for the long term, for the generation of Autistics might be causing them harm. Yes, I know how that sounds, but isn't that the role of genetics? To adapt to the environment to survive?

In fact if you compare autism rates to the reduction of mercury you might see an interesting coorelation:

https://upload.wikimedia.org/wikipedia/ ... 07.svg.png

http://www.ec.gc.ca/dd-sd/1F994D29-95B2-4C9F-9637-014A92210D02/ate_hg_national_en.gif

I am going to put up all the genes I see implicating Austim in a future post. Once we know these pathways I feel we can increase plasticity by changing diet and supplementing with cofactors of the genes in question. So far I see reducing serotonin and increasing glutamate as a combined effort to increase placticity and stabilize mood.
Last edited by crzxn on Wed Aug 12, 2015 6:49 pm, edited 1 time in total.

crzxn
Posts: 23
Joined: Sun Jul 12, 2015 12:24 pm

Re: Receptors in brain linked to schizophrenia, autism

Postby crzxn » Wed Aug 12, 2015 6:48 pm

Santosg wrote:Interesting article. Thanks for sharing. The problem with this approach, in my mind, is that it takes the end result of a neurological process and identifies it as causal as opposed to simply being a symptom. The single and striking similarity between the brain of people with autism and schizophrenia is precisely the fact that they have brains that are not correctly and completely connected. We have distinct parts of our brain, each assigned with distinct tasks. These parts of the brain, however, only truly work when they are able to work with the entire brain.

For instance, we all have an 'inner voice.' We have spoken to ourselves, scolded ourselves, had an internal dialogue and even shouted out-loud 'I can't believe you did that.' In sense, we are both processing the behavior as well as having distinct parts of the brain weight our actions. Even so, we recognize this as entirely 'ourselves.' Schizophrenia is a condition in which that 'inner voice' is not recognized as parts of the self, but instead belonging to someone else. One part of the brain is talking but the other part of the brain cannot recognize it as simply an element of its own production. Is this the result of a specific receptor gene. Not really.

Certainly, there is a genetic link to schizophrenia. There is also one with autism. But to treat either as strictly genetic is mistaken. In the case of both autism and schizophrenia, all of the science is pointing towards the increasingly role of environment as playing a very significant role. There are plenty of people with GRM5 receptor genes that are not schizophrenic. Hell, I'd say that almost 90 percent of the people with the mutation don't have anything resembling autism or schizophrenia.

Most of these studies don't reveal anything useful or significant. Genetics is a statistical discipline, and as such, almost all of what it reveals are correlations. From these, a few important causal variables will be identified. However, even then the conclusions that are drawn are often tentative and based on a number of caveats.


Single studies are irrelevant, but when you step back these single studies the pattern becomes clear.

You are making an assumption that I am treating autism as solely genetic. I am and I am not. I see it as a genetic and environmental, but I see it as an adaptation to an environment which we now see as bad. I think Autism might be and adaptation to mercury in the environment, and as we reduced mercury in the environment these children are now suffering. I explained this in my other post and I know it sounds crazy but I can't make it not make sense. The lowering of mercury emmisions seems to correspond with rising rates of autism. It is our grandparents and parents mercury poisoning that singled that the genes need to adapt to that environment. But now we took the mercury away and a system designed to be balanced with mercury as a factor is now out of wack again. This is the science of Nutritional Epigenetics. This effect has been explained with Choline in eggs by Dr. Steven Zeisel.

My statistics in my small sample size is 100%, it points to low glutamate and high serotonin. This might be a relatively easy fix, the issue I do not know is that how much can be repaired by the increased plasticity after a certain age.

crzxn
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Re: Receptors in brain linked to schizophrenia, autism

Postby crzxn » Wed Aug 12, 2015 8:39 pm

And in case you all think I am nuts, this is what I am talking about:

Five Hundred Years of Mercury Exposure and Adaptation
http://www.hindawi.com/journals/bmri/2012/472858/

Thus, evidence of mercury’s toxicity in ANS function was found without other signs of intoxication. Our findings are consistent with the hypothesis of partial transgenerational inheritance of tolerance to mercury in Huancavelica, Peru. This would generally benefit survival in the Anthropocene, the man-made world, we now live in.

Santosg
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Joined: Sun Aug 17, 2014 5:33 am

Re: Receptors in brain linked to schizophrenia, autism

Postby Santosg » Thu Aug 13, 2015 2:28 am

Hi Crzxn,

I think that you make an interesting argument. I always like hearing out of the box ideas on this kind of issues. The more I research autism, the more I find it is beneficial to read outside of the current 'autism' literature. Instead, I read a lot of studies that research related but distinct fields.

In terms of your argument, however, I think that it asks an interesting question but that it is not supported. Let me put it another way: the original hypothesis does not lead to the logically appropriate conclusion.

There is very little question that individuals that worked in mining and around mercury were inherently better adapted to tolerating mercury than other individuals. Individuals who were mercury sensitive would have died in very high numbers. This is particularly true during the early period of Spanish colonialism, where a feudal system of labor was put in place. Originally, given the burdens of the mines, large numbers of slaves were imported to be used in mining. They were working at incredibly high altitudes and many of them died. So many, in fact, that it become too expensive to use slave labor. I was born in Bolivia. Native indigenous Bolivians are evolutionarily adapted to high altitudes, much like Tibetans. They have barrel chests, huge lungs for small bodies. I am not indigenous, however, and although born at a very high altitude don't exibit the same physiology. The point to all this being simply that will no doubt it had an epigenetic influence on my own development, it is not enough to actually alter my overall genetic makeup.

Epigenetics is important, but when dealing with macroevolutionry processes, you're inevitablly returning to pure Darwinian genetic selection.

So what does it mean to have a tolerance to mercury and other heavy metals? There is really only one answer to this: effective elimination. This is only possible through the bodies internal production of glutathione and super oxide dismutase. These are very old biological mechanisms. So old, in fact, that they are the same mechanisms that plants use to cope with heavy metals. They've found organisms that can live in mercury, but they do so simply because they are constantly replenishing their glutathione. Any organism that retains mercury is going to be evolutionarily punished as it serves absolutely no purpose.

So, if the above argument is correct, it means that the adaptation that would be selected for is 'increased levels of glutathione and super oxide dismutase.' In other words, the adaptation would help us get ride of mercury and not retain it. This inherently would lead to lower rates of autism and not higher rates of autism. You can find children with autism have higher oxidative stress, lower levels--often significantly lower levels--of glutathione.

Individuals exposed to mercury, even ones with greater tolerance, accumulate greater amounts of errors in their DNA. Further, mercury accumulates and the burden of mercury is passed from mother to child both in utero and through breast feeding. Even if the environment has lower levels of mercury--and I don't think that's actually accurate if examined closely (to long for this post), it still is accumulating in the body burden of individuals each generation.

People who have members of their family with a higher sensitivity to mercury also have an increased risk of autism. The opposite of what your hypothesis would predict.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173747/

Analogous to the pink disease experience, Hg exposure is widespread yet only a fraction of exposed children develop an ASD, suggesting sensitivity to Hg may also be present in children with an ASD. The objective of this study was to test the hypothesis that individuals with a known hypersensitivity to Hg (pink disease survivors) may be more likely to have descendants with an ASD. Five hundred and twenty-two participants who had previously been diagnosed with pink disease completed a survey on the health outcomes of their descendants. The prevalence rates of ASD and a variety of other clinical conditions diagnosed in childhood (attention deficit hyperactivity disorder, epilepsy, Fragile X syndrome, and Down syndrome) were compared to well-established general population prevalence rates. The results showed the prevalence rate of ASD among the grandchildren of pink disease survivors (1 in 25) to be significantly higher than the comparable general population prevalence rate (1 in 160). The results support the hypothesis that Hg sensitivity may be a heritable/genetic risk factor for ASD.


Evolutionary is arbitrary. To the degree that we can consider autism evolutionary, it is without doubt a negative evolutionary trait, a maladaptation. It reduces the chances of an individual to pass on their genes. Autistic people have greater social and relational difficulties. Besides that, autism has grown at a rate way beyond what could be considered something of truly 'genetic' origin. The rate of autism is increasing faster than the rate of HIV. Nothing that grows at epidemic proportions is or can be considered a 'genetic' issue.


Interested to hear your thoughts on the above.

crzxn
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Joined: Sun Jul 12, 2015 12:24 pm

Re: Receptors in brain linked to schizophrenia, autism

Postby crzxn » Thu Aug 13, 2015 12:42 pm

Yes, I want you all to know that this is just an idea I am playing with and I have no attachment to it. Also I believe ASD is a nature and nurture disorder.

But wow, thank you! You helped me find another piece of the puzzle.

It is interesting you brought up possible changes in super oxide dimutase and glutathione peroxidase because that is exactly the change I see in the one sample I have of a mother and her children that I could not explain so I put it aside. Her one child with more severe autism has more beneficial SOD2 polymorphisms, than his mother and his brother whose symptoms are not as severe. The link with GPX is not so clear.

And I read this:
http://www.ncbi.nlm.nih.gov/pubmed/10856185
The results indicate that the oxidative metabolism and, in particular, superoxide dismutase may be perturbed in mercury-intolerant patients.

And this:
http://www.ncbi.nlm.nih.gov/pubmed/9654245
Furthermore, the results of these studies also demonstrate that there is a causal relationship between the induction of H2O2 by these metals and mutagenesis.

There is another antioxidant gene I have just started looking at, Thioredoxin reductase 2, but will get back to you with the data.

So, the other polymorphism I look at like MAOA, SUOX, TPH2, FADS1, FADS2, MCM6 might just higheten the risk of having more hydrogen perioxides and superoxides when the or mother child is exposed to mercury and other heavy metals.

(And by the way, those two enzymes do not get rid of mercury. SOD and GPX just handle the oxidation create by their exposure)

So here I think, what if now that the mercury is gone and these children are not faced with the assault of H2O2 and O2-?

You see, maybe they are not making enough H2O2 anymore because they are not being poisoned? maybe that explains the foods they prefer, like carbs and sugar, because it increases H2O2 production:

Image

Just thinking out loud.

I am preparing a spreadsheet with the genes and hopefully the pattern I see will be clearer.


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