142 replies to this topic

[jack black]

 

Interestingly, there is good evidence that multiple different psychiatric diseases and personality disorders are linked to the genetic polymorphism of sodium channels. Not surprizingly as drugs modulating sodium channel work well for a number of diverse psychiatric diseases and personality disorders.

 

 

In case anyone needs some references on this emerging topic:

 

http://www.ncbi.nlm....les/PMC3646240/ (full length, long read).

http://www.ncbi.nlm....les/PMC4408861/ (OP: you might be amused by the ANK3 reference).

 

 

[farware]

Interesting, it's quite a rare disease. This is actually within my professional expertise. Are you of northern European ethnicity? By keeping eye on iron, you mean not too high, right?

 

Are you taking plenty of B12 with your methylfolate?

 

 

 

I'm from central Europe, not Scandinavian although my 23andme analysis said I was like 4.3% Scandinavian, 12% British. Rest 50% French/German origin. 

 

Haplogroup H2 if anyone wants to know so I guess there is a small link to Northern Europe, yes 

 

I'm taking Methyl-B12 yes but still need to work out the dosage, possibly taking too little. As for Iron, yes I want to avoid overload however I read a study that people without splenectomy (removal of spleen) actually often develop a deficiency so from to time I make sure its ok. 

 

Fortunately, this is not causing a lot of problems yet aside from the mentioned exhaustion after physical activity and yellow eyes. 

 

Edit: Well, we could very well take a look at the genetic origin of ADHD/Schizophrenia as well. Here's more about my own haplogoup H/H2:

 

Today H is the most common haplogroup in Europe, especially in Scandinavia, where it is present in half the population. H2 is one of the older branches of H; although concentrated in Turkey and the Caucasus throughout its history, the haplogroup has made its way across Europe in two separate passes, eventually reaching the British Isles. Source: 

23andme.com

 

 

 

 

 

 

 

 

 

Edited by farware, 29 June 2016 - 02:01 PM.

[farware]

 

 

Interestingly, there is good evidence that multiple different psychiatric diseases and personality disorders are linked to the genetic polymorphism of sodium channels. Not surprizingly as drugs modulating sodium channel work well for a number of diverse psychiatric diseases and personality disorders.

 

 

In case anyone needs some references on this emerging topic:

 

http://www.ncbi.nlm....les/PMC3646240/ (full length, long read).

http://www.ncbi.nlm....les/PMC4408861/ (OP: you might be amused by the ANK3 reference).

 

 

Never head about the sodium channels, was only aware of the Calcium channels  and the possible connection to potassium. A subset of ADHD patients react positively to Potassium supplementation

 

In the May 2009 edition of Nature Medicine, the researchers reported that their analysis pinpointed 4 variations in a small region of a gene called KCNH2. The KCNH2 gene encodes a potassium channel, a type of protein that regulates the flow of potassium ions into or out of cells. 

 

 

In the brain, KCNH2 is known to be active primarily in the prefrontal cortex and hippocampus

https://www.nih.gov/...d-schizophrenia

Edited by farware, 29 June 2016 - 02:13 PM.

[jack black]

 

I'm taking Methyl-B12 yes but still need to work out the dosage, possibly taking too little.

 

 

My understanding is methylB9 with methylB12 may result in too much methylation (anxiety, mental fog). Some recommend regular B12 with methylB9.

 

See this (very long, but very good read): http://www.longecity...ohol-hangovers/

 

And yes, it's more than just sodium channels. I should have said cations channels. I said sodium bacause there are lots of psych drugs working on that one.

 

BTW, i'm also central european with several % scandinavian. I undestand Vikings settled along rivers in the central europe and assimilated with locals.
 

Edited by jack black, 29 June 2016 - 02:39 PM.

[YOLF]

Ah, I gave up all my hobbies except this... life's too short for hobbies. Nothing important to do like stay healthy and young!

[YOLF]

Yellow eyes? How's your liver? Does taurine, Ca Mg Zn Cu, or milk thistle help?

 

B12 is fairly long lasting iirc. It can actually accumulate continuously. B2 will also help with homocysteine and then of course, you might want to just round out your b vits with thiamine HCl, and a mixed B3.

[farware]

Yellow eyes? How's your liver? Does taurine, Ca Mg Zn Cu, or milk thistle help?

 

B12 is fairly long lasting iirc. It can actually accumulate continuously. B2 will also help with homocysteine and then of course, you might want to just round out your b vits with thiamine HCl, and a mixed B3.

 

Yea its a typical symptom, when red blood cells die too quickly they increase levels of bilirubin fairly quickly which then shows up in your eyes, on the skin and can accumulate in certain regions. Fortunately that only happens every other day and goes along with symptoms of exhaustion. I am supplementing Taurin frequently and use Epsom salts in baths so most of that I have figured out already. 

 

Main problem really is ADHD / depression but I'm very optimistic that I am going to make progress in that regard as well once my body adjusts to me supplementing P5P. I am dreaming again after years or lets say my dream recall has returned after years which would be more precise since everyone dreams I suppose so this will hopefully help to boost mood and neuroplasticity further. LongeCity is really a great resource and has helped me a lot with my research.  

[jack black]

 

Main problem really is ADHD / depression but I'm very optimistic that I am going to make progress in that regard as well once my body adjusts to me supplementing P5P. I am dreaming again after years or lets say my dream recall has returned after years which would be more precise since everyone dreams I suppose so this will hopefully help to boost mood and neuroplasticity further. LongeCity is really a great resource and has helped me a lot with my research.  

 

 

Dreaming doesn't mean much IMHO. I had the most vivid dreams after starting phosphatylserine, yet it did nothing for my mood, except for making it worse from lack of sleep from too vivid dreams.

 

The strongest mood boost I've noticed was SAM-e that i currently take (400mg/day). Before that, there was a moderate effect from either methyl-B9 (400ug/day), inosytol (2x 6g/day), tyrosine (2x 500mg/day), saffron (2x 15mg/day), or nicotine gum. I got mild effects from taking B-50 supplement (high dose B-complex) and/or DMAE (300mg/day).

 

SAM-e is so strong for me, that I discontiunued the other supplements (except for B-vitamins). However, if i take methyl-B9 everyday, it feels like too much metylation, thus i skip doses.

[farware]

I need to do a lot more research so this is just a first draft for me with some quotes from studies I find interesting. I still haven't figured out what spectrum I'm on, but leaning towards ADHD because I do so well on NDMA antagonists like Inositol which has been implicated in major depressive disorder. My anhedonia is completely lifting on Ginkgo and PEA from raw cacao. Ginkgo is my major go to supp right now.  

 

My Initial Theory That I Will Work On (Finding proof against/for):

 

ADHD is a result of NDMA overstimulation and a direct result of excitotoxicity. Antagonists that can upregulate dopamine can induce schizophrenia-like symptoms in otherwise healthy people (Ritalin, Ketamine, Stims?). In ADHD patients they do not because they are possibly low in dopamine in the striatum (possibly high dopamine in prefrontal cortex = higher IQ? From memory, need citation?) 

___________________________________________________________________________

 

 

The neurosteroid pregnenolone sulfate blocks NMDA antagonist-induced deficits in a passive avoidance memory task. Pregnenolone sulfate (PS) has been recently shown to positively modulate NMDA receptors and to have memory enhancing properties in mice. [4]

 

 

 

___________________________________________________________________________

Ginkgo biloba against excitotoxicity induced by NMDA receports (beneficial for ADHD)**** Best supplement for me personally

 

 

 

http://www.ncbi.nlm....pubmed/17156678

 

___________________________________________________________________________

 

Brain imaging studies have suggested that the NMDA antagonist ketamine is as potent a releaser of striatal dopamine as amphetamine. [3]

 

 

 

___________________________________________________________________________

 

NMDA antagonism upregulates dopamine (possibly bad in schizo where dopa is high in striatum?)

 

• Magnesium,
• Taurine,
• Inositol,
• PEA[1],
• PQQ

 

 

GamesGuru Thread: "striatal hyperdopamine AND frontal hypodopamine are implicated in schizophrenia." [2]

 

______________________________________________________________________

 

[1] http://herbpedia.wik.../phenethylamine

[2] http://www.longecity...al-otc-options/

[3] http://www.ncbi.nlm....pubmed/11746729

[4] http://www.ncbi.nlm..../pubmed/7862949

 

___________________________________________________________________________

 

Personal observations

• Do very good on: Inositol (1g+), Gingko (500mg+), PEA (2 cups of raw cacao), Pregnenolone (Adrenals / Neuroprotective?!)
• Supplements Of Note: Lysine, Vitamin D3+K2
• Mental Boost: 2400 mg Piracetam
• Energy Boost: DHEA, Ginko, PEA (Cacao)

1. I do ok on: Curcumin, Taurine
2. I do bad on: Theanine (Fog), L-Tyrosine (Dopa downregulation?), Alpha-GPC (strange rebound, mild depression) 
3. Side effects too harsh: Bacopa (Celiac, Gastric Side Effects!) 
4. Stopping temporarily: P5P (Neurotoxicity? Very Sleepy!) 
5. Ordering: PQQ 
6. More testing: NAD+

• Diet: 100% Glutenfree, Tryptophan Cravings
• Sugar-Craving: Raw Cacao Best Alternative (Filtered Water, Not Boiling, Hot)

[farware]

My goal is to modulate NMDA receptors to fix the glutamate issues that are apparently present in affected people. That's also why some supps will benefit both ADHD / Schizophrenics because they dont necessarily directly increase/decrease dopamine but do it indirectly 

 

I also believe there is a genetic link. Celiac is found in many patients and I would bet a lot of money that our instruments are not sophisticated enough to properly diagnose it reliably which means 100% of Schizophrenic could have celiac disease and we wouldnt even know it. It's also apparent that the CLOCK gene variation may be involved as schizophrenics have different bio-cycles. This is the sole reason why I am still not excluding evolutionary reasons for either disease rather than an infection/virus. Much more likely there's a link to gluten and the immune system.  

 

__

 

Also of note regarding PQQ - it may enhance longevity through neurogenesis and could be a powerful supp but requires more research. Possibly rather bad for some people and potentially better suited for ADHDs

 

A key molecule that will be discussed is called brain-derived neurotrophic factor (BDNF). This “neuro-horomone” is essential to the structure of nerve cells and it stimulates neuroplasticity and neurogenesis.

 

 

Edited by farware, 02 July 2016 - 12:57 AM.

[jack black]

 

My Initial Theory That I Will Work On (Finding proof against/for):

 

ADHD is a result of NDMA overstimulation and a direct result of excitotoxicity. Antagonists that can upregulate dopamine can induce schizophrenia-like symptoms in otherwise healthy people (Ritalin, Ketamine, Stims?). In ADHD patients they do not because they are possibly low in dopamine in the striatum (possibly high dopamine in prefrontal cortex = higher IQ? From memory, need citation?) 

 

 

 

My goal is to modulate NMDA receptors to fix the glutamate issues that are apparently present in affected people. That's also why some supps will benefit both ADHD / Schizophrenics because they dont necessarily directly increase/decrease dopamine but do it indirectly 

 

I also believe there is a genetic link. Celiac is found in many patients and I would bet a lot of money that our instruments are not sophisticated enough to properly diagnose it reliably which means 100% of Schizophrenic could have celiac disease and we wouldnt even know it. It's also apparent that the CLOCK gene variation may be involved as schizophrenics have different bio-cycles. This is the sole reason why I am still not excluding evolutionary reasons for either disease rather than an infection/virus. Much more likely there's a link to gluten and the immune system.  

 

I don't think it's that simple. According to: https://en.wikipedia...tamate_receptor

 

 

Attention deficit hyperactivity disorder (ADHD)

In 2006 the glutamate receptor subunit gene GRIN2B (responsible for key functions in memory and learning) was associated with ADHD.^[50] This followed earlier studies showing a link between glutamate modulation and hyperactivity (2001),^[51][51] and then between the SLC1A3 solute carrier gene-encoding part of the glutamate transporter process that mapped to a chromosome (5p12) noted in multiple ADHD genome scans.^[52]

Further mutations to four different metabotropic glutamate receptor genes were identified in a study of 1013 children with ADHD compared to 4105 controls with non-ADHD, replicated in a subsequent study of 2500 more patients. Deletions and duplications affected GRM1, GRM5, GRM7 and GRM8. The study concluded that "CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 × 10−9)", "over 200 genes interacting with glutamate receptors [. .] were collectively affected by CNVs", "major hubs of the (affected genes') network include TNIK50, GNAQ51, and CALM", and "the fact that children with ADHD are more likely to have alterations in these genes reinforces previous evidence that the GRM pathway is important in ADHD".^[47]

A SciBX article in January 2012 commented that "UPenn and MIT teams have independently converged on mGluRs as players in ADHD and autism. The findings suggest agonizing mGluRs in patients with ADHD".

 

Schizophrenia

In schizophrenia, the expression of the mRNA for the NR2A subunit of the NMDA glutamate receptor was found to be decreased in a subset of inhibitory interneurons in the cerebral cortex.^[64] This is suggested by upregulation of GABA, an inhibitory neurotransmitter. In schizophrenia, the expression of the NR2A subunit of NDMA receptors in mRNA was experimentally undetectable in 49-73% in GABA neurons that usually express it. These are mainly in GABA cells expressing the calcium-buffering protein parvalbumin (PV), which exhibits fast-spiking firing properties and target the perisomatic (basket cells) and axo-axonic (chandelier cells) compartments of pyramidal neurons.^[64] The study found the density of NR2A mRNA-expressing PV neurons was decreased by as much as 50% in subjects with schizophrenia. In addition, density of immunohistochemically labeled glutamatergic terminals with an antibody against the vesicular glutamate transporter vGluT1 also exhibited a reduction that paralleled the reduction in the NR2A-expressing PV neurons. Together, these observations suggest glutamatergic innervation of PV-containing inhibitory neurons appears to be deficient in schizophrenia.^[64] Expression of NR2A mRNA has also been found to be altered in the inhibitory neurons that contain another calcium buffer, calbindin, targeting the dendrites of pyramidal neurons,^[65] and the expression of the mRNA for the GluR5 kainate receptor in GABA neurons has also been found to be changed in organisms with schizophrenia.^[66] Current research is targeting glutamate receptor antagonists as potential treatments for schizophrenia. Memantine, a weak, nonselective NMDA receptor antagonist, was used as an add-on to clozapine therapy in a clinical trial. Refractory schizophrenia patients showed associated improvements in both negative and positive symptoms, underscoring the potential uses of GluR antagonists as antipsychotics.^[67] Furthermore, administration of noncompetitive NMDA receptor antagonists have been tested on rat models. Scientists proposed that specific antagonists can act on GABAergic interneurons, enhancing cortical inhibition and preventing excessive glutamatergic transmission associated with schizophrenia. These and other atypical antipsychotic drugs can be used together to inhibit excessive excitability in pyramidal cells, decreasing the symptoms of schizophrenia.

 

Autism

The etiology of autism may include excessive glutamatergic mechanisms. In small studies, memantine has been shown to significantly improve language function and social behavior in children with autism.^[54][55] Research is underway on the effects of memantine in adults with autism spectrum disorders.^[56]

A link between glutamate receptors and autism was also identified via the structural protein ProSAP1 SHANK2 and potentially ProSAP2 SHANK3. The study authors concluded that the study "illustrates the significant role glutamatergic systems play in autism" and "By comparing the data on ProSAP1/Shank2^−/− mutants with ProSAP2/Shank3αβ^−/− mice, we show that different abnormalities in synaptic glutamate receptor expression can cause alterations in social interactions and communication. Accordingly, we propose that appropriate therapies for autism spectrum disorders are to be carefully matched to the underlying synaptopathic phenotype."^[48]

 

 

Different receptors, different mechanism. On the other hand, what you propose fits autism well.

 

But, IMHO, the current concept of ADHD is a wastebasket of various conditions, just like various psychological, psychiatric, or even medical conditions can produce depression.

Thus, you might be right, some people with ADHD can benefit from NMDA antagonists. This supports it: https://en.wikipedia.../wiki/Memantine

 

 

It has shown promising results in studies for treatment of obsessive compulsive disorder,^[10][11]generalized anxiety disorder, as an augmentation therapy for anxiety disorders,^[12]ADHD,^[13] as well as to help slowing down or even reversing the tolerance development to opioids.^[14]

 

You are absolutely right about the current state of testing for gluten sensitivity. Besides, one can be allergic or sensitive to other substances in grains and not exactly gluten. Grain and dairy foods are known to be addictive by poorly understood mechanisms: http://kellybroganmd...sabotage-brain/

Edited by jack black, 02 July 2016 - 05:16 AM.

[farware]

Apparently ADHD symptoms overlap with Asperger/Autism 

 

Some genes that I also have related to Autism:

 

 

rs7794745(A;T)

slightly increased risk for autism

 

rs1858830(C;C)

2x risk of autism The C allele appears to increase risk of autism by an odds ratio of perhaps 1.8x

 

rs3819331(C;T)

increased risk of autism Increased risk of autism.[http://www.ncbi.nlm....es/PMC2784255/]

 

rs1801133(C;T)

This reduced activity (i.e. this SNP) has been linked at least once to each of the following disorders (though not necessarily reproducibly): * autism *

 

rs53576(A;G)

Lack of empathy? You have a SNP in the oxytocin receptor which may make you less empathetic than most people.

 

rs4307059(T;T)

1.42x risk of Autism Worse cell adhesion in neurons.[http://www.ncbi.nlm....es/PMC3008767/]Increased risk of Autism Spectrum Disorders.

 

 

 

 

Also of note: rs4741652(C;C), rs2799573(G;G), rs4675502(G;G), rs1896731(C;C), rs3735520(T;T), rs159788(A;G), rs12871532(C;C)

 

I think its best to look at your own behaviour throughout the day. If you frequently switch tasks, its probably ADHD, but if you obsess with 1 task it's probably a little closer to Asperger / Autism. Really needs a doctor to make the diagnosis, doesn't seem that easy. 

 

Both share lots of common characteristics like sensitivity to light, sound. 

 

It's very difficult to diagnose someone because other mental diseases like major depressive disorder, schizophrenia, bipolar also often share the same characteristics. So I bet there are a lot of people that get incorrectly diagnosed for one and then take meds based on that initial diagnosis that can then potentially make the problems worse and then end up with more problems. 

 

 

 

 

 

 

 

 

 

[Mind_Paralysis]

Farware... did you read my prototypical paper regarding KYNA and ADHD...? This stuff you're going through regarding the NMDA-network and ADHD, and the NMDA-network and Schizophrenia, is something I've already gone through - extensively.

 

If you didn't read my paper, you are honestly, wasting quite a bit of time.

 

I explain how KYNA is an extremely potent NMDA-antagonist - how it modulates dopaminergic activity, how the NMDA-network is directly modulated by the D4-receptor, and how it's NOT modulated when said receptor is faulty.

 

I explain how Schizophrenics have such an altered neuro-anathomy from ADHD-ers that they can't possibly coexist... the proposed main mechanism of psychosis, KYNA-superproduction, is wholly absent from ADHD! ADHD shows decreased KYNA-production, not increased.

 

I show how Tryptophan metabolism is altered in ADHD (KYNA, Serotonin and Melatonin are all a result of tryptophan metabolism), and how it relates to the following:

 

Disturbed cirkadian rhytm (almost everyone with either ADHD or SCT has a disturbed CR - it may even be why Agomelatine shows some effect - it has synergistic properties for adjusting CR and increasing DA and NE)

Ketogenic diet - kyna increases substantially from ketogenic diet (LCHF) - said diet has shown symptom-relief in ADHD

NMDA-network - KYNA modulates the NMDA-network

 

I even list two possible compounds that could increase KYNA-production: Nicotinylalanine and AV-101 (4-CI-KYN).

 

Now, I don't recommend you try those, because if you are schizophrenic, then these could literally kill you...! o.o If you are only SCT or ADHD though... no way in hell! They will either do nothing, decrease symptoms, or cure anhedonia. (they are both nootropics and antidepressants)

 

Also, you seem to have missed my research and contacts with Hakon Hakonarson, the researcher employed by Human Genome Project who found the link between ADHD and mGlur -mutations. He did a trial of the mGlur -agonist Fasoracetam, since he figured it would help a subset of ADHD-ers.

 

Well, it does - but that subset? They ALL have Intellectual Disability as comorbidity...! Decreased glutamatergic metabotropic signalling is implicated in low IQ, you see - if you don't have ID (which we can both obviously tell that you don't) then your benefit from mGlur-agonists are bound to be limited. Me, and several other ADHD-PI/SCT-ers on this board and Reddit have tried it - the results were limited. Hakonarson found this out as well, which is why nothing much came from that trial of his - he realized only the people who are ID will be helped by Fasoracetam - a potent mGlur-agonist at several receptor-sites.

 

I wish you would actually listen to me.

 

Focus on A-412,997 and other selective D4-agonists.

 

It's the only compounds shown to benefit both ADHD and Schizo.

[Mind_Paralysis]

Apparently ADHD symptoms overlap with Asperger/Autism 

 

Some genes that I also have related to Autism:

 

 

rs7794745(A;T)

slightly increased risk for autism

 

rs1858830(C;C)

2x risk of autism The C allele appears to increase risk of autism by an odds ratio of perhaps 1.8x

 

rs3819331(C;T)

increased risk of autism Increased risk of autism.[http://www.ncbi.nlm....es/PMC2784255/]

 

rs1801133(C;T)

This reduced activity (i.e. this SNP) has been linked at least once to each of the following disorders (though not necessarily reproducibly): * autism *

 

rs53576(A;G)

Lack of empathy? You have a SNP in the oxytocin receptor which may make you less empathetic than most people.

 

rs4307059(T;T)

1.42x risk of Autism Worse cell adhesion in neurons.[http://www.ncbi.nlm....es/PMC3008767/]Increased risk of Autism Spectrum Disorders.

 

 

 

 

Also of note: rs4741652(C;C), rs2799573(G;G), rs4675502(G;G), rs1896731(C;C), rs3735520(T;T), rs159788(A;G), rs12871532(C;C)

 

I think its best to look at your own behaviour throughout the day. If you frequently switch tasks, its probably ADHD, but if you obsess with 1 task it's probably a little closer to Asperger / Autism. Really needs a doctor to make the diagnosis, doesn't seem that easy. 

 

Both share lots of common characteristics like sensitivity to light, sound. 

 

It's very difficult to diagnose someone because other mental diseases like major depressive disorder, schizophrenia, bipolar also often share the same characteristics. So I bet there are a lot of people that get incorrectly diagnosed for one and then take meds based on that initial diagnosis that can then potentially make the problems worse and then end up with more problems. 

 

I actually proposed a reason for why Autism shares traits with ADHD recently, it's the same reason why ADHD shares traits with SCT:

 

Autism* is the third attention-disorder.

*(Well, a subset of Autism is)
 

If you check what the autists who describe attentional problems are describing, then it's not what ADHD is - problems with sustained attention, or SCT is - problems with engaging attention.

 

No, what they are describing is actually the THIRD dimension of attention: Switching attention. Autists have problems with attention when they are forced to switch tasks, this ruins their focus utterly.

 

Check out what Russelly Barkley says about the 5-6 dimensions of Attention - SCT is an impairment of a different dimension of attention than ADHD. Autism is yet another. There would then still be 2-3 EVEN MORE Attention-disorders than these three.

 

I don't blame you or anyone else for not knowing that though - I have no proof, and no-one seems to have considered it yet, so there's no way you could know that, or why you should believe me!

 

I just have... a gut-feeling, that I'm right. It just makes sense, within the logic of the parameters I have found.

Edited by Stinkorninjor, 05 July 2016 - 02:16 AM.

[jack black]

 

 

I actually proposed a reason for why Autism shares traits with ADHD recently, it's the same reason why ADHD shares traits with SCT:

 

Autism* is the third attention-disorder.

*(Well, a subset of Autism is)
 

If you check what the autists who describe attentional problems are describing, then it's not what ADHD is - problems with sustained attention, or SCT is - problems with engaging attention.

 

No, what they are describing is actually the THIRD dimension of attention: Switching attention. Autists have problems with attention when they are forced to switch tasks, this ruins their focus utterly.

 

Check out what Russelly Barkley says about the 5-6 dimensions of Attention - SCT is an impairment of a different dimension of attention than ADHD. Autism is yet another. There would then still be 2-3 EVEN MORE Attention-disorders than these three.

 

I don't blame you or anyone else for not knowing that though - I have no proof, and no-one seems to have considered it yet, so there's no way you could know that, or why you should believe me!

 

I just have... a gut-feeling, that I'm right. It just makes sense, within the logic of the parameters I have found.

 

 

Well, there are some prominent docs who don't believe the traditional ADHD classification.

Are you familiar with Dr. Daniel Amen's Healing ADD?

 

He recognises 7 types, and one is indeed characterised by switching attention problems. He calls it Over-Focused ADD: difficulty with shifting attention. Worries and holds grudges. If things don't go their way, they get upset. They tend to be argumentative, oppositional, and see all kinds of things wrong in situations and people.

 

Some folks in my family have that plus social enxiety and poor interpersonal skills. I'm still not sure if that's really ADHD or rather a form of borderline personality disorder or maybe a mild form of Aspergers.

 

But, I would like to hear more about your theory. Do you have a link?

Edited by jack black, 05 July 2016 - 03:07 AM.

[farware]

Farware... did you read my prototypical paper regarding KYNA and ADHD...? This stuff you're going through regarding the NMDA-network and ADHD, and the NMDA-network and Schizophrenia, is something I've already gone through - extensively.

 

If you didn't read my paper, you are honestly, wasting quite a bit of time.

 

 

I show how Tryptophan metabolism is altered in ADHD (KYNA, Serotonin and Melatonin are all a result of tryptophan metabolism), and how it relates to the following:

 

Disturbed cirkadian rhytm (almost everyone with either ADHD or SCT has a disturbed CR - it may even be why Agomelatine shows some effect - it has synergistic properties for adjusting CR and increasing DA and NE)

Ketogenic diet - kyna increases substantially from ketogenic diet (LCHF) - said diet has shown symptom-relief in ADHD

NMDA-network - KYNA modulates the NMDA-network

 

 

Focus on A-412,997 and other selective D4-agonists.

 

It's the only compounds shown to benefit both ADHD and Schizo.

 

 

Thank you for bringing that up again. I am going to read the paper as soon as I can. At this point however I am seriously considering Aspergers more than anything else because of my comorbid symptoms: Hashi, celiac and food allergies. I believ and this is still a theory that gut permability is linked to autism and that ADHD is often a misdiagnosis and Aspergers is the real disease behind ADHD. When I went to college it was so stressful I quit 2 months in and had to undergo surgery just months later. I believe that the stress exacerbated my leaky gut and that that set of a chain reaction that would play out over several years and give me ADHD, food sensitives and what not. Gluten is inflamming the brain via the proven gut-brain vagus nerve (this is scientifically proven to exist today and is no more pseudo-science). 

 

Therefore right now I am focusing my entire research on exactly 2 supplements which I have identified as the most helpful: Low dose natrexone and its counterpart Tianeptine. There are already some threads on longecity regarding this which I found to be very interesting. 

 

Also it would explain why SSRIs make problems worse for a lot of people as they increase Serotonin. People on the autistic spectrum already have very high serotonin. This also explains my personal reaction to St Johns Wort, Rhodiala and 5-HTP: Very bad to mixed reaction. 

 

Asperger would also explain a large part of my life, why I have focused interests (still a variety of interest but always focusing on 1 entirely for 1 to 5 years) and have trouble making eye contact and have been dependent on other people for much longer than my peers. I also recently dated a women who as it turned out later has aspergers and we have a lot in common. 

Edited by farware, 05 July 2016 - 03:01 PM.

[farware]

Let me quickly post some of the studies that led me to my conclusions

 

http://www.ncbi.nlm....pubmed/12858327

Tianeptine: a novel strategy of psychopharmacological treatment of children with autistic disorder. (2003)

 

http://www.ncbi.nlm....ubmed/25407511 

Intestinal permeability--a new target for disease prevention and therapy. (2014)

 

http://www.ncbi.nlm....pubmed/25446201

Gastrointestinal microbiota in children with autism in Slovakia. (2015)

 

http://www.ncbi.nlm....pubmed/20683204

Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives.

 

__

 

LDN and Tianeptine Thread on Longecity http://www.longecity...-would-it-work/

My own Tianeptine review thread: http://www.longecity...reams-insomnia/

 

__

 

Thank you @jackblack for bringing up autism in the first place. 

 

I think there is a link somewhere connecting all of this. The gut is the prime contender. Mainstream medicine can no longer ignore the brain-gut connection and thats why they are only making progress on this now because they failed to overcome their own bias. 

 

 

 

 

 

Edited by farware, 05 July 2016 - 03:24 PM.

[farware]

As for the difference between the different types of attention problems in Asperger, ADHD, Schizophrenia check out the link I posted at the very beginning of the thread: 

http://www.sciencedi...887617707001278

 

Executive function is completed impaired in Schizophrenia. They cant initiate focus at all so that is probably the worst form. 

 

That there are different subsets of attention disorder is not surprising but as an affected person I really dont care, what I care about is repairing the receptors and getting on with my life. Different genes and your environment and upbringing can lead to a great variety of symptoms but what does it matter when in all types the same receptors are implicated? 

[Mind_Paralysis]

Well, there are some prominent docs who don't believe the traditional ADHD classification.

Are you familiar with Dr. Daniel Amen's Healing ADD?

 

He recognises 7 types, and one is indeed characterised by switching attention problems. He calls it Over-Focused ADD: difficulty with shifting attention. Worries and holds grudges. If things don't go their way, they get upset. They tend to be argumentative, oppositional, and see all kinds of things wrong in situations and people.

 

Some folks in my family have that plus social enxiety and poor interpersonal skills. I'm still not sure if that's really ADHD or rather a form of borderline personality disorder or maybe a mild form of Aspergers.

 

But, I would like to hear more about your theory. Do you have a link?

 

 

Yeah, I know about Amen - alas, I also know that he's a somewhat conspicuous fellow - not really the Dr. Russell Barkley -type, who is more respected in the scientific communit - I'm among those that feel Amen can alas, not be trusted - and his results are fairly weak.

 

That doesn't mean that he may not have some valid ideas and observations - but unless someone else reports similar things, it's hard to take them seriously.

 

Cheers for being interested tho', mate - I'd love to hear what you think of my own ruminations on the subject matter.

 

Here's my original, very thin and insubstantial post on the matter:

 

Right, I'm experiencing the symptoms of Pathological Rumination right now, so I CAN'T be made to dig up all of the quotes and studies by Dr. Russell Barkley, but suffice to say...

It's got NOTHING to do with Autism - the people with autism are experiencing a different, but similar deficit in attention.

Pathological Rumination is what Dr. Barkley calls it - the inability to to execute attention in the first place - we overthink everything, to the point of complete mental and physical fatigue.

Basically, our minds are stuck at PREPARING to go, but never getting to GO,GO,GO,GO,GOOOO!!! Which the hyperactives, the people with REAL ADHD have.

There are 5-6 aspects of attention, according to the cognitive model currently used by science - and SCT seems to correlate with deficits in one of them, ADHD seems to correlate with deficits in another.

That actually means there are 4 more aspects to disturb... I'm guessing that what some of these autists are experiencing, is indeed a disturbance in a completely different aspect.

Hold on... I'm getting a second wind from writing this... it's hard...!

Ah - here we go.

https://en.wikipedia...#Clinical_model
 

• Focused attention: The ability to respond discretely to specific visual, auditory or tactile stimuli.
  (Deficits in this one correlates to ADHD)
• Sustained attention (vigilance and concentration): The ability to maintain a consistent behavioral response during continuous and repetitive activity.
  (Deficits in this one correlates to SCT)
• Selective attention: The ability to maintain a behavioral or cognitive set in the face of distracting or competing stimuli. Therefore, it incorporates the notion of "freedom from distractibility."
• Alternating attention: The ability of mental flexibility that allows individuals to shift their focus of attention and move between tasks having different cognitive requirements.
  (THIS seems to be the autistic problem. It's a completely different thing, ya'll! Btw, if this is correct... that these are all independent attention-disorders... then maybe the autists on anotherdrum have some HOPE! Because, this implies it's something similar to ADHD and SCT - and NOT autism! Well, that, or they have a comorbid attention-disorder, which is certainly common, lot's of ADHD-ers who have Autism as well. Guess it makes sense.)
• Divided attention: This is the highest level of attention and it refers to the ability to respond simultaneously to multiple tasks or multiple task demands.

 

 

What I find interesting is how Dr. Russell Barkley mentions in a video that there is SIX dimensions of Attention, yet the only references I can find, all mention only FIVE dimensions. Am I misinterpreting the info? Or just not looking into it hard enough? Other than the 5 dimensions above, what possible other aspects of Attention could there be, that could be impaired?

 

Also, which disorders would you say fits the best into Selective Attention and Divided Attention -deficits? The Divided Attention dimension seems the toughest to pin down, since that's such a general and easily disturbed aspect - it may also be the LEAST impairing of all of these disorders - since it's also the highest level, a level which probably until only just recently, would never have been much of a problem in every day life. This one could be just about anything...

 

I'm also curious if Selective Attention could correspond to the CHOLINERGIC aspects of adhd... hmm... there's some proof that a Cholinergic subset of ADHD exists, hence why there's a development of nicotinergic medications to treat ADHD - and since classic ADHD seems to respond the best to Dopaminergics, while SCT seems to respond the most to Norepinephrinergics, then it stands to reason that the peeps that respond to Cholinergics are a different disorder in themselves - something else than ADHD or SCT.

 

No idea what those symptoms would be though... what ARE the symptoms of disturbances in Cholinergic receptors? Are there any variations of traumatic brain injury that causes impairment in the cholinergic systems? I figure that would be an area to look into, to start figuring out who these people are. (Dr. Barkley mentions how some PFC-injuries are highly similar to ADHD - with over-eating, difficulty to control impulses and emotions, and how injuries to the Parietal Lobe seems to correspond to the symptoms of SCT - spaciness, slowness, et c)

 

 

 

Thank you for bringing that up again. I am going to read the paper as soon as I can. At this point however I am seriously considering Aspergers more than anything else because of my comorbid symptoms: Hashi, celiac and food allergies. I believ and this is still a theory that gut permability is linked to autism and that ADHD is often a misdiagnosis and Aspergers is the real disease behind ADHD. When I went to college it was so stressful I quit 2 months in and had to undergo surgery just months later. I believe that the stress exacerbated my leaky gut and that that set of a chain reaction that would play out over several years and give me ADHD, food sensitives and what not. Gluten is inflamming the brain via the proven gut-brain vagus nerve (this is scientifically proven to exist today and is no more pseudo-science). 

 

Therefore right now I am focusing my entire research on exactly 2 supplements which I have identified as the most helpful: Low dose natrexone and its counterpart Tianeptine. There are already some threads on longecity regarding this which I found to be very interesting. 

 

Also it would explain why SSRIs make problems worse for a lot of people as they increase Serotonin. People on the autistic spectrum already have very high serotonin. This also explains my personal reaction to St Johns Wort, Rhodiala and 5-HTP: Very bad to mixed reaction. 

 

Asperger would also explain a large part of my life, why I have focused interests (still a variety of interest but always focusing on 1 entirely for 1 to 5 years) and have trouble making eye contact and have been dependent on other people for much longer than my peers. I also recently dated a women who as it turned out later has aspergers and we have a lot in common. 

 

Let me quickly post some of the studies that led me to my conclusions

 

http://www.ncbi.nlm....pubmed/12858327

Tianeptine: a novel strategy of psychopharmacological treatment of children with autistic disorder. (2003)

 

http://www.ncbi.nlm....ubmed/25407511 

Intestinal permeability--a new target for disease prevention and therapy. (2014)

 

http://www.ncbi.nlm....pubmed/25446201

Gastrointestinal microbiota in children with autism in Slovakia. (2015)

 

http://www.ncbi.nlm....pubmed/20683204

Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives.

 

__

 

LDN and Tianeptine Thread on Longecity http://www.longecity...-would-it-work/

My own Tianeptine review thread: http://www.longecity...reams-insomnia/

 

__

 

Thank you @jackblack for bringing up autism in the first place. 

 

I think there is a link somewhere connecting all of this. The gut is the prime contender. Mainstream medicine can no longer ignore the brain-gut connection and thats why they are only making progress on this now because they failed to overcome their own bias.

 

 

Cheers for wanting to have a look - I'm actually feeling rather like a "life-failure" right now, so I was actually projecting a bit of hostility in the last post, just trying my best to control it and mask it.

 

You certainly make a good case for a connection between the gut and Autism - but I'm not so sure that connection is equally clear in ADHD - sure, Tryptophan metabolism is affected by diet, but not to much of an extent - it's all hardcoded in there, not much one can do with the soft solutions - you're going to need compounds that alter the process substantially.

 

I would agree that you do show some symptoms of Autism, but there is also the problem that some symptoms are comorbid with other disorders, wholly different from both ADHD and Autism - SCT for instance, can be misdiagnosed as BOTH, since it has features of both.

 

(fewer friends, impaired coordination, impaired attention, et c)
 

But in reality, it is neither.

 

Why I think differentiating between variations and disorders is important is exactly the fact that it does matter though - SCT can't really be treated with the same compounds as ADHD - that's a fallacy, and the treatment-results bear it out. There's any number of us populating Longecity and Reddit, throwing our woes around about how the traditional ADHD-treatments just aren't working - and about how different we are as patients, compared to the hyperactives.

 

If you listen to Russell Barkley, you will hear him mention this - about how he finds it difficult to treat SCT, and how he has observed that the response and success-rate of stimulant-therapy just isn't there for SCT.

 

Even if the same receptors are implicated, the location and function of the structures where they are situated, alters the results of a medication substantially - if SCT is impairment in the Parietal Lobe, while ADHD is impairment in the Frontal Lobe, then medications are not going to have the same results.

 

The way Barkley uses the difference between Anxiety and Depression to describe the difference between ADHD and SCT is certainly an apt one - both are treated with SSRI's and SNRI's, but the results of both on Anxiety is substantially less than on Depression - there are also medications that do affect Anxiety, which have very, very little effect on depression  - like Gabaergics, Benzodiasepines and Z-analogues.

 

(newer research also implies that while there is some weak evidence that Depression is caused by low serotonin, there is actually SUBSTANTIAL evidence showing Anxiety being caused by HIGH Serotonin - which mean Serotonin-enhancing drugs may actually be counterindicated in treating Anxiety - which may be why SNRI's are more efficient in treating anxiety, while the same can't be said for Depression - SSRI's are still the king of the hill there.)

 

 

Btw, in closing, have you looked into NitroMemantine any? That's actually one of the few novel compounds that showed promise in both Autism AND adhd. It was extensively discussed on these boards about 1-2 years back (I can proudly say I was one of the folks drumming up interest in the compound) - only problem of course being that the nitrate-group makes it MUTAGENIC...

 

(lol! you don't wanna' turn into a ninja-turtle, dude!)

 

But still, perhaps there are then other NMDA-antagonists which could be useful in treating Autism, yeah? Nitromemantine is why I started looking into KYNA, since it seemed to be a far more elegant and gentle method to increase NMDA-antagonism - and lo and behold... AV-101 does seem to have far less side-effects than Memantine or Nitro-memantine, and even greater effect!

Certainly not the right compound for Schizo's tho... HRRRrrMm! 0__0

 

(seriously, if someone Schizo takes AV-101... then that may well be the most dangerous compound on Earth to them - it could trigger a psychotic episode in a matter of minutes - no different from stuff like Ketamine or Psilocybin - one false move...! And you'd be essentially dead - damaged in a way that no antipsychotic treatment will be able to help you.)

[farware]

Just an update on this. Since ion channels are implicated in ADHD/Asperger I have added Potassium to my stake. That should help with the exchange of positive and negative ions and it is generally believed to be a helpful supplement for autism. Calcium channels are also implicated but I need to read more about the science behind it and learn a little chemistry first.  

 

==> Here's a gene that could be somewhat related 

 

 

rs4307059(T;T)

1.42x risk of Autism Worse cell adhesion in neurons.[http://www.ncbi.nlm....es/PMC3008767/]Increased risk of Autism Spectrum Disorders.

 

 

 

Adhesions serve several critical processes including cell migration, signal transduction, tissue development and repair.

https://en.wikipedia...ral_development

 

These adhesion systems are important for brain morphology and highly coordinated brain functions, such as memory and learning

http://www.ncbi.nlm....les/PMC2675146/

 

 

Aside from that I am now taking folate daily instead of once a week to completely avoid any of the homocysteine issues that could also interfere with this process on a daily basis. 

 

Some further studies to look into to understand ADHD, Schizophrenia and Autism links:

http://www.ncbi.nlm....les/PMC4820035/

 

 Our aim was to test for enrichment of neurodevelopmental gene sets, implicated by recent exome sequencing studies of a) schizophrenia and b) autism as a means of testing the hypothesis that common pathogenic mechanisms underlie ADHD and these other neurodevelopmental disorders.

 

 

In these analyses of ADHD case-control CNV data, the largest to date, we found highly significant enrichment of CNVs in many, though not all, hypothesised neurodevelopmental gene sets.

 

 

 

 

 

For me personally this discussion has helped me a lot. I show a lot of autistic traits like being very sensitive to sounds and light which I am more aware of now but I'm now 28, so any diagnosis would be complicated by that and the doctors in my area do not concern themselves with such issues and lack any understanding of the disease(s) in the first place. Due to the similarities in comorbid symptoms among all of the diseases in particular gut problems its very difficult to differentiate between the diseases and I guess you have to look very closely at the symptoms a person displays to really get to the bottom. 

 

I believe we touched on a lot of critical subjects in this thread and it has contributed a lot to my understanding, thank you for the constructive replies. 

 

 

[jack black]

This is a good discussion indeed. Based on this, I ordered generic memantine from overseas pharmacy.

[farware]

ADHD treatment with Memantine

 

The vast majority of children and adults with ADHD also have trouble with executive functions, the cognitive and mental abilities that help people engage in goal-directed action. Even when they try very hard, they fall short because of a malfunction in the prefrontal cortex. These executive function problems were previously difficult to treat with medication.

 

 

http://www.medscape....warticle/846627

http://www.additudem...s/19/11431.html

 

Here's the longecity thread on Memantine: 

http://www.longecity...-anxiety/page-2

 

 

GetOutofBox on this board, which had a great, great thread regarding ADD ( ADhD-PI, hypoactive, instead of HYPER-active) reported that Coluracetam was in essence USELESS for him.

That's what got him on the track of NMDA-antagonism actually, since he felt that Glutamate-agonists, seemed to worsen some of his symptoms.

 

 

 

There's a lot you can learn from how you react to antagonists vs agonists. It certainly has helped me to figure some things out.

 

 

 

Also of note 

 

Memantine May Reverse Tolerance for Almost everything

This is due to its incredible action as a moderate affinity, uncompetitive NMDA receptor antagonist with strong voltage-dependency and fast kinetics. 

 

 

 

http://www.khemcorp....iate-tolerance/

 

Looks like Memantine can also be helpful to avoid opiate tolerance and a bunch of of other tolerances so it may be a good addon for Tianeptine as well as it could prevent the body from building a tolerance to it which it ultimately will even at therapeutic doses. 

 

It would be interesting to see whether it may help people on the autism spectrum 

 

 

Edited by farware, 10 July 2016 - 02:00 PM.

[farware]

Developmental delays are described premorbidly in samples of children and adults with schizophrenia. More recently, the notion that ASD and schizophrenia can present comorbidly in a subset of patients has received further attention in the literature.7,29 Yet our current diagnostic hierarchy implies that the two conditions are distinct.

http://www.psychiatr...d-schizophrenia

 

Also of note: "Conversely, we also see adolescents or young adults with schizophrenia who have a developmental history consistent with ASD (typically higher functioning) and who continue to have comorbid ASD. Yet some have not previously received a diagnosis of ASD"

 

 

Unfortunately for me that means I cant rule out anything at this point since autism seems to be quite common in schizophrenics as well and could be part of a prodromal phase. Given my age, its possible I will be able to rule it out within 12 to 24 months.  

 

On the other hand I found this study very telling:

 

Phencyclidine, ketamine, and other agents that block NMDA glutamate receptors trigger a schizophrenia-like psychosis in humans and induce pathomorphological changes in cerebrocortical neurons in rat brain. 

 

 

If I was really low in glutamate (hypo) then I possibly wouldn't have such a positive reaction to NMDA antagonists that block glutamate release in particular. Inositol.  Inositol stands out because it seems to be helpful for Depression but not for SCT

 

Inositol can lower glutamate release and works exceptionally well for me at times and helps with the digestion of certain foods or at least improves the reaction possibly by lowering the inflammatory reaction? Inositol does not seem to act as much on  AChE (acetylcholinesterase). 

 

http://onlinelibrary...080109/abstract

 

However, the study below about memantine contradicts this because you can have hypofunctioning receptors that try to compensate by releasing excessive amounts of glutamate given you similar symptoms to those displayed in autism, ADHD and related disorders.  

 

"It is possible that the hypofunctional NMDA receptors could lead to a compensatory excessive glutamate release trying to overcome that deficit; reversing this trend may be helpful in reducing schizophrenia symptoms"

 

 

--

 

Memantine used for negative schizophrenia symptoms:

http://www.hindawi.c...ps/2014/384783/

 

 

Memantine is an NMDA-receptor antagonist that partially blocks NMDA receptors thus preventing a toxic influx of calcium and the resultant cell death [9]. It has been hypothesized that it could ameliorate schizophrenia symptoms—the negative ones among them [10].

http://www.hindawi.c...ps/2014/384783/

 

 

Since Tianeptine and Memantine dont directly affect glutamate receptors but work indirectly through modulating receptors its possible they can help a variety of issues that at first glance seem distinc from each other but really are not e.g. ADHD, Autism, Schizophrenia

 

Memantine binds to an open channel binding site. That means the neuron must depolarize, and the magnesium blockage clear, before it can bind. Since tianeptine is modulating the AMPA to NMDA current, it will affect the clearing of that channel. Whether or not that will adversely affect each other, I am not sure of. If anything it will support memantine's mechanism, by lowering the possibility for too much calcium transmission.

 

https://www.reddit.c...or_antagnostic/

 

 

Edited by farware, 10 July 2016 - 09:04 PM.

[Mind_Paralysis]

Interesting. I never thought Memantine could be helpful for Schizo - seemed contraindicated to me.

Have you looked into Nitromemantine btw? It's super-rare and very, very expensive, but unlike Memantine the animal-trials actually showed some effect on Autistic traits.

 

I was actually really into that one, until the research was shelved because of the possibility of mutagenic effects - that nitrate-group ain't no joke.

Alas, it's also what makes it many times more powerful than Memantine.

 

But, perhaps there are other compounds with similar, highly powerful NMDA-modulating properties? AV-101 is obviously out of the question for you, what with the potential Schizo, but it's proof that there are other powerful NMDA-modulators in the works, with similar modes of action.

 

Are there any other variations of Memantine in the works? What about Magnesium-L-thrionate? Or Magnesium Glycinate?

 

Btw, my brain is fried from burnout-fatigue but just seeing you fighting and trying in this thread is giving me back some will to fight - just keep up the good work mate - your work ain't for nuthin', it's gotten me thinking more, and studying more about this stuff too.

[farware]

So my first conclusions from all this: 

 

• 1) ADHD and Autism can be comborbid symptoms or part of a prodromal phase of Schizophrenia - All three are linked together very closely
• 2) NDMA-Antagonist are not solely working for Autism/ADHD but also for Schizophrenia - the reasoning behind that is that hypofunctioning receptors try to compensate with excess glutamate release which makes sense, so all three can have very similar symptoms.

 

Basically looking at your symptoms you cant exclude one or the other unless you show more severe symptoms of hallucinations, hearing voices, etc. or have passed a certain age. 

 

I have completely dismissed the entire dopamine part for now because there is simply no way to target NTs properly and you can seriously mess up your NT balance by using something like Ritalin or Adderall. No thank you. 

 

 

 

 

Edited by farware, 10 July 2016 - 09:19 PM.

[farware]

Interesting. I never thought Memantine could be helpful for Schizo - seemed contraindicated to me.

Have you looked into Nitromemantine btw? It's super-rare and very, very expensive, but unlike Memantine the animal-trials actually showed some effect on Autistic traits.

 

I was actually really into that one, until the research was shelved because of the possibility of mutagenic effects - that nitrate-group ain't no joke.

Alas, it's also what makes it many times more powerful than Memantine.

 

But, perhaps there are other compounds with similar, highly powerful NMDA-modulating properties? AV-101 is obviously out of the question for you, what with the potential Schizo, but it's proof that there are other powerful NMDA-modulators in the works, with similar modes of action.

 

Are there any other variations of Memantine in the works? What about Magnesium-L-thrionate? Or Magnesium Glycinate?

 

Btw, my brain is fried from burnout-fatigue but just seeing you fighting and trying in this thread is giving me back some will to fight - just keep up the good work mate - your work ain't for nuthin', it's gotten me thinking more, and studying more about this stuff too.

 

Yup I read about Nitromemantine but not sure if its worth trying. I react very strongly to even very low doses of medications. 

 

Right now I am just trying to simplify the topic so much that I can actually understand it and draw some reasonable conclusions. Thats very difficult because its such a complex topic.

 

Here's more information on why certain medication seem counterintuitive at first glance but can have great potential:

 

 

The studies described above are all using NMDA agonists but there is another possible method that might be successful at increasing levels of NMDA. That is the use of an NMDA antagonist that would work like the current SSRI anti-depressants. The current class of anti-depressants work by preventing serotonin from being degraded after it has done its job. When serotonin, or any other neurotransmitter, delivers its message across the synapse and reaches the receptor on the next neuron, it is eliminated or neutralized. The SSRIs prevent that from happening thus enabling more serotonin to remain in the brain. They are serotinin antagonists.

 

http://www.schizophr...com/glycine.htm

 

 

 

Basically what they are suggesting is that certain NMDA antagonists can act in a similar fashion as SSRIs. 

 

AMPAKINES

 

Ampas are subtypes of receptors that recognize glutamate and are involved in a process known as long-term potentiation, or LTP that is involved with memory. It is believed that AMPA receptor activity modulated with AMPAKINE drugs may provide a new and highly affective approach to treating a number of central nervous system disorders such as Alzheimer’s disease and schizophrenia.

 

This is the research direction that Dr. Donald C Goff of Harvard is taking. He told the workshop that ampakines are able to open the gated NMDA channels in the brain by depolarization. That is, changing the membrane cells electrically to become more positive. This has the effect of removing the magnesium blockade, opens the channel and allows more NMDA to be present.

 

 

 

Memantine seems to be one of those paradox findings. At first glance it should be avoided in SCT but Memantine would clear a possible Mg blockage from what Ive read so far and would actually allow more NMDA in the neurons? 

 

It makes sense that various membrance defects / cell adhesion defects can result in problems with the uptake but I dont have the background to speculate on that and need to read more about membranes and polarization first before I could draw a conclusion. 

 

Anyway, I am going to try various things as a preventive strategy. I am just not good at just "letting things happen" and then rely on others to fix me. Nah, sorry I'd rather take some personal risks and do more research to get a better understanding than any doctors that are most often generalists and wouldnt even have the time for this kind of specific research. 

 

Also of note:

 

http://www.ncbi.nlm....les/PMC4358648/

Edited by farware, 10 July 2016 - 10:23 PM.

[Mind_Paralysis]

So my first conclusions from all this: 

 

• 1) ADHD and Autism can be comborbid symptoms or part of a prodromal phase of Schizophrenia - All three are linked together very closely
• 2) NDMA-Antagonist are not solely working for Autism/ADHD but also for Schizophrenia - the reasoning behind that is that hypofunctioning receptors try to compensate with excess glutamate release which makes sense, so all three can have very similar symptoms.

 

Basically looking at your symptoms you cant exclude one or the other unless you show more severe symptoms of hallucinations, hearing voices, etc. or have passed a certain age. 

 

I have completely dismissed the entire dopamine part for now because there is simply no way to target NTs properly and you can seriously mess up your NT balance by using something like Ritalin or Adderall. No thank you. 

 

You can't dismiss dopaminergics if you haven't actually trialled them though - the scientific evidence for stimulants in the treatment of classic ADHD is some of the highest in all of medicine - with a 85-98% response-rate, they are some of the most effective treatment-options for any disease out there.

 

I've been through so many aspects and rabbit-holes with this disorder, and neuroscience in general, that I've come to the conclusion that the lack of mechanistic data can't be allowed to take precedence over efficacy-data: if it works, it works.

 

Depression isn't caused by low Serotonin either, but SSRI's work - they treat a lot of sick people, and they cause neurogenesis. Yeah, we have to do better, and we probably will, but until then we can't NOT treat people who are sick.

 

 

Mate... please... I've been through all of this - like GetOutofBox before me - eventually you have to accept that there isn't any way to hold off treatment until you have the "perfect" stuff that helps just right - your life will continue to be empty and meaningless then - science could take decades to catch up.

 

Take the precautions - start extremely low, perhaps even in a protective environment, like living with your parents, and not leaving their side. (you can even have some antipsychotics handy, just in case - and have your family-members observe you and alert you to any signs of psychosis)

 

 

I would start with the B12 analogues - Metadoxine and Pyritinol (yes, I know the mechanism is very unclear, but the side-effects and safety -profiles are also tremendously good - if it doesn't work, it won't break you) and then move up to Intuniv, then Strattera, Modafinil - and the stimulants last.

 

Heck, I WANT to shout "TRY STIMULANTS FIRST!" - but with schizo hanging over you, that's probably not a good idea.

 

 

Still... you have to start looking at the dirty, yet common, treatments now.

[farware]

One more thing to look into is Vitamin D, Calcicum Absorption and Vitamin K. 

 

Ive actually been taking a supplement with all three (Calcium,K2,D3) on an off and I have always wondered why its working so well - it feels neuroprotective. Its not stimulating but cognitive processes seem to work a lot smoother and here's why:

 

Calcium, in tandem with the neurotransmitter glutamate, is essential to the functioning of the excitatory cells of the nervous system: once glutamate opens the neuronal cell’s calcium channel, calcium pours into the channel and triggers the neuron to fire. The concentration of glutamate within the nervous system is therefore carefully regulated by the nervous system (specifically the astrocytes, which can be negatively affected by mercury and by neurotoxins produced by Lyme spirochetes) because excess glutamate will keep the calcium channels open, allowing calcium to continue to enter, and excite, the neurons. Dr. Russell Blaylock, among others, has written extensively about the neurotoxicity associated with an excess of glutamate.16 However, I believe that unregulated calcium may play an unappreciated role in triggering the incessant neuronal firing and resultant cell death that are a hallmark of excess glutamate in the nervous system. If a child is unable to regulate calcium due to a Vitamin K deficiency, that child may display signs of glutamate toxicity and uncontrolled neuronal firing that manifest as the cluster of behavioral disorders called autism

 

 

 

Vitamin K is a fat-soluble vitamin important in blood coagulation and bone metabolism. One of its functions is to keep calcium in the bones and out of soft tissues, blood vessels, and the nervous system

 

• Vitamin K regulates calcium in the body through osteocalcin and the matrix G1A protein.3 Both bone proteins are active only after undergoing carboxylation, a process in which Vitamin K is a required cofactor. Carboxylated bone proteins have a strong affinity for calcium and control its movement, directing it to the bones and teeth and preventing its deposition in soft tissues.

Calcium management appears to be dysregulated in people with the E4 form of Apolipoprotein.4,5,6 Osteocalcin is found in the brain; in its absence, it appears that brain cells become more vulnerable to the effects of calcium

 

• Vitamin K inhibits production of Interleukin-6, an inflammatory cytokine.11

 

• Vitamin K, an anti-oxidant that is more powerful than Vitamin E or CoQ10, is able to potently inhibit glutathione depletion-mediated oxidative cell death.9,10

 

• Vitamin K has a role in glutamate conversion14 and its absence affects the rate of activity of the enzyme glutamate dehydrogenase15. 

 

 

http://discoveringsc...-to-autism.html

 

 

 

There must a link to the central nervous system and the immune system. Also, Vitamin D is known to help with ADHD. If it helps with that, it should be part of any preventive stack. 

 

I think I will focus my research on Vitamin K, Calcium-Glutamate connection and NDMA. Seems to be the most promising. Vitamin K is definitely going into my daily stack. 

 

Edited by farware, 10 July 2016 - 10:58 PM.

[farware]

 

So my first conclusions from all this: 

 

• 1) ADHD and Autism can be comborbid symptoms or part of a prodromal phase of Schizophrenia - All three are linked together very closely
• 2) NDMA-Antagonist are not solely working for Autism/ADHD but also for Schizophrenia - the reasoning behind that is that hypofunctioning receptors try to compensate with excess glutamate release which makes sense, so all three can have very similar symptoms.

 

Basically looking at your symptoms you cant exclude one or the other unless you show more severe symptoms of hallucinations, hearing voices, etc. or have passed a certain age. 

 

I have completely dismissed the entire dopamine part for now because there is simply no way to target NTs properly and you can seriously mess up your NT balance by using something like Ritalin or Adderall. No thank you. 

 

You can't dismiss dopaminergics if you haven't actually trialled them though - the scientific evidence for stimulants in the treatment of classic ADHD is some of the highest in all of medicine - with a 85-98% response-rate, they are some of the most effective treatment-options for any disease out there.

 

I've been through so many aspects and rabbit-holes with this disorder, and neuroscience in general, that I've come to the conclusion that the lack of mechanistic data can't be allowed to take precedence over efficacy-data: if it works, it works.

 

Depression isn't caused by low Serotonin either, but SSRI's work - they treat a lot of sick people, and they cause neurogenesis. Yeah, we have to do better, and we probably will, but until then we can't NOT treat people who are sick.

 

 

Mate... please... I've been through all of this - like GetOutofBox before me - eventually you have to accept that there isn't any way to hold off treatment until you have the "perfect" stuff that helps just right - your life will continue to be empty and meaningless then - science could take decades to catch up.

 

Take the precautions - start extremely low, perhaps even in a protective environment, like living with your parents, and not leaving their side. (you can even have some antipsychotics handy, just in case - and have your family-members observe you and alert you to any signs of psychosis)

 

 

I would start with the B12 analogues - Metadoxine and Pyritinol (yes, I know the mechanism is very unclear, but the side-effects and safety -profiles are also tremendously good - if it doesn't work, it won't break you) and then move up to Intuniv, then Strattera, Modafinil - and the stimulants last.

 

Heck, I WANT to shout "TRY STIMULANTS FIRST!" - but with schizo hanging over you, that's probably not a good idea.

 

 

Still... you have to start looking at the dirty, yet common, treatments now.

 

 

 There is a root cause to ADHD as we discussed in this thread. 

 

As discussed there are underlying root causes such as excess glutamate release, so stimulants do nothing for you longterm. They dont fix the problem. As far as I understand it the 

real thing you want to take is a glutamate receptor modulator and preferably one that depolarizes neurons. You dont want too much calcium to enter your neurons because they excite the neurons too much giving 

you ADHD and autistic traits. This is not possible to treat with stims. Stims only treat some of the symptoms, not the root cause. 

 

I am not saying NDMA antagonists and vitamin K/D3 will cure you of ADHD but the current situation with stims reminds me a lot of the situation with depression and SSRIs, trying to make patients dependent and milk them for everything they've got. It's flawed and they know it. 

 

My doctor wasn't open to the suggestion that I may have ADHD with the reason that I was ok in school, but I know very well that he has the same concerns that I do, only that he could be held liable. Thats one of the reasons why I am self-treating this because I dont want them to make that decision for me. With the knowledge they have its a 50/50 chance really that it could go wrong.

Edited by farware, 10 July 2016 - 11:57 PM.

[farware]

I have now come to the final conclusion that amphetamines are probably the worst thing you can take longterm. Longterm this will cause Alzheimer and Parkinson and does not address the underlying causes. 

 

Here's a potential stack for ASD, still working on it:

 

• Vitamin K => Regulate calcium transmission in neurons
• Vitamin D3 => Combo, Thyroid, Deficiency common
• Inositol => NDMA antagonist, longterm modulation, severely depressed in schizo/ASD postmorbid 
• PEA => mood regulation, low in ASD, preferably from raw sources such as raw cacao 
• Ginkgo => Small and subtle dopamine boost that is not causing longterm issues like stims 
• Pregnenolone => Neuroprotective
• Tianeptine => Use sparingly, opiate, glutamate receptor modulator, not antagonist/agonist
• Potassium => Electrolyte regulation

Its time to look at what the Russians do opposed to the Americans that are financially motivated to promote Amphetamines. They actually stimulate NDMA release in neurons by use of Glycine and some other very specific drugs, rather than inhibit NDMA. Not sure if that makes sense since Glycine is the one amino acid that is high in ASD but maybe its best for ADHD without the ASD. 

 

It's also time for more studies on the compensation of glutamate receptors in SCT .. if they also react with excessive glutamate release, then its no wonder that ASD, SCT are not so different. In fact, autism was once considered a subtype of schizophrenia. 

 

It will take time to figure it all out, but considering how obvious it is that there is a link between thyroid disorders and gluten, I am pretty much convinced that toxins in our environment and food are the main reason for the incredible rise in ASD, SCT, etc... so the only way to treat that is by boosting detox pathways (boost glutathione) to get rid off chemicals, toxins and completely avoid gluten and hidden sources of gluten that constantly trigger excessive glutamate release. 

 

All of our foods are contaminated and lack minerals. How is one to supposed not to develop disorders in this world? Then the big pharma corps try to sell your stims to get rid of symptoms instead of treating underlying root causes. Fuked up world. Fortunately the world is changing. New technology will emerge that will put publicly funded research immediately into the public domain instead of hiding them behind paywalls.