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Memantine Has Obliterated My Depression and Social Anxiety

memantine namenda anxiety social anxiety depression add adhd

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#1 AlwaysLearning

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Posted 02 June 2014 - 12:27 AM


Hey all, just wanted to briefly share my experience here. I have ADHD, best described as the "Ring of Fire" subtype if you buy into the Amen Clinics' categorizations. My flavor comes with all the core features, along with anger, 'mood swings', brain fog, depression and anxiety, including terrible social anxiety making eye contact a painful experience. I've been on Namenda (memantine) for about a month and a half; I've been on Namenda XR 21 mg for about a month. While it does not seem to help directly with the core ADHD symptoms, it has almost entirely eliminated my depression and social anxiety (and I believe has decreased my anxiety in general). The effect has been so profound that a couple of days after switching to my current dosage and formulation (I started on the instant release, which btw is being discontinued in August), I seemed to experience at least a few hours of rapid synaptogenesis, in which my perceptions of the world seemed new (or encoded differently) and I felt that I was learning it all over again. During this period, novelty seemed to cause a euphoric sensation, which I found concerning but thankfully was short-lived and manageable by throttling the novelty, which otherwise might have been overwhelming. To a much lesser degree this process seems to continue (without euphoria), as I occasionally seem to relearn things that I had perceived differently when I was depressed. Also, I have found that my coordination has improved, best evidenced by my improved pool playing. For the first time in my life, I have been able to feel relatively normal and content, and comfortable around other people, becoming far more extroverted. I no longer constantly worry about being judged, and do not feel inferior to the people around me. Eye contact is pleasurable rather than painful, as is exerting my will and expressing my desires. I am able to truly enjoy physical and emotional intimacy now. I see people more for who they truly are (their pain, their anxiety, their joy, etc.). The list goes on, but I'll end it here.

 

My best guess regarding the mechanism by which memantine has been effective is this:

 

- proinflammatory cytokines/mediators cause astrocytes to downregulate glutamate transporters EAAT-1 and EAAT-2 (underactivity of EAAT-1 in general may explain my intolerance to (sub-)chronic aspartame exposure)

 

- Due to underactivity of these astrocytic glutamate transporters, either (1) excessive glutamate builds up in the synapses and causes oversaturation/downregulation/desensitization of the glutamate receptors, or (2) presynaptic release or synthesis of glutamate is downregulated to compensate. In light of the efficacy of memantine, (2) would seem to depend upon the use of presynaptic NMDA receptors to regulate release or synthesis, which is rather dubious, so I lean toward (1). If (2) were shown to be true, it would raise a concern regarding excitotoxicity.

 

- (Assuming (1) above) memantine reduces the effect of excessive glutamate on NMDA receptors, allowing them to function more normally, through e.g. upregulation/translocation/sensitization, turning down/off natural pathways guarding against excitotoxicity. In other words, shifting the balance of stimulation from tonic to phasic.

 

Of course, plenty of downstream effects on other neurotransmitter "systems" are then possible.

 

I am hoping the reason the remainder of my ADHD symptoms have not been resolved is due to the fact that I am merely dealing with one of the effects of reduced synaptic glutamate clearance. I am presently looking into ways to upregulate EAAT-1 or EAAT-2 or (less desirably) antagonize the various other glutamate receptors. In the meantime, I continue to use Vyvanse, albeit at a reduced dosage. I am hoping to try ceftriaxone (unfortunately only available via IV or IM routes) or celecoxib to see whether they treat my brain fog and hyperactivity and comfortably replace memantine, Vyvanse, and omega-3s.

 

In case anyone is curious, my current best guess at the etiology of my ADHD is the rs6565113 variant of the CDH13 (T-Cadherin) gene. This is statistically linked to ADHD and is likely to have significant inflammatory implications. (The state of knowledge regarding CDH13 is still rudimentary but highly intriguing.)

 

Btw, I have a naturally high level of testosterone and a very youthful appearance, and I am aware of the possibility that properly treating my ADHD will normalize these traits, but that price would be well worth paying.

 

I could go on, but I think I've covered all the big stuff. Btw for those who are interested in memantine but are unable to get it, you may consider trying gentian root, which I've found to be relaxing and likely also works via NMDA receptors.

 

I hope this helps someone! I'm sure there are lots of people out there who, like me, have tried the standard treatments for depression and anxiety and been gravely disappointed. I'd be happy to answer questions regarding my experiences or thought processes, so fire away but please stay on topic and don't get off into the weeds trying to show how smart you are. ;)

 

EDIT: Forgot to mention, I do not seem to be experiencing any side effects. I tapered and stopped Cymbalta (which did not seem to help me) after starting memantine and this seems to have caused "brain zaps" which are still tapering off - I believe this is unrelated to the memantine but am mentioning it just in case.

 

EDIT: Also forgot to mention that (1) my sexual proclivities have normalized somewhat (no, I will not go into detail) and (2) I'm wondering whether an NMDA receptor agonist could be used (esp. intramuscularly) as a treatment for psychopathia/sociopathia, to increase their anterior cingulate gyrus activity and their sensitivity to others' feelings/opinions/reactions. Just a thought. ;)


Edited by AlwaysLearning, 02 June 2014 - 12:53 AM.

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#2 lorreann

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Posted 03 June 2014 - 09:52 AM

This is fascinating! I wasn't familiar with Menantine. I would be curious to know if it was prescribed for your ADHD, or other off label reasons. And how hard is it to get prescribed.



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#3 xsiv1

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Posted 03 June 2014 - 07:20 PM

This is fascinating! I wasn't familiar with Menantine. I would be curious to know if it was prescribed for your ADHD, or other off label reasons. And how hard is it to get prescribed.

 

I believe Memantine can be purchased at Ceretropic now. I've never tried it myself but have tried a couple of their other nootropics. They're reputable in my experience. 



#4 mrnootropic

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Posted 04 June 2014 - 11:33 AM

 

This is fascinating! I wasn't familiar with Menantine. I would be curious to know if it was prescribed for your ADHD, or other off label reasons. And how hard is it to get prescribed.

 

I believe Memantine can be purchased at Ceretropic now. I've never tried it myself but have tried a couple of their other nootropics. They're reputable in my experience. 

 

 

Ceretropic is an online store created by people over at Reddit.

I would try get it on prescription, but if not then it could be worth a shot.

 

The Memantine is a Solution from Ceretropic, it is normally taken in pills but whatever floats your boat.


Edited by Mr.Nootropic, 04 June 2014 - 11:33 AM.


#5 xsiv1

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Posted 04 June 2014 - 12:36 PM

 

 

This is fascinating! I wasn't familiar with Menantine. I would be curious to know if it was prescribed for your ADHD, or other off label reasons. And how hard is it to get prescribed.

 

I believe Memantine can be purchased at Ceretropic now. I've never tried it myself but have tried a couple of their other nootropics. They're reputable in my experience. 

 

 

Ceretropic is an online store created by people over at Reddit.

I would try get it on prescription, but if not then it could be worth a shot.

 

The Memantine is a Solution from Ceretropic, it is normally taken in pills but whatever floats your boat.

 

 

Ceretropic has a good reputation for testing the composition and purity of their solutions as far as I understand, but I'd agree with you..it's best to talk to your doctor to see if they'd be willing to prescribe it to you for depression and/or social anxiety since it's primarily used for Alzheimer's patients. It is probably used off-label for various other reasons. Here's a link http://www.psycheduc...s/memantine.htm

 

 


Edited by xsiv1, 04 June 2014 - 12:37 PM.


#6 adamh

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Posted 04 June 2014 - 09:19 PM

AlwaysLearning, what is your daily dosage of memantine?

#7 AlwaysLearning

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Posted 05 June 2014 - 12:33 AM

21 mg of XR. (SWIM may have been augmenting with 5 mg of the regular formulation recently. :) )



#8 YOLF

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Posted 05 June 2014 - 08:42 PM

I'm going to move this topic to Brain Health so it will get more views. Retailer/Products forum is more for the discussion of specific products. If there are any objects, please contact me via PM and if necessary or warranted I'll move it back. More details on the Retailer/Products forum.


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#9 Al Capacino

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Posted 06 June 2014 - 08:52 AM

Always learning eh! Thanks for this post. You've inspired me to research this subject and indeed there are a lot of glowing recommendations of this product so I found myself a nice online pharmacy to buy some.
I used sunshine pharma-uk. They are a company around Australia/New Zealand region of the world. Got myself some other antidepressants aswell to speed up finding something that works for me as everything's at a snail's pace with psychiatrist. I need to sort out my circumstances quick or I'll lose everything.
So again, thanks for this little ounce of hope buddy!

#10 AlwaysLearning

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Posted 06 June 2014 - 09:34 AM

You're most welcome! Please let us know how it goes! :)


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#11 Galaxyshock

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Posted 06 June 2014 - 04:32 PM

NMDA-antagonism makes the brain forget. The depressive anxiety-inducing pathways are de-learned


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#12 AlwaysLearning

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Posted 06 June 2014 - 05:24 PM

Galaxyshock, I don't think it's quite that simple. :)


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#13 Kompota

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Posted 06 June 2014 - 06:05 PM

NMDA-antagonism makes the brain forget. The depressive anxiety-inducing pathways are de-learned

 

It depends. In theory NMDA-antagonism should be considered anti-nootropic, and it is unnecessary with healthy individuals. However, some people experience too much NMDA activity, which is even worse, because it causes excitotoxicity (neuronal death). Also, there is a difference between full antagonists like Ketamine and DXM, and Memantine. Memantine is a partial antagonist and seems to eliminate only excessive glutamate without impairing normal receptor function.  



#14 AlwaysLearning

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Posted 06 June 2014 - 06:06 PM

Can you provide references for that please? I haven't seen any research indicating it's a "partial antagonist".


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Edited by AlwaysLearning, 06 June 2014 - 06:07 PM.


#15 owtsgmi

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Posted 06 June 2014 - 11:18 PM

 

 

This is fascinating! I wasn't familiar with Menantine. I would be curious to know if it was prescribed for your ADHD, or other off label reasons. And how hard is it to get prescribed.

 

I believe Memantine can be purchased at Ceretropic now. I've never tried it myself but have tried a couple of their other nootropics. They're reputable in my experience. 

 

 

Ceretropic is an online store created by people over at Reddit.

I would try get it on prescription, but if not then it could be worth a shot.

 

The Memantine is a Solution from Ceretropic, it is normally taken in pills but whatever floats your boat.

 

This is the only type of memantine I can use, since even fractions of a pill make me cognitively impaired big time.. I recommend this product.


Edited by owtsgmi, 07 June 2014 - 12:08 AM.


#16 FW900

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Posted 07 June 2014 - 03:07 AM

Can you provide references for that please? I haven't seen any research indicating it's a "partial antagonist".


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It is an NMDA receptor channel blocker which reduces the influx of Ca2+ to NMDA receptors. The definition partial antagonist has been thrown around for things like magnesium, which functions in much the same way as memantine at a lesser extent. I'd argue that partial antagonist is not an incorrect term. This being said, you probably would not see it listed in any research named as a partial antagonist.

 

If memantine was not a partial antagonist, I assume you have mistaken it for a full NMDA receptor antagonist? Even MK-801 technically is not a full blown antagonist. Strong NMDA receptor antagonism, as with the case of MK-801, will probably result in a psychosis like state with an inability to make sense of language and an almost non-existent short-term memory.

 

NMDA.jpg


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#17 AlwaysLearning

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Posted 07 June 2014 - 03:09 AM

Interesting thanks. Can you please provide references?


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#18 FW900

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Posted 07 June 2014 - 03:19 AM

Interesting thanks. Can you please provide references?


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Mechanism of action of memantine

Memantine is a clinically useful drug in many neurological disorders, including Alzheimer's disease. The principal mechanism of action of memantine is believed to be the blockade of current flow through channels of N-methyl-d-aspartate (NMDA) receptors — a glutamate receptor subfamily broadly involved in brain function. Surprisingly, other drugs that block NMDA receptor channels, such as ketamine, exhibit serious deleterious effects. The unusual therapeutic utility of memantine probably results from inhibitory mechanisms shared with ketamine, combined with actions specific to memantine. These potentially important differences between memantine and ketamine include effects on gating of blocked channels and binding of memantine to two sites on NMDA receptors. Because modulation of NMDA receptor activity can increase or decrease excitability of neuronal circuits, subtle differences in the mechanisms of action of NMDA receptor antagonists can strongly impact on their clinical effects.

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The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonism.

Excitotoxic neuronal cell death is mediated in part by overactivation of N-methyl-d-aspartate (NMDA)-type glutamate receptors, which results in excessive Ca2+ influx through the receptor's associated ion channel. Physiological NMDA receptor activity, however, is also essential for normal neuronal function. This means that potential neuroprotective agents that block virtually all NMDA receptor activity will very likely have unacceptable clinical side effects. For this reason many previous NMDA receptor antagonists have disappointingly failed advanced clinical trials for a number of neurodegenerative disorders. In contrast, studies in our laboratory have shown that the adamantane derivative, memantine, preferentially blocks excessive NMDA receptor activity without disrupting normal activity. Memantine does this through its action as an uncompetitive, low-affinity, open-channel blocker; it enters the receptor-associated ion channel preferentially when it is excessively open, and, most importantly, its off-rate is relatively fast so that it does not substantially accumulate in the channel to interfere with normal synaptic transmission.

→ source (external link)



#19 AlwaysLearning

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Posted 07 June 2014 - 03:24 AM

Fabulous, thank you. :)


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#20 satsumass

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Posted 08 June 2014 - 03:59 PM

Hey OP thanks for your post and congrats. I'm actually a big fan of namenda too and I am bipolar 2 with significant social phobia and ADHD issues (very intelligent). I've been on namenda a number if times over the years and always end up back on it. I'm also on 21mg, but would advise that initial namenda responses are typically VERY different than long term. Initially you are getting a ton of nicotinic and d2 action as you build up blood levels. I'm VERY interested in how you do long term. I've found long term for me it tends to lose some punch but whenever I decrease my dose I get a bit more unstable, more disnhibited, less able to focus and definitely more compulsive.

However, I've found dosing is incredibly difficult. I've been on up to 45 of the IR and believe high dose has it's place but sweet spot for me is. Etween 10-20 now.

Big issue is that it tends to cause sustained disassociation and a sense of being somewhat apart from reality and emotions. This is of course useful at times especially for anxiety but I question ling term effects.

What else do you take. I used to take it with vyvanse but now take it with nardil.

#21 lorreann

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Posted 10 June 2014 - 06:29 AM

Well I received my bottle of Memantine today from Ceretropic (http://www.ceretropic.com/memantine-solution/) and my first experience was very positive. I found myself following through with projects around the house that I originally had no intention of doing today. My energy level was good and my focus and sense of well being was better than it has been for a long time. Thank you for the comments that led me to try this!



#22 AlwaysLearning

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Posted 11 June 2014 - 12:57 AM

Hey OP thanks for your post and congrats. I'm actually a big fan of namenda too and I am bipolar 2 with significant social phobia and ADHD issues (very intelligent). I've been on namenda a number if times over the years and always end up back on it. I'm also on 21mg, but would advise that initial namenda responses are typically VERY different than long term. Initially you are getting a ton of nicotinic and d2 action as you build up blood levels. I'm VERY interested in how you do long term. I've found long term for me it tends to lose some punch but whenever I decrease my dose I get a bit more unstable, more disnhibited, less able to focus and definitely more compulsive.

Thanks satsumass. :) I'm actually very wary of supposed comorbid and attention deficit disorders - in fact, I'm very wary of all bipolar diagnoses other than type I to begin with. ADHD easily causes mood swings, however in the case of ADHD they are dependent upon behavior and stimuli, they are not random. But enough of my rant. :) Afaik Namenda does not act on dopamine receptors and with regard to nicotonic receptors, if anything it's an antagonist (at 7 I think). (I have actually been toying with nicotine gum and patches as well, and it does seem to be helpful but highly dose-sensitive.)

 

Remember that, in vivo, no neurotransmitter "system" is an island - tweaking one will have broad downstream effects on others.

 

I should caution that the novelty of the sensations caused initially by the treatment as it lifts depression is a sort of treatment for ADHD but as that novelty wears off, the core ADHD symptoms are likely to return. Hence the combination treatment memantine + Vyvanse. I tried doing without Vyvanse but I wound up rather unproductive during that time.

 

I have found that the effect on depression remains quite well in force. Some of the social anxiety may have crept back but there may be other reasons for that.

 

Also I'd like to note that some of the positive effects I've noticed recently are likely due to gentian root, so I would love to hear from others trying it independently of memantine. In the interest of minimizing bias, I'd prefer not to mention specifics at this point. :)

 

I was on mirapex when I started memantine - I have subsequently stopped it but may try it again to see whether it still helps. It was definitely helpful before I started memantine, as it reduced my feelings of restlessness, and in so doing, greatly reduced my mood swings. However it worsened my brain fog and, I think, my anhedonia.

 

Btw I think we should be careful to make a distinction between "disinhibited" and "impulsive". In my case, I've had trouble with being both too inhibited and too impulsive (perhaps one was a coping mechanism for the other?). It's rather tricky.... Think about it - anxiety tends to cause inhibition, ADHD tends to cause impulsiveness, and OCD is an anxiety disorder.

 

Big issue is that it tends to cause sustained disassociation and a sense of being somewhat apart from reality and emotions. This is of course useful at times especially for anxiety but I question ling term effects.

 

 

This does not occur for me. I have previously had problems with depersonalization and derealization and have found omega-3s and Wellbutrin XL (separately) to be effective against those problems. I've found Zoloft to have an emotionally numbing effect.

 

 

I cannot emphasize enough that mileage will vary greatly depending upon etiology and concurrent treatments. Anyone with a different genetic mutation will likely have a significantly different experience with this medication. If your problem does not involve NMDA receptors, then this medication will probably not be effective for you in the long term. As always, these things vary from person to person.


Edited by AlwaysLearning, 11 June 2014 - 01:47 AM.


#23 AlwaysLearning

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Posted 11 June 2014 - 02:51 AM

Btw, regarding MAO inhibitors, I've tried Emsam which at low doses did little or nothing for me, and at higher doses caused myalgia. Moclobemide did that to me as well. So, for me it seems MAO-B inhibition was not helpful, and MAO-A inhibition was harmful. However, I was on other medications at the time so this data is not very useful.


Edited by AlwaysLearning, 11 June 2014 - 02:52 AM.


#24 ocean.soul

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Posted 16 June 2014 - 10:16 AM

How is your memory? I mean long term memory?



#25 AlwaysLearning

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Posted 17 June 2014 - 11:54 PM

The quality of my long term memory has always been mixed - I don't know whether this has been a matter of storage or retrieval but I lean toward the former. I've never been very good at remembering dates, names, foreign words, etc. but I've always been good at remembering concepts and such. I'm not a fan of the standard categorizations of long term memory - you could say my "episodic memory" has always been poor, my "procedural memory" has been mixed, and my "semantic memory" has been mixed. (Clearly these categories do not model my neurology well.)

I have not noticed a change in my long term memory performance since starting memantine (which I imagine is probably what you are curious about). I am more clear-headed though, and advanced concepts that I pull from my memory *seem* to make a bit more sense now than they used to. I do not seem readily able to reinterpret old episodic memories of people to re-evaluate my conclusions about those people, it seems I have to make new observations to effectively revise these evaluations. (This is a fun bit of data to ponder.)

Your question does lead me to wonder whether my "long term potentiation" is now improved for new memories, and I honestly don't know but I will keep an eye on it. If that is improved, I will tend to conclude that the original dysfunction was probably one of storage rather than retrieval.

#26 tunt01

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Posted 18 June 2014 - 12:49 AM

It depends. In theory NMDA-antagonism should be considered anti-nootropic, and it is unnecessary with healthy individuals. However, some people experience too much NMDA activity, which is even worse, because it causes excitotoxicity (neuronal death). Also, there is a difference between full antagonists like Ketamine and DXM, and Memantine. Memantine is a partial antagonist and seems to eliminate only excessive glutamate without impairing normal receptor function.  

 

 

This is pretty much my understanding.  It's counter-intuitive, but the usage of Memantine and NMDA-antagonism does not occur the same way in every person.  In a normal person NMDA-antagonism would be considered anti-nootropic.  However, some people are may exhibit an epigenetic misprogramming, often due to environmental factors early in life, such there is an increased synaptic expression of NMDAR subunit proteins (increased synaptic expression of NMDA receptor subunits).

 

My understanding is that there is a homeostatic, self-regulating process in the synapses.  To the extent that this self-regulatory process is malfunctioning because of an overreaction to glutamate (i.e. neuronal death/excitotoxicity) then you don't get normal LTD/LTP functionality.  The NMDAR antagonist improves this homeostatic process, by taking the person down from an extreme level back toward the middle of the U-curve (ideally).  And too little (full antagonism) or too much (uninhibited levels of glutamate -- hello alzheimers?) are both bad.

 

I don't fully understand it 100%, but I was actually reading this subject matter the other day and this is how it was laid out (if I'm making sense).


Edited by prophets, 18 June 2014 - 12:50 AM.

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#27 AlwaysLearning

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Posted 18 June 2014 - 01:12 AM

Thanks that does make some sense, however I don't expect NMDAR expression abnormalities to persist long past their causes (though of course I could be very wrong about that). Even if there is an epigenetic factor, there would probably be an underlying genetic susceptibility, so either way, I'd be hunting for one or more causative mutations to try to make sense of things.

Remember that you don't get complete antagonism until you have full receptor occupancy, and even then it's not 100% because you still have tunneling effects. So it's really dose-dependent. Plus you probably get upregulation of receptor expression (I don't think the subunits are expressed separately and then somehow combined but again I could of course be wrong) or translocation of receptors relative to the cell membranes, to compensate. And of course there may be many other mechanisms to compensate. Remember that nature tends to favor equilibria (which are often dynamic). What I think I have naturally is a less-than-ideal equilibrium/homeostasis, with chronic and not excitotoxic acute features (well, maybe there was some of that in utero, who knows?).

In my case I'm really leaning toward an astrocytic etiology at this point, as I haven't [yet?] seen any mutations correlated with ADHD or similar disorders that seem to have any putative direct effect on neuronal glutamatergic functioning.

That being said, NMDARs do seem rather complex and potentially susceptible to a number of factors.

#28 tunt01

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Posted 18 June 2014 - 01:30 AM

Thanks that does make some sense, however I don't expect NMDAR expression abnormalities to persist long past their causes (though of course I could be very wrong about that). Even if there is an epigenetic factor, there would probably be an underlying genetic susceptibility, so either way, I'd be hunting for one or more causative mutations to try to make sense of things.
 

 

You are incorrect on this.  While epigenetic (methylation, demethylation etc.) is a dynamic process, it is more or a less programmed for stability early on in a mammal's life, such that you can see the same programmed pathways later in life.  There are numerous studies which show 50 year old men (aged rats, aged mice, etc.) with the same epigenetic programming which were induced in gestation or early post-weaning environments.

 

It's really where pathologies like autism come from.  Autism covers a broad spectrum of misprogrammed epigenetic pathways that are abnormal and stable in their abnormality even years later.  These misprogrammings can become progressively maladaptive over time.

 

If you want to look for a mutation, I would probably look at your SLC6A4 gene.  There two versions a short and a long allele.  The short version has been implicated in OCD behavior.  But I don't think that's what you are facing, from what it sounds like.  It's more anxiety/ADHD, which is typically epigenetic, not genetic.


Edited by prophets, 18 June 2014 - 01:44 AM.

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#29 AlwaysLearning

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Posted 18 June 2014 - 01:58 AM

Interesting, I'll have to read up on that. If you could provide some links to papers, I'd appreciate it. I don't know how that sort of stabilizing feedback would occur, apart from something like immunological sensitization.

ADHD is usually genetic according to current knowledge. The only suggestion of epigenetic influence I recall seeing had to do with allergy.

I have generalized anxiety problems, including OCD-type features. These seem to be reduced presently under the influence of memantine. I've noticed no benefit from serotonergics.

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#30 tunt01

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Posted 18 June 2014 - 02:52 AM

Variations in postnatal maternal care and the epigenetic regulation of metabotropic glutamate receptor 1 expression and hippocampal function in the rat

 

There are a couple groups of scientists, notably in McGill, who have been programming anxiety and other psychiatric disorders in rats via early-life interactions (psycho-social, behavioral, etc.).  This paper looks at how poor motherly care (low Licking and Grooming) vs. high motherly care (high LG) impacts Grm1 gene expression and ultimately downstream increased synaptic expression of NMDAR subunit proteins.  They show the differential effects on LTD, etc.

 

It is fascinating work that they've done (Szyf, Meaney).  I've read about 10 of their papers.  


Edited by prophets, 18 June 2014 - 02:53 AM.

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