[FollowingTheDao]

NMDA is a receptor, not a molecule.

Memantine slows the amount of calcium that enters the NMDA receptor in a way similar to magneisum. Zicn also inhibits NMDA but by a different mechanism

https://ars.els-cdn.com/content/image/1-s2.0-S00283908070022...

It is the calcium in the cell that triggers nerve excitement and oxidative stress that triggers the anxiety. I am over simplfying all of this.

I have the opposite problem. I have slow NMDA receptor function but my Anxiety is caused by issues inside the neuron (NOS1). Magnesium gives me anxiety.It may be that my porr NMDA receptor function helps me a bit.

Really the root cause is low Cyclic Adenosine Monophosphate (cAMP) signaling in the neuron stemming from low Nitric Oxide or slow NMDA receptor function.

https://onlinelibrary.wiley.com/cms/asset/2bc96085-ac06-4a3b...

Klonopin and ethanol increase the flow of GABA into the cell and this

[the-angry-dome]

I'm definitely curious as to how you got to such a nuanced diagnosis / underlying mechanism for your anxiety. After an overnight sudden change, I'm told I've been stuck in 'fight or flight', constantly, for about 20 years. I've gone from MRI to many medication trials to genetic testing / perfunctory bloodwork, to therapy to yoga to sriracha enemas (kidding), but never got anywhere beyond feeling like the science overall is nascent at best, and a total load of snake-oil quackery at worst.

Your miles seemed to have played out differently. How did you go about arriving at the underlying pathology, so to speak, and how confident are you that it is 'the right answer'? Are you under the care of a doc / neuro / psych? And if so, do they take your NOS1 explanation into account when treating you?

[FollowingTheDao]

> After an over night and sudden change

This is important, you need to look at your total environment to see what changed. It could be anything from air pollution, diet, EMFs. Anxiety always has a trigger and it is not always psychological.

> I'm definitely curious as to how you got to such a nuanced diagnosis / underlying mechanism for your anxiety.

I went through everything you did, but once I noticed so many people were doing the woo woo route and nothing helped, so I decided to learn about neurobiology, genetics and nutrition. Almost everything you will read about anxiety and mood is wrong. (For example, low serotonin is the result of high GABA, and it is the high GABA that causes depression, not the low serotonin or dopmaine, that is just a result of the low GABA. https://www.nature.com/articles/s41380-022-01730-4)

I was anxious as a child, and had OCD, so I knew it was genetics. My mother had mental health issues as well all up her side of the family. 20 years ago I ended up on disability and doctors were of little help, just felt drugged all the time, so I set off to research neurobiology since I had the spare time and lived next to a university research hospital.

Then when 23andMe appeared I jumped on it and it was all right there. But it took years for more research to come out which narrowed in on my problem. First it was genes like CACNA1C and SLC6A4, but when I saw many immune genes linking to my Ankylosing Spondylitis (ERAP1) it became a bit more confusing. I kept seeing so many genes that needed zinc flagging in my genome. High does zinc fixed my autoimmune issues, as did long chain omega 3 (FADS1, FADS2 also linked to mood). But the studies I began to read about NOS1AP matched my genetics so I dove head first into that pathway at it ll became clear how glutamate was casueing my anxiety and paranoina and psychosis.

I also have changes in GCH1 that controls the amount of serotoin and dopmaine we make. I am in a study at Stanford as they feel it is linked to ME/CFS. I was diagnosed with CFS years ago but I only have infrequent symptoms now.

I have one doctor who knows I know what I am talking about and gets me some tests that might help me see what is going on but this is all research level stuff, nothing and doctor will see for years if ever. I am on Medicare, fully disabled, so it is hard for her to get some weird tests but she tries. She also helps me get meds I feel might help that might not be her first thought. But meds are no answer, they work until they do not.

Glutamate/GABA imbalance and nitric oxide will soon be recognized as the drivers of mood disorders.

I am confidant I am right because all my friends have see the change in me. Plus I no longer needs meds.

If I had you genetics I could probably see what is going on with you. Let me know if you want me to take a look: [e-mail]

[solarmist]

Thank you for clarifying. I know a bit about the brain and brain chemistry, but I was unfamiliar with NMDA receptors.

Unfortunately the rest of your explanation was too technical and I didn’t follow any of it. Can you explain what NMDA receptors are for and what the link to anxiety, in either direction, is?

My anxiety wasn’t caused by this, but I was able to treat it because of the memantine. I just stopped memanitine a month ago after about 5 years and all the symptoms seem resolved now.

[FollowingTheDao]

You are saying that your anxiety was not casued my NMDA receptor changes, but it was. Traumatic events change the function and density of these receptors.

https://www.nature.com/articles/1301605

NMDA receptors allow calcium into the neurons. The more calcium in a neuron the more excitable it is, like in hyper-arousal.

By taking the memantine you allowed you possible grow more healthy neural pathways, away from the hypervigilance and towards calmness. I am assuning you have been in therapy?

[solarmist]

Sure, on a technical level, but the cause of it, globally, was several layers up the abstraction stack. It feels like blaming the add and multiply instructions for poorly written firmware/software, especially since it resolved itself once I addressed the issues I listed below.

Thank you for the paper. That's just the kind of thing I was hoping to find.

The experience of going on memantine for the first time was like becoming in sync with my body for the first time that I could remember. My body, mind, and thoughts stopped being out of sync, like a video that wasn't streaming well. That allowed me to slow down (and not try to anticipate the ten different ways a conversation could go), stop rambling, and listen to what people were saying to me instead of what I expected them to say.

I'm only seriously pursuing therapy now; hyper-independence is another symptom of my CPTSD. I learned all this by trial and error and reading ungodly amounts of self-help books (moving to psychology books lately), helping my wife through losing her parents at 21, and teaching my wife to work through her PTSD.

What allowed me to be calm was learning to trust, at least to some extent, people again (which I didn't even realize was an issue) and learning to express my emotions (I had nearly total blocks on sadness and fear). Then slowly processing the traumatic events from my childhood. After I forced myself to cry about one event (the last time I cried as a child) and allowed myself to feel fear about things I couldn't control, my chronic anxiety faded, and now it is situational. I continue to work on the underlying causes of these distinct reactions.

It is very difficult because fear of being like my dad or being poor drove me so hard for 20+ years to become a software engineer and make it into a top-tier company. Without that desperation, I have to relearn (learn?) how to live and do things.

[FollowingTheDao]

Yeah, I get it. My condition is more of a genetic sensitivity to foods/environment. Yours was more caused my the environment alone.

Different causes, different cures.

Glad you are doing therapy. While it had no impact on my anxiety it helped me deal with the ramifications.