Calcium, ACTH, Cortisol - Conjecture of HPPD-Anxiety-Cognition relations

[onedayillsailagain]

I don't really have any concrete/specific evidence of calcium's role in HPPD.. So that makes for a flawed start.
However, of note is that many Calcium Blockers (like Keppra, yet Keppra is unique from other CCB's) seem to be very helpful in treating HPPD.
Furthermore, excess calcium causes excitotoxicity, and some believe HPPD is a form of Toxic Encephalitis.
Also see this theory.

Anyways, recently I was reading a bit about Cortisol, which lead me to this:
 

The primary control of cortisol is the pituitary gland peptide, adrenocorticotropic hormone (ACTH). ACTH probably controls cortisol by controlling the movement of calcium into the cortisol-secreting target cells

source

Which was based on this:

Removal of free calcium ions from the incubation medium of isolated bovine adrenocortical cells with EGTA reduced basal cortisol synthesis and blocked the effects of ACTH; additional calcium restored normal steroid synthesis. Calcium channel blockers, verapamil and nitrendipine and the calmodulin antagonist, trifluoperazine inhibited ACTH-stimulated cortisol synthesis in a dose-dependent manner (IC50s of 6.2, 10 and 5.2 microM, respectively)

source

 

So perhaps there's a link here between anxiety, cognitive dysfunction, and HPPD? I know this is very inconclusive, and I'd like to portray it more concretely, but not much springs to mind at the moment. Basically, Cortisol production is regulated by ACTH, which mediates through calcium, where excess calcium would cause an increase in cortisol levels, and calcium inhibition would then cause a decrease in cortisol levels, ultimately altering stress/anxiety and cognition, which when altered, have a better chance of returning to homeostasis, for we all know stress can cause stress.

Any thoughts to add here? I'll add more later if I think of a way to clarify.

[VisualDude]

To understand what is going on, it is important to grasp the concept and importance of brain 'modes' or 'states'.  While a lot is going on in the grey matter, you are primarily conscious of one thing at a time.

 

I'll briefly synopsis this, but you need to read a bunch of research articles on what the locus coruleus (LC) does and how it works - two little blue dots in the brain where 90% of the norepinephrine is found.

 

There are many 'modes'.  Even emotional states - thus the use of SNRIs to control mood.

 

There are three main modes of attention: sleep, concentration, and vigilance.  You cannot, for example, be asleep and vigilant at the same time.  You cannot be vigilant and concentrate.  Just to further show the power-of-the-LC, even sleep has modes: REM and sleep paralysis as examples.

 

As discussed elsewhere, cortisol rises as a stress response.  This enables the 'fright, fight, and flight' state which brings you to the midbrain area and the amygdala.  This is a high-speed, 'primitive' area that must respond faster than you can think - or else you may parish.  To illustrate with visual processing, the high speed area can respond within a few milliseconds whereas visual 'thinking' takes about 1/4 of a seconds (look up Ambient Visual processing and compare with Focal Visual processing).

 

So one link between anxiety, cognitive dysfunction and HPPD is hyper-vigilance.  Hyper-active (pre-seizure) is a kissing cousin of hyper-vigilance ... the latter literally causes the former!  While in a vigilant state, anxiety increases, it is hard to sleep, and it is hard to learn and remember things.

 

A little more.  The LC doesn't decide what state you are in.  It facilitates it like a giant relay station - essentially turning on parts of the brain and turning off other parts.  The executive center primarily decides the mode.  And it is the executive center that is affected by COMT polymorphisms ... one of our HPPD puzzle pieces.

 

 

Well, I have to round it off here.  Am on a laptop that has 'reset' the post 3 times now.  So this is the 4th attempt at this post ... my brain is scrambled and feel like punching a hole in a wall.  Blame it on 'Keppra rage'? ... blame in to Microsoft - they must be hyperfocused on profits and can't seem to make a product that actually works ... is it HPPD or brain damage?!?

[onedayillsailagain]

Hey Visual,

it's kind of late so I'll keep this short for now.
Thanks for responding! I'll have a look into the LC tomorrow.. I'm aware that the brain is infinitely complex, hence I'm always weary of drawing any conclusions at all, for there's always a "Yes, but" lurking around the corner. Which is fine, makes it all the more interesting.

Anyway, tomorrow I'll also be doing some info-gathering of Guanfacine, an apha 2a adrenergic agonist. So I'm sure I'll also refresh my (nor)epinephrine knowledge.
I'd appreciate it if you could comment on that once it's finished, as I might consider it as an adjunct for in the future. Seems superior to Clonidine so far.
If your referring to the Val/Val - Val/Met polymorphisms.. I thought those were just models used to prove a point, but that they weren't intrinsically involved with the pathogenesis of HPPD.. Only that a COMT disruption may worsen HPPD symptoms, or so I could imagine. Hmm, I covered COMT way too long ago to remember properly.

If you say hyper-vigilance causes hyper-excitability/pre-seizural activity... then just out of curiosity, would you say PTSD has seizural activity involved?

 

Yeah I make sure to Ctrl+C the hell out of the things I write.. One wrong move and all is lost. Frustrating, cause even then sometimes your computer may randomly decide to reboot itself for an unauthorized update.. Screw Microsoft though, go for Linux!

Hmm I'm gonna continue reading "Why Zebras Don't Have Ulcers".. Or actually I'm reading "Waarom krijgen zebra's geen maagzweer?"... Dutch is arguably the worst language to discuss science in. But hey, at least it covers some basic autonomic nervous system stuff, which gives for a light read (as opposed to the usual "damnit this crap is too complicated for my damaged brain, nevermind").

I'll might add some thoughts on this tomorrow, for now I'm quite tired.
Cheers.