178 replies to this topic

[Mind_Paralysis]

Right, here's the study about the neuroanatomy of ODD - oppositional defiance disorder.

"A Systematic Review and Meta-analysis of Neuroimaging in Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) Taking Attention-Deficit Hyperactivity Disorder into account"
www.ncbi.nlm.nih.gov/pmc/articles/PMC4762933/

Now, as you can see they come to the conclusion that it's the alterations in the amygdala that are the key to ODD, much like the previous study on BPD showed that alterations to the amygdala were at the heart of that disorder.

I think there are some clear differences between the two though...
ODD shows abnormalities primarily in the bilateral amygdala, but I believe BPD showed errors of a different type... can someone go through the fMRI review on BPD that I posted earlier? To try and find some quotes on the amygdala structures.

I'm also reviewing Guanfacine's use as a treatment for ODD, and this review for prison i

[Mind_Paralysis]

...mobile can be a really tricky platform at times.

Back on topic:
This prison-review makes note of the ability of Guanfacine to treat symptoms of ODD.

https://www.google.s...mRtU4vtOuFvSy6g

So, what do you think guys? Is my reasoning sound so far?

I will admit, there is greater evidence for anticholinergics, but there is some merit to enhancing PFC-funtionality as well.

[Mind_Paralysis]

Some excellent work in the last post Jack - it brought to light mechanisms in disease which I hadn't previously considered.

I am moving away from Alpha-2 agonists and "traditional" amygdala-inhibitors, and returning to cholinergics.

Could the enhanced cholinergic synthesis in BPD-sufferers actually be an effect of faulty a7-receptors than a core-symptom of the disease - more like the cns trying to compensate by increasing overall aCh?

Alpha-2-agonists actually lower global norepinephrine-levels, so could the same be true for alpha-7-agonists?

Once again I return to the question: will nicotinic agonism or antagonism help?

I checked out Galantamine btw - and although the pharmacologic properties are encouraging, the side-effectsprofile is not. And then there's the fact it increases aCh even further...! We still don't know if that's the right thing.

Hmm...

Right, we need some new ligands - more selective experiments. Time to dig deep...

[Mind_Paralysis]

Just found this review, it seems robust, so some ideas might be had - especially for immediate treatment - it goes through a lot of current in-use meds.

"Psychopharmacologic treatment of borderline personality disorder"
www.ncbi.nlm.nih.gov/pmc/articles/PMC3811092/

[jack black]

 

 

The study above says that BPD-ers have abnormally high methylation of PRIMA1 - which leads to global, excessive Acetylcholine! Which is logical - since excess aCh often includes difficulty in controlling emotions, and detrimentally high empathy - hallmarks of some sub-types of BPD.

 

 

Interesting, but I need to digest it more. I thought high ACh was associated with depression and anxiety? I didn't know about borderline.

 

 

Thanks Stinkorninjor for that fruitful idea. I looked more into the association of ACh and borderline (BPD) and there appears to be a link indeed. People with BPD are more sensitive to high ACh levels causing depression:  http://www.ncbi.nlm..../pubmed/9326751

 

This could be precipitated by diet (high choline) or Choline acetyltransferase inhibitors (Physostigmine or pesticides, etc). Irritability and aggression can also be seen in high ACh states in some conditions (rat experiment where ACh was injected into amygdala).

 

Here is an interesting tidbit. The BPD lady became more irritable and angry lately. There appears to be a recent pattern of more eating out (contamination/pesticides?) and more chicken (high choline food) consumption. I have access to her 23andMe results and 2 things showed up when searched for acetylcholinesterase: rs733722 and rs1799807. She is heterozygous for both and both can contribute to more ACh, especially when exposed to acetylcholinesterase inhibitors (pesticides, etc).

 

Interestingly, Dr Daniel Amen talks about low-protein (thus, low-choline) diet in his "Over-Focused ADD" type that sounds a bit like BPD. Alternatively, high protein diet could cause just decreased tryptophan absorption and create problems with serotonin/kenuric acid systems, too.

 

BTW, I found this (old) book with a wealth of info on this subject: Brain Acetylcholine and Neuropsychiatric Disease Davis Kenneth L. Paperback.

 

 

Just found this review, it seems robust, so some ideas might be had - especially for immediate treatment - it goes through a lot of current in-use meds.

"Psychopharmacologic treatment of borderline personality disorder"
www.ncbi.nlm.nih.gov/pmc/articles/PMC3811092/

 

I saw it a while ago. Good read and I like table 3 the most.

 

BTW, totally apart from this discussion, it appeared to me the whole BiPolar disease could be explained by cycling levels of ACh (high=depression; low=mania). Obviously there has to be some conduction instability and positive neurotransmitter feedbacks to cause that cycling in the first place.

Edited by jack black, 02 August 2016 - 06:22 PM.

[Mind_Paralysis]

Well, sonuva'-gun...!

I just started finding reports on how PIRACETAM helps people with BPD to control outbursts and mood-swings!

 

At last. SOME confirmation on the hypothesis that cholinergic modulation will have an effect on the disorder.

 

There are tons of these anecdotal reports:

 

http://be-a-betterma...brain-drug.html

"My wife who has Borderline Personality Disorder (BPD), finds that Piracetam helps her tremendously. It helps keep her wild mood swings and perceptions under control."

 

https://www.reddit.c...tam_kicking_in/

"Immediately. When I first took piracetam I didn't notice anything, but that was before I had anxiety/borderline issues... piracetam was sort of a last ditch effort since I had it on my shelf, really helped me get back on track!

edit I take ~800mg when I need it now, been having good luck with other stuff though like L-phenylalanine"

 

http://nootriment.co...for-depression/

“When I started to use Piracetam, I noticed some stimulating effects like increased mental and physical activity, decreased fatigue and trouble sleeping. Later on my severe mood swings (because of BPD), impulsivity and inadequate behavior started to disappear. I became more active, very productive, no more sluggish in the morning, positive and noticed that depressive symptoms are gone. – Parapsychiatrist"

 

http://www.depressio...total-recovery/

"I'd like to share my experiences and thoughts what could have caused my recovery (from bipolar, insomnia and severe manifestation of bpd)

Piracetam course was supposed to last only month, but because of such 'magical' effects, my doctor allowed me to continue using it."

 

http://forum.bodybui...d.php?t=5185783

"I've shown symptoms ranging from bipolar disorder, borderline personality disorder, ADD, depression and obsessive compulsive disorder.

Well odd thing is that when I cut back on the choline bitartrate, I actually started to feel better. - Random907"

 

There's also reports on how it's a helpful adjunct in Bipolar type 1 patients. (which I assume many rapid-cycling patients will be grouped in)

 

Also, also - there's this study...

Double-blind, placebo-controlled trial on the effect of piracetam on breath-holding spells.

http://www.ncbi.nlm....pubmed/22302459

 

There was a significant decline of number of attacks after piracetam treatment compared to placebo (p value<0.001).

 

 

Why am I including this, you ask? Well, because holding your breath, sometimes until you turn blue, or pass out (a relative actually did this as a child) is both a symptom of an inability to control emotional response, as well as an act of self-harm and "overly obvious manipulation".

 

I.e - BORDERLINE symptoms! ^^

 

Piracetam modulates the cholinergic system.

 

We may have a winner.

Until we have a true, selective Alpha-7-modulator, this may be our best bet.

 

Jack_Black: your thoughts?

[jack black]

 

Piracetam modulates the cholinergic system.

 

We may have a winner.

Until we have a true, selective Alpha-7-modulator, this may be our best bet.

 

Jack_Black: your thoughts?

 

Agree 100%. The BPD lady is taking it already and it contributes to her mood improvement, considering the low dose of BP and Li she takes (150 and 300 mg respectively). I had her started on it as soon as I learned it upregulated BDNF (way back when she was discharged after suicide attempt). She takes that only once a day, 1g dose. I guess she could take a second dose in PM to help her study and feel better. But here is one problem. She is supposed to travel overseas soon. I don't think it's a good idea to cross borders while packing white powders (same with DMAE). I'll have to come out with some sort of replacement, or just increase the BP/Li/Namenda dose.

 

Now, why selective Alpha-7-modulator? Is is because that amygdala paper (that is a bit confusing)?
 

Edited by jack black, 03 August 2016 - 08:59 PM.

[Mind_Paralysis]

 

 

Piracetam modulates the cholinergic system.

 

We may have a winner.

Until we have a true, selective Alpha-7-modulator, this may be our best bet.

 

Jack_Black: your thoughts?

 

Agree 100%. The BPD lady is taking it already and it contributes to her mood improvement, considering the low dose of BP and Li she takes (150 and 300 mg respectively). I had her started on it as soon as I learned it upregulated BDNF (way back when she was discharged after suicide attempt). She takes that only once a day, 1g dose. I guess she could take a second dose in PM to help her study and feel better. But here is one problem. She is supposed to travel overseas soon. I don't think it's a good idea to cross borders while packing white powders (same with DMAE). I'll have to come out with some sort of replacement, or just increase the BP/Li/Namenda dose.

 

Now, why selective Alpha-7-modulator? Is is because that amygdala paper (that is a bit confusing)?
 

 

 

I won't lie: I'M REALLY EXCITED ABOUT THIS! ^^

I feel really, really clever, actually. Quite a good evening for me, discovering this! It even all chains together fully logically.
 

You can have her get it prescribed possibly? There are several genuine brand-name products. That, or just buy some Indian pills, and try to get a prescription from somewhere - there are such services in Eastern Europe - you log on and chat with a doc, and then they prescribe you the compound.

Here, have a look at the brands available:
 

http://www.medindia....e/piracetam.htm

 

At least pills in genuine boxes and blisters will look less conspicuous.

 

Btw, there are many other racetams - do we know how others affect the Choline systems? Perhaps Aniracetam, for instance, could be even more effective.

 

And yes, it all comes back to that initial Alpha-7 role in amygdala -study.

 

1. fMRI studies prove that BPD is a neuropsychiatric disorder - suspected pathology is a faulty Fronto-amygdal loop. (compare to ADHD: Fronto-Striatal, or SCT: Fronto-Parietal)

 

2. Study proves that BPD-ers have abnormally high choline-production.

 

3. Another study shows that the Alpha-7-nicotinic acetylcholine receptor is a very important site in the Amygdala - controlling outward traffic to other networks. (like the PFC!)

 

4. The effects of Alpha-7 modulating compounds like Memantine and Lithium is found.

 

5. Piracetam reports of effects on BPD is found.

 

6. aCh-modulation hypothesis is born - combining knowledge from several sources! It ties everything together nicely...

 

 

So yeah, that's why I think an Alpha-7-modulator could be the bees-knees - it controls so much of the signalling out of the amygdala - that, coupled with their enhanced choline-levels is what makes me think such a compound is the perfect one hit, one kill -bullet here.

 

Until then, we shall go with the somewhat dirty option: Racetams! Much like stimulants are the easy, dirty option to treat ADHD. (interesting how there are mirroring aspects to the pathology and treatment-options, isn't it? a dark symmetry of nature, if you like.)

[PeaceAndProsperity]

Contraceptives seem to worsen the condition in women, especially if they contain estrogen. 

[jack black]

 

So yeah, that's why I think an Alpha-7-modulator could be the bees-knees - it controls so much of the signalling out of the amygdala - that, coupled with their enhanced choline-levels is what makes me think such a compound is the perfect one hit, one kill -bullet here.

 

Until then, we shall go with the somewhat dirty option: Racetams! Much like stimulants are the easy, dirty option to treat ADHD. (interesting how there are mirroring aspects to the pathology and treatment-options, isn't it? a dark symmetry of nature, if you like.)

 

 

This is an important discovery alright, but i don't share your enthusiasm about the cure. Reading about Namenda taught me that alpha-7 NAChR are very quick to up-regulate in response to antagonists. I guess this is already happening for the BDP lady of interests. She is having a bad week this week with many emotional outbursts despite no change in treatment. Initially i suspected diet, but it could be something else.

 

This is not unlike stimulants in ADHD losing their potency long term. you can work around it by drug holidays on weekends/vacations, but it's too risky in BPD (10% completed suicide risk).

 

RatherBeUnknown, Good point about estrogen. I'll try to figure out if the emotions are related to timing of period.

[Mind_Paralysis]

 

 

So yeah, that's why I think an Alpha-7-modulator could be the bees-knees - it controls so much of the signalling out of the amygdala - that, coupled with their enhanced choline-levels is what makes me think such a compound is the perfect one hit, one kill -bullet here.

 

Until then, we shall go with the somewhat dirty option: Racetams! Much like stimulants are the easy, dirty option to treat ADHD. (interesting how there are mirroring aspects to the pathology and treatment-options, isn't it? a dark symmetry of nature, if you like.)

 

 

This is an important discovery alright, but i don't share your enthusiasm about the cure. Reading about Namenda taught me that alpha-7 NAChR are very quick to up-regulate in response to antagonists. I guess this is already happening for the BDP lady of interests. She is having a bad week this week with many emotional outbursts despite no change in treatment. Initially i suspected diet, but it could be something else.

 

This is not unlike stimulants in ADHD losing their potency long term. you can work around it by drug holidays on weekends/vacations, but it's too risky in BPD (10% completed suicide risk).

 

RatherBeUnknown, Good point about estrogen. I'll try to figure out if the emotions are related to timing of period.

 

 

I'm not entirely certain that antagonisation is the complete answer to this - because Alpha-7 inhibits signals from the amygdala as well - this implies that depending on the stimulus the BPD-person is responding to, the alpha-7-receptor may need either antagonisation or agonisation.

 

That's why I think the racetams could work - they lower global aCh while still stimulating cholinergic receptors. Admittedly, Piracetam seems to be more selective for Muscarinic receptors.

 

Do we know if there is a racetam which has affinity for nicotinic receptors?
 

And hey, the Alpha-7-receptors can only upregulate so much - eventually the body can't compensate for the antagonisation. (and I'm not so sure a modulating drug causes much, if any, desensitisation - atypical antipsychotics remain efficient long-term, and they have modulating properties.)

 

If the BPD-er is treated with a selective enough drug, then I see no problem with increasing the dosage - these drugs do not cause the same sort of toxicity as stimulants do - they've got several neuroprotective and even neurogenic effects.

 

 

EDIT: Perhaps we can find a way to prevent up-regulation as well? Memantine does reverse stimulant tolerance, so there may be a possibility to find a corresponding substance or mechanism regarding nicotinic receptors.

 

Another example is valproic acid and the melatonin-receptors - it reverses tolerance and upregulates the receptor - returning efficacy of Melatonin and Agomelatine.

Edited by Stinkorninjor, 05 August 2016 - 06:04 PM.

[Mind_Paralysis]

RatherBeUnknown: "Contraceptives seem to worsen the condition in women, especially if they contain estrogen."

 

 

 

This is an important discovery alright, but i don't share your enthusiasm about the cure. Reading about Namenda taught me that alpha-7 NAChR are very quick to up-regulate in response to antagonists. I guess this is already happening for the BDP lady of interests. She is having a bad week this week with many emotional outbursts despite no change in treatment. Initially i suspected diet, but it could be something else.

 

This is not unlike stimulants in ADHD losing their potency long term. you can work around it by drug holidays on weekends/vacations, but it's too risky in BPD (10% completed suicide risk).

 

RatherBeUnknown, Good point about estrogen. I'll try to figure out if the emotions are related to timing of period.

 

 

Intriguing.

 

Now... observe as I connect global Choline-levels to global Estrogen-levels!

 

Dietary choline requirements of women: effects of estrogen and genetic variation¹,²,³

http://ajcn.nutritio.../92/5/1113.full

"Because of their lower estrogen concentrations, postmenopausal women have a higher dietary requirement for choline than do premenopausal women."

"The PEMT gene has several estrogen response elements in its promoter region, and the gene is induced by estrogen (5)."
 

 

Menstrual cycle-related brain metabolite changes using 1H magnetic resonance spectroscopy in premenopausal women: a pilot study.

http://www.ncbi.nlm....pubmed/11231099

 

The menstrual phase-dependent significant increase in the ratio of choline to creatine was observed in the parietal white matter.

 

 

Influence of menstrual cycle on serum cholinesterase.

"five used exogenous hormones (oral contraceptives, estrogen supplements, or progesterone therapy)"
"There was a significant positive correlation between serum ChE and progesterone values only for the two women on oral contraceptives although there were large weekly variations within individuals (CV: 4-32%). Age significantly affected ChE values with 36-40 year olds having the lowest values and 30-35 year olds the highest. This variation in serum ChE probably is due to the influence of some sex steroid"

 

 

If I was to vaguer a guess, the two women who had significant ChE-decrease both used Estrogen-supplements.

 

 

This would explain why Borderline-women go crazy when they have their period: their Choline-levels go EVEN HIGHER UP! Hence, all symptoms are increased

 

 

This would be the moment where you all say: "STINK! You sweet, sick, son of a Bitch!"

 

 

Now, let's get back to modulating the cholinergic system.

[gamesguru]

okay so these guys on reddit who say bacopa or ginkgo or tea, all moderate cholinergics, make them more emotional. they're (perhaps) fessing up to bpd?

[Mind_Paralysis]

okay so these guys on reddit who say bacopa or ginkgo or tea, all moderate cholinergics, make them more emotional. they're (perhaps) fessing up to bpd?

 

 

Well, considering the data we see in this thread, I suppose it's possible? Those compounds affect a lot of other things too, though.

 

Interesting side-note... my BPD-lady has a great interest in TEA! She has a fairly big collection, with a wide variety of types. She also drinks quite a lot of tea... Could she in fact be self-medicating with this?? Or should she stop this tea-drinking, so as to not worsen her condition?

 

(fat chance! she's a big fan)

 

HOLD!

 

I just realized something... BPD symptoms are supposedly lessened after the age of 40, or menopause for women: could this actually be in response to the changes in the cholinergic system that comes with age?? In perticular, I am intrigued by the possibility that the altered hormonal system could have on female cholinergic systems.

 

This would explain a lot...

 

 

EDIT:

 

I'm finding some more info on NaCh-antagonists.

 

http://www.pharmacor...choline_5_2.php

 

I've once more got burnout so I can't absorb the text worth sh*t - so, what do you guys think about this tidbit:

 

However an acetylcholine excess tends competitively to shift these antagonists from acetylcholine receptors and to restore transmission. Every compound able to increase the acetylcholine concentration has an opposite effect to the competitive antagonists.

 

 

Can't make any heads of it whatsoever... brain fog clouds everything. But does it imply that both agonisation and antagonisation will cause a very quick feedback-mechanism that will counteract this effect? Or... I don't know.

 

Have a read though fellas, because it seems to speak a great deal about potential modulation of the nicotinic receptors - tons and tons of anesthesive agents are apparently available. Dangerous stuff though, obviously.

Edited by Stinkorninjor, 06 August 2016 - 08:36 AM.

[gamesguru]

Severity of symptoms tends to decrease with age in men, also (unlike schizotypy, where they tend to increase with age).  My gut says levels of dopamine, serotonin, and glutamate are also "normalized" with age. That's because the testosterone has gone down, when high T normally helps maintain healthy mood and baseline cognition. And BPD is really a lack of reason and abundance of passion.

 

And my bad for lumping. The bacopa definitely makes you more moody than the tea or ginkgo, for which the effect is very minor, if at all pronounced. The tea definitely helps with the procrastination and the deficiency in self-declarative memory (which contributes to identity crises), but even the light coffee drinker it comes at the expense of anxiety and exaggerated manic symptoms. The heavy coffee drinker may notice signs of irritability and even aggression. But it's nothing like bacopa's effect, which seems to be more akin driving a splint down your amygdala, in my experience, bacopa just really throws wood onto the fire of existential crises.

Edited by gamesguru, 06 August 2016 - 02:10 PM.

[jack black]

 

 

 

This would explain why Borderline-women go crazy when they have their period: their Choline-levels go EVEN HIGHER UP! Hence, all symptoms are increased

 

 

you theory seems to check out.

 

 

I'm finding some more info on NaCh-antagonists.

 

http://www.pharmacor...choline_5_2.php

 

However an acetylcholine excess tends competitively to shift these antagonists from acetylcholine receptors and to restore transmission. Every compound able to increase the acetylcholine concentration has an opposite effect to the competitive antagonists.

 

 

 

i checked that out and seems to deal with neuromuscular blocking and not CNS.

 

And my bad for lumping. The bacopa definitely makes you more moody than the tea or ginkgo, for which the effect is very minor, if at all pronounced. The tea definitely helps with the procrastination and the deficiency in self-declarative memory (which contributes to identity crises), but even the light coffee drinker it comes at the expense of anxiety and exaggerated manic symptoms. The heavy coffee drinker may notice signs of irritability and even aggression. But it's nothing like bacopa's effect, which seems to be more akin driving a splint down your amygdala, in my experience, bacopa just really throws wood onto the fire of existential crises.

 

i just checked and looks like bacopa increases ACh indeed (never tried it myself). I drink tea and take green tea extract and find them stimulating alright. Same with ginko. if they increase ACh, it doesn't seem to effect me.

[Mind_Paralysis]

Well, it makes sense if you don't have a cholinergic disturbance Jack - people ussually don't get anxiety from eating a lot of eggs either.

Hmm... I wonder if this could be used in forming a evolutionary theory on BPD/EDD - could there be an increased survival benefit in certain environments with a stronger reaction to choline-rich foods, and a more emotional response as a result?

Remember, it's not just negative emotion which is enhanced - positive emotions as well.

Perhaps this could explain a bit why BPD/EDD-ers have greater rates of obesity? An atypical response to food-sources now common, could be a factor.

Holy moly, bat-finks! I feel a bout of megalomania and improved mood coming out of this!

Am I a GENIOUS if this pans out?! o-0

[PeaceAndProsperity]

This might sound stupid or irresponsible, but I think women with this disorder might benefit from a cycle of test. or anadrol or something like that.

I have yet to see a roided up woman be anything but apathetic and calm.

[Mind_Paralysis]

This might sound stupid or irresponsible, but I think women with this disorder might benefit from a cycle of test. or anadrol or something like that.

I have yet to see a roided up woman be anything but apathetic and calm.

 

It is stupid and irresponsible.

 

There are better options available for women: SERM's.

 

http://www.breastcan.../hormonal/serms

 

Some SERM's cause global estrogen to fall, and you can control the amount to a fairly good extent - which means they could be useful for this purpose.

 

 

But anyways, there's no need to mess with the hormonal system - modulating the cholinergic should affect the problem at its core.

[jack black]

Holy moly, bat-finks! I feel a bout of megalomania and improved mood coming out of this!

Am I a GENIOUS if this pans out?! o-0

 

LOL, you do sound hypomaniac. maybe you should dial down the stimulants and nicotine?
 

[Mind_Paralysis]

Well, my genious is lessened this evening. xD I'm still starting to feel better about myself though, methinks.

 

The change of environment, rest and distance from my BPD-er have had some effect. Last evening was actually the first on stimulants, after a break post-move - go figure!

[Mind_Paralysis]

Lads, I started thinking about if there are other racetams that could be more potent in possibly treating BPD/EDD and I'm looking into Aniracetam, since it's the closest to Piracetam, and it supposedly has a very powerful anxiolytic effect.

 

Aniracetam: Its Novel Therapeutic Potential

in Cerebral Dysfunctional Disorders Based on Recent

Pharmacological Discoveries

http://onlinelibrary...2.tb00216.x/pdf

 

It's more potent all right, but is that a good thing? I believe it mentions how it's a more potent AMPA-modulator as well - which in some patients seems to cause mood-stability. Piracetam has this property as well. Could my aCh-hypothesis be disproven already? Is it the AMPA-modulation that allows for enhanced emotional control while on Piracetam?

And is Aniracetam then superior?

 

Can't make heads or tails of it... blurred vision from bupropion today, and all tired from helping this girl with whatchamacallit complex OCD and Binge-eating Disorder.

[Mind_Paralysis]

Ey, it's time for another bump.

 

The muscarinic receptors also play a role in mood, it would seem.

 

Antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine: a review.

http://www.ncbi.nlm....pubmed/23200525

 

While effective in male and female subjects, the change in depression ratings was greater in female subjects. Clinical improvement persisted more than 2 weeks following the final infusion.

 

 

So, perhaps a combo of Bupropion + Scopolamin could be effective as well? It goes on to say that the AD-effect was probably related to neuroplasticity and BDNF like with a lot of other AD's though...

 

There is some evidence that Scopolamine may have a slightly higher affinity for the M1-receptor though.

 

The relative selectivity of anticholinergic drugs for the M1 and M2 muscarinic receptor subtypes.

https://www.ncbi.nlm.../pubmed/2904117

 

What exactly does that receptor do? Is there any data regarding some pathway that could be related to emotional response? Similar to the Alpha-7 receptor.

 

https://en.wikipedia...ine_receptor_M1

 

Hmm... it controls something called... Excitatory postsynaptic potential - EPSP. But primarily in the post-ganglionic nerve? Sounds like it could be related to activity all right! But would it affect emotional response or not...

 

Well, if it does, then Oxomemazine should help - it's a cough-syrup which is highly selective for the M1 -receptor. Seems like there are sub-types of this sub-type of aCh-receptor though.

 

The PGN is apparently responsible for periferal nervous system thingies.

 

https://en.wikipedia...ic_nerve_fibers

 

HOLD! There is something here...

 

Notable exceptions to this rule include the sympathetic innervation of sweat glands and arrectores pilorum muscles where the neurotransmitter at both pre and post ganglionic synapses is acetylcholine.

 

 

My BPD-lady actually suffers from EXCESSIVE SWEATING! Hmm... does your BPD-lady have any problems with sweat, or gets goose-bumps a lot? (apparently controls that as well) Hyper-production of aCh should logically actually lead to problems of that sort, since it's over-loading those receptors as well.

 

 

And what is this, if I may ask?

 

In both divisions of the autonomic nervous system, postganglionic neurons express nicotinic acetylcholine receptors to receive signals from preganglionic neurons.^[2]

 

 

What's that supposed to mean...? Does it mean that my theory was RIGHT? That the M1-receptors are involved in controlling the NaCh-alpha-7-receptors firing-rate?!

 

Too burnt out to figure it out.

 

Jack_black: you must tie this together, am I but a madman rambling in the darkness regarding this connection, or is it there? Could a combo of Bupropion and Oxomemazine be synergistic and lead to enhanced emotional control? Come on man... throw me a bone here. My mind ain't what it used to be.

[gamesguru]

Stinky, the study you posted, "Psychopharmacologic treatment of borderline personality disorder"

Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms.

 

It's always the same story.  The interpersonal problems are harder to address from a pharmacologic standpoint.  These problems are deeply ingrained, with opposite (+, -) expressions in different brain areas.  Better response yields to therapy.  Still pitiful and awful.

[Mind_Paralysis]

Stinky, the study you posted, "Psychopharmacologic treatment of borderline personality disorder"

Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms.

 

It's always the same story.  The interpersonal problems are harder to address from a pharmacologic standpoint.  These problems are deeply ingrained, with opposite (+, -) expressions in different brain areas.  Better response yields to therapy.  Still pitiful and awful.

 

I know, but IMHO, that's because none of the meds they get truly focus on the underlying brain-structures or prime neurotransmitters: the Amygdala, the PFC and the Acetylcholine receptors.

 

SSRI's, SNRI's, MAOI, even TCA, aren't gonna' do jack if they can't even hit the target - the target is like a MILE away.

 

And although you are right that psychotherapy is the preferred method of treatment at the moment, it still doesn't help to any greater degree - in fact, there's a lot implying that it's a misstep, because there's a very high placebo-response, in all BPD/EDD treatments - much higher than other patient-groups, in essence - they fool themselves into thinking they're ok.

 

Soon enough, the therapy doesn't work either, and they're back in the destructive cycles. Rinse, repeat.

 

 

And I would say the reason why therapy doesn't work, is because as we've previously established, BPD isn't really a PD - it's a Neuropsychiatric disorder, similar in some ways to Hyperactive ADHD. They are born with abnormalities in their amygdala and their PFC - psychotherapy doesn't work for other NPD's either - it's completely useless for ADHD or ASD for instance. (I would say it's completely useless for my own as well: CDD - but apparently the jury's out on that one. Not to me though, IMNSHO!)

 

If psychotherapy worked, then how come everyone involved in their care always feel BPD-ers are the hardest to treat? How come, even though they get that treatment, they still have the highest suicide-rate?

 

It means nothing, because the true problem is genetic.

 

Psychotherapy for suicidal patients with borderline personality disorder: an expert consensus review of common factors across five therapies

http://www.ncbi.nlm....les/PMC4579509/

 

Borderline personality disorder is a heritable brain disease

 

 

 

 

http://www.currentps...cd15566bde.html

 

 

Btw, could you please have a look at my latest reasoning: are the post-ganglionic nerves involved in the disorder, and they can as a matter of fact impact the CNS in the BPD/EDD patient? Do the M1-receptor have a role as well, after all?

[Mind_Paralysis]

I just saw that there IS now a highly potent Alpha-7-agonist out on the market! : D

 

VARENICLINE!

 

https://en.wikipedia...iki/Varenicline

 

I immediately started thinking, that maybe this could be something which would be useful for BPD/EDD? Then I saw these notes...

 

Varenicline-triggered borderline moodiness

http://www.medicatio.../chantix/31994#

 

Possible varenicline-induced paranoia and irritability in a patient with major depressive disorder, borderline personality disorder, and methamphetamine abuse in remission.

http://www.ncbi.nlm....pubmed/19011454

 

Bipolars: Stay the hell away from Champix/Chantix

http://www.healthcen...lars-stay-hell/

 

 

I *THINK* this means that we can safely say that Alpha-7-AGONISM is NOT the way to treat EDD. What are you guys thoughts on this? And does this lend credence to my idea regarding the usefulness of alpha-7-modulation in the treatment of EDD?

 

Now... if alpha-7-agonism does this to BPD-ers... then what will ANTAGONISM do? Could it be... a... reversed, IMMENSELY stabilizing effect??


Meanwhile, I've also been going through the documentation regarding EDD fMRI-scans, and such, and there doesn't seem to be any focus on the cholinergic system, but rather the interest is put on some other neurotransmitters, primarily N-acetylaspartate:

 

Neurochemical alterations associated with borderline personality disorder.

http://www.ncbi.nlm....pubmed/25817526

 

Can someone inform me on the relationship, if any, between acetylcholine and n-acetylaspartate? The BPD-ers showed decreased amounts of NAA in the prefrontal cortex AS WELL as in the amygdala.

 

More info here:

Borderline personality disorder is a heritable brain  disease

http://www.currentps...cd15566bde.html

 

 

The focus also seems to be on the Anterior Cingulate Cortex, which is interesting, since that is a locus responsible for the filtering of signals signifying pain - emotional and physical. Impairing activity in this part of the brain is the mode of action of Acetaminophen aka Paracetamol. Recent studies revealed that this is also the mode of action which Cannabis has when inhibiting pain: THC is also a modulator of the ACC.

 

As I recall it... there was also signs that Acetaminophen may actually inhibit emotion overall, as a way of inhibiting emotional pain and fear. (I've posted about it before, too burnt out to dig up the thread now though)

 

So... uh... effin' TYLENOL as a treatment of BPD?? THC is of course easier, liver toxicity and all that, but is alas, not legal in very many jurisdictions either.

 

Still, I'm not ready to give up on the cholinergic connection yet! There's too much evidence imho, pointing towards a connection. Now, can you boys tell me if there's an inverse relationship between acetylcholine and n-acetylaspartate? Is the synthesis of NAA dependent on acetyl-groups not going towards the synthesis of aCh, for instance? And is the aCh-pathway preferable to the brain?

Edited by Stinkorninjor, 19 August 2016 - 09:50 AM.

[jack black]

Ey, it's time for another bump.

The muscarinic receptors also play a role in mood, it would seem.
Antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine: a review.
http://www.ncbi.nlm....pubmed/23200525

While effective in male and female subjects, the change in depression ratings was greater in female subjects. Clinical improvement persisted more than 2 weeks following the final infusion.

So, perhaps a combo of Bupropion + Scopolamin could be effective as well? It goes on to say that the AD-effect was probably related to neuroplasticity and BDNF like with a lot of other AD's though...

There is some evidence that Scopolamine may have a slightly higher affinity for the M1-receptor though.
The relative selectivity of anticholinergic drugs for the M1 and M2 muscarinic receptor subtypes.
https://www.ncbi.nlm.../pubmed/2904117

What exactly does that receptor do? Is there any data regarding some pathway that could be related to emotional response? Similar to the Alpha-7 receptor.

https://en.wikipedia...ine_receptor_M1

Hmm... it controls something called... Excitatory postsynaptic potential - EPSP. But primarily in the post-ganglionic nerve? Sounds like it could be related to activity all right! But would it affect emotional response or not...

Well, if it does, then Oxomemazine should help - it's a cough-syrup which is highly selective for the M1 -receptor. Seems like there are sub-types of this sub-type of aCh-receptor though.

The PGN is apparently responsible for periferal nervous system thingies.

https://en.wikipedia...ic_nerve_fibers

HOLD! There is something here...

Notable exceptions to this rule include the sympathetic innervation of sweat glands and arrectores pilorum muscles where the neurotransmitter at both pre and post ganglionic synapses is acetylcholine.

My BPD-lady actually suffers from EXCESSIVE SWEATING! Hmm... does your BPD-lady have any problems with sweat, or gets goose-bumps a lot? (apparently controls that as well) Hyper-production of aCh should logically actually lead to problems of that sort, since it's over-loading those receptors as well.


And what is this, if I may ask?

In both divisions of the autonomic nervous system, postganglionic neurons express nicotinic acetylcholine receptors to receive signals from preganglionic neurons.^[2]

What's that supposed to mean...? Does it mean that my theory was RIGHT? That the M1-receptors are involved in controlling the NaCh-alpha-7-receptors firing-rate?!

Too burnt out to figure it out.

Jack_black: you must tie this together, am I but a madman rambling in the darkness regarding this connection, or is it there? Could a combo of Bupropion and Oxomemazine be synergistic and lead to enhanced emotional control? Come on man... throw me a bone here. My mind ain't what it used to be.

thanks for keeping the thread alive. I'm traveling and frequently away from the interweb. This is a bit over my head too. The only thing i know about the BPD lady cousin of mine is there is a drug complience issue and she is not doing too well.

[thedevinroy]

I talked to someone in the field of mental health, and they said that cognitive restructuring to treat the PTSD side of BPD is really helpful in their experience.  She was dealing with a child with sexual abuse (sex slavery, actually), so if it's helpful for that... maybe it will also be beneficial for less traumatic things.  Cognitive restructuring is where the therapist hears a self reflection that is damaging, asks the person to validate this claim on a scale of 0-100%, then asks a series of yes or no / true or false questions designed to restructure that thought like "Do you think children are sexual?"  "Do you think children want sex?"  "Do you actually want sex?" and so on... then repeats back the replies to the questions and asks the patient to re-evaluate their answer on a scale of 0-100%.  If it drops by 20%, the session was successful.

[Mind_Paralysis]

I'm afraid that's a bit like throwing buckets of water on a fire, Devin.

Recent research has shown that BPD-ers overinterpret events that others would not find traumatic to such an extent that they BECOME trauma. In essence, for a BPD-er, parents divorcing is like becoming an orphan, falling with your bike is like being in a car-crash, et c.

 

They have hyper-attention to emotional cues, which means that they'll automatically accumulate far more trauma than pretty much any other neurological profile.

 

They vast majority of the population will eventually be exposed to significant trauma - yet, the BPD-ers make out only a small minority of a few percent... How does that add up? It adds up with the idea that it's a neuropsychiatric disorder, and not a trauma-acquired disease.

For instance, I've had my fair share of trauma - the incredible pressure of growing up ADHD-PI under a narcissistic step-father, being bullied, being involved in an immense car-crash, a majority of my relatives dying at a young age, having a mentally violent relationship. (with a BPD-er)

 

Yet I don't have BPD. Heck! I'd say I don't have any significant PTSD even!

 

I'm sure Cognitive Restructuring will help some, but it won't be enough, a temporary fix at best. It will make the damaged BPD-ers function somewhat better, but it won't really treat the core problem.

 

 

If I was to vaguer an evolutionary guess, then just like ADHD, SCT, ASD and perhaps even Schizophrenia, BPD is an NPD which once, in a completely different environment than modern society, had a useful function -

- hyperawareness of emotional cues could mean that they are extra aware of tensions within a tight-knit group, helping to identify them earlier, before they get disruptive. Perhaps it makes it easier to spread a feeling of victory and happiness after a good fortune (the BPD-er alerting everyone to the fantastic news very powerfully), et c, et c. And within a stoneage tribe you essentially have a MUCH BIGGER extended family, which helps to offset the negatives, with a tight-knit group which has no choice but to accept you during the periods of particularly great emotional instability.

 

Could be diet has an effect too... was there much choline in a stoneage diet?

 

 

BTW... hyperawareness of emotional cues strikes me as the OPPOSITE of Autism...! I see possibilities here... Perhaps the emotional hyperawareness comes from the decreased levels of NAA in the PFC? Perhaps some kind of Selective NAA Reuptake Enhancer could work as treatment of the sociability-issues Autists have...! By increasing awareness to emotional cues, the MOST important symptom of ASD might be treatable! : D Man, I better tell our ASD-friends about this idea!

[gamesguru]

Alright there, ya wanker, ya pisshead. Alright there, ya indigent.  Keep a level head, don't get frustrated, be real, don't listen to too much music, don't worry about anyone who doesn't worry about you, stay focused, venture out of your comfort zone but stay true to your roots, thrive on the unfamiliar, stay confident but open-minded, partake an ongoing educated, keep your cool, and last of all: don't neglect your physical.