178 replies to this topic

[jack black]

A few family members in my family seem to fit BPD closely even though none of them were officially diagnosed as such. I just heard that one of them, a young woman and university student, is in a hospital after a very serious suicide attempt. She was officially diagnosed with ADHD in her teenage years but non compliant with medication (concerta) due to unpleasent side affects. More recently, she was diagnosed with depression after a breakup with her long term boyfriend. She saw psychotherapy, was given welbutrin and felt seemingly better. However, after talking to her parents, she has a long history of mystery diseases (she was considered a sickly person with bad health and eating habits) that turned out to be suicide attempts that she kept secret from everyone and only now indirectly admitted to past self harm and suicide attempts.

 

Now, it all makes sense as self harm and suicide attempts are incredibly common in BPD. She is supposed to continue psychoterapy after the hospital stay. To me this a complete BS as I don't believe in the psychoterapy that failed her in the first place.

 

I'm reading about the Low-dose naltrexone. Is this legit? Has anyone seen it working firshand? Any other things to consider?

 

I was going to suggest getting a script for lamotrigine (based on few studies and good reviews on drug.com), but found studies showing increased risk of suicide. Looks like Lithium is the only drug proven to lower suicide, right?

 

I'm also looking for strategies increasing BDNF, and there is a recent good discussion on that. Supposedly BDNF is low in brains of suicide victims.

 

Anything else I need to look into?

 

Thanks!

 

Edited by jack black, 06 July 2016 - 05:52 AM.

[jack black]

No takers on BPD?

I'm checking Memantine, too.

[Mind_Paralysis]

I'll take.

I was dating a dashing young woman recently, but the relationship fell apart, because of her emotional instability and volatility, caused by BPD.

I suggested a regimen of:

Intuniv - to enhance PFC-function, hence overriding the amygdala, since it has been shown through mri-studies that BPD has been associated with a weakened connection between these two regions, leading to the amygdala overriding the regulation of the Pfc - emotion over rationality.

www.ncbi.nlm.nih.gov/pubmed/17203018

psychcentral.com/news/2016/01/14/brain-differences-tied-to-emotional-tumult-in-borderline-illness/97654.html

Propanolol - at certain doses, this beta-blocker inhibits EMOTIONAL response to stress, and not just physical, through, you guessed it - inhibition of the amygdala.

www.ncbi.nlm.nih.gov/pubmed/11420072

According to my calculations, for a 60 kilos human, 20 mg of Propanolol should be the sweet-spot.

D-Cycloserine - inhibits amygdala.

www.ncbi.nlm.nih.gov/pubmed/17667888

The same effect has been observed in Psilocybin, but alas, I don't think that's a drug which a bpd-er can be trusted to use responsibly.

This SHOULD, enhance reason and inhibit emotion, which is at the core of BPD pathology, however... a word of warning, it may not be benefficial to present these findings and mechanisms in this way to the no doubt dashing young lady - as when I did so to my own dashing young lady, she became quite upset, interpreting my intention as "wanting to lobotomize her" or "turn her into a robot".

You have to be sneaky how you present this... these ladies actually feel that their enhanced feelings have some merit as well.

[gamesguru]

i'm sure lithium orotate and lappaconitine would suffice to produce a similar emotional flattening. then green tea and ginkgo to promote executive function, and you have a very similar effect with purely natural substances. girls seem to favor natural herbs or OTCs to pharms. framing it like this might give you the upper hand in reasoning and leverage. maybe you could throw in some adrenergic substances, but then you're overwhelming her.

 

as for success stories, how about nietzsche? anyways, i think mindfulness and therapy (even self-therapy) are useful adjunctives to pharmaceutical interventions. nevertheless your life will never be completely normal.

[jack black]

Thank you both for replying to this!

 

I'll take.

I was dating a dashing young woman recently, but the relationship fell apart, because of her emotional instability and volatility, caused by BPD.

I suggested a regimen of:

Intuniv - to enhance PFC-function, hence overriding the amygdala, since it has been shown through mri-studies that BPD has been associated with a weakened connection between these two regions, leading to the amygdala overriding the regulation of the Pfc - emotion over rationality.

www.ncbi.nlm.nih.gov/pubmed/17203018

psychcentral.com/news/2016/01/14/brain-differences-tied-to-emotional-tumult-in-borderline-illness/97654.html

Propanolol - at certain doses, this beta-blocker inhibits EMOTIONAL response to stress, and not just physical, through, you guessed it - inhibition of the amygdala.

www.ncbi.nlm.nih.gov/pubmed/11420072

According to my calculations, for a 60 kilos human, 20 mg of Propanolol should be the sweet-spot.

D-Cycloserine - inhibits amygdala.

www.ncbi.nlm.nih.gov/pubmed/17667888

The same effect has been observed in Psilocybin, but alas, I don't think that's a drug which a bpd-er can be trusted to use responsibly.

This SHOULD, enhance reason and inhibit emotion, which is at the core of BPD pathology, however... a word of warning, it may not be benefficial to present these findings and mechanisms in this way to the no doubt dashing young lady - as when I did so to my own dashing young lady, she became quite upset, interpreting my intention as "wanting to lobotomize her" or "turn her into a robot".

You have to be sneaky how you present this... these ladies actually feel that their enhanced feelings have some merit as well.

 

The main issue with the "dashing young woman" cousin of mine she had several near death experiences.

 

Re: Intuniv. Apparently, she was prescribed Clonidine (also alpha2 agonist) some weeks before the last incident. Not sure if guanfacine (Intuniv) would have been different, except for the extended release and dosing benefit.

 

Re: Propranolol. She was prescribed that too for social anxiety PRN, but reportedly she said it didn't help and it made her feel worse (not sure how).

 

Re: Cycloserine. This came up in my reading, but the side effects (including depression) sound prohibitive.

 

Re: Selling the treatment to her. I think this is the least of her problems. She knows she is messed up big time, the challenge is to keep her alive. The parents wanted her locked up in a mental institution after this hospitalization, but I'm reading now that inpatient treatment is not indicated/helpful in BPD.

 

The weirdest thing is while one of her parents and and one grandparent have similar BPD-like issues, they never had issues with suicide or self harming (short of overeating). They are also fairly accomplished professionals and while she herself is intelligent, she is struggling to finish her school due to mental health issues.

 

i'm sure lithium orotate and lappaconitine would suffice to produce a similar emotional flattening. then green tea and ginkgo to promote executive function, and you have a very similar effect with purely natural substances. girls seem to favor natural herbs or OTCs to pharms. framing it like this might give you the upper hand in reasoning and leverage. maybe you could throw in some adrenergic substances, but then you're overwhelming her.

 

as for success stories, how about nietzsche? anyways, i think mindfulness and therapy (even self-therapy) are useful adjunctives to pharmaceutical interventions. nevertheless your life will never be completely normal.

 

She was taking that low dose lithium orotate supplement already before the last incident. This was my idea (together with fish oil, vitamins, SAMe, and NAC). Now I think she needs a full dose lithium carbonate.

 

I'll look up lappaconitine as I'm not familiar with. Green tea extract came up in my readings, but I thought she shouldn't take it because she is homozygous for 2 different COMT SNPs and supposedly green tea suppresses it more.

 

I agree with you about the mindfulness meditations. She is resistant to those type of things, but I guess her parents and/or therapist could work with her on that.

 

I'll keep you posted!

Edited by jack black, 07 July 2016 - 03:29 PM.

[gamesguru]

CBD can be helpful for both PTSD and BPD, not sure what the underlying mechanism is. Possibly glutamate or alpha-7 related? Ginkgo, ginseng, bacopa don't affect COMT (afaik). Ginseng promotes TH and inhibits DBH. Ginkgo improves GABAergic tone, promotes dopamine, serotonin, acetylcholine, and all three neurotrophins (GDNF too). Bacopa favorably affects several neurotransmitters, however the serotonin-releasing effects can cause emotional lability at high doses (IME). The green tea can be taken at a low dose? Maybe just zencha's "sencha moe", at 1-2 cups daily? The caffeine sometimes helps too.

 

Maybe just more orotate (1.5 tabs of the Swanson brand), and combined with magnesium (hemp protein!) and zinc. Possibly dietary sources of chromium too. They all play a role in the brain, can't be without those essential elements. Yeah another thing that really helped me, just reading stuff (from credible sites, on whimsical google searches) at a digestible pace. Also, just a bit of exercise and the right foods! I don't know what other routes to take, dopaminergic, adrenergic, hormonal? The lappaconitine isn't easy to find, but it works as a sodium channel blocker like Valproate. These things tend to get better on their own with age (but without the proper mindfulness it takes decades, and the progress is not as good)

Edited by gamesguru, 07 July 2016 - 09:17 PM.

[jack black]

You are right about magnesium. She was supposed to take it regularly, but for some reasons didn't. Sure enough, her Mg (and K) levels were low in a hospital. I told her parents to make sure she takes Mg and K supplements now. 

 

I'm lost with your alphabet soup of abbreviations:

 

 

CBD TH DBH GDNF IME

 

What are those?

[gamesguru]

cannabidiol, tyrosine hydroxylase, dopamine beta hydroxylase, glial cell derived neurotrophic factor, in my experience (sorry!)

[thedevinroy]

The best happy pill I've ever taken was Selegiline. Chipper all day. Not sure if it helps with BPD, but if it is depression related, then yeah it should help immensely.

Here is an article regarding the areas of the brain and sadness:

http://www.nytimes.c...nt-centers.html

So I'd check out supplements that seem to calm the anterior limbic system both short and long term, hopefully with high half life.


Sent from my iPhone using Tapatalk

[jack black]

The best happy pill I've ever taken was Selegiline. Chipper all day. Not sure if it helps with BPD, but if it is depression related, then yeah it should help immensely.

Here is an article regarding the areas of the brain and sadness:

http://www.nytimes.c...nt-centers.html

So I'd check out supplements that seem to calm the anterior limbic system both short and long term, hopefully with high half life.


Sent from my iPhone using Tapatalk

 

Good read.

 

 

When his 11 subjects felt happy, the characteristic pattern was a decrease of activity in the regions of the cerebral cortex that are committed to forethought and planning. These regions are in the temporal-parietal area of the cortex, located just over and a bit behind the ears, and the right prefrontal lobe, just behind the forehead. "Those neocortical regions are used in complex planning -- it's interesting these shut down in happiness," Dr. George said.

 

Looks like you can be happy or motivated, but not both. I suspected that for a long time after a couple of years of SSRI burned out motivation circuits in my brain.

 

I don't belive antidepressants is the solution for BPD. It makes it easier to attempt suicide.

[thedevinroy]

 

When his 11 subjects felt happy, the characteristic pattern was a decrease of activity in the regions of the cerebral cortex that are committed to forethought and planning. These regions are in the temporal-parietal area of the cortex, located just over and a bit behind the ears, and the right prefrontal lobe, just behind the forehead. "Those neocortical regions are used in complex planning -- it's interesting these shut down in happiness," Dr. George said.

 

Looks like you can be happy or motivated, but not both. I suspected that for a long time after a couple of years of SSRI burned out motivation circuits in my brain.

 

I don't belive antidepressants is the solution for BPD. It makes it easier to attempt suicide.

 

 

Yeah, well I don't truly believe that is always the case, just the case that they were able to reproduce it in a controlled environment.  I've been happy and planning, and in fact, I do it well, and I do it often.  It's called musical improv.  Music therapy is an alternative treatment for BPD.

 

I hear ya.  Attempting suicide is a bit easier when you have the capacity to plan it out, when you are feeling a bit sluggish and useless.

 

I was more interested in the area of the brain - area 25 of the brain.  I saw it on a TED talk.  Here is the transcript:

 

http://www.ted.com/t..._off/transcript

 

On wiki:

 

https://en.wikipedia...rodmann_area_25

 

Guess it isn't quite the same area as anterior limbic system... oh well!  Sorry about that.  Anyhow, area 25 can also be modulated (negatively) by area 46:

 

https://en.wikipedia...rodmann_area_46

 

And here is the technology cited to increase 46/25 ratio activity (which has marginal blinding success, but I would think that is only because heating/ionizing your brain with large inductors is a noticeable effect!):

 

https://en.wikipedia...tic_stimulation

 

Anyhow, you can imagine that area 25 being rich in serotonin transporters already overactive is probably going to get even more active once those transporters are inhibited by SSRI's.  Makes me think that too much serotonin might be causing overactive production of transporters.  It's almost as if you'd need a 5HT receptor blocker of some sort... has she ever tried an atypical antipsychotic?

 

Also associated with area 25 (subgenual cingulate) is cortisol signalling:

 

http://www.nature.co...l/1300862a.html

 

Interesting that Sertraline, an SSRI could potentially swing cortisol sensitivity in the wrong direction (at least in PTSD patients):

 

http://www.nature.co...l/1300862a.html

 

Anyhow, as you can imagine, the cortisol sensitivity rabbit trail is a long (and a good one).  There is a surprising amount of research having to do with glucocorticoid receptor (GR) regulation and sensitivity in genetics of treatment-resistant MDD patients.  In fact, at least in rats, it is regulated differently in females than males in response to stress.  I realize it is not to useful in its conclusion, but it is a useful articles as it goes over the different genes that sensitize GR's:

 

http://www.ncbi.nlm....les/PMC3443296/

Edited by devinthayer, 09 July 2016 - 05:18 AM.

[thedevinroy]

Totally separate from this, but regarding BDNF:

 

http://www.ncbi.nlm....les/PMC3214041/

 

Figure 2 explanation is pretty great.  It seems even though post-treatment after scopolamine damage was in effective for restoring BDNF, pre-treatment prevented BDNF loss and also raised BDNF levels.  I'd wager that over time, the BDNF levels can return to their full function with chronic Ashwagandha use but their mechanism of action was inhibited slightly, though not completely.  You can see at least in Example 3 that the SC-->I-Extract columns went up in proportion to SC alone in both cases A and B for glial cells.

 

So yeah, Ashwagandha is great.  I recommend people double or triple the dose if they don't see an effect, then keep going up until the right level of cognition/mood is achieved.

 

Also interesting is the role stress has on the amygdala.  Stress tends to shrink up dendrites, which shrinks the amygdala.  BPD patients have smaller amygdala's on average.  Ashwagandha is known to increase neuronal growth by extending dendrites...

 

http://www.ncbi.nlm....pubmed/12395110

 

Just saying... pretty amazing stuff...

[jack black]

Totally separate from this, but regarding BDNF:

 

http://www.ncbi.nlm....les/PMC3214041/

 

Figure 2 explanation is pretty great.  It seems even though post-treatment after scopolamine damage was in effective for restoring BDNF, pre-treatment prevented BDNF loss and also raised BDNF levels.  I'd wager that over time, the BDNF levels can return to their full function with chronic Ashwagandha use but their mechanism of action was inhibited slightly, though not completely.  You can see at least in Example 3 that the SC-->I-Extract columns went up in proportion to SC alone in both cases A and B for glial cells.

 

So yeah, Ashwagandha is great.  I recommend people double or triple the dose if they don't see an effect, then keep going up until the right level of cognition/mood is achieved.

 

Also interesting is the role stress has on the amygdala.  Stress tends to shrink up dendrites, which shrinks the amygdala.  BPD patients have smaller amygdala's on average.  Ashwagandha is known to increase neuronal growth by extending dendrites...

 

http://www.ncbi.nlm....pubmed/12395110

 

Just saying... pretty amazing stuff...

 

Thanks for bringing this to my attention. I was familiar a bit with ashwagandha as my wife takes that for hypothyroidism. It totally makes sense that it increases BDNF as BDNF is deacreased by stress and cortisol and ashwagandha deacreases stress and cortisol. My cousin can use that as her problems are frequently linked to stress.

Edited by jack black, 10 July 2016 - 03:55 PM.

[thedevinroy]

Totally separate from this, but regarding BDNF:

http://www.ncbi.nlm....les/PMC3214041/

Figure 2 explanation is pretty great. It seems even though post-treatment after scopolamine damage was in effective for restoring BDNF, pre-treatment prevented BDNF loss and also raised BDNF levels. I'd wager that over time, the BDNF levels can return to their full function with chronic Ashwagandha use but their mechanism of action was inhibited slightly, though not completely. You can see at least in Example 3 that the SC-->I-Extract columns went up in proportion to SC alone in both cases A and B for glial cells.

So yeah, Ashwagandha is great. I recommend people double or triple the dose if they don't see an effect, then keep going up until the right level of cognition/mood is achieved.

Also interesting is the role stress has on the amygdala. Stress tends to shrink up dendrites, which shrinks the amygdala. BPD patients have smaller amygdala's on average. Ashwagandha is known to increase neuronal growth by extending dendrites...

http://www.ncbi.nlm....pubmed/12395110

Just saying... pretty amazing stuff...

Thanks for bringing this to my attention. I was familiar a bit with ashwagandha as my wife takes that for hypothyroidism. It totally makes sense that it increases BDNF as BDNF is deacreased by stress and cortisol and ashwagandha deacreases stress and cortisol. My cousin can use that as her problems are frequently linked to stress.

Well here's the thing with treatment resistant depression... It actually is linked to low cortisol receptor density in the area 25 I described. I mean BDNF might correct that, but you won't know until you try.

I still think an MAOi-B regime is good if you're against atypical antipsychotics. Hard to be sad when life feels so good. If the Ashwagandha at any dose doesn't seem to work, that's an option that is still on the table. Selegiline was kickass as an antidepressant but not much in the way for my CDD/ADD, so I kicked it. For supplements, there is the black tea (or blueberry) and Yerba mate synergy to test that theory.

Edited by devinthayer, 10 July 2016 - 05:11 PM.

[Mind_Paralysis]

I'm afraid this idea about a BPD being caused or highly linked to depression is somewhat false guys - AD's obviously doesn't help a lot, since they're not prescribed in the DSM, and the studies I posted showed different structural abnormalities than those in depression.

 

Seems like BPD is more like a neuropsychiatric condition - fairly similar to ADHD actually, since they both feature behavioural dysregulation, and are often misdiagnosed as each other.

 

 

That's partially what got me thinking about Intuniv - and YES, there are significant differences in the effects of Guanfacine and Clonidine - Clonidine is far more sedating, Guanfacine is actually reported by some to be stimulating, in comparison. (most people report it as sedating however)

 

Clonidine is also far less selective than Guanfacine, hitting the Alpha-2 *and* Alpha-1-receptors, as well as primarily affecting the PRE-synaptic Alpha-receptors, while Guanfacine hits the POST-synaptic receptors. Guanfacine also has better test-scores in the treatment of ADHD as far as I know, so with all these things in consideration, I don't think it's entirely correct to assume one is interchangeable with the other. And there's also the fact that the response-curve to Guanfacine is somewhat linear - until you hit the right dosage (for ADHD the majority seems to be at 3 mg +), you won't feel much of an effect other than blood-pressure. Guanfacine has also seen updated prescribing-information, apparently the dosing goes all the way up to 7 mg's now, while before it was locked to 4 mg.

 

If she didn't have any response at 3 mg's or what-have-you, that may not mean anything - she may well need 6 mg. Also, remember how the dosing between SCT and ADHD is different, yeah? The same is probably true for BPD - much like there's a distinct dosing-discrepancy between anxiety and depression when it comes to SSRI's.

 

 

Still, combining Intuniv with Propanolol, which I figured was the best bet of the given amygdala-inhibitors might be a problem, since it might inhibit sympathetic tone too much, yeah? Are there any amygdala-inhibitors that increase blood-pressure?

 

 

 

 

Anyhow, you can imagine that area 25 being rich in serotonin transporters already overactive is probably going to get even more active once those transporters are inhibited by SSRI's.  Makes me think that too much serotonin might be causing overactive production of transporters.  It's almost as if you'd need a 5HT receptor blocker of some sort... has she ever tried an atypical antipsychotic?

 

Also associated with area 25 (subgenual cingulate) is cortisol signalling:

 

http://www.nature.co...l/1300862a.html

 

Interesting that Sertraline, an SSRI could potentially swing cortisol sensitivity in the wrong direction (at least in PTSD patients):

 

http://www.nature.co...l/1300862a.html

 

Anyhow, as you can imagine, the cortisol sensitivity rabbit trail is a long (and a good one).  There is a surprising amount of research having to do with glucocorticoid receptor (GR) regulation and sensitivity in genetics of treatment-resistant MDD patients.  In fact, at least in rats, it is regulated differently in females than males in response to stress.  I realize it is not to useful in its conclusion, but it is a useful articles as it goes over the different genes that sensitize GR's:

 

http://www.ncbi.nlm....les/PMC3443296/

 

 

Ey, Devin did you catch those Swedish MRI and molecular studies that showed increased Serotonin-activity in anxiety-disorders? Do you figure there's a connection between Cortisol and Serotonin?

 

 

[thedevinroy]

I'm afraid this idea about a BPD being caused or highly linked to depression is somewhat false guys - AD's obviously doesn't help a lot, since they're not prescribed in the DSM, and the studies I posted showed different structural abnormalities than those in depression.

Seems like BPD is more like a neuropsychiatric condition - fairly similar to ADHD actually, since they both feature behavioural dysregulation, and are often misdiagnosed as each other.


That's partially what got me thinking about Intuniv - and YES, there are significant differences in the effects of Guanfacine and Clonidine - Clonidine is far more sedating, Guanfacine is actually reported by some to be stimulating, in comparison. (most people report it as sedating however)

Clonidine is also far less selective than Guanfacine, hitting the Alpha-2 *and* Alpha-1-receptors, as well as primarily affecting the PRE-synaptic Alpha-receptors, while Guanfacine hits the POST-synaptic receptors. Guanfacine also has better test-scores in the treatment of ADHD as far as I know, so with all these things in consideration, I don't think it's entirely correct to assume one is interchangeable with the other. And there's also the fact that the response-curve to Guanfacine is somewhat linear - until you hit the right dosage (for ADHD the majority seems to be at 3 mg +), you won't feel much of an effect other than blood-pressure. Guanfacine has also seen updated prescribing-information, apparently the dosing goes all the way up to 7 mg's now, while before it was locked to 4 mg.

If she didn't have any response at 3 mg's or what-have-you, that may not mean anything - she may well need 6 mg. Also, remember how the dosing between SCT and ADHD is different, yeah? The same is probably true for BPD - much like there's a distinct dosing-discrepancy between anxiety and depression when it comes to SSRI's.


Still, combining Intuniv with Propanolol, which I figured was the best bet of the given amygdala-inhibitors might be a problem, since it might inhibit sympathetic tone too much, yeah? Are there any amygdala-inhibitors that increase blood-pressure?

Anyhow, you can imagine that area 25 being rich in serotonin transporters already overactive is probably going to get even more active once those transporters are inhibited by SSRI's. Makes me think that too much serotonin might be causing overactive production of transporters. It's almost as if you'd need a 5HT receptor blocker of some sort... has she ever tried an atypical antipsychotic?

Also associated with area 25 (subgenual cingulate) is cortisol signalling:

http://www.nature.co...l/1300862a.html

Interesting that Sertraline, an SSRI could potentially swing cortisol sensitivity in the wrong direction (at least in PTSD patients):

http://www.nature.co...l/1300862a.html

Anyhow, as you can imagine, the cortisol sensitivity rabbit trail is a long (and a good one). There is a surprising amount of research having to do with glucocorticoid receptor (GR) regulation and sensitivity in genetics of treatment-resistant MDD patients. In fact, at least in rats, it is regulated differently in females than males in response to stress. I realize it is not to useful in its conclusion, but it is a useful articles as it goes over the different genes that sensitize GR's:

http://www.ncbi.nlm....les/PMC3443296/

Ey, Devin did you catch those Swedish MRI and molecular studies that showed increased Serotonin-activity in anxiety-disorders? Do you figure there's a connection between Cortisol and Serotonin?

Depending on the part of the brain, yeah cortisol pathways are definitely affected by serotonin pathways. Hard to see if it's global.

Also, I focused on area 25 since BPD seems pretty close to treatment resistant depression, like ADHD is in a way.

[Mind_Paralysis]

Btw, I forgot to mention - but Propanolol's effect on inhibiting emotional response - it's HIGHLY dose-dependent - if you go below, it won't work - if you go too high, it won't work.

 

There's a way to calculate the dose, based on the dosages they used in the rat-experiments - but sadly my burnout shutdown -mind cannot produce the study + the formula I discovered earlier.

 

As I recall, the perfect dose for a 60 kilos human was about 20 mg's. Depending on weight, she might need less, or more.

Remember... unless the dosage is right, it won't work.

 

Likewise of course for Intuniv - hence why I still say it's worth trying out.

[Mind_Paralysis]

I'm bumping because I just found two studies which are intriguing, and actually somewhat contradictory:

 

Aberrant DNA Methylation of rDNA and PRIMA1 in Borderline Personality Disorder

http://www.ncbi.nlm....les/PMC4730312/

 

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.

 

But then there's this study:
 

α7-Containing nicotinic acetylcholine receptors on interneurons of the basolateral amygdala and their role in the regulation of the network excitability.

http://www.ncbi.nlm....pubmed/24004528

 

Which says that a specific Cholinergic receptor, the Alpha-7-nicotinic one, is very important in controlling signalling from the Amygdala to other parts of the brain. However, the study suggests that they INHIBIT far more of the activity in the amygdala, than they enhance it! What. The. H...?!

 

*confused*

Help me out here guys... would antagonizing or agonizing cholinergic receptors help with BPD-symptoms? It seems like a more elegant, less dirty solution than using D-cycloserine and Propanolol - especially since a combo of Propanolol and Guanfacine, which would enhance PFC-gating, could trigger anti-hypertensive crisis.
 

Hmm... wait a minute... a choline-modulator! Enhancing or decreasing cholinergic neurotransmission! But does such a thing even exist...?

Edited by Stinkorninjor, 18 July 2016 - 07:53 PM.

[jack black]

I'm bumping because I just found two studies which are intriguing, and actually somewhat contradictory:

 

Aberrant DNA Methylation of rDNA and PRIMA1 in Borderline Personality Disorder

http://www.ncbi.nlm....les/PMC4730312/

 

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.

 

But then there's this study:
 

α7-Containing nicotinic acetylcholine receptors on interneurons of the basolateral amygdala and their role in the regulation of the network excitability.

http://www.ncbi.nlm....pubmed/24004528

 

Which says that a specific Cholinergic receptor, the Alpha-7-nicotinic one, is very important in controlling signalling from the Amygdala to other parts of the brain. However, the study suggests that they INHIBIT far more of the activity in the amygdala, than they enhance it! What. The. H...?!

 

*confused*

Help me out here guys... would antagonizing or agonizing cholinergic receptors help with BPD-symptoms? It seems like a more elegant, less dirty solution than using D-cycloserine and Propanolol - especially since a combo of Propanolol and Guanfacine, which would enhance PFC-gating, could trigger anti-hypertensive crisis.
 

Hmm... wait a minute... a choline-modulator! Enhancing or decreasing cholinergic neurotransmission! But does such a thing even exist...?

 

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

As for modulation, some familiar compounds antagonise the Alpha-7-nicotinic ACh receptor:

 

• Ketamine
• Kynurenic acid (controversial)
• Memantine
• Bupropion (weak)

 

[gamesguru]

Globally, it's complicated. But according to what you say (about inhibitory pathways in the amygdala) we want to increase alpha-7 activity. Lithium has some effect there. And cannabis too, which may explain a tendency to self-medicate (however counterproductive it may be long-term). Have a look at bacopa too. But I think with bacopa, the acetylcholine and serotonin release is too dramatic (not mere modulation) and might contribute to emotionality. Last thing popping to my mind, galantamine. It increases choline and positively allosterically modulates the alpha-7 site.

Ginkgo biloba's direct cholinergic actions include reduction of scopolamine-induced amnesia, modulation of pre-synaptic choline uptake and acetylcholine release, upregulation of post-synaptic muscarnic receptors and indirect effects on cholinergic function by modulation of the serotonergic system

 

Lithium decreases 5-HT1A and 5-HT2 receptor and alpha 2-adrenoceptor mediated function in mice.
Goodwin GM, DeSouza RJ, Wood AJ, Green AR. (1986)

Lithium administration (LiCl, 10 mmol/kg, SC on day 1, followed by 3 mmol/kg twice daily subsequently) for 14 days to mice produced attenuation of the hypothermic response to injection of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.5 mg/kg SC). Head twitch responses to the 5-HT-receptor agonist 5-methoxy-N,N-dimethyltryptamine (2.5 mg/kg IP) and to precursor loading with carbidopa (25 mg/kg, IP) and 5-hydroxytryptophan (100 mg/kg IP) were similarly attenuated. By contrast with this reduction of 5-hydroxytryptamine (5-HT) function mediated by the 5-HT1A and 5-HT2 receptor sub-types, repeated lithium administration had no effect on the motor response to a putative 5-HT1B receptor agonist 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole (RU 24969, 3 mg/kg IP). alpha 2 adrenoceptor function, assessed by the sedation response to clonidine (0.25 mg/kg, IP), was also attenuated by repeated lithium administration. It is proposed that these actions may explain the emergence of lithium as an adjunct to the treatment of refractory depressive illness.

[Mind_Paralysis]

Hmm... I'm starting to think here... My BPD -lady does not have verbal memory deficit from her Bupropion-use - but I did. And she says that it's actually a little bit helpful to her, in controlling her BPD-symptoms...

Hmm... what's the affinity for the naCh-receptors from Bupropion again? A fairly weak antagonist at the Alpha-7-site I believe.

 

Btw, regarding DEmethylation of PRIMA1 as a possible treatment-avenue - what do you guys figure is a valid method there? How does one impair methylation of aCh? On the one hand... that could indeed lead to turning the patients into emotionally stable, yet utterly non-functional. But for some reason I'm thinking the cognitive impairments would be less severe than with antagonists... Thoughts, gentlemen?

 

In the meantime, I'm trying to check out Alpha-7 affinity with some of the Amygdala-inhibitors - perhaps there IS some affinity in Propanolol?

 

Alpha7-nicotinic acetylcholine receptor subunit is not required for parasympathetic control of the heart in the mouse.

http://www.ncbi.nlm....pubmed/15797970

 

The Amygdala / emotion -inhibition was highly dose-specific in Propanolol - and the above study shows that apparently heart and blood-pressure is NOT a function of the A7-receptors. Would this be more proof that the A7-receptors handle emotional signalling, and not parasympathetic? I'd say it is... The dose-specificity of Propanolol may mean that such results would not be detected - nor where they looking for them.

 

All right, let's follow this train of thought...

 

Role of central nicotinic and beta-adrenergic receptors in the onset and further development of tail-tremor induced by repeated nicotine administration to rats.

http://www.ncbi.nlm..../pubmed/9151294

 

Propranolol (20 mg/kg, i.p.), administered before the nicotine on each day, suppressed the appearance of tail-tremor. After the discontinuation of propranolol treatment, the degree of tail-tremor induced by a single injection of nicotine on day 9 was much greater in the propranolol-treated group than in the saline-treated control group

 

 

Hmm! Hmm-hmm-hmm...! Does this imply some affinity of Propanolol to the Alpha-7-Nicotinic receptor? Maybe... at least there seems to be some relation? Let's keep at it.

 

EDIT:

Gamesguru! Something just struck me from your post - Propanolol apparently has weak affinity for the 5ht1a and 5ht2 -receptors! Could there be a relation? A feedback-loop to the Alpha-7-nicotinic receptors?

Edited by Stinkorninjor, 19 July 2016 - 07:19 PM.

[jack black]

Than you all who contributed to this interesting discussion. Good stuff. Keep it coming.

I totally agree that BPD is a genetically determined dysfunction of the brain and not some some touchy-feely nonsense that is still propagated by many (if not most) psychologists.

 

Case in point is the subject here. The parents are highly functioning professionals, but totally committed to their kids, and there was no history of child abuse or trauma of any sort. The girl was considered somewhat weird by her peers at daycare/school from the very beginning, she was clearly introvert, and preferred to play alone. Her siblings raised in the same environment are free of BPD, and are very social and outgoing, but have various combinations of mild anxiety and mild ADHD.

 

Anyhow, I don't share all that enthusiasm for cloninidine and propranol, as the young woman tried that at some point and felt worse. I checked and both are known to cause depression indeed. She is doing reasonably but not yet completely well. She was started on Lamictal, but stopped early on due to skin rash. She currently takes low therapeutic doses of wellbutrin XR and lithium carbonate (due to tolerance issues). In addition, she takes vitamins/supplements I suggested earlier (listed in the initial post). She was observed to have angry outbursts when she skipped lithium and was exposed to (slight) stress. That indirectly suggests lithium is working as it should in BPD. She is going to see another doc soon, so there may be a change in treatment. 

 

Now, I understand that one of the core issues in BPD is low self esteem and hence the need for validation via pathologic relationships (that invariably fail).  I noticed myself that memantine helps with functioning and self esteem in ADHD (I was so impressed, I started a separate thread on it). Since the lady supposedly has ADHD comorbility too, I'm going to recommend a trial of memantine too. I could not find much published on it, but there is an ongoing trial of memantine vs BPD in Australia. I'll keep you posted.

 

Edited by jack black, 20 July 2016 - 04:50 PM.

[jack black]

update:

the young lady cousin of mine saw another doc who didn't agree with the diagnosis of BPD due to the fact that she doesn't have several emotional outbursts every day. of course he saw her medicated already. weird, i saw the official criteria and that wasn't one of them. IMHO, she meets all the official criteria very well. it's possible he didn't want her labeled as borderline due to its stigma. of course we don't know what he put in her chart.

 

he recomended no change in treatment. it's a low dose lithium and bupriopion combo (plus the supplements i think mentioned before). she is doing much better than before mood wise, but has deficits in motivation and atention (her old ADHD).

Edited by jack black, 31 July 2016 - 12:10 AM.

[gamesguru]

the outbursts don't happen everyday, just under stress. and they would quite obviously be lessened already, if she had been inundated with lithium and bupro prior to the follow-up assessment. the doctors also don't like the borderline cause it means their meds aren't justified and they have to turn her over to dialectical therapists (not 100%, but as a rule, yes)

[Mind_Paralysis]

Well, she could of course have some form of atypical Bipolar Disorder... the fact that she's responding to lithium is a sign towards that.

Can we get some affinity-charts concerning memantine, lithium and bupropion here though?

I still don't want to give up on that connection - especially since she's showing improvements on two drugs with alpha-7 affinity.

Which one binds the most? And, in what parts of the brain do all 3 drugs alter overall activity the most?

[gamesguru]

Bipolar Disorder... the fact that she's responding to lithium is a sign towards that.

The first mood stabilizer considered for the treatment of patients with BPD is lithium carbonate; its effectiveness has been reported in 3 reviews since the late 1980s.13-15 Concerning the mechanism of action, 3 interacting systems appear critical for lithium activity: modulation of neurotransmitters, which may contribute to neuroprotection by readjusting excitatory and inhibitory activity balance; modulation of signals impacting on the cytoskeleton, including glycogen synthase kinase-3β, cyclic AMP-dependent kinase, and protein kinase C, which may be critical for the neural plasticity involved in mood stabilization; and regulation of second messengers, transcription factors, and gene expression.16

The results of a 6-week, doubleblind, placebo-controlled crossover study that compared lithium with desipramine in 10 patients with BPD showed the efficacy of lithium on core features of borderline psychopathology, such as irritability, anger, and selfmutilation.17 A review by Stein18 concerning lithium and the anticonvulsant agent carbamazepine in the treatment of patients with BPD or antisocial personality disorder pointed out the effectiveness of both agents on behavioral dysregulation and aggressiveness.

[Mind_Paralysis]

 

Bipolar Disorder... the fact that she's responding to lithium is a sign towards that.

The first mood stabilizer considered for the treatment of patients with BPD is lithium carbonate; its effectiveness has been reported in 3 reviews since the late 1980s.13-15 Concerning the mechanism of action, 3 interacting systems appear critical for lithium activity: modulation of neurotransmitters, which may contribute to neuroprotection by readjusting excitatory and inhibitory activity balance; modulation of signals impacting on the cytoskeleton, including glycogen synthase kinase-3β, cyclic AMP-dependent kinase, and protein kinase C, which may be critical for the neural plasticity involved in mood stabilization; and regulation of second messengers, transcription factors, and gene expression.16

The results of a 6-week, doubleblind, placebo-controlled crossover study that compared lithium with desipramine in 10 patients with BPD showed the efficacy of lithium on core features of borderline psychopathology, such as irritability, anger, and selfmutilation.17 A review by Stein18 concerning lithium and the anticonvulsant agent carbamazepine in the treatment of patients with BPD or antisocial personality disorder pointed out the effectiveness of both agents on behavioral dysregulation and aggressiveness.

 

 

When you say BPD you mean BiPolar Disorder, right? (just want to be sure)

 

The fact that Borderline-symptoms are triggered by stress btw, is IMHO more evidence towards what the scans show: there are abnormalities in the amygdala.

 

BTW, just saw a study which showed substantial evidence towards ODD - Oppositional Defiance Disorder, being a distinct neuroanatomical disorder in itself - separate from ADHD.

 

The study, showed abnormalities in the Amygdala as one of the call-signs, which so happens to be what the Borderline-scan study showed. And the symptoms are similar, aren't they? Guess which medication is usually prescribed to deal with the symptoms? Guanfacine.

 

Currently having trouble with my own Borderline-lady at the moment... as I have made the mistake of accepting her invite to house me in her loft until my move is complete.

She's a terror and a half. I really wish she had the right treatment - an alpha-7-modulator.

[jack black]

 

 

When you say BPD you mean BiPolar Disorder, right? (just want to be sure)

 

 

This thread is about borderline personality disorder, so we have been using BPD for that. I'm sure this is what gamesguru meant. But, you are right, BiPolar Disorder is also BPD.

 

Besides, from my understanding BPD and BiPolar, especially the rapid cycling variety, are closely related.

 

A few mental diseases are closely related (and I guess epilepsy, too), but with some important differences of course: http://www.nimh.nih....disorders.shtml

 

 

After all, we are the sum of our genes (including epigenetics).

 

From that study, it's clear that the mood stabilizers that work on ion channels are going to be helpful in a variety of conditions (including ADHD, I guess).

 

BTW, that BPD in the above illustration is actually BiPolar. They didn't include Borderline cases (I guess because it's a "personality" and not a real disease, LOL).

Edited by jack black, 01 August 2016 - 04:59 PM.

[Mind_Paralysis]

I must say... the results in that study is rather astounding.

NO negative heritability on ADHD and Schizophrenia?! And negligeable heritability on Autism and Major Depression?!

I'm rather shocked tell ya' the truth... does this mean all those depressed autistics are in fact not depressed? They've got dystymia and PTSD or something? What's the proposed explanation? There's clearly a great amount of ASD-people feeling bad as we speak.

And even though the comorbidity on Schiz and ADHD seems to be very low, I wouldn't say it's negligible.
There's still a small amount of people that have both... but the neuroanatomy... the alterations SHOULD be counteracting each other - causing the combined sufferer to become... mostly neurotypical.

But apparently that's not always the case.

My word...

[jack black]

I must say... the results in that study is rather astounding.

NO negative heritability on ADHD and Schizophrenia?! And negligeable heritability on Autism and Major Depression?!

I'm rather shocked tell ya' the truth... does this mean all those depressed autistics are in fact not depressed? They've got dystymia and PTSD or something? What's the proposed explanation? There's clearly a great amount of ASD-people feeling bad as we speak.

And even though the comorbidity on Schiz and ADHD seems to be very low, I wouldn't say it's negligible.
There's still a small amount of people that have both... but the neuroanatomy... the alterations SHOULD be counteracting each other - causing the combined sufferer to become... mostly neurotypical.

But apparently that's not always the case.

My word...

 

The way I read the study is they looked at the amount that could be attributed to inherited component linked to handful of genes (mostly ion channels).

So yes, you can have depression in autism, but depression is secondary to maladjustment and not primary due to genes. Depression is merely a symptom.

Same with attention deficit; it's a symptom that could arise from a number of distinct diseases (like SCT, ADHD, ADHD-PI, ADHD-C, ASD, Schizo, etc).

 

And if one has an inherited risk of mental diseases (and/or epilepsy) that come from disturbed ion channels, it's the other genes and SNPs that are going the shape the symptoms and/or severity of the disease.

Edited by jack black, 01 August 2016 - 05:35 PM.