26 replies to this topic

[thedevinroy]

http://palgrave.natu.../mp201674a.html

Study on genetic variance and new findings in body chemistry of Adult ADHDer's. Came out this month.

Seems to confirm findings of BAIAP2 differences in childhood ADHD from a 2013 study by Lu Liu.

https://www.research...se_Han_subjects

Makes you wonder how important insulin signaling is in the brain in... making some growth cones? I need those...

[thedevinroy]

Here is an almost relevant dive into growth cones and their mechanism involving RNA and antennae proteins:

http://psychcentral....ired/55790.html


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[Finn]

http://palgrave.natu.../mp201674a.html

 

Link didn't work for me, until I removed "palgrave" from the beginning, then it worked.

 

http://www.nature.co.../mp201674a.html

[thedevinroy]

http://www.ncbi.nlm.nih.gov/gene/10458

 

 

BAIAP2 BAI1 associated protein 2 [ Homo sapiens (human) ]

 

The protein encoded by this gene has been identified as a brain-specific angiogenesis inhibitor (BAI1)-binding protein. This adaptor protein links membrane bound G-proteins to cytoplasmic effector proteins. This protein functions as an insulin receptor tyrosine kinase substrate and suggests a role for insulin in the central nervous system. It also associates with a downstream effector of Rho small G proteins, which is associated with the formation of stress fibers and cytokinesis. This protein is involved in lamellipodia and filopodia formation in motile cells and may affect neuronal growth-cone guidance. This protein has also been identified as interacting with the dentatorubral-pallidoluysian atrophy gene, which is associated with an autosomal dominant neurodegenerative disease. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

 

 

 

That's all fun and interesting... suggesting that insulin helps with growth cone guidance.  I could see that.  Your axons shouldn't grow around areas without capillaries, and if they do... you might need more blood flow.

 

Here's the scary part:

 

http://www.ncbi.nlm....ubmed/26275848/

 

 

IRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders.

 

IRSp53 (also known as BAIAP2) is a multi-domain scaffolding and adaptor protein that has been implicated in the regulation of membrane and actin dynamics at subcellular structures, including filopodia and lamellipodia. Accumulating evidence indicates that IRSp53 is an abundant component of the postsynaptic density at excitatory synapses and an important regulator of actin-rich dendritic spines. In addition, IRSp53 has been implicated in diverse psychiatric disorders, including autism spectrum disorders, schizophrenia, and attention deficit/hyperactivity disorder. Mice lacking IRSp53 display enhanced NMDA (N-methyl-d-aspartate) receptor function accompanied by social and cognitive deficits, which are reversed by pharmacological suppression of NMDA receptor function. These results suggest the hypothesis that defective actin/membrane modulation in IRSp53-deficient dendritic spines may lead to social and cognitive deficits through NMDA receptor dysfunction. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.

 

 

 

 

Makes you wonder if that's why NMDA antagonists seem to help those with ADHD, autism, and schizophrenia.  The brain has too much noise... figuratively, mostly.

 

 

[psychejunkie]

Wow

 

 

 

This protein has also been identified as interacting with the dentatorubral-pallidoluysian atrophy gene, which is associated with an autosomal dominant neurodegenerative disease

 

Is this interaction negative or positive?

 

enhanced NMDA receptors? maybe that's why most ADD sufferers have exceptional powerful long-term memory like a library full of shits without order

Edited by psychejunkie, 24 July 2016 - 04:11 AM.

[thedevinroy]

Seems that increased mutations in actin depolymerization genes (from combination of ADF and n-cofilin signalling) can lead to ADHD-like symptoms in mice:

 

http://www.ncbi.nlm....pubmed/24768258

 

Actin is nerve membrane used in growth of axons.  Too much will cause "social and congitive deficits" according to that last quote.  Here is some more explanation of ADF signalling:

 

http://chemistry.ber...try/2012/mm_is/

 

Goes on to talk about the link with malaria, which is interesting.  Cognitive impairment by malaria occurs with a very strong correlation, even after recovery ( http://www.ncbi.nlm....les/PMC3018393/ ).  Malaria needs extracellular ADF in order to split, but it may be more than that.  Consider that malaria actually steals the actin from blood cells, then re-arranges it ( http://www.nature.co...y-solved-1.9342 ).  It's very survival is determined by the existence of actin and ADF to help re-arrange it for their benefit.  So, with malaria in your blood, not only do you get inflammation from missing actin, but you get the cognitive issues from it sucking up all the ADF which would have been otherwise used in the brain for directing traffic, so to speak.

Edited by devinthayer, 24 July 2016 - 05:13 AM.

[thedevinroy]

Wow

 

 

 

This protein has also been identified as interacting with the dentatorubral-pallidoluysian atrophy gene, which is associated with an autosomal dominant neurodegenerative disease

 

Is this interaction negative or positive?

 

enhanced NMDA receptors? maybe that's why most ADD sufferers have exceptional powerful long-term memory like a library full of shits without order

 

You are definitely not talking about me.  I have the inattentive type.  But yeah, I know some ADHDer's with exceptional long term memories and a tendency towards reliving past experiences, talking about the good old days, stuff like that.  Hyperactive types, at least from what I've seen, are more likely to have crazy strong long term memory for things you didn't even know they were paying attention to.  Since this BAIAP2 gene is more strongly correlated in inattentive subtypes, I question that theory on personal experience.  My long term memory is awful, like my hard drive is full, so it just deletes stuff I haven't used in a while like birthdays and first names and especially things that I have said to other people that were questionably important to my first impression, which is why my second impression is so terrible IRL.  I have pretty terrible recall without supplementation - tip of the tongue syndrome like 24-7. 

 

But, to answer your question as to good or bad, it seems that BAIAP2 (also called IRSp53) is required in order for neurodegeneration in DRPLA gene rat models:

 

http://www.ncbi.nlm....pubmed/11514062

 

Therefore, it is contraindicated to have the bad DRPLA gene and the bad BAIAP2 expression for neurodegeneration to occur.  As to whether or not this is good for long term memory is unclear, only that a person with low BAIAP2 activity will likely not be affected as much by the rare genetic disorder.  It certainly makes you wonder if a person with ADD and good long term memory has a BAIAP2 deficiency.

Edited by devinthayer, 24 July 2016 - 05:59 AM.

[Mind_Paralysis]

Hmm! Fascinating stuff this - especially the connection to the NMDA-network. It certainly suggests that ADHD is a truly complicated disease - easily up there with the likes of Autism and Schizophrenia.

 

Regarding BAIAP2 though - what would be the result of activating this gene further, in adults? Have they tried, or are going to try - any epigenetic treatments on Mice?

 

On another note - my mind works similarly to Devinthayer's I would say - tip of the tongue quite often. So even though Devin is doing some good work here, I'm not sure how relevant it is to either of our symptoms - seeing as ADHD is not actually the same disorder as SCT, after all. I'm no longer so sure NMDA-antagonists would be as useful for SCT-ers as they would for ADHD-ers.

[thedevinroy]

I have to say am not quite sure myself. I've had noticeable positive effects to both Huperzine A, Stattera, and Memantine but not Cat's Claw alone which seems to be on the sedating side. Magnesium is a good tool to tone down the drugged feeling of stims, and in synergy with other aqueous minerals works well to help concentration... But that could be just as an absorption enhancer. Zinc has some good effects but that could also be from GABA antagonism or B6 activation.

Hard to say! NMDA antagonists usually have other psychotropic properties...


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[Mind_Paralysis]

There is one way that is bound to work if you want to try a super-pure NMDA-antagonist or two...

Av-101 - it's gotten a bit of talk recently, as another fast-acting antidepressant, as well as showing promising results in alzheimers. It's a pro-drug that passes the blood-brain barrier and then becomes KYNA - the body's own NMDA-antagonist.

I was actually really surprised about this one - because I never figured any researcher would be creative enough to look up KYNA as a possible multi-purpose psychiatric drug! I thought I was the only guy in the world who still had an interest...

Nicotinylalanine - I still think this is the better option - it's a compound discovered by Italian scientists about 30 years ago, among them Dr Pelicari whom I e-mailed about it. It works in two ways: by altering the enzymatic pathway that creates KYNA out of tryptophan, and by increasing TRANSPORT of KYNA! : O This doesn't mean what you think it does: it actually means it makes sure KYNA is spread to more places. Astounding stuff - it was meant as a treatment for alzheimers, but funding was cut by the investment-company to instead focus on compounds like Memantine, which seemed more profitable...

Dr. Pelicari actually told me about several OTHER KYNA-dehibitors which they had in their pipeline before they were shut down, which were actually many times more powerful than NAL.



*This section is pointless ranting*
-------------------------------------

He also told me that I had a very intriguing idea, and that he was prepared to share any info I thought relevant...

...and I never replied, because Pathological mindwandering hit me in the project, while other issues caused burnout and social withdrawl which lead to Pathological rumination - I can't even bear to look at this e-mail now!


THIS is why I feel this disorder causes MORE suffering than either ADHD or Aspergers, perhaps even to some Schizoid disorders - it impairs us in a way that barely any one else who doesn't have the disease can even fathom - because it keeps us in a state in-between truly Suicidal/depressed/OCD and perfectly functional - a f*cking purgatory of existence!

It crushes our lives enough to take away ALL meaning, but not enough to actually make us extinguish them (ADD is actually not connected to any decrease in longevity).


"What is this thing that builds our dreams, yet slips away from us?"


(cudos to anyone who gets the reference. And I don't care what any of the haters say! It's one of their *best* albums.)

[psychejunkie]

Dr.Pelicari had spend time to reply and share his info with you, the least proper behavior of yours would be spending some time and share your ideas with him. 

[thedevinroy]

Dr.Pelicari had spend time to reply and share his info with you, the least proper behavior of yours would be spending some time and share your ideas with him.

Yeah that was his point. He knows he should but doesn't. Guilt drives no adrenaline in ADHD - it's not motivating or even relevant to getting something done. In fact, it reinforces his avoidance behavior by simply being a weight - one that the harder he tries to do something about, the more his mind resists it and goes into something else. Anxiety occurs only when things are about to explode or spiral out of control, and only then does something important get done.

HPA Axis is severely impaired in ADD, CDD, etc. Means stress does different things. In a concentration deficit disorder, the weight of importance becomes negligible next to the draw of excitement. Whereas a normal person would ignore or put off responsibilities consciously, it's automatic or never even enters the mind in CDD. When asked why, they don't know.

We're starting to learn why now - stress has a different effect on the mind when there is low norepinephrine, low cortisol, high NMDA activity, low acetylcholine, and low dopamine. It's one of the most common comorbid disorders, so it may also include high or low serotonin, high stratial dopamine, low or high basal GABA, low opiod density, low nicotinic receptor activity, etc. which makes finding someone just like us equally frustrating and consuming. There is no normal ADD, CDD, SCT, ADHD-PI, etc.

Commonly, paying bills, following up, and other mundane adult activities are too daunting to even think about and when we do, the guilt or shame in putting it off is hardly motivating. You want to change, but you also want the world to change. You want to get work done, but you lose track of time doing little stuff that doesn't matter. You want to care, but it's whatever.

Brain scans show that at rest, a normal ADD brain and regular brain work the same, but when asked to concentrate use entirely different areas. You can look at problems totally differently - detached almost, looking for a creative solution before looking for an obvious one... Which is good sometimes, but other times, the world outside or in your head causes a bouncing between reality that is truly frustrating. I would love to say it's intentional, but it's not. I would love to say it is habitual, but it's not.

Using will power is about as effective as trying to move a muscle that fell asleep. It's not impossible, but it doesn't work the way it should, either. Eventually enough blood flow returns to the PFC with enough hype and breathing and smiling and even anxiety or anger - all have stimulating and channeling or motivating effects on ADD cognition... Similar to blood returning to a muscle. But, unlike sleeping funny, you can't just shift and make it better.

Thus goes the search to normalize or enhance the ADD brain and avoid all mundane tasks until we've procrastinated enough to do something important. ADD cortisol levels stabilize in the evenings, so there exists the reward to stay up late to get something done. Like this post. And so goes the cycle to have hyper somnolence and ADD - or more of a CDD characteristic.

Edited by devinthayer, 26 July 2016 - 05:13 AM.

[thedevinroy]

On the link between ADHD and cortisol, the study I posted found no correlations which were really bizarre, seeing as how there are multiple studies with p values in a correlative range for reduced salivary cortisol levels and ADHD-H and ADHD-PI. Here is a study that basically says that a child's response to their parent's and teacher's criticism is highly relevant - even more so the warmth in which a parent or teacher towards the child is likely to cause the child to act up. They discuss why that might be in detail, but essentially it would have to mean that cortisol levels in negative (criticism) ADHD children did not decrease in a similar fashion than controls or even to ADHD positive reinforcement or at all - seems steady like a child with ADHD seems to get the same amount of stress response from repeated negative reinforcement whereas a normal child can blunt the response. If you follow the actual curves of cortisol in positive ADHD va. Controls there is very little difference. This is the only study I have seen thus far that shows no baseline correlation:

http://behavioraland.../1744-9081-6-45


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[Mind_Paralysis]

Devin said it better than me. = ) I'll try to reply to the good Dr. as we speak though! Sometimes I get this activation from affirmative reinforcement - it's not as strong as stress-induced enforcement, but it'll do, at times.

 

Annd, as we speak - I have finally been motivated to send a letter of reply. And it was actually Prof. Moroni, one of Prof. Pelliciari's colleagues from back in the day of researching into SKHI-compounds.

(coined my own little frase there - Selective Kynurenine Hydroxylase Inhibitor - I actually think SKHModulator would be the future though: by combining hydroxylase inhibition and enhancement, but in different parts of the brain, one could conceive of a compound, perhaps created out of the combination of two drugs, that would provide a more balanced alteration of the Kynurenine Hydroxylase pathway - such a drug would be FAR more suitable for the treatment of Schizoid disorders, for instance.)

[thedevinroy]

I remember watching a cartoon that the army general said, "I only respond to negative reinforcement," as he thwarts the protagonist.


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[jack black]

Guilt drives no adrenaline in ADHD - it's not motivating or even relevant to getting something done. In fact, it reinforces his avoidance behavior by simply being a weight - one that the harder he tries to do something about, the more his mind resists it and goes into something else. Anxiety occurs only when things are about to explode or spiral out of control, and only then does something important get done.

HPA Axis is severely impaired in ADD, CDD, etc. Means stress does different things. In a concentration deficit disorder, the weight of importance becomes negligible next to the draw of excitement. Whereas a normal person would ignore or put off responsibilities consciously, it's automatic or never even enters the mind in CDD. When asked why, they don't know.

We're starting to learn why now - stress has a different effect on the mind when there is low norepinephrine, low cortisol, high NMDA activity, low acetylcholine, and low dopamine. It's one of the most common comorbid disorders, so it may also include high or low serotonin, high stratial dopamine, low or high basal GABA, low opiod density, low nicotinic receptor activity, etc. which makes finding someone just like us equally frustrating and consuming. There is no normal ADD, CDD, SCT, ADHD-PI, etc.

Commonly, paying bills, following up, and other mundane adult activities are too daunting to even think about and when we do, the guilt or shame in putting it off is hardly motivating. You want to change, but you also want the world to change. You want to get work done, but you lose track of time doing little stuff that doesn't matter. You want to care, but it's whatever.

Brain scans show that at rest, a normal ADD brain and regular brain work the same, but when asked to concentrate use entirely different areas. You can look at problems totally differently - detached almost, looking for a creative solution before looking for an obvious one... Which is good sometimes, but other times, the world outside or in your head causes a bouncing between reality that is truly frustrating. I would love to say it's intentional, but it's not. I would love to say it is habitual, but it's not.

Using will power is about as effective as trying to move a muscle that fell asleep. It's not impossible, but it doesn't work the way it should, either. Eventually enough blood flow returns to the PFC with enough hype and breathing and smiling and even anxiety or anger - all have stimulating and channeling or motivating effects on ADD cognition... Similar to blood returning to a muscle. But, unlike sleeping funny, you can't just shift and make it better.

Thus goes the search to normalize or enhance the ADD brain and avoid all mundane tasks until we've procrastinated enough to do something important. ADD cortisol levels stabilize in the evenings, so there exists the reward to stay up late to get something done. Like this post. And so goes the cycle to have hyper somnolence and ADD - or more of a CDD characteristic.

 

 

What you said is very interesting and summarizes ADD (i guess ADHD-PI) very well. But I wish I understood everything you said.

By saying HPA Axis is severely impaired, what specifically do you mean? Is it up-regulated or down-regulated?

 

RE: stress has a different effect on the mind when there is low norepinephrine, low cortisol, high NMDA activity, low acetylcholine, and low dopamine. It's one of the most common comorbid disorders, so it may also include high or low serotonin, high stratial dopamine, low or high basal GABA, low opiod density, low nicotinic receptor activity, etc. Would you mind expanding on that?

 

About: ADD cortisol levels stabilize in the evenings. Do you meant normalize from abnormally low or abnormally high levels?

 

What is CDD?

 

 

On the link between ADHD and cortisol, the study I posted found no correlations which were really bizarre, seeing as how there are multiple studies with p values in a correlative range for reduced salivary cortisol levels and ADHD-H and ADHD-PI. Here is a study that basically says that a child's response to their parent's and teacher's criticism is highly relevant - even more so the warmth in which a parent or teacher towards the child is likely to cause the child to act up. They discuss why that might be in detail, but essentially it would have to mean that cortisol levels in negative (criticism) ADHD children did not decrease in a similar fashion than controls or even to ADHD positive reinforcement or at all - seems steady like a child with ADHD seems to get the same amount of stress response from repeated negative reinforcement whereas a normal child can blunt the response. If you follow the actual curves of cortisol in positive ADHD va. Controls there is very little difference. This is the only study I have seen thus far that shows no baseline correlation:

http://behavioraland.../1744-9081-6-45


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I'm going to read that study more later on. Maybe that'll provide some clues to things you said. But the first thought i had was the parents of ADHD children have likely ADHD themself, so maybe the abnormal EE are coming from that?

[jack black]

 

 

What you said is very interesting and summarizes ADD (i guess ADHD-PI) very well. But I wish I understood everything you said.

By saying HPA Axis is severely impaired, what specifically do you mean? Is it up-regulated or down-regulated?

 

RE: stress has a different effect on the mind when there is low norepinephrine, low cortisol, high NMDA activity, low acetylcholine, and low dopamine. It's one of the most common comorbid disorders, so it may also include high or low serotonin, high stratial dopamine, low or high basal GABA, low opiod density, low nicotinic receptor activity, etc. Would you mind expanding on that?

 

About: ADD cortisol levels stabilize in the evenings. Do you meant normalize from abnormally low or abnormally high levels?

 

What is CDD?

 

 

I'm going to read that study more later on. Maybe that'll provide some clues to things you said. But the first thought i had was the parents of ADHD children have likely ADHD themself, so maybe the abnormal EE are coming from that?

 

 

Too late to edit the post, but the study answered some of my questions.

However, the study has a number of flaws and cannot be fully trusted.

I'm not certain the study showed how and if stress and cortisol play a role in ADHD.

 

This paper is a good review of the topic and plainly shows how ADHD is too heterogeneic to make any generalizations: http://www.ncbi.nlm....pubmed/22576746
 

Edited by jack black, 26 July 2016 - 07:07 PM.

[Mind_Paralysis]

CDD = Concentration Deficit Disorder = Sluggish Cognitive Tempo = ADD (but not necessarily ADHD-PI).

 

It's the new proposed name for the disorder, by Dr. Charles Barkley - I would say it does describe the disorder somewhat better, since the Sluggishness is only parts of the symptoms - like how ADHD describes more than just the hyperactivity.

 

And I would agree with you Jack, but, CDD is actually not as inheritable as ADHD - or at least the factor for developing the disorder is not quite as strong - 0.63, compared to ADHD's 0.83. Which is certainly interesting - there's actually some speculation that external psychoactive trauma of some kind may be involved in developing the disorder - and when they say that, they mean that it could well be in the uteris, and perhaps even independent of any obvious modern toxic chemicals - the disorder, much like ADHD, have actually been fairly accurately described back in the 1760's. So, it's not exactly new. The fact that it, much like ADHD, has a similar percent of the population afflicted, indifferent of nation-borders, is also another sign, that it may not have anything to do with the modern world.

 

Interestingly, there's NO gender-disparity in CDD - but in ADHD, AST and a whole bunch of other neuropsychiatric disorders, there IS.

 

Regarding the HPA-axis, that was actually something me and the now-legendary retired Longecity-poster GetOutofBox discussed - he brought up how there were signs towards an HPA-axis dysfunction in ADHD - and the info came from a Swedish study on the effects of synthetic Glucocorticoids - aka Asthma-meds, on the HPA-axis during adolescence. As I recall it though, we ended up not putting too much weight to it - because I believe we came to the conclusion that the HPA-dysfunction might be a result OF ADHD, and not the CAUSE of ADHD. Because of the stress-response people with ADHD get from life, a detrimental effect on the HPA-axis is not unexpected.

 

Impact of asthma medication and familial factors on the association between childhood asthma and attention-deficit/hyperactivity disorder: a combined twin- and register-based study

http://onlinelibrary....12529/abstract

 

This was before it was known that there seems to be an environmental effect on the development of CDD - it was assumed that it was like ADHD - almost entirely genetic - but that actually turns out to NOT be the case... biochemical trauma of some sort, perhaps during infancy or in the embryonic stage is also a part of it. It's still mostly genes, just not to the same extent as ADHD. So, with that in mind, it might be worth it to take a look at the HPA-axis again. I honestly think we should still be talking norepinephrin, DRD4 and the Superior Parietal Lobe instead though.

 

 

Back on-topic - I still don't get how one affects BAIAP2 and DHA in adults? And if there is any hypothetical treatment to be gained from altering the expression of these. I do see how there is potential for another molecular test to take, that could give another important puzzle-piece in the ongoing struggle to develop a reasonable biological test to ascertain ADHD.

Edited by Stinkorninjor, 26 July 2016 - 08:38 PM.

[thedevinroy]

You guys are great. I was truly avoiding to reply to this message until I had ample mental energy. In my retraction, you have beat the HPA Axis topic in CDD to a bloody pulp. Thanks for that. I think you both summarized what I was thinking - cortisol has an effect on CDD symptoms, but it is not causal to CDD nor is completely ruled out or studied enough to make a generalized distinction. It appears at least to me to have a slight effect overall, significant, but not in a way that is environmentally and heterogeneously understood at the moment. It's all theory and debate. Fun to pick a side, though. I myself am going to look at getting a kit to take my own cortisol levels in saliva on one of my next eBay/Amazon runs.

From what I can tell, there is no doubt an HPA axis dysfunction in CDD. However, it seems to be from low norepinephrine - one of the adrenal hormones/transmitters that has an effect on cortisol release. The bro-science on body building forums was something like watch out for your nads because I guess high norepinephrine leads to higher cortisol which can stunt testosterone production for gaining mass. It was an interesting argument, and there are a few studies in the link between adrenal receptors and estrogen receptors, so I wouldn't be surprised if there were other sex hormone effects. I just think that I'm not too worried about getting massive gains by reducing my ability to concentrate and to rabble rouse the anxiety in men to not get their cognition fixed so that their balls may or may not be more stimulated. Generalizations that are only worth mentioning to the truly insane. Body building increases norepinephrine so it's kind of like controlling your heart rate so you can accumulate more oxygen in the blood - just doesn't make any sense.

Back on topic. I have not posted any studies showing how one would affect their BAIAP2 or DHA levels or even if that's the right way to go about it. There were some serious discrepancies in the types of alleles and their effects on health and cognition in rodents, and the rodent gene alleles in this case I was not sure were the same as the human genes. That's why the solution to correcting for these genetic traits has not been posted by me just yet for BAIAP2.

DHA is an easy one, though. It crosses the BBB and intestinal lining, so make sure you get your fish oil or algae oil in your diet. Not sure how long it takes to build up in your arteries and brain... Or how to test for it either. Have to dig into that a little deeper as well.

A lot of rabbit holes we could go down...

Edited by devinthayer, 27 July 2016 - 12:02 PM.

[jack black]

The bro-science on body building forums was something like watch out for your nads because I guess high norepinephrine leads to higher cortisol which can stunt testosterone production for gaining mass. It was an interesting argument, and there are a few studies in the link between adrenal receptors and estrogen receptors, so I wouldn't be surprised if there were other sex hormone effects. I just think that I'm not too worried about getting massive gains by reducing my ability to concentrate and to rabble rouse the anxiety in men to not get their cognition fixed so that their balls may or may not be more stimulated.

 

Speaking of testosterone, I tend to have low levels and I can assure you it certainly feels similar to a bad case of SCT with low energy levels, apathy, and depression. Interestingly, various stimulants can help some with energy, but obviously fail in the libido part.  On the other hand, boosting T helps the overall energy and wood, but obviously does nothing for motivation and executive functions. BTW, just today i got a call from collection agency about a medical bill I forgot about long time ago. Fortunately it's only $26.

[thedevinroy]

Lifting (especially in the legs) not only increases testosterone and energy but also endorphins, blood flow, brain serotonin (vs. peripheral), and therefore provides a mood stabilizing effect and increase in cognition. It's like 5 supplements in 1. Bro science. Do it.

And back to the DHA question...

From my experience, fish oil in medium high doses is decent for reducing mental fatigue, brain fog, and even scatterbrain hyperness from caffeine, but it does not seem to have a desirable effect at higher doses (almost sedating). The happy place for me is between 2x 1000mg of triple strength per meal up to twice that that. I got it from Walmart, but only when there was a sale, haha. The strongest effect by far was not on my head, but on my heart - literally. Because it seemed so trivial, I decided not to put any money towards it except this one time where I ate way too much beef and was having cardiovascular issues (angina). ALA has a similar heart relaxing effect, so nowadays I just make sure I get enough lighter vegetable oils like walnut oils and almond oils and green food.

Now for some actual science...

http://www.ncbi.nlm....les/PMC4321799/

Seems that teachers reported that the ADHD kids were less hyperactive on fish oil, but only the parents noticed an increase in attention. I say this points to an increased ability to relax and shift focus, but not necessarily an all around fix. Anecdotally, I also noticed more of a relaxed state and fluid of thought, but like I said... Not the most profound effect, nor is it worth comparing to actual ADD medicine in core symptomatic relief. I think that the fact that the psychiatrists weren't involved in the study points to a big question mark on its neuroplastic effect. Would the students taking fish oil vs. placebo by their psychiatrists compare any better in terms of attention? I think so

Here is a study on adult hippocampus, neuroplasticity, and fish oil:

http://www.ncbi.nlm....ubmed/23746276/

Seems pretty pro-fish oil.

Edited by devinthayer, 28 July 2016 - 11:52 AM.

[jack black]

LOL, speaking of procrastination (how do you fix it?). I finally made the effort to click on all the great links provided by devinthayer.

 

Why is it that I can't quote the very first post? Is it just me?

 

A few reflections (in random order):

 

1. Wow, great info. Insulin signaling is very important in brain. Some people refer to Alzheimer's disease as "type 3 diabetes" (of course it's a bit controversial): http://www.ncbi.nlm....les/PMC2769828/

2. The second link had a number of SNPs implicated. I checked my 23andMe results and found none of them :-(

3. The link (via IRSp53/BAIAP2) between autism spectrum disorders, schizophrenia, and attention deficit/hyperactivity disorder doesn't surprise me. I postulated here that the current mental disorders classification based on symptoms is wrong and the real classification should be based on molecular.

4. The connection between IRSp53/BAIAP2 and NMDA receptor is fascinating. That explains the good results I'm getting from Namenda (except for increased dyslexia that still persists).

5. The last links seem to suggest that it's actually EPA and not DHA that it's helpful. This is what Dr Amen has been saying for some time now. I personally never saw any noticeable effects from fish oil. Maybe I didn't take enough? Maybe I should look for pure EPA supplements?

 

[jack black]

Regarding the HPA-axis, that was actually something me and the now-legendary retired Longecity-poster GetOutofBox discussed

 

What happened to that guy? I read his monster 10-page thread:

http://www.longecity...elopment/page-1

and it was very informative.  And then he disappeared.  No good bye, no f-you, no nothin.

Edited by jack black, 30 July 2016 - 09:57 PM.

[Mind_Paralysis]

He's still active in discussion concerning SCT and Nootropics on Reddit though.

As to why he left - as I recall it, he felt that Longecity had become a very homogenous environment, and where generalities where suggested as solutions to all manor of problems.

[thedevinroy]

LOL, speaking of procrastination (how do you fix it?). I finally made the effort to click on all the great links provided by devinthayer.

Why is it that I can't quote the very first post? Is it just me?

A few reflections (in random order):

1. Wow, great info. Insulin signaling is very important in brain. Some people refer to Alzheimer's disease as "type 3 diabetes" (of course it's a bit controversial): http://www.ncbi.nlm....les/PMC2769828/
2. The second link had a number of SNPs implicated. I checked my 23andMe results and found none of them :-(
3. The link (via IRSp53/BAIAP2) between autism spectrum disorders, schizophrenia, and attention deficit/hyperactivity disorder doesn't surprise me. I postulated here that the current mental disorders classification based on symptoms is wrong and the real classification should be based on molecular.
4. The connection between IRSp53/BAIAP2 and NMDA receptor is fascinating. That explains the good results I'm getting from Namenda (except for increased dyslexia that still persists).
5. The last links seem to suggest that it's actually EPA and not DHA that it's helpful. This is what Dr Amen has been saying for some time now. I personally never saw any noticeable effects from fish oil. Maybe I didn't take enough? Maybe I should look for pure EPA supplements?

I don't know if you fix procrastination. There is always going to be unconscious resistance to the feeling of overwhelm. All that ADD medicine does to help is shift the feeling of overwhelm to a higher standard for a baseline qualification - why normies think you have no excuse. On the other hand, you can overcome procrastination by setting alarms, changing your alarms up, blabbing to others your confession that will be hard on you if you don't pull through, and visualizing before bedtime as well as other mental tricks to look at your situation in a less dreadful way.

By the way. Thanks for reading those.

In another side note, I'm not sure 23andme would have screened for those. The reason why those services were in trouble was because the industry wasn't standardized and had no consistency on which information to use where and what qualifies as relevant vs. irrelevant with what degree of certainty it could be used. All of it was proprietary and the BS factor was as transparent as mud.

Edited by devinthayer, 31 July 2016 - 09:37 PM.

[thedevinroy]

Here's a pretty pro-fish oil podcast from back in the day: http://smartdrugsmar...-origins-brain/

I guess it's your mom's fault.

[Mind_Paralysis]

Regarding the procrastination - I believe it's primarily caused by two aspects in tandem:

1. Sluggishness.
Low norepinephrine is the culprit and this then leads to fatigue, when trying to complete tasks.

2. Punishment-sensitivity.
Since extreme stress is the only natural stimulator for NE, a life-time of negative affirmation on performance leads to a fear of effort (since effort for us is pain-inducing) and because we are so used to failure and then punishment, the logical subconscious response is to do nothing at all.


That's why I think kappa-antagonists can be useful - they'll remove the final obstacles - but only if we are loaded with NE and success from an NRI.