How Antidepressants Work, at Last?(blogs.sciencemag.org)
blogs.sciencemag.org
How Antidepressants Work, at Last?
https://blogs.sciencemag.org/pipeline/archives/2021/02/19/how-antidepressants-work-at-last
178 comments
I like to say that the brain is very good at adjusting to adversity, but apparently very bad at adjusting to it's absence. I've heard that people who went through the Great Depression (unrelated :-), tended to spend the rest of their lives hording supplies.
Is it reasonable to rephrase this as brains are good at learning, but not unlearning.
That dealing with trauma is not forgetting old behaviours but learning new ones?
That dealing with trauma is not forgetting old behaviours but learning new ones?
I think it's well established that negative experiences impact most people more highly than positive ones, even if logically they are of the same degree. Based on your conjecture I suppose this would simply mean this lingers, informing the brain how to react in the future.
https://www.nytimes.com/2012/03/24/your-money/why-people-rem...
“Put another way, you are more upset about losing $50 than you are happy about gaining $50,” the paper states.
https://www.nytimes.com/2012/03/24/your-money/why-people-rem...
“Put another way, you are more upset about losing $50 than you are happy about gaining $50,” the paper states.
Yes. Anyone who has had to handle the affairs of someone in that "greatest generation" who has passed away knows, the amount of stuff they have accumulated is immense, almost overwhelming.
It was a charming part of their lives (e.g. going to see all 7 of grandma's prized typewriters in their basement), but trying to sell those 7 typewriters on ebay only to just give up and have some estate sale person come through and basically pay a small portion of the value of things just to get it off your hands is the only option.
It was a charming part of their lives (e.g. going to see all 7 of grandma's prized typewriters in their basement), but trying to sell those 7 typewriters on ebay only to just give up and have some estate sale person come through and basically pay a small portion of the value of things just to get it off your hands is the only option.
I believe my grandma, who survived the war, never threw away any glass jar for similar reasons. It was also hard to convince her not to eat molded food.
Are hording and depression related, aside from the Great Depression, which is unrelated?
Not sure about hoarding specifically, but depression can definitely cause similar outcomes. It usually causes a lack of motivation, resulting in many consequences ranging from procrastination up to neglect of personal hygiene and of course keeping things tidy. Pair this with a potential shopping addiction or something in that vein and the differences start to blur.
I mean thats an excellent description of the experience of depression. But is that a mode induced by chemistry, biology, learned behaviour, etc?
Yes
Some people suffer from a state of what we call depression due to their life circumstances, not because their brain is malfunctioning.
Isn't the definition of depression basically feeling that way over anextended period despite not having a logical reason to do so?
Regardless, if you're depression is because your life sucks so much that it makes sense to be that way, and has so for years, something is still very wrong.
Regardless, if you're depression is because your life sucks so much that it makes sense to be that way, and has so for years, something is still very wrong.
Not necessarily. You can split a definition in many different ways depending on what you're trying to explore, but one way of differentiating types of depression is exogenous vs endogenous. Exogenous depression is a reasonable reaction to bad circumstances - a close family member dying - whereas endogenous depression is internally generated and not related to any circumstances. There are many different ways of talking about "depression", many of them talking about different things - one of the difficulties with psychological terminology is that often that it's just descriptive of someone's behaviour rather than underlying causes, because it's such a complex area.
Some people have existential anxiety and call it depression. Hell, some people have narrow Generalized Anxiety Disorder and still call it depression.
I think I have both, and it’s often hard to tell them apart.
Yes and no? In such a situation their brain has high confidence in a bad world. If the world is actually bad, then that's not a malfunction, but among the strengths of the predictive hypothesis is that it allows the same explanation for the malfunctioning and normal cases.
>If the world is actually bad, then that's not a malfunction
In either case the treatment is the same. Doctors and psychiatrists are powerless to do anything to actually put their patients in safe and wholesome environments.
In either case the treatment is the same. Doctors and psychiatrists are powerless to do anything to actually put their patients in safe and wholesome environments.
Absolutely true, and a huge issue in mental health treatment. That being said, I wonder if there's something to be said for medicine even in such situations. Maybe we should consider the basis for treatment to be 'is better able to function in current situation'. For instance, ADD is realistically just rounding out the wrong end of the focus bell curve, and depending on how much focus is needed in your day to day life you might be functional or nonfunctional with the same natural level.
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SituationAl depression.
A lot of people with an unknown medical issue are dismissed as depressed.
A lot of people with an unknown medical issue are dismissed as depressed.
> brain underweighs evidence from new experiences in favor of pre-existing [...] prior assumptions.
Isn't this what brains do typically, outside of depression?
I omitted the word "negative" from the quote as that part I don't think is universal. It still seems a somewhat limited modifier in modelling depression.
The linked article's paragraph on "lumping together depression and trauma" also seems to accidentally expand on this conflation. I understand the causes of depression are likely numerous, so natural tendencies of those not prone to depression can't be ruled out as contributory factors, but I'm not sure I see an argument there for their being significant.
Isn't this what brains do typically, outside of depression?
I omitted the word "negative" from the quote as that part I don't think is universal. It still seems a somewhat limited modifier in modelling depression.
The linked article's paragraph on "lumping together depression and trauma" also seems to accidentally expand on this conflation. I understand the causes of depression are likely numerous, so natural tendencies of those not prone to depression can't be ruled out as contributory factors, but I'm not sure I see an argument there for their being significant.
> I omitted the word "negative" from the quote as that part I don't think is universal.
For a definition of "depression", it is. If somebody always believes that everything is great, regardless of the evidence, that might be a problem, but that problem would not be called "depression".
> Isn't this what brains do typically, outside of depression?
No; the theory is that typical brains do a certain amount of consideration of new evidence, and depressed brains do less than that.
The same article goes on to point out that there must be more to it, since as described this model would still result in depression naturally clearing up.
For a definition of "depression", it is. If somebody always believes that everything is great, regardless of the evidence, that might be a problem, but that problem would not be called "depression".
> Isn't this what brains do typically, outside of depression?
No; the theory is that typical brains do a certain amount of consideration of new evidence, and depressed brains do less than that.
The same article goes on to point out that there must be more to it, since as described this model would still result in depression naturally clearing up.
[deleted]
Another good (and recurring[0]) resource for a model of depression can be Robert Sapolsky's Stanford lecture on it[1]
[0] https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que...
[1] https://www.youtube.com/watch?v=NOAgplgTxfc
[0] https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que...
[1] https://www.youtube.com/watch?v=NOAgplgTxfc
The sentence you cited is also (mutandi) a good description of mania.
What drugs are best at extinguishing those negative priors? Vorinostat worked for me when a slew of antidepressants did not, but it's hard to find and can have side effects. It was really astounding. I just felt normal, unafraid, but not in a weird amped up way as with Adderall. I could just talk to people fluidly and think normally.
Antidepressants aren't just used for depression, they're also used to treat a spectrum of anxiety disorders like OCD and panic disorder, although the doses used to treat anxiety disorders are much higher than those used for depression. I don't think the BDNF-related hypothesis explains the efficacy of antidepressants in treating anxiety disorders, but I could be wrong.
Under the maladaptive neuroplasticity theory which motivates the BDNF connection, I think anxiety could be taken into account naturally: just as depression is a maladaptive persistent overlearned estimate of the world as threatening, unrewarding, and pointless, which persists despite regular experiences which should falsify those beliefs and lead to learning (but doesn't), anxiety is persistent overestimation of risks which persist despite regular experiences of dangerous risks not happening which should lead to learning (but doesn't). So if boosts to neuroplasticity can help a depressive learn that life doesn't suck, it makes sense if boosts could also help an anxious person learn that life isn't so dangerous.
> just as depression is a maladaptive persistent overlearned estimate of the world as threatening, unrewarding, and pointless
That we can look at the lives of millions of people in America in 2021 and call their abject misery 'maladaptive' or 'overlearned' is ghastly. I know I'm supposed to offer more in an HN comment, and I'm not trying to call you names. But if I told that to someone in psychotherapy I'd deserve more than just losing my license.
I don't doubt that looking inside people's biology for clues about what's going on when they suffer these kinds of anguish is interesting or potentially helpful, but I can say two things quite confidently on the matter:
1) After 60 years of dominance, the biological-psychiatric project's track record is dismal and has failed to move any population-level needle on the levels of suffering it tries to study and ameliorate
2) Focusing on biology at the expense of questions about "context" or "environment" or "maybe this depressive is reacting exactly appropriately to their horrible existence" is a staggering waste of brainpower and money and time, and it leaves me at a loss for words. Outside of the social strata represented on HN (and probably within it to some degree) the world is "threatening, unrewarding, and pointless" for vast numbers of human beings, and I'd challenge anyone to sit in front of such a person and tell them to their face that it isn't. If there exist "regular experiences which should falsify those beliefs and lead to learning (but doesn't)", I got news for you: those experiences aren't prompting "learning" because they're not enough. This is like telling hungry people to feel more full after feeding them a saltine cracker.
You can't "cure" depression by pumping people full of prescribed psychotropics - the major mental health effort of the past half century - any more than you can do so by pumping them full of vodka. Address poverty, address violence, address a litany of social ills - and I mean really address them - and you'll see what happens to depression.
Excuse me, but this touched a nerve.
That we can look at the lives of millions of people in America in 2021 and call their abject misery 'maladaptive' or 'overlearned' is ghastly. I know I'm supposed to offer more in an HN comment, and I'm not trying to call you names. But if I told that to someone in psychotherapy I'd deserve more than just losing my license.
I don't doubt that looking inside people's biology for clues about what's going on when they suffer these kinds of anguish is interesting or potentially helpful, but I can say two things quite confidently on the matter:
1) After 60 years of dominance, the biological-psychiatric project's track record is dismal and has failed to move any population-level needle on the levels of suffering it tries to study and ameliorate
2) Focusing on biology at the expense of questions about "context" or "environment" or "maybe this depressive is reacting exactly appropriately to their horrible existence" is a staggering waste of brainpower and money and time, and it leaves me at a loss for words. Outside of the social strata represented on HN (and probably within it to some degree) the world is "threatening, unrewarding, and pointless" for vast numbers of human beings, and I'd challenge anyone to sit in front of such a person and tell them to their face that it isn't. If there exist "regular experiences which should falsify those beliefs and lead to learning (but doesn't)", I got news for you: those experiences aren't prompting "learning" because they're not enough. This is like telling hungry people to feel more full after feeding them a saltine cracker.
You can't "cure" depression by pumping people full of prescribed psychotropics - the major mental health effort of the past half century - any more than you can do so by pumping them full of vodka. Address poverty, address violence, address a litany of social ills - and I mean really address them - and you'll see what happens to depression.
Excuse me, but this touched a nerve.
That I never understood. US is an extremely rich country. Of course there are poor people, but there are lots of not poor people. In my country we don't have money if one does not work. He'll die from starvation. Well, probably some friends will help him not to die, but you got the idea. If you don't have a house, you don't really have any recourse, you have to live in basements under buildings and you'll eventually die as usual temperatures at winter are around -20 Celsius degrees. You can be beaten to death by some crazy person (well, at least you can't be shot, as guns are prohibited). People drive like crazy, so you can be killed by a car accident. If something unjust happens, you can't really rely on police, it might be corrupt and it happens in everyday life. If you need something from government, you might need to bribe the officials and I'm talking about ordinary person needs, not some enterprise stuff. I don't think that there are many grown-up people who did not bribe officials in their life.
Life is miserable here. And people don't run to hang themselves. They are trying to find happy moments and relish in those moments.
It's absolutely normal for a man to live in misery. Our humanity lived in misery for thousands of years and billions of people are living in misery right now. Our brain should be adapted to it by now.
Life is miserable here. And people don't run to hang themselves. They are trying to find happy moments and relish in those moments.
It's absolutely normal for a man to live in misery. Our humanity lived in misery for thousands of years and billions of people are living in misery right now. Our brain should be adapted to it by now.
Agreed, but depression in modern wealthy countries could potentially be less due to objectively comparable misery and pain on average and more due to a combined physiological, neurological, and psychological stagnation effect. It's very common to feel a profound dearth of meaning, purpose, higher goals, terminal goals, interpersonal connection, physical ambulation, sunlight, fresh air, or any idea of anything they should be doing but mindlessly scrolling some stream of text and projected imagery like a drug addict taking their 9th hit of the day while not actually feeling anything from it.
I know it's a tired trope to throw around at this point, but it just shows there are countless variables that factor into one's mood and disposition and sense of motivation even before you dig down to the neurological and biological levels. Leave a healthy, well-fed, "rich" rat or chimpanzee alone in a low-stimuli, not very large room for long enough and they'll often become depressed. Embed someone born in a wealthy country into an indigenous group and they often report feeling more alive and not depressed. Do the reverse and you often get the reverse.
And of course many people feel all these things not due to any sort of stagnation they have any personal control over but due to neurological systems which may be difficult to alter. Or both.
I think the original reply post may have partly misinterpreted what the commenter was trying to say. The hypothesis being discussed is something like that even if you reintroduce the rat back to its previous happy environment, their potential predictive processing dysfunction may cause them to not be able to do anything but treat all stimuli the same: not worth caring about or trying to derive enjoyment from.
I know it's a tired trope to throw around at this point, but it just shows there are countless variables that factor into one's mood and disposition and sense of motivation even before you dig down to the neurological and biological levels. Leave a healthy, well-fed, "rich" rat or chimpanzee alone in a low-stimuli, not very large room for long enough and they'll often become depressed. Embed someone born in a wealthy country into an indigenous group and they often report feeling more alive and not depressed. Do the reverse and you often get the reverse.
And of course many people feel all these things not due to any sort of stagnation they have any personal control over but due to neurological systems which may be difficult to alter. Or both.
I think the original reply post may have partly misinterpreted what the commenter was trying to say. The hypothesis being discussed is something like that even if you reintroduce the rat back to its previous happy environment, their potential predictive processing dysfunction may cause them to not be able to do anything but treat all stimuli the same: not worth caring about or trying to derive enjoyment from.
> Life is miserable here. And people don't run to hang themselves. They are trying to find happy moments and relish in those moments.
What country is this? Your domain seems to indicate Kazakhstan, but they have one of the highest suicide rates in the world, so I suppose that's not it?
What country is this? Your domain seems to indicate Kazakhstan, but they have one of the highest suicide rates in the world, so I suppose that's not it?
Depression is maladaptive. My environment was shitty and that’s part of how I developed depression, but depression didn’t make surviving that easier. It made it far, far worse. There were also good things in my life; but I couldn’t experience pleasure from those good things because of the depression. Even after I got out of that environment I couldn’t enjoy life.
Meds were a godsend. They allowed me to escape from depression long enough to deal with depression. Could I have done so even while still in a shitty environment? Probably, because the key ingredients for me were: meds, learning to identify good things, and not burying my feelings.
That’s not to say we shouldn’t be solving all these problems, but in the meantime let’s not tear down things that work for people because they don’t directly address a more intractable root cause.
Meds were a godsend. They allowed me to escape from depression long enough to deal with depression. Could I have done so even while still in a shitty environment? Probably, because the key ingredients for me were: meds, learning to identify good things, and not burying my feelings.
That’s not to say we shouldn’t be solving all these problems, but in the meantime let’s not tear down things that work for people because they don’t directly address a more intractable root cause.
There's a quotation from Abraham Maslow that I really like, which I think is similar to your point.
> I am deliberately rejecting our present easy distinction between sickness and health, at least as far as surface symptoms are concerned. Does sickness mean having symptoms? I maintain now that sickness might consist of not having symptoms when you should. Does health mean being symptom-free? I deny it. Which of the Nazis at Auschwitz or Dachau were healthy? Those with a stricken conscience or those with a nice, clear, happy conscience? Was it possible for a profoundly human person not to feel conflict, suffering, depression, rage, etc.? In a word if you tell me you have a personality problem, I am not certain until I know you better whether to say "Good" or "I'm sorry". It depends on the reasons. And these, it seems, may be bad reasons, or they may be good reasons.
https://en.wikiquote.org/wiki/Abraham_Maslow
> I am deliberately rejecting our present easy distinction between sickness and health, at least as far as surface symptoms are concerned. Does sickness mean having symptoms? I maintain now that sickness might consist of not having symptoms when you should. Does health mean being symptom-free? I deny it. Which of the Nazis at Auschwitz or Dachau were healthy? Those with a stricken conscience or those with a nice, clear, happy conscience? Was it possible for a profoundly human person not to feel conflict, suffering, depression, rage, etc.? In a word if you tell me you have a personality problem, I am not certain until I know you better whether to say "Good" or "I'm sorry". It depends on the reasons. And these, it seems, may be bad reasons, or they may be good reasons.
https://en.wikiquote.org/wiki/Abraham_Maslow
Well said.
I’ve used ADs as a “band-aid”: something for three months or so at a time when necessary, to stop me a) killing myself [though thankfully it’s been a long long time since I had those intrusive thoughts] and b) giving me just enough “normality” to go and make whatever changes I can that pushed me in the direction of an episode or made an extant one worse, and lastly c) give me enough motivation that I can work properly with my psychologist/psychotherapist.
I’ve had very good “reasons” for my crippling depression, but usually I can’t see the forest for the trees to work out what it is while deep inside the episode.
Luckily for me, citalopram works with basically no side effects when taken for a couple of months. I’m glad that’s the case, but I’ve seen so many of my friends get no relief from ADs at all, along with so many (sometimes life altering!) side effects, that it makes me sad at times.
Lastly, buprenorphine is remarkable for me in terms of its anti depressive effect. Once monthly Buvidal injection not only solves my past issues with drug abuse, but neatly solves my depression. Fascinating stuff.
I’ve used ADs as a “band-aid”: something for three months or so at a time when necessary, to stop me a) killing myself [though thankfully it’s been a long long time since I had those intrusive thoughts] and b) giving me just enough “normality” to go and make whatever changes I can that pushed me in the direction of an episode or made an extant one worse, and lastly c) give me enough motivation that I can work properly with my psychologist/psychotherapist.
I’ve had very good “reasons” for my crippling depression, but usually I can’t see the forest for the trees to work out what it is while deep inside the episode.
Luckily for me, citalopram works with basically no side effects when taken for a couple of months. I’m glad that’s the case, but I’ve seen so many of my friends get no relief from ADs at all, along with so many (sometimes life altering!) side effects, that it makes me sad at times.
Lastly, buprenorphine is remarkable for me in terms of its anti depressive effect. Once monthly Buvidal injection not only solves my past issues with drug abuse, but neatly solves my depression. Fascinating stuff.
> just as depression is a maladaptive persistent overlearned estimate of the world as threatening, unrewarding, and pointless, which persists despite regular experiences which should falsify those beliefs and lead to learning (but doesn't), anxiety is persistent overestimation of risks which
people with depression have been shown to have a more accurate perception of reality. it's the rose-colored glasses view which is adaptive.
people with depression have been shown to have a more accurate perception of reality. it's the rose-colored glasses view which is adaptive.
Is it actually maladaptive or society wide is it normal and adaptive? If everyone was so easily influenced or moved into different states - perhaps then the traits differentiating those who are more conservative or more liberal in their behaviours wouldn't be possible. There are lessons to be learned from suffering, your own and others - and people becoming so imbalanced that they are stuck in suffering is easily arguable as a canary for society and signal for how we treat others.
I thought life sucked and was on anti anxiety medications for year then realized I was simply allergic to half the food I was eating.
Your ancestors and my ancestors stuck around long enough to reproduce and raise their kids without offing themselves from depression, has something changed to make the environment less conducive to being a living human?
Your ancestors and my ancestors stuck around long enough to reproduce and raise their kids without offing themselves from depression, has something changed to make the environment less conducive to being a living human?
Obvious fallacy here: we are all descendants of those humans who survived - at least until having children. Those who offed themselves early are selected out of the genepool.
Note the above is not to suggest that there’s not a number of factors of a modern environment that we’re not properly/perfectly adapted for. But the handwavy “people weren’t depressed and anxious in the old days” is an illusion.
Note the above is not to suggest that there’s not a number of factors of a modern environment that we’re not properly/perfectly adapted for. But the handwavy “people weren’t depressed and anxious in the old days” is an illusion.
Hi, how did you find out you were allergic to half the food you were eating? I would like to know more about tests/elimination diets you have tried.
You'd be surprised what people can put up with cheerfully. A relative of mine turned out, around high school or so, to be allergic to wheat (which is in half the stuff you eat). It gave him regular diarrhea. He had grown up with it and simply assumed it was normal. How would he know otherwise? (A version of the 'typical mind fallacy' https://www.lesswrong.com/posts/baTWMegR42PAsH9qJ/generalizi... one might say.)
It's not as if people go around saying, 'good morning! I had my usual poop today, a good #3 on the Bristol stool scale, placing me within 1SD of the human norm! And yourself?' 'Likewise, likewise; good checking in with you and discussing our morning defecation, as is very normal for us human beings, ha ha.'
It's not as if people go around saying, 'good morning! I had my usual poop today, a good #3 on the Bristol stool scale, placing me within 1SD of the human norm! And yourself?' 'Likewise, likewise; good checking in with you and discussing our morning defecation, as is very normal for us human beings, ha ha.'
Start an elimination diet. Chicken and green vegetables are a good starting point.
I did chicken and sweet potatoes for a month. Had a ton of issues go away.
Turned out practically everything bothers me.
AIP diet has been a life changer.
Turned out practically everything bothers me.
AIP diet has been a life changer.
Go to an allergist. You may end up getting referred to a GI. But it's a sure-fire way to know if you have actual allergies or not.
Source: Wife's visit to allergist & subsequent referral to GI doc today (no allergies).
Source: Wife's visit to allergist & subsequent referral to GI doc today (no allergies).
I dont believe that people have anxiety disorders for no reason at all...
e.g. an autistic teenager who got beaten up for being socially clueless or abrasive. Anxiety might be the thing that saved them from being seriously harmed.
e.g. an autistic teenager who got beaten up for being socially clueless or abrasive. Anxiety might be the thing that saved them from being seriously harmed.
[deleted]
A perfect show of how little is know about the effect of those drugs:
>they're also used to treat a spectrum of anxiety disorders like OCD and panic disorder
A massive amount of people treated for depression have panic disorder because of these drugs, so they can treat or induce the same thing in different people.
>they're also used to treat a spectrum of anxiety disorders like OCD and panic disorder
A massive amount of people treated for depression have panic disorder because of these drugs, so they can treat or induce the same thing in different people.
And vice-versa. I'm taking vilazodone and lamotrigine (anti-epileptic), and they're just barely working.
Without going into too much detail on my own situation, in addition to other meds I'm also on Modafinil. This is mainly to combat fatigue side effects, but modafinil is also a very good (for me at least) anti-depressant. I'm depressed less often on it, and when depressed it keeps me much more functional. There's a decent body of research in its use for this purpose as a second-line anti-depressant, such as: https://pubmed.ncbi.nlm.nih.gov/16035049/
Not all doctors are familiar with its use in this way. When I had to switch doctors after mine retired, I had to educate them in its use so that they would continue prescribing it.
It is also not an automatic approval by insurance companies. However, if denied by your insurance, you can get it at a fairly reasonable price using GoodRX.
If you're still struggling after what you're already one, and have gone through a few other options (and maybe even if you haven't) then I would highly recommend talking to your doctor about this.
Something to keep in mind though is that this will, mostly in the first week, impact your sleeping patterns. Taking it first thing in the morning would be the best time, and perhaps ask your doctor about using an over-the-counter sleep aid such as diphenhydramine during initial usage.
Not all doctors are familiar with its use in this way. When I had to switch doctors after mine retired, I had to educate them in its use so that they would continue prescribing it.
It is also not an automatic approval by insurance companies. However, if denied by your insurance, you can get it at a fairly reasonable price using GoodRX.
If you're still struggling after what you're already one, and have gone through a few other options (and maybe even if you haven't) then I would highly recommend talking to your doctor about this.
Something to keep in mind though is that this will, mostly in the first week, impact your sleeping patterns. Taking it first thing in the morning would be the best time, and perhaps ask your doctor about using an over-the-counter sleep aid such as diphenhydramine during initial usage.
Out of curiosity, do you feel antidepressive qualities from other dopaminergic substances? (Part of modafinil's mechanism of action is thought to be dopaminergic.) Also, do you feel like you might have ADHD?
Just asking this out of curiosity, because I'm also someone who consistently experiences antidepressive effects from modafinil. Though for me it's typically more of a feeling that lasts for about 1 - 4 hours after use rather than a steady, stable mood lifting effect.
Just asking this out of curiosity, because I'm also someone who consistently experiences antidepressive effects from modafinil. Though for me it's typically more of a feeling that lasts for about 1 - 4 hours after use rather than a steady, stable mood lifting effect.
I took modafinil for about 6 months while having under treated depression. It only seemed to improve wakefulness like super caffeine minus jitters and anxiety.
Like mainly sleep “aids”, DPH just puts you into a fatigued state that is unlike naturalistic sleep. If insomnia / rumination / etc would otherwise keep one up and the diphenhydramine allows one to fall asleep and get a night of suboptimal sleep as opposed to no sleep, it’s of course worth it, but otherwise stay well away.
Interestingly almost everything that induces sleep harms the actual sleep quality. However I remember reading that GHB appears to improve sleep architecture, although I’ve never tried it personally
Interestingly almost everything that induces sleep harms the actual sleep quality. However I remember reading that GHB appears to improve sleep architecture, although I’ve never tried it personally
In general, DPH seems like a terrible anticholinergic and obsolete antihistamine with limited uses. My ex-stepfather abused it nightly as a "sleep aid," his personality altered, became very depressed, and I think entered a pre-dementia/Alzheimer's state sooner than he would've otherwise.
Probably not a good idea to experiment personally with GHB because it's Class I in the US and associated with date-rape, but it's worth considering in studies and research.
It does seem to be the case that disordered sleep is the keystone of depression; I can also confirm missing one dose of mirtazapine at night feels exactly like an alcohol-induced hangover in the morning. I suspect depression accumulates during sleep.
Interestingly, mirtazapine is a powerful H1 antihistamine that induces sleep at lower doses that are swamped by noradrenergic effects at higher doses. I would guess patients on mirtazapine have fewer incidents of seasonal allergies.
Probably not a good idea to experiment personally with GHB because it's Class I in the US and associated with date-rape, but it's worth considering in studies and research.
It does seem to be the case that disordered sleep is the keystone of depression; I can also confirm missing one dose of mirtazapine at night feels exactly like an alcohol-induced hangover in the morning. I suspect depression accumulates during sleep.
Interestingly, mirtazapine is a powerful H1 antihistamine that induces sleep at lower doses that are swamped by noradrenergic effects at higher doses. I would guess patients on mirtazapine have fewer incidents of seasonal allergies.
1. Modafinil is the opposite of a sleep aid, so the first paragraph doesn't really apply.
2. Using GHB/Alcohol/Marijuana to help you feel more rested really depends on if the person has a medical condition or not. All of these drugs will suppress REM sleep (so will your typical SSRI), which for the average person may not be a good thing. However, those with narcolepsy have a much higher rate of REM sleep, preventing their body from going into deep sleep and thus (says the hypothesis) they don't get the awakeness/alerting benefits from sleep.
Interestingly, those with depression and PTSD also have increased rates of REM sleep, so there is an interesting question of causality there.
2. Using GHB/Alcohol/Marijuana to help you feel more rested really depends on if the person has a medical condition or not. All of these drugs will suppress REM sleep (so will your typical SSRI), which for the average person may not be a good thing. However, those with narcolepsy have a much higher rate of REM sleep, preventing their body from going into deep sleep and thus (says the hypothesis) they don't get the awakeness/alerting benefits from sleep.
Interestingly, those with depression and PTSD also have increased rates of REM sleep, so there is an interesting question of causality there.
The first paragraph was about diphenhydramine (DPH) as a sleep aid. And I agree with the point. Any time I’ve tried to use it to help me sleep it sets me off on a downward spiral of bad sleep habits.
I can confirm DPH is awful. In general, I would only take it if were life-and-death.
>All of these drugs will suppress REM sleep (so will your typical SSRI)
Citation needed about the SSRI part, because one typical side effect of SSRIs is unusually vivid dreams.
Citation needed about the SSRI part, because one typical side effect of SSRIs is unusually vivid dreams.
"Reductions in the amount of REM sleep and increases in REM sleep onset latency are seen after taking antidepressants, both in healthy volunteers and in depressed patients. Antidepressants that increase serotonin function by blocking reuptake or by inhibiting metabolism have the greatest effect on REM sleep. The decrease in amount of REM sleep appears to be greatest early in treatment, and gradually diminishes during long-term treatment, except after monoamine oxidase inhibitors when REM sleep is often absent for many months."[1]
I agree that the two data points are paradoxical, and I'm not sure what to make of it. Personally I have a much larger than average amount of REM sleep (confirmed by professionals when I was tested for narcolepsy/daytime sleepiness), but I do not have vivid dreams and seldom recall dreaming at all, despite talking and moving in my sleep. Nevertheless it's quite interesting.
One hypothesis could be that less time in REM sleep leads to more intense bursts of REM, thus more vivid dreams? Or perhaps I am lacking knowledge and there is more to dreams than REM sleep.
[1]https://pubmed.ncbi.nlm.nih.gov/15892588/
I agree that the two data points are paradoxical, and I'm not sure what to make of it. Personally I have a much larger than average amount of REM sleep (confirmed by professionals when I was tested for narcolepsy/daytime sleepiness), but I do not have vivid dreams and seldom recall dreaming at all, despite talking and moving in my sleep. Nevertheless it's quite interesting.
One hypothesis could be that less time in REM sleep leads to more intense bursts of REM, thus more vivid dreams? Or perhaps I am lacking knowledge and there is more to dreams than REM sleep.
[1]https://pubmed.ncbi.nlm.nih.gov/15892588/
Trazodone actually improves sleep quality when you take it for insomnia. Oddly I looked it up and apparently there is no evidence it objectively improves start time for sleep, but it sure feels like it does.
Melatonin isn't too bad for actual sleep I think, but almost all supplements give you way too much - something like 1/3mg is enough. It does give me really bad dry eyes in the morning for some reason.
Melatonin isn't too bad for actual sleep I think, but almost all supplements give you way too much - something like 1/3mg is enough. It does give me really bad dry eyes in the morning for some reason.
Trazodone knocks me out. It also makes me lethargic the following day and less productive. I would only take half the lowest available dose (cut the lowest dose in half with a pill cutter) and it still gave me greatest sleep than anything else I'd ever tried. I still take it for flights and business travel (weird hotels) but otherwise it's too much for me.
For a number of years, Mirtazapine helped me sleep, although it reduced dreaming to nil. Interestingly, the antihistamine sedation effect of it decreases at increased doses.
I have Medicare now after a 9 year battle.
If you decide to switch up your medications, the strongest combination I ever found was Latuda and Remeron. Remeron also has a fairly light side effect profile for an anti-depressant, though weight gain can be a problem for a lot of people who take it.
This doesn't really seem to address how they work, in two fundamental ways:
1) We've had a good idea of the pharmacokinetics for a little while. All this research does is enhance that knowledge and take it one level deeper. Essentially, we've just gone one turtle lower in the pile of turtles standing on backs.
2) No theory of how antidepressants work will complete until we also understand why they so often do not work for many people.
1) We've had a good idea of the pharmacokinetics for a little while. All this research does is enhance that knowledge and take it one level deeper. Essentially, we've just gone one turtle lower in the pile of turtles standing on backs.
2) No theory of how antidepressants work will complete until we also understand why they so often do not work for many people.
Prior to this article, I’ve never heard of the theory that SSRIs works by improving BDNF. Was this actually a widely accepted possibility?
Agreed. This article doesn't address "how they work" - whether they "work" in the first place isn't at all clear, given how often they appear to either harm their users or simply do nothing - it's just elucidating "what they do" a little further. Two very different questions.
No small task, of course, and the paper's pretty interesting, but it's not clear this has anything to do with what we call depression.
No small task, of course, and the paper's pretty interesting, but it's not clear this has anything to do with what we call depression.
Trying to find how ADs work is like injecting a small piece of machine code to a running computer system and trying to find out what changes are produced. Its clinical effects are like the effects on the GUI.
There are many abstraction levels in the process and mostly we have to make large jumps over them.
Discl: I am a doctor specialized, among others, in adult psychiatry
There are many abstraction levels in the process and mostly we have to make large jumps over them.
Discl: I am a doctor specialized, among others, in adult psychiatry
While I appreciate the intention, I think it's a bad analogy.
Can you think of a small piece of machine code that you could inject into arbitrary computers that would produce useful effects in some significant proportion of the computer population? (Don't think so...)
Computers and biological systems are so wildly different. Although perhaps you'd find better analogies comparing brains to machine learning systems. Eg. "Trying to find out how ADs work is like applying some simple numerical transformation on some particular part of a deep neural network and trying to find out what changes are produced".
Oddly enough.. I think ML researchers often do find little "tricks" that improve the performance of neural nets without being able to fully grasp how or why. It's somewhat similar to how we use and understand ADs.
Can you think of a small piece of machine code that you could inject into arbitrary computers that would produce useful effects in some significant proportion of the computer population? (Don't think so...)
Computers and biological systems are so wildly different. Although perhaps you'd find better analogies comparing brains to machine learning systems. Eg. "Trying to find out how ADs work is like applying some simple numerical transformation on some particular part of a deep neural network and trying to find out what changes are produced".
Oddly enough.. I think ML researchers often do find little "tricks" that improve the performance of neural nets without being able to fully grasp how or why. It's somewhat similar to how we use and understand ADs.
Similarly, if you prescribe an AD to an 'arbitrary' person, most probably you do more harm than good, but I am sure you can find an appropriate code to try to 'cure' an 'ill' system.
The difference between biomedical and electronic systems vanishes when you approach them from the same abstraction levels, where the complexity of the brain forces us to stand: either extremely high (clinical/GUI) or extremely low (drugs/'therapeutic' machine code).
My understanding of brain is on par with that most of HW audience has about computers and vice-versa. So, as you correctly thought, the intent was to brigde this gap. Another analogy I like is, treating brain diseases with drugs is like repairing a car by spraying chemicals.
The difference between biomedical and electronic systems vanishes when you approach them from the same abstraction levels, where the complexity of the brain forces us to stand: either extremely high (clinical/GUI) or extremely low (drugs/'therapeutic' machine code).
My understanding of brain is on par with that most of HW audience has about computers and vice-versa. So, as you correctly thought, the intent was to brigde this gap. Another analogy I like is, treating brain diseases with drugs is like repairing a car by spraying chemicals.
Talk about arbitrary, on the pharmaceutical front some very revealing and somewhat forgotten info seems to be in the comments:
>anon the II says: 19 February, 2021 at 1:03 pm
>About 27 years ago, a little company that I worked for was going through another transmutation in order to survive. We became a high-throughput screening/combinatorial chemistry company. The CEO told a story about how, by the time anyone figured out that we didn’t know what we were doing, we might actually figure out what we were doing. I volunteered to be the technical lead on the combi-chem side. Anyhow, we managed to get bought by Lilly in 1994 and shortly afterwards, we got a visit from Bryan Malloy (https://en.wikipedia.org/wiki/Bryan_Molloy), the inventor of Prozac, who came down to see what his company had purchased. I met with Bryan and we had a lovely chat. But, he let me know that he thought that what we were doing was no better than “pissing in the wind”.
>I guess this means that he was doing much the same.
>anon the II says: 19 February, 2021 at 1:03 pm
>About 27 years ago, a little company that I worked for was going through another transmutation in order to survive. We became a high-throughput screening/combinatorial chemistry company. The CEO told a story about how, by the time anyone figured out that we didn’t know what we were doing, we might actually figure out what we were doing. I volunteered to be the technical lead on the combi-chem side. Anyhow, we managed to get bought by Lilly in 1994 and shortly afterwards, we got a visit from Bryan Malloy (https://en.wikipedia.org/wiki/Bryan_Molloy), the inventor of Prozac, who came down to see what his company had purchased. I met with Bryan and we had a lovely chat. But, he let me know that he thought that what we were doing was no better than “pissing in the wind”.
>I guess this means that he was doing much the same.
I have a feeling SSRIs work for a reason we would never expect. In fact, I have a feeling nearly all mental disorders work according to rules we do not even imagine now. It seems to me medical psychology has some great analogies to 1320s science, and the only answers that will come will be after my death.
There is an effective, rigorous school of psychology called Neurolinguistic Programming but it's got a bad rep in scientific/academic circles (the Wikipedia entry calls it out as pseudoscience.)
FWIW I was cured of a chronic, crushing depression in a single session that lasted no more than ten minutes or so. (I don't know exactly how long it was because I was in a deep trance. Subjectively it was only a few moments.)
FWIW I was cured of a chronic, crushing depression in a single session that lasted no more than ten minutes or so. (I don't know exactly how long it was because I was in a deep trance. Subjectively it was only a few moments.)
Hypnosis is effective, NLP is not. NLP is just combining a bunch of things that do work with a theory that someone just made up.
(Even the stuff that made it to education science doesn't work. There's no such thing as a "visual learner".)
(Even the stuff that made it to education science doesn't work. There's no such thing as a "visual learner".)
The things that work should get more attention from the mainstream psychologists IMO. (It's been nearly fifty years since we have had a cure for phobias. At some point it stops being funny and starts being tragic. Everyone today who has a phobia is suffering needlessly.)
As for the "theory that someone just made up." That sounds weird to me, because my experience has been that theory is treated as no more than a prop to support hypnosis. The emphasis is always on the pragmatic and empirical. If you go read the books like "TRANCE-Formations" they are really upfront that they have no idea why this stuff works.
Whatever NLP is, they collected "a bunch of things that do work" many of which no one ever noticed and wrote down before, eh?
As for the "theory that someone just made up." That sounds weird to me, because my experience has been that theory is treated as no more than a prop to support hypnosis. The emphasis is always on the pragmatic and empirical. If you go read the books like "TRANCE-Formations" they are really upfront that they have no idea why this stuff works.
Whatever NLP is, they collected "a bunch of things that do work" many of which no one ever noticed and wrote down before, eh?
What's the cure for phobias? A quick ddg search brought up CBT and exposure therapy, is this what you're referring to?
> CBT and exposure therapy, is this what you're referring to?
No, this is something totally different.
The core of the process is a double-disassociation and a kind of time reversal. You watch yourself watching yourself watching yourself and then play the movie backwards. Somehow that changes, quickly and durably, the way the brain responds (to kittens or elevators or whatever.)
Here's a brief video of Dr. Bandler talking about the background and how he developed it: https://www.youtube.com/watch?v=tGUXQRubBrY
And here's an example: https://www.youtube.com/watch?v=syIXq7e41sY
No, this is something totally different.
The core of the process is a double-disassociation and a kind of time reversal. You watch yourself watching yourself watching yourself and then play the movie backwards. Somehow that changes, quickly and durably, the way the brain responds (to kittens or elevators or whatever.)
Here's a brief video of Dr. Bandler talking about the background and how he developed it: https://www.youtube.com/watch?v=tGUXQRubBrY
And here's an example: https://www.youtube.com/watch?v=syIXq7e41sY
What the heck did they do in that session?
I made my first account just to respond since no one else has.
Think back to something that made you angry, that annoyed or frustrated you. Think back to a time where you got really riled up. A time where you were really pissed off at someone.
You're going to close your eyes for 20 seconds and think about it, feel it, really try to go back to that day and immerse yourself in that moment. Now, close your eyes.
Did you notice anything? Did anything in your body change in the last 20 seconds?
By thought alone, you can change your physiology, your mental state, your blood pressure and heart rate. Nothing in your environment changed, you're still sitting here reading this, yet to your brain you were momentarily somewhere else. For me, stuck in traffic and some wanker just cut me off, nearly caused an accident and seemed oblivious to it all. I wanted to crash my car into his just to teach him a lesson. It can make your blood boil just thinking back to past events where you were wronged.
I had you think back to something that made you angry, and you probably felt that same way you did that day but to a slightly lesser degree. If you continue to think about it, think about how wrong it was, you can feel EVEN MORE ANGRY. But you don't have to.
You can think back to these moments in your life and feel less or more of the emotion by altering the memory, or your perception of the event.
Your past influences who you are. Your past only exists as memories within your mind. Memories can be recalled and changed by your mind.
You can think back to past events and change the way you perceive them. That's the practice of NLP from my perspective. Changing your memories so that they benefit you.
All those times you've been embarrassed, angry, frustrated or annoyed, you can look back at these moments and laugh at them. Think about some negative moment in your life and then literally laugh out loud about how absurd it was.
Seeing a memory in your minds eye you can turn the colour down so it's only in greyscale. You can mute the person saying hurtful things, or change their voice to that of a cartoon character, something absurd and comical. While you're doing all this, recalling past events and memory manipulation, you're comparing your emotions and how your body is responding, before and after each change.
This might be something you can learn how to do in one session, but for me it took lots of purposeful practice. Like a muscle you develop, you become better at this over time.
Think back to something that made you angry, that annoyed or frustrated you. Think back to a time where you got really riled up. A time where you were really pissed off at someone.
You're going to close your eyes for 20 seconds and think about it, feel it, really try to go back to that day and immerse yourself in that moment. Now, close your eyes.
Did you notice anything? Did anything in your body change in the last 20 seconds?
By thought alone, you can change your physiology, your mental state, your blood pressure and heart rate. Nothing in your environment changed, you're still sitting here reading this, yet to your brain you were momentarily somewhere else. For me, stuck in traffic and some wanker just cut me off, nearly caused an accident and seemed oblivious to it all. I wanted to crash my car into his just to teach him a lesson. It can make your blood boil just thinking back to past events where you were wronged.
I had you think back to something that made you angry, and you probably felt that same way you did that day but to a slightly lesser degree. If you continue to think about it, think about how wrong it was, you can feel EVEN MORE ANGRY. But you don't have to.
You can think back to these moments in your life and feel less or more of the emotion by altering the memory, or your perception of the event.
Your past influences who you are. Your past only exists as memories within your mind. Memories can be recalled and changed by your mind.
You can think back to past events and change the way you perceive them. That's the practice of NLP from my perspective. Changing your memories so that they benefit you.
All those times you've been embarrassed, angry, frustrated or annoyed, you can look back at these moments and laugh at them. Think about some negative moment in your life and then literally laugh out loud about how absurd it was.
Seeing a memory in your minds eye you can turn the colour down so it's only in greyscale. You can mute the person saying hurtful things, or change their voice to that of a cartoon character, something absurd and comical. While you're doing all this, recalling past events and memory manipulation, you're comparing your emotions and how your body is responding, before and after each change.
This might be something you can learn how to do in one session, but for me it took lots of purposeful practice. Like a muscle you develop, you become better at this over time.
That's awesome! Well met.
I want to emphasis that NLP "is" lots of different things depending on who you ask. The most important aspect IMO is the act of "going meta-" to your own psychology, learning to "reprogram" your "biocomputer".
It's a fundamental shift. People talk about education that adds facts to your store of knowledge vs. education that changes who you are. Learning to operate your own mind+body changes your self-image in a deep way, and raises the level on which you operate.
What excites me is the possibility that enough people learn to take responsibility for their own thoughts and emotional reactions, and we can collectively get over our shit and make e.g. some sort of cool Star Trek future, where humans are mostly sane and healthy. (And "we can hang out with cool aliens that like us." ~Dude, Where's My Car?)
I want to emphasis that NLP "is" lots of different things depending on who you ask. The most important aspect IMO is the act of "going meta-" to your own psychology, learning to "reprogram" your "biocomputer".
It's a fundamental shift. People talk about education that adds facts to your store of knowledge vs. education that changes who you are. Learning to operate your own mind+body changes your self-image in a deep way, and raises the level on which you operate.
What excites me is the possibility that enough people learn to take responsibility for their own thoughts and emotional reactions, and we can collectively get over our shit and make e.g. some sort of cool Star Trek future, where humans are mostly sane and healthy. (And "we can hang out with cool aliens that like us." ~Dude, Where's My Car?)
Thank you for such a concise description. Now I understand what NLP is. Just created a laugh-out-loud image of one of my most painful job rejections.
I don't know. I was in a deep trance. Subjectively, I went up on stage (it was a demonstration at a seminar) sat down in a chair, closed my eyes, and the last thing I remember is Dr. Bandler saying something like "Oh I love it when they fight me..." and then a few moments of darkness and indescribable subjective somethings, then I opened my eyes. Later on people who were watching told me I was up there for about ten minutes.
Since then, except for one (terrifying) three-day period, I've been free from the depression that was ruining my life.
So yeah, like I say, I don't know what he did. (Frankly, in a sense, I don't care. I'm cured! I have a life!) I actually lost interest in NLP after that. I only promote it because it feels irresponsible not to, so many people are suffering needlessly and many of the solutions to their problems are right there if only they knew.
Since then, except for one (terrifying) three-day period, I've been free from the depression that was ruining my life.
So yeah, like I say, I don't know what he did. (Frankly, in a sense, I don't care. I'm cured! I have a life!) I actually lost interest in NLP after that. I only promote it because it feels irresponsible not to, so many people are suffering needlessly and many of the solutions to their problems are right there if only they knew.
They did this one weird trick! Doctors hate them!
I'm sure they'll tell us for just one easy payment.
Which is to say, it's probably just a simple lie - either one they are telling us, or one that has been told to them.
I'm sure they'll tell us for just one easy payment.
Which is to say, it's probably just a simple lie - either one they are telling us, or one that has been told to them.
Dude, I'm right here. You're calling me a liar|fool and that's not very civil. C'mon.
The seminar cost US$4000 but I only used about ten minutes of it. Best investment of my life.
Helped me stop being homeless and kick off my career as a professional programmer.
Ah, story time... I just remembered how I couldn't bring myself to go to CodeCon.
I had a ticket.
I got as close as the corner.
I just stood there and watched my fellow nerds walk up and go into the building for a while and then went home.
(You can't explain these things to normal people. They can't relate. My mom once said to me, "I know you're not faking this because no one would ever choose to be this miserable." which was actually more comforting than you might imagine.)
Anyway, next time, after my depression was cured, not only did I attend CodeCon, but I gave a presentation that went really well, and got my first job as a professional programmer. Literally a guy walked up to me after the presentation and asked if I would be willing to move.
Turns out with out the crushing depression holding me back I'm not too shabby. Yay!
- - - -
Ha! The audio of my presentation is on the Archive!
https://archive.org/details/codecon-2004-audio/CodeCon_2004-...
(Man, I sound so soupy. Packed nasal passages, no resonance. Allergies.)
I'm still bangin' away on the idea from time to time: https://sr.ht/~sforman/Xerblin/
The seminar cost US$4000 but I only used about ten minutes of it. Best investment of my life.
Helped me stop being homeless and kick off my career as a professional programmer.
Ah, story time... I just remembered how I couldn't bring myself to go to CodeCon.
I had a ticket.
I got as close as the corner.
I just stood there and watched my fellow nerds walk up and go into the building for a while and then went home.
(You can't explain these things to normal people. They can't relate. My mom once said to me, "I know you're not faking this because no one would ever choose to be this miserable." which was actually more comforting than you might imagine.)
Anyway, next time, after my depression was cured, not only did I attend CodeCon, but I gave a presentation that went really well, and got my first job as a professional programmer. Literally a guy walked up to me after the presentation and asked if I would be willing to move.
Turns out with out the crushing depression holding me back I'm not too shabby. Yay!
- - - -
Ha! The audio of my presentation is on the Archive!
https://archive.org/details/codecon-2004-audio/CodeCon_2004-...
(Man, I sound so soupy. Packed nasal passages, no resonance. Allergies.)
I'm still bangin' away on the idea from time to time: https://sr.ht/~sforman/Xerblin/
I'm sorry, but you're claiming you spent 4000 dollars and 10 minutes to cure a disease that millions of doctors and patients struggle with their entire lives. Furthermore, based on this personal experience, you claim that NLP is not the pure crackpot lunacy that it is, but some advanced, misunderstood science.
You may have personally been extremely lucky and experienced essentially a miracle.
But what you are claiming is similar to people claiming they cured cancer with healing crystals, or prayed the lupus away. There is no way to take your claim any more seriously: you are either lying or you experienced an extremely lucky break, and were lied to about the cause.
There is no other way to react to people promoting pseudoscience, especially in medicine. Someone else who is suffering could be duped by your well-meaning sharing of this experience into throwing their good money away on bullshit in hopes of reproducing a miracle.
You may have personally been extremely lucky and experienced essentially a miracle.
But what you are claiming is similar to people claiming they cured cancer with healing crystals, or prayed the lupus away. There is no way to take your claim any more seriously: you are either lying or you experienced an extremely lucky break, and were lied to about the cause.
There is no other way to react to people promoting pseudoscience, especially in medicine. Someone else who is suffering could be duped by your well-meaning sharing of this experience into throwing their good money away on bullshit in hopes of reproducing a miracle.
> you're claiming you spent 4000 dollars and 10 minutes to cure a disease that millions of doctors and patients struggle with their entire lives.
Yes. Exactly that.
(In a sense I did get lucky: Dr. Bandler could have picked someone else for the demo.)
> based on this personal experience,
And a lot of other personal experience, and a pretty good understanding of the formal grammar analysis that spawned it (and that also underpins computer languages.)
> you claim that NLP is not the pure crackpot lunacy that it is,
That you claim it is...
Do you have any experience? I find a common denominator among strident skeptics like yourself is that they have no actual experience and have done no personal investigation. Are you an armchair skeptic? Have you any experience whatsoever with hypnosis or NLP?
> but some advanced, misunderstood
...yes...
> science.
No. Not yet. But it should be.
You insist that I must be a liar or a fool and yet you would prefer a miracle to rational investigation.
Well I'm no liar, but certainly one of us (at least) is a fool.
Good day sir.
Yes. Exactly that.
(In a sense I did get lucky: Dr. Bandler could have picked someone else for the demo.)
> based on this personal experience,
And a lot of other personal experience, and a pretty good understanding of the formal grammar analysis that spawned it (and that also underpins computer languages.)
> you claim that NLP is not the pure crackpot lunacy that it is,
That you claim it is...
Do you have any experience? I find a common denominator among strident skeptics like yourself is that they have no actual experience and have done no personal investigation. Are you an armchair skeptic? Have you any experience whatsoever with hypnosis or NLP?
> but some advanced, misunderstood
...yes...
> science.
No. Not yet. But it should be.
You insist that I must be a liar or a fool and yet you would prefer a miracle to rational investigation.
Well I'm no liar, but certainly one of us (at least) is a fool.
Good day sir.
> And a lot of other personal experience, and a pretty good understanding of the formal grammar analysis that spawned it (and that also underpins computer languages.)
You see, this is where you lose me. Chomsky's work has absolutely no applicability to treating mental illness, and he would be the first to explain that. His work is not even applicable to language translation, and has no hope of being in the foreseeable future. It is just a framework for discussing some basics of how human language works and can be learned.
Hell, it's barely applicable to computer languages, where again, it's only a framework for discussion. It certainly doesn't 'underpin' computer languages (the work of Alan Turing, John von Neumann and others does instead).
> Have you any experience whatsoever with hypnosis or NLP?
No, and neither do I with crystal healing, praying the lupus away, acupuncture and a myriad others.
You see, this is where you lose me. Chomsky's work has absolutely no applicability to treating mental illness, and he would be the first to explain that. His work is not even applicable to language translation, and has no hope of being in the foreseeable future. It is just a framework for discussing some basics of how human language works and can be learned.
Hell, it's barely applicable to computer languages, where again, it's only a framework for discussion. It certainly doesn't 'underpin' computer languages (the work of Alan Turing, John von Neumann and others does instead).
> Have you any experience whatsoever with hypnosis or NLP?
No, and neither do I with crystal healing, praying the lupus away, acupuncture and a myriad others.
If history is any guide it involved an ice pick.
Would you please stop posting unsubstantive and/or flamebait comments to HN? You've been doing it repeatedly and we ban that sort of account. We're trying for something different here.
https://news.ycombinator.com/newsguidelines.html
https://news.ycombinator.com/newsguidelines.html
Yeah it's pretty much witchcraft at this point still.
Funny you should put it that way, because Psychiatry as a field historically evolved directly out of the witch hunts of the Inquisition.[1]
As the Church fell out of favor during the Enlightenment the very first Psychiatrists literally asserted that all the people who were labeled witches by the Inquisition were actually just "mentally ill", even though their understanding of the mind and their methods used to "treat" it (torture, mostly) had hardly changed at all.
[1]https://www.amazon.com/Manufacture-Madness-Comparative-Inqui...
As the Church fell out of favor during the Enlightenment the very first Psychiatrists literally asserted that all the people who were labeled witches by the Inquisition were actually just "mentally ill", even though their understanding of the mind and their methods used to "treat" it (torture, mostly) had hardly changed at all.
[1]https://www.amazon.com/Manufacture-Madness-Comparative-Inqui...
Nuplazid seems to have a pretty clear theory of what it is doing.
It's an anti-psychotic that is currently targeted at Parkinson's disease related psychosis; hallucinations and delusions are fairly common in people with Parkinson's disease.
It's an anti-psychotic that is currently targeted at Parkinson's disease related psychosis; hallucinations and delusions are fairly common in people with Parkinson's disease.
So cholesterol plays a huge role! The brain is the fattiest organ, so it makes a lot of sense. That we haven't found a correlation between statins and depression is certainly a quandary though.
I wonder if our national obsession with anti-fat dietary advice has had an impact on depression's prevalence in our population. It would seem to make sense that if we depress people with low-fat frankenfoods they naturally react with lower physical activity levels.
I wonder if omega-3 / omega-6 dietary balance changes the structure of the cell membranes to make them less permeable. Greater omega-3 cell membrane composition certainly seems to have a real impact on retina cells and the overall function of the retina[1].
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174995/
I wonder if our national obsession with anti-fat dietary advice has had an impact on depression's prevalence in our population. It would seem to make sense that if we depress people with low-fat frankenfoods they naturally react with lower physical activity levels.
I wonder if omega-3 / omega-6 dietary balance changes the structure of the cell membranes to make them less permeable. Greater omega-3 cell membrane composition certainly seems to have a real impact on retina cells and the overall function of the retina[1].
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174995/
You might be on to something. I think what the US has done to yogurt should be banned under the Geneva convention.
What did the US do to yogurt?
Almost every yogurt is full of added sugar. Sometimes the ingredients pretend it isn't sugar by calling it "evaporated cane juice".
You can get actual healthy yogurt with plain Greek yogurt or skyr, though, it's not hard anymore.
You can get actual healthy yogurt with plain Greek yogurt or skyr, though, it's not hard anymore.
We switched to Skyr and now all other yogurts taste disgustingly sweet to me. I've been cutting sugar way back and even a regular Boba tea was grossly sweet now. I'm taking it to mean this is working!
Basically, you have to go to specialty food stores (the arabian ones are really awesome from my experience) to actually find yogurt that's deserving of the name. For some reason the yogurt sold in regular supermarkets in the US is 'low fat' and 'strange consistency'.
I can buy full fat goat milk yogurt at 5 different grocery stores within 2 miles of my house here in the good ol' US of A.
I'm honestly glad to hear that, it's been a while since I've been to the US and I was quite confused about the yogurt-availability back then :D
(Or maybe I was just unlucky and in an anti-full-fat-yogurt part of the country.)
Most of the cholesterol in your body is synthesized, not from your diet.
Cholesterols are a family of lipids (lipoproteins to be precise), not just one thing molecule.
I've seen you say this a couple of times, but cholesterol in this context refers to something very specific. Essentially the ratio of cholesterol to other lipids in the cell membrane has influence on the bilayer dynamics of lipid raft formation and in this case receptor orientation.
Will this make the "chemical imbalance" (i.e. low-serotonin) theory of depression obsolete once and for all?
I’ve always understood the chemical imbalance description of depression (and other mental health conditions) to be a casual way of describing the conditions as being part of the person rather than a choice — and not a way to describe the internal mechanics of the conditions. I’ve found it effective when having conversations about mental health conditions: how would you describe depression without using that phrase, based on what this paper reveals?
I'm not saying there isn't a biochemical component to depression (or any other mood disorders). The specific theory that I'm talking about is "low serotonin causes depression" (as in the proximate cause, not the ultimate cause). When SSRIs were first discovered to be useful for treating depression, one of the theories about why they worked was that they boosted levels of serotonin, but we know now that's not true. It doesn't mean it can't be explained in other ways (like the one this article discusses).
Also, if there is a behavioral component to depression as well, then it doesn't necessarily mean someone is to blame for their disorder. You don't control the environment you grow up in, which has an enormous impact even on traits that are highly heritable (the whole subject of heritability is very misunderstood anyway).
So basically if I were going to describe depression's cause, I'd say it's a mixture of biochemical reactions, behavioural traits, and environmental stresses that cause it.
Also, if there is a behavioral component to depression as well, then it doesn't necessarily mean someone is to blame for their disorder. You don't control the environment you grow up in, which has an enormous impact even on traits that are highly heritable (the whole subject of heritability is very misunderstood anyway).
So basically if I were going to describe depression's cause, I'd say it's a mixture of biochemical reactions, behavioural traits, and environmental stresses that cause it.
A behavioral component manifests itself as a chemical process within the brain. So it may be used to explain the cause of certain chemical processes, but it's still the chemical processes that have to be dealt with. Though it doesn't necessarily follow that a chemical intervention is necessary: If the cause of the chemical change was behavioral, the solution might be as well, such in the form of various type of therapy.
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In the article they discuss that known SSRIs weakly bind a different receptor which may be why they have an antidepressant effect. It would explain why more specific SSRIs that are thought to target serotonin receptors selectively do not work.
That they see a bunch of them doing the same thing is pretty convincing.
to quote: "Now to the BDNF hypothesis. I used the phrase “unknown mechanism” above, and that’s exactly what this work may have cleared up. The authors show that when the TrkB protein forms a dimer in the cell membrane, a binding site for small molecules is formed at the interface. A whole list of known antidepressants (fluoxetine, imipramine, venlafaxine, moclobemide, ketamine, esketamine, and R,R-hydroxynorketamine) bind to this site at about 1 micromolar levels (and can displace each other in binding assays(, while a set of control CNS compounds like chlorpromazine, diphenhydramine, and indeed S,S-hydroxynorketamine do not. It will not be lost on those who’ve done research in the field that the antidepressant compounds listed above have been thought to work through completely different mechanisms. "
to quote: "Now to the BDNF hypothesis. I used the phrase “unknown mechanism” above, and that’s exactly what this work may have cleared up. The authors show that when the TrkB protein forms a dimer in the cell membrane, a binding site for small molecules is formed at the interface. A whole list of known antidepressants (fluoxetine, imipramine, venlafaxine, moclobemide, ketamine, esketamine, and R,R-hydroxynorketamine) bind to this site at about 1 micromolar levels (and can displace each other in binding assays(, while a set of control CNS compounds like chlorpromazine, diphenhydramine, and indeed S,S-hydroxynorketamine do not. It will not be lost on those who’ve done research in the field that the antidepressant compounds listed above have been thought to work through completely different mechanisms. "
How antidepressants work (this article) and what causes depression (your postulate) are two completely different things.
"The monoamine hypothesis, like the neurotrophic hypothesis, is at best incomplete. Many studies have not found an alteration in function or levels of monoamines in depressed patients. In addition, some candidate antidepressant agents under study do not act directly on the monoamine system. In addition to the monoamines, the excitatory neurotransmitter glutamate appears to be important in the pathophysiology of depression. A number of studies of depressed patients have found elevated glutamate content in the cerebrospinal fluid of depressed patients and decreased glutamine/glutamate ratios in their plasma.
In addition, postmortem studies have revealed significant increases in the frontal and dorsolateral prefrontal cortex of depressed patients. Likewise, structural neuroimaging studies have consistently found volumetric changes in the brain areas of depressed patients in which glutamate neurons and their connections are most abundant, including the amygdala and hippocampus."
"Given the effect of antidepressants on the glutamate system, there has been a growing interest in the development of pharmaceutical agents that might modulate the glutamate system. Ketamine is a potent, high-affinity, noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist that has long been used in anesthesia and is a common drug of abuse in some parts of the world."
Novel antidepressants now are NMDA receptor antagonists, or take a look at tianeptine which works just as well, yet it only affects your opioid receptors. None of which have to do with the monoamine hypothesis.
"Given the effect of antidepressants on the glutamate system, there has been a growing interest in the development of pharmaceutical agents that might modulate the glutamate system. Ketamine is a potent, high-affinity, noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist that has long been used in anesthesia and is a common drug of abuse in some parts of the world."
Novel antidepressants now are NMDA receptor antagonists, or take a look at tianeptine which works just as well, yet it only affects your opioid receptors. None of which have to do with the monoamine hypothesis.
Forgive my ignorance, but what alternative is there to a chemical imbalance of some sort? Structural differences? I have schizoaffective bipolar subtype, and wouldn't mind some links to more current literature, I'm obviously very behind.
It used to be the case that the theory for why people have depression was "people who are depressed don't have enough serotonin" (in very simple terms), and the reason why SSRIs work was supposed to be that they increase levels of serotonin, but scientists have found that boosting levels of serotonin alone does not help with depression.
Here's a good journal article on the subject https://sci-hub.st/https://www.sciencedirect.com/science/art...
Here's a good journal article on the subject https://sci-hub.st/https://www.sciencedirect.com/science/art...
After a long battle with depression, this is how I interpret the phenomenon that "boosting" serotonin levels does not work.
SSRI's do not increase the pool of available serotonin, they just artificially increase the amount that remains in the synaptic cleft, facilitating additional firing of the neuron (or for a longer duration, I'm not sure which). They do not increase a neuron's ability to synthesize serotonin and release it into the synaptic cleft at the appropriate time. SSRI's cause our neurons to reuse serotonin longer than they normally would, which is not how we evolved to use serotonin.
The way this felt to me as a human interacting with the world around me was artificial happiness and artificial feelings of ease. I felt "better", but it didn't feel like it was grounded in anything real. I felt happy when happy things happened, but I also felt happy when sad things happened. Eventually it wore off and SSRI's no longer had any effect on me.
I eventually tried tryptophan and B vitamins (specifically B6), which our bodies use to synthesize serotonin. I got a similar effect to when I first started SSRI's, but it felt real. I was able to be happy when something happy happened. But when something sad happened I also felt sad. This effect has endured for 4 years now.
I have since found that I had a serious problem with a particular toxin which poisons many of the pathways involved with serotonin synthesis (among many many others including one of the most fundamental, the Citrate Cycle). A way around the poisoning is large doses of the appropriate nutrients. This is because the toxicity causes serious inefficiencies in their use by the body's biochemical pathways.
This was my personal experience. Depression is caused by many factors and I'm sure what works for me would not work for many. It can be genetic issues, other kinds of toxins, and overwhelming amount of trauma, chronic infections, unhealthy relationships, etc. Or a combination of those.
SSRI's do not increase the pool of available serotonin, they just artificially increase the amount that remains in the synaptic cleft, facilitating additional firing of the neuron (or for a longer duration, I'm not sure which). They do not increase a neuron's ability to synthesize serotonin and release it into the synaptic cleft at the appropriate time. SSRI's cause our neurons to reuse serotonin longer than they normally would, which is not how we evolved to use serotonin.
The way this felt to me as a human interacting with the world around me was artificial happiness and artificial feelings of ease. I felt "better", but it didn't feel like it was grounded in anything real. I felt happy when happy things happened, but I also felt happy when sad things happened. Eventually it wore off and SSRI's no longer had any effect on me.
I eventually tried tryptophan and B vitamins (specifically B6), which our bodies use to synthesize serotonin. I got a similar effect to when I first started SSRI's, but it felt real. I was able to be happy when something happy happened. But when something sad happened I also felt sad. This effect has endured for 4 years now.
I have since found that I had a serious problem with a particular toxin which poisons many of the pathways involved with serotonin synthesis (among many many others including one of the most fundamental, the Citrate Cycle). A way around the poisoning is large doses of the appropriate nutrients. This is because the toxicity causes serious inefficiencies in their use by the body's biochemical pathways.
This was my personal experience. Depression is caused by many factors and I'm sure what works for me would not work for many. It can be genetic issues, other kinds of toxins, and overwhelming amount of trauma, chronic infections, unhealthy relationships, etc. Or a combination of those.
Can you post more about the cause? I'm not familiar with this toxicity as a cause of depression. Thanks!
Sure. I usually don't bring it up unless asked because it is very controversial.
Chronic mercury toxicity was the cause. I've confirmed this diagnosis with dramatic improvement to chelation therapy. I've also done some novel testing that indirectly confirms the diagnosis. It's not something you can test for directly unless you start taking biopsies of tissues you wouldn't want to cut out of someone alive. It resides in "deeper" tissues, not in the blood. The effect of mercury on biochemical pathways has been mapped out quite extensively, and we even know what and why certain genes make some people more susceptible than others. Not something you'll find in mainstream medicine, but the research is extensive and still rapidly growing. Particularly in the toxicology and chemistry circles.
I use a newer chelator called emeramide. It's currently in Phase II clinical trials and will probably be approved within 10 years. Although, it can be very dangerous if someone takes a too large of a dose, and the person pushing it through FDA approval does not seem to be fully aware of how bad it can be. Generally, the sicker you are the lower the dose you need to start on. This phenomenon is extensively documented in the Facebook groups where mercury toxic people discuss their experiences and results.
Emeramide binds to mercury the strongest, but also chelates other toxic metals like lead and cadmium, so those could certainly be complicating factors. Especially lead, as I grew up in a home and neighborhood with lots of it.
As for where the mercury came from, the timeline of my symptoms, animal toxicology studies, and it's removal in 2001, and more, all point towards the vax(inations I received as a child. For example, I had random and inexplicable symptoms as a kid like attacks of projectile vomiting without being sick, and bloody noses that would last for hours.
Chronic mercury toxicity was the cause. I've confirmed this diagnosis with dramatic improvement to chelation therapy. I've also done some novel testing that indirectly confirms the diagnosis. It's not something you can test for directly unless you start taking biopsies of tissues you wouldn't want to cut out of someone alive. It resides in "deeper" tissues, not in the blood. The effect of mercury on biochemical pathways has been mapped out quite extensively, and we even know what and why certain genes make some people more susceptible than others. Not something you'll find in mainstream medicine, but the research is extensive and still rapidly growing. Particularly in the toxicology and chemistry circles.
I use a newer chelator called emeramide. It's currently in Phase II clinical trials and will probably be approved within 10 years. Although, it can be very dangerous if someone takes a too large of a dose, and the person pushing it through FDA approval does not seem to be fully aware of how bad it can be. Generally, the sicker you are the lower the dose you need to start on. This phenomenon is extensively documented in the Facebook groups where mercury toxic people discuss their experiences and results.
Emeramide binds to mercury the strongest, but also chelates other toxic metals like lead and cadmium, so those could certainly be complicating factors. Especially lead, as I grew up in a home and neighborhood with lots of it.
As for where the mercury came from, the timeline of my symptoms, animal toxicology studies, and it's removal in 2001, and more, all point towards the vax(inations I received as a child. For example, I had random and inexplicable symptoms as a kid like attacks of projectile vomiting without being sick, and bloody noses that would last for hours.
Thanks for the context, very interesting. When did you get those shots as a child (ie what year, if you don't mind), and do you have any sense of which ones might have been the cause?
My parents followed the usual schedule. I was born in 1986. I'm not sure what the schedule was exactly back then, but I had several shots under the age of 5, a few more leading up to age 10, and a few more up until my last shot in 2016. Iirc the majority of them before 2001 included thimerosal as a preservative. I don't think any one shot was a specific cause, and rather it was a cumulative thing. I do know that the MMR shot does not contain thimerosal.
This FDA Q&A is a good read, although obviously biased against my perspective:
https://www.fda.gov/vaccines-blood-biologics/vaccines/thimer...
The FDA does acknowledge that kids in my generation were exposed to mercury slightly exceeding the established safety limit for oral exposure, but makes no mention as to how it is not appropriate to use an oral limit when the exposure is through injection. Toxicologists know that the exposure route makes all the difference in how toxic a substance is, and it is specifically written into environmental regulations like RCRA. For example, ingested substances are first directed straight to the liver through the portal vein for detoxification before being spread to the rest of the body. Injected substances bypass this defense mechanism. No exposure limits have ever been developed for injection, because the laws are all written for pollution, and people obviously do not inject pollution into themselves. (I was an environmental engineer for several years.)
That FDA Q&A also discusses how there was a lot of concern expressed by healthcare professionals regarding thimerosal, and that's why it was (mostly) removed, but they stress that it was just to be safe, and they have no reason to believe that it's dangerous. To be honest, it sounds like covering-their-ass double-speak to me, and reminds me of how polluting companies handle their coverups. The reality is that these things are so difficult to prove one way or the other, and the liability and denial issues are immense. No one wants to admit to themselves or others that they accidentally poisoned someone. Not just for financial reasons but for their own psychological well-being.
This FDA Q&A is a good read, although obviously biased against my perspective:
https://www.fda.gov/vaccines-blood-biologics/vaccines/thimer...
The FDA does acknowledge that kids in my generation were exposed to mercury slightly exceeding the established safety limit for oral exposure, but makes no mention as to how it is not appropriate to use an oral limit when the exposure is through injection. Toxicologists know that the exposure route makes all the difference in how toxic a substance is, and it is specifically written into environmental regulations like RCRA. For example, ingested substances are first directed straight to the liver through the portal vein for detoxification before being spread to the rest of the body. Injected substances bypass this defense mechanism. No exposure limits have ever been developed for injection, because the laws are all written for pollution, and people obviously do not inject pollution into themselves. (I was an environmental engineer for several years.)
That FDA Q&A also discusses how there was a lot of concern expressed by healthcare professionals regarding thimerosal, and that's why it was (mostly) removed, but they stress that it was just to be safe, and they have no reason to believe that it's dangerous. To be honest, it sounds like covering-their-ass double-speak to me, and reminds me of how polluting companies handle their coverups. The reality is that these things are so difficult to prove one way or the other, and the liability and denial issues are immense. No one wants to admit to themselves or others that they accidentally poisoned someone. Not just for financial reasons but for their own psychological well-being.
If that theory is definitely wrong, it hasn't yet worked its way out of common use. Examples:
NHS current website "This type of medication [SSRIs] works by increasing the level of a chemical called serotonin in your brain." https://www.nhs.uk/conditions/generalised-anxiety-disorder/t...
Wikipedia "It is believed to work by blocking the re-uptake of the chemical serotonin by neurons in the brain." https://en.wikipedia.org/wiki/Paroxetine
etc.
NHS current website "This type of medication [SSRIs] works by increasing the level of a chemical called serotonin in your brain." https://www.nhs.uk/conditions/generalised-anxiety-disorder/t...
Wikipedia "It is believed to work by blocking the re-uptake of the chemical serotonin by neurons in the brain." https://en.wikipedia.org/wiki/Paroxetine
etc.
I'm not sure that the reason why some (e.g. official) health information sources keep repeating that isn't just a combination of having an easy explanation and making a (benign) attempt to induce a placebo effect in unknowledgeable patients.
If you either get massively technical about complex things that would make most laymen's heads spin, or shrugged your shoulders and said that we don't really know, you might miss on the potential psychological effects that you can get by projecting some kind of confidence.
If you either get massively technical about complex things that would make most laymen's heads spin, or shrugged your shoulders and said that we don't really know, you might miss on the potential psychological effects that you can get by projecting some kind of confidence.
It’s a bit like saying a software bug is caused by “differing levels of electricity”.
"Low serotonin" was never the actual medical position on why antidepressants worked, it was marketing. The medical position is "we don't know why they work"; some antidepressants actually lower serotonin (SNRI) and some increase it (SSRI) and they both seem to help.
Also, they take weeks to take effect which doesn't make sense for a neurotransmitter effect, since Adderall (which raises dopamine) works instantly for ADHD.
I've heard theories that just doing anything to your brain knocks it out of state enough to stop being depressed (eg psychadelics do this), or that antidepressants actually improve your sleep quality and your brain cleans itself up over time.
Also, they take weeks to take effect which doesn't make sense for a neurotransmitter effect, since Adderall (which raises dopamine) works instantly for ADHD.
I've heard theories that just doing anything to your brain knocks it out of state enough to stop being depressed (eg psychadelics do this), or that antidepressants actually improve your sleep quality and your brain cleans itself up over time.
Where do you see SNRI lowers serotonin?
It's a re-uptake inhibitor for both serotonin and norepinephrine which keeps your body from flushing our those chemicals which raises serotonin levels as long as production is stable.
High doses of SNRI will contribute to Serotonin syndrome, which makes your argument hard to believe.
It's a re-uptake inhibitor for both serotonin and norepinephrine which keeps your body from flushing our those chemicals which raises serotonin levels as long as production is stable.
High doses of SNRI will contribute to Serotonin syndrome, which makes your argument hard to believe.
Oh, I was going from memory, so I guess that part's wrong.
But there are effective antidepressants that aren't strongly based on the serotonin effects SSRIs have, like trazodone (weakly increases it) and especially ketamine (doesn't do it, works better than most antidepressants, works near-instantly instead of taking weeks).
But there are effective antidepressants that aren't strongly based on the serotonin effects SSRIs have, like trazodone (weakly increases it) and especially ketamine (doesn't do it, works better than most antidepressants, works near-instantly instead of taking weeks).
And I would like to add that ketamine has nothing to do with the monoamine hypothesis, it is an NMDA receptor antagonist. It has nothing to do with serotonin, dopamine, and noradrenalin.
See my other comment about the growing interest in the glutamate system instead of serotonin and the like.
See my other comment about the growing interest in the glutamate system instead of serotonin and the like.
Can you please explain what seratonin syndrome is, particularly (like the above hypnosis / nlp split) where the edge of medical literature is? Highly interested, however for some reason was previously inclided to believe the phenomenon did not exist, akin to how adrenal fatigue can't be proven.
> "Low serotonin" was never the actual medical position on why antidepressants worked, it was marketing. The medical position is "we don't know why they work"; some antidepressants actually lower serotonin (SNRI) and some increase it (SSRI) and they both seem to help.
This just isn't the case. Maybe the more accurate thing to say is that there have been a few "medical positions" on this issue in the past six to eight decades, and "low serotonin" as well as "we don't know how they work" were both out there in the ether. But even that's not fully accurate, because you'd have to be pretty bold to argue that there wasn't a dominant "medical position" on the matter since biological psychiatry finished supplanting the Freudians for control of the field in the 1970s. The dominant position was the chemical imbalance theory, of which "low serotonin" was one of several variations trotted out over the years to both the public and the medical community.
Psychiatry is one of the medical specialties most profoundly co-opted by pharmaceutical industry interests, and both research and clinical practice have been rife with the effects of this influence. You don't even have to appeal to systematic analyses of how profoundly poor the quality of psychiatric research is, or how much pharma ghostwrites those studies, or anything of the kind. You can just ask a researcher in cancer or in neurology; they'll happily tell you.
To cleave the "medical position" from "marketing", as in your comment, elides what really happened: marketing decided what the medical position would be, and both doctors and the public mostly bought it.
This just isn't the case. Maybe the more accurate thing to say is that there have been a few "medical positions" on this issue in the past six to eight decades, and "low serotonin" as well as "we don't know how they work" were both out there in the ether. But even that's not fully accurate, because you'd have to be pretty bold to argue that there wasn't a dominant "medical position" on the matter since biological psychiatry finished supplanting the Freudians for control of the field in the 1970s. The dominant position was the chemical imbalance theory, of which "low serotonin" was one of several variations trotted out over the years to both the public and the medical community.
Psychiatry is one of the medical specialties most profoundly co-opted by pharmaceutical industry interests, and both research and clinical practice have been rife with the effects of this influence. You don't even have to appeal to systematic analyses of how profoundly poor the quality of psychiatric research is, or how much pharma ghostwrites those studies, or anything of the kind. You can just ask a researcher in cancer or in neurology; they'll happily tell you.
To cleave the "medical position" from "marketing", as in your comment, elides what really happened: marketing decided what the medical position would be, and both doctors and the public mostly bought it.
Have you ever tried Niacin/magnesium approach for treatment?
That theory makes as much sense as the theory that "chemical imbalances" (i.e. low-alcohol) cause social anxiety.
Alcohols are produced in your brain naturally and adding more changes behavior. Clinical trials show that more alcohol increases sociability compared to placebos (but with side effects). There are some concerns about giving alcohol to three year olds, but it is better that they become socialized at a young age than deal with the consequences for life.
In short: science + tons of money = not science.
Alcohols are produced in your brain naturally and adding more changes behavior. Clinical trials show that more alcohol increases sociability compared to placebos (but with side effects). There are some concerns about giving alcohol to three year olds, but it is better that they become socialized at a young age than deal with the consequences for life.
In short: science + tons of money = not science.
I don’t know, tons of alcohol makes me very social ;)
I am not a neuro anything, but has that been the a big debate in the antidepressant discussion long? The low level of serotonin? Is that a fallacy or an i missing something?
It's been a persistent myth perpetuated in the media/journalism/society/etc for a few decades, but there is a lot of scientific evidence showing that it doesn't really explain how depression works, and the fact that SSRIs boost serotonin doesn't explain why they work as a treatment. See https://sci-hub.st/https://www.sciencedirect.com/science/art... for example.
We have new insight now into how antidepressants interface with specific signaling molecules, making them more effectively permeate the neuron cell membrane.
It's still about chemical balance. It's a highly complex system involving more than serotonin, though.
He mentions serotonin reuptake inhibitors once, but it looks like this finding applies to other substances identified as anti-depressants that aren't necessarily serotonin targeting.
It's still about chemical balance. It's a highly complex system involving more than serotonin, though.
He mentions serotonin reuptake inhibitors once, but it looks like this finding applies to other substances identified as anti-depressants that aren't necessarily serotonin targeting.
Not really, it’s just proposing a different chemical imbalance than the “monoamine hypothesis” (i.e. serotonin, etc.). That one has already been disfavored for the past few decades, due to a lot of findings that it has trouble explaining. In particular the discovery of effective antidepressants that don’t affect the monoamine receptors enough or in sufficiently similar ways.
To my knowledge the idea that depression is a result of low serotonin has not been accepted by the scientific community at any time; immediately after SSRIs were shown to have an effect lots of people assumed that serotonin was important, but reuptake inhibition wouldn't even treat low levels overall, let alone matching the super weird timing effects.
This topic is often a red herring and source of conflation. I strongly recommend this series of articles from a psychiatrist about it: https://slatestarcodex.com/2015/04/05/chemical-imbalance/, https://slatestarcodex.com/2015/04/18/polemical-imbalance/
I linked to a paper published and written by several psychiatrists and psychologists that explains the history of the monoamine hypothesis, and why it's not a good theory. Why would they spend so much time debunking a theory nobody believes?
Quoting directly from the article
> Despite decades of research, the role serotonin plays in depressive phenotypes has not been conclusively determined. The original clue that monoamines (serotonin, norepinephrine, and dopamine) were involved in depression came from two serendipitous discoveries (Baumeister et al., 2003; Valenstein, 1998). First, during the investigations of iproniazid as a treatment for tuberculosis and imipramine as a treatment for schizophrenia, clinicians reported that these drugs could reduce depressive symptoms. An effort was then made to find a common pharmacological property that could explain their antidepressant effect. Eventually, researchers found that iproniazid inhibits the enzymes that break down the monoamines, while imipramine blocks the serotonin transporter (SERT) and the norepinephrine transporter (NET). Second, clinical observations suggested that reserpine, a drug known to deplete monoamines, increased depressive symptoms. These findings appeared to solve the puzzle. By preventing the breakdown of norepinephrine and serotonin, or preventing their clearance from the synapse, iproniazid and imipramine appeared to increase forebrain monoamine levels.
> The monoamine-enhancing effect of antidepressant medications (ADMs), coupled with the depression-inducing effects of reserpine, suggested that depression was caused by reduced monoamine neurotransmission (Everett and Toman, 1959; Jacobsen, 1964; Schildkraut, 1965)
https://sci-hub.st/https://www.sciencedirect.com/science/art...
Additionaly, this is something that lots of undergraduate psychology textbooks still mention as a potential explanation (one of mine did ~6 or 7 years ago, although at least they said that it was an implausible theory).
Quoting directly from the article
> Despite decades of research, the role serotonin plays in depressive phenotypes has not been conclusively determined. The original clue that monoamines (serotonin, norepinephrine, and dopamine) were involved in depression came from two serendipitous discoveries (Baumeister et al., 2003; Valenstein, 1998). First, during the investigations of iproniazid as a treatment for tuberculosis and imipramine as a treatment for schizophrenia, clinicians reported that these drugs could reduce depressive symptoms. An effort was then made to find a common pharmacological property that could explain their antidepressant effect. Eventually, researchers found that iproniazid inhibits the enzymes that break down the monoamines, while imipramine blocks the serotonin transporter (SERT) and the norepinephrine transporter (NET). Second, clinical observations suggested that reserpine, a drug known to deplete monoamines, increased depressive symptoms. These findings appeared to solve the puzzle. By preventing the breakdown of norepinephrine and serotonin, or preventing their clearance from the synapse, iproniazid and imipramine appeared to increase forebrain monoamine levels.
> The monoamine-enhancing effect of antidepressant medications (ADMs), coupled with the depression-inducing effects of reserpine, suggested that depression was caused by reduced monoamine neurotransmission (Everett and Toman, 1959; Jacobsen, 1964; Schildkraut, 1965)
https://sci-hub.st/https://www.sciencedirect.com/science/art...
Additionaly, this is something that lots of undergraduate psychology textbooks still mention as a potential explanation (one of mine did ~6 or 7 years ago, although at least they said that it was an implausible theory).
pid_0(2)
This is fascinating. Cholesterol has long be associated with depression.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606915/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606915/
That associates statin use with depression, not cholesterol. That’s a huge difference. Those results (which are not an RCT) could easily be explained by those that are less depressed are more likely to seek any non-psychiatric outside medical treatment.
First: cholesterols are a family of molecules, like alcohols, not just one thing.
Second: statins inhibit cholesterols so while it is associated, it's good to mention that cholesterols are anti-depressive, which is something anyone with any university bio education will know.
Second: statins inhibit cholesterols so while it is associated, it's good to mention that cholesterols are anti-depressive, which is something anyone with any university bio education will know.
So will this lead to a cure since I've tried 15 and only mirtazapine worked for a few years?
Psilocybin genuinely works for me - when I can get it (difficult because it's class A and seasonal).
The last time I had it was a bad night - I took about 7g.
However, the suicidal thoughts that had been getting progressively more serious stopped overnight.
I'll never touch another fucking SSRI. I'd rather not exist at all than become the unperson those things turn me into.
The last time I had it was a bad night - I took about 7g.
However, the suicidal thoughts that had been getting progressively more serious stopped overnight.
I'll never touch another fucking SSRI. I'd rather not exist at all than become the unperson those things turn me into.
Mushrooms are pretty easy to grow btw. If it was the difference between me feeling depressed or not I certainly wouldn't be relying on spotty supply.
I live in New Zealand - I can't afford land.
The only possibility for getting around the seasonalilty is growing indoors - and I really don't have the space for that.
Depression for me has caused me to spiral down - so far down that there's no apparent path back up.
I've been down and out for so long that even finding work is damned near impossible - so I can never even get to the point where renting my own place is feasible.
The only possibility for getting around the seasonalilty is growing indoors - and I really don't have the space for that.
Depression for me has caused me to spiral down - so far down that there's no apparent path back up.
I've been down and out for so long that even finding work is damned near impossible - so I can never even get to the point where renting my own place is feasible.
I was on SSRIs many years ago. I don’t recall feeling any better or worse, with them. I was also on other things with larger risks that’s thankfully didn’t materialize. But again, didn’t feel like they did anything.
Unfortunately psychedelics I’ve tried just up anxiety and paranoia. My last experience had me crouched up on the couch alternating between sweating and chills, hating the time dilation and just waiting it out.
Unfortunately psychedelics I’ve tried just up anxiety and paranoia. My last experience had me crouched up on the couch alternating between sweating and chills, hating the time dilation and just waiting it out.
I want to die too...
More than I want to die, I want not to be a part of the omnicidal stupidity that seems to define humanity.
I really do want not to die, and I see a viable path forward with that as a result.
An illegal and seasonal path.
I last took a dose in July, and those malignant fucking thoughts are returning.
And nurses keep telling me that psilocybin clearly has not worked (all the while advocating a pill a day, pill a day, pill a day).
If you see a drowning man take a gasp of air, and the keep right on drowning that does not mean that the air did not work.
The system is fucked - but try not to let it eat you.
I really do want not to die, and I see a viable path forward with that as a result.
An illegal and seasonal path.
I last took a dose in July, and those malignant fucking thoughts are returning.
And nurses keep telling me that psilocybin clearly has not worked (all the while advocating a pill a day, pill a day, pill a day).
If you see a drowning man take a gasp of air, and the keep right on drowning that does not mean that the air did not work.
The system is fucked - but try not to let it eat you.
God I hope so. Just found a blend that's helping me feel human for the first time in these 35 years of living. I'm in the same boat with Mirtaz, altho I'm finding success with pairing it with Viibryd.
A big help is genesight testing for upfront compatibility/sensitivity for a consultancy approach, rather than spray and pray.
A big help is genesight testing for upfront compatibility/sensitivity for a consultancy approach, rather than spray and pray.
There is very little evidence GeneSight results mean anything for efficacy. Tolerability and dose metabolism in the best case.
Mirtazapine was a nightmare for me. Even at high doses. I’ve tried a half dozen.
My next experiment pending warmer weather here in MI: a hunt for wild psilocybin mushrooms. I’m convinced the best way to achieve my goals is to rewire my brain with psychedelic experiences.
My next experiment pending warmer weather here in MI: a hunt for wild psilocybin mushrooms. I’m convinced the best way to achieve my goals is to rewire my brain with psychedelic experiences.
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Although this seems compelling, there is also the role of 5HT2A receptors in weighting priors as Carhart-Harris and Friston discuss in
https://www.researchgate.net/publication/333911957_REBUS_and...
While this primarily has to do with psychedelics, they address depression as well in the above.
While this primarily has to do with psychedelics, they address depression as well in the above.
Sometimes I try to think in more philosophically terms about the word "disease".
It's often said depression is natural, and it only becomes a problem because of sedentary lifestyle.
Diseases are bad, but when you dig, nature doesn't work in term of good or bad. I think it's difficult to really know at what point depression becomes problematic, since doctors have a hard time making a good diagnostic. Brains are complicated.
It's often said depression is natural, and it only becomes a problem because of sedentary lifestyle.
Diseases are bad, but when you dig, nature doesn't work in term of good or bad. I think it's difficult to really know at what point depression becomes problematic, since doctors have a hard time making a good diagnostic. Brains are complicated.
For the cognitive aspect of depression a nice comprehensive and dense video I found is [0], key factors in slide at 24:10 and the reasons for this approach are at a slide at 23:00 including why a medication only approach is intractable in the long term.
[0]: https://youtu.be/TVgQ_tgWMyU
[0]: https://youtu.be/TVgQ_tgWMyU
TLDR; conditions like depression may stem from a poor distribution of cholesterol in the neurotransmitter signaling process in the brain.
What I'm hearing you say is 'eat more bacon'.
Sorry what was that? You're breaking up. I'm off to the store, ttyl.
Sorry what was that? You're breaking up. I'm off to the store, ttyl.
Eating cholesterol doesn't affect your levels of internal cholesterol.
(Do people who like bacon know they can just eat chashu?)
(Do people who like bacon know they can just eat chashu?)
Yet, eating bacon and cha siu makes me happy...
Saturated fat does.
I will read this in full later - though anyone care to reply with a TL;DR for everyone here?
I am not a biologist by any stretch, but I will try.
A common mechanism of action may have been found across antidepressants where none was found before. This common mechanism between both Prozac and Ketamine has some impacts on how cholesterol is used in the brain and BDNF (neuron survival and growth regulator).
A common mechanism of action may have been found across antidepressants where none was found before. This common mechanism between both Prozac and Ketamine has some impacts on how cholesterol is used in the brain and BDNF (neuron survival and growth regulator).
Thank you - interesting. I wonder if the cholesterol changing mechanism is why some people seem to gain body weight/fat who are on certain medications.
My amateur guess is that because some of these drugs are associated with weight gain and some are not that this mechanism of action is not the primary actor for antidepressants with weight gain side effects.
It's a short article. Just read it.
I think there's more value in the comment you're replying to than your own comment - I imagine you took the time to downvote too? At least thank you for spending the effort of writing something.
I did not, because I thought enough others had done so already. Asking other people to do your thinking for you is noise, and belongs at the bottom of the thread. It's fine if you can't be bothered to read it right away: HN has a save feature just for that. But don't inflict your laziness on the commons, especially for an article that is so very short.
I think this article was written for a more medically/biologically literate audience than the typical HR member. It assumes a level of jargon and background knowledge. I think it’s reasonable to ask for a summary targeted towards the HR audience.
That would be more reasonable, but it's not what they asked for.
Glad you can at least admit there's value to my question now - maybe you shouldn't assume why someone's asking for something or what their capabilities generally are. In reality I did start reading the beginning of it and it was dense, I didn't check how long it was either, but that's what lead me to coming back to HN and posting. So yes, I see now if I had explained that in full you would have likely had compassion for my asking the question.
I didn't assume. As far as could tell, you said your reason up front. Don't pretend it's my fault for taking you at your word.
I stand corrected.
"But don't inflict your laziness on the commons"
So you must be against the downvote mechanism as it's a lazy, near effortless way for people to get a hit of dopamine vs. your qualitative response that actually shares thoughts that I am more likely to respect and take note of?
"But don't inflict your laziness on the commons"
So you must be against the downvote mechanism as it's a lazy, near effortless way for people to get a hit of dopamine vs. your qualitative response that actually shares thoughts that I am more likely to respect and take note of?
No, I'm in favor of the downvote mechanism as a way to sideline noise. I'm only against lazy usage thereof.
It's a long read, but my short version would be this: "Depression is a mode where the brain underweighs evidence from new experiences in favor of pre-existing negative prior assumptions."