Comment by paufernandez 3 days ago
Agree. But sometimes there is no "root cause", the brain is still a mystery. If you had been depressed even when you knew there was nothing to worry about, you would see it differently, because then you deduce that the black cloud is produced within.
Chemistry trumps psychology. Good enough chemistry enables cognitive treatments. But to fix the wrong chemistry you need chemistry.
> Chemistry trumps psychology
To nitpick: The mind is applied biochemistry. Psychology intervenes in the chemistry, like many other activities do. The goal of that is to solve the root cause so that your future levels will be maintained at the right level, instead of just forcing the level by sourcing the respective chemicals externally.
A good rule of thumb in biology and particular any kind of hormone production and balance is "use it or lose it" - if you start regularly receiving something externally, internal production will scale back and atrophy in response, in many cases permanently.
Psychology can change neurochemistry but only in certain limited ways. Many people are on antidepressants long term because that's the only thing that works for them. Taking antidepressants is already stigmatized enough. People should just do what makes them feel best over the long run. Your rule of thumb does not trump hard-won personal experiences.
We don't really know how SSRIs work, but there's some evidence that it's through desensitizing serotonin receptors, not directly addressing the lack of serotonin. If so, "use it or lose it" doesn't apply; long-term adaptation is the point, and SOMETIMES does persist after quitting.
>A good rule of thumb in biology and particular any kind of hormone production and balance is "use it or lose it" - if you start regularly receiving something externally, internal production will scale back and atrophy in response, in many cases permanently.
There are ways to "hack it".
For example, ~6 months ago I started trt (testosterone replacement). It was the best decision health wise ever. I feel way better psychologically, first time in my life I managed to stick with cardio training for so long (before 3 months was the most). There are other benefits too.
So what about the "loose it" part? Well there is a hormone called HCG one can take a twice a week to trick one's balls into producing some natural testosterone. Its use prevents atrophy and infertility.
> Some cancerous tumors produce this hormone; therefore, elevated levels measured when the patient is not pregnant may lead to a diagnosis of cancer and, if high enough, of paraneoplastic syndromes. It is unknown however whether this production is a contributing cause or an effect of carcinogenesis.
Interesting.
Well, I don't think you'll be able to avoid testicle atrophy even if it minimizes it, but the important part is understanding the tradeoff. Particularly, that adding testosterone will cause changes throughout your entire body (including, for example, shortening life expectancy a bit), and that adding other hormones to the mix will likewise cause changes around the entire body and not just one single process or organ.
But it's your body, your life, your priorities and decision. I also wouldn't consider it a good decision health-wise to take steroids to get huge, but I have no problem with someone deciding that absurd bulk is their main goal in life and worth the tradeoff.
>A good rule of thumb in biology and particular any kind of hormone production and balance is "use it or lose it" -
Very basic and very often wrong rule, so take it with a grain of salt.
Insulin for example is the opposite. "lose it then use it" would be a general rule for type 2 diabetics where insulin resistance commonly due to weight gain is the primary problem. Losing the weight leads to better uptake and usage. For a type 1 "lose it then use it" you typically lose the ability to produce insulin to an an autoimmune disorder, then are stuck using insulin for the rest of your life.
The body itself typically attempts to main homeostasis, but at population scales this is something that is going to have a massive range of ways it shows up. Evolution, at grand scales, doesn't care if you survive as long as enough of your population survives and breeds. At the end of the day you might just be one of those people that was born broken and to work properly you need replacement parts/chemicals. A working medical system should be there to figure out which case is which.
> Insulin for example is the opposite.
You're describing entirely orthogonal issues. In case of insulin resistance, your natural production is running full blast with demand exceeding supply because the consumer stopped caring about the hormone. In case of autoimmune disease, the natural production was killed - you can neither use nor lose what is already dead, and even if some capacity was left it will either soon be killed or atrophy under external insulin, but it will not be mourned.
So no I would say it is exactly the same - "use it or lose it" - but that does not mean that there is never a reason to manually overrule your body's attempt at homeostasis through direct manipulation. It just means that there is a very significant consequence to the process.
> The body itself typically attempts to main homeostasis, but at population scales this is something that is going to have a massive range of ways it shows up.
As a somewhat sidenote, this is also why I dislike the idea of trying to classify people into "normal" and "divergent/atypical". In my eyes we're all normal people and an entirely normal aspect of being a human is that we all differ and have individually specific needs by virtue of being built by a trillion micro-meter sized workers, each with their own hand-copied version of the blueprint, only caring about the millimeter of you in their immediate vincinity and not really talking to any of the others.
The creator of the Serotonin hypothesis admitted it was wrong, and he shifted to melatonin's precursor later in his career. The challange with any research in this area is Serotonin and Melatonin both affect biological functions by gradient activity not lock and key receptor models. This pair is how plants and animals respond to seasonal changes which vary year to year. Serotonin is the warm and light lide melatonin is for cool and or dark.
My personal preference is to always suggest getting actual daylight on your retina for 20 min three times a week. Not through glasses, including eyeglasses, but can be through eyelids. That loads transferatin, as in transfer, this loads the enzyme that make serotonin. This then allows the body a better chance to make the intermediate between Serotionin and Melatonin, and is the one believed to help. But the patents have expired so it is like an orphan drug now.
If you view a world at a certain angle there is always something to worry about: 1. World in not perfect, it doesn't confirm to how we want it to be (and could not even in theory given that different people want it to be different) 2. The future cannot be predicted with 100% accuracy so even if all is perfect today you can worry that it will turn bad in the future.
When looking at the same reality one persons sees the situation as OK and another as a an endless and hopeless disaster it is hard to tell who is right. A depressed person would tell that most people around him are wrong and are optimistic only because they don't understand how bad all is.
That's incredibly reductive. I'm sure some people's depression can boil down to a matter of perspective, but it's naive to extrapolate that to everyone with depression.
I'm incredibly optimistic and am content with my position in life. My default state is being mindful of the present and I don't think about things too far into the future. I very rarely ever feel stressed out over things in life.
However, none of that changes the fact that I feel completely empty and find no joy in things. Interests are nearly non-existent, emotions dialed to 1, and the only thing I'm motivated to do is lay in bed staring at the ceiling... unless I'm on sertraline.
Admittedly that's just anecdotal, but I worked in a clinical neuroscience lab researching treatments for severe treatment-resistant depression (read: people who tried so many options including CBT that they even tried electroshock therapy). The only thing that helped those subjects was a regimen of personalized neuroimaging-guided transcranial magnetic stimulation for 10 minutes every hour for 10 hours every day for a week. Even then, it wasn't permanent. Some saw improvement for months, others only weeks.
For some people, it's not just a matter of "perspective".
I'm not telling it's a matter of perspective, my point is that I see no objective metrics to tell apart if the situation is bad so it's one expected to be depressed and when the situation is good (so only medication / therapy would help). And it makes discussions around this topic harder.
Depression is increasingly starting to be seen as a neurobiological disorder as we learn more.
In my own opinion, we need to stop viewing "mental health" as a separate class of conditions from general/physical health. A mental illness is a health/medical condition just like any other and shifting our views and diagnostic criteria in that direction would do a lot to remove the stigma associated with mental illness.
Someone with depression has a chronic illness, not a temporary "it's just in your head" condition.
> I feel completely empty and find no joy in things.
Maybe the idea that we should find joy and feel full is wrong?
We are on a random planet circling a random star in an unfathomable Universe.
STOP looking for meaning and you are liberated. The quest for meaning by itself might be exhausting and makes you feel depressed.
Who said I'm looking for meaning? I'm not.
It's not as liberating as you might think. A joyless existence is either suffering or nothingness. A life without meaning, either internal or external, is one where nothing is meaningful with no motivation thus one of crippling catatonia til death.
All I can say is just that it doesn't feel good and if you can't feel good about anything, your calculus of your life inevitably leads to the conclusion that existence isn't worth it.
This is the "people with anxiety should just stop being worried" attitude that failed to help for centuries. Whether or not you believe SSRI's are clinically effective, denying the existence of mental health disorders is not helping.
No, anxiety and depression aren't simply a matter of perspective.
> A depressed person would tell that most people around him are wrong and are optimistic only because they don't understand how bad all is.
Or because of a legitimate chemical imbalance or some other cognitive issue they can’t control alone. Right?
> "There is no convincing evidence that depression is caused by serotonin abnormalities"
- https://www.psychologytoday.com/us/blog/insight-therapy/2022...
and
> "the etiology of depression is incredibly complex, the narrative that it is caused by a simple “chemical imbalance” persists in lay settings. We sought to understand where people are exposed to this explanation"
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11752450/
and
> "Onset of depression more complex than a brain chemical imbalance. It's often said that depression results from a chemical imbalance, but that figure of speech doesn't capture how complex the disease is. Research suggests that depression doesn't spring from simply having too much or too little of certain brain chemicals."
- https://www.health.harvard.edu/mind-and-mood/what-causes-dep...
and
> "Analysis: Depression is probably not caused by a chemical imbalance in the brain – new study"
- https://www.ucl.ac.uk/news/2022/jul/analysis-depression-prob...
(These are not thoroughly checked articles, they're the first few search results; however claims that depression is caused by a chemical imbalance ought to be able to show where that idea originated, how the imbalance is measured in patients, where that hypothesis is supported by evidence, why antidepressents don't fix depression in half of patients, and several more suspicious things).
I didn’t say it was simply that. You’re twisting my words and these studies to discount all of behavioral health.
Arguably specific chemical patterns don't emerge and persist on their own. Basic causality will indicate that something caused that pattern, whether it is a disorder or a traumatic event. Chemical processes are not random. Otherwise, carbon based life forms would have never lasted this long
The parent commenter describes seasonal Winter depression. If the problem was brain chemistry, wouldn't it be with them from birth until treatment? Who has Seasonal Type 1 Diabetes, or Seasonal Dwarfism, or Seasonal Missing-an-Eye-From-Birth? Depression generally isn't something children have from birth, it's something adults get temporarily.
A few HN submissions recently are in the style "thinking about doing the thing is not doing the thing. Planning the thing is not doing the thing. <etc etc>. Only doing the thing is doing the thing". Comparing a brain to a large software project with bugs hiding in it, in that vein giving the computer 11 hours of 'sleep' each night is not debugging the code; overclocking or undervolting the CPU is not debugging the code; installing the latest updates and patches is not debugging the code. 'knowing there is nothing to worry about' is not debugging the code. Only debugging the code is debugging the code. Reading a badly explained idea on an internet comment and dismissing it with a mocking "thanks I'm cured" isn't debugging the code. Saying "I've tried everything" isn't debugging the code.
A more specific example, if you are going on a rollercoaster and you are experiencing physical and mental symptoms of worry - nervous, anxious, angry at the person pushing you to ride, twitching and trying to back away, eyes looking around searching for an exit, coming up with excuses to do something else instead, nervous shaking, dread tightness in the chest, affected breathing, perspiring, gritted teeth, etc. etc. then washing over all that with "I know there is nothing to worry about so this must be a problem of brain chemistry" seems a clearly incorrect conclusion.
Such a person clearly has a worry. Quite likely one that's out of proportion (e.g. "rollercoasters kill thousands of people every day!"). Possibly one that's completely incorrect (e.g. "going more than 10mph makes people's insides fall out!"). Quite likely a less clear and less obvious one - which could be anything, e.g. they saw a documentary about a rollercoaster which behaded a child and that's their only thought about rollercoasters; they saw a show about fighter pilots pulling high-G maneouvres and passing out and think that will happen to them on a big rollercoaster; they see the rollercoaster track and support flexing and don't understand that a some flexibility doesn't mean weakness; they went to a theme park as a child and older children bullied them into riding a scary ride and they wet themselves and figuratively died of shame and buried the memory; they were pushed into learning to drive at 15 by their wicked stepfather and this is pattern matching to the same kind of experience; etc. etc.
Saying "there is nothing to worry about, rollercoasters are safe enough and you know it, so your brain chemistry must be broken" isn't debugging the problem. It isn't even explaining the problem. Why would broken brain chemistry particularly affect them at a theme park, or in Winter, and not the rest of the time? How was this broken chemistry identified and measured and quantified and that hypothesis proven?
Likewise, just because the parent poster has tried sleeping and exercising and taking Vitamin D, doesn't address that humans evolved in Africa, connected to oceans and trees and tribal living, and not commuting to a fluourescent lit beige box filled with strangers writing JavaScript while being bombarded with news items about wars and genocides and stories of how everyone else is having a wonderful Christmas, earning more money than you, with a cost of living crises always on their mind, etc.
> "Good enough chemistry enables cognitive treatments."
Drugs can force people to carry on with a life that's making them miserable when they have no other available options to find out why and fix it. That isn't evidence that "there is no root cause"(!). Any more than turning it off and on again can let you get on with your job, but that doesn't show there's no root cause for a program locking up.
> "then you deduce that the black cloud is produced within."
And you have a lifetime of your prior experiences affecting your mood. When you remember that your aunt hit you when you swore at the dinner table, or you saw someone slip on ice and fall over and break their wrist, or watever, every life learning experience is "the mood is produced within".
> If the problem was brain chemistry, wouldn't it be with them from birth until treatment
Ha, of course it can be! Our brain chemistry is not stable through our life! Many children are born with epilepsy, but some people develop it later in life. epilepsy, like all neurological disorders are nature AND nurture, genes AND the environment.
Using your roller coaster analogy, there very well may be genes that control; how much fear someone experiences when riding a roller coaster. The problem society has is telling people that they all should be able to not have feear riding a roller coaster and if youa re too afraid to ride a roller coaster you should take xanax.
> "Our brain chemistry is not stable through our life!"
Citation requested. Because, y'know, it's not like your leg muscles suddenly don't work from age 40-50 and then start working again and we say it's because of unstable "leg chemistry". It's not like your stomach, liver, kidneys, <organs> suddenly stop working after you lose your job or your life partner and we say it's both inexplicable and because of a deficit of "body chemicals" and nod agreement with each other that "body chemistry isn't stable" through a lifetime.
These are just unsatisfyingly crappy non-explanations.
And quick attempts to assume that Doctors, Neuroscientists, Psychiatrists, Psychologists must have a better detailed knowledge of brain chemistry and I'm just falling for nonsense seems to find that they actually don't, and they don't agree that "brain chemistry" is a good explanation, and it can't be measured in a patient, and the idea isn't strongly supported by evidence, and even the mechanism of action of "drugs which correct brain chemistry" isn't agreed on, and when given to people to "correct brain chemistry" it often doesn't make the problem that was blamed on brain chemistry go away.
> "there very well may be genes that control; how much fear someone experiences when riding a roller coaster."
I will lump "genetics" in as another pet-hate unsatisfyingly crappy non-explanation that people tag onto whatever they want so they can stop thinking about it further. There probably are many genes which affect how much fat bodies store, or burn, or food cravings, or what constitutes hunger, or production of various leptins and grehlins and insulins and stomach acids, but that doesn't mean "I'm obese because of my genetics" is any kind of explanation at all. Or "I have this personality because my parents and grandparents had it, it's genetic" is an explanation. Downe's Syndrome is a good use for genetics as an explanation. "I have a macro-scale set of vaguely related behaviours, symptoms and body effects and no clear cause, it's my genetics" isn't.
Even if you have sequenced your genome, and have some specific gene that is associated with extra fat storage, genes can be turned on and off through a lifetime by behaviours and environment. Having a gene from birth doesn't mean it's being expressed and is therefore causing a specific problem, or that the problem can't go away and can't be fixed. ( https://www.cdc.gov/genomics-and-health/epigenetics/index.ht... )
> "The problem society has is telling people that they all should be able to not have feear riding a roller coaster and if you are too afraid to ride a roller coaster you should take xanax."
I agree with this. Society likes assuming everyone is the same. Imagine if we collectively noticed that Adrenaline gives people "a burst of strength" and decided that daily exercise, individual strength training plans, gym visits, were all too much bother and that ageing adults were suffering from "an imbalance of Adrenaline" and when they struggle to carry their massive haul of groceries in from their car they should carry an auto-injector of Adrenaline to help their chemical deficiency.
> Citation requested. Because, y'know, it's not like your leg muscles suddenly don't work from age 40-50 and then start working again and we say it's because of unstable "leg chemistry".
Ohhh, leg chemistry, good choice! You know that leg "chemistry" is control by neurotransmitter release, yes? So you must have never heard of Familial Periodic Paralysis then. Let me tell you what happens with that, because it happened to me while taking Seroquel. Familial Periodic Paralysis is also called Hyperkalemic periodic paralysis and is due to mutations in the gene that encodes the alpha-subunit of the skeletal muscle sodium channel (SCN4A).
https://www.ncbi.nlm.nih.gov/books/NBK1338/
"The paralytic attacks are characterized by decreased muscle tone (flaccidity) more marked proximally than distally with normal to decreased deep tendon reflexes. The episodes develop over minutes to hours and last several minutes to several days with spontaneous recovery.
Some individuals have only one episode in a lifetime; more commonly, crises occur repeatedly: daily, weekly, monthly, or less often. The major triggering factors are cessation of effort following strenuous exercise and carbohydrate-rich evening meals. "
Look at that! Their muscles stopped and stared working again!
And yes, this happened to me while taking seroquel because it lowered my potassium so much it affected my nervous system.
Any good psychiatrist will tell you that they have no idea what is going on. But that does not mean neurotransmitters cannot be changed and that they do not effect behavior.
> I will lump "genetics" in as another pet-hate unsatisfyingly crappy non-explanation that people tag onto whatever they want so they can stop thinking about it further.
As someone who, as an armature geneticist, helped design a genetic study for Stanford, can I say that I put more energy into thinking about these things over the last 45 years than you can even imagine?
>Or "I have this personality because my parents and grandparents had it, it's genetic" is an explanation.
I have my hair color, height, skin color, all the physical traits from my parents, so why do you think the brain is not physical as well? Or or adrenal system? The brain is effected by genetics, this is true as has been shown clearly as a risk for schizophrenia. I have no idea why people think our mood, which is dictated by our thoughts which are created and sensed by our brain, which is a physical organ, does not have anything to do with genetics and neurotransmitters.
and then you go on to talk about epigenetics, like that matters by genes don't? Do you know that genes control the epigentic response? Genes like DNMT1? So people with differences in DNMT1 will have different epigenetic responses?
> I agree with this. Society likes assuming everyone is the same.
So how are we different? nature AND nurture. Genes AND environment. I agree the solution to these problems are wrong, but your solution are just as bad as the ones your are prescribing.
Listen, there are times when our neurtranmitters are supposed to be different, like when we are in pain or when some one dies. But some people, like me, have these changes regardless of the situation and we can like them to other environmental factors like diet, sunlight, weather, etc.
I could tell you whey and why I think am so sensitive to the world but I doubt you would listen, because no one listens, because everyone knows.
You're replying as if I said that drugs can't change neurochemistry and can't change mood or behaviour, and genetics doesn't exist and can't explain anything. I wrote quite a lot because I wanted to make it pretty clear that I wasn't saying either of those things.
If your old fashioned TV glitches and you hit it and it works, that doesn't mean it had a percussive imbalance. If you sledgehammer your brain chemistry that can change your mood and behaviour, and that doesn't mean you had a chemical imbalance and need a sledgehammer every week forever. It's the lack of supported good explanation that I'm against, especially after becoming convinced that a lot (not all) depressions and anxieties are addressable with therapy - but not just any therapy with any technique, just like a TV problem can be traced to a bad solder joint or a loose wire or a warped chassis shorting out a wire, but not by just randomly poking wires and replacing components without any training or experience and saying "I tried everything so it must need hitting". Similarly, "genetics" can be a fine explanation which is why I edited Downes Syndrome into my comment, also blue eyes, Trisomy 21, Huntington's Disease, and many others.
> "As someone who, as an armature geneticist, helped design a genetic study for Stanford, can I say that I put more energy into thinking about these things over the last 45 years than you can even imagine?"
And how do you feel about these quotes I just found on Reddit: "I think my genetics are stopping me from losing weight. I am 25F 5'2 and 145lbs and I have been having the hardest time trying to lose 20 lbs; or "I hate my genetics. I'm lifting 5~6 days a week since october last year, what means almost 10 months of consistent training, but my measureaments and bodyshape still like shit" or "Are my genetics/health screwing me over or am I just shit? r/GuitarQuestions"
Do you think those uses of 'genetics' are good explanations, that the poster should be satisfied with? Explanations that have good predictive power and a clear model of finding other people with the same problem, and suggest what to do next to compensate? Or are they (as I grumble) bad explanations which don't have any predictive power because they don't specify any particular gene or its effects, in much the same way that saying "it's fate"?
> "your solution are just as bad as the ones your are prescribing."
My solution of fix the TV electronics is just as bad as "hit the TV and accept a bad explanation for how that helped"?
> Chemistry trumps psychology. Good enough chemistry enables cognitive treatments. But to fix the wrong chemistry you need chemistry.
It's not at all clear that chemistry is the root issue. The brain is a synaptic graph that does something. Some graphs can have weird paths that lead to pathologies (maybe bad feedback loops). Chemistry seems like fairly a blunt instrument for bludgeoning a "bad" graph into one that's "better".
Forced habits, like cognitive exercises from psychology, can sometimes rewire the graph by themselves because that's how the brain learns/adapts, but we still don't have a good grasp on how to do this truly effectively in many cases.
That said, the blunt instrument of chemistry can sometimes be useful, particularly if it enhances neuroplasticity, as I think psychedelic research is beginning to show.