The culture of medicalizing depression perplexes me. There seems to be a staunch commitment to studying it as if it were like a disease of the brain tissue, like Alzheimer's, and staying well clear of simple explanations like "maybe the subject's life is shit?".
Because it turns out, and trust me on this one, that having a shit life causes depression. In particular: a shit life that the subject feels no hope of getting out of.
I suffered really severe, debilitating depression for years. I tried all the usual crap that know-nothings recommend, doing exercise and the like, and working hard to try and do better at life, but none of it budged the needle. Beyond that I was told I of course need to drug myself to feel better (SSRIs).
The depression was permanently solved, not by any of that, but just ditching my old life in full, and doing something else. Once your life stops being shit, you stop feeling depressed.
All the "chemical imbalance" talk is to avoid having to think about this, and instead reduces the problem in the same way a heroin addict does.
The main complexity in fixing it is that the subject often doesn't know their life is shit and just keeps trying to do that life better, or that they fear leaving that life will make things worse.
My non-psychologist tip for anyone suffering from severe depression like I was is simple: you have to make a very big, easy change to your life.
Big means not tweaking this or that, but completely changing everything. What's the most extreme change you could make, in your mind? Is it go and be a monk in Nepal for a couple of years? Then do that.
Easy means it can't be a struggle - if you're depressed you don't have the energy to do that.
I’m not an expert in the field, but I am someone who has recovered from depression. The “lack of serotonin” theory always made me laugh. It’s like if your computer was running abnormally and you said it “doesn’t have enough electricity”.
Neurotransmitters send signals. The amount of neurotransmitter tells you nothing about what information is actually encoded in those signals. You can transmit happy and sad music using electricity, for example. It seems to me that you can transmit happy and sad thoughts using neurotransmitters. (And of course the brain is much more complicated than a computer, because a computer “just” uses electricity, whereas in the brain some processing happens at each neuron, and signals coming in on one neurotransmitter can cause signals to leave in others.)
I see the term antidepressant as a bit of a misnomer. A drug that inhibits re-uptake of neurotransmitters will amplify the “loudness” of the signals. If you only have negative thoughts, and you take such a drug, your depression could realistically get worse (and this does happen to some people).
If you can get in to a positive feedback loop (e.g. an activity that leads to positive thoughts that lead to more of that activity) and _then_ start amplifying those signals, then these drugs can do wonders.
>The “lack of serotonin” theory always made me laugh. It’s like if your computer was running abnormally and you said it “doesn’t have enough electricity”.
A computer is a digital device, so it's more like all or nothing. It either powers up or not.
Analog electrical devices however can indeed behave suboptimally without enough electricity.
>If you can get in to a positive feedback loop (e.g. an activity that leads to positive thoughts that lead to more of that activity) and _then_ start amplifying those signals, then these drugs can do wonders.
this is how alcohol works on me and why I never drink if I'm not in a good mood. But I'd be careful about generalizing what effects drugs have on people.
Harking back to neurons compsci: neurotransmitters can modulate by their amount transmitted (saturation of the receptors, or not), so I can imagine if there's just not enough around, that certain signals will not (optimally) be transmitted.
I think ketamine is niche, and it will remain so. It's one of many tools. MDMA also assists in restoring brain plasticity[0].
For me, by far the most interesting development in mental health is Chris Palmer's work, which asserts that most mental illness is primarily a metabolic issue. If you think that can't be possible, read his 2022 book[1]. Here's a podcast[2].
I think basically there are three camps - those with problems they can't solve easily (trauma, situation) general unhappiness
- Those with biological issues, not getting enough sleep or bad nutrition etc
And the combo of those above which becomes much harder to solve and understand since both feed into each other. People might say x or y helped but it could be anywhere in this spectrum.
The biggest problem with depression is the failure to see that it's essentially only women affected; men are only secondary victims.
In 2014 is was 200-300% more women then men. 2020 it was about 500% more women. 2024 and it's pushing up toward 600%. The pandemic was particularly bad on women.
The not-a-paradox at all issue has been well studied.
You might say but there are men who are depressed; but the men who are depressed are almost certainly a cause of depressed mothers or spouses whose depression and abuse and depress the man.
>KRYSTAL: Well, the story is more complicated than one neurotransmitter per nerve cell.
It's old news that SSRIs are of low efficacy because it's but 1 of the transmitters. But the take away isn't that we need 50 more SSRI equivalents. It's that perhaps we should help women with their depression. But from my point of view every man who has ever attempted to help has been called sexist, misogynistic, etc.
Out of interest, if a guy is stranded on an island alone, and he's depressed, how do you work out the woman who's actually the depressed one? Do you work out the geographically closest one and say it's her?
Depression in men presents differently (anger instead of hopelessness) and is likely to go undiagnosed because of that and the taboo against men making negative emotional displays.
or mayyyybe men don't report depression because they're not used to speaking about their feelings, are made fun of when they do, and instead they're repeatedly told not to cry, and to tough it out
This was a great read! I generally find quanta magazine articles and podcasts to be of higher quality than a lot of other pop science journalism.
Can somebody point me towards a good review article or textbook to learn about the chemistry of the brain? Any exciting startups working in this field? Or any startups trying to come up with unconventional treatments for mental health problems?
More important question is : What happens in the gut that causes depression?
High evidence of diet/gut science creating neurally diverse states. Different ethnic groups react differently to the staple foods that is local to its incumbent (ex. flour, bread, cereal)
Too much focus has been on manipulating the chemistry upstairs (dangerous) but have largely been bandaid solutions (leading to new age psychdellic science)
This. You can find hundreds if not thousand of testemonies in the keto space where their depresion completely disspeared after between 1 to 6 months on keto or at least their needs to meds drasticaly reduced and their symptoms improved.
Nothing? Something happens in the brain (and body) which is depression, at a lower level of abstraction.
The world outside of the brain "causes" depression.
Sometimes things inside the brain or body (ideas, beliefs, emotions) cause the certain things to happen in the outside world (actions or inaction).
Sometimes these form a cycle: undesired life circumstances cause the brain to become depressive, which causes inaction, which prevents the circumstances from changing.
Sometimes nature/nurture/nutrition play a part in those internal ideas/beliefs/emotions, causing certain people to tend to get in depressive states more than others.
I'm certain 95% of depressions is this, but don't bother coming after me for the last 5%, keep it to yourself.
If somebody is in an abusive relationship, in financial turmoil, and has a terrible job, it's probably not a serotonin imbalance causing them to feel depressed.
There's actually a name for the above, it's called "Shit life syndrome" [0]. I don't know why society sees it as acceptable to load someone up with SSRIs when it's environmental factors causing them to feel the way they do. If you're going to drug someone up to make them feel numb to their awful circumstances why not just go the whole way and give them literal happy pills?
Given the scary, common side effects of SSRIs such as suicidal ideation and sexual dysfunction, I don't know how doctors can prescribe these things. It breaks the Hippocratic oath in my opinion.
> And so I would say, in response to what’s often asked, which is: If depression isn’t simply an abnormality in serotonin, why would you prescribe an SSRI? And I think the answer is that through serotonin and norepinephrine, we can promote the brain’s capacity for resilience against the adverse effects of stress and depression on the brain.
The people I know who have been in serious inpatient treatment for major depression have told me that in group every single person there shared some horrible shit in their past that directly contributed to their being there.
I found Johann Hari good on this with “Lost Connections” where he talks a lot about chemical imbalance vs life situation and their impacts on depression. Found it very enlightening.
Many people are in horrible situations and don't get depressed though. For instance, being bombed in WW2 apparently made British people happier. Not that they are ever very happy, being British.
(Also, every person who ever lived before modernity kind of had a shitty life. Often very literally. Usually horses are involved.)
Another clickbait title. Nobody knows. "It's complex" is the best summary. "(S-)Ketamine works better than older drugs" is also a claim, but unfortunately the podcast guest has an interest in it.
Our entire nervous system is neural network, gut has more neurons than brain, heart has neurons and it talks to brain more than brain talks to heart etc.
It’s hard for me to accept this idea that it’s just about the brain. In many other areas brain looks like result of what happened before, not the cause. Why this would be different?
How would you train depressed model? Maybe that gives some clues. Maybe it’s more about our environment and our relationship with that? Our actions are feedforward, brain chemistry is feedback.
Anyways, I don’t know anything but I like to ask different questions. And now.. let the downvotes pour in (like usual hah)
Some time in the future, they will no doubt look back at our age and pity us for not having realized that things usually have many causes, as well as types of causes. And while human behavior certainly has a biochemical component, and a neurological component, it is pitiful that these things seem to be the main line of inquiry when it comes to understanding behavior.
When asked for an opinion on why so many young people suffer from depression:
> the political turmoil that we’ve been through, the racial issues that we’ve been through in this country, the global wars that are going on. It’s pretty discouraging.
That doesn't really make sense, does it? These issues have been going on for centuries; how does that explain a rising trend?
I'd rather assume that the lack of a framework to understand the harshness of the world is what makes people go crazy.
Could it maybe be related to spending most of one's life working, with the only reward being just enough resources to keep working another day, and the majority of the productive output getting used for regime change wars, questionable science experiments, and entertainment for the 0.00001%?
You have just described the lives of most humans for all of recorded history. Seriously -- not being sarcastic. Subsistence agriculture does not provide a secure life, and (more recently) neither does working 14-hour days in a factory. And a lot of the surplus wealth produced by that labor went to.... wars and luxury for the wealthy.
There's definitely physiological and psychological kinds of depression, just as with of addiction.
Like a kid that's playing way too much <insert popular game here> having their parents take it away might make them annoyed and irate for a while, but they ultimately won't be worse for wear. Meanwhile take drinks away from an alcoholic and they will literally die from withdrawal symptoms.
As such you also have the natural kind of depression that's being caused by outside circumstances which is solvable by altering them. Then you have the type where the brain gets stuck in that same state constantly because of some internal chemical imbalance which can't be resolved without medication.
No, by far most public spending goes towards welfare for poor and elderly people.
Almost everything people believe about "funding wars" is false and comes from believing headlines written to make you angry. (For instance, those are often humanitarian funds, or the other people are paying us, or the bill they're thinking of got vetoed. Spending on the MIC has actually continually gone down over time as % GDP.)
I don't think that this is the root of depression. A lot of people get a lot of joy from working, and aren't that sad about having just barely enough resources to keep living another day. A lot of people even aspire to entertain the 0.00001%; thinking about it makes them happier.
As a data point, I feel like this. I'm excited about going to work on Tuesday. I'm also excited about not going to work tomorrow. There is a lot of pain and suffering in the world. Watching the 2024 campaign unfold is maddening and scary. But I still look forward to every day. I think depression is something different than merely realizing that society has a lot it needs to work on. That's just my perspective, though, and there are many others; all equally valid.
This is actually not a universally good idea because doctors 1. don't keep up with new research in other fields 2. don't know anything about diet/nutrition 3. are very bad at making decisions when there "is no evidence" for something and eg often act like this means "it is bad".
You should talk to a dietician or a specialist. But not any old doctor.
[+] [-] jalapenos|1 year ago|reply
Because it turns out, and trust me on this one, that having a shit life causes depression. In particular: a shit life that the subject feels no hope of getting out of.
I suffered really severe, debilitating depression for years. I tried all the usual crap that know-nothings recommend, doing exercise and the like, and working hard to try and do better at life, but none of it budged the needle. Beyond that I was told I of course need to drug myself to feel better (SSRIs).
The depression was permanently solved, not by any of that, but just ditching my old life in full, and doing something else. Once your life stops being shit, you stop feeling depressed.
All the "chemical imbalance" talk is to avoid having to think about this, and instead reduces the problem in the same way a heroin addict does.
The main complexity in fixing it is that the subject often doesn't know their life is shit and just keeps trying to do that life better, or that they fear leaving that life will make things worse.
My non-psychologist tip for anyone suffering from severe depression like I was is simple: you have to make a very big, easy change to your life.
Big means not tweaking this or that, but completely changing everything. What's the most extreme change you could make, in your mind? Is it go and be a monk in Nepal for a couple of years? Then do that.
Easy means it can't be a struggle - if you're depressed you don't have the energy to do that.
[+] [-] g3e0|1 year ago|reply
Neurotransmitters send signals. The amount of neurotransmitter tells you nothing about what information is actually encoded in those signals. You can transmit happy and sad music using electricity, for example. It seems to me that you can transmit happy and sad thoughts using neurotransmitters. (And of course the brain is much more complicated than a computer, because a computer “just” uses electricity, whereas in the brain some processing happens at each neuron, and signals coming in on one neurotransmitter can cause signals to leave in others.)
I see the term antidepressant as a bit of a misnomer. A drug that inhibits re-uptake of neurotransmitters will amplify the “loudness” of the signals. If you only have negative thoughts, and you take such a drug, your depression could realistically get worse (and this does happen to some people).
If you can get in to a positive feedback loop (e.g. an activity that leads to positive thoughts that lead to more of that activity) and _then_ start amplifying those signals, then these drugs can do wonders.
[+] [-] coldtea|1 year ago|reply
A computer is a digital device, so it's more like all or nothing. It either powers up or not.
Analog electrical devices however can indeed behave suboptimally without enough electricity.
[+] [-] taskforcegemini|1 year ago|reply
this is how alcohol works on me and why I never drink if I'm not in a good mood. But I'd be careful about generalizing what effects drugs have on people.
[+] [-] brnt|1 year ago|reply
[+] [-] getpost|1 year ago|reply
For me, by far the most interesting development in mental health is Chris Palmer's work, which asserts that most mental illness is primarily a metabolic issue. If you think that can't be possible, read his 2022 book[1]. Here's a podcast[2].
[0] https://www.nature.com/articles/d41586-022-02871-w [1] https://www.amazon.com/Brain-Energy-Revolutionary-Understand... [2] https://www.youtube.com/watch?v=oC-sQogfh3Q
[+] [-] softsound|1 year ago|reply
- Those with biological issues, not getting enough sleep or bad nutrition etc
And the combo of those above which becomes much harder to solve and understand since both feed into each other. People might say x or y helped but it could be anywhere in this spectrum.
[+] [-] incomingpain|1 year ago|reply
In 2014 is was 200-300% more women then men. 2020 it was about 500% more women. 2024 and it's pushing up toward 600%. The pandemic was particularly bad on women.
https://law.yale.edu/sites/default/files/documents/pdf/Intel...
The not-a-paradox at all issue has been well studied.
You might say but there are men who are depressed; but the men who are depressed are almost certainly a cause of depressed mothers or spouses whose depression and abuse and depress the man.
>KRYSTAL: Well, the story is more complicated than one neurotransmitter per nerve cell.
It's old news that SSRIs are of low efficacy because it's but 1 of the transmitters. But the take away isn't that we need 50 more SSRI equivalents. It's that perhaps we should help women with their depression. But from my point of view every man who has ever attempted to help has been called sexist, misogynistic, etc.
[+] [-] jalapenos|1 year ago|reply
Out of interest, if a guy is stranded on an island alone, and he's depressed, how do you work out the woman who's actually the depressed one? Do you work out the geographically closest one and say it's her?
[+] [-] SR2Z|1 year ago|reply
[+] [-] agos|1 year ago|reply
[+] [-] Harmohit|1 year ago|reply
Can somebody point me towards a good review article or textbook to learn about the chemistry of the brain? Any exciting startups working in this field? Or any startups trying to come up with unconventional treatments for mental health problems?
[+] [-] localfirst|1 year ago|reply
High evidence of diet/gut science creating neurally diverse states. Different ethnic groups react differently to the staple foods that is local to its incumbent (ex. flour, bread, cereal)
Too much focus has been on manipulating the chemistry upstairs (dangerous) but have largely been bandaid solutions (leading to new age psychdellic science)
[+] [-] billwashere|1 year ago|reply
https://brainenergy.com/
[+] [-] NotGMan|1 year ago|reply
[+] [-] sixo|1 year ago|reply
The world outside of the brain "causes" depression.
Sometimes things inside the brain or body (ideas, beliefs, emotions) cause the certain things to happen in the outside world (actions or inaction).
Sometimes these form a cycle: undesired life circumstances cause the brain to become depressive, which causes inaction, which prevents the circumstances from changing.
Sometimes nature/nurture/nutrition play a part in those internal ideas/beliefs/emotions, causing certain people to tend to get in depressive states more than others.
I'm certain 95% of depressions is this, but don't bother coming after me for the last 5%, keep it to yourself.
[+] [-] cedws|1 year ago|reply
There's actually a name for the above, it's called "Shit life syndrome" [0]. I don't know why society sees it as acceptable to load someone up with SSRIs when it's environmental factors causing them to feel the way they do. If you're going to drug someone up to make them feel numb to their awful circumstances why not just go the whole way and give them literal happy pills?
Given the scary, common side effects of SSRIs such as suicidal ideation and sexual dysfunction, I don't know how doctors can prescribe these things. It breaks the Hippocratic oath in my opinion.
[0]: https://en.wikipedia.org/wiki/Shit_life_syndrome
[+] [-] biot|1 year ago|reply
> And so I would say, in response to what’s often asked, which is: If depression isn’t simply an abnormality in serotonin, why would you prescribe an SSRI? And I think the answer is that through serotonin and norepinephrine, we can promote the brain’s capacity for resilience against the adverse effects of stress and depression on the brain.
[+] [-] User23|1 year ago|reply
[+] [-] dmje|1 year ago|reply
[0] https://thelostconnections.com
[+] [-] Jerrrrry|1 year ago|reply
[deleted]
[+] [-] BonoboIO|1 year ago|reply
I have no idea how you come to that conclusion and devalue people, that have the medical need for medication.
[+] [-] astrange|1 year ago|reply
(Also, every person who ever lived before modernity kind of had a shitty life. Often very literally. Usually horses are involved.)
[+] [-] froh|1 year ago|reply
Dr John Krystal talks about treatment of severe depression with ketamine and related substances, and findings how and why it works
He's cofounder Freedom Biosciences, a Yale Psychiatry spinoff with focus on ketamine, and ketamine versions
https://www.freedombio.co/#page-section-6223c55f53f5a65b449b...
A paper led by John Krystal, in the same vein:
https://www.pnas.org/doi/10.1073/pnas.2305772120
[+] [-] 3abiton|1 year ago|reply
[+] [-] tgv|1 year ago|reply
[+] [-] unknown|1 year ago|reply
[deleted]
[+] [-] 11101010001100|1 year ago|reply
[+] [-] miika|1 year ago|reply
It’s hard for me to accept this idea that it’s just about the brain. In many other areas brain looks like result of what happened before, not the cause. Why this would be different?
How would you train depressed model? Maybe that gives some clues. Maybe it’s more about our environment and our relationship with that? Our actions are feedforward, brain chemistry is feedback.
Anyways, I don’t know anything but I like to ask different questions. And now.. let the downvotes pour in (like usual hah)
[+] [-] efilife|1 year ago|reply
[+] [-] stareatgoats|1 year ago|reply
[+] [-] smokel|1 year ago|reply
> the political turmoil that we’ve been through, the racial issues that we’ve been through in this country, the global wars that are going on. It’s pretty discouraging.
That doesn't really make sense, does it? These issues have been going on for centuries; how does that explain a rising trend?
I'd rather assume that the lack of a framework to understand the harshness of the world is what makes people go crazy.
[+] [-] riehwvfbk|1 year ago|reply
[+] [-] AdamH12113|1 year ago|reply
None of this is new.
[+] [-] moffkalast|1 year ago|reply
Like a kid that's playing way too much <insert popular game here> having their parents take it away might make them annoyed and irate for a while, but they ultimately won't be worse for wear. Meanwhile take drinks away from an alcoholic and they will literally die from withdrawal symptoms.
As such you also have the natural kind of depression that's being caused by outside circumstances which is solvable by altering them. Then you have the type where the brain gets stuck in that same state constantly because of some internal chemical imbalance which can't be resolved without medication.
[+] [-] astrange|1 year ago|reply
Almost everything people believe about "funding wars" is false and comes from believing headlines written to make you angry. (For instance, those are often humanitarian funds, or the other people are paying us, or the bill they're thinking of got vetoed. Spending on the MIC has actually continually gone down over time as % GDP.)
[+] [-] jrockway|1 year ago|reply
As a data point, I feel like this. I'm excited about going to work on Tuesday. I'm also excited about not going to work tomorrow. There is a lot of pain and suffering in the world. Watching the 2024 campaign unfold is maddening and scary. But I still look forward to every day. I think depression is something different than merely realizing that society has a lot it needs to work on. That's just my perspective, though, and there are many others; all equally valid.
[+] [-] unknown|1 year ago|reply
[deleted]
[+] [-] Euphorbium|1 year ago|reply
[+] [-] kenjackson|1 year ago|reply
[+] [-] alberth|1 year ago|reply
[+] [-] astrange|1 year ago|reply
You should talk to a dietician or a specialist. But not any old doctor.
[+] [-] throw_pm23|1 year ago|reply
[+] [-] xcv123|1 year ago|reply
[+] [-] mellosouls|1 year ago|reply
It's very understandable that people should reach out for the many useful resources online first.
[+] [-] Jerrrrry|1 year ago|reply
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