Toward a Predictive Theory of Depression | Hacker News Reader

Toward a Predictive Theory of Depression

slatestarcodex.com

249 pointsmpweiher109 comments

Professor of psychiatry here - I've spent the past 20 years trying to help folks with depression, and related illnesses, and trying to study these diseases at a genetic level. I suspect this will get me down-voted as I know the medical/biological perspective is often unwelcome on hn. However: a key error people make here and elsewhere in speculating about depression (and suicide, and ADHD, and...) is either extrapolating only from their own experience, or from a vastly oversimplified psychology 101 perspective. For example: "Depressed people move more slowly, in a characteristic pattern called “psychomotor retardation”. Well, yes - except when they have agitated depression, characterized by psychomotor restlessness. Or, when they have neither of these. Likewise, oversimplifying by claiming it is a disease of dopamine, or serotonin, doesn't much help. When my car stops working, is it a disease of gasoline? Part of the challenge of depression is its very heterogeneity. What we need is not more theorizing, it is more recognition that we need better treatments of all sorts.

Without commenting on content, I will point out that the author of the article is a psychiatrist as well.

Yes. This is one reason I bothered to comment. Psychiatrists who step into the public space bear a particular obligation both to advocate for our patients and to push back against misinformation.

I don't think this article was meant to be widely shared, especially not in a public space like Hacker News. Alexander has a number of articles about depression grounded in actual established psychiatry and is, unsurprisingly, a big proponent of treating it - I'm not sure how you're getting "doesn't advocate for his patients" from this article. Also, it literally starts with the words "total wild speculation". It certainly looks like it's supposed to start a discussion rather than be informative.

There is Twitter and Facebook share buttons embedded in the article that was posted to a pretty high traffic blog...

The article is prefaced with: "Epistemic status: wild speculation." It seems like we rather do need more theorizing, because we don't currently have a theoretical description of depression that leads us to solutions. I know I've also seen him write about the possibility that depression is a set of interrelated diseases that look the same, and talked frankly about the inefficacy of treatments.

It's a fairly ungenerous read that would lead you to imply he's failing in some professional obligation. It's like discussing murder - how often do you need to state that you think murder is A Very Bad Thing? Do oncologists need to talk about how bad cancer is every time that they write about it in a public space? Eh.

>> Do oncologists need to talk about how bad cancer is every time that they write about it in a public space? Eh.

They would if a surprisingly large portion of the public believed cancer didn't actually exist.

"How dare you allow your malignant cells to unboundedly replicate! What would your mother say?"

He highlights the speculative nature of the theory quite frequently within the article. It would take pretty poor reading comprehension or deliberate misreading to conclude that he was presenting established scientific facts.

In my experience and observation, the physical world of the subject has been far too discounted.

And, I'll add, there are manifold variances in personal experiences and circumstances.

Why? Well, among other things, and in a simple reduction: Because the physical world is a "hard" problem. And one that does not involve just the subject him-/her-self.

Actually, also, in my observation, often the "hard" part isn't a determination of what should or needs to be done. It's finding the resources to accomplish this.

For example, remove people from their circumstances and sources of -- often extreme -- stress! (Or, enable them to do this, once they elect to. And/or effectively deal with the sources, themselves -- as an individual, a community, a society, or whatever effective agency.)

Yeah, but...

So, you come up with, as a profession, professionally blessed compensation mechanisms and assignment of responsibility to the subject -- perhaps, the victim -- instead.

I'm not saying everyone does this. Nor that all cases reduce to it. But, it is well worth considering, as a part of the continuing problem of mental illness and its treatment.

I would hope the opposite is true, and that medical expertise is particularly welcomed and appreciated on HN (you aren't the only doctor here). Thank you for taking the time to comment!

Could they be several different illnesses with different underlying causes, but similar symptoms that mistakenly get classified under the same name?

Yes, that certainly could be the case. Unfortunately there doesn't seem to be much (if any) understanding of what is different about those illnesses, and in particular no practical test that can distinguish between them to help identify the proper treatment.

By contrast, it is now very well recognized that there is no single disease called "cancer". There are many subtypes, not just based on tissue (e.g., breast cancer vs. lung cancer) but also on the molecular etiology (i.e., which mutations are present in the tumor and therefore which pathways of oncogenesis are involved). Because of this, it is in some cases possible to determine based on DNA sequencing which is the appropriate drug to use to treat a particular cancer. Depression is not anywhere near as well understood.

I’ve never been sure why it’s treated as a disease rather than a symptom. It’s like saying someone with a high temperature is suffering from fever. Which is nice and descriptive and treatable with the right medications, but does nothing to describe the underlying cause.

Lots of what we now consider symptoms were thought of as diseases until the underlying problem was better understood. It wasn’t that long ago that your fever example was how people thought. The fever was the disease regardless of the unknown underlying cause.

That depression is considered a disease by itself and not a symptom of many, possibly related, problems suggests how little we understand it.

There's an opioid epidemic sweeping the nation. If psychiatry has anything more effective for treatment than court-mandated AA (well, NA), now would be the time to do something, because people are dying left and right. Current treatment regimes are totally ineffectual. 30-days of rehab, along with religion-based and "addition is a moral failing" 12-step programs isn't cutting it.

It's not the number of theories that count, what counts is if there is a theory is actually useful in modeling results. If the car won't run and there's no gasoline, call it a disease of gasoline if you have to, but adding gas does wonders for my car actually running.

The late 1800's opiate epidemic called; they want to know if psychiatry has actually advanced in the interceding years.

It's a weird coincidence to read this. I was doing basic research on depression and saw that dopamine played a role in helping people feel good. One WikiHow article [0] later, I had an idea: Start reaching goals. I started very small, like taking progressively longer walks.

Since that time I have earned something like five different certificates in various areas of interest (ARRL coming up next) and as a very recent development, completed my university degree after 15 years of delay due to, among other things, depression.

I find that depression can still affect me, but the episodes don't last as long (around 2h max, lately) and I have a bunch of tools for dealing with them.

[0] http://m.wikihow.com/Increase-Dopamine

Great idea. I usually make checklists for small things when I feel lost and achieve them and feel accomplished. Things like "check x", "read about xx", 'backup file", "congratulate people with birthdays on FB"

When i mark them as done I feel better.

This works very well for low-grade depression for sure. There seems to be a threshold where this type of intervention becomes completely ineffective (personal experience).

I agree. From keeping logs over the last few years, severe depression was more likely to occur due to e.g. not enough sleep or just illness, and in those cases accomplishments were impossible. Rest was it, and I felt lucky if I could get good rest before acting on any depressing thoughts or ruminations. So I wouldn't call goal-reaching a standalone cure; far from it. Also there's the fact that people accept/reject potentially helpful information based on different criteria, from very rational (is it in a reputable journal) to irrational (do I like the person who gave the information) to incredibly subjective (did I think of it on my own?). So the idea of "why not try accomplishment" may be doomed from the start, due to factors outside of the advisor's control.

I noticed that rest only somewhat helped, but was significantly more effective if absent of any worry of external responsibilities. E.g. If I took vacation from work and didn’t tell my girlfriend about it so she wouldn’t worry about me and text me incessantly... I could turn off the thoughts/worries of the outside world completely for a few days and that made a pretty dramatic difference. I didn’t cure me at all, but it took me out of the really dangerous zone after about 2 days. Also, sleeping in a hammock, haha. So much better than breathing stale air for 2 days.

This is more circumstantial however, as my trigger at the time was accumulating too many perceived responsibilities and fearing failure. To be honest I feel the triggers are nearly irrelevant, but removing myself from them gives me enough temporary relief for my body to get out of stress mode. Which in turn removes some of the depressive overhead to give myself a golden window of opportunity.

Absolutely, but don't let this caveat stop you from considering this sort of advice if your depression has crossed that threshold. For those of us who have been there it's little strategies like this that keep us from crossing that threshold for too long.

As someone who’s been there, these tricks and tips make things worse, not better. Most depression advice is pretty terrible, this thread included.

My point is that people have to figure out what helps themselves. All of the terrible advice amounts to knowing there are people who have learned to manage themselves and therefore most people can learn to manage themselves.

Fair point. I like this view. Seeing all the anecdotal ways people have gotten themselves out of severe episodes may not work for the person seeking help, but it may give them enough hope to keep looking for the next approach before calling it quits for good.

Don’t really think there are that many. The vast majority are some form of “work out, eat healthy, ...”

I agree. It's clear from this thread (and it fits with my experience as well) that the usual advice only goes so far, and for obvious reasons: if I had enough energy, motivation, and discipline to work out, eat healthy, meditate, whatever -- all the standard advice for lifting my mood -- I wouldn't be depressed!

I've been wondering lately if there isn't a model of care that goes beyond just a psychiatrist (to prescribe the meds) and a therapist (to administer therapy along with the standard advice about exercise and eating well). Something more like a "nanny" or a caretaker who could help the patient with those things: bug the patient daily to make sure they're taking their meds (and/or supplements, if you're going that route); buy and cook that nice healthy food; get you out of the house and into the gym; etc. Something more than just seeing a therapist once a week, but less intensive than any form of institutional care (even on an outpatient basis).

Asking for a friend... :(

Personally decided the advice isn’t helpful at all for me and am trying other things. Talking to my mom helps some. Lots of things for me to figure out still though. Not very hopeful.

Maybe it’s more fair to say that much of the advice is unhelpful for many sufferers, but for those it does help, it’s a good toolkit to have.

Do you not discover that even a minor failure to reach a goal leaves you with feelings of disappointment, anger, and rejection that make it difficult to re-start the process of working towards the goal?

Prior to learning to analyze, yes, I did feel that way. In fact I was swallowed up by those feelings quite often, for years.

After learning more about analysis, not so much. Analytical thinking is more tactical and adaptive. It says, "forget about the big picture of who you are and what this says about you, and just focus on what this situation seems to demand. Which changes would seem to give you the most leverage on your next try?" So I'd try different things the next time and kind of keep a log, asking how it was all working. "Star date..." I was Jean-luc Picard and today was another episode. An internal monologue helped.

Tactical / analytical thinkers are good negotiators. I began to admire those who were in it to _win_ it, not just to give it a shot and see what happened. I followed study blogs and watched presentations by negotiators. For all they knew, if they failed at reaching a goal, it was the goal's fault! This was a real reset to my thinking.

I also have a son who is a very gifted tactical thinker. He's constantly analyzing and negotiating. Analyzing his behavior, I've learned that he will ask again and again until you get sick of him asking for things. The asking comes at little cost to him and there's a good chance that the asked will give in.

So: I'm more of an asker now. And I find that I accomplish more as a result.

I don't mean to communicate that I'm perfect, some kind of ubermensch, btw. Just sharing what I've learned. Also, I don't think this advice will work for everybody, but I hope it can help you somehow.

> Depressed people move more slowly, in a characteristic pattern called “psychomotor retardation”. They display perceptual abnormalities. They’re more likely to get sick. There are lots of results like this.

> Depression has to be about something more than just beliefs; it has to be something fundamental to the nervous system.

Depression is frequently related to metabolic problems: people are exhausted because their mitochondria aren't putting out enough ATP to run their nervous system.

There are various interventions that can help. B-vitamins are important cofactors for burning sugar to make energy. T4 thyroid is activated by the liver to make T3, which is one factor that boosts the metabolism. If the liver is overworked (alcohol, drugs, hormonal imbalance, too much pufa, etc), it can have trouble activating adequate thyroid.

Emotional resiliency is a big factor here too. My friend was really just lonely before she met me. She's doing better now because she now has a 'vision' for her future (she originally 'lost her future' when she was expelled from high school, essentially for being depressed and self-medicating with drugs that are now being investigated for treating depression).

I find that creatine helps, which weight lifters take to make it easier for your muscles to use ATP.

I wouldn't recommend taking creatine if you don't work out or get cardio. Without that, creatine can cause weight gain due to water retention. If you do exercise, creatine should an essential be part of your stack.

Why is water weight gain an issue?

You don't want to take a group of people with notoriously low self esteem and make them fat.

Creatine weight gain doesn't make you fat: it plumps up muscles, making you look more muscular, which, in turn, makes you look like you've lost weight.

Why would you be worried about weight gain if you know it's just water?

I strongly disagree. You can be an extremely good athlete without any supplement "stack" whatsoever. Maybe creatine helps eke out slightly better performance in certain activities, but like with most supplements it's really not worth the risk to your kidneys and other internal organs. If you exercise, eating well and sleeping enough is sufficient.

Dunno. I take significantly less than the recommended amount, and still find that I have significantly more mental and physical energy for everything. I recently tested this when I stopped taking it while on a certain medicine.

Got any links to the "risk to your kidneys"?

Note that creatine should be avoided if you're bipolar, according to a study or two and a lot of anecdotes.

Kidneys: https://examine.com/nutrition/does-creatine-cause-kidney-pro...

Overall, it's a very safe and moderately effective supplement, particularly if you don't eat a lot of red meat. Just make sure to drink enough water.

I wouldn't say I've been depressed (a psychiatrist might disagree, I've been dx'ed with it in the past), but daily 5mg creatine and 2k IU vitamin D have made a remarkable difference in mood/energy for me this year.

there's a difference between doing a bunch of molly every weekend for fun and self medicating.

There is, it's usually pretty easy to tell the difference. Doubt anyone would mistake them, and I doubt the OP is.

> There is, it's usually pretty easy to tell the difference. Doubt anyone would mistake them, and I doubt the OP is.

A few months ago a young man (early 20's) came into a shop I sometimes hang out at. "What brought you to town?" "Recovery." He'd been in town for 3 weeks, and sober for 3 weeks and 1 day.

I asked him, "People usually know when their problems when substances started, when did it start for you?"

When he was in 3rd grade his teacher thought he was disruptive. They put him on some kind of medication for "ADHD". He told his parents in 9th grade that he was going to kill himself if they didn't take him off the pills. Soon after discontinuing his "ADHD" medications was when he started experimenting with self-medicating... Tobacco, alcohol, etc.

His latest bender was on alcohol & laughing gas (nitrous oxide [0], for the euphoria).

[0] https://en.wikipedia.org/wiki/Nitrous_oxide#Recreational_use

After a bit I told him, "I bet you're exhausted."

"YEAH!"

"Recovery" is good for getting people to feel like failures, so I thought it'd be helpful for putting a different 'frame' on his last 15 years. I told him that he doesn't actually have a substance abuse problem, he's just been exhausted this whole time, and didn't know what to do to help improve his energy levels. I gave a few suggestions for keeping his energy levels up.

Saw him three or four more times over the next 2-3 months, and he was doing much better. I saw him last 2 days before he returned to where he came from. I think he's got a chance this time.

Would you mind to elaborate a little bit on your suggestions? That is if it's not too specific.

The only thing that fellow could really do for himself was buy some coconut oil. The brains of alcoholics become insulin-resistant and switch to running on acetate, one of the breakdown products of ethanol. The medium-chain-triglycerides in coconut oil provide brain cells with an alternate source of fuel. (I understand that Coconut fatty acids are short enough to be burned without having to go through another step that longer saturated fats [butter, etc] require; I don't remember exactly what that step is.)

I don't think that guy was able to get the coconut oil while at the recovery center. I think giving a more helpful context for viewing his history of addiction was much more helpful than the recommendation for coconut oil.

Another heavy drinker I know does fine while on "vacation", but "stress" in his every day life leads to excess drinking. I have no influence with this one, but I'd try to get him to eat more sweets when in stressful situations - juices/etc. I've heard an old treatment for alcohol withdrawal is to feed them lots of sugar. Here's a random NY Times article that says sugar helps reduce cortisol levels: https://well.blogs.nytimes.com/2015/04/23/sugar-as-a-stress-...

IMHO, sugar in juices and other foods is basically fine; starch is 100% glucose and is a greater contributor to excess weight. Lots of caveats with regards to the sugar issue...

I was a heroin addict for 6 years, and have been clean for 5. The sweets thing was very true for most addicts I knew as well as myself: in withdrawals I’d crave sugar something fierce. Gummy bears would temporarily make me feel better. It was interesting.

> molly

TIL molly is slang for MDMA.

every weekend? that's self medicating.

When I was depressed I had perfect trust in my ability to predict events, it was just that no matter how much I tried I couldn't predict a future where I weren't constantly in agony. I got over it by letting go of most things that were hurting me like friends, family, dreams etc. So now I live a fairly unassuming life but I am content. It might sound a bit boring but it is much better than living in agony every day for the rest of your life.

How did you let go? I've tried things like meditation, but it always feels like things keep coming back.

It wasn't something I just decided to do, 15 years of hating my life eroded almost everything but my basic needs. Now I can look back at that time and with confidence say 'no' when asked to do something which would cause me to relapse.

> it was just that no matter how much I tried I couldn't predict a future where I weren't constantly in agony

That's a great way to put it. I had a few depressive episodes in my life, I know that these thoughts and feelings are symptoms. The inability to feel, even the hopelessness are symptoms of the disease. Usually, I can even pinpoint the cause of the episode. But another symptom is the inability to imagine a state of mind without depression. And no matter how rational you are, it is very difficult to believe in something that you cannot imagine.

Take the medicines so you can enjoy an even better life.

I have been prescribed several kinds but they didn't really fix the problem. I have also had both CPT and psychoanalysis sessions for years and they didn't really help either. They took blood tests etc and found nothing. In the end I realized that they didn't understand my problem any better than I did so I stopped looking for help and just did my own thing.

What I have found through my experiences with depressed people is that the vast majority of them are not insane people in a sane society, but perfectly sane people in an insane society, people who have maladapted to their environment but would otherwise (if they had a better one) be perfectly healthy individuals. Many of them internalize their sadness and helplessness and make it a part of their identity, further reinforcing the common belief among depressed people that they are ill at a biological level (and are not merely healthy people in an unhealthy environment). I don't think the solution to this is ever going to lay in the hands of psychologists, and certainly not psychiatrists (SSRI's and SNRI's work only slightly better than chance in most people, and taking other antidepressant/mood-stabilizing medication is a hellish experience all its own) - it lays in the hands of the people who construct the environment we live in, the people in charge of its development and health, the people who have the most power over society. These are the people who have destroyed it and made the environment we all have to live in such a hellish place, and their successors will certainly be the only people who can fix it.

I don't know. Depression has been recorded for thousands of years, so either society has always been insane (quite likely), in which case it's not likely to turn around any time soon, or there are other causes of depression. Some people can also fall into a depression for no identifiable reason (I can vouch for that from experience).

SSRIs and SNRIs and other medications have saved my life and some of my sanity, and I have high confidence that it's not a placebo - for me - having tried and failed with probably a dozen of these over the years, before hitting on a workable combination.

And after maybe 5 years or so, that combination became ineffective, and I had to try a few more.

But that's just me, so this is anecdata.

>I don't know. Depression has been recorded for thousands of years, so either society has always been insane (quite likely), in which case it's not likely to turn around any time soon, or there are other causes of depression. Some people can also fall into a depression for no identifiable reason (I can vouch for that from experience).

Of course there have always been depressed people, but the modern phenomenon where supposedly 10% of the population will have it in their lives, or where entire countries experience skyrocketing suicide rates, is certainly not related - I find it very difficult to believe that they all have a biological problem, instead of a cultural or societal problem.

>SSRIs and SNRIs and other medications have saved my life and some of my sanity, and I have high confidence that it's not a placebo - for me - having tried and failed with probably a dozen of these over the years, before hitting on a workable combination.

I don't doubt this - I only said that the vast majority of sufferers of depression do not seem to suffer from a biological problem. From my personal experience, I have seen that most of the depressed people I have known have gotten better not through medicine or medical procedure, but by consciously trying to make their lives better and be the best person they can be. Obviously this won't work for everyone - there really is such a thing as biologically-caused mental illness (see: schizophrenia, for example), but I think it is much rarer than people are willing to admit.

>But that's just me, so this is anecdata.

All data is anecdata. It's not worthless just because it happens to be your actual life and not collated and tallied by some detached scientist, it has meaning and value even without being a part of some anonymous dataset you can take confidence intervals on.

You make your points persuasively and elegantly, and I agree with you for the most part. I think much of what is diagnosed as depression in recent times may be a synonym for despair at these times (echoing Cicero : "O tempora! O mores!"). On the other hand, clinical depression of the kind that has assailed me since my teenage years (and from which my son suffers and showed signs of since 5 or 6 years old) appears most certainly to be genetically caused.

I suspect that maybe a physical cause of depression is less rare than you think.

> Depression has to be about something more than just beliefs; it has to be something fundamental to the nervous system.

Is he saying thoughts and beliefs aren't fundamental to the nervous system/CNS/brain?

What if people get depressed because their lives suck and they had a shitty childhood?

Also, why are women twice as likely to get depressed than men?[0] If "happiness is the derivative of neural confidence"... then do men have more neural confidence?

[0] http://www.mayoclinic.org/diseases-conditions/depression/in-...

> Not only became adaption to the given reality the goal of development, but the pathological was seen as a failure to adapt to reality. The validity of that reality was not questioned. The sick carried the blame for being sick. That the pathological could sometimes be the only way to maintain autonomy itself in the face of pseudo-social realities was completely outside the ken of such a mode of thought.

-- Arno Gruen, "The Betrayal of the Self"

That people get depressed or sick in other ways isn't terribly surprising. Look at the world we're making for ourselves and others to live in. It's like toddlers getting sick when crawling on a floor so dirty you can hardly see the floor, and if our first and only reaction is to ask why would the toddler get sick and what kind of protective clothing could they wear, because we're unwilling to face those shitting on the floor, it does not take a scientist to see what's going on. Putting your head over a microscope like an ostrich is what's required to not see it.

Yes, there are actual intricate mechanisms. Just like there are for getting infected in an environment full of pathogens. I'm not even saying they are not interesting or worth studying and quantifying and whatnot. Microscopes are useful, for some things essential. But sometimes the lame, boring answer, like "the world is still too unjust, too many children get abused or neglected in so many ways, often enough because their parents get trampled on, too", is the correct one, that is, it's the correct first part, it requires then acting on that. Until that sentence is no longer true. It's like a spoon to a soup; whoever told you using a fork is more elegant is trapped and trying to trap you.

> What if people get depressed because their lives suck and they had a shitty childhood?

But people don't only get depressed because of those things; plenty of people's "lives suck" who aren't depressed, and plenty of people with good lives _are_ depressed.

https://en.wikipedia.org/wiki/Major_depressive_disorder says:

"The cause is believed to be a combination of genetic, environmental, and psychological factors.... About 40% of the risk appears to be related to genetics."

So yes, thoughts and beliefs are part of depression, but they certainly don't explain all of it.

Beliefs are passed down like genes.

This is true in the case of my family. My brother and I learned how the world worked from my parents, and it's taken years for me to unlearn what they taught me instead of some actually useful beliefs.

True, but you can't unlearn your genes (yet).

Dopamine and norepinephrine dysfunction exists heavily in men too. ADHD is significantly over-represented in males. I think the added serotonin dysfunction is more prevalent in women, and the resulting condition manifests differently.

This doesn’t make sense to me. Pretty much every purported treatment for depression involves either increasing the amount of sensory stimulation you’re getting or else becoming more attuned to sensory stimulation: exercise, acupuncture, aromatherapy, drugs, meditation, float tanks, social interaction, music, intensely flavored foods, cold therapy, saunas, electroshock therapy, etc.

Occam’s razor would suggest its more likely that lack of sensory stimulation causes some sort of brain damage, e.g. inflammataion or receptor density changes, and that it just takes a few weeks to reverse. I’m not seeing what evidence there is for this pereptual confidence model beyond what I’m proposing. I wouldn’t doubt if people do get more confident in some aspects of their sensory experience, but it would seem difficult to prove this as an explanatory model.

> exercise, acupuncture, aromatherapy, drugs, meditation, float tanks, social interaction, music, intensely flavored foods, cold therapy, saunas, electroshock therapy, etc.

None of those are guaranteed to work though, a significant number of depressed people never gets over it and it wouldn't be that way if we knew effective treatment methods.

The current answer is we don’t yet have full functional pathologies of types of depression, noninvasive, specific mood disorders classified down to exact neurological dysfunctions, accurate and precise knowledge of how existing antidepressants work and evidenced-based application of particular therapies based on such scientifically-identified presentations. Clinical psychiatry has been mostly a scattergun, guesswork that lacks scientific rigor.

For example, I just tapered-off mirtazepene as it stopped working after 9 years and, so far, bupropion isn’t helping. I’d really like to try S32212 if it proves safe enough in human models because it likely lacks the GI and weight-gain issues.

I've tried almost every anti depressant on the market and none of them worked. What did work for me is kratom. I've been taking it daily for about six months and it has completely turned around my mood and general enthusiasm. There are some minor side effects but they went away after six weeks or so. I know it might frowned upon to recommend what is basically an opiate for depression, but it has been a minor miracle for me.

And what if your depression is cause of beliefs/behaviors and not curable with pills?

Sublingual ketamine has worked well for my girlfriends depression. Dissolved into water at 30mg/mL, she takes 1mL every three to four weeks. A threshold dose, the dissasociative effects are rather weak there, but the antidepressant effects are rather rapid and work wonders for her.

If you’re in the US, I believe you can go to clinics and have it administered by a doctor which is safer.

Depression to take a few weeks to reverse if you just get enough stimulation? Gee, nice to hear. Maybe I'll just try that.

> Depression to take a few weeks to reverse if you just get enough stimulation?

On average it will reverse regardless since the half-life of depression is only a few weeks, unless you take antidepressants in which case it's perhaps less severe but is also less likely to go away.

> but is also less likely to go away.

Why are you posting absolute nonsense here?

Charitably, the parent has misphrased the following sentiment: "taking antidepressants correlates with having worse depression (in the same way as taking antibiotics correlates with having worse infections)".

> the half-life of depression is only a few weeks

Are you referring to a single major depressive episode? And presumably not referring to the various other depressive disorders that last months to years?

FWIW, this one of many things that makes treating "depression" challenging - there are many different forms of depression, and not infrequently the underlying pathology is quite different.

> Are you referring to a single major depressive episode?

Yeah if you read Anatomy of an Epidemic, Robert Whitaker has a good research review of all the large scale NIMH/NIH studies.

What you're saying is not in any way in conflict with the predictive processing model, as far as I can see.

You might want to read the article he posted earlier where he reviews Surfing Uncertainty[0]. It discusses this model in more detail.

[0] http://slatestarcodex.com/2017/09/05/book-review-surfing-unc...

For context check out the book he's referencing, or at least his review of it:

https://slatestarcodex.com/2017/09/05/book-review-surfing-un...

Umm, not sure this is universal but partial. Depression seems evolutionary psych for multiple, overlapping purposes:

- Reducing aggression (and hence conflict) in larger groups.

- Focusing on existential re/purpose by turning inward (ie find a new job/hobby/outlook/philosophy). Lots of reading, writing and ideation. Hopefully rebuild confidence/positivity with completing something.

- Retreating for terminal resource consumption minimization. Leave more for the young.

Also, anecdotally, I did everything “right” (ie CBT, frequent vigorous exercise, solid career, friends, sleep hygiene, address sleep apnea) and still couldn’t escape depression’s “mind pain” and depressive state. Only medication worked, like parting the clouds, waking up refreshed and organized thinking instead of a jumble.

Medication will stop working, it always does.

That's the spirit!

In all seriousness, what else is there to do? Take whatever relief you can get while you can get it.

Remove bad habits/ behaviors/people... cure the problem

So you are hoping there will be an ELE for the human species? Because that's the only way your prescription is going to cure the problem on a global basis for the foreseeable future.

When I say remove I didn’t mean remove from existence lol, just from your life. It’s true this isn’t a solution that can be implemented by governments, it has to be implemented by the patient.

>One complicating factor – how do we explain depressed people’s frequent certainty that they’ll fail? A proper Bayesian, barred from having confident beliefs about anything, will be maximally uncertain about whether she’ll fail or succeed – but some depressed people have really strong opinions on this issue. I’m not really sure about this, and admit it’s a point against this theory. I can only appeal to the math class example again – if there was a math class where I just had no confidence about anything I thought or said, I would probably be pretty sure I’d fail there too.

I think the model actually fits here better than the author realizes. Predicting failure is much safer than predicting success, it's erring on the side of caution. If you predict that you will fail at something and prepare for the consequences of that failure, but succeed instead, you are better off than if you had predicted success, prepared for success, and failed. To me, it makes sense that, when uncertain, the default would be to predict failure.

And later:

>One problem with this theory is the time course. Sure, if you’re eternally successful, you should raise your confidence. But eternally successful people are rarely eternally happy. If we’re thinking of happiness-as-felt-emotion,itt seems more like they’re happy for a few hours after they win an award or make their first million or whatever, then go back down to baseline. I’m not sure it makes sense to start lots of new projects in the hour after you win an award.

Wouldn't a rise in confidence have a corresponding rise in expectations? New goals mean a return to the state of "haven't succeeded yet".

Personally I'm finding this model seems to fit better than any other model I've heard of. Of course, I'm just some idiot on the internet, not a psychiatrist.

This sounds a lot like Martin Seligman's work. https://en.m.wikipedia.org/wiki/Martin_Seligman

Or rather there is no predicting failure. You only predict success and when you have low confidence in success, you're certain of failure.

It's great to see this here.

For context, this is the model the author is referencing:

https://slatestarcodex.com/2017/09/05/book-review-surfing-un...

Scott Alexander is currently my favorite essayist. I just wasted most of yesterday reading the last 18 months of his "links" posts.

I regularly pass his work on to friends and would do so more often if I didn't think it would upset people.

This particular topic is very much of interest to me; I've spent a good amount of time thinking about how depression relates to ADHD.

Depression and ADHD are both related to dopamine and norepinephrine dysfunction, but depression has a strong element of serotonin dysfunction as well.

One of the defining characteristics of hyperactive individuals is their addiction to stimulation (work, learning, leisure), which to me seems like it's fed by negative reinforcement. Removal of these things sends them into a depressive state because there simply isn't anything keeping them excited (and perhaps distracted from neuroticism).

It seems like depression is kind of the contrapositive. There is the same element of dopamine dysfunction, spawning disinterest and hopelessness, but they lack the positive reinforcement of anything to pull them out of. I think this is where the sprinkling of serotonin dysfunction into the pie comes in. There's a very low level of security or confidence in any sort of endeavor.

I typically have odd thoughts that are often wrong. But I really like quote from 'The Martian', "let's science the shit out of it".

I don't know if it's possible to science your way out of depression. If in some way the curiosity gives a small enough lift to keep you getting one foot in front of the other and learning about what's causing your depression.

It at least seems relatively risk free way of tackling depression. Learn about the beast and track what you do and what changes your mood.

But is this something you can tell people that are seriously depressed or is it just another useless bit of advice?

> But is this something you can tell people that are seriously depressed or is it just another useless bit of advice?

From my point of view, it's not useful advice, partly because severe depression utterly saps the motivation to do virtually anything, and partly because depression is highly resistant to rationality.

Mandatory references to "Hyperbole and a Half"[1][2].

[1]: http://hyperboleandahalf.blogspot.com/2011/10/adventures-in-...

[2]: http://hyperboleandahalf.blogspot.com/2013/05/depression-par...

Yes, this wouldn't work for the most serious cases of depression. It might help for those who are at a stage where they're willing to try something.

I’m not sure why none of the studies touch on seasonal variation. I think I will research more of that but does anyone has a reference?

This? https://en.wikipedia.org/wiki/Seasonal_affective_disorder

No mention of sleep?

* http://www.thelancet.com/journals/lanpsy/article/PIIS2215-03...

I think there's a lot of agreement that sleep is important, but not much consensus around models that are useful for treating it. Right now there's a big push for CBT-I, but the evidence is mostly low-quality and not really focused on anything except reducing subjective insomnia severity (this study is better than most in that respect).

A book review[1] linked in the article is also very interesting.

[1] http://slatestarcodex.com/2017/09/05/book-review-surfing-unc...

Chekroud (2015) here - just wanted to say that I think SSC is awesome, and does a terrific job discussing complex problems in psychiatry & philosophy.

Could you give any recommendations of great articles on that blog? Or should people just go to the About/Top Posts[1] page and go down the rabbit hole from there?

[1] http://slatestarcodex.com/about/

Here’s a reddit survey of people’s favorite posts, which closely matches my own:

https://www.reddit.com/r/slatestarcodex/comments/61qrm2/favo...

If your main interest is psychology, though, note that many of the top posts are more in the sociology and politics realm.

Meditations on Moloch: http://slatestarcodex.com/2014/07/30/meditations-on-moloch/

For me, it was a mind-blowing read. Highly recommended.

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