22 ms·

Researchers treat depression by reversing brain signals traveling the wrong way

325 points by CharlesW 4y ago

alex-moon 4y ago
Really fascinating stuff. I immediately wonder if there is any explanation for this reversed flow of signals that might tie it into an evolutionary theory of depression e.g. the social withdrawal hypothesis - is the brain using less energy doing things this way?
- throwuwu 4y ago
  Interesting thought. My mind went to the possibility that since they reversed signals are allowing your mood to determine how you feel physically that it might allow you to leverage a good mood to overcome negative signals from your body i.e. power through pain or exhaustion. Maybe it became maladaptive when more opportunity for rumination became available.
e79 4y ago
It’s fascinating how many potential modalities are at play with depression. Serotonin, inflammation, direction of brain signals. This suggests that depression may be a label that points to one of many underlying conditions, which could also explain why it’s so tricky to treat for some individuals.
- asdfman123 4y ago
  As someone who has more or less successfully learned to deal with depression, ADHD, anxiety, etc., the trick is basically doing everything considered "healthy." We don't understand all of the mechanisms of long-term illnesses like depression, diabetes, heart disease, Alzheimer's, etc. but we do know how to fight them: exercise and good diet. * Some processes in the human body obviously get disrupted under modern conditions, so it's important to give your body something it's a little more used to: more movement, more traditional foods. * (Obviously, it's not going to automatically fix depression in all cases, but it's absolutely worth fighting the good fight if you can. Other treatments are definitely worth trying too.)
  - leksak 4y ago
    > But I also believe that if you don't exercise, eat nutritious food, get sunlight, get enough sleep, consume positive material, surround yourself with support, then you aren't giving yourself a fighting chance.” - Jim Carrey Sometimes though, any one of those or all of them can end up seeming impossible because of the depression one is fighting.
    - asdfman123 4y ago
      Absolutely. I will point out that depressed people struggle with black-and-white thinking, so just taking the smallest steps in the right direction are a good start. Slowly build up incrementally better habits over years. It might start with a 10 minute walk.
    - deleted 4y ago
      [deleted]
  - e79 4y ago
    Agreed, but with the caveat that depressed people often struggle with making the changes they need the most. Similar thing with obesity. There often needs to be some kind of intervention, such as a medication, to offer enough relief for someone to break the cycle and start making changes. Willpower alone isn’t always realistic.
  - hirvi74 4y ago
    My issue is that the disorders/symptoms interfere with my ability to do "everything considered healthy." The ADHD makes it impossible for me to stick to exercise routines as well as other routines. The depressive symptoms make me feel like I am carrying a ball and chain and every little thing requires so much energy. The worst part is that I am treated for ADHD, and even that has basically any negligible difference anymore. I feel like I am trapped in a negative feedback loop that I cannot escape.
    - asdfman123 4y ago
      Does your ADHD make you feel antsy, like you need to get up and move around?
- jaggederest 4y ago
  I have a pet theory that much of what we call mental health and chronic illness will eventually be traced back as a symptom of some causative factor - most likely infectious or environmental - rather than being a base illness as we think of them now. Much as we don't think of "fever" as an illness any more, I suspect "depression" will become descriptive rather than predictive - which, to an extent, it already is, at least according to the DSM as I understand. It's also possible that we'll see it as something that is multifactorial - some genetic susceptibility combined with environmental and/or infectious triggers.
  - _yb2s 4y ago
    I agree but I think we will find that emotional trauma is also a big component of the multifactorial causes.
  - bitL 4y ago
    I think they should first stop treating depression as a single illness. There are likely thousands different reasons for brain to end up with similar symptoms. Many forms of nutritional deficiencies likely turn into something that can be symptomatically classified as depression and sometimes be fully reversible by just restocking that missing nutrient or reducing its intake. Yet we clinically classify such conditions the same as ones caused by some brain injury or mentally horrible experiences that rewire brain circuits in weird ways.
- spacephysics 4y ago
  Fully agree, to me depression is a common symptom that the system of biological processes “outputs”, if you will, when some process isn’t running optimally. Stopped sugar suddenly? Inflammation from food you’re eating? IBS in general? Traumatic upbringing leading to entrenched “thought loops”? Undiagnosed disease? These all and more can have depression as a symptom. My armchair psychologist opinion is the DSM 5 category process isn’t fitting correctly to how humans operate. I believe there’s a completely different modality that has yet to be discovered (or known in mainstream science) that gives us a better way to diagnose people. I find it nuts that you subjectively, in most cases, ask the patient if they fit in usually 3 of 5 categories, or what not, and that determines the diagnoses. Countless times it’s like “okay, what does hyper mean?” “What does intense rumination mean?” We need a more objective way to measure these criteria. I was diagnosed with depression for a while, tried a bunch of drugs, none really worked. Then for shits I do a neurological adhd battery and lo and behold, seems like that’s it. Now using the correct behavioral changes leads to the depression going away, and far higher quality of life. I know the system, DSM 5, is best we have now, but we need more innovation in this space
  - franl 4y ago
    Which behavioral changes got you there?
    - simonswords82 4y ago
      Not OP and I can’t speak for the entire human population but for me it was changing the relationship I have with myself. Make a mistake? No big deal it’ll be better next time. Learn from it rather than beat myself up for it. Hit that red traffic light? Time for self contemplation and putting the heated seats on rather than being pissed off I’m delayed 30 seconds. Get an email that triggers my threat response? Take a breath and think about who I have around me who can help rather than take it all on myself. Have a read of learned optimism. Great book. Get therapy. Hit the gym. Go for walks. Brush your teeth for 2 mins. Moisturise. Show yourself as much self care as you can.
      - 3y ago
- Choco31415 4y ago
  I went through a few different versions of depression myself and it absolutely feels that way. Each was caused by a different trigger, and the strangest thing is, despite all the tests doctors ran, everything came back normal. They couldn’t figure out what was happening.
deleted 4y ago
[deleted]
asdfman123 4y ago
> “It’s almost as if you’d already decided how you were going to feel, and then everything you were sensing was filtered through that,” he said. “The mood has become primary.” This is 1000% what depression feels like, once you've properly come to terms with it. Your brain seems absolutely compelled to apply the most horrific, negative interpretation to everything that happens to you. Even when you understand it's wrong, or at least heavily negatively biased, fighting those interpretations feels like trying to swim upstream in a terrific current.
- comrh 4y ago
  Which makes sense why CBT style therapy has shown effectiveness because its main focus is challenging those interpretations. No doubt even with those tools it is still a major challenge.
  - asdfman123 4y ago
    One interesting thing to point out is CBT is so effective because it's somewhat easier to stick to than other approaches. Meditation, for instance, is equally effective if you keep with it, but most people realistically won't.
- AndrewKemendo 4y ago
  This is one of the few times I've heard an accurate and concise description of what it feels like. I like the metaphor of the spiral wishingwell. The coin/ball represents the level of depression you sink into. The gravitational draw of the void makes the spiral go faster unless you figure out a way to pull out of it and the longer you wait the harder it is to pull out cause it's moving too quickly. So the trick becomes keeping the coin/ball off of the spiral
  - hanselot 4y ago
    The only way out is through. One way or another, once you reach the shore on the other side, the time spent in the water doesn't seem so bad anymore. Just another perspective to lean on when understanding others. Once you confront it in the most absolute sense, something akin to ego-death occurs, and you make a decision about whether it is worthwhile to continue. Everything comes from and swings back to chaos. Embrace it and you will be free.
JohnMakin 4y ago
Unfortunately, TMS is extremely expensive and not likely to be covered by most insurance plans. Even with a decent PPO, I was quoted about $1k a treatment and they said I needed at minimum 30 treatments.
- radicaldreamer 4y ago
  There are effective alternatives which are a fraction of the cost: ketamine (sublingual ~100mg every few days), psilocybin (free? cheap 2-3g ~4 weeks), rapamycin + ketamine also seems promising (https://www.nature.com/articles/s41386-020-0644-9 https://www.nature.com/articles/s41386-020-0644-9).
  - wizzwizz4 4y ago
    I would recommend against trying to self-prescribe addictive substances.
    - rozularen 4y ago
      I don't think any of those are addictive actually
      - marcellus23 4y ago
        just because they're not chemically addictive doesn't mean they're not addictive. Weed isn't chemically addictive but plenty of people struggle with it nonetheless.
        blastro 4y ago
        same with food?
        marcellus23 4y ago
        Well, yes. That's what "food addiction" is.
endisneigh 4y ago
disclaimer: I acknowledge depression as an illness and state of being. that being said, if you take someone who is objectively "not depressed" and apply these same depression treatments, what would happen? some state of euphoria? heightened mood? happiness? suppose that new state is now the normal state in which people are judged against. now, the before-mentioned person who was not depressed, may be considered depressed, relatively. so you now apply the same thought experiment again. clearly this can be recursively done infinitely... such is an inflationary view. so my question really is around the cultural vs. biological construct of depression. what if it's ok to be depressed? this is not to say that we shouldn't be trying to "treat" it (and the symptoms), but I do wonder at what point do we say it's OK.
- supernikio2 4y ago
  What brain signals would you reverse on a non-depressed person?
- admax88qqq 4y ago
  It's not okay to be depressed because it sucks to be a person who is depressed. Being depressed is not a nice state to be in. This isn't an "ooo society is wrong" type of situation. Sure there are some societal pressures to appear happy which can make depression _worse_, but depression is still awful regardless of those and we treat it because it's awful.
- ebolyen 4y ago
  Instead of imagining that it works like a number line and then observing that you can use induction, you could measure outcomes: suicide, suicidal ideation, quality of life, etc. That puts a pretty reasonable lower bound on what is or isn't depressed. It is absolutely an altered state of mind, and an information processing disorder. For anyone who might feel like "it's ok to be depressed", this is not a normal thought, and there is no normal amount of suicidal ideation. Seek professional help or strong social support; just ask for help anywhere it might exist (go to an emergency room and just have a seat if you must). If you aren't depressed, these thoughts literally don't happen, as strange as that may sound if you are in the thick of it.
kypro 4y ago
I hate this idea that signals can move the "wrong" way. There have been few days in my adult life that I wouldn't have preferred to not be here. Depression sucks. Yet, I don't think people are right when they tell me I'm wrong to be depressed. I hear that some people feel their depression shouldn't be there and that they should feel happy, and in those cases I think this sounds like it could be an excellent solution, but in my case (and I think others too) I could give you very well reasoned arguments for why I would prefer to not to be here and why I feel a sense of sadness as my default state. At least in my case I believe arguments for optimism are more wrong than my depression. Interestingly, my girlfriend is the total opposite to me. She's the happiest person ever met and I often wonder why she isn't also considered to be suffering from some kind of mental defect – I guess in her case the signals must be moving the "right" way because obviously the "right" way to feel is happy 24/7 and prolonged sadness is "wrong". I guess I always kinda liked the idea that any advanced intelligence would end up as some iteration of Marvin the Paranoid Android, since the logical conclusion should perhaps be that life is pointless and hard, so therefore why bother? Perhaps the "right" way for signals to travel is in the direction of depression and hopelessness. Sorry I know this isn't really on topic and I sound like a complete downer. I'm certainly not trying to diminish this research. I've guess I've just always found it interesting how some people feel they can categorise mental states as "right" or "wrong".
- airstrike 4y ago
  I have full sympathy for people dealing with depression but I don't think this logic holds. People who are depressed have suicidal ideations, suffer in quality of life and generally struggle to accomplish otherwise simple tasks. It is "wrong" in the sense that it has all of these objectively negative consequences whereas being blissfully happy does not, so it can be claimed to be "right" in relative terms. I think you are attributing to the word "right" a sense of an obligation to feel happy, with "wrong" therefore being a deviation from that True Path, but I don't think that is the intended meaning when people use those words to describe depression. I would argue that "right" in this context means something closer to "nominal", as in "working as intended". Nobody is faulting you (or me or others) for constantly feeling down. I hope that helps.
poorbutdebtfree 4y ago
Is depression a first world problem? Maybe if we can send over our highly trained and effective therapists to the third world we'd find that 95% are depressed too. It'd make depression much easier to deal with if we knew everybody had it regardless of qualify of life issues.
- jiveturkey42 4y ago
  Probably just people with the luxury to sit inside all day in climate control, completely disregulating the hormones
- rybosworld 4y ago
  It is certainly not just a first world problem. There are many problems in advanced nations that get a spotlight on them, but that doesn't mean those problems don't exist in less developed places. In some parts of the world, getting fresh water is the biggest concern. Solving that problem becomes so important that topics like mental health may be completely ignored. I would wager a guess that North Korean citizens rank especially high in prevalence of depression, but it's not even a top 5 concern for them. The historical record has many descriptions of depression dating all the way to B.C. times. Depression has been a thing that has affected humanity for at least as long as organized civilization has existed. I think a good question to ask is: Do uncontacted ("lost tribe" cultures if you will) peoples have differing prevalence of depression compared to the connected world? I don't know the answer to that question, but I wouldn't be surprised if the rates of depression in those cultures is lower.
- igravious 3y ago
  No, depression is not limited to any specific region or socioeconomic group. Why would you think that it is?
robotburrito 4y ago
We are always trying to solve this problem while avoiding the elephant in the room, the current state of society is not very healthy for most people.
- walleeee 4y ago
  There are two truths here which are often taken to preclude one another, but I think they can coexist 1. Depression can be treated and even overcome in some circumstances 2. There are very justifiable reasons many people might be depressed
  - throitallaway 4y ago
    What I find most troubling is how resources and power get concentrated in hands of the few, and the rest of us (99%+ of the population) are left to deal with the consequences. The few laws that do exist to prevent benefiting parties from raping and pillaging the earth and society at large are slaps on the wrist at best. The default is to toe the line and/or overstep legality and morality. That's what's so depressing about it all.
    - somebody78978 4y ago
      Yeah, but that's also been the case for thousands of years.
    - eastof 4y ago
      I commented about this above since this type of thinking is what I see most commonly in my anxious/depressed friends. Really think on it deeply for a bit and you'll realize this belief can't possibly be justified rationally. Who are you to say that resources and power shouldn't be concentrated in the 1%? You say they overstep morality? That's your morality and you can't defend it rationally (no one can). Plus you can't change these things anyway, so you have no moral responsibility to do so (my morality). Media, politicians, advertisers, etc. all instill FUD to make you feel this way so the default option is pessimism. Try optimism. It may be wrong, but pessimism may be wrong as well and no one will ever find out so why even care who is right?
aszantu 4y ago
Don't know who needs to hear this. I started a food diary after an elimination diet which restored my energy levels. I don't know the reasons, but you're looking in a time window of four-seven days. When I stray from my diet (meat and water) one day. I become mentally unstable after 4 days. It says for 3 day, then gets good again. Crying for no reason, ruminating, poor sleep, strong sour smell that can't seem to be removed by washing but can be suppressed by a strong anti transpirant. Going for sibo testing soon, if it's not hereditary, enzymes might be a solution. If it is, Pankreas is up for investigation next. Been looking for solutions since 2018, no doctor could offer an explanation so far.
- stuckinhell 4y ago
  thank you for this! I have something very similar
  - aszantu 4y ago
    Have you noticed something else? I seem to tolerate sour apples and 1 teaspoon of sauerkraut per day, but not much more. Also garlic seems to be okay, but not onions, chilly powder is okay but not chilli-peppers or pepper, or tomato or seeds in general. Allergy tests all came back negative
    - stuckinhell 3y ago
      I'm leaning towards maybe some gut bacteria causing this illness maybe. My allergy tests were negative too.
- NeuNeurosis 4y ago
  Definitely have experience with the same thing with food. I did end up finding out it was my Pancreas and take enzymes with every meal. Really really helps and has given me way more energy and my guts feel 90% better. Still have to watch certain foods and drink plenty of water but it is way better. Good luck.
  - 4y ago
fpgaminer 4y ago
Other comments have proposed that depression may have multiple underlying causes, and thus may require different treatments. I'm curious about the other direction of thinking. What do SSRIs, psychedelics, CBT, and TMS all have in common? Suppose that there is one common cause, or one at least one cause that applies to 90% of cases. And it's treated by all these seemingly disparate methods. That's what tickles my curiosity the most, as it begs a more fundamental question about the functioning of the brain. Maybe the author's theory is correct: brain signals between certain regions are going the "wrong" way in depressed patients. That would imply that SSRIs are causing the same shift. God, I would love if the authors tested that. And then we can finally dig into why SSRIs work (we don't current know). If they're causing shifts in brain activity flow, then we can find out how. And from there maybe we can treat other mental diseases with better pharmacological or TMS solutions. Are things like schizophrenia arising from a similar bad pathing of information around the brain? Psychedelics is also a weird one. People have proposed many theories as to their mode of operation for treating depression. But now I wonder, based on this research, if the key factor was just the disassociation from one's body and altering of senses. The other effects like connecting disparate thoughts, forming more brain connections, ego death, etc may not be related at all. That could lead the way to more targeted drugs. Really cool stuff. If if pans out, of course. But unlike other theories of depression, at least this one is easy to test.
- opportune 4y ago
  If you consider that CBT scratches a need for deep socialization, they all basically act on serotonin in different ways. I don’t buy the oversimplified “depression is when your brain doesn’t make enough serotonin” model but it does seem there is a strong connection. Maybe there is some kind of local optimum your serotonin-mediated pathways can get stuck in and need help getting out of. In fact, this (generalized outside of just serotonin) is something I do buy as a basis for depression: your brain enters some local optima or learns some poor but good-enough coping mechanisms that keep you going but prevent you from fixing underlying issues (whether it be due to maladaptive behavior, framing or interpreting things negatively, low self esteem leading to poor social performance and consequently lower self esteem). That’s also kinda what CBT is about addressing
- 4y ago
brainmagnets 4y ago
I recently went through a round of rTMS and participated in a study that used EEG to attempt to find biomarkers for responders vs non-responders. This was largely based on previous findings that altered functional network activity in the brain (namely the default mode network) is correlated with depression in some people, and that EEG could relatively inexpensively detect functional network changes over the course of treatment. This study seems to follow a similar vein and I suspect we'll see more like it in the near future. I'm really glad to see more research being done with TMS - the particular protocol mentioned in this study (SAINT protocol) has had truly amazing success with 80-90% remission rate in already treatment-resistant individuals in a couple of studies. Even ECT, which is currently considered the most effective treatment for treatment-resistant depression, has only a 70-80% response/60% remission ("regular" rTMS is about 60% response/30% remission). The only problem is that SAINT requires fMRI which is expensive and complicated, on top of already expensive rTMS treatment. Hopefully as more research is done it'll become more accessible, personally it was very helpful for me in overcoming many years of intractable depression.
mynameisash 4y ago
My son, who is diagnosed with ADHD, anxiety, depression, and OCD, and who has been in talk therapy, on SSRIs, and other interventions for years, recently started LENS therapy, also called neurofeedback. (I'm on mobile device, otherwise I'd find the link.) It sounds a lot like a form of TMS. He's had something like 7 sessions, each lasting maybe 15 minutes. The results are nothing short of astounding for our family. He's typically been... Extremely difficult to parent. After his LENS, lasting about a week, he is a pretty happy kid who participates in family and social life. His anxiety previously prevented him from engaging with friends for more than an hour. Just the other day, he was out at a birthday party for eight hours and still cheerful afterward. I'm very hopeful that there is a long term, lasting effect for this kind of thing.
- fourg 4y ago
  That's wonderful that it's helped your son so much. I have done TMS and am curious about LENS for myself and family who have symptoms similar to what you shared. We too have tried most everything else and daily life is an absolute grind. How many sessions did your son require and how long are the results expected to last?
  - mynameisash 4y ago
    To be honest, I don't know how long LENS will be for us. We're doing weekly sessions. It's not supposed to be indefinite, but I don't know at that point we taper down or stop. Results were pretty much immediate, though. After his first session (maybe only a few hours later), he self-reported improvements and we noticed a definite change in his mood and attitude.
- deleted 4y ago
  [deleted]
- cactusplant7374 4y ago
  Is this a therapy that can be done at home?
- aerophilic 4y ago
udev 4y ago
Very interesting, so it could be that depression is essentially a race condition in the brain.
carabiner 4y ago
The commercialization of this treatment is being handled by https://www.magnusmed.com/ https://www.magnusmed.com/. Some existing TMS treatment centers claim to be performing the SAINT protocol right now, but the researchers have never fully revealed the treatment plan (using fMRI, algorithm for targeting) and so the claims can't be substantiated as being exactly SAINT. I'm pretty desperate to get onto a trial. Here's hoping that this gets FDA approval ASAP.
flippinburgers 4y ago
I have had what seems to me to be depression for most of my life (40+ years). I have been fortunate enough to have a kid and, now, I guess I just don't have time to be depressed or something because most of my thoughts of ending life etc have, quite thankfully, gone away. I'm really not trying to be off-putting when I say this but I do sometimes wonder if some instances of depression aren't simply a cause of people not having families. I'm not totally confident about this, but ... really I think having kids gets looked down on for all the wrong reasons and maybe our deepest drives are all tied to having them.
- bendbro 4y ago
  I agree, I wonder if depression is not always rooted in some random, mental problem but rather a reasonable reaction to reality.
  - EGreg 4y ago
    I kept saying this for years on HN but until the 2022 study it was always voted down and told that NO, it is due to a chemical imbalance and that we don’t understand
    - notnaut 4y ago
      There is the chemical imbalance and then there is the diagnosis. Complete guess, but wouldn’t be surprised if the rate of people with the imbalance has climbed less dramatically over the last several years than the rate of people being positively diagnosed.
    - bendbro 4y ago
      I recall that study! I suspect those downvotes are due to people recognizing that it implies depression is sometimes within the control of someone afflicted by it and conflating that with blaming the person afflicted by it. People seem offended by critiques of modern ideas that rationalize away an individual's control, agency, and especially culpability for their behavior or outcomes. Sometimes these rationalizations are fair, other times not.
burglekutt 4y ago
Sometimes I feel like programming is physically and mentally designed to create bad health and mood, at least if you’re not very careful about how you’re _being_ while doing it. Maybe it’s just me, but I have to work hard to avoid: - Bad posture, hunching towards the monitor - Scrunching the face - Feeling impatient because my fingers and the computer can’t keep up with where I am in my mind - “Damn you, computer!” frustration in small doses throughout - Frequent interruptions via email, Slack, texts, coworkers, etc - In some cultures, it’s very hard to have a plan for what to get done in the day and then execute on it due to getting sucked into meetings and stuff.
- polalavik 4y ago
  Ya I’m really interested in what I do and side projects I work on but I feel like absolute shit after focusing on either. Not sure how to solve this. it feels unsustainable to find equal amounts of joy(?) and ~bad feelings physically and mentally~ from partaking.
iandanforth 4y ago
What does "brain signals traveling" even mean? The brain is highly interconnected with both forward and feedback connections at all levels. Both of the mentioned regions are always active and always sending signals bidirectionally. fMRI is a slow, low resolution approximation of brain activity, so I'd really like to know what they are actually measuring as opposed to some clearly reductive analogy of what they suspect might be an underlying cause for that observation.
- makeitdouble 4y ago
  I assume they are checking the timing of the activation cycles ? For instance if sending a strong sensory stimulation first triggers a higher activity level in one part before the other, that could be interpreted as directionality.
ChicagoDave 4y ago
Does it work with people that suffer Bi-Polar Syndrome though? That would be another level.
levi_n 4y ago
I have ADHD, major depression, and I did 8 weeks of TMS therapy last year. In the end it did help my depression some, but it isn't a night-and-day difference. It did, however, completely change how I see myself, to the point where I feel disconnected and separate from the person in my memory. Likewise, my sense of empathy and how I few the world is completely different, for the better. I plan to do another round this summer.
machiaweliczny 3y ago
Tangential but to anyone who is tired and anxious I recommend also checking for Tetany[0]. I got diagnosed with that and just supplementing minerals had positive effect on my wellbeeing. Before I was miss?diagnosed with mild depression and put on SSRI(which helps) but my muscles got so tense recently that I went for dry needling and they recommended I check for Tetany. BTW seems like predisposition to this might be genetic as my mother has similar issues. [0] https://en.m.wikipedia.org/wiki/Tetany https://en.m.wikipedia.org/wiki/Tetany
jscipione 3y ago
Depression is natural given the state of the world right now. There is nothing wrong with the brains of depressed people, anyone who sees clearly ought to be depressed.

325 points by CharlesW 4y ago

Really fascinating stuff. I immediately wonder if there is any explanation for this reversed flow of signals that might tie it into an evolutionary theory of depression e.g. the social withdrawal hypothesis - is the brain using less energy doing things this way?

throwuwu 4y ago
Interesting thought. My mind went to the possibility that since they reversed signals are allowing your mood to determine how you feel physically that it might allow you to leverage a good mood to overcome negative signals from your body i.e. power through pain or exhaustion. Maybe it became maladaptive when more opportunity for rumination became available.

e79 4y ago

It’s fascinating how many potential modalities are at play with depression. Serotonin, inflammation, direction of brain signals. This suggests that depression may be a label that points to one of many underlying conditions, which could also explain why it’s so tricky to treat for some individuals.

asdfman123 4y ago
As someone who has more or less successfully learned to deal with depression, ADHD, anxiety, etc., the trick is basically doing everything considered "healthy." We don't understand all of the mechanisms of long-term illnesses like depression, diabetes, heart disease, Alzheimer's, etc. but we do know how to fight them: exercise and good diet. * Some processes in the human body obviously get disrupted under modern conditions, so it's important to give your body something it's a little more used to: more movement, more traditional foods. * (Obviously, it's not going to automatically fix depression in all cases, but it's absolutely worth fighting the good fight if you can. Other treatments are definitely worth trying too.)
- leksak 4y ago
  > But I also believe that if you don't exercise, eat nutritious food, get sunlight, get enough sleep, consume positive material, surround yourself with support, then you aren't giving yourself a fighting chance.” - Jim Carrey Sometimes though, any one of those or all of them can end up seeming impossible because of the depression one is fighting.
  - asdfman123 4y ago
    Absolutely. I will point out that depressed people struggle with black-and-white thinking, so just taking the smallest steps in the right direction are a good start. Slowly build up incrementally better habits over years. It might start with a 10 minute walk.
  - deleted 4y ago
    [deleted]
- e79 4y ago
  Agreed, but with the caveat that depressed people often struggle with making the changes they need the most. Similar thing with obesity. There often needs to be some kind of intervention, such as a medication, to offer enough relief for someone to break the cycle and start making changes. Willpower alone isn’t always realistic.
- hirvi74 4y ago
  My issue is that the disorders/symptoms interfere with my ability to do "everything considered healthy." The ADHD makes it impossible for me to stick to exercise routines as well as other routines. The depressive symptoms make me feel like I am carrying a ball and chain and every little thing requires so much energy. The worst part is that I am treated for ADHD, and even that has basically any negligible difference anymore. I feel like I am trapped in a negative feedback loop that I cannot escape.
  - asdfman123 4y ago
    Does your ADHD make you feel antsy, like you need to get up and move around?
jaggederest 4y ago
I have a pet theory that much of what we call mental health and chronic illness will eventually be traced back as a symptom of some causative factor - most likely infectious or environmental - rather than being a base illness as we think of them now. Much as we don't think of "fever" as an illness any more, I suspect "depression" will become descriptive rather than predictive - which, to an extent, it already is, at least according to the DSM as I understand. It's also possible that we'll see it as something that is multifactorial - some genetic susceptibility combined with environmental and/or infectious triggers.
- _yb2s 4y ago
  I agree but I think we will find that emotional trauma is also a big component of the multifactorial causes.
- bitL 4y ago
  I think they should first stop treating depression as a single illness. There are likely thousands different reasons for brain to end up with similar symptoms. Many forms of nutritional deficiencies likely turn into something that can be symptomatically classified as depression and sometimes be fully reversible by just restocking that missing nutrient or reducing its intake. Yet we clinically classify such conditions the same as ones caused by some brain injury or mentally horrible experiences that rewire brain circuits in weird ways.
spacephysics 4y ago
Fully agree, to me depression is a common symptom that the system of biological processes “outputs”, if you will, when some process isn’t running optimally. Stopped sugar suddenly? Inflammation from food you’re eating? IBS in general? Traumatic upbringing leading to entrenched “thought loops”? Undiagnosed disease? These all and more can have depression as a symptom. My armchair psychologist opinion is the DSM 5 category process isn’t fitting correctly to how humans operate. I believe there’s a completely different modality that has yet to be discovered (or known in mainstream science) that gives us a better way to diagnose people. I find it nuts that you subjectively, in most cases, ask the patient if they fit in usually 3 of 5 categories, or what not, and that determines the diagnoses. Countless times it’s like “okay, what does hyper mean?” “What does intense rumination mean?” We need a more objective way to measure these criteria. I was diagnosed with depression for a while, tried a bunch of drugs, none really worked. Then for shits I do a neurological adhd battery and lo and behold, seems like that’s it. Now using the correct behavioral changes leads to the depression going away, and far higher quality of life. I know the system, DSM 5, is best we have now, but we need more innovation in this space
- franl 4y ago
  Which behavioral changes got you there?
  - simonswords82 4y ago
    Not OP and I can’t speak for the entire human population but for me it was changing the relationship I have with myself. Make a mistake? No big deal it’ll be better next time. Learn from it rather than beat myself up for it. Hit that red traffic light? Time for self contemplation and putting the heated seats on rather than being pissed off I’m delayed 30 seconds. Get an email that triggers my threat response? Take a breath and think about who I have around me who can help rather than take it all on myself. Have a read of learned optimism. Great book. Get therapy. Hit the gym. Go for walks. Brush your teeth for 2 mins. Moisturise. Show yourself as much self care as you can.
    - 3y ago
Choco31415 4y ago
I went through a few different versions of depression myself and it absolutely feels that way. Each was caused by a different trigger, and the strangest thing is, despite all the tests doctors ran, everything came back normal. They couldn’t figure out what was happening.

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asdfman123 4y ago

> “It’s almost as if you’d already decided how you were going to feel, and then everything you were sensing was filtered through that,” he said. “The mood has become primary.” This is 1000% what depression feels like, once you've properly come to terms with it. Your brain seems absolutely compelled to apply the most horrific, negative interpretation to everything that happens to you. Even when you understand it's wrong, or at least heavily negatively biased, fighting those interpretations feels like trying to swim upstream in a terrific current.

comrh 4y ago
Which makes sense why CBT style therapy has shown effectiveness because its main focus is challenging those interpretations. No doubt even with those tools it is still a major challenge.
- asdfman123 4y ago
  One interesting thing to point out is CBT is so effective because it's somewhat easier to stick to than other approaches. Meditation, for instance, is equally effective if you keep with it, but most people realistically won't.
AndrewKemendo 4y ago
This is one of the few times I've heard an accurate and concise description of what it feels like. I like the metaphor of the spiral wishingwell. The coin/ball represents the level of depression you sink into. The gravitational draw of the void makes the spiral go faster unless you figure out a way to pull out of it and the longer you wait the harder it is to pull out cause it's moving too quickly. So the trick becomes keeping the coin/ball off of the spiral
- hanselot 4y ago
  The only way out is through. One way or another, once you reach the shore on the other side, the time spent in the water doesn't seem so bad anymore. Just another perspective to lean on when understanding others. Once you confront it in the most absolute sense, something akin to ego-death occurs, and you make a decision about whether it is worthwhile to continue. Everything comes from and swings back to chaos. Embrace it and you will be free.

JohnMakin 4y ago

Unfortunately, TMS is extremely expensive and not likely to be covered by most insurance plans. Even with a decent PPO, I was quoted about $1k a treatment and they said I needed at minimum 30 treatments.

radicaldreamer 4y ago
There are effective alternatives which are a fraction of the cost: ketamine (sublingual ~100mg every few days), psilocybin (free? cheap 2-3g ~4 weeks), rapamycin + ketamine also seems promising (https://www.nature.com/articles/s41386-020-0644-9 https://www.nature.com/articles/s41386-020-0644-9).
- wizzwizz4 4y ago
  I would recommend against trying to self-prescribe addictive substances.
  - rozularen 4y ago
    I don't think any of those are addictive actually
    - marcellus23 4y ago
      just because they're not chemically addictive doesn't mean they're not addictive. Weed isn't chemically addictive but plenty of people struggle with it nonetheless.
      - blastro 4y ago
        same with food?
        marcellus23 4y ago
        Well, yes. That's what "food addiction" is.

endisneigh 4y ago

disclaimer: I acknowledge depression as an illness and state of being. that being said, if you take someone who is objectively "not depressed" and apply these same depression treatments, what would happen? some state of euphoria? heightened mood? happiness? suppose that new state is now the normal state in which people are judged against. now, the before-mentioned person who was not depressed, may be considered depressed, relatively. so you now apply the same thought experiment again. clearly this can be recursively done infinitely... such is an inflationary view. so my question really is around the cultural vs. biological construct of depression. what if it's ok to be depressed? this is not to say that we shouldn't be trying to "treat" it (and the symptoms), but I do wonder at what point do we say it's OK.

supernikio2 4y ago
What brain signals would you reverse on a non-depressed person?
admax88qqq 4y ago
It's not okay to be depressed because it sucks to be a person who is depressed. Being depressed is not a nice state to be in. This isn't an "ooo society is wrong" type of situation. Sure there are some societal pressures to appear happy which can make depression _worse_, but depression is still awful regardless of those and we treat it because it's awful.
ebolyen 4y ago
Instead of imagining that it works like a number line and then observing that you can use induction, you could measure outcomes: suicide, suicidal ideation, quality of life, etc. That puts a pretty reasonable lower bound on what is or isn't depressed. It is absolutely an altered state of mind, and an information processing disorder. For anyone who might feel like "it's ok to be depressed", this is not a normal thought, and there is no normal amount of suicidal ideation. Seek professional help or strong social support; just ask for help anywhere it might exist (go to an emergency room and just have a seat if you must). If you aren't depressed, these thoughts literally don't happen, as strange as that may sound if you are in the thick of it.

kypro 4y ago

I hate this idea that signals can move the "wrong" way. There have been few days in my adult life that I wouldn't have preferred to not be here. Depression sucks. Yet, I don't think people are right when they tell me I'm wrong to be depressed. I hear that some people feel their depression shouldn't be there and that they should feel happy, and in those cases I think this sounds like it could be an excellent solution, but in my case (and I think others too) I could give you very well reasoned arguments for why I would prefer to not to be here and why I feel a sense of sadness as my default state. At least in my case I believe arguments for optimism are more wrong than my depression. Interestingly, my girlfriend is the total opposite to me. She's the happiest person ever met and I often wonder why she isn't also considered to be suffering from some kind of mental defect – I guess in her case the signals must be moving the "right" way because obviously the "right" way to feel is happy 24/7 and prolonged sadness is "wrong". I guess I always kinda liked the idea that any advanced intelligence would end up as some iteration of Marvin the Paranoid Android, since the logical conclusion should perhaps be that life is pointless and hard, so therefore why bother? Perhaps the "right" way for signals to travel is in the direction of depression and hopelessness. Sorry I know this isn't really on topic and I sound like a complete downer. I'm certainly not trying to diminish this research. I've guess I've just always found it interesting how some people feel they can categorise mental states as "right" or "wrong".

airstrike 4y ago
I have full sympathy for people dealing with depression but I don't think this logic holds. People who are depressed have suicidal ideations, suffer in quality of life and generally struggle to accomplish otherwise simple tasks. It is "wrong" in the sense that it has all of these objectively negative consequences whereas being blissfully happy does not, so it can be claimed to be "right" in relative terms. I think you are attributing to the word "right" a sense of an obligation to feel happy, with "wrong" therefore being a deviation from that True Path, but I don't think that is the intended meaning when people use those words to describe depression. I would argue that "right" in this context means something closer to "nominal", as in "working as intended". Nobody is faulting you (or me or others) for constantly feeling down. I hope that helps.

poorbutdebtfree 4y ago

Is depression a first world problem? Maybe if we can send over our highly trained and effective therapists to the third world we'd find that 95% are depressed too. It'd make depression much easier to deal with if we knew everybody had it regardless of qualify of life issues.

jiveturkey42 4y ago
Probably just people with the luxury to sit inside all day in climate control, completely disregulating the hormones
rybosworld 4y ago
It is certainly not just a first world problem. There are many problems in advanced nations that get a spotlight on them, but that doesn't mean those problems don't exist in less developed places. In some parts of the world, getting fresh water is the biggest concern. Solving that problem becomes so important that topics like mental health may be completely ignored. I would wager a guess that North Korean citizens rank especially high in prevalence of depression, but it's not even a top 5 concern for them. The historical record has many descriptions of depression dating all the way to B.C. times. Depression has been a thing that has affected humanity for at least as long as organized civilization has existed. I think a good question to ask is: Do uncontacted ("lost tribe" cultures if you will) peoples have differing prevalence of depression compared to the connected world? I don't know the answer to that question, but I wouldn't be surprised if the rates of depression in those cultures is lower.
igravious 3y ago
No, depression is not limited to any specific region or socioeconomic group. Why would you think that it is?

robotburrito 4y ago

We are always trying to solve this problem while avoiding the elephant in the room, the current state of society is not very healthy for most people.

walleeee 4y ago
There are two truths here which are often taken to preclude one another, but I think they can coexist 1. Depression can be treated and even overcome in some circumstances 2. There are very justifiable reasons many people might be depressed
- throitallaway 4y ago
  What I find most troubling is how resources and power get concentrated in hands of the few, and the rest of us (99%+ of the population) are left to deal with the consequences. The few laws that do exist to prevent benefiting parties from raping and pillaging the earth and society at large are slaps on the wrist at best. The default is to toe the line and/or overstep legality and morality. That's what's so depressing about it all.
  - somebody78978 4y ago
    Yeah, but that's also been the case for thousands of years.
  - eastof 4y ago
    I commented about this above since this type of thinking is what I see most commonly in my anxious/depressed friends. Really think on it deeply for a bit and you'll realize this belief can't possibly be justified rationally. Who are you to say that resources and power shouldn't be concentrated in the 1%? You say they overstep morality? That's your morality and you can't defend it rationally (no one can). Plus you can't change these things anyway, so you have no moral responsibility to do so (my morality). Media, politicians, advertisers, etc. all instill FUD to make you feel this way so the default option is pessimism. Try optimism. It may be wrong, but pessimism may be wrong as well and no one will ever find out so why even care who is right?

aszantu 4y ago

Don't know who needs to hear this. I started a food diary after an elimination diet which restored my energy levels. I don't know the reasons, but you're looking in a time window of four-seven days. When I stray from my diet (meat and water) one day. I become mentally unstable after 4 days. It says for 3 day, then gets good again. Crying for no reason, ruminating, poor sleep, strong sour smell that can't seem to be removed by washing but can be suppressed by a strong anti transpirant. Going for sibo testing soon, if it's not hereditary, enzymes might be a solution. If it is, Pankreas is up for investigation next. Been looking for solutions since 2018, no doctor could offer an explanation so far.

stuckinhell 4y ago
thank you for this! I have something very similar
- aszantu 4y ago
  Have you noticed something else? I seem to tolerate sour apples and 1 teaspoon of sauerkraut per day, but not much more. Also garlic seems to be okay, but not onions, chilly powder is okay but not chilli-peppers or pepper, or tomato or seeds in general. Allergy tests all came back negative
  - stuckinhell 3y ago
    I'm leaning towards maybe some gut bacteria causing this illness maybe. My allergy tests were negative too.
NeuNeurosis 4y ago
Definitely have experience with the same thing with food. I did end up finding out it was my Pancreas and take enzymes with every meal. Really really helps and has given me way more energy and my guts feel 90% better. Still have to watch certain foods and drink plenty of water but it is way better. Good luck.
- 4y ago

fpgaminer 4y ago

Other comments have proposed that depression may have multiple underlying causes, and thus may require different treatments. I'm curious about the other direction of thinking. What do SSRIs, psychedelics, CBT, and TMS all have in common? Suppose that there is one common cause, or one at least one cause that applies to 90% of cases. And it's treated by all these seemingly disparate methods. That's what tickles my curiosity the most, as it begs a more fundamental question about the functioning of the brain. Maybe the author's theory is correct: brain signals between certain regions are going the "wrong" way in depressed patients. That would imply that SSRIs are causing the same shift. God, I would love if the authors tested that. And then we can finally dig into why SSRIs work (we don't current know). If they're causing shifts in brain activity flow, then we can find out how. And from there maybe we can treat other mental diseases with better pharmacological or TMS solutions. Are things like schizophrenia arising from a similar bad pathing of information around the brain? Psychedelics is also a weird one. People have proposed many theories as to their mode of operation for treating depression. But now I wonder, based on this research, if the key factor was just the disassociation from one's body and altering of senses. The other effects like connecting disparate thoughts, forming more brain connections, ego death, etc may not be related at all. That could lead the way to more targeted drugs. Really cool stuff. If if pans out, of course. But unlike other theories of depression, at least this one is easy to test.

opportune 4y ago
If you consider that CBT scratches a need for deep socialization, they all basically act on serotonin in different ways. I don’t buy the oversimplified “depression is when your brain doesn’t make enough serotonin” model but it does seem there is a strong connection. Maybe there is some kind of local optimum your serotonin-mediated pathways can get stuck in and need help getting out of. In fact, this (generalized outside of just serotonin) is something I do buy as a basis for depression: your brain enters some local optima or learns some poor but good-enough coping mechanisms that keep you going but prevent you from fixing underlying issues (whether it be due to maladaptive behavior, framing or interpreting things negatively, low self esteem leading to poor social performance and consequently lower self esteem). That’s also kinda what CBT is about addressing
4y ago

brainmagnets 4y ago

I recently went through a round of rTMS and participated in a study that used EEG to attempt to find biomarkers for responders vs non-responders. This was largely based on previous findings that altered functional network activity in the brain (namely the default mode network) is correlated with depression in some people, and that EEG could relatively inexpensively detect functional network changes over the course of treatment. This study seems to follow a similar vein and I suspect we'll see more like it in the near future. I'm really glad to see more research being done with TMS - the particular protocol mentioned in this study (SAINT protocol) has had truly amazing success with 80-90% remission rate in already treatment-resistant individuals in a couple of studies. Even ECT, which is currently considered the most effective treatment for treatment-resistant depression, has only a 70-80% response/60% remission ("regular" rTMS is about 60% response/30% remission). The only problem is that SAINT requires fMRI which is expensive and complicated, on top of already expensive rTMS treatment. Hopefully as more research is done it'll become more accessible, personally it was very helpful for me in overcoming many years of intractable depression.

mynameisash 4y ago

My son, who is diagnosed with ADHD, anxiety, depression, and OCD, and who has been in talk therapy, on SSRIs, and other interventions for years, recently started LENS therapy, also called neurofeedback. (I'm on mobile device, otherwise I'd find the link.) It sounds a lot like a form of TMS. He's had something like 7 sessions, each lasting maybe 15 minutes. The results are nothing short of astounding for our family. He's typically been... Extremely difficult to parent. After his LENS, lasting about a week, he is a pretty happy kid who participates in family and social life. His anxiety previously prevented him from engaging with friends for more than an hour. Just the other day, he was out at a birthday party for eight hours and still cheerful afterward. I'm very hopeful that there is a long term, lasting effect for this kind of thing.

fourg 4y ago
That's wonderful that it's helped your son so much. I have done TMS and am curious about LENS for myself and family who have symptoms similar to what you shared. We too have tried most everything else and daily life is an absolute grind. How many sessions did your son require and how long are the results expected to last?
- mynameisash 4y ago
  To be honest, I don't know how long LENS will be for us. We're doing weekly sessions. It's not supposed to be indefinite, but I don't know at that point we taper down or stop. Results were pretty much immediate, though. After his first session (maybe only a few hours later), he self-reported improvements and we noticed a definite change in his mood and attitude.
deleted 4y ago
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cactusplant7374 4y ago
Is this a therapy that can be done at home?
aerophilic 4y ago

udev 4y ago

Very interesting, so it could be that depression is essentially a race condition in the brain.

carabiner 4y ago

The commercialization of this treatment is being handled by https://www.magnusmed.com/ https://www.magnusmed.com/. Some existing TMS treatment centers claim to be performing the SAINT protocol right now, but the researchers have never fully revealed the treatment plan (using fMRI, algorithm for targeting) and so the claims can't be substantiated as being exactly SAINT. I'm pretty desperate to get onto a trial. Here's hoping that this gets FDA approval ASAP.

flippinburgers 4y ago

I have had what seems to me to be depression for most of my life (40+ years). I have been fortunate enough to have a kid and, now, I guess I just don't have time to be depressed or something because most of my thoughts of ending life etc have, quite thankfully, gone away. I'm really not trying to be off-putting when I say this but I do sometimes wonder if some instances of depression aren't simply a cause of people not having families. I'm not totally confident about this, but ... really I think having kids gets looked down on for all the wrong reasons and maybe our deepest drives are all tied to having them.

bendbro 4y ago
I agree, I wonder if depression is not always rooted in some random, mental problem but rather a reasonable reaction to reality.
- EGreg 4y ago
  I kept saying this for years on HN but until the 2022 study it was always voted down and told that NO, it is due to a chemical imbalance and that we don’t understand
  - notnaut 4y ago
    There is the chemical imbalance and then there is the diagnosis. Complete guess, but wouldn’t be surprised if the rate of people with the imbalance has climbed less dramatically over the last several years than the rate of people being positively diagnosed.
  - bendbro 4y ago
    I recall that study! I suspect those downvotes are due to people recognizing that it implies depression is sometimes within the control of someone afflicted by it and conflating that with blaming the person afflicted by it. People seem offended by critiques of modern ideas that rationalize away an individual's control, agency, and especially culpability for their behavior or outcomes. Sometimes these rationalizations are fair, other times not.

burglekutt 4y ago

Sometimes I feel like programming is physically and mentally designed to create bad health and mood, at least if you’re not very careful about how you’re _being_ while doing it. Maybe it’s just me, but I have to work hard to avoid: - Bad posture, hunching towards the monitor - Scrunching the face - Feeling impatient because my fingers and the computer can’t keep up with where I am in my mind - “Damn you, computer!” frustration in small doses throughout - Frequent interruptions via email, Slack, texts, coworkers, etc - In some cultures, it’s very hard to have a plan for what to get done in the day and then execute on it due to getting sucked into meetings and stuff.

polalavik 4y ago
Ya I’m really interested in what I do and side projects I work on but I feel like absolute shit after focusing on either. Not sure how to solve this. it feels unsustainable to find equal amounts of joy(?) and ~bad feelings physically and mentally~ from partaking.

iandanforth 4y ago

What does "brain signals traveling" even mean? The brain is highly interconnected with both forward and feedback connections at all levels. Both of the mentioned regions are always active and always sending signals bidirectionally. fMRI is a slow, low resolution approximation of brain activity, so I'd really like to know what they are actually measuring as opposed to some clearly reductive analogy of what they suspect might be an underlying cause for that observation.

makeitdouble 4y ago
I assume they are checking the timing of the activation cycles ? For instance if sending a strong sensory stimulation first triggers a higher activity level in one part before the other, that could be interpreted as directionality.

ChicagoDave 4y ago

Does it work with people that suffer Bi-Polar Syndrome though? That would be another level.

levi_n 4y ago

I have ADHD, major depression, and I did 8 weeks of TMS therapy last year. In the end it did help my depression some, but it isn't a night-and-day difference. It did, however, completely change how I see myself, to the point where I feel disconnected and separate from the person in my memory. Likewise, my sense of empathy and how I few the world is completely different, for the better. I plan to do another round this summer.

machiaweliczny 3y ago

Tangential but to anyone who is tired and anxious I recommend also checking for Tetany[0]. I got diagnosed with that and just supplementing minerals had positive effect on my wellbeeing. Before I was miss?diagnosed with mild depression and put on SSRI(which helps) but my muscles got so tense recently that I went for dry needling and they recommended I check for Tetany. BTW seems like predisposition to this might be genetic as my mother has similar issues. [0] https://en.m.wikipedia.org/wiki/Tetany https://en.m.wikipedia.org/wiki/Tetany

jscipione 3y ago

Depression is natural given the state of the world right now. There is nothing wrong with the brains of depressed people, anyone who sees clearly ought to be depressed.