[HN Gopher] How Antidepressants Work, at Last? ___________________________________________________________________ How Antidepressants Work, at Last? Author : eightysixfour Score : 68 points Date : 2021-02-19 19:41 UTC (3 hours ago) (HTM) web link (blogs.sciencemag.org) (TXT) w3m dump (blogs.sciencemag.org) | doggodaddo78 wrote: | So will this lead to a cure since I've tried 15 and only | mirtazapine worked for a few years? | royaltjames wrote: | God I hope so. Just found a blend that's helping me feel human | for the first time in these 35 years of living. I'm in the same | boat with Mirtaz, altho I'm finding success with pairing it | with Viibryd. | | A big help is genesight testing for upfront | compatibility/sensitivity for a consultancy approach, rather | than spray and pray. | omegaworks wrote: | So cholesterol plays a huge role! The brain is the fattiest | organ, so it makes a lot of sense. That we haven't found a | correlation between statins and depression is certainly a | quandary though. | | I wonder if our national obsession with anti-fat dietary advice | has had an impact on depression's prevalence in our population. | It would seem to make sense that if we depress people with low- | fat frankenfoods they naturally react with lower physical | activity levels. | | I wonder if omega-3 / omega-6 dietary balance changes the | structure of the cell membranes to make them less permeable. | Greater omega-3 cell membrane composition certainly seems to have | a real impact on retina cells and the overall function of the | retina[1]. | | 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174995/ | mckirk wrote: | You might be on to something. I think what the US has done to | yogurt should be banned under the Geneva convention. | heavyset_go wrote: | Antidepressants aren't just used for depression, they're also | used to treat a spectrum of anxiety disorders like OCD and panic | disorder, although the doses used to treat anxiety disorders are | much higher than those used for depression. I don't think the | BDNF-related hypothesis explains the efficacy of antidepressants | in treating anxiety disorders, but I could be wrong. | [deleted] | doggodaddo78 wrote: | And vice-versa. I'm taking vilazodone and lamotrigine (anti- | epileptic), and they're just barely working. | gwern wrote: | Under the maladaptive neuroplasticity theory which motivates | the BDNF connection, I think anxiety could be taken into | account naturally: just as depression is a maladaptive | persistent overlearned estimate of the world as threatening, | unrewarding, and pointless, which persists despite regular | experiences which should falsify those beliefs and lead to | learning (but doesn't), anxiety is persistent overestimation of | risks which persist despite regular experiences of dangerous | risks not happening which should lead to learning (but | doesn't). So if boosts to neuroplasticity can help a depressive | learn that life doesn't suck, it makes sense if boosts could | also help an anxious person learn that life isn't so dangerous. | sjg007 wrote: | This is fascinating. Cholesterol has long be associated with | depression. | | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606915/ | momszack wrote: | That associates statin use with depression, not cholesterol. | That's a huge difference. Those results (which are not an RCT) | could easily be explained by those that are less depressed are | more likely to seek any non-psychiatric outside medical | treatment. | mastrsushi wrote: | I'm sure the people of Hacker News will find this article | relatable. | anaphor wrote: | Will this make the "chemical imbalance" (i.e. low-serotonin) | theory of depression obsolete once and for all? | hammock wrote: | How antidepressants work (this article) and what causes | depression (your postulate) are two completely different | things. | sekh60 wrote: | Forgive my ignorance, but what alternative is there to a | chemical imbalance of some sort? Structural differences? I have | schizoaffective bipolar subtype, and wouldn't mind some links | to more current literature, I'm obviously very behind. | anaphor wrote: | It used to be the case that the theory for why people have | depression was "people who are depressed don't have enough | serotonin" (in very simple terms), and the reason why SSRIs | work was supposed to be that they increase levels of | serotonin, but scientists have found that boosting levels of | serotonin alone does not help with depression. | | Here's a good journal article on the subject https://sci- | hub.st/https://www.sciencedirect.com/science/art... | aantix wrote: | Have you ever tried Niacin/magnesium approach for treatment? | astrange wrote: | "Low serotonin" was never the actual medical position on why | antidepressants worked, it was marketing. The medical | position is "we don't know why they work"; some | antidepressants actually lower serotonin (SNRI) and some | increase it (SSRI) and they both seem to help. | | Also, they take weeks to take effect which doesn't make sense | for a neurotransmitter effect, since Adderall (which raises | dopamine) works instantly for ADHD. | | I've heard theories that just doing anything to your brain | knocks it out of state enough to stop being depressed (eg | psychadelics do this), or that antidepressants actually | improve your sleep quality and your brain cleans itself up | over time. | johncolanduoni wrote: | Not really, it's just proposing a different chemical imbalance | than the "monoamine hypothesis" (i.e. serotonin, etc.). That | one has already been disfavored for the past few decades, due | to a lot of findings that it has trouble explaining. In | particular the discovery of effective antidepressants that | don't affect the monoamine receptors enough or in sufficiently | similar ways. | pid_0 wrote: | Isn't it already though? Besides for those self-diagnosed | tumbrlinas complaining about "no serotonin". It's pretty well | established that Dopamine, Norepinephrine, etc play a huge role | in depression. Serotonin is a small part of it. | | And anyway, I would bet almost all cases of depression | ultimately stem from ineffective behaviors and thoughts, not | some fundamental chemical imbalance. | loceng wrote: | Arguably it's life experiences and environmental stimuli that | actually play a role in depression et al - it's just these | neurotransmitters you speak of are the communicators. E.g. | Self-protective mechanism from trauma (physical and/or | emotional) to "close ones heart" or develop defensive | behaviours - and then being locked into that state, | indoctrinated into it - without the ability to disconnect | from that pattern until say dramatically changing the | chemical supply of transmitters - say either MDMA flooding | the brain with serotonin, more than the brain naturally can | at once, or say through ketamine or Ayahuasca or other | psychedelics that give the opportunity for a perception | change outside of the indoctrinated state(s) and behaviours. | | I imagine the vast majority of people who's circumstances | aren't due to a chemical issue, more so the lack of adequate | support for them and/or any element of Maslow's Hierarchy of | Needs not being met during rapid and crucial childhood | development. | johncolanduoni wrote: | Mood disorders found to be are significantly heritable in | twin studies so I don't think one can say the "vast | majority" aren't due to a chemical issue here. It's also | worth noting that BDNF is not a neurotransmitter, and so | having a direct connection with thoughts and personality | seems unlikely, though there is reason to believe it may be | downstream of long term psychological stresses. | toiletfuneral wrote: | wow, super constructive comment. You seem very proud of | yourself | omegaworks wrote: | We have new insight now into how antidepressants interface with | specific signaling molecules, making them more effectively | permeate the neuron cell membrane. | | It's still about chemical balance. It's a highly complex system | involving more than serotonin, though. | | He mentions serotonin reuptake inhibitors once, but it looks | like this finding applies to other substances identified as | anti-depressants that aren't necessarily serotonin targeting. | vegannet wrote: | I've always understood the chemical imbalance description of | depression (and other mental health conditions) to be a casual | way of describing the conditions as being part of the person | rather than a choice -- and not a way to describe the internal | mechanics of the conditions. I've found it effective when | having conversations about mental health conditions: how would | you describe depression without using that phrase, based on | what this paper reveals? | anaphor wrote: | I'm not saying there isn't a biochemical component to | depression (or any other mood disorders). The specific theory | that I'm talking about is "low serotonin causes depression" | (as in the proximate cause, not the ultimate cause). When | SSRIs were first discovered to be useful for treating | depression, one of the theories about why they worked was | that they boosted levels of serotonin, but we know now that's | not true. It doesn't mean it can't be explained in other ways | (like the one this article discusses). | | Also, if there is a behavioral component to depression as | well, then it doesn't necessarily mean someone is to blame | for their disorder. You don't control the environment you | grow up in, which has an enormous impact even on traits that | are highly heritable (the whole subject of heritability is | very misunderstood anyway). | | So basically if I were going to describe depression's cause, | I'd say it's a mixture of biochemical reactions, behavioural | traits, and environmental stresses that cause it. | danielovichdk wrote: | I am not a neuro anything, but has that been the a big debate | in the antidepressant discussion long? The low level of | serotonin? Is that a fallacy or an i missing something? | anaphor wrote: | It's been a persistent myth perpetuated in the | media/journalism/society/etc for a few decades, but there is | a lot of scientific evidence showing that it doesn't really | explain how depression works, and the fact that SSRIs boost | serotonin doesn't explain why they work as a treatment. See | https://sci- | hub.st/https://www.sciencedirect.com/science/art... for | example. | loceng wrote: | I will read this in full later - though anyone care to reply with | a TL;DR for everyone here? | Nbox9 wrote: | I am not a biologist by any stretch, but I will try. | | A common mechanism of action may have been found across | antidepressants where none was found before. This common | mechanism between both Prozac and Ketamine has some impacts on | how cholesterol is used in the brain and BDNF (neuron survival | and growth regulator). | loceng wrote: | Thank you - interesting. I wonder if the cholesterol changing | mechanism is why some people seem to gain body weight/fat who | are on certain medications. | andrewflnr wrote: | It's a short article. Just read it. | loceng wrote: | I think there's more value in the comment you're replying to | than your own comment - I imagine you took the time to | downvote too? At least thank you for spending the effort of | writing something. | justinboogaard wrote: | TLDR; conditions like depression may stem from a poor | distribution of cholesterol in the neurotransmitter signaling | process in the brain. | hinkley wrote: | What I'm hearing you say is 'eat more bacon'. | | Sorry what was that? You're breaking up. I'm off to the store, | ttyl. | astrange wrote: | Eating cholesterol doesn't affect your levels of internal | cholesterol. ___________________________________________________________________ (page generated 2021-02-19 23:00 UTC)