[HN Gopher] How Antidepressants Work, at Last?
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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.
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