[HN Gopher] Fasudil is found to reverse key symptoms of schizoph...
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Fasudil is found to reverse key symptoms of schizophrenia in mice
Author : gmays
Score : 47 points
Date : 2023-02-21 14:36 UTC (8 hours ago)
(HTM) web link (www.nagoya-u.ac.jp)
(TXT) w3m dump (www.nagoya-u.ac.jp)
| ZoomZoomZoom wrote:
| The researches obviously treat the word "symptom" in a strictly
| professional way, so all those questioning themselves "How do you
| find enough mice with symptoms of schizophrenia in the first
| place?" are in no luck.
|
| The symptoms are: - Reduced density of pyramidal neurons -
| Cognitive dysfunction associated with methamphetamine treatment
| Taniwha wrote:
| Since this is treatment of schizophrenia caused by a particular
| genetic mutation, surely the answer is "you get them by
| breeding them"
| PaulHoule wrote:
| Some of the positive symptoms of schizophrenia are delusions,
| hallucinations, and thought disorder. I'd imagine a mouse could
| have all those things but how you would know without language
| is beyond me.
|
| Schizophrenia and the related schizotaxia (a condition that is
| conjectured to be present in anyone who is schizophrenic) has a
| number of hidden phenotypes however, such as deficits in eye
| tracking
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3212396/
|
| something like that must be detectable in animal models.
| comfypotato wrote:
| I don't think it's far fetched to assume that this sort of
| research is backed by years (decades?) of evidence showing we
| know how to identify schizophrenia in mice. Whether or not
| this particular study actually matters (or it's just a flashy
| headline) is a totally different discussion, but the same
| patterns human schizophrenics exhibit can't be that hard to
| identify without language. Hell, the first picture in the
| article makes sense to me. Amphetamine salts make humans with
| this disease nuts in a way that they don't affect normies.
| derefr wrote:
| In medical jargon, wouldn't those be "signs"? I thought
| "symptoms" specifically refer to the qualia of the disease as
| experienced by the patient (e.g. pain, "feeling of ____", etc.)
| mtlmtlmtlmtl wrote:
| Technically yes, although in practice the overlap between
| symptoms and signs is pretty significamt and so the
| distinction is pretty blurry.
| ccooffee wrote:
| Perhaps, but in that case there are no symptoms of
| schizophrenia in mice, correct? I suppose we might be able to
| deduce "feeling of ___" via behavior monitoring (e.g. hunger)
| or possibly even brain imaging (e.g. seeing "fear centers
| light up"), but even then it isn't "as experienced by the
| patient".
| profstasiak wrote:
| the model exhibits behaviour that we can deduce a
| schizophrenic mouse would have. Like social withdrawal. Are
| we sure they have schizophrenia? I am not so sure, and not
| that qualified to tell if that makes sense
| onemoresoop wrote:
| How are mice diagnosed with schizophrenia? Obviously asking
| relevant questions or having them fill out a form is not possible
| with mice
| mtlmtlmtlmtl wrote:
| Typically animal models are created that are thought to overlap
| with the mechanism of the disorder they're studying. Sometimes
| this is done genetically, sometimes by toxic drugs.
|
| In this case, neural damage is induced through methamphetamine,
| this is thought to damage some of the same neurons that
| schizophrenia affects.
|
| The results may or may not transfer to the actual disease in
| human. There's a reason most animal based research doesn't pan
| out in the end.
| onemoresoop wrote:
| Thanks. I figured it may not be accurate but seems like I was
| underestimating it.
| bitwize wrote:
| Reminds me of the study that suggested lamotrigine as a potent
| autism treatment... in mice. That had been genetically
| engineered, drugged, surgically messed with, or otherwise altered
| to manifest autism "symptoms".
|
| As usual, wake me when there are promising results in humans that
| actually manifest the condition.
| colechristensen wrote:
| Yup.
|
| One of the foundational studies supporting SSRIs involved a
| model of "depression" which was regularly delivering electric
| shocks to mice. So SSRIs provide statistically significant
| improvements for mice being mildly tortured.
|
| To be fair, this is probably a good model of what lots of
| people on SSRIs actually have as a life experience.
|
| "Chemical imbalance", my ass.
| astrange wrote:
| Hopefully no professional ever thought depression was caused
| by "chemical imbalances". That's a pop science myth, although
| one people strongly believe for some reason.
|
| The correct answer is we don't know why SSRIs work, which
| isn't unusual for medicine.
| creata wrote:
| > The idea was also endorsed by official institutions such
| as the American Psychiatric Association, which still tells
| the public that "differences in certain chemicals in the
| brain may contribute to symptoms of depression". [1]
|
| It's not _just_ a pop science myth, and there are, somehow,
| still many professionals who think it is or could be a good
| explanation.
|
| [1]: https://theconversation.com/depression-is-probably-
| not-cause...
| catskul2 wrote:
| They have and do regularly describe it in those terms to
| patients.
| nsxwolf wrote:
| The name "Selective Serotonin Reuptake Inhibitor" vaguely
| sounds like it has something to do with rebalancing
| chemicals.
| PaulHoule wrote:
| SSRIs are exactly what they say. They inhibit the
| function of this thing
|
| https://en.wikipedia.org/wiki/Serotonin_transporter
|
| Now what happens after you block the serotonin
| transporter and how that leads to relieved symptoms of
| depression and anxiety, that's much more controversial.
| There is a strong association between social dominance
| and serotonin, and "low serotonin levels" are associated
| with being an underdog. It's a reasonable assumption that
| SSRIs attenuate stress-related brain damage caused by
| being an underdog.
|
| https://www.nature.com/articles/s41598-018-33410-1
|
| https://link.springer.com/article/10.1007/s00213-002-1049
| -7
|
| You don't hear that one very much because if you took it
| seriously it would mean you shouldn't take a pill but
| rather you should join a revolutionary party.
| astrange wrote:
| Yellow card for insufficient dialectics. Joining a
| revolutionary party makes you more of an underdog!
|
| Obviously there's no way to just become someone who can
| feel successful, but having social hobbies is a more
| normal way to get there. But if you're depressed you have
| a harder time doing that.
|
| It's probably not what SSRIs are doing though. It might
| be something BDNF related, or brain inflammation
| (everything's inflammation...).
|
| https://www.science.org/content/blog-post/how-
| antidepressant...
| rozab wrote:
| As far as I can tell, the standard measure of depression in
| rodents is something called the forced swim test. It's what
| it sounds like. This appears to be the primary way all
| antidepressants are assessed.
|
| I'm no expert, but this measure would seem to have
| innumerable potential confounds. I guess it was chosen
| because it's fast to carry out.
| sva_ wrote:
| > _They found that treatment restored the density of pyramidal
| neurons in the medial prefrontal cortex, a part of the brain
| associated with attention and long-term memory. As a result, mice
| with methamphetamine-induced cognitive impairment treated with
| the drug also performed better on visual discrimination tests._
|
| Interesting.
| whitehexagon wrote:
| Is Fasudil a naturally occurring compound, or something that has
| been engineered? Wikipedia just describes it as a discovery.
| Regardless it sounds like an interesting result.
| nimbius wrote:
| [flagged]
| vanattab wrote:
| How does one diagnosis schizophrenia in a mouse? Are there simple
| chemical tests for schizophrenia?
| kerpotgh wrote:
| It's methamphetamine induced.
| zoklet-enjoyer wrote:
| That's not even the same thing though
| jonny_eh wrote:
| Welcome to mouse models.
| magicalhippo wrote:
| Reminds me of when I read up on a few of those "radiation
| from mobile phones are dangerous" articles.
|
| I converted the energy per mass the mice had been exposed
| for and found it wasn't far off what a microwave meal
| receives (and in similar frequency range). Hardly a
| shocker that wasn't healthy for the mice. Far cry from a
| mobile phone tho.
| [deleted]
| iroh2727 wrote:
| Schizophrenia is usually a kind of coping mechanism to handle an
| unhandleable environment (e.g. family in the case of a young
| schizophrenic person). It's also, as some psychologists (e.g. RD
| Laing) have argued, a kind of "journey". If people are allowed to
| go through the journey, they often come out the other end healed.
|
| ECT has always served to remove symptoms or "normalize" people by
| just frying them until they're a hollow drone.
|
| Drugs can be useful. I know many schizophrenic people are happy
| for their drugs. But we shouldn't forget that "real
| schizophrenia" is impossible to model in mice (how do you model a
| terrible parental situation for example?). And more generally, we
| shouldn't forget that schizophrenia is mostly social and
| psychological in origin, rather than purely biological. A drug
| can target some chemical that is present in this process, but the
| cause is not some exogenous chemical, so it does not treat the
| "real cause" (see e.g. The Myth of the Chemical Cure). Another
| way of saying this is that the biological system that needs to be
| modeled is really the holistic biological system of society,
| family, etc (can also be useful to think about this in a
| cybernetics kind of way--see e.g. Bateson who developed the
| "double bind" theory of schizophrenia).
|
| Moral of the story, at least in my view: we should care and treat
| schizophrenic people with empathy and simultaneously aim to
| improve the social situations that induce schizophrenia. And how
| do we improve the social situations? Well, first, if needed, we
| just work on ourselves, our own self-respect, competence, moral
| agency, etc., and spread goodness to the people in our vicinity,
| whilst having faith that others who are quite equal to us and who
| we have no control over can do the same.
| _a_a_a_ wrote:
| Lang's ideas were Self-indulgent hippy stuff back then. His
| idea of schizophrenia being a journey, well psychiatric nurses
| I know have no patience for that.
|
| > And more generally, we shouldn't forget that schizophrenia is
| mostly social and psychological in origin, rather than purely
| biological
|
| I'd be curious if you could provide references for that.
|
| > ECT has always served to remove symptoms or "normalize"
| people by just frying them until they're a hollow drone.
|
| ditto
| iroh2727 wrote:
| Well the classic work on sociology of mental illness is not
| about schizophrenia but about suicide (Emile Durkheim's
| Suicide). The same types of social causes can be observed
| with schizophrenia, though, in the facts of geographic
| disparities in diagnosis as well as changes (usually
| increases in recent history) over time. See for example, how
| urban environments are more likely to give rise to
| schizophrenia [1].
|
| Also recommend like I said Gregory Bateson's work, or more
| recently books like The Myth of the Chemical Cure by Dr.
| Joanna Moncrieff.
|
| The general point is that if we want to model causality we
| have to include the full system in question. If we narrow our
| perspective to an inner sub-system, then anything outside
| looks like an exogenous cause. But we may have to keep
| expanding wider and wider to get an accurate picture.
| Intervention can be done at any level of granularity, but the
| lower it is done, the more we'll be missing on the root cause
| of damage, which is likely causing harm elsewhere too.
|
| [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5049530/
| creata wrote:
| > psychiatric nurses I know have no patience for that.
|
| Psychiatric nurses have no patience full stop.
| Llamamoe wrote:
| Do you have any sources for that? Because last I've read
| neuropsychiatry literature on the topic, schizophrenia is a
| brain-wide neuronal dysfunction, with psychosis being a
| downstream consequence of erroneous information processing - as
| in "2+2=5" type of erroneous.
|
| I get that some people really want to believe that everything
| affecting the mind must be psychogenic, but with schizophrenia
| you're seriously stretching it. Schizophrenia isn't just a
| psychiatric disorder, it's a heavy duty brain dysfunction.
| shredprez wrote:
| I'm pretty confident there's good evidence supporting a
| connection between "early childhood adversity" and the
| development of schizophrenia, but I'm inclined to agree: once
| the system has gone off the rails, it's probably too late for
| environmental intervention to rein things back in. And that's
| assuming there's any reliable way to initiate and maintain
| those environmental changes.
|
| Realigning the internal systems involved in schizophrenia
| seems at least as important as improving external systems
| that might provoke it.
| iroh2727 wrote:
| Preventative is always more important than fixing after the
| fact where like you said it may be very difficult to do so.
|
| Basically what I was indicating though, and which I get
| from for example, RD Laing and Gregory Bateson, is that the
| best "cure", societally-willing, is to provide a safe
| community environment where the schizophrenia is allowed to
| "run its course". I know capitalist societies always want a
| commoditized solution like a pill, and certainly those can
| be useful, but we shouldn't forget that a more personal,
| human solution is always better.
|
| Western medicine can also learn a lot from eastern medicine
| in this regard. Luckily there's a lot of research being
| done on what the pros and cons of each system are.
| Definitely recommend the book The Web that Has No Weaver
| for example.
| catskul2 wrote:
| > we shouldn't forget that schizophrenia is mostly social and
| psychological in origin
|
| While it's not possible to completely decouple biological and
| social risk factors, my understanding of schizophrenia is in
| direct contradiction with your claim that it's primarily
| social.
|
| As I understand it schizophrenia, the extremely high
| heritability strongly implicates biological factors. Beyond
| heritability, many of the other risk factors also implicate a
| biological basis, from microbe infections, drug use, and pre-
| natal biological stress (nutrition, maternal health, etc).
|
| None of that contradicts the need to treat people suffering
| from schizophrenia with empathy, or to improve the social
| situations they're in, but I think your central claim about
| "mostly social" is wrong, and undermines the rest of your
| argument.
| iroh2727 wrote:
| Agree, but really the question is: why is it going up and why
| is it going up much faster in certain locations or among
| certain demographics? Or why are outcomes much better in
| certain locations/environments/demographics?
|
| For example, it is more prevalent in urban environments, more
| prevalent among minorities in western countries, etc. it has
| better outcomes in "developing" countries.
|
| Core human biology likely hasn't changed much in recent
| history, so what had changed? Many of these factors that have
| changed, like drug use, are also very much related to social
| and economic factors. Of course these are all psychologically
| related and biologically related. But the point is we need to
| model the whole system, and focus on what has been changing
| if we want to get to root causes of change.
| photochemsyn wrote:
| This article claims that: "Genetic vulnerability is generally
| accepted to be involved in the development of schizophrenia."
|
| It might be more accurate to say its accepted that it _may_ be
| involved in particular cases, but is not a general feature in all
| cases, nor is it determinative (i.e. some genetic makeups may be
| correlated with a higher risk of schizophrenia, but only by a
| small factor, and many people with such genetic makeups never
| develop the condition). This is an area of active debate whose
| outcome remains uncertain. For example (2021):
|
| "Schizophrenia: a classic battle ground of nature versus nurture
| debate", Clair & Lang
|
| https://sci-hub.se/10.1016/j.scib.2021.01.032
|
| Note that twin studies are heavily skewed by shared environmental
| conditions and so are not that valid of an argument regarding
| genetic determinism (in this as well as many other psychiatric
| conditions). The current state seems to be:
|
| > "However, little is known about the causal biochemical and
| molecular mechanisms involved that translate genetic and
| environmental risk into the schizophrenia phenotype. It is also
| now clear that environmental exposures that increase the risk of
| schizophrenia can occur at any point across the life span and
| probably include pre-conceptional exposure."
|
| This is probably a case where mice studies are not very relevant
| to the human condition.
| y-c-o-m-b wrote:
| They should add my family to a study around this. Grandfather
| was full schizophrenic. Father is schizotypal. I am
| schizotypal. My teenager has borderline personality disorder -
| which has a lot of overlap with schizotypal personality
| disorder - and I have another child that is showing early signs
| of schizotypal PD but we'll have to see if they get diagnosed
| later in life. Teenage years - approx 15-18 years of age - seem
| to be when it presents itself at the worst and when we get
| diagnosed.
|
| My father's siblings also have various conditions ranging from
| BPD, Narcissistic PD, and schizotypal personality disorder.
| Many of them grew up in different environments. Me and my
| children grew up in different continents and social structures
| altogether.
| kayodelycaon wrote:
| The meta study in question is saying genetics may not be
| involved because they couldn't find exact genes for it.
|
| It's pretty well accepted that bipolar and schizophrenia are
| both highly inheritable. It's also known that not everyone with
| the genes develops the disorder. Environment is thought to play
| a significant part here in the disorder appearing.
|
| Both disorders are known to get worse if left untreated. For
| some people, it's a matter of sufficient time or stress before
| the disorder appears. In my case, I started showing symptoms
| when I was 5. (This was misdiagnosed as ADD. As was the style
| at the time.) Others never develop it.
| PaulHoule wrote:
| "Schizophrenia tends to run in families, but no single gene is
| thought to be responsible."
|
| https://www.nhs.uk/mental-health/conditions/schizophrenia/ca...
|
| Paul Meehl was associated with the hypothesis of _schizotaxia_
| and _schizotypy_ in the 1960s, he believed the first was caused
| by a single dominant gene. Schizotaxia would cause you to have
| 'synaptic slippage' which would cause negative social learning
| which would cause you to develop as a schizotype, which is
| related to
|
| https://en.wikipedia.org/wiki/Schizotypal_personality_disord...
|
| Schizotaxia, for instance, makes you liable to paranoia, but if
| it makes you a bullying magnet in school _and_ the authorities
| blow off your concerns and refuse to protect you you learn that
| _they really are out to get you_ which has many kinds of
| negative impact on your development which leads you to become a
| schizotype who might further develop schizophrenia if you are
| unlucky.
|
| Maybe 5% of the population is schizotypal, maybe 5% of those
| develop schizophrenia.
|
| Schizotypy is a form of neurodivergence that is similar in
| prevalence to autism and ADHD but unlike the others there are
| not institutions in place to diagnose it so if you present as a
| schizotype to a therapist under distress they will probably say
| you have "adjustment disorder with depression|anxiety|conduct
| concerns" and if they get so far as to think there is a
| developmental problem they will probably think it is autism or
| adhd since those are fashionable to have. (So fashionable that
| people who don't know anything about psychodiagnosis self-
| diagnose with autism or ADHD but a person who reads about
| psychology as a hobby might take decades to have that fateful
| moment where they read a long list of 20+ signs and symptoms
| and find they have 15 of them... But the similarity to autism
| is apt since schizotypes develop 'special interests' and tend
| to be loners because they learn that it is completely unsafe to
| reveal their difference to other people, even if they have no
| idea what that difference is.)
|
| It is not so safe to tell people you are a schizotype because
| of the stigma associated with schizophrenia and the fact that
| schizotypy is not well known among either the public or medical
| professionals. Some authorities think the pediatric syndrome
| described in this book
|
| https://www.amazon.com/Loners-Life-Path-Unusual-Children/dp/...
|
| is usually schizotypy.
| phkahler wrote:
| >> It might be more accurate to say its accepted that it may be
| involved in particular cases,
|
| It has been confirmed in at least one case "see Glenn Close
| schizophrenia relative" or something. I think genetic
| susceptibility IS involved in some cases and presumed to be a
| factor in many. But this all feels like splitting hairs on
| words describing probability ;-)
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