I think this doesn’t bode well for the research into neurotransmitter modulation.
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Schizophrenia is super complex. .i hope the cause of sz would come faster then any other disease.take care. and have a lovely day.my friend andrey…love from nepal…
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As for your comment at the end, I agree. Still perhaps negative symptoms are caused by a combo of abnormal neurotransmission and brain tissue structural abnormalities. You also have to acknowledge that in different people the amount of one contributing abnormality can be different from the next person.
I wouldn’t give up hope on min-101. I think its main mechanism of action is supposed to increase dopaminergic neurotransmission in the pfc. Without D2 blocking effects this might lead to a significant improvement in our negative or cognitive symptoms. Of course that’s a big if. If Dopaminergic blocking causes secondary negative symptoms in the individual min-101 could be a completely different world for that person.
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Could someone explain it in easy language?
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In easy language: these studies show that negative symptoms are associated with, but not necessarily caused by, defects in brain anatomy.
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They’ve found structural changes in predominately positive symptom schizophrenia too. I can’t remember what structure it was, but there was one that was significantly shorter in people who had visual hallucinations vs only auditory, and vs none.
Also, onset is not at birth as it is in some neurodevelopmental disorders. While I do think this is neurodevelopmental, clearly, enough of the brain is organized as it should be to function for many years. Then something happens. The balance of chemicals changes, inflammation sets in, we don’t know exactly. But if the brain could function normally prior to onset, it probably could again were conditions restored, whether that be thru drugs or something else.
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Unless the psychosis proves to be “toxic” and responsible for some brain damage. That could explain why some patients never recover their premorbid level of functioning.
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This is one high level discussion, but i think i get it
Is this right? They are a step closer to the cause of sz
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They are closing in on the causes, but it will still take a while until they finish.
If that’s the case, and it might be, the treatment would have to include some form of neurogenesis. Although, there are people who have suffered psychosis for a long time, but are still able to get back some form of stability on drugs, so it probably is an individual thing depending on individual brain structure. After all, those structures are what is responsible for creating and modulating those brain chemicals. The addition of the right drugs might be able to restore a balance even in the presence of brain damage. But, still I’m also inclined to lean toward a biological vs drug “cure” as well.
There’s a few drugs that seem to have an effect in neurogenesis, but we’re probably looking at stem cells. My favorite idea, anyway.
I think we’ve all seen the schizophrenia reversed in mice (and rats) experiments a few years ago. I think those both used transplants of interneurons, specifically. There’s some other research in neurodevelopmental disorders and stem cells (in rats) where they are using stem cells on rat brains after the rats have been prenatally exposed to heroin or brain damaged at birth. And it’s been working, apparently creating a new “critical period” for brain development and reversing the symptoms of prenatal drug exposure, and induced hypoxia at birth. With the “schizophrenic” rats, it appears that increasing the amount of interneurons reversed the symptoms, but with the prenatally damaged rats, it was more than just an increase in interneurons. So there’s a lot of possibilities there.
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Recreate the critical plasticity window - yes, sounds like a wonderful plan. It might come at the expense of immunity or stuff like that though. I’ve read some articles on this topic, researchers advise a cautious optimism.
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Yeah, I think I read that too, was it Berkeley? Mice genetically changed to have greater brain plasticity, but no immune system basically. However, in the prenatally damaged mice, they were just intracranially injecting stem cells (lol I say “just” like it was a simple thing). If the donors own cells are used, immune response shouldn’t be a problem. There is actually a word for how stem cells seem to “know” what to do, but I can’t remember what it is. It’s pretty cool.
I suspect in the near term that drugs are still going to be able to make a difference. The D3 receptor is expressed in brain regions controlling reward, emotions, and motivation and they’re working on meds targeting that. The Min-101 results are encouraging although I have a ton of questions about it that the Internet can’t answer. What was particularly encouraging about it though was that the patients in that trial continued to see improvements throughout the extension phase without reaching a plateau.
Anyway, if meds can take voices away, and voices come from a part of the brain that is smaller and not as well integrated in schizophrenia, then I don’t see why it shouldn’t be possible to take away negative symptoms with drugs even though they also have a physical/structural origin.
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These publications were really heavy on the jargon. I found my self easily getting lost trying to understand them.
Maybe it is a stupid question, but do you mean by there wasnt a plateau that the people of the trial kept improving?
Yes, there was a 3 month trial followed by a 6 month extension phase and during that whole time, participants continued to get better, as opposed to reaching some level of improvement and then not improving any further.
There’s a graph you can see on that page.
One of my questions for the Minerva people however is what about the people who dropped out? 142 people started, and 88 finished. There is probably some selection bias there because why would you drop out if you were getting better? Unless you had a lack of insight, felt better, and decided you weren’t sick after all. But it seems all meds help some people and not others, so why not this one as well.
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Does that mean min 101 can transform people into superpeople?
@twinklestars does min-101 show promise for cognitive symptoms in particular?
I have big trouble reading so I would appreciate concise input.
Probably not, I would expect that at some point the benefits would level off. If it could just get people to “mostly normal” that’d be pretty life changing. But, since receptor occupancy occurs pretty quickly, but improvement continues, it does suggest some healing or reorganization might be going on in the brain. Just speculation at this point.
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It’s not a “primary endpoint” but it is a “secondary endpoint” and they did say it showed statistically significant benefit in cognition.
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@patient I gather that you are worried about negative and cognitive symptoms
and are from Europe.
Why not try low dose amisulpride?( say 50-300 mg per day).
In that dose it is supposed to be effective for negative symptoms,
with little side effects.
This is what I am going to try next.
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