Psycho-Babble Medication Thread 1117719

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Novel treatment for schizophrenia

Posted by SLS on December 9, 2021, at 8:42:24


A potential new approach for the treatment for both positive and negative
symptoms of schizophrenia:


-------------------------------------------------------------------------

From MDLinks:

https://tinyurl.com/3e63t2r5

A potential new approach for the treatment of schizophrenia:

"A new study led by Jeff Conn, Lee E. Limbird Chair in Pharmacology, James
Maksymetz, a former graduate student in the Conn laboratory, and other
collaborators at the Warren Center for Neuroscience Drug Discovery has
identified a protein in the central nervous system, known as mGlu1, as a
potential target for novel treatments of schizophrenia.

Schizophrenia, which affects approximately 1 percent of the global population,
has been historically difficult to treat. Current clinically approved antipsychotics
are effective at reducing "positive symptoms" like hallucinations and delusions in
some patients, but they fail to treat "negative symptoms," such as social
withdrawal, lack of motivation and cognitive deficits associated with the disease.
The new research focused on identifying a new approach that would treat
positive and negative symptoms, Maksymetz said.

Schizophrenia is thought to occur when a region of the brain called the
prefrontal cortex becomes abnormally active because interneurons, which
connect neuron circuits or neuron groups, become dysfunctional and stop
regulating neuronal activity. Conn's team sought to modulate the activity of those
cells.

After identifying mGlu1an abbreviation of metabotropic glutamate receptor
subtype 1as a potentially druggable target, they tested it with a compound that
enhances its function: a positive allosteric modulator. The PAM was previously
developed by Conn in close collaboration with other labs in the WCNDD,
including those of Craig Lindsley, University Professor of Chemistry and
Pharmacology, and Colleen Niswender, associate professor of pharmacology.
Using this compound, they found that enhancing the activity of mGlu1 selectively
increased the activity of specific inhibitory interneurons, restoring their ability to
inhibit the neuronal circuits they control.

Further, the researchers saw that by working with the PAM, symptoms
characteristic of schizophrenia in human patients were reversed. These results
suggest that using a PAM to enhance mGlu1 activity is an effective treatment for
schizophrenia.

Why it matters

Schizophrenia is an important clinical and societal concern. "Inadequate
treatment responses and failures to address 'negative symptoms' and cognitive
deficits result in poor patient outcomes," Maksymetz said. "And they incur a
huge financial burden on the U.S. and global economies."

Researchers hope that this novel treatment strategy "may eventually provide
relief for patients, allow them to reintegrate into and contribute to society, and
diminish the burden on our health care systems." The results of this research are
particularly exciting because the drug reverses working memory deficits, a
hallmark of schizophrenia for which there is currently no treatment.

Today's pharmaceutical schizophrenia treatments were serendipitously
discovered half a century ago and were not derived from good understanding of
disease biology. Decades of clinical findings have improved researchers'
understanding of the biological basis of the disease, opening the door for the
development of better-targeted, more efficacious drugs. "We reasoned that if
we addressed the underlying disease biology by boosting the function of these
interneurons, then we might be able to rescue cognitive deficits associated with
prefrontal cortex dysfunction," Maksymetz said.

What's next

The results of this study raise a number of questions about mGlu1 biology.
Ongoing studies in the Conn lab are investigating the role and effects of mGlu1
in various regions within the brain.

To translate these findings to the clinic, scientists will need to investigate the
efficacy of PAMs when used chronically rather than in the short term, evaluate
potential side-effects, and determine whether enhancing mGlu1 reduces other
symptoms in schizophrenia, especially "negative symptoms" like a lack of
motivation and social withdrawal, which are frequently treatment-resistant.

"We think this study is a good foundation to build upon," Maksymetz said.
"Hopefully we will be able to test the hypothesis that mGlu1 PAMs can actually
treat patients with schizophrenia someday soon. I truly believe that
understanding how neural circuits function and dysfunction will lead to a
revolution in treating neuroscience-related diseases, and I'm excited to be a part
of it."

The research was published in Cell Reports."

 

Re: Novel treatment for schizophrenia

Posted by undopaminergic on December 9, 2021, at 13:38:46

In reply to Novel treatment for schizophrenia, posted by SLS on December 9, 2021, at 8:42:24

>
>
>
> A potential new approach for the treatment for both positive and negative
> symptoms of schizophrenia:
>
>
> -------------------------------------------------------------------------
>
> From MDLinks:
>
> https://tinyurl.com/3e63t2r5
>
> A potential new approach for the treatment of schizophrenia:
>
[...]
> The research was published in Cell Reports."
>

This maybe?
https://www.cell.com/cell-reports/pdf/S2211-1247(21)01427-3.pdf

-undopaminergic

 

Re: Novel treatment for schizophrenia

Posted by Lamdage22 on December 10, 2021, at 10:22:06

In reply to Novel treatment for schizophrenia, posted by SLS on December 9, 2021, at 8:42:24

Thanks. Not any time soon though :( Not sure if I have negative symptoms or depression or if it even matters.

 

Re: Novel treatment for schizophrenia

Posted by undopaminergic on December 10, 2021, at 10:49:15

In reply to Re: Novel treatment for schizophrenia, posted by Lamdage22 on December 10, 2021, at 10:22:06

> Thanks. Not any time soon though :(

Actually, I think it would be possible to acquire the drug they used as a research chemical.

> Not sure if I have negative symptoms or depression or if it even matters.

I'm not sure about that either.

-undopaminergic

 

Re: Novel treatment for schizophrenia

Posted by Lamdage22 on December 10, 2021, at 10:53:35

In reply to Re: Novel treatment for schizophrenia, posted by undopaminergic on December 10, 2021, at 10:49:15

Too risky for my taste. I can understand how you can be compelled to do it though, as I have been there.

> Actually, I think it would be possible to acquire the drug they used as a research chemical.

 

Re: Novel treatment for schizophrenia

Posted by undopaminergic on December 10, 2021, at 11:21:50

In reply to Re: Novel treatment for schizophrenia, posted by Lamdage22 on December 10, 2021, at 10:53:35

When was that, if you don't mind telling?

> Too risky for my taste. I can understand how you can be compelled to do it though, as I have been there.
>
> > Actually, I think it would be possible to acquire the drug they used as a research chemical.
>
>

-undopaminergic

 

Re: Novel treatment for schizophrenia

Posted by Lamdage22 on December 10, 2021, at 12:04:47

In reply to Re: Novel treatment for schizophrenia, posted by undopaminergic on December 10, 2021, at 11:21:50

Basically few years ago before I started supplements. I was in a clinic focused on non-medical approaches at the same time I started the supplements. No med changes. Not for two years before that. Not until today. My recuperation seems to be based on psychotherapy and nutrient therapy. It is why I am advocating for these things here, because they may help others, here, too. Not saying to quit all meds, just dont make it a religion.

 

Re: Novel treatment for schizophrenia

Posted by undopaminergic on December 10, 2021, at 12:13:23

In reply to Re: Novel treatment for schizophrenia, posted by Lamdage22 on December 10, 2021, at 12:04:47

What substance(s) would you have liked to acquire?

> Basically few years ago before I started supplements. I was in a clinic focused on non-medical approaches at the same time I started the supplements. No med changes. Not for two years before that. Not until today. My recuperation seems to be based on psychotherapy and nutrient therapy. It is why I am advocating for these things here, because they may help others, here, too. Not saying to quit all meds, just dont make it a religion.

-undopaminergic

 

Re: Novel treatment for schizophrenia

Posted by Lamdage22 on December 10, 2021, at 12:21:19

In reply to Re: Novel treatment for schizophrenia, posted by undopaminergic on December 10, 2021, at 12:13:23

Rapastinel. I wasnt too close to doing it. It occupied my mind for a few days. Thats all. I could have invested that time into the things I mentioned in my last post, and would have gotten more out of it. Rapastinel proved to be a failure in trials. Unfortunately, that happens to many previously promising compounds. It could have been dangerous, too.

 

Re: Novel treatment for schizophrenia

Posted by undopaminergic on December 10, 2021, at 14:12:48

In reply to Re: Novel treatment for schizophrenia, posted by Lamdage22 on December 10, 2021, at 12:21:19

> Rapastinel. I wasnt too close to doing it. It occupied my mind for a few days. Thats all. I could have invested that time into the things I mentioned in my last post, and would have gotten more out of it. Rapastinel proved to be a failure in trials. Unfortunately, that happens to many previously promising compounds.
>

I think most of these compounds would be very useful in select individuals, so they should be made clinically available.

-undopaminergic

 

Re: Novel treatment for schizophrenia

Posted by Lamdage22 on December 10, 2021, at 23:52:37

In reply to Re: Novel treatment for schizophrenia, posted by undopaminergic on December 10, 2021, at 14:12:48

$$$... it wouldn't be profitable...

> I think most of these compounds would be very useful in select individuals, so they should be made clinically available.
>
> -undopaminergic
>

 

Re: Novel treatment for schizophrenia

Posted by undopaminergic on December 11, 2021, at 7:23:45

In reply to Re: Novel treatment for schizophrenia, posted by Lamdage22 on December 10, 2021, at 23:52:37

Well, it's better than nothing, isn't it? It's usually the failure to outperform placebo that keeps them from the market. Placebo is actually a pretty powerful treatment, especially in a randomised trial population.

> $$$... it wouldn't be profitable...
>
> > I think most of these compounds would be very useful in select individuals, so they should be made clinically available.
> >
> > -undopaminergic
> >
>
>

-undopaminergic

 

Re: Novel treatment for schizophrenia

Posted by Lamdage22 on December 13, 2021, at 7:29:47

In reply to Re: Novel treatment for schizophrenia, posted by undopaminergic on December 11, 2021, at 7:23:45

I agree, what I meant is that if only a minority benefits from rapastinel, the drug company wont pursue it, because it is not economical. That is part of the problem that I see. Most of the time you only get the substances that support the manufacturer the most, not you.

There are exceptions but generally

 

Re: Novel treatment for schizophrenia undopaminergic

Posted by SLS on December 13, 2021, at 8:22:27

In reply to Re: Novel treatment for schizophrenia, posted by undopaminergic on December 9, 2021, at 13:38:46

Hi, UD.

> > A potential new approach for the treatment for both positive and negative
> > symptoms of schizophrenia:
> >
> >
> > -------------------------------------------------------------------------
> >
> > From MDLinks:
> >
> > https://tinyurl.com/3e63t2r5
> >
> > A potential new approach for the treatment of schizophrenia:
> >
> [...]
> > The research was published in Cell Reports."
> >
>
> This maybe?
> https://www.cell.com/cell-reports/pdf/S2211-1247(21)01427-3.pdf
>
> -undopaminergic


I interpret this article as referring to positive symptoms only.


- Scott

 

Re: Novel treatment for schizophrenia SLS

Posted by undopaminergic on December 13, 2021, at 8:32:21

In reply to Re: Novel treatment for schizophrenia undopaminergic, posted by SLS on December 13, 2021, at 8:22:27

> Hi, UD.

Hi, SLS.

> > https://www.cell.com/cell-reports/pdf/S2211-1247(21)01427-3.pdf
> >
> > -undopaminergic
>
>
> I interpret this article as referring to positive symptoms only.

Actually, I read it and it focussed mostly on cognitive symptoms.

-undopaminergic

 

Re: Novel treatment for schizophrenia

Posted by Lamdage22 on December 13, 2021, at 9:58:57

In reply to Re: Novel treatment for schizophrenia, posted by undopaminergic on December 10, 2021, at 11:21:50

Can something that improves negative symptoms cause depression? I dont get it. The two problems sound identical.

 

Re: Novel treatment for schizophrenia

Posted by undopaminergic on December 13, 2021, at 10:15:27

In reply to Re: Novel treatment for schizophrenia, posted by Lamdage22 on December 13, 2021, at 9:58:57

> Can something that improves negative symptoms cause depression?

Probably not in the same individual, but as you know, a drug that works for someone may not work for someone else.

> I dont get it. The two problems sound identical.

The anhedonia and apathy are identical, but negative symptoms does not necessarily include a depressed mood, more likely it's flat.

-undopaminergic

 

Re: Novel treatment for schizophrenia

Posted by Lamdage22 on December 13, 2021, at 14:42:06

In reply to Re: Novel treatment for schizophrenia, posted by undopaminergic on December 13, 2021, at 10:15:27

So according to that definition, I have both negative symptoms and depression. That would make most sense. For most of my life I have been depressed and socially anxious/withdrawn but never psychotic until I tried MAOI. So the negative symtoms came ontop of that after I was psychotic.

It would be best if doctors found a cause rather than treating symtoms. Like they do with NMDA receptor encephalitis. An underlying issue. I bet you that most of the time there is something going on beneath the symptoms. Psychiatrists admit that they are not treating root causes most of the time.

> but negative symptoms does not necessarily include a depressed mood, more likely it's flat.
>
> -undopaminergic
>

 

Re: Novel treatment for schizophrenia undopaminergic

Posted by SLS on December 14, 2021, at 8:30:46

In reply to Re: Novel treatment for schizophrenia, posted by undopaminergic on December 13, 2021, at 10:15:27

> > Can something that improves negative symptoms cause depression?
>
> Probably not in the same individual, but as you know, a drug that works for someone may not work for someone else.
>
> > I dont get it. The two problems sound identical.
>
> The anhedonia and apathy are identical, but negative symptoms does not necessarily include a depressed mood, more likely it's flat.
>
> -undopaminergic

While I was hunting for articles that refer to any differences that may exist between anhedonia and apathy, I found something that is more important than nomenclature. The dichotomy described in the two major subtypes of Major Depressive Disorder has been applied since 1980. To my knowledge, Michael Liebowitz and the research team at Columbia were the first to identify this difference.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042519/

"Features of depression: melancholia, anhedonia, apathy

Different types of depression are associated with markedly different symptoms. Depression with melancholic features is associated with anhedonia, lack of mood reactivity, sadness, weight loss, insomnia, psychomotor agitation, and worse mood in the morning. Depression with atypical features, on the other hand, is associated with a distinct cluster of symptoms, and includes leaden paralysis, fatigue, weight gain, hypersomnia, mood reactivity, sensitivity to social rejection, and worse mood in the evening. It is currently unclear whether the inclusion of such profoundly different clusters of symptoms under the umbrella of a single disorder is a help or a hindrance for the development of treatments. The association of tricyclic antidepressants with better outcomes for melancholic depression [12] and bupropion for atypical depression [13], suggests (but does not mandate) differences in the underlying biology."


- Scott

 

Re: Novel treatment for schizophrenia

Posted by undopaminergic on December 14, 2021, at 8:54:33

In reply to Re: Novel treatment for schizophrenia, posted by Lamdage22 on December 13, 2021, at 14:42:06

> So according to that definition, I have both negative symptoms and depression. That would make most sense. For most of my life I have been depressed and socially anxious/withdrawn but never psychotic until I tried MAOI. So the negative symtoms came ontop of that after I was psychotic.
>

What negative symptoms appeared after the psychosis?

For many people, the negative symptoms actually precede psychosis, sometimes by a long time.

> It would be best if doctors found a cause rather than treating symtoms.

Of course.

> Like they do with NMDA receptor encephalitis. An underlying issue. I bet you that most of the time there is something going on beneath the symptoms. Psychiatrists admit that they are not treating root causes most of the time.
>

If the disorder/disease is understood, such as with Parkinson's disease, it is a neurological and not psychatric condition. So psychiatrists are kind of doomed to treat patients without knowledge of the underlying causes.

-undopaminergic

 

Re: Novel treatment for schizophrenia Lamdage22

Posted by SLS on December 14, 2021, at 9:15:50

In reply to Re: Novel treatment for schizophrenia, posted by Lamdage22 on December 13, 2021, at 14:42:06

> It would be best if doctors found a cause rather than treating symtoms. Like they do with NMDA receptor encephalitis. An underlying issue. I bet you that most of the time there is something going on beneath the symptoms. Psychiatrists admit that they are not treating root causes most of the time.

This has been the focus of scientific research since the 1950s. Unfortunately, there is no consistency in findings.


- Scott

 

Re: Novel treatment for schizophrenia undopaminergic

Posted by SLS on December 14, 2021, at 10:04:41

In reply to Re: Novel treatment for schizophrenia, posted by undopaminergic on December 14, 2021, at 8:54:33

UD,

> If the disorder/disease is understood, such as with Parkinson's disease, it is a neurological and not psychatric condition.

Is Bipolar Disorder a neurological disease?

Why or why not?


- Scott

 

Re: Novel treatment for schizophrenia

Posted by Lamdage22 on December 14, 2021, at 12:08:12

In reply to Re: Novel treatment for schizophrenia Lamdage22, posted by SLS on December 14, 2021, at 9:15:50

So you could say mental disorders are not understood very well, although they have been trying? I really hope they make some progress. Id be much more willing to try medical treatment if it would take care of the root cause. Its psychological for me too. Some crazys were/are made crazy.

> This has been the focus of scientific research since the 1950s. Unfortunately, there is no consistency in findings.
>
>
> - Scott

 

Re: Novel treatment for schizophrenia SLS

Posted by undopaminergic on December 14, 2021, at 12:40:23

In reply to Re: Novel treatment for schizophrenia undopaminergic, posted by SLS on December 14, 2021, at 8:30:46

> > > Can something that improves negative symptoms cause depression?
> >
> > Probably not in the same individual, but as you know, a drug that works for someone may not work for someone else.
> >
> > > I dont get it. The two problems sound identical.
> >
> > The anhedonia and apathy are identical, but negative symptoms does not necessarily include a depressed mood, more likely it's flat.
> >
> > -undopaminergic
>
>
>
> While I was hunting for articles that refer to any differences that may exist between anhedonia and apathy,
>

The two are very different in my experience and understanding. Anhedonia is the lack of reward, pleasure, enjoyment from doing things you would normally. While that is of course a symptom that reduces motivation to engage in activities, it's nothing like apathy, which takes away *all* (or most) of the motivation and interest for doing things. I think you could summarise it as anhedonia taking away the "liking" of activities, and apathy taking away the "desire" for activities. You can also call apathy "anticipatory" anhedonia, with "regular" anhedonia being "consummatory".

> I found something that is more important than nomenclature. The dichotomy described in the two major subtypes of Major Depressive Disorder has been applied since 1980. To my knowledge, Michael Liebowitz and the research team at Columbia were the first to identify this difference.
>
> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042519/
>
> "Features of depression: melancholia, anhedonia, apathy
>
> Different types of depression are associated with markedly different symptoms. Depression with melancholic features is associated with anhedonia, lack of mood reactivity, sadness, weight loss, insomnia, psychomotor agitation, and worse mood in the morning. Depression with atypical features, on the other hand, is associated with a distinct cluster of symptoms, and includes leaden paralysis, fatigue, weight gain, hypersomnia, mood reactivity, sensitivity to social rejection, and worse mood in the evening. ...
>

I have a little of both. I have anhedonia, worse mood in the morning, fatigue, and initial insomnia that is followed by hypersomnia.

-undopaminergic

 

Re: Novel treatment for schizophrenia SLS

Posted by undopaminergic on December 14, 2021, at 13:18:26

In reply to Re: Novel treatment for schizophrenia undopaminergic, posted by SLS on December 14, 2021, at 10:04:41

> UD,

SLS,

> > If the disorder/disease is understood, such as with Parkinson's disease, it is a neurological and not psychatric condition.
>
> Is Bipolar Disorder a neurological disease?

Not at present.

> Why or why not?

It's too poorly understood to be considered a neurological condition, and much for that reason, the treatment consists mostly of experimentation to find mood stabilising drugs. Compare that to Parkinson's disease where L-dopa is a safe bet (if it does not respond to L-dopa, it's probably not Parkinson's -- could be manganism for instance).

Also, there are often psychological factors involved in bipolar disorder.

-undopaminergic


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