Similarity between schizophrenia and dementia discovered for the first time

[Mysterier]

Similarity between schizophrenia and dementia discovered for the first time

Researchers for the first time compared schizophrenia and frontotemporal dementia, disorders that are both located in the frontal and temporal lobe regions of the brain. The idea can be traced back to Emil Kraepelin, who coined the term "dementia praecox" in 1899 to describe the progressive...

www.cbs.mpg.de

 

[Fertile]

But don't the neuroleptics cause these observed changes in brain structure? I'm also aware that their seems to be 2 distinct changes in brain chemistry that medication seeks to treat. We have had 'the dopamine hypothesis' since 1952 and then 'the glutamate hypothesis' since 1974. We have observed that their is either an excess of DOPAC, a shortage of NMDA or both features in the cerebrospinal fluid of those suffering from schizophrenia. That may mean that the true cause is upstream, but in terms of medication, it means some people respond well to dopamine antagonists while some are refractive. But NMDA receptor modulators are very often successful in such patients.

It would have been nice if the article had reference.

One of my childhood friends developed refractive schizophrenia. When you have no experience of it, it's deeply frightening. I have kept looking for him on the internet and the last mention was him setting fire to his home in 2002. That was about 8 years after I last saw him.

He's a lovely guy and none of us can put a finder on when the symptoms started, or at least when others could see that things were very wrong.

 

[izo]

I felt really psychotic on a full dose of olanzapine (15mg). It’s dirty stuff, maybe useful at 5mg, nothing more. Haloperidol at 5mg was very nice indeed. I think it can be rather euphoric under 10mg. Quetiapin and prothipendyl are really nice and sedating too without tolerance at low dose. I don’t see the effort in people giving high dose neuroleptics like risperidon, haloperidol, olanzapine, aripiprazol or any of the older Ring substituted ones like chlorpromazine. I think they have their use if a person is really agitated for short term treatment but I’ve seen normal dumb speedfreaks being on abilify for weeks, not being able to shower and barely making it to the dinner table. Makes no sense, where is the treatment success in that? Plus social workers on the same station appear to work on tilidine. Well that just makes sense, psychiatry is still full of flaws until today, at least here in Germany. Psychiatrist are the least useful doctors there are and I’ve seen a bunch of them not doing anything really useful and cash in around 4500eur for that, at least that’s the case with most station doctors.

 

[Fertile]

In the UK, the standard treatment for agitated patents is colloquially known as a B52 which is 5mg haloperidol and 2mg of lorazepam.

But their are still some patients refractive to the effects of the B52. In these cases, paraldehyde is used. Clinicians have to use glass syringes and needles composed of a special steel because the drug attacks plastics and tarnishes some metals.

Paraldehyde is an interesting compound - it has 3 chiral centres and 4 isomers.... It's often used by lecturers to confuse students,

 

[izo]

Here I’ve Seen random people,not agitated on 25mg haldol, plus one alcoholic became it due to withdrawal which seem to have helped.
aripiprazol too, people run around the whole not being able to fulfill simple tasks and that helps them how? It was a 19 yo speed boy, supposedly came in intoxicated, after one night of sleep hes fine again and has to stay there for a week for control, sober. That’s standard protocol I’d say and make a zombie until he leaves the hospital. Again, what sort of treatment success should that be. Others that are severly depressed get nothing. And that’s psychiatric ward everyday life in Germany. At least they don’t do electron spasm therapy anymore or pump poor old ladies so full with haldol that they developed permanent Parkinson like symptoms and have to stay in a wheelchair all the time. This happened not long ago.

 

[Fertile]

I had to complete an entire 4 month module on neuroleptics. What I learnt was that they all have serious side-effects that would preclude them from being licenced for ANY OTHER ILLNESS apart from schizophrenia only quadriplegia is considered to be the most disabling long-term illness known to science. I mean it knocks an average of 10 years off anyone prescribed them long-term, they cause diabetes, dystonia, bradykinesia, rigidity, tremor, neuroleptic malignant syndrome, tardive dyskinesia, akathisia, sexual dysfunction, reduced affect, anhedonia leading to refractive depression AND many idiopathic symptoms. Well, I say idiopathic BUT they all clear off when neuroleptics are discontinued so not really idiopathic and likely not even a mystery to the pharma companies who supply neuroleptics.... but a mystery to anyone outside of those companies.

There are even BETTER medications but each one of them only works for about 10% of sufferers and so rather than burdening a consultant with an average of 5 consultations to find the RIGHT medication, they go with the much more dangerous medicines that give people a terrible quality of life.

Knowing this, can you see why I didn't pursue medical chemistry as a career. Actually, it was the neuroleptics and 'sacrificing' animals to test new medicines. I believe SOME animal testing is needed but 90% of it can be replaced with cellular models. In fact, until thalidomide VERY FEW animal models were used. I have met and been disgusted by how 'gung ho' many medicinal chemists ARE.

I am someone who believes that first-into-man should be the team leader. If you read the story of buprenorphine, you will discover that all of the human tests were members of the team. There was also a hilarious (in retrospect) mistake. John Lewis (team-lead) asked the lab assistant to make the daily 11AM cup of tea for the team. So a nice teapot was washed first with cold water and then with hot water (to warm the pot). 4 teabags were placed into the teapot and the mixture was stirred with a glass rod...

A glass rod that had previously been used to mix a saturated solution of buprenorphine. At 11.05 everyone got out their favourite mug, the lab assistant added milk and each member had a lovely cup of tea poured for them with sugar added as specified.

At 11.15 AM a chemist on another project walked past the lab and looked through the glass pane in the door. He saw all 11 team members flat out on the floor of the lab. He reacted quickly ringing the office to get ambulance, regional poisons unit and police. THEN he did something that saved 11 lives. This was in the days before naloxone, naltrexone, nalmefene. Diprenorphine WAS in the building but it's considered to be VERYtoxic in man and at the time nobody had found an appropriate dose schedule. You might say 'well, better than nothing' but diprenorphine had killed many peoplee.

But what they DID have was nalorphine. Now nalorphine isn't exactly a bed or roses either. it possesses a great deal of κ-agonism as well as a very short duration. So short that it has to be given about once every 10 minutes (actually it's longer than 10 minutes but their wasn't enough evidence to give it less frequently.

So the chemist call downto his lab and soon 8 medicinal chemists are passing among the buprenorphine victims (who are having tremendous, dysphoric hallucinations and are physically fighting off the people who are trying to save them. That must have been 'quite some day at the office'.

The outcome? Reckitt Benckiser decree that staff must not eat and drink in the lab.

They didn't ban smoking, BTW,

 

[izo]

Yeah, I heard that story, the people over at Jansen pharm must have worked more carefully. Btw Paul Adrian janssen got ennobled to a baron in his later years.

 

[paranoid android]

For more psychosis was most like tripping on dramine

 

[Fertile]

There was a (very, very ethically dubious) study in the 1970s. Patients suffering from serious long-term schizophrenia but whose medication was very successful were given PCP. Every single one of them displayed florid signs of schizophrenia. Of course, PCP is not only an NMDA antagonist but a potent dopamine reuptake inhibitor.

So it wasn't proof of one cause or another - but it proved (?) that ALL cases of schizophrenia were due to excess dopamine and/or to little NMDA.

It's a terrible document with people to sick to make an informed choice being given a potent drug that sent them back into their nightmare world of schizophrenia. Truly if any of those researchers are still alive, they should be tried for criminal actions.

Interestingly, ketamine does NOT accurately mimic schizophrenia. But I have always wanted to develop a prodrug of dizocilpine, a depot injection if you will. With something like that you could induce schizophrenia in ANYONE for 28 days. I've read trip-reports of people who HAVE suffered schizophrenia who then took dizocilpine and confirmed that the effects of the drug and of the illness are identical.

The only positive thing about dizocilpine is that it's key to finding the QSAR of such drugs. It has the 'magic angle' of 109.5 degrees between aryl and N:.

Dramamine may well act upstream and actually teach us more about the illness but sadly since it's been abused on the street, using it in formal trials would be VERY difficult.

 

[thegreenhand]

but it proved (?) that ALL cases of schizophrenia were due to excess dopamine and/or to little NMDA.

that doesn't prove that all cases of schizophrenia were due to alterations in dopamine levels or NMDA receptor functions.

you stated that they only used long term patients, and people who had success with antipsychotic medication

that excludes a lot of subpopulations

 

[Fertile]

that doesn't prove that all cases of schizophrenia were due to alterations in dopamine levels or NMDA receptor functions.

you stated that they only used long term patients, and people who had success with antipsychotic medication

that excludes a lot of subpopulations

You would have to test every single person diagnosed with schizophrenia to know all cases were associated with one of those two neurotransmitters but if memory serves their sample size was over 260 people. I believe that has the statistical significance for it to be stated as a fact.

We also know that the illness can be produced in man using PCP & dizocilpine (both of which which will increase serotonin and reduce NMDA) but also we know stimulant psychosis is usually differentiated from schizophrenia by preventing the sufferer from taking said stimulants so I presume it's symptoms are very similar.

But I did suggest that their could be something common upstream that we haven't found yet.

All told, it's still a very mysterious disease.

I just think it's a terrible loss that medicines such as Pomaglumetad never reached market. It only worked on a minority of patients (those lacking NMDA) but it's side-effect profile meant that for that group, it could have significantly improved quality of life.