April 10, 2005

Psychotic Behavior Explained?

The following is from a press release from Oregon Health & Science University:

OHSU scientist helping explain basis of psychotic behavior
Findings could lead to improved treatments for schizophrenics, amphetamine abusers

PORTLAND, Ore. -- An Oregon Health & Science University researcher is among an international team closing in on why many people with schizophrenia and other psychotic disorders are "supersensitive" to the powerful neurotransmitter dopamine.

David Grandy, Ph.D., associate professor of physiology and pharmacology, OHSU School of Medicine, co-authored a study appearing recently in Proceedings of the National Academy of Sciences that found a link between dopamine supersensitivity and increased levels of a dopamine receptor with a particularly high affinity for dopamine.

Dopamine is a neurotransmitter found in the brain that plays an important role in the regulation of behavior involved in movement control, motivation and reward, and the dopamine system is thought to be essential to the brain's response to drugs of abuse, especially opiates and psychostimulants.

Supersensitivity to dopamine, which affects some 70 percent of individuals with schizophrenia, can take the form of a low tolerance to antipsychotics, amphetamines and other drugs, including drugs of abuse, that trigger dopamine's release in the brain. The latest discovery could someday lead to the development of drug therapies that temporarily bring people with psychosis into a more normal, less-sensitive state and make them more amenable to antipsychotic treatment.

It also could help scientists find ways to turn down the activity of the dopamine D2 receptor in individuals for whom dopamine sensitivity can be dangerous, such as prolonged drug abusers.

"It does appear that wherever you see supersensitivity, you see high-affinity dopamine D2 receptors as the predominant form," said Grandy, a pioneer in the study of the dopamine neurotransmitter system. "But to say you're going to then reverse supersensitivity by changing the D2-high status, we haven't done that. To do that, we have to be able to selectively manipulate the system in such a way that we could drive the receptor from high-to low-affinity or otherwise effect its ability to signal efficiently by some drug treatment."

While supersensitivity is only determined by observing behavioral changes, and the high-affinity D2 is verified pharmacologically, "what we're showing is a very strong correlation between the presence of a higher proportion of high-affinity D2 in a population of receptors in animals that show supersensitivity to dopaminergic drugs," Grandy added.

The study also further confirms the importance of the dopamine system in understanding and treating psychosis.

"The bottom-line, take-home message is that there are a lot of different things that all seem to converge on this system," Grandy said. "It's like all roads lead to Rome. The D2 system still seems to be very important in terms of psychosis and amphetamine-mediated disorders."

To create dopamine supersensitivity in animal models, researchers used mice bred to lack the D2 gene as well as rats treated with PCP, alcohol, amphetamine and other dopamine-inducing drugs. They found that while there were small increases in the total population of D2 receptors among the animal models, the increases were small compared with the jump in densities of D2 receptors in the high-affinity state.

The protein product of the dopamine D2 receptor gene already is the primary target for antipsychotic drugs used to treat schizophrenia, prolonged drug abuse and other diseases with psychotic symptoms. But scientists are only beginning to understand the cascade of events that allow dopamine receptors to signal that they have found and bound the neurotransmitter dopamine.

"The more we understand about the receptors, their physical characteristics, how they put themselves into this high-affinity state, and then signal this event in the brain, the closer we'll be to better treating and maybe even preventing the development of psychoses," Grandy said.


###
The study was led by Philip Seeman, M.D., Ph.D., professor emeritus of pharmacology at the University of Toronto, Canada. Grandy's work in this study was supported by the National Institute on Drug Abuse and the National Institute of Mental Health.

Source: OHSU news releases, visit www.ohsu.edu/news/

To access all OHSU news releases, visit www.ohsu.edu/news/


Comments

My daughter has schizophrenia and I noticed that even before she started taking medications but when she started having symptoms, the pupils of her eyes were unusually dialated. Is this related to dopamine? She uses no illicit drugs. Her pupils are still larger than normal. She had a MRI of her brain, but the doctor could find nothing wrong.

Posted by: Christie M. Carman at May 24, 2005 03:13 PM

Yes, I have always noticed the pupils of my wife(ex). This was ALWAYS a predictor of onset of symptoms. I also discovered that SUGAR in even minute amounts will always cause this same reaction. Often times a binging on sugars and carbs seems to be a precursor to psychotic behavior onset.

Posted by: Jeffrey Closson at July 1, 2005 01:17 AM

What's the current research for what is suspected there new cure in trinity college and the new treatment for the disease.

Posted by: Sharon at July 5, 2005 01:58 AM

My question is, has anyone noticed that when schzophrenics do a little bit of, specifically "crack cocaine" it seems to bring them back to normal? And I do mean "Normal" as how they used to be before the disease? Have anyone also noticed that when they stop it takes approximately 1 month to 1-1/2 month for the symptoms of schizo to become full blown again. AND IF SO Then what are the implications? Happened with my 31 year old son. Please, has anyone noticed this or is it just a "fluke" that it happened?

Posted by: Rose-May Gardere at July 19, 2005 09:52 AM

I've only had one episode that led to the discovery of me having this illness. It's only been a few months and I'm still wading through the thoughts and images that I had and the things/days that I can't remember continues to haunt me. I want to know and then I don't. I'm just praising God that he brought me through that valley of death. I can only imagine where I'd be if he hadn't. Praise God, he can keep you safe too.

Posted by: Vickie Ivy at August 17, 2005 08:11 AM

the person with the son, yes i have seen normalcy in crack user then when they came down
they became worse not better.
but like you said as long as they were using they were fine. Also found in people with biopolar. same effect. it levels them out for some reason.

Posted by: Angela at August 31, 2005 04:00 PM

I have had three severe schizophrenic psychotic episodes in the last 15 years. Partially the first two were explained by lack of or too little thyroxine prescribed following a thyroidectomy for Graves' Disease (hypothyroid psychosis or myxoedemic psychosis is little recorded but known of), which was since well-managed with thyroxine replacement and no ongoing drugs required on leaving hospital, but the most recent had apparently no cause at all.

Recently I read that schizophrenic episodes in recurring patients were related to a hypersensitivity to dopamine in the brain, which I had not heard about before, except in the context of an article in the first UK edition of Psychologies magazine in reference to high dopamine levels being produced in the initial stages of attraction to someone (Dr. Helen Fisher, Rutgers University, New Jersey - anthropologist) and that MRI imaging showed dopamine flooding into the receptive areas of the brain in couples in love when shown a picture of each other. Later after reading about dopamine and schizophrenia, I was able to see exactly what the trigger for my own schizophrenia is - I have never had a relationship, but have on a number of occassions experienced strong unrequited crushes on men, and instead of feeling happy and euphoric at being attracted to someone, feelings which I have never experienced at all, I felt invariably afraid, paranoid, angry, upset, irrational and spent most of the duration of the attraction until I never saw the person again withdrawn and awkward - and the three psychotic episodes requiring hospitalisation and drug treatment coincided with the unrequited infatuations I felt strongest and could not avoid seeing in person because they were work colleagues or co-students. If it is true that physically seeing the person to whom you are attracted produces dopamine, then in myself where dopamine is the most likely cause of psychotic episodes (which I have noticed emerging mental images again on other occassions being attracted to someone, which fade after time if I do not see the person again), then for me the trigger is 'falling in love' where so far I have been unreciprocated in my imagined feelings and emotions and mental images which are created. As I have not yet experienced mutual attraction or what my reaction would be if a relationship actually developed, I have to resign myself to the fact that I only need to feel attracted to someone to trigger off a chain reaction leading possibly to mental and auditory hallucinations, suggestible, destructive and irrational behaviour, and suicidal feelings - even hospitalisation. The rest of the time I am not attracted to anybody, I'm fine - I work and study full-time and fully function as a single parent, my souvenir from a drunken episode on holiday - which was not connected to any feelings of attraction or psychotic thoughts at all. But alcohol on occassion has also stimulated irrational thought patterns if I am attracted to someone at the time, so I avoid alcohol and try to steer clear of any individual concerned if I am out drinking with friends.

I'm interested to know if a psychologist would be able to re-educate my brain to changing the self-destructive emotions I feel when attracted to a person that lead to these breakdowns?

Posted by: Lisa S. at January 4, 2006 11:24 AM

I am the new wife of a 41-year old man who was a drug addict most of his life, but managed to stop cold turkey. But now he has been an intense alcoholic for the past five to ten years with only occasional remission. Several years ago, I've discovered, he was diagnosed OCDP and Bi-Polar, and receives medication for both as well as in-patient, AA, etc. treatment for his addictions. He still has relapses, and I have noted too often that when he is drinking very intensely, his behavior becomes downright psychotic, and he tries to destroy his environment, and even harm himself (tho not direct suicide attempts) ... but never physically attacks me or others. At such times, his contact with reality and reason seems minimal. So far, his psychotic behavior has not been addressed directly by any physician, and I am frustrated as to 'why not! Any comments or suggestions?

Posted by: Beverly V. at February 19, 2006 08:43 PM

i see the walls in my room buckle and i have no idea why.sometimes i say somthin or do somthin and it almost seems like a dream,like talking to someone,or riding my dirt bike.it has only been happening for a year but i have had about five concusions,two before these things have been happenning is this psychotic behavior or symptums from all the concusions?

NO I AM NOT ON DRUGS AND I HAVE NEVER BEEN ON THEM.

Posted by: ACE at May 12, 2006 04:23 PM

It seems like almost every person I meet that the Dr's have labeled "schizophrenic" have been drug users. Its true that when they use drugs again they become "normal". It's amazing. All the other legal drugs prescribed by the Dr. just make them more angry and have sooo much side effects (Parkinson like symptoms) I just wish I knew of a natural legal way to affect that part of the brain where the drugs have created an imbalance. Im tired of Dr's labeling people instead of finding a real solution. Every problem can not be fixed with a pill. I am tired of the "pill" theory.

Posted by: me at August 2, 2007 04:31 PM

Since Schizophrenia is an organic illness, isn't there some kind of surgical procedure to treat it?

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