Saturday, October 14, 2006

A Beautiful Mind

"Imagine if you'd suddenly learnt that the people, the places, the moments most important to you were not gone, not dead, but worse- had never been. What kind of hell would that be?". - A Beautiful Mind, 2001.

I saw the movie for the second time last night and it got me thinking about the complex disorder that is schizophrenia, and the intense effects it has on an individual, making him lose the distinction between real and imaginary. So what is it that makes a person harbour irrational thoughts and so convinced about the his false fears? I tried to poke around the literature to try to understand how much of the organic basis for this disorder is understood. There is the genetic component- the heritable nature of this disorder has been well documented over the years. Mutations in genes that are involved in brain function can be inherited, causing offspring of schizophrenics to be that much more at risk of developing the disorder. The environment plays an equal role, stress and psychological trauma are known to have a causal or triggering effect in schizophrenia, translating genetic predisposition to development of the disorder.

The neuropathology of the disease itself is closely linked to the above described factors. Bad genes, as well as early trauma to the brain, prenatal exposure to infections and psychological trauma result in brain abnormalities that cause cognitive defects and result in the disorder. There are two aspects to understanding how impaired brain function leads to this condition. Firstly the anatomic location of neural systems that are disrupted govern the types of symptoms exhibited by a patient. Various regions of the brain are involved in different functions such as processing impulses, perceiving thoughts and producing a reaction to a stimulus. The distortion in reality observed in schizophrenics is attributed to one region of the brain, thought disorganisation involves malfunction of a different circuit, while a decline in perceptive and physical responses are traced to malfunction in yet another circuit.

Secondly, brain chemistry- in terms of fluctuations in neurotransmitters (the chemicals that transmit signals in the brain cells) control the duration of above mentioned symptoms, to add another layer of complexity to this intricate orchestration. The sum effect of all of this is disorganised thinking, delusional and paranoid thought processes and auditory hallucinations that manifest as schizophrenia.

Dopamine, glutamate and NMDA are some of the neurotransmitters that have been implicated in schizophrenia. The "Dopamine hypothesis" is particularly famous, as it was one of the first major biological causes that could be attributed to schizophrenia. However, it is now thought to be an oversimplification at understanding the disorder, since there are other factors that play a role. Nevertheless, I will discuss the hypothesis because it provides atleast some insight into the process, and is quite fascinating.

Dopamine is a neurotransmitter, and in one of it's functions it is associated with the "pleasure system" of the brain, providing feelings of enjoyment and motivating a person proactively to perform certain activities. Essentially, it mediates the conversion of an outside stimulus from being a "cold" or neutral bit of sensory information into an "attractive" or an "aversive" entity.

For example- normally an external stimulus such as a bright red sports car zipping past a pedestrian might result in a surge of dopamine to cause an appropriate reaction- like the pedestrian turning his head to look at the car. However, the reaction elicited also depends upon the the pedestrian's predispositions and experiences. A race-car enthusiast may turn to look, while a person not interested in sports cars will not exhibit any reaction. In any case, dopamine here mediates a contextually relevant reaction.

In the 1970s, it was discovered that drugs that block dopamine function reduced psychotic symptoms. Further studies led to the hypotheses that dysregulated dopamine transmission causes an abnormal release of dopamine, so that what would have been a normally neutral stimulus results in firing up of neurones and causes aberrant reactions to external objects or their internal representations. Remember Nash in the movie reacting to something as simple as his wife turning on the light by saying "Why did you turn on the lights? Why would you do that? Why?" ?

In this stage, the patient develops a sense of anxiety and confusion, and an intense need to make sense of the new "realities" being experienced. Any and every normal occurrence can produce an exaggerated response in his mind, and he keeps looking for meanings and explanations to calm himself down. As he forms delusions in his mind to explain the occurrences, he experiences a feeling of relief and reduced perplexity. These delusions then persist, even after the stimulus is taken away, eventually taking on a life of their own. Hallucinations arise from similar aberrant thought processes, as the patient conceives an incorrect internal image of a thought or a memory that is percieved and reinforced with such intensity as though it were real.

This is, like I said earlier, just one aspect of cause and development of psychoses but enough to give us a peek into the on-goings in the brain of a schizophrenic. Imbalances in other neurotransmitters and pathways have different ways of interfering with normal thought process and causing psychological disturbances. Given the limited knowledge and understanding of this disorder, how is it brought under control?

Anti-psychotics are useful in the treatment of psychoses, because, in one way, they dampen the effect of the excessive dopamine (in this example) and thus restore a chemical balance that calms the patient. However, they do not change the underlying thought process- all they can do is prevent neutral stimuli from producing abnormal reactions, and quenching aberrant reactions produced initially. Thus, patients are able to "ignore" or control their reactions to stimuli, but are not entirely free of the delusional thoughts that have already formed. This underscores the importance of staying on the drugs as long as is necessary, and also protecting the patient from high stress environments that can cause a resurgence of symptoms. Modern drugs are now being developed to limit side-effects in patients. Imaging technologies have improved to better visualise brain abnormalities associated with schizophrenia. With the availability of genome sequences and better tools, more genes are being discovered that may play a role in the disorder. Emerging tools in pharmacogenomics can make the best of these discoveries to improve treatment. Social acceptance and sensitivity towards the ailment is also needed , to create a support system that does not stigmatise patients.

John Nash's story is a very encouraging one in the face of this complex disorder. His story shows that one can be successful in bringing the disorder under control to a large extent. Eventually, Nash learns to ignore his irrational fears and focus on his passion. The same brain that gave rise to abnormal thought processes also contributed to his Nobel-prize-winning work on the game theory. Indeed, the mind is a beautiful thing!

References: 1) Wikipedia
2) Schizophrenia: challenging the orthodox McDonald et al
3) Schizophrenia in a molecular age. Carol A Tamminga

46 comments:

Isha said...

the reality is merely a realm of perception.. i read sumwhere.. a really simple experiment that i recall doing in a physiology lab is .. where you sit on a rotating chair blind folded (so ur visual cues are cut off) .. and once the fluid in your inner ear .. is in equilibrium with ur perception.. you will believe .. that you are perfectly stationery .. a person standing next to you in the same spot jogging .. would sound like he or she is running around you in circles.. :) .. its a strange thing the human mind.

Unknown said...

hi isha,
yeah, realm of perception. a strange thing indeed.

Prashanth said...

TGFI, try reading the book by the same title which is a biography of John Nash. I promise you, you will be surprised by a lot of things... it gives a fuller picture than the movie...

Unknown said...

prashanth,
yes, i heard that the movie distorted several facts, like the representation of visual hallucinations for one, will try to get my hands on it.

Born a Libran said...

Interesting read. All this tells me how little we know about the molecular aspects of our own selves. For example, how are dopamine levels regulated within the cell?, how is it made? (this they should hopefully know), What is it's final molecular function? (this also they should know)?, When did evolution decide to use dopamine for this purpose?, Can we learn something from the other organisms that use dopamine for the same function? Are there multiple pathways to regulate and make it?

Unknown said...

libran,
good points you bring up. cannot do justice to them all here..maybe a follow up post ;)
but yeah, the at the molecular level, a good bit is known about dopamine regulation and function. However, the problem in schizophrenia is that it arises from a multitude of causes, so dopamine is just one player in the game.
as for other systems..unfortunately, model systems have not proven to be very useful in studying psychological disorders, mainly because the manifestation is so complex in the human being..but from an evolutionary p.o.v it should be interesting.

Sakshi said...

Just keep your eye out for papers from Tonegawa lab - they have a developed a mutant mouse as a model for Schizophrenia. They should be coming up with more insights into the exact role of Dopamine in the disorder and possible cures.

Unknown said...

sakshi,
ok! thanks for the heads up. will look out.

Raindrop said...

I have disproved most known sciences, rendering this blog unnecessary. Please go to www.vogongirl.blogspot.com for posts on why science doesn't work.

Skyblue said...

This underscores the importance of staying on the drugs as long as is necessary, and also protecting the patient from high stress environments that can cause a resurgence of symptoms. Modern drugs are now being developed to limit side-effects in patients. Imaging technologies have improved to better visualize brain abnormalities associated with schizophrenia. With the availability of genome sequences and better tools, more genes are being discovered that may play a role in the disorder. Emerging tools in pharmacogenomics can make the best of these discoveries to improve treatment. Social acceptance and sensitivity towards the ailment is also needed , to create a support system that does not stigmatize patients.

What utter despicable crud! This is propaganda and ignorance destructive to the health of individuals and our entire society. You start off well understanding that the illness might be caused by both biochemical and psychosocial factors but end up regurgitating the pharmaceutical propaganda that psychological illness is a brain disease and that there is simply something wrong with the person's biology. The reason why there is a genetic inheritance is that environment has produced it. The genetic inheritance changes according to what the person's life transmits.If the person is cured through growth oriented actions their genetic transmission will change. Also, you make it sound as if finally the person's brain has become irretrievable damaged. You are totally ignorant because you live in a world without real experience and you, like the pharmaceutical-psychiatric alliance you represent do not even consider or think of how human beings can achieve health. It is not even in remotely in your world model and your world view. Your interest in biochemicals instead of human beings makes you a dysfunctional monster. In light of that, it seems people like yourself are the absurdly robotic machines while the people whose brains you study are the real human beings and the ones who have a real chance of actualizing their full emotional and psychological function.
The fact is you will get what you look for.If you wish to cure schizophrenia through psychosocial activity you can. If you wish to murder the psyches of humans or assist in the propaganda to encourage this with drugs that are in effect no better than pre-war icepick lobotomies then you can do that also.

I tell you and everyone like yourself from the inside circle of one who has been cured that it is possible to cure schizophrenia through psychosocial means.
..
What is the matter? Surprised? Did you think we do not exist? Is someone who says this supposed to be crazy.? Did you not consider how we might react to your "opinions/propaganda"? Do you feel an urge to cross yourself and look for the torches and pitchforks?
I say that because you people are missing the models of cure so you must be living in ignorance and superstition.

We exist and I exist and I know what I know from experience. I use words to try to relate known experience while you people research words to try to find the experience of psychological reality.
By cure, I mean totally construct full emotional functioning in such individuals The use of drugs as you outline is simply to murder or kill the individuals functioning. I have known the emotional death of schizophrenia. I have also known the even worse death of drugs that simply suppressed my symptoms and cut me off from all possible hope of contacting my emotional life. I was very fortunate to find psychotherapists who from their experiences in the holocaust had learned the secrets of life and death of the human psyche, and learned by absolute necessity what is necessary for growth process.
.
You can no more cure a person by means of drugs than by building a human being from spare parts and electronic tubes. Humans ARE their emotions and their consciousness. All humans can be guided to a full emotional life. They can only be accessed from their consciousness by the consciousness of another person. Biochemicals are things and they are not consciousness nor are they psychological process. Psychological process is universal in functioning for all humans. It doesn't matter if the illness is from childhood abuse of neglect In this context. drugs can be a temporary assist. Even LSD is useful as well as tranquilizers. But if there is no concurrent attempt to cure then the drugs simply are murder of the psyche for the symptoms themselves, even the psychotic symptoms are the human psyche's attempt to cure itself and should be to a large extent allowed to continue to completion.

Also let me debunk a great myth that people say when they say "There was nothing wrong in my family" , For the vast majority it means there was nothing "right " either. Evolution does not reward vapidity not vacuousness. Those families which want to be positive and never negative and always living the happy face lie are doomed to dysfunction and illness. For the large part these are attitudes of dysfunction which are mirrored and transmitted in the larger society. It is the society itself which is dysfunctional and acts with it's destructive processes upon individuals and breaks down specific individuals and their genetic makeup gets transmitted. If you want to stop the negative genetic transmission the obvious solution id to start creating through your own individual actions a society based on healthy emotional growth principles.

Trying to manipulate genes through biochemistry in such a context is absurd, you can never access the world of love and consciousness through impersonal genetics.

If you or anyone else want a vision I suggest you throw out your useless biochemical books and set the goal of actually assisting humans to change. Simply wanting to do this and working towards it will give you the answers. The sad fact is that none of you in the biochemical and biochemical propaganda world are actually trying to effect personality change in ill individuals.
Every year you waste is a year of life the person you neglect to help will lose.You have to have courage and the ability to share and get involved and the ability to love negative emotions. I would say that someone who writes such garbage as the above essay is in fact creating an anti-emotional climate a, a climate of illness waiting to happen. a You are only sane or "not ill " because you have not been exposed and lived emotionally in the negative life e. Over generations family of such persons will develop a predilection for mental illness and you will become prey to the very "genetics" you study. The simple fact is that your loveless attitude and failure to affirm life makes those genetics and the development of bad genes a certainty. .


John Nash's story is a very encouraging one in the face of this complex disorder. His story shows that one can be successful in bringing the disorder under control to a large extent.


There is nothing "encouraging" about this movie unless you are a manufacturer of pharmaceuticals. It is a sad statement of failure, ignorance and despair. If you think that a half-life is a life, then I am here to affirm you are sadly wrong for I have been there. Life is life and a half-life is death. The only success in a half-life is for the mindless soulless people and institutions of society. Bringing the person "under control" makes everything easy for the soulless, uncaring mechanisms of exploitive and abusive social institutions that tare concerned with maintaining economic power over other individuals.

The movie should be re-titled "an ugly story" which reflects the ugly minds of the storytellers and the ugly mind-face of contemporary medical establishment. Let me congratulate you on your assistance of the mass dysfunction and mental illness of modern society. and congratulate you on your assistance to help the drug establishment murder beautiful minds such as John Nash's.. The movie shows that John Nash DID have a beautiful mind. His psychosis and delusions were not problems, they were attempts to solve emotional problems. Expunging them without resolving the emotional problem is pointless. I know all about what psychosocial techniques are available such as bio energetics and emotional confrontative techniques. Absolutely none of them were tried with John Nash. The reason for that is the techniques of health and growth are abhorrent to mainstream society and an independent emotionally healthy society is not wanted by the power elite who wish a manipulable controllable population. Thirty percent mental illness rate is acceptable to them to give them a nation of serfs. The techniques of health involve confronting, accepting and loving negative emotions and being emotionally involved in helping those who are ill. IE exposing oneself to risk and confrontation

Physicians and scientists cure yourselves! If you want to cure others you will first have to understand how the human psyche works and that requires intense confrontation with yourselves. For you ignorant fools who study biochemical textbooks I gather you do not have one iota of the courage that is required for self-inspection and the facing and sharing of human emotions

..
Basically the movie show how a brilliant mind was murdered with insulin therapy and psychiatric drugs. In the end there is no success, there is only the ghost of a disintegrated person who does not have a holistic emotional self. All his extraordinary genius is laid to waste forever shattered and unable to be used because he did not achieve emotional integration. John Nash's great contribution to science was made under his so called "psychosis" At that point he still had a beautiful mind. When the attempt was made to remove his psychosis without instead of integrating it, he was destroyed.
The movie shows a person who has been murdered by an ignorant social world and an ignorant society.
And the movie celebrates this as some kind of sick triumph.
Read it for what it is: A failure and a propaganda piece for the pharmaceutical establishment propagating the lies that mental illness is the result of genetics, can never be cured but can be controlled by the almighty MAGIC DRUG which has replaced God in the human cosmology smiting down the Satan's Snakes of bad genetics.

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It is true the schizophrenia is something very serious pathology and there are different types of it and is something that you can't control and people use to go to the psychiatric but is good to have a therapy too.

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It is true. It is a good movie and I have seen three times. I think that the problem telling on the movie is so serious.

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