FW: Reelin and Rockin' - Science and Musical Art

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Reelin and Rockin' - Science and Musical Art

FEAT DAILY NEWSLETTER Sacramento, California http://www.feat.org

" Healing Autism: No Finer a Cause on the Planet "

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June 4, 2001 Search www.feat.org/search/news.asp

SCIENCE, MEDICINE AND ART

Also: * More on Reelin

* Mercury Warning in the UK

* Music as Therapy for the Body and Soul

Promising New Research On Schizophrenia Causes: Reelin

From associated editor :

This is a press release describing the work of Erminio Costa and his

colleagues at the University of Illinois, Chicago. Costa was the first to

find reelin deficits in bipolar disorder and in schizophrenia; he is also

the person who has put forward the hypothesis that reelin is intimately

involved in learning and memory.

The connection to bipolar disorder (which this release does not go

into) is especially interesting in light of strong epidemiological evidence

showing that bipolar disorder is far more common in families of children

with autism than in families of children who do not have autism.

DeLong, of Duke University, has speculated that autism is

another expression of the genes for bipolar disorder. In essence, autism is

bipolar disorder expressed at birth.

One of the most hopeful aspects of Costa's work is his 'two-hit'

theory of schizophrenia. Costa believes that the subtle structural

differences in the brain of people with reelin deficits are not enough, in

and of themselves, to produce a serious brain disorder.

Something else has to happen, too.

For me this is encouraging because it implies that, assuming reelin is

involved in autism, the problem isn't a structural difference in the brain.

The problem, at least as I read this, is likely to be something

" neurochemical, " and thus more susceptible to treatment.

That's good!

http://www.uic.edu/depts/paff/opa/releases/2000/schizo_release.html

Research by a prominent neuroscientist at UIC is providing new clues

to the molecular origins of schizophrenia, a devastating mental illness that

afflicts nearly 2.5 million Americans.

Erminio Costa, a member of the National Academy of Sciences and

scientific director of UIC's Psychiatric Institute, is studying a chemical

found in the brain called reelin. Reelin plays a role in correctly

positioning and aligning neurons in the developing brain. It is also present

in certain areas of the adult brain, including the cerebral cortex, the

region responsible for higher mental functions like language and problem

solving.

In a postmortem study of the brains of schizophrenics, obtained from

brain banks, Costa and his colleagues found that the level of reelin was

half that in normal human brains.

To confirm that finding, the UIC scientists conducted a blind study of

60 brains taken postmortem from individuals diagnosed with schizophrenia,

unipolar depression or bipolar disorder with psychosis, and individuals with

no psychiatric abnormalities. They correctly identified those that came from

psychotic patients by testing for levels of reelin. Controls in the

experiment ruled out the possibility that the decrease in reelin was due to

drugs the individuals had taken to treat their psychoses or to other

possible effects.

Costa is now investigating the mechanism by which reelin acts, in

collaboration with UIC neuroscientists Caruncho, Dennis Grayson,

Alessandro Guidotti, Pappas, Pesold, Neil Smalheiser and

Doncho Uzunov. In a paper to be published in the Proceedings of the National

Academy of Science, Costa and his colleagues report finding reelin

associated with the dendritic spines of neurons in the cortex. These

dendritic spines - branching fingerlike extensions of the neurons that

receive inputs from a complex of other neurons - are thought to be involved

in learning. The UIC scientists suggest that reelin may act by interfering

with biochemical mechanisms important for memory and learning. In the

schizophrenic brain, the density of dendritic spines in the cortex is far

lower than in the normal brain. Costa speculates that the decreased levels

of reelin may be indirectly related to this phenomenon.

Costa has also advanced a " two hit " model of schizophrenia. First, a

defect in the gene for reelin causes the misplacement of cortical neurons.

This misplacement alone is not sufficient to precipitate mental illness,

according to Costa. Rather, it creates a " genetic vulnerability, " or a

predisposition for psychosis. This first hit is then followed by a second

hit later in puberty or in early adulthood when the final pruning of

neuronal connections occurs. While this pruning is a normal part of brain

maturation, Costa speculates that in schizophrenics it somehow unveils the

defects laid down during fetal development. Schizophrenia typically becomes

evident when individuals are in their late teens or early twenties.

" If future scientific studies confirm that a defect in the expression

of the reelin gene causes a predisposition for psychosis, there are

important implications for treatment, " Costa said. " We may one day be able

to alter the gene's mechanisms that regulate the production of reelin.

Moreover, early identification of the genetic defect through laboratory

analysis, which is currently under study at UIC by Dr. Smalheiser, might

help us take remedial steps before psychotic symptoms arise.”

* * *

More on Reelin

Journal Watch Psychiatry Summary and Comment: The Pathophysiology of

Psychosis May Be Nonspecific

[The earlier material we have posted on Reelin, a potentially

break-through discovery for autism, was from a lay medical report. This

comes from a medical journal with all the scientific nitty-gritty and

technological skinny. This article appears thanks to associated editor

.]

http://www.jwatch.org/psy/

Years after Kraepelin differentiated between dementia praecox and

manic-depressive insanity, he could no longer tell them apart with

certainty. In postmortem brain studies of 15 patients with schizophrenia, 15

with bipolar disorder (11psychotic), 15 with nonpsychotic unipolar

depression, and 15 controls, researchers measured messenger RNA and proteins

associated with reelin, glutamic acid decarboxylase67 (GAD67), GAD65, and

disabled-1 gene product(DAB-1).

The glycoprotein reelin acts via intracellular DAB-1 to promote

synaptic spine maturation and plasticity associated with learning. GAD67

regulates the activity of GABAergic neurons, which downregulate reelin

expression in cortical areas implicated in schizophrenia.

Compared with controls, patients with schizophrenia or psychotic

bipolar disorder, but not nonpsychotic bipolar disorder or unipolar

depression, had 50 percent reductions of reelin messenger RNA and GAD67

protein in the prefrontal cortex. Cell loss did not cause these reductions

because other neuronal markers such as GAD65 andDAB-1 messenger RNA and

protein were not altered in the psychotic patients.

The degree of reduction did not correlate with lifetime dose of

antipsychotic drugs; psychotic patients who had never received antipsychotic

medications had the same changes.

Comment: Because reelin is involved in learning and early development

of neuronal architecture, loss of reelin could lead to abnormal synaptic

structure and function in the prefrontal cortex and other areas found to be

abnormal in schizophrenia. Reelin loss also could account for indicators of

abnormal information processing, such as the sensory-gating deficit found in

patients with schizophrenia and bipolar disorder. The findings of this study

suggest that the interactions among risk factors for psychosis, defective

social interaction, and mood regulation, all of which may have entirely

different etiologies, determine whether someone will develop schizophrenia,

psychotic mood disorder, or another psychotic illness.-- S Dubovsky

Publishedin Journal Watch Psychiatry 9 January 2001 Decrease in reelin and

glutamic acid decarboxylase67 (GAD67) expression in schizophreniaand bipolar

disorder: A postmortem brain study. Guidotti A et al., Arch Gen Psychiatry

2000 Nov; 57:1061-1069.

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* * *

Patients Get Mercury Vaccine Warning

http://www.sunday-times.co.uk/news/pages/sti/2001/06/03/stinwenws01030.html

The UK government's medicines safety watchdog has taken action to warn

patients and GPs of potential serious adverse reactions to vaccines

containing a preservative which is almost 50% mercury. Manufacturers have

been told to add a warning to the summary of product characteristics for all

vaccines with Thimerosal. A warning will also be added to the patient

information leaflet.

* * *

Music As Therapy For Body And Soul

[The material presented in the following article contains elements of

musical art, medicine and philosophy and may not be appropriate subject

matter for the hollywood-weaned pedestrian reader. It may induce drowsiness

and orificial bilabial fricatives; in which case it is advised that you do

not read before driving or operating heavy equipment. By Thanasis Dritsas in

the International Herald Tribune in Greece and Cyprus.]

http://www.ekathimerini.com/news/content.asp?aid=85368

In the ancient traditions of all peoples, music has been held as

sacred and of therapeutic value. In ancient Greece, it was a basic component

in the education of young people - although the Platonic concept of the word

included all arts, not only that of sounds.

These days, for most people the purpose of music is entertainment -

for which the modern Greek word originates in the ancient Greek word meaning

" to divert concentration. " The person who is being entertained tries not to

concentrate, but to be diverted, to forget.

The concept of entertainment is completely different from that of

recreation (again the Greek word " psychagogia " means the " development of the

soul " ), which is closer to the ancient meaning and value of music.

The expression " this music touches my heart " is often heard, yet one

never hears the phrase " this music touches my mind. " In fact, the battle

between the brain and the heart as the main center of perception is a very

old one.

The heart-centered theory originates in the Aristotelian view that

considers the heart to be the seat of emotion, passions and the intellect,

in line with the views of the ancient Jews and of Homer.

Plato, however, and the medical academy of Hippocrates clearly opted

for the brain-centered view, which holds that the seat of emotion and

intellect is in the brain.

The development of neuroscience showed by observation and experiment

that the seat of perception is indeed in the brain. However, the

Aristotelian view, which prevailed in medieval philosophy, managed to

survive until the 18th century and still lingers in collective folk memory.

In the " Merchant of Venice, " Shakespeare poses the question: " Tell me

where is fancy bred, in the heart or in the head?”

Over the past decade, scientific research into music and the brain has

somewhat restored the approach to music as something sacred and therapeutic,

by showing the effects of music on the functioning of the human body.

Selected pieces of music can relax the body by reducing stress -

lowering the rate of respiration and heartbeat as well as arterial pressure

in heart patients in intensive care units.

It has also been shown that the reduction in the heartbeat rate and

arterial pressure is related to the reduction in hormones such as

adrenaline, noradrenaline, cortisone and corticotropine (ACTH) which

circulate in the blood, causing stress if their levels increase suddenly.

Music achieves the same goals as those effected by pharmaceutical

drugs but in a painless and harmless manner.

It appears that music - chiefly by means of the rhythm - acts by

influencing instinctive functions related to the relevant parts of the human

brain. Neuroanatomical observations by Shell and Stratton showed that

cochlear nuclei, an important sector of the route taken by the acoustic

nerve to the brain stem, border on crucial nuclei that function

independently and comprise the centers that regulate breathing and blood

circulation (dorsal motor nucleus, vagal nucleus, nucleus ambiguous).

It is likely that nearby nerves are stimulated to increase the rate of

respiration and heartbeat when we hear a fast tempo and vice versa with a

slow beat.

This initial effect of music - mainly through the rhythm - is

unconscious and occurs in all people, irrespective of ethnic or cultural

background.

On a second level, comprehension of the succession of tones and the

architecture of the music demands the participation of extremely specialized

higher functions of the cortex where functioning is conscious (where the

kind of training we have had is more of an influence).

For example, we say " feel the beat " but not " feel the melody. "

Different cultures have different " recordings " at the level of the brain's

cortex, and so the perception of melody varies from person to person.

Important research carried out recently at Piedmont Hospital in

Atlanta, Georgia, USA showed that newborn (particularly premature) infants

exposed to " womb sounds " and their own mother's voice singing a lullaby,

gain weight faster than those not exposed to these sounds.

American researchers have shown that listening to Mozart's piano

sonata K448 can improve college students' ability to solve complicated

mathematical problems. The same sonata has been used as a way of preventing

epileptic fits.

A study at McGill University in Canada (Cognitive Neuroscience

Department, led by Dr. Zattore) showed that linguistic and musical stimuli

travel along different neural pathways in the brain. After a cerebral

hemorrhage, many patients who can no longer speak retain the ability to hear

music and to sing.

The Russian composer Shebalin (1901-1963) lost the power of speech

after a massive stroke but could still evaluate his students' works and

compose his own music.

Another stroke victim, the French composer and organist Langlais

(1907-1991), lost the ability to speak, write and recognize words, but could

still read musical scores, compose and improvise music. Various researchers

have shown that exposure to music and systematic music education before the

age of seven years can stimulate the human brain to develop more and

different neural pathways separate to those associated exclusively with

speech. Theoretically, this could provide a form of security for someone who

will suffer a stroke in the future.

The brain could manage to communicate via " musical neural pathways " if

others associated with speech were destroyed.

All this modern research into the mind-music relationship has made use

of magnetic resonance imaging (MRI) and in positron emission tomography (PET

scans).

Music therapy has a number of applications as a complementary form of

therapy, either in the form of receptive music therapy or active music

therapy, that requires the presence of a trained music therapist who

combines advanced musical training with specialized training in psychology.

Active music therapy is used with autistic children and is

particularly prescriptive for all kinds of pain, in psychosomatic stress,

and in strengthening the human immune system.

Music helps maintain psychosomatic health and the regular functioning

of the brain, just as physical exercise and a healthy diet reduce the

likelihood of cardiovascular disease.

This is a most important message in an age when universities are

cutting funds for human sciences and arts. On the contrary, more and more

money is wasted on entertainment and show biz, a world that promotes

oblivion and escape from reality.

Education in classical and traditional music is taking second place to

technocratic subjects such as economics and computer science. The ancient

idea that demanded that music be a core part of education (as in the

quadrivium of the Roman education system: arithmetic, geometry, astromony

and music) is making a comeback in the 21st century, based on the findings

of cognitive neuroscience.

Given the results of modern research, Plato is revealed as a prophet.

In his " Timaeus, " perhaps his most scientific work, he sets out precisely

and in detail the essence and meaning of music - that the gods gave us

musical harmony to impose order in the disturbed movements of our soul and

to bring them closer to their god-like prototype.

Dr. Dritsas is a cardiologist at the Onassis Cardiology Center, Fellow

of the European Society of Cardiology, composer and researcher into the

biological effects of music and its clinical applications in medicine (Music

in Medicine). He is a member of the American Music Therapy Association, the

British Society of Music Therapy, and the International Society of Music in

Medicine.

* * *

Reader’s Posts

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upcoming story. To learn about or order either CD, visit:

www.savagerecords.com

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