Re: Stanley Brain-bank and proteins

[Guest guest]

Here's another article from the s-Hopkins website. It's interesting

because the science going on with this article (looking at proteins in the

brain) is groundbreaking... and the Dr. doing it is Yolken... here's

his bio...

" Dr. Yolken is a virologist who became interested in the study of serious

psychiatric disease at the suggestion of Dr. E. Fuller Torrey, now of the

Stanley Medical Research Institute. Dr. Yolken developed many of the

diagnostic assays for viral infections which are in current use. He has

applied these methods for the detection of infectious agents which might be

involved in schizophrenia, bipolar disorder, autism and related disorder

(see Department/Programs section of this website). He is author or coauthor

of more than 250 scientific papers and several recent books, including the

Manual of Clinical Microbiology and Beasts of the Earth. "

Anyway, it made me wonder what is going on in this area that might relate to

our kids, and what a protein profile of their brains might look like (and

how they might fall into subgroups)... we know they have " autistic " brains

there that the research could be done on because Dr. Pardo used them in his

study.

Caroline

Riches of the Brain Bank

Seeking clues to mental illness, gene hunters discover proteins

By

R. Winstead

Safely stored in 52 freezers in a federal building outside Washington, DC,

are the Brain Bank's holdings: brain tissue from hundreds of individuals

with schizophrenia, bipolar disorder, and severe depression. Scientists in a

dozen countries have analyzed tissue from this collection, but the genes

involved in these diseases remain at large. Now, a leading gene hunter says

that proteins‹and what they reveal about the diseased brain‹may be the

bank's greatest asset.

In the last five years, the Brain Bank has provided some 70 laboratories

worldwide with postmortem brain tissue at no cost to researchers. The

roughly 350 specimens currently in the bank were collected by medical

examiners and always with the permission of the family. The Brain Bank is

part of the Stanley Foundation, which will spend $21 million this year for

research on schizophrenia and bipolar disorder, also known as manic

depression.

Safely stored in 52 freezers in a federal building outside Washington, DC,

are the Brain Bank's holdings: brain tissue from hundreds of individuals

with schizophrenia, bipolar disorder, and severe depression. Scientists in a

dozen countries have analyzed tissue from this collection, but the genes

involved in these diseases remain at large. Now, a leading gene hunter says

that proteins‹and what they reveal about the diseased brain‹may be the

bank's greatest asset.

In the last five years, the Brain Bank has provided some 70 laboratories

worldwide with postmortem brain tissue at no cost to researchers. The

roughly 350 specimens currently in the bank were collected by medical

examiners and always with the permission of the family. The Brain Bank is

part of the Stanley Foundation, which will spend $21 million this year for

research on schizophrenia and bipolar disorder, also known as manic

depression.

Advances in protein technology and the frustrations of the gene search

recently persuaded Yolken to investigate proteins as disease markers.

Lacking expertise in the latest tools, his laboratory teamed up with

researchers at Large Scale Biology, a land corporation that specializes

in isolating and identifying proteins‹what is now called proteomics.

The collaborators compared the levels of hundreds of proteins in the

postmortem tissue of 89 Brain Bank specimens. The analysis revealed that

eight proteins in the brains of affected individuals had significantly

higher or lower levels than those in the control group. The sample included

24 schizophrenics, 23 individuals with bipolar disorder, 19 with major

depression, and 23 who were unaffected by these diseases.

More interesting than the specific findings, says Yolken, is the fact that

protein differences in postmortem tissue were detected. Although some

colleagues had predicted success, Yolken was surprised by the quality of the

results.

" We've done both genomics and proteomics with postmortem tissue in these

diseases, " says Yolken, " and the more useful information has come from

proteomics. "

In fact, the two approaches are complementary, because each offers a glimpse

of brain cells at a different point in time. With genomics, a gene's

activity in the cell is estimated using 'messenger RNA,' the chemical that

signals the cell to produce a protein when a gene is expressed. But Yolken

points out that the half-life of this chemical is relatively short. " Protein

lasts longer in the cell than messenger RNA, so proteomics allows us to go

farther back in time, " he says.

A related advantage of proteomics is the potential for detecting changes

that occur after the messenger-RNA step. " The concept, " explains Yolken, " is

that a cell makes protein and then something happens to the protein related

to disease. In theory, proteomics will be able to pick up these changes. "

These changes are likely to be critical in the anatomy of brain disease and

could be a diagnostic tool if they show up in spinal fluid.

The main disadvantage of proteomics is that getting results takes time.

Although the basic techniques are not new, protein analysis is laborious and

requires separating proteins and determining their molecular weight and

electric charge. Researchers in this study used a method called 2-D gel

electrophoresis that employs gels and electric fields to isolate and sort

proteins by weight and charge. Their results appear in the latest issue of

Molecular Psychiatry.

Despite drawbacks, proteomics may be the right approach for schizophrenia,

says E. Fuller Torrey, executive director of the Stanley Foundation Research

Programs. The field is known for a long string of failures to replicate

findings. " About half the human chromosomes have been linked to

schizophrenia, " says Torrey, who collaborated on the study. " But the pattern

has been that three months after a gene is proposed a contradictory study

appears. "

The study's most interesting finding involved a protein called GFAP (glial

fibrillary acidic protein), which is thought to play a role in the brain's

ability to adjust to certain insults. The researchers detected abnormal GFAP

in the diseased brains, a discovery consistent with Yolken's hypothesis that

viruses can trigger mental illness. The Stanley Neurovirology Laboratory at

s Hopkins is the world's only laboratory focused on infectious agents as

the cause of schizophrenia and bipolar disorder.

The reason that proteomics may be more useful in discovering disease-related

markers than genomics is that any set of brains will have greater variation

in its messenger RNA than proteins, according to Yolken. The key to finding

markers is spotting deviations from the norm, and abnormalities are more

likely to stand out when the normal range is relatively small, as with

proteins.

All research on Brain Bank specimens is performed with the researcher blind

to the diagnosis. More than 20 variables are known about each brain,

including the donor's diagnosis, medical history, and how the individual

died, but brains are sent to researchers coded. Once a study is complete,

the researchers and the Stanley Foundation exchange information: The

researchers get the key to the code and the Foundation gets the results,

which are entered into a database.

The practice of using coded brains has fostered a kind of

cross-fertilization, with schizophrenia researchers generating information

that has helped researchers in other fields and vice versa. " The Brain Bank

is a grandiose undertaking, but it has been very successful, " says Torrey.

[Guest guest]

Caroline,

I chatted with both Drs noted below at the Stanley Institute

about 2 yrs ago. They had just recd a rather large sum of money

for research into viral infections and bi polar.

'Hey, can't you expand that a bit into autism?'

No was their respond and they were quite brief - didn't want

to discuss a viral - 'autism' connection.

Perhaps one day they will change their mind

Doris

land

>

> Here's another article from the s-Hopkins website. It's interesting

> because the science going on with this article (looking at proteins

in the

> brain) is groundbreaking... and the Dr. doing it is Yolken...

here's

> his bio...

>

> " Dr. Yolken is a virologist who became interested in the study of

serious

> psychiatric disease at the suggestion of Dr. E. Fuller Torrey, now

of the

> Stanley Medical Research Institute. Dr. Yolken developed many of the

> diagnostic assays for viral infections which are in current use. He has

> applied these methods for the detection of infectious agents which

might be

> involved in schizophrenia, bipolar disorder, autism and related disorder

> (see Department/Programs section of this website). He is author or

coauthor

> of more than 250 scientific papers and several recent books,

including the

> Manual of Clinical Microbiology and Beasts of the Earth. "

>

> Anyway, it made me wonder what is going on in this area that might

relate to

> our kids, and what a protein profile of their brains might look like

(and

> how they might fall into subgroups)... we know they have " autistic "

brains

> there that the research could be done on because Dr. Pardo used them

in his

> study.

>

> Caroline

>

>

>

>

> Riches of the Brain Bank

> Seeking clues to mental illness, gene hunters discover proteins

>

> By

> R. Winstead

>

> Safely stored in 52 freezers in a federal building outside

Washington, DC,

> are the Brain Bank's holdings: brain tissue from hundreds of individuals

> with schizophrenia, bipolar disorder, and severe depression.

Scientists in a

> dozen countries have analyzed tissue from this collection, but the genes

> involved in these diseases remain at large. Now, a leading gene

hunter says

> that proteins‹and what they reveal about the diseased brain‹may be the

> bank's greatest asset.

>

> In the last five years, the Brain Bank has provided some 70 laboratories

> worldwide with postmortem brain tissue at no cost to researchers. The

> roughly 350 specimens currently in the bank were collected by medical

> examiners and always with the permission of the family. The Brain

Bank is

> part of the Stanley Foundation, which will spend $21 million this

year for

> research on schizophrenia and bipolar disorder, also known as manic

> depression.

>

> Safely stored in 52 freezers in a federal building outside

Washington, DC,

> are the Brain Bank's holdings: brain tissue from hundreds of individuals

> with schizophrenia, bipolar disorder, and severe depression.

Scientists in a

> dozen countries have analyzed tissue from this collection, but the genes

> involved in these diseases remain at large. Now, a leading gene

hunter says

> that proteins‹and what they reveal about the diseased brain‹may be the

> bank's greatest asset.

>

> In the last five years, the Brain Bank has provided some 70 laboratories

> worldwide with postmortem brain tissue at no cost to researchers. The

> roughly 350 specimens currently in the bank were collected by medical

> examiners and always with the permission of the family. The Brain

Bank is

> part of the Stanley Foundation, which will spend $21 million this

year for

> research on schizophrenia and bipolar disorder, also known as manic

> depression.

>

> Advances in protein technology and the frustrations of the gene search

> recently persuaded Yolken to investigate proteins as disease markers.

> Lacking expertise in the latest tools, his laboratory teamed up with

> researchers at Large Scale Biology, a land corporation that

specializes

> in isolating and identifying proteins‹what is now called proteomics.

>

> The collaborators compared the levels of hundreds of proteins in the

> postmortem tissue of 89 Brain Bank specimens. The analysis revealed that

> eight proteins in the brains of affected individuals had significantly

> higher or lower levels than those in the control group. The sample

included

> 24 schizophrenics, 23 individuals with bipolar disorder, 19 with major

> depression, and 23 who were unaffected by these diseases.

>

> More interesting than the specific findings, says Yolken, is the

fact that

> protein differences in postmortem tissue were detected. Although some

> colleagues had predicted success, Yolken was surprised by the

quality of the

> results.

>

> " We've done both genomics and proteomics with postmortem tissue in these

> diseases, " says Yolken, " and the more useful information has come from

> proteomics. "

>

> In fact, the two approaches are complementary, because each offers a

glimpse

> of brain cells at a different point in time. With genomics, a gene's

> activity in the cell is estimated using 'messenger RNA,' the

chemical that

> signals the cell to produce a protein when a gene is expressed. But

Yolken

> points out that the half-life of this chemical is relatively short.

" Protein

> lasts longer in the cell than messenger RNA, so proteomics allows us

to go

> farther back in time, " he says.

>

> A related advantage of proteomics is the potential for detecting changes

> that occur after the messenger-RNA step. " The concept, " explains

Yolken, " is

> that a cell makes protein and then something happens to the protein

related

> to disease. In theory, proteomics will be able to pick up these

changes. "

> These changes are likely to be critical in the anatomy of brain

disease and

> could be a diagnostic tool if they show up in spinal fluid.

>

> The main disadvantage of proteomics is that getting results takes time.

> Although the basic techniques are not new, protein analysis is

laborious and

> requires separating proteins and determining their molecular weight and

> electric charge. Researchers in this study used a method called 2-D gel

> electrophoresis that employs gels and electric fields to isolate and

sort

> proteins by weight and charge. Their results appear in the latest

issue of

> Molecular Psychiatry.

>

> Despite drawbacks, proteomics may be the right approach for

schizophrenia,

> says E. Fuller Torrey, executive director of the Stanley Foundation

Research

> Programs. The field is known for a long string of failures to replicate

> findings. " About half the human chromosomes have been linked to

> schizophrenia, " says Torrey, who collaborated on the study. " But the

pattern

> has been that three months after a gene is proposed a contradictory

study

> appears. "

>

> The study's most interesting finding involved a protein called GFAP

(glial

> fibrillary acidic protein), which is thought to play a role in the

brain's

> ability to adjust to certain insults. The researchers detected

abnormal GFAP

> in the diseased brains, a discovery consistent with Yolken's

hypothesis that

> viruses can trigger mental illness. The Stanley Neurovirology

Laboratory at

> s Hopkins is the world's only laboratory focused on infectious

agents as

> the cause of schizophrenia and bipolar disorder.

>

> The reason that proteomics may be more useful in discovering

disease-related

> markers than genomics is that any set of brains will have greater

variation

> in its messenger RNA than proteins, according to Yolken. The key to

finding

> markers is spotting deviations from the norm, and abnormalities are more

> likely to stand out when the normal range is relatively small, as with

> proteins.

>

> All research on Brain Bank specimens is performed with the

researcher blind

> to the diagnosis. More than 20 variables are known about each brain,

> including the donor's diagnosis, medical history, and how the individual

> died, but brains are sent to researchers coded. Once a study is

complete,

> the researchers and the Stanley Foundation exchange information: The

> researchers get the key to the code and the Foundation gets the results,

> which are entered into a database.

>

> The practice of using coded brains has fostered a kind of

> cross-fertilization, with schizophrenia researchers generating

information

> that has helped researchers in other fields and vice versa. " The

Brain Bank

> is a grandiose undertaking, but it has been very successful, " says

Torrey.

>