Gene Influences Antidepressant Response

[Guest guest]

They don't even know how antidepressants work - by their own admission on all

the patient warnings they " think " or " believe " SSRI's blah, blah, blah. And now

they are claiming to know which genes make which person respond which way?

Bullsh*t!

Terry

http://www.nih.gov/news/pr/mar2006/nimh-15.htm

Gene Influences Antidepressant Response

Whether depressed patients will respond to an antidepressant depends, in part,

on which version of a gene they inherit, a study led by scientists at the

National Institutes of Health (NIH) has discovered. Having two copies of one

version of a gene that codes for a component of the brain’s mood-regulating

system increased the odds of a favorable response to an antidepressant by up to

18 percent, compared to having two copies of the other, more common version.

Since the less common version was over 6 times more prevalent in white than in

black patients — and fewer blacks responded — the researchers suggest that the

gene may help to explain racial differences in the outcome of antidepressant

treatment. The findings also add to evidence that the component, a receptor for

the chemical messenger serotonin, plays a pivotal role in the mechanism of

antidepressant action.

The study, authored by National Institute of Mental Health (NIMH) researchers

Francis J. McMahon, M.D., Silvia Buervenich, Ph.D., and Husseini Manji, M.D.,

along with collaborators at several other institutions, was posted online March

8 and will appear in the May, 2006 American Journal of Human Genetics.

“This discovery brings us closer to the day when clinicians will be able to

offer treatment options and medications that are tailored and personalized to be

optimally effective for individual patients,” said NIH Director Elias A.

Zerhouni, M.D.

However, the findings cannot yet guide treatment decisions.

“To our knowledge, this is the first demonstration of significant, replicated

association between genetic variation and outcome of antidepressant treatment,”

added Manji, director of the NIMH’s Mood and Anxiety Disorders Program.

In the initial phase of the NIMH-funded STAR*D (Sequenced Treatment

Alternatives for Depression) trial, about 47 percent of the 2,876 participants

experienced some improvement with the serotonin selective reuptake inhibitor

(SSRI) citalopram (Celexa). The NIH scientists set out to find genetic factors

that might help to explain why some patients fared better than others.

They screened genetic material from 1,953 of the STAR*D patients, a sample

with a higher percentage of responders (69 percent), in part because patients

who were doing well tended to stay in contact longer and were more likely to

allow a blood sample to be drawn. The researchers looked for associations

between treatment response and 768 known sites of variability in 68 suspect

genes — sites where letters in the genetic code vary across individuals.

They found the strongest connection in the gene that codes for the serotonin

2A receptor, one of several proteins to which serotonin binds when brain cells

communicate.

Located on cells in the brain’s thinking center (cortex), the serotonin 2A

receptor regulates circuits implicated in depression. Antidepressants, including

citalopram, reduce the number of serotonin 2A receptors in animal cortex over

the course of a few weeks — the same time-frame required for the drugs to work

in humans — suggesting that the receptors are important in the drugs’ mechanism

of action.

Everyone inherits two copies of the serotonin 2A receptor gene, one from each

parent. A tiny glitch in the gene’s chemical sequence results in some people

having an adenine (A) at the same point that other people have a guanine (G). So

an individual can have gene types AA, AG or GG. Overall, the prevalence of the A

version was 38 percent, compared to 62 percent for the G version in this sample.

Fourteen percent had AA gene type, 43 percent AG and 43 percent GG. Since the

site of variation is located in a stretch of genetic material with no known

function, the researchers suspect that it may be just a marker for a

still-undiscovered functional variation nearby in the gene.

Based on scores on a depression rating scale, close to 80 percent of patients

who had AA responded to the antidepressant, compared to about 62 percent of

those with GG. Thus, patients with the AA gene type were 16-18 percent more

likely to benefit from the medication. Even patients with AG showed some

increased benefit.

But this only applied to white patients, in whom the A version was more than

six times more frequent than in black patients. There was no significant

association between gene type and treatment outcome in black patients, who

tended to fare less well in the trial overall.

“We now have to consider genetic factors as well as psychosocial issues in our

attempts to explain why antidepressants do not help our black patients as much

as they should,” McMahon said. “The new findings help make a compelling case for

a key role of the serotonin 2A receptor in the mechanism of antidepressant

action.”

Also participating in the study were: A. Rush and Madhukar Trivedi,

University of Texas Southwestern Medical Center; Gonzalo Laje, NIMH; Dennis

Charney, Mount Sinai Hospital; Lipsky, National Institute on Alcohol

Abuse and Alcoholism (NIAAA); , a Sorant, and

Papanicolaou, National Human Genome Research Institute (NHGRI); Maurizio Fava,

Massachusetts General Hospital; and Wisniewski, University of

Pittsburgh.

NIMH, NIAAA and NHGRI are part of the National Institutes of Health (NIH), the

Federal Government's primary agency for biomedical and behavioral research. NIH

and CDC are components of the U.S. Department of Health and Human Services.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency

— includes 27 Institutes and Centers and is a component of the U.S. Department

of Health and Human Services. It is the primary federal agency for conducting

and supporting basic, clinical and translational medical research, and it

investigates the causes, treatments, and cures for both common and rare

diseases. For more information about NIH and its programs, visit

http://www.nih.gov.

---------------------------------

---------------------------------

Bring photos to life! New PhotoMail makes sharing a breeze.

[Guest guest]

They don't even know how antidepressants work - by their own admission on all

the patient warnings they " think " or " believe " SSRI's blah, blah, blah. And now

they are claiming to know which genes make which person respond which way?

Bullsh*t!

Terry

http://www.nih.gov/news/pr/mar2006/nimh-15.htm

Gene Influences Antidepressant Response

Whether depressed patients will respond to an antidepressant depends, in part,

on which version of a gene they inherit, a study led by scientists at the

National Institutes of Health (NIH) has discovered. Having two copies of one

version of a gene that codes for a component of the brain’s mood-regulating

system increased the odds of a favorable response to an antidepressant by up to

18 percent, compared to having two copies of the other, more common version.

Since the less common version was over 6 times more prevalent in white than in

black patients — and fewer blacks responded — the researchers suggest that the

gene may help to explain racial differences in the outcome of antidepressant

treatment. The findings also add to evidence that the component, a receptor for

the chemical messenger serotonin, plays a pivotal role in the mechanism of

antidepressant action.

The study, authored by National Institute of Mental Health (NIMH) researchers

Francis J. McMahon, M.D., Silvia Buervenich, Ph.D., and Husseini Manji, M.D.,

along with collaborators at several other institutions, was posted online March

8 and will appear in the May, 2006 American Journal of Human Genetics.

“This discovery brings us closer to the day when clinicians will be able to

offer treatment options and medications that are tailored and personalized to be

optimally effective for individual patients,” said NIH Director Elias A.

Zerhouni, M.D.

However, the findings cannot yet guide treatment decisions.

“To our knowledge, this is the first demonstration of significant, replicated

association between genetic variation and outcome of antidepressant treatment,”

added Manji, director of the NIMH’s Mood and Anxiety Disorders Program.

In the initial phase of the NIMH-funded STAR*D (Sequenced Treatment

Alternatives for Depression) trial, about 47 percent of the 2,876 participants

experienced some improvement with the serotonin selective reuptake inhibitor

(SSRI) citalopram (Celexa). The NIH scientists set out to find genetic factors

that might help to explain why some patients fared better than others.

They screened genetic material from 1,953 of the STAR*D patients, a sample

with a higher percentage of responders (69 percent), in part because patients

who were doing well tended to stay in contact longer and were more likely to

allow a blood sample to be drawn. The researchers looked for associations

between treatment response and 768 known sites of variability in 68 suspect

genes — sites where letters in the genetic code vary across individuals.

They found the strongest connection in the gene that codes for the serotonin

2A receptor, one of several proteins to which serotonin binds when brain cells

communicate.

Located on cells in the brain’s thinking center (cortex), the serotonin 2A

receptor regulates circuits implicated in depression. Antidepressants, including

citalopram, reduce the number of serotonin 2A receptors in animal cortex over

the course of a few weeks — the same time-frame required for the drugs to work

in humans — suggesting that the receptors are important in the drugs’ mechanism

of action.

Everyone inherits two copies of the serotonin 2A receptor gene, one from each

parent. A tiny glitch in the gene’s chemical sequence results in some people

having an adenine (A) at the same point that other people have a guanine (G). So

an individual can have gene types AA, AG or GG. Overall, the prevalence of the A

version was 38 percent, compared to 62 percent for the G version in this sample.

Fourteen percent had AA gene type, 43 percent AG and 43 percent GG. Since the

site of variation is located in a stretch of genetic material with no known

function, the researchers suspect that it may be just a marker for a

still-undiscovered functional variation nearby in the gene.

Based on scores on a depression rating scale, close to 80 percent of patients

who had AA responded to the antidepressant, compared to about 62 percent of

those with GG. Thus, patients with the AA gene type were 16-18 percent more

likely to benefit from the medication. Even patients with AG showed some

increased benefit.

But this only applied to white patients, in whom the A version was more than

six times more frequent than in black patients. There was no significant

association between gene type and treatment outcome in black patients, who

tended to fare less well in the trial overall.

“We now have to consider genetic factors as well as psychosocial issues in our

attempts to explain why antidepressants do not help our black patients as much

as they should,” McMahon said. “The new findings help make a compelling case for

a key role of the serotonin 2A receptor in the mechanism of antidepressant

action.”

Also participating in the study were: A. Rush and Madhukar Trivedi,

University of Texas Southwestern Medical Center; Gonzalo Laje, NIMH; Dennis

Charney, Mount Sinai Hospital; Lipsky, National Institute on Alcohol

Abuse and Alcoholism (NIAAA); , a Sorant, and

Papanicolaou, National Human Genome Research Institute (NHGRI); Maurizio Fava,

Massachusetts General Hospital; and Wisniewski, University of

Pittsburgh.

NIMH, NIAAA and NHGRI are part of the National Institutes of Health (NIH), the

Federal Government's primary agency for biomedical and behavioral research. NIH

and CDC are components of the U.S. Department of Health and Human Services.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency

— includes 27 Institutes and Centers and is a component of the U.S. Department

of Health and Human Services. It is the primary federal agency for conducting

and supporting basic, clinical and translational medical research, and it

investigates the causes, treatments, and cures for both common and rare

diseases. For more information about NIH and its programs, visit

http://www.nih.gov.

---------------------------------

---------------------------------

Bring photos to life! New PhotoMail makes sharing a breeze.

[Guest guest]

They don't even know how antidepressants work - by their own admission on all

the patient warnings they " think " or " believe " SSRI's blah, blah, blah. And now

they are claiming to know which genes make which person respond which way?

Bullsh*t!

Terry

http://www.nih.gov/news/pr/mar2006/nimh-15.htm

Gene Influences Antidepressant Response

Whether depressed patients will respond to an antidepressant depends, in part,

on which version of a gene they inherit, a study led by scientists at the

National Institutes of Health (NIH) has discovered. Having two copies of one

version of a gene that codes for a component of the brain’s mood-regulating

system increased the odds of a favorable response to an antidepressant by up to

18 percent, compared to having two copies of the other, more common version.

Since the less common version was over 6 times more prevalent in white than in

black patients — and fewer blacks responded — the researchers suggest that the

gene may help to explain racial differences in the outcome of antidepressant

treatment. The findings also add to evidence that the component, a receptor for

the chemical messenger serotonin, plays a pivotal role in the mechanism of

antidepressant action.

The study, authored by National Institute of Mental Health (NIMH) researchers

Francis J. McMahon, M.D., Silvia Buervenich, Ph.D., and Husseini Manji, M.D.,

along with collaborators at several other institutions, was posted online March

8 and will appear in the May, 2006 American Journal of Human Genetics.

“This discovery brings us closer to the day when clinicians will be able to

offer treatment options and medications that are tailored and personalized to be

optimally effective for individual patients,” said NIH Director Elias A.

Zerhouni, M.D.

However, the findings cannot yet guide treatment decisions.

“To our knowledge, this is the first demonstration of significant, replicated

association between genetic variation and outcome of antidepressant treatment,”

added Manji, director of the NIMH’s Mood and Anxiety Disorders Program.

In the initial phase of the NIMH-funded STAR*D (Sequenced Treatment

Alternatives for Depression) trial, about 47 percent of the 2,876 participants

experienced some improvement with the serotonin selective reuptake inhibitor

(SSRI) citalopram (Celexa). The NIH scientists set out to find genetic factors

that might help to explain why some patients fared better than others.

They screened genetic material from 1,953 of the STAR*D patients, a sample

with a higher percentage of responders (69 percent), in part because patients

who were doing well tended to stay in contact longer and were more likely to

allow a blood sample to be drawn. The researchers looked for associations

between treatment response and 768 known sites of variability in 68 suspect

genes — sites where letters in the genetic code vary across individuals.

They found the strongest connection in the gene that codes for the serotonin

2A receptor, one of several proteins to which serotonin binds when brain cells

communicate.

Located on cells in the brain’s thinking center (cortex), the serotonin 2A

receptor regulates circuits implicated in depression. Antidepressants, including

citalopram, reduce the number of serotonin 2A receptors in animal cortex over

the course of a few weeks — the same time-frame required for the drugs to work

in humans — suggesting that the receptors are important in the drugs’ mechanism

of action.

Everyone inherits two copies of the serotonin 2A receptor gene, one from each

parent. A tiny glitch in the gene’s chemical sequence results in some people

having an adenine (A) at the same point that other people have a guanine (G). So

an individual can have gene types AA, AG or GG. Overall, the prevalence of the A

version was 38 percent, compared to 62 percent for the G version in this sample.

Fourteen percent had AA gene type, 43 percent AG and 43 percent GG. Since the

site of variation is located in a stretch of genetic material with no known

function, the researchers suspect that it may be just a marker for a

still-undiscovered functional variation nearby in the gene.

Based on scores on a depression rating scale, close to 80 percent of patients

who had AA responded to the antidepressant, compared to about 62 percent of

those with GG. Thus, patients with the AA gene type were 16-18 percent more

likely to benefit from the medication. Even patients with AG showed some

increased benefit.

But this only applied to white patients, in whom the A version was more than

six times more frequent than in black patients. There was no significant

association between gene type and treatment outcome in black patients, who

tended to fare less well in the trial overall.

“We now have to consider genetic factors as well as psychosocial issues in our

attempts to explain why antidepressants do not help our black patients as much

as they should,” McMahon said. “The new findings help make a compelling case for

a key role of the serotonin 2A receptor in the mechanism of antidepressant

action.”

Also participating in the study were: A. Rush and Madhukar Trivedi,

University of Texas Southwestern Medical Center; Gonzalo Laje, NIMH; Dennis

Charney, Mount Sinai Hospital; Lipsky, National Institute on Alcohol

Abuse and Alcoholism (NIAAA); , a Sorant, and

Papanicolaou, National Human Genome Research Institute (NHGRI); Maurizio Fava,

Massachusetts General Hospital; and Wisniewski, University of

Pittsburgh.

NIMH, NIAAA and NHGRI are part of the National Institutes of Health (NIH), the

Federal Government's primary agency for biomedical and behavioral research. NIH

and CDC are components of the U.S. Department of Health and Human Services.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency

— includes 27 Institutes and Centers and is a component of the U.S. Department

of Health and Human Services. It is the primary federal agency for conducting

and supporting basic, clinical and translational medical research, and it

investigates the causes, treatments, and cures for both common and rare

diseases. For more information about NIH and its programs, visit

http://www.nih.gov.

---------------------------------

---------------------------------

Bring photos to life! New PhotoMail makes sharing a breeze.

[Guest guest]

They don't even know how antidepressants work - by their own admission on all

the patient warnings they " think " or " believe " SSRI's blah, blah, blah. And now

they are claiming to know which genes make which person respond which way?

Bullsh*t!

Terry

http://www.nih.gov/news/pr/mar2006/nimh-15.htm

Gene Influences Antidepressant Response

Whether depressed patients will respond to an antidepressant depends, in part,

on which version of a gene they inherit, a study led by scientists at the

National Institutes of Health (NIH) has discovered. Having two copies of one

version of a gene that codes for a component of the brain’s mood-regulating

system increased the odds of a favorable response to an antidepressant by up to

18 percent, compared to having two copies of the other, more common version.

Since the less common version was over 6 times more prevalent in white than in

black patients — and fewer blacks responded — the researchers suggest that the

gene may help to explain racial differences in the outcome of antidepressant

treatment. The findings also add to evidence that the component, a receptor for

the chemical messenger serotonin, plays a pivotal role in the mechanism of

antidepressant action.

The study, authored by National Institute of Mental Health (NIMH) researchers

Francis J. McMahon, M.D., Silvia Buervenich, Ph.D., and Husseini Manji, M.D.,

along with collaborators at several other institutions, was posted online March

8 and will appear in the May, 2006 American Journal of Human Genetics.

“This discovery brings us closer to the day when clinicians will be able to

offer treatment options and medications that are tailored and personalized to be

optimally effective for individual patients,” said NIH Director Elias A.

Zerhouni, M.D.

However, the findings cannot yet guide treatment decisions.

“To our knowledge, this is the first demonstration of significant, replicated

association between genetic variation and outcome of antidepressant treatment,”

added Manji, director of the NIMH’s Mood and Anxiety Disorders Program.

In the initial phase of the NIMH-funded STAR*D (Sequenced Treatment

Alternatives for Depression) trial, about 47 percent of the 2,876 participants

experienced some improvement with the serotonin selective reuptake inhibitor

(SSRI) citalopram (Celexa). The NIH scientists set out to find genetic factors

that might help to explain why some patients fared better than others.

They screened genetic material from 1,953 of the STAR*D patients, a sample

with a higher percentage of responders (69 percent), in part because patients

who were doing well tended to stay in contact longer and were more likely to

allow a blood sample to be drawn. The researchers looked for associations

between treatment response and 768 known sites of variability in 68 suspect

genes — sites where letters in the genetic code vary across individuals.

They found the strongest connection in the gene that codes for the serotonin

2A receptor, one of several proteins to which serotonin binds when brain cells

communicate.

Located on cells in the brain’s thinking center (cortex), the serotonin 2A

receptor regulates circuits implicated in depression. Antidepressants, including

citalopram, reduce the number of serotonin 2A receptors in animal cortex over

the course of a few weeks — the same time-frame required for the drugs to work

in humans — suggesting that the receptors are important in the drugs’ mechanism

of action.

Everyone inherits two copies of the serotonin 2A receptor gene, one from each

parent. A tiny glitch in the gene’s chemical sequence results in some people

having an adenine (A) at the same point that other people have a guanine (G). So

an individual can have gene types AA, AG or GG. Overall, the prevalence of the A

version was 38 percent, compared to 62 percent for the G version in this sample.

Fourteen percent had AA gene type, 43 percent AG and 43 percent GG. Since the

site of variation is located in a stretch of genetic material with no known

function, the researchers suspect that it may be just a marker for a

still-undiscovered functional variation nearby in the gene.

Based on scores on a depression rating scale, close to 80 percent of patients

who had AA responded to the antidepressant, compared to about 62 percent of

those with GG. Thus, patients with the AA gene type were 16-18 percent more

likely to benefit from the medication. Even patients with AG showed some

increased benefit.

But this only applied to white patients, in whom the A version was more than

six times more frequent than in black patients. There was no significant

association between gene type and treatment outcome in black patients, who

tended to fare less well in the trial overall.

“We now have to consider genetic factors as well as psychosocial issues in our

attempts to explain why antidepressants do not help our black patients as much

as they should,” McMahon said. “The new findings help make a compelling case for

a key role of the serotonin 2A receptor in the mechanism of antidepressant

action.”

Also participating in the study were: A. Rush and Madhukar Trivedi,

University of Texas Southwestern Medical Center; Gonzalo Laje, NIMH; Dennis

Charney, Mount Sinai Hospital; Lipsky, National Institute on Alcohol

Abuse and Alcoholism (NIAAA); , a Sorant, and

Papanicolaou, National Human Genome Research Institute (NHGRI); Maurizio Fava,

Massachusetts General Hospital; and Wisniewski, University of

Pittsburgh.

NIMH, NIAAA and NHGRI are part of the National Institutes of Health (NIH), the

Federal Government's primary agency for biomedical and behavioral research. NIH

and CDC are components of the U.S. Department of Health and Human Services.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency

— includes 27 Institutes and Centers and is a component of the U.S. Department

of Health and Human Services. It is the primary federal agency for conducting

and supporting basic, clinical and translational medical research, and it

investigates the causes, treatments, and cures for both common and rare

diseases. For more information about NIH and its programs, visit

http://www.nih.gov.

---------------------------------

---------------------------------

Bring photos to life! New PhotoMail makes sharing a breeze.