Re: New Role For Serotonin 'Ironed Out'

[Guest guest]

That is amazing. I wonder how many of our kids are iron deficient? I know my

three sons, who are on the protocol, are. I'll definitely be more diligent in

making sure they get their iron supplement three times per week.

Thanks for the article.

Robyn

> From: Doris and Steve <sjsmith@...>

> Subject: New Role For Serotonin 'Ironed Out'

> " " < >, " Gail Zepp " <gazepp@...>,

mdcatch22fan@..., ljdboofie@..., linda_smith@...,

jdlusby@..., " Darrah " <ldarrah@...>, " frank "

<fjsanfellipo@...>, " Dyer, H " <mhdyer@...>, plumbs@...,

" Tammy Wylie " <Mrs_Wylie@...>, " Wise "

<jennifer_is_wise@...>, royplu2002@..., " "

<giggig@...>, colinandlinda@..., denise_mch@...,

mpmitch4@..., Bern9876@..., StoneroadM@...,

Aryal@..., " Mulcahy " <mcmulcahy2002@...>,

fernandezjuankaren@..., " Echo Reardanz " <znadraer@...>,

info@..., hanklecrew@..., jermegjohnson@...,

kara1000@..., fagand@..., bernitierney@...,

carrollfamily15@..., " RSL Berry " <berrybunchfive@...>, " Berry,

" <scberry@...>, whatanut@..., slyselitto@...,

dbemm1@..., janenemill@..., rmiller220@..., lltwinnie@...,

stacy673@..., larchers@..., " Cheryl Antlitz " <cantlitz@...>,

stacy673@..., jeffnteddi@..., " Keele " <pakeele@...>,

" Gouker " <briangouker@...>, " nps_rls@... " <nps_rls@...>,

susanjohnson@..., " j vester " <jvester2003@...>, nbirner@...

> Date: Friday, January 30, 2009, 4:03 AM

> >New Role For Serotonin 'Ironed Out'

> >ScienceDaily (Jan. 29, 2009) —

> >http://www.sciencedaily.com/releases/2009/01/090127123009.htm

> >

> >Vanderbilt University Medical Center investigators have

> found a

> >surprising link between brain iron levels and

> serotonin, a

> >neurotransmitter involved in neuropsychiatric

> conditions ranging from

> >autism to major depression.

> >

> >Appearing in the Proceedings of the National Academy of

> Sciences the

> >week of January 27, the study by Randy Blakely, Ph.D.,

> and colleagues

> >also demonstrates the utility of a powerful in silico

> approach for

> >discovering novel traits linked to subtle genetic

> variation.

> >

> >The serotonin transporter protein (SERT) regulates

> serotonin

> >availability in the brain and periphery, and variations

> in human SERT

> >have been linked to many neurobehavioral disorders –

> including

> >alcoholism, depression, autism and obsessive-compulsive

> disorder. SERT

> >is also a major target for medications like the

> selective serotonin

> >reuptake inhibitors (SSRI) used for treating

> depression.

> >

> >Thanks to a serendipitous mix-up in an animal order,

> Blakely and

> >first author Ana Carnerio, Ph.D., discovered that a

> mouse strain they

> >had been using to studying SERT function – called

> C57BL/6 –

> >actually carries a mutation that reduces the function

> of the

> >transporter.

> >

> > " Importantly, low-functioning variants of human

> SERT have been

> >associated with anxiety, depression, and reduced

> efficacy of SSRI

> >medications, " notes Blakely, senior author and

> director of the

> >Vanderbilt Center for Molecular Neuroscience.

> >

> >By querying an online resource called the Mouse Phenome

> Database,

> >they found that most mouse strains possess a SERT

> version called " ER "

> >– which is identical to the sequence found in human

> SERT. A small

> >number of strains, however, including the commonly

> studied C57BL/6

> >strain, carry a different version (called

> " GK " ).

> >

> >Carneiro realized that she could utilize her

> identification of SERT

> >GK to elucidate new aspects of brain chemistry and

> behavior.

> >Vanderbilt collaborator Airey, Ph.D., helped

> Carneiro and

> >Blakely exploit a separate panel of mice where the SERT

> GK variant is

> >presented on many different genetic backgrounds – a

> so-called

> > " recombinant inbred " population termed BXD

> mice.

> >

> >Using lines from this population, the team found that

> SERT GK mice

> >performed differently than SERT ER mice on tests of

> anxiety and

> >depression, consistent with reduced function of SERT

> GK. Importantly,

> >a public database of anatomical, biochemical and

> behavioral features

> >exists for all mice in the BXD population, allowing

> Blakely and

> >colleagues to identify novel traits linked with the low

> functioning

> >SERT. From this in silico approach, Blakely and

> colleagues identified

> >multiple trait differences affected by the SERT GK/ER

> variation,

> >including traits associated with alcohol consumption

> and brain

> >dopamine signaling.

> >

> >Additionally, they found that iron levels in the brains

> of mice with

> >the GK variant were significantly higher than in the ER

> variant mice.

> >Iron is required to synthesize both serotonin and

> dopamine, and

> >serotonin receptors are known to regulate iron-carrying

> proteins. But

> >SERT had not been previously shown to control brain

> iron levels.

> >Follow-up studies with mice where the SERT gene was

> eliminated (SERT

> > " knock-out " mice) verified a critical role

> for the transporter in

> >controlling brain iron levels.

> >

> > " Because SERT is such an important drug target in

> treating anxiety,

> >depression and OCD, we need to stop and think about how

> iron might be

> >influencing these disorders, " Blakely said. The

> study also

> >demonstrates the power of an in silico approach –

> combined with

> >traditional experimentation – in understanding how

> genes affect

> >complex traits.

> >

> > " The broader number of findings in our paper

> derives not from

> >(experiments) we did, but from what the (scientific)

> community

> >collectively did to populate the BXD database, "

> Blakely noted.

> >

> > " Indeed, this is a great example of how

> biostatistical approaches can

> >help limit the amount of experimentation that is needed

> with animals. "

> >

> >Other authors included Brent and Chong-Bin

> Zhu, M.D., Ph.D.,

> >from Vanderbilt, and researchers from Nantong

> University, the

> >University of Tennessee Heath Science Center, Oak Ridge

> National

> >Laboratory and the University of North Carolina at

> Greensboro. The

> >research was supported by the National Institutes of

> Health.

> >

> >Blakely is also the Allan D. Bass Professor of

> Pharmacology and a

> >professor of Pharmacology and of Psychiatry.

> >

> >

> >

> >

> >

> >

> >

[Guest guest]

From what Dr G has found, most kids are Iron deficient. Ours is, and as we

have experimented with dosages, the iron levels vary accordingly. This is a

very interesting study, and might explain more about why SSRI's and iron

therapy help a lot.

_____

From: [mailto: ] On Behalf Of Robyn

& Greg Coggins

Sent: Friday, January 30, 2009 11:49 AM

Subject: Re: New Role For Serotonin 'Ironed Out'

That is amazing. I wonder how many of our kids are iron deficient? I know my

three sons, who are on the protocol, are. I'll definitely be more diligent

in making sure they get their iron supplement three times per week.

Thanks for the article.

Robyn

> From: Doris and Steve <sjsmithcablespeed (DOT)

<mailto:sjsmith%40cablespeed.com> com>

> Subject: New Role For Serotonin 'Ironed Out'

> " " <groups (DOT) <mailto:%40> com>, " Gail

Zepp " <gazeppverizon (DOT) <mailto:gazepp%40verizon.net> net>, mdcatch22fan@

<mailto:mdcatch22fan%40comcast.net> comcast.net, ljdboofiecomcast (DOT)

<mailto:ljdboofie%40comcast.net> net, linda_smith@

<mailto:linda_smith%40acm.org> acm.org, jdlusbyverizon (DOT)

<mailto:jdlusby%40verizon.net> net, " Darrah " <ldarrahatlanticbb (DOT)

<mailto:ldarrah%40atlanticbb.net> net>, " frank " <fjsanfellipo@

<mailto:fjsanfellipo%40netzero.net> netzero.net>, " Dyer, H "

<mhdyer@... <mailto:mhdyer%40nsa.gov> >, plumbsgavtron (DOT)

<mailto:plumbs%40gavtron.com> com, " Tammy Wylie " <Mrs_Wylieverizon (DOT)

<mailto:Mrs_Wylie%40verizon.net> net>, " Wise " <jennifer_is_

<mailto:jennifer_is_wise%40hotmail.com> wise@...>, royplu2002 (DOT)

<mailto:royplu2002%40> com, " " <giggigcomcast (DOT)

<mailto:giggig%40comcast.net> net>, colinandlinda@

<mailto:colinandlinda%40ozemail.com.au> ozemail.com.au, denise_mch (DOT)

<mailto:denise_mch%40> com, mpmitch4 (DOT)

<mailto:mpmitch4%40> com, Bern9876comcast (DOT)

<mailto:Bern9876%40comcast.net> net, StoneroadMaol (DOT)

<mailto:StoneroadM%40aol.com> com, Aryal@

<mailto:Aryal%40aol.com> aol.com, " Mulcahy " <mcmulcahy2002@

<mailto:mcmulcahy2002%40> >, fernandezjuankaren@

<mailto:fernandezjuankaren%40att.net> att.net, " Echo Reardanz "

<znadraer (DOT) <mailto:znadraer%40> com>, infoautismlink (DOT)

<mailto:info%40autismlink.com> com, hanklecrew@cablespe

<mailto:hanklecrew%40cablespeed.com> ed.com, jermegjohnson@

<mailto:jermegjohnson%40> , kara1000@rocketmail

<mailto:kara1000%40rocketmail.com> .com, fagand@...

<mailto:fagand%40ctc.com> , bernitierney@ <mailto:bernitierney%40aol.com>

aol.com, carrollfamily15@ <mailto:carrollfamily15%40comcast.net>

comcast.net, " RSL Berry " <berrybunchfive@

<mailto:berrybunchfive%40hotmail.com> hotmail.com>, " Berry, "

<scberrynsa (DOT) <mailto:scberry%40nsa.gov> gov>, whatanutgmail (DOT)

<mailto:whatanut%40gmail.com> com, slyselitto (DOT)

<mailto:slyselitto%40> com,

dbemm1comcast (DOT) <mailto:dbemm1%40comcast.net> net, janenemillaol (DOT)

<mailto:janenemill%40aol.com> com, rmiller220aol (DOT)

<mailto:rmiller220%40aol.com> com, lltwinnieaol (DOT)

<mailto:lltwinnie%40aol.com> com, stacy673msn (DOT) <mailto:stacy673%40msn.com>

com, larchersverizon (DOT) <mailto:larchers%40verizon.net> net, " Cheryl Antlitz "

<cantlitzhotmail (DOT) <mailto:cantlitz%40hotmail.com> com>, stacy673msn (DOT)

<mailto:stacy673%40msn.com> com, jeffnteddi (DOT)

<mailto:jeffnteddi%40> com, " Keele " <pakeele (DOT)

<mailto:pakeele%40> com>, " Gouker " <briangouker@

<mailto:briangouker%40> >, " nps_rlsjuno (DOT)

<mailto:nps_rls%40juno.com> com " <nps_rlsjuno (DOT) <mailto:nps_rls%40juno.com>

com>, susanjohnson@ <mailto:susanjohnson%40hughes.net> hughes.net, " j

vester " <jvester2003@ <mailto:jvester2003%40> >,

nbirnercomcast (DOT) <mailto:nbirner%40comcast.net> net

> Date: Friday, January 30, 2009, 4:03 AM

> >New Role For Serotonin 'Ironed Out'

> >ScienceDaily (Jan. 29, 2009) -

> >http://www.scienced

<http://www.sciencedaily.com/releases/2009/01/090127123009.htm>

aily.com/releases/2009/01/090127123009.htm

> >

> >Vanderbilt University Medical Center investigators have

> found a

> >surprising link between brain iron levels and

> serotonin, a

> >neurotransmitter involved in neuropsychiatric

> conditions ranging from

> >autism to major depression.

> >

> >Appearing in the Proceedings of the National Academy of

> Sciences the

> >week of January 27, the study by Randy Blakely, Ph.D.,

> and colleagues

> >also demonstrates the utility of a powerful in silico

> approach for

> >discovering novel traits linked to subtle genetic

> variation.

> >

> >The serotonin transporter protein (SERT) regulates

> serotonin

> >availability in the brain and periphery, and variations

> in human SERT

> >have been linked to many neurobehavioral disorders -

> including

> >alcoholism, depression, autism and obsessive-compulsive

> disorder. SERT

> >is also a major target for medications like the

> selective serotonin

> >reuptake inhibitors (SSRI) used for treating

> depression.

> >

> >Thanks to a serendipitous mix-up in an animal order,

> Blakely and

> >first author Ana Carnerio, Ph.D., discovered that a

> mouse strain they

> >had been using to studying SERT function - called

> C57BL/6 -

> >actually carries a mutation that reduces the function

> of the

> >transporter.

> >

> > " Importantly, low-functioning variants of human

> SERT have been

> >associated with anxiety, depression, and reduced

> efficacy of SSRI

> >medications, " notes Blakely, senior author and

> director of the

> >Vanderbilt Center for Molecular Neuroscience.

> >

> >By querying an online resource called the Mouse Phenome

> Database,

> >they found that most mouse strains possess a SERT

> version called " ER "

> >- which is identical to the sequence found in human

> SERT. A small

> >number of strains, however, including the commonly

> studied C57BL/6

> >strain, carry a different version (called

> " GK " ).

> >

> >Carneiro realized that she could utilize her

> identification of SERT

> >GK to elucidate new aspects of brain chemistry and

> behavior.

> >Vanderbilt collaborator Airey, Ph.D., helped

> Carneiro and

> >Blakely exploit a separate panel of mice where the SERT

> GK variant is

> >presented on many different genetic backgrounds - a

> so-called

> > " recombinant inbred " population termed BXD

> mice.

> >

> >Using lines from this population, the team found that

> SERT GK mice

> >performed differently than SERT ER mice on tests of

> anxiety and

> >depression, consistent with reduced function of SERT

> GK. Importantly,

> >a public database of anatomical, biochemical and

> behavioral features

> >exists for all mice in the BXD population, allowing

> Blakely and

> >colleagues to identify novel traits linked with the low

> functioning

> >SERT. From this in silico approach, Blakely and

> colleagues identified

> >multiple trait differences affected by the SERT GK/ER

> variation,

> >including traits associated with alcohol consumption

> and brain

> >dopamine signaling.

> >

> >Additionally, they found that iron levels in the brains

> of mice with

> >the GK variant were significantly higher than in the ER

> variant mice.

> >Iron is required to synthesize both serotonin and

> dopamine, and

> >serotonin receptors are known to regulate iron-carrying

> proteins. But

> >SERT had not been previously shown to control brain

> iron levels.

> >Follow-up studies with mice where the SERT gene was

> eliminated (SERT

> > " knock-out " mice) verified a critical role

> for the transporter in

> >controlling brain iron levels.

> >

> > " Because SERT is such an important drug target in

> treating anxiety,

> >depression and OCD, we need to stop and think about how

> iron might be

> >influencing these disorders, " Blakely said. The

> study also

> >demonstrates the power of an in silico approach -

> combined with

> >traditional experimentation - in understanding how

> genes affect

> >complex traits.

> >

> > " The broader number of findings in our paper

> derives not from

> >(experiments) we did, but from what the (scientific)

> community

> >collectively did to populate the BXD database, "

> Blakely noted.

> >

> > " Indeed, this is a great example of how

> biostatistical approaches can

> >help limit the amount of experimentation that is needed

> with animals. "

> >

> >Other authors included Brent and Chong-Bin

> Zhu, M.D., Ph.D.,

> >from Vanderbilt, and researchers from Nantong

> University, the

> >University of Tennessee Heath Science Center, Oak Ridge

> National

> >Laboratory and the University of North Carolina at

> Greensboro. The

> >research was supported by the National Institutes of

> Health.

> >

> >Blakely is also the Allan D. Bass Professor of

> Pharmacology and a

> >professor of Pharmacology and of Psychiatry.

> >

> >

> >

> >

> >

> >

> >

[Guest guest]

I wish I had someone to explain this one.  It mentions some things...

I'm always anemic unless I take doxycycline (at least over the last few years,

and previous decades), but if I take iron - the more iron I take, the more very

depressed I become.  I already have sometimes severe ocd and anxiety, but not

usually depression.  Taking the iron did not help my anemia at all - it kept

going down, and along with it the depression and fatigue was constant.  I begged

my doctor (prior to Dr ) to let me prove to him that the anemia would

improve on doxy without any iron at all, if he would just give me the

antifungals to go with it.  .  It worked - doxycycline improved my anemia (and

boy does it improve my cognitive function), taking iron absolutely did not.

But if I drink 1 or 2 drinks of alcohol (and my ability to 'hold my liqour' or

drink people under the table is more legendary -before children- than I would

care to admit), I tend to feel depressed later.  I also discovered that 2 drinks

can now make me tipsy (while being treated on the protocol) - something that

never would have happened 10 years ago.  I don't care to drink so it doesn't

matter - it's just a curiosity I have (among many) as to why alcohol did not

intoxicate me (much) like it did other people.  I couldn't tell what it meant re

the alcohol.

It said: Importantly, low-functioning variants of human SERT have been

associated with anxiety, depression, and reduced efficacy of SSRI medications, "

notes Blakely, senior author and director of the Vanderbilt Center for Molecular

Neuroscience.    I've tried to find an SSRI (off and on) for 20 years - always

bad news - I'm done trying.  But an SNRI was ok for a few weeks.

Anyway, Dr did state that there is a small percentage of people that

don't respond to SSRIs.  I've always wondered (after the fact) if I have a fear

of the med that drives me to blame symptoms on it or if my hypervigilance has

caused me to stop taking them (I can usually make it about 6 weeks before I lose

my mind), which is I why I willingly try again.  It is frustrating that other

doctors would listen to what I said about my SSRI experiences and then just go

on and give another, and I wonder if this is actually validating what I've

experienced or not....

Anyway, sorry for the TMI,

________________________________

From: Doris and Steve <sjsmith@...>

< >; Gail Zepp <gazepp@...>;

mdcatch22fan@...; ljdboofie@...; linda_smith@...;

jdlusby@...; Darrah <ldarrah@...>; frank

<fjsanfellipo@...>; " Dyer, H " <mhdyer@...>; plumbs@...;

Tammy Wylie <Mrs_Wylie@...>; Wise

<jennifer_is_wise@...>; royplu2002@...;

<giggig@...>; colinandlinda@...; denise_mch@...;

mpmitch4@...; Bern9876@...; StoneroadM@...;

Aryal@...; Mulcahy <mcmulcahy2002@...>;

fernandezjuankaren@...; Echo Reardanz <znadraer@...>;

info@...; hanklecrew@...; jermegjohnson@...;

kara1000@...; fagand@...; bernitierney@...;

carrollfamily15@...; RSL Berry <berrybunchfive@...>; " Berry,

" <scberry@...>; whatanut@...; slyselitto@...;

dbemm1@...;

janenemill@...; rmiller220@...; lltwinnie@...; stacy673@...;

larchers@...; Cheryl Antlitz <cantlitz@...>; stacy673@...;

jeffnteddi@...; Keele <pakeele@...>; Gouker

<briangouker@...>; " nps_rls@... " <nps_rls@...>;

susanjohnson@...; j vester <jvester2003@...>; nbirner@...

Sent: Friday, January 30, 2009 6:03:35 AM

Subject: New Role For Serotonin 'Ironed Out'

>New Role For Serotonin 'Ironed Out'

>ScienceDaily (Jan. 29, 2009) —

>http://www.scienced aily.com/ releases/ 2009/01/09012712 3009.htm

>

>Vanderbilt University Medical Center investigators have found a

>surprising link between brain iron levels and serotonin, a

>neurotransmitter involved in neuropsychiatric conditions ranging from

>autism to major depression.

>

>Appearing in the Proceedings of the National Academy of Sciences the

>week of January 27, the study by Randy Blakely, Ph.D., and colleagues

>also demonstrates the utility of a powerful in silico approach for

>discovering novel traits linked to subtle genetic variation.

>

>The serotonin transporter protein (SERT) regulates serotonin

>availability in the brain and periphery, and variations in human SERT

>have been linked to many neurobehavioral disorders – including

>alcoholism, depression, autism and obsessive-compulsiv e disorder. SERT

>is also a major target for medications like the selective serotonin

>reuptake inhibitors (SSRI) used for treating depression.

>

>Thanks to a serendipitous mix-up in an animal order, Blakely and

>first author Ana Carnerio, Ph.D., discovered that a mouse strain they

>had been using to studying SERT function – called C57BL/6 –

>actually carries a mutation that reduces the function of the

>transporter.

>

> " Importantly, low-functioning variants of human SERT have been

>associated with anxiety, depression, and reduced efficacy of SSRI

>medications, " notes Blakely, senior author and director of the

>Vanderbilt Center for Molecular Neuroscience.

>

>By querying an online resource called the Mouse Phenome Database,

>they found that most mouse strains possess a SERT version called " ER "

>– which is identical to the sequence found in human SERT. A small

>number of strains, however, including the commonly studied C57BL/6

>strain, carry a different version (called " GK " ).

>

>Carneiro realized that she could utilize her identification of SERT

>GK to elucidate new aspects of brain chemistry and behavior.

>Vanderbilt collaborator Airey, Ph.D., helped Carneiro and

>Blakely exploit a separate panel of mice where the SERT GK variant is

>presented on many different genetic backgrounds – a so-called

> " recombinant inbred " population termed BXD mice.

>

>Using lines from this population, the team found that SERT GK mice

>performed differently than SERT ER mice on tests of anxiety and

>depression, consistent with reduced function of SERT GK. Importantly,

>a public database of anatomical, biochemical and behavioral features

>exists for all mice in the BXD population, allowing Blakely and

>colleagues to identify novel traits linked with the low functioning

>SERT. From this in silico approach, Blakely and colleagues identified

>multiple trait differences affected by the SERT GK/ER variation,

>including traits associated with alcohol consumption and brain

>dopamine signaling.

>

>Additionally, they found that iron levels in the brains of mice with

>the GK variant were significantly higher than in the ER variant mice.

>Iron is required to synthesize both serotonin and dopamine, and

>serotonin receptors are known to regulate iron-carrying proteins. But

>SERT had not been previously shown to control brain iron levels.

>Follow-up studies with mice where the SERT gene was eliminated (SERT

> " knock-out " mice) verified a critical role for the transporter in

>controlling brain iron levels.

>

> " Because SERT is such an important drug target in treating anxiety,

>depression and OCD, we need to stop and think about how iron might be

>influencing these disorders, " Blakely said. The study also

>demonstrates the power of an in silico approach – combined with

>traditional experimentation – in understanding how genes affect

>complex traits.

>

> " The broader number of findings in our paper derives not from

>(experiments) we did, but from what the (scientific) community

>collectively did to populate the BXD database, " Blakely noted.

>

> " Indeed, this is a great example of how biostatistical approaches can

>help limit the amount of experimentation that is needed with animals. "

>

>Other authors included Brent and Chong-Bin Zhu, M.D., Ph.D.,

>from Vanderbilt, and researchers from Nantong University, the

>University of Tennessee Heath Science Center, Oak Ridge National

>Laboratory and the University of North Carolina at Greensboro. The

>research was supported by the National Institutes of Health.

>

>Blakely is also the Allan D. Bass Professor of Pharmacology and a

>professor of Pharmacology and of Psychiatry.

>

>

>

>

>

>

>