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Old 03-15-09, 12:55 PM
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High Dopamine Transporter Levels Not Correlated With ADHD

Results from a brain-imaging study conducted at the U.S. Department of Energy's Brookhaven National Laboratory in collaboration with Mount Sinai School of Medicine in New York indicate that levels of a brain protein proposed as a diagnostic marker for attention-deficit hyperactivity disorder (ADHD) are not positively correlated with the disease. In fact, the study found lower levels of these "dopamine transporter" proteins in certain brain regions of ADHD patients compared with controls. The study, which will be published in an upcoming issue of the journal Neuroimage and is now available online, also found that for any given level of dopamine transporters in the brain, ADHD patients experienced much higher levels of inattention compared with control subjects.

"These results suggest that dopamine transporter levels alone cannot account for the severity of symptoms of inattention in ADHD," said Nora Volkow, Director of the National Institute on Drug Abuse and the lead author of the study. Added Gene-Jack Wang, who led Brookhaven's role in the research, "It is clear from these results that clinical measures of dopamine transporters should not be used as a basis for a diagnosis of ADHD."

ADHD is the most frequently recognized psychiatric disorder in children, with some 3 million children younger than 18 currently receiving treatment in the U.S. Yet the mechanism underlying this disorder and its treatment are still poorly understood. One prominent theory of ADHD is that there is a dysfunction in brain circuits that depend on the neurotransmitter dopamine to modulate attention, motivation, and interest. If, for example, ADHD subjects have elevated levels of dopamine transporters - proteins on dopamine-producing cells that take up excess dopamine - they could end up with depleted dopamine levels and reduced motivation/attention.

Four independent studies have reported that ADHD subjects have higher than normal levels of dopamine transporters in a brain region called the striatum. But the magnitude of the increase has varied widely, ranging from 70 percent to 5 percent elevations in transporter levels. Two other studies found no elevation of transporter levels, though one found a decrease in dopamine transporter levels in a different brain region.

"Because these discrepancies could reflect differences in medication or drug-abuse histories among subjects, we designed the current study to investigate dopamine transporter levels in ADHD subjects and control subjects while excluding these potentially confounding factors," Wang said.

The researchers measured dopamine transporter levels in 20 adult ADHD subjects who had never received medication, never abused drugs (except nicotine), and had no past or present history of mental or neurological disease or other medical conditions that could affect cerebral function. They also asked subjects to respond to a questionnaire to gauge levels of inattention. The scientists ran the same tests in 25 healthy control subjects with the same exclusion criteria.

To measure dopamine transporter levels, each subject was given an injection of a radiotracer (a radioactively labeled chemical) designed to bind to dopamine transporters while lying in a positron emission tomography (PET) scanner. The PET camera picks up the radioactive signal from the tracer to precisely measure the level of dopamine transporters.

The PET scans revealed that ADHD subjects had significantly fewer dopamine transporters than control subjects in the nucleus accumbens, an area of the ventral striatum that is one of the main reward centers in the brain. In a dorsal striatum region known as the putamen, which plays an important role in habits and is also involved with attention, dopamine transporter levels did not differ between the two groups.

In both groups, levels of dopamine transporters in the putamen were positively associated with scores of inattention on the self-report questionnaire: the higher the level of transporters, the higher the score of inattention. This finding makes it clear that dopamine transporters play an important role in modulating attention in all people. Yet, for a given level of dopamine transporters, scores of inattention were, on average, five times greater for ADHD subjects than for controls in this study.

"These findings suggest that an additional variable in conjunction with dopamine transporters would be required to account for the severity of the symptoms of inattention in ADHD," Volkow said. "We speculate that this other variable may be lower levels of dopamine release in ADHD subjects."

If ADHD subjects release less dopamine to start with, they may end up with lower levels of dopamine transporters as a result of down regulation - that is, the body's attempt to compensate for lower dopamine levels by reducing the number of reuptake proteins. This would explain the positive correlation between transporter levels and inattention: as the number of reuptake proteins rises, the amount of dopamine would decline, leading to a higher level of inattention. This would also explain why control subjects, with higher dopamine release levels, had lower scores of inattention than did subjects with ADHD with similar levels of dopamine transporters.

Jeffrey Newcorn, a child and adolescent psychiatrist and lead collaborator from Mount Sinai, emphasized that ADHD is not a simple, one-type-fits-all disorder. There are very likely variations in dopamine transporter levels among and even within ADHD subgroups.

"The significant differences across studies and investigators clearly highlight the need to look for factors affecting these inconsistencies to improve our ability to diagnose and treat ADHD," he said. "Although levels of dopamine transporters alone do not determine whether an individual has ADHD, the association of inattention ratings and transporter levels in both ADHD and normal subjects is consistent with the use of treatments such as stimulant medications, which block activity of the transporter, in ADHD."

Ongoing research in adults with ADHD, currently being conducted at Brookhaven National Laboratory and Mount Sinai, is investigating the potential long-term impact of treatment with stimulants on the dopamine system.

----------------------------
Article adapted by Medical News Today from original press release.
----------------------------

This study was funded by the Office of Biological and Environmental Research within the U.S. Department of Energy's Office of Science and by the Intramural Research Program of the National Institutes of Health. DOE has a long-standing interest in brain-imaging studies. Brain-imaging techniques such as PET are a direct outgrowth of DOE's support of basic physics and chemistry research.

One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization. Visit Brookhaven Lab's electronic newsroom for links, news archives, graphics, and more: http://www.bnl.gov/newsroom

Located in Manhattan, Mount Sinai School of Medicine is internationally recognized for ground-breaking clinical and basic-science research, and innovative approaches to medical education. Through the Mount Sinai Graduate School of Biological Sciences, Mount Sinai trains biomedical researchers with an emphasis on the rapid translation of discoveries of basic research into new techniques for fighting disease. One indication of Mount Sinai's leadership in scientific investigation is its receipt during fiscal year 2005 of $252.2 million. Mount Sinai now ranks 20th among the nation's medical schools in receipt of research support from NIH. Mount Sinai School of Medicine also is known for unique educational programs such as the Humanities in Medicine program, which creates opportunities for liberal arts students to pursue medical school, and instructional innovations like The Morchand Center, the nation's largest program teaching students and physicians with "standardized patients" to become not only highly skilled, but compassionate caregivers. Long dedicated to improving its community, the School extends its boundaries to work with East Harlem and surrounding communities to provide access to health care and educational programs to at risk populations.

Contact: Karen McNulty Walsh
DOE/Brookhaven National Laboratory

Link: http://www.medicalnewstoday.com/articles/57831.php
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Old 07-19-10, 05:28 PM
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Re: High Dopamine Transporter Levels Not Correlated With ADHD

Quite interesting; though to make this statistically sound, they should have more than 45 subjects in the entire sample.
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Old 07-21-10, 10:40 AM
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Re: High Dopamine Transporter Levels Not Correlated With ADHD

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Old 05-09-11, 08:14 AM
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Re: High Dopamine Transporter Levels Not Correlated With ADHD

More psychobabble and non scientific bs. Are you guys funded by big pharma? There is no, and never will be, evidence of an objective, biological or scientific nature to support or justify the existence of so called ADD or ADHD. It's just slick marketing to sell dope to little kids and uninformed adults. Get the facts and think for yourself at cchr.org.




Quote:
Originally Posted by Mincan View Post
Results from a brain-imaging study conducted at the U.S. Department of Energy's Brookhaven National Laboratory in collaboration with Mount Sinai School of Medicine in New York indicate that levels of a brain protein proposed as a diagnostic marker for attention-deficit hyperactivity disorder (ADHD) are not positively correlated with the disease. In fact, the study found lower levels of these "dopamine transporter" proteins in certain brain regions of ADHD patients compared with controls. The study, which will be published in an upcoming issue of the journal Neuroimage and is now available online, also found that for any given level of dopamine transporters in the brain, ADHD patients experienced much higher levels of inattention compared with control subjects.

"These results suggest that dopamine transporter levels alone cannot account for the severity of symptoms of inattention in ADHD," said Nora Volkow, Director of the National Institute on Drug Abuse and the lead author of the study. Added Gene-Jack Wang, who led Brookhaven's role in the research, "It is clear from these results that clinical measures of dopamine transporters should not be used as a basis for a diagnosis of ADHD."

ADHD is the most frequently recognized psychiatric disorder in children, with some 3 million children younger than 18 currently receiving treatment in the U.S. Yet the mechanism underlying this disorder and its treatment are still poorly understood. One prominent theory of ADHD is that there is a dysfunction in brain circuits that depend on the neurotransmitter dopamine to modulate attention, motivation, and interest. If, for example, ADHD subjects have elevated levels of dopamine transporters - proteins on dopamine-producing cells that take up excess dopamine - they could end up with depleted dopamine levels and reduced motivation/attention.

Four independent studies have reported that ADHD subjects have higher than normal levels of dopamine transporters in a brain region called the striatum. But the magnitude of the increase has varied widely, ranging from 70 percent to 5 percent elevations in transporter levels. Two other studies found no elevation of transporter levels, though one found a decrease in dopamine transporter levels in a different brain region.

"Because these discrepancies could reflect differences in medication or drug-abuse histories among subjects, we designed the current study to investigate dopamine transporter levels in ADHD subjects and control subjects while excluding these potentially confounding factors," Wang said.

The researchers measured dopamine transporter levels in 20 adult ADHD subjects who had never received medication, never abused drugs (except nicotine), and had no past or present history of mental or neurological disease or other medical conditions that could affect cerebral function. They also asked subjects to respond to a questionnaire to gauge levels of inattention. The scientists ran the same tests in 25 healthy control subjects with the same exclusion criteria.

To measure dopamine transporter levels, each subject was given an injection of a radiotracer (a radioactively labeled chemical) designed to bind to dopamine transporters while lying in a positron emission tomography (PET) scanner. The PET camera picks up the radioactive signal from the tracer to precisely measure the level of dopamine transporters.

The PET scans revealed that ADHD subjects had significantly fewer dopamine transporters than control subjects in the nucleus accumbens, an area of the ventral striatum that is one of the main reward centers in the brain. In a dorsal striatum region known as the putamen, which plays an important role in habits and is also involved with attention, dopamine transporter levels did not differ between the two groups.

In both groups, levels of dopamine transporters in the putamen were positively associated with scores of inattention on the self-report questionnaire: the higher the level of transporters, the higher the score of inattention. This finding makes it clear that dopamine transporters play an important role in modulating attention in all people. Yet, for a given level of dopamine transporters, scores of inattention were, on average, five times greater for ADHD subjects than for controls in this study.

"These findings suggest that an additional variable in conjunction with dopamine transporters would be required to account for the severity of the symptoms of inattention in ADHD," Volkow said. "We speculate that this other variable may be lower levels of dopamine release in ADHD subjects."

If ADHD subjects release less dopamine to start with, they may end up with lower levels of dopamine transporters as a result of down regulation - that is, the body's attempt to compensate for lower dopamine levels by reducing the number of reuptake proteins. This would explain the positive correlation between transporter levels and inattention: as the number of reuptake proteins rises, the amount of dopamine would decline, leading to a higher level of inattention. This would also explain why control subjects, with higher dopamine release levels, had lower scores of inattention than did subjects with ADHD with similar levels of dopamine transporters.

Jeffrey Newcorn, a child and adolescent psychiatrist and lead collaborator from Mount Sinai, emphasized that ADHD is not a simple, one-type-fits-all disorder. There are very likely variations in dopamine transporter levels among and even within ADHD subgroups.

"The significant differences across studies and investigators clearly highlight the need to look for factors affecting these inconsistencies to improve our ability to diagnose and treat ADHD," he said. "Although levels of dopamine transporters alone do not determine whether an individual has ADHD, the association of inattention ratings and transporter levels in both ADHD and normal subjects is consistent with the use of treatments such as stimulant medications, which block activity of the transporter, in ADHD."

Ongoing research in adults with ADHD, currently being conducted at Brookhaven National Laboratory and Mount Sinai, is investigating the potential long-term impact of treatment with stimulants on the dopamine system.

----------------------------
Article adapted by Medical News Today from original press release.
----------------------------

This study was funded by the Office of Biological and Environmental Research within the U.S. Department of Energy's Office of Science and by the Intramural Research Program of the National Institutes of Health. DOE has a long-standing interest in brain-imaging studies. Brain-imaging techniques such as PET are a direct outgrowth of DOE's support of basic physics and chemistry research.

One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization. Visit Brookhaven Lab's electronic newsroom for links, news archives, graphics, and more: http://www.bnl.gov/newsroom

Located in Manhattan, Mount Sinai School of Medicine is internationally recognized for ground-breaking clinical and basic-science research, and innovative approaches to medical education. Through the Mount Sinai Graduate School of Biological Sciences, Mount Sinai trains biomedical researchers with an emphasis on the rapid translation of discoveries of basic research into new techniques for fighting disease. One indication of Mount Sinai's leadership in scientific investigation is its receipt during fiscal year 2005 of $252.2 million. Mount Sinai now ranks 20th among the nation's medical schools in receipt of research support from NIH. Mount Sinai School of Medicine also is known for unique educational programs such as the Humanities in Medicine program, which creates opportunities for liberal arts students to pursue medical school, and instructional innovations like The Morchand Center, the nation's largest program teaching students and physicians with "standardized patients" to become not only highly skilled, but compassionate caregivers. Long dedicated to improving its community, the School extends its boundaries to work with East Harlem and surrounding communities to provide access to health care and educational programs to at risk populations.

Contact: Karen McNulty Walsh
DOE/Brookhaven National Laboratory

Link: http://www.medicalnewstoday.com/articles/57831.php
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Old 05-09-11, 05:20 PM
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Re: High Dopamine Transporter Levels Not Correlated With ADHD

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Originally Posted by mapster2 View Post
More psychobabble and non scientific bs. Are you guys funded by big pharma? There is no, and never will be, evidence of an objective, biological or scientific nature to support or justify the existence of so called ADD or ADHD. It's just slick marketing to sell dope to little kids and uninformed adults. Get the facts and think for yourself at cchr.org.
It's weird that you'd tell people to think for THEMselves and then send them directly to another website. I know you're too far gone to be reasoned with, but you should at least be honest about your affiliation.

CCHR is a Scientology-founded and controlled website which is specifically designed to end the practice of psychiatry. If you were at least up front about that, I'd have a teensy bit more respect for you. If CCHR included ANYTHING about Scientology on their website, I'd have a teensy bit more respect for them.

{Nothing we say to this guy will inform him or change his opinion, so I'm sorry for feeding the troll, but I felt the need to call him out on his hypocrisy.}

I do have to thank you though, mapster. I teach 7th grade and when we write research papers, it's hard to teach them about bias, as they tend to think any "official" looking website is credible, when in fact many have hidden agendas. CCHR is the perfect example! It will help me give them enough of a critical eye to hopefully stay away from such ideologues as you.

In contrast, while a large forum such as this one can contain many opinions, fallacies, hidden agendas, etc., the number of its users contribute to the overall wealth of knowledge, and the inherent system of "checks and balances" keeps things pretty well-rounded, as a whole.

Anyway...I guess in the old days this guy would have been out on the street with his sign board, but lucky for us Scientology hasn't decided that the internet is evil (yet.)
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Old 05-09-11, 07:31 PM
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Re: High Dopamine Transporter Levels Not Correlated With ADHD

So why the title that higher dopamine transporter levels are not correlated to ADHD when looking at this study I saw this?


both groups, levels of dopamine transporters in the putamen were positively associated with scores of inattention on the self-report questionnaire: the higher the level of transporters, the higher the score of inattention.This finding makes it clear that dopamine transporters play an important role in modulating attention in all people. Yet, for a given level of dopamine transporters, scores of inattention were, on average, five times greater for ADHD subjects than for controls in this study.
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Old 05-26-11, 08:06 AM
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Re: High Dopamine Transporter Levels Not Correlated With ADHD

This press release was issued in 2006, and probably refers to this paper[1], which investigated difference in density of usable dopamine transporters between never treated ADHD patients and normal people.

Dopamine transporters (DAT) suck dopamine back out of the synaptic cleft after it has been dumped in there by the source cell to trigger activation of the sink cell.
One theory on ADHD and why ritalin (MP) might help is that people with ADHD might have too many DAT, which sucks dopamine out of the cleft too quickly, reducing ability to transmit information between nerve cells that use dopamine. MP molecules go and sit in some of the DATs, jamming them up so that they are not useful for sucking up dopamine. The idea was that MP makes people with too many DAT function like people with the right number by jamming some of the DAT.

However, studies in rats showed that over time, exposure to substantial amounts of stimulant increased the number of DAT. I'm sure we are all familiar with (and scared of) developed tolerance.
This raised the question - studies were showing that people with ADHD had up to 10-70% more DAT, depending who you asked. But was that because the ADHD subjects had been dosed with MP for ages, and it had increased tier DAT density?

So, this study looked at ADHD subjects who had never had stimulants, and should have the standard ADHD number of DAT.

Sensible.

From there, the study becomes a complete mess.

They recruited 20 ADHD cases, and 25 normals. As someone has commented, you expect to see variation between people, so unless you saw a really strong swing with 20 cases, you would not be able to call it statistically significant (scientifically valid).
But it gets worse. They split the groups by gender and race, so they had groups of like 6 cases and 6 controls. That's terrible. I don't know that such low numbers could strongly associate car crashes with broken limbs.

The results of the study showed no significant difference anywhere. The writers act like it did, but they just don't. They look at a p value of 0.5 (which means it's 50/50 that the result was by chance and means nothing), and say "wow, our lowest P value is in the caudate". That's terrible.

They do however, print a nice table of other studies. All of them suffer from stupidly low numbers of cases, but most of the others never medicated ADHD cases as well, and completely disagree.

I think that the splitting of the groups was a major weakness in this study, it makes the statistics a mess. Even when the groups are merged, the results reported are completely inconclusive.

Since 2006 there has been much research on this topic. Mutations in dopamine receptors DA D2 and DA D3 were shown to be assosiated with ADHD, using massive scale genetic studies. Obviously, genetic mutation is not effected by drug use. This marks them as suspects only.

I'd read those studies and write them up here too, but I'm lazy and hungry, maybe someone else wants to do it?

Anyway, dopamine is hardly the only pathway associated with ADHD, and DAT is just one part of it. I know enough statistics to spot a poor study but not enough about brains to give a real explanation.
And credit to the scientists - it takes guts to ask your boss for radioactive cocaine (which was part of it). But if they can do it, we can too.


[1] http://www.sciencedirect.com/science...5381190601024X
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Old 05-27-11, 09:07 AM
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Re: High Dopamine Transporter Levels Not Correlated With ADHD

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Originally Posted by TimThompson View Post
The results of the study showed no significant difference anywhere. The writers act like it did, but they just don't. They look at a p value of 0.5 (which means it's 50/50 that the result was by chance and means nothing), and say "wow, our lowest P value is in the caudate". That's terrible.
http://www.sciencedirect.com/science...5381190601024X
I'm not saying that I understand the study, but check the paper again, it's p<0.05, not p=0.5. Big difference.
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Old 05-27-11, 10:29 AM
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Re: High Dopamine Transporter Levels Not Correlated With ADHD

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Quite interesting; though to make this statistically sound, they should have more than 45 subjects in the entire sample.
25 is sufficient to normalize something, so 45 is a pretty decent sample for a pilot or even an initial study. I'd need to see the actual paper to check the math, but at the face of it, 45 subjects is sufficient to perform the ANOVA and linear regressions they need to look for correlations, and p=0.05 is the standard for medical research.
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Old 05-27-11, 11:11 AM
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Re: High Dopamine Transporter Levels Not Correlated With ADHD

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So why the title that higher dopamine transporter levels are not correlated to ADHD when looking at this study I saw this?


both groups, levels of dopamine transporters in the putamen were positively associated with scores of inattention on the self-report questionnaire: the higher the level of transporters, the higher the score of inattention.This finding makes it clear that dopamine transporters play an important role in modulating attention in all people. Yet, for a given level of dopamine transporters, scores of inattention were, on average, five times greater for ADHD subjects than for controls in this study.
I would agree that it's a misleading title.

They're not saying transporters don't play a part. The say they do play a part, but can't play a five-fold increase in inattention part. The rest they are saying is due to a deficiency in dopamine itself. Too many transporters plus too little dopamine equals more inattention. Thus the drugs that are being used today, dopamine reuptake inhibitors for the transporters and dopamine releasing agents for the low level of dopamine. Methylphenidate is only an inhibitor which leaves more dopamine around though too, whereas Amphetamine is an inhibitor and a releasing agent.
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Old 06-12-11, 08:36 PM
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Re: High Dopamine Transporter Levels Not Correlated With ADHD

Quantitative inter-subject studies with PET are absurd. I think they used some of their own "reagent" themselves before, during and after this study. Also, there seem to be some astounding ethical lapses in using a class II/should be class I substance. I can't imagine how this paper got published. Shame on you NeuroImage editors! Also, BNL = your tax dollars at play.
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Old 04-04-14, 12:06 AM
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Re: High Dopamine Transporter Levels Not Correlated With ADHD

I think what he was saying is that the reward part of the brain has less dopamine transporters, thus causing people with adhd to get hyper concentrated on things they like, that creats reward. Lower levels of dopamine would be responsible for inattention in that other part of the brain... It makes perfect sence to me and would explain all symptoms of adhd and I'm glad there's someone out there that took the time to do the research, thank you sir, I once read something else posted by you... I like how you describe yourself as quiet but the life of the party. That's my life as well.
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