Brain size and ADHD

This study done by NIMH was reasurring to parents who medicate their kids because it found that stimulants do not make the brains of ADHD kids smaller than kids with ADHD who do not use medication.

You are right. If you are referring to my misinterpretation, the reasons are my layman interpretation plus memory for details is less than it should be.

While ADHD’ers brains are smaller than non-ADHD’er by a small percentage, non-medicated ADHD’er have less white matter than medicated ADHD’ers. White matter helps different parts of the brain communicate with each other and I believe reside mostly in the front part of the brain where it is believed ADHD brain “misfiring” or “non-firing” occurs. (Feel free to correct me here.) According to the second piece of info. below, poorly functioning white matter may be related to dyslexia.

My dd is a remediated dyslexic ADHD’er. While I’m not a scientist and probably both butchering and grossly violating research interpretation rules, I think it is incredibly interesting that 1) the sources are reputable and 2) white matter is a factor in both. It’s too coincidental to me that a disproportionate amount of ADHD’ers also have learning differences like reading problems. If and we don’t know this as linked/proven scientifically, there is the chance my dd may have more/better functioning white matter from med treatment and reading intervention, I would think that is a *good* for her. Somehow/someway, white matter was affected in medicated ADHD’ers - specifically how they need to determine.

Here are the two links of information with some paragraphs copied (exactly) from each:
__________________________________________________________
http://www.nimh.nih.gov/events/pradhdmri.cfm

Brain Shrinkage in ADHD Not Caused by Medications
A 10-year study by National Institute of Mental Health (NIMH) scientists has found that brains of children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) are 3-4 percent smaller than those of children who don’t have the disorder - and that medication treatment is not the cause. Indeed, in this first major study to scan previously never-medicated patients, they found “strikingly smaller” white matter volumes in children who had not taken stimulant drugs. Still, the course of brain development in the ADHD patients paralleled that of normal subjects, suggesting that whatever caused the disorder happened earlier.

As a group, ADHD patients showed 3-4 percent smaller brain volumes, in all regions. The more severe a patient’s ADHD symptoms - as rated by parents and clinicians - the smaller were their frontal lobes, temporal gray matter, caudate nucleus and cerebellum.

While medicated patients’ white matter volume did not differ from that of controls, white matter volume was abnormally small in 49 never medicated patients scanned. These results held up even after the researchers controlled for the fact that the unmedicated children tended to be younger.

Fibers that establish neurons’ long-distance connections between brain regions, white matter normally thickens as a child grows older and represents one gauge of the brain’s maturation. A layer of insulation called myelin progressively envelops these nerve fibers, making them more efficient, just like insulation on electric wires improves their conductivity.

“Children with ADHD are often described as less mature than their peers and this may relate to delays in white matter maturation,” explained Castellanos. “While we do not yet know if medication can accelerate white matter growth, we do know that treating children with medication helps their behavior while they’re taking the drugs. There is no evidence that it helps after they stop.” Animal studies will be required to determine the impact of medication on brain maturation, he added.

Posted: October 08, 2002
___________________________________________________________
And here is the second:

http://www.stanford.edu/dept/news/report/news/march1/dyslexia-31.html

Brain abnormality linked to dyslexia

BY KATHLEEN O’TOOLE

Researchers at Stanford have for the first time found clear evidence that some reading problems are tied to a specific defect in neuron function, according to a report published in the February issue of the journal Neuron.

“We found that adults with reading deficits have an abnormality in white matter of the brain, which is vital for transmitting information between the brain areas involved in language comprehension,” said psychology Professor John Gabrieli, who was the senior researcher on the study team.

The white matter abnormality may indicate that the neuron’s myelin is defective, he said. A neuron sends vital messages in the brain by transmitting electrical signals along an extended appendage called an axon. The axon often is covered with an insulating fatty sheath, known as myelin, that speeds up the transmission of the signals. Myelin is a major constituent of white matter.

In the study, the researchers examined the brains of six adults with a history of dyslexia and 11 adults who had no history of reading difficulties using a new technique involving magnetic resonance imaging. The scanner gauged the cellular structure of the white matter by measuring the microscopic movement of water molecules in the brain. Abnormal water movement indicated faulty white matter, Gabrieli said.

The researchers found that the dyslexic group had poor functioning white matter that may therefore slow message transmission in the regions that are thought to connect the language processing areas of the temporal and frontal lobes of the brain.

“We also found that the level of reading performance of the dyslexic group, as well as the healthy group, related to white matter function,” Gabrieli said. In the dyslexic group the poorest readers had the poorest functioning white matter, and in the healthy group the poorest readers had the poorest functioning white matter.

Yes, that is how I interpreted the study.

I don’t understand the other interpretation.

I think different summaries of that study are misleading.

I could see how you could misinterpret this. Others have as well. It is poorly worded in this summary.

I suggest you read the full report from JAMA.

I try to keep up to date on the research involving neuro plasticity. An enriched environment seems to be the only thing proven (in other animals) to make new neural connections.

It would be nice if medication could do this but it just in not the case.

Maybe someday.

Here is the Medline abstract of the JAMA article:

JAMA 2002 Oct 9;288(14):1740-8 (ISSN: 0098-7484)
Castellanos FX; Lee PP; Sharp W; Jeffries NO; Greenstein DK; Clasen LS; Blumenthal JD; James RS; Ebens CL; Walter
JM; Zijdenbos A; Evans AC; Giedd JN; Rapoport JL
Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
[email protected].
CONTEXT: Various anatomic brain abnormalities have been reported for attention-deficit/hyperactivity disorder
(ADHD), with varying methods, small samples, cross-sectional designs, and without accounting for stimulant drug
exposure. OBJECTIVE: To compare regional brain volumes at initial scan and their change over time in medicated and
previously unmedicated male and female patients with ADHD and healthy controls. DESIGN, SETTING, AND
PARTICIPANTS: Case-control study conducted from 1991-2001 at the National Institute of Mental Health, Bethesda, Md,
of 152 children and adolescents with ADHD (age range, 5-18 years) and 139 age- and sex-matched controls (age
range, 4.5-19 years) recruited from the local community, who contributed 544 anatomic magnetic resonance images.
MAIN OUTCOME MEASURES: Using completely automated methods, initial volumes and prospective age-related
changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes, and caudate nucleus of the
brain were compared in patients and controls. RESULTS: On initial scan, patients with ADHD had significantly smaller
brain volumes in all regions, even after adjustment for significant covariates. This global difference was reflected in
smaller total cerebral volumes (-3.2%, adjusted F(1,280) = 8.30, P =.004) and in significantly smaller cerebellar
volumes (-3.5%, adjusted F(1,280) = 12.29, P =.001). Compared with controls, previously unmedicated children with
ADHD demonstrated significantly smaller total cerebral volumes (overall F(2,288) = 6.65; all pairwise comparisons
Bonferroni corrected, -5.8%; P =.002) and cerebellar volumes (-6.2%, F( 2,288) = 8.97, P<.001). Unmedicated children
with ADHD also exhibited strikingly smaller total white matter volumes (F(2,288) = 11.65) compared with controls
(-10.7%, P<.001) and with medicated children with ADHD (-8.9%, P<.001). Volumetric abnormalities persisted with
age in total and regional cerebral measures (P =.002) and in the cerebellum (P =.003). Caudate nucleus volumes were
initially abnormal for patients with ADHD (P =.05), but diagnostic differences disappeared as caudate volumes
decreased for patients and controls during adolescence. Results were comparable for male and female patients on all
measures. Frontal and temporal gray matter, caudate, and cerebellar volumes correlated significantly with parent-
and clinician-rated severity measures within the ADHD sample (Pearson coefficients between -0.16 and -0.26; all P
values were <.05). CONCLUSIONS: Developmental trajectories for all structures, except caudate, remain roughly
parallel for patients and controls during childhood and adolescence, suggesting that genetic and/or early
environmental influences on brain development in ADHD are fixed, nonprogressive, and unrelated to stimulant
treatment.

Andrea

I’m sure I’d butcher interpretation of that article - if I could get through it.

The study was conducted by NIMH scientists and the text/link was NIMH’s interpretation.

Here is the NIMH press release about the study, which was headed by Castellanos, a very well-respected and highly-credentialed researcher in this field. The press releaseis quite clear that, in this study, the white matter volume observed in children with ADHD who had never been medicated with stimulants was lower than that observed in children with ADHD who had received stimulant treatment, but that both groups showed reduced volume as compared to the control. Castellanos comments that there is no evidence that stimulants harm the brain and postulates that medication might have a positive effect on brain development, but ultimately concludes that we don’t yet know if medication can accellerate white matter growth and that further studies will be required to make that determination.

Andrea

October 8, 2002
CONTACT: Jules Asher
NIMH Press Office
301-443-4536
[email protected]

Brain Shrinkage in ADHD Not Caused by Medications

A 10-year study by National Institute of Mental Health (NIMH) scientists has found that brains of children and adolescents with
Attention Deficit Hyperactivity Disorder (ADHD) are 3-4 percent smaller than those of children who don’t have the disorder - and
that medication treatment is not the cause. Indeed, in this first major study to scan previously never-medicated patients, they found
“strikingly smaller” white matter volumes in children who had not taken stimulant drugs. Still, the course of brain development in the
ADHD patients paralleled that of normal subjects, suggesting that whatever caused the disorder happened earlier.

Drs. Xavier Castellanos, Judith Rapoport, NIMH Child Psychiatry Branch, and colleagues, report on their magnetic resonance
imaging (MRI) study of 152 boys and girls with ADHD in the October 9, 2002 Journal of the American Medical Association.

Affecting 3-5 percent of school-age children, ADHD is characterized by over-activity, distractibility and impulsiveness. The disorder
affects two to three times as many boys as girls, with as many as 20 percent of boys taking stimulant medication in some school
systems. The new study strengthens the validity of the diagnosis by helping to put to rest criticism that structural brain abnormalities
seen in ADHD might be drug-induced.

“There is no evidence that medication harms the brain,” said Castellanos, who conducted the study at NIMH before joining New York
University. “It’s possible that medication may promote brain maturation.” “There is no evidence that medication harms the brain,” said Castellanos, who conducted the study at NIMH before joining New York
University. “It’s possible that medication may promote brain maturation.”

Launched in l991, the study used MRI to scan 89 male and 63 female patients ages 5-18, with ADHD, and 139 age- and
gender-matched controls, children and adolescents without ADHD. Most patients were scanned at least twice, and some up to four
times over the decade.

As a group, ADHD patients showed 3-4 percent smaller brain volumes, in all regions. The more severe a patient’s ADHD symptoms -
as rated by parents and clinicians - the smaller were their frontal lobes, temporal gray matter, caudate nucleus and cerebellum.

While medicated patients’ white matter volume did not differ from that of controls, white matter volume was abnormally small in 49
never medicated patients scanned. These results held up even after the researchers controlled for the fact that the unmedicated
children tended to be younger.

Fibers that establish neurons’ long-distance connections between brain regions, white matter normally thickens as a child grows
older and represents one gauge of the brain’s maturation. A layer of insulation called myelin progressively envelops these nerve
fibers, making them more efficient, just like insulation on electric wires improves their conductivity.

“Children with ADHD are often described as less mature than their peers and this may relate to delays in white matter maturation,”
explained Castellanos. “While we do not yet know if medication can accelerate white matter growth, we do know that treating
children with medication helps their behavior while they’re taking the drugs. There is no evidence that it helps after they stop.” Animal
studies will be required to determine the impact of medication on brain maturation, he added.

In the current study, ADHD patients’ developmental trajectories for nearly all brain regions paralleled growth curves for controls, but
on a slightly lower track. “Fundamental developmental processes active during late childhood and adolescence are essentially
healthy in ADHD,” say the researchers. “Symptoms appear to reflect fixed earlier neurobiological insults or abnormalities.” Evidence
suggests that ADHD runs in families and may have genetic roots.

As might be expected with hyperactive subjects, the investigators had to discard 50 of 594 total scans due to blurring by motion in
the scanner. Volumes of various brain structures and tissue were measured and analyzed by an automated system incorporating
more than 100 networked computer workstations, developed in collaboration with researchers at the Montreal Neurological Institute
(MNI).

While the NIMH group had earlier thought that only certain brain structures were smaller in ADHD, this largest and most
sophisticated study found that the whole brain is affected. It’s possible that a recently discovered gene that determines brain size
could play a role in the disorder, Castellanos suggested. He also suspects that what is now called ADHD may ultimately prove to be
a group of disorders with different causes. To identify these subtypes, he suggests that the field begin studying “endophenotypes,”
factors that may predict the risk of ADHD in the same way that cholesterol predicts the risk of heart disease.

“MRI remains a research tool and cannot be used to diagnose ADHD in any given child, due to normal genetic variation in brain
structure,” noted Rapoport. “The measured influence of ADHD on brain volume can only be discerned statistically across groups of
children with and without the disorder.”

Also participating in the research were: Drs. Patti Lee, Deanna Greenstein, Liv Clasen, Regina James, Jay Giedd, and Wendy Sharp,
Christen Ebens, Jonathan Blumenthal, James Walter, NIMH Child Psychiatry Branch; Dr. Neal Jeffries, National Institute of
Neurological Disorders and Stroke (NINDS); Drs. Alex Zijdenbos, Alan Evans, MNI, McGill University.

This includes some subjective postulation. The official conclusion from the research done as reported in JAMA does not make this conclusion.

Still it is interesting that he postulates this in this article. None of the other sources reporting this that I found stated anything like this.

Yes - to my knowledge learning remediation is the only intervention proven to ‘rewire’ the brain.

I don’t think the NIMH research said that the ADHD meds didn’t affect the white matter volume - just that it wasn’t specifically proven in the study like scientists like to do. That doesn’t mean the opposite assumption - meds don’t help make neural connections - can be made either. So the statement “just not the case” is misleading.

Something affected the white matter volume statistically in that study - and my leap in thinking is that it could be attributable to meds - although yet to be scientfically proven it may be suggestive or a possibility since it was the only variable noted and signifcant.

Now, here I go getting myself into more trouble here. Seperately, studies indicate that the single most effective ADHD intervention is meds, but a combination of whatever interventions (social, learning differences, behavioral) necessary is the most effective. I took that one to heart when I read it - it just makes sense to treat the whole child.

As a mother of an ADHD’er with learning differences, I saw first-hand both what treating the learning differences but not the ADHD did and treating both did. My experience is consistent with the above - a combination of interventions - was the most effective for dd.

Anyway, not looking for contention - just a mother with a vested interest in learning about this. I look forward to more and more research.

Hope I was remotely articulate here.

GL

More than remotely articulate. I just didn’t want anyone believe that if they gave their child meds they would increase their child’s brain size. This was just not the conclusion of this study.

As we always say we need several studies before we can come to any conclusions.
I don’t mean to be argumentative, not in the least.

We need more studies and more information.

…

The research article does state that white matter is significantly smaller in unmediacated children compared to medicated children (all with ADHD). Since there are a number of controls, a reasonable hypothesis is that medication somehow leads to or facilitates white matter growth. I think that is suggested in the original research as well.

It may be that medication–->experiences–->white matter growth as opposed to medication directly leading to white matter growth. Certainly, there is no way to ever tease this out competely.

Beth

I emailed the doctor.

He agreed the results were confusing and that it is ‘possible’ that white matter growth was related to meds.

My issue with those making this a declarative statement. It has not in any way been proven.
I believe, long term animal studies will help to show if neural pathways are being formed with meds or something else is happening, if anything at all is happening.

Castellanos agrees with you. He is quoted as saying such studies will be necessary to determine whether there is a link between meds and white matter growth. Also, one study does not necessarily establish anything, even a well-conducted, long-term study such as the NIMH study. Remember that they were not looking at whether meds caused brain growth. They were looking at whether meds caused brain shrinkage. The differences in white matter volume between medicated and unmedicated kids with ADHD needs to be reproduced in other reliable studies before we can know whether there is a link. There are lots of things that affect brain development and it certainly is a reasonable hypothesis to link white matter growth with meds, but it is only a hypothesis. It cannot yet be said to be a fact.

As a parent whose child takes stimulants, I would be happy to see such a link established. My own observations of my child make me think it is possible. When my son began taking meds he grew by leaps and bounds. Even off the meds, such as on vacations or over the weekend, I see big changes in him. Of course, my son began taking meds at age 9 1/2, and ten years old is a kind of magic age for for most children. (He is now 12.) Often kids make great leaps at 10 because that is the age when the cerebral cortex experiences growth. According to Martha Denckla, at this age many kids with LDs and ADHD may show impressive improvement. Who is to say whether meds, or other interventions, or merely the passage of time made him better? As much as my eyes tell me it was the meds, I am a parent, not a scientific measuing instrument. I look forward to more research on this and other interventions for kids with ADHD.

Andrea

I saw my dd make tremendous strides with academic + med intervention. I would *love* to be able to assess what drove what to what degree. Right now, we know the meds made her ‘available’ for the scientifically ‘proven’ learning interventions. But the med benefits extend well beyond academic interventions. I wouldn’t be surprised either if the link was eventually scientifically proven from what I’ve seen in dd.

OK, more speculation Andrea and consistent with your comments. My dd will be 10 shortly. Her ped neuro similarly told us kids change during the pre-adolescent (10-12) age - many ADHD’ers require med adjustments with some no longer needing them to the degree they once did during this time. The NIMH research said ADHD brain development mirrors the maturation of non-ADHD growth (but probably on a different curve?).

Anyway, it is exciting that dd could potentially “blossom” further with more coming together for her than we see now. It’s different hearing a doctor offer medical explanation/observation versus a mother relaying her child’s ‘magic’ age.

(Linda F - I think Ball was impersonating you on Parenting LD last night. “Your” comments as “LindaF” struck me as uncharacteristic from what I’ve seen of your posts. The entire thread mysteriously disappeared overnight.)

I hardly think it is an established fact, especially from one cross sectional study. As Andrea pointed out, it also was not the point of the study. It is an interesting finding though which will have to be subject to further study. I would hypothesize that if there is a relationship between medication and white matter growth, it is because the medication makes kids more available for other learning rather than because it directly causes white matter growth (unlike, for example, undepressants which seem to directly make people less depressed).

I also don’t think it implies in anyway that those of us whose kids are doing OK without meds should use them. There are other ways to acheive some of the same things—if your child is available enough to learn.

Beth

The board has a new feature, above, to report inappropriate postings, and some of us have been making use of it. If anything is insulting or obscene etc., go ahead and report it.

It seems that our moderator has been wiping off the entire thread when it goes off into arguing about this kind of thing. You may want to request that only the offending post be removed — I haven’t tried it, but why not?

LindaF what part of the brain effects motor function and what types of motor function are you refering to?

Those studies are flawed at best.

Look at the article on ldonline that addresses this study.
It goes into more detail.

Sorry I can’t be of more help.

I completely agree. Perhaps similar white matter growth would happen with IM, just for example. Who knows. I look forward to the research.

Andrea