Neurofeedback for ADHD : Is EEG Biofeedback Treatment Effective for ADHD ?

NIMH Study on Neurofeedback and ADHD

Ed note: See the update below

A recent press release from the National Institute of Mental Health (NIMH) on ADHD and Neurofeedback surprised me. NIMH is funding two research projects on what they term novel and innovative approaches to treating children who have Attention Deficit Hyperactivity Disorder (ADHD), and one of these studies will be focused on EEG Biofeedback (neurofeedback) training.

Attention Deficit Hyperactivity Disorder is a childhood disorder linked with attention problems, impulsivity, and hyperactivity. It is a genetic condition that affects an estimated five percent of U.S. children, although some studies suggest as many as just under nine percent of children are affected. Current diagnostic criteria include the presence of impairing symptoms by age 7, although children may not actually be diagnosed until later, most commonly in the third grade. While the symptoms of hyperactivity generally decrease with age as the brain matures, other symptoms tend to persist, and it is not uncommon for ADHD-associated impairments to continue through the teenage years and into adulthood.

L.Eugene Arnold, M.D., and Nicholas Lofthouse, Ph.D., of The Ohio State University, will lead the study on the use of Neurofeedback, which is also known as EEG biofeedback. Neurofeedback training is an alternative treatment sometimes used to treat ADHD, and other conditions. We offered Neurofeedback training to our patients for a number of years at our practice, and were impressed with how effective it could be with children as young as six or seven years old. The biggest drawback that we saw with EEG biofeedback training was that it took at least twenty session, and often up to forty sessions to make a significant and lasting difference, and that these sessions could be expensive to the family.

The way that eeg biofeedback training works is that the subject is given information about how his or her brain is working at the moment, and the subject uses that information to learn to change and control his own brain waves. The information is often provided in the form of a video game, so that the training is more interesting. The player becomes successful at playing the game by changing his brainwave frequencies to be more optimal for his particular condition. A person with ADHD will be trained to produce more brain waves in the higher frequencies that are associated with focus, and to produce less of the slow brain waves associated with day-dreaming, or even sleep. We have seen the technology successfully used for ADHD, sleep disorders, alcoholism, and anxiety disorders. We have also used the technology with athletes for peak performance training and greater situational awareness.

Studies by Lubar and others have shown the potential value of this treatment, but the medical community, often backed by pharmaceutical dollars, never really bought into it. The medical community typically replied with the demand for double-blind studies, as one would do with pills. But there are many things that do not need to be studied with double-blind studies.

Take for example a study on the effectiveness of weight lifting to increase strength. Would such a study be done with a double-blind protocol? No, of course not. You cannot trick a person into thinking they are lifting weights hard when they are not. Another example would be the relationship between reading and learning. If one were to study the question of whether or not reading can increase learning, the researcher would not be able to look at the effectiveness of reading by use of a double-blind study design. There are no placebos for books, and the subject would know whether he was reading or not. And EEG biofeedback training is similar. Its effectiveness does not need to be studied through a double-blind protocol, as the control group will quickly know that they are being tricked. The control group becomes unnecessary to the researcher, and unmotivated to participate, very quickly. The pharmaceutical companies know this, and the medical community knows this, but this is the argument that they have used to minimize the potential contribution that EEG Biofeedback training could make in the treatment of ADHD.

Unfortunately, or fortunately, a double-blind protocol will be the research design for the Ohio State study.

In the upcoming research project, Dr. Arnold and Dr. Lofthouse will randomly assign 36 children ages six to twelve to receive either EEG neurofeedback in the context of computer games or a placebo EEG treatment. The researchers say that during the placebo treatments the participant will experience pre-programmed game effects that are not affected by his or her brain wave activity, but the reality of it is that it will take about three sessions before everyone in the placebo group knows that they are being tricked. People learn quickly when they are controlling what is taking place on the computer, and when they are not, so the control group part of the study will be a waste of time very soon into the project.

Further, if the study were to use a CPT test, such as the TOVA, to measure changes in performance, there would be no need for a placebo group as these tests have no placebo effect. These tests are not impacted at all by placebos. People either perform better on the tasks or they do not.

But the good news is that by using the double-blind study design, although unnecessary, the study will potentially be published in medical journals where the results will have to be considered by the medical community.

Participants in the neurofeedback treatment group also will be randomly assigned to have either two or three sessions of EEG biofeedback training each week to assess if the frequency of treatment makes any difference on the results. All participants will complete forty training sessions. Parent and teacher rating scales will be used as the measure of improved performance, which is too bad as they are highly subjective.

We certainly wish L.Eugene Arnold, M.D., and Nicholas Lofthouse, Ph.D., of The Ohio State University all the best of success in this project, and believe that they will contribute a great deal of information to the medical community on the effectiveness of EEG Biofeedback training.

If the reader would like to learn more about the effectiveness of Neurofeedback in treating ADHD, consider the study entitled, A Comparison of EEG Biofeedback and Psychostimulants in Treating Attention Deficit/Hyperactivity Disorders, by Thomas P. Rossiter, and Theodore J. La Vaque. It is published in the Journal of Neurotherapy, Summer 1995. Also visit these two websites: the Brian Othmer Foundation at http://brianothmerfoundation.org/scientificarticlehome.html and the EEG Spectrum website at http://eegspectrum.com/Articles/ScientificArticles/ for a more research articles. Finally, Google the keywords: Joel Lubar (he is at the University of Tennessee), Neurofeedback ADHD, or EEG Biofeedback ADHD, for other articles on neurofeedback and adhd.

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Update

2011 Research Results and Updates

The research supported by National Institute of Mental Health Award R34 MH080775 & Award UL1RR025755 from the National Center for Research Resources (OSU Center for Clinical & Translational Science). The research team had free use of SmartBrain NF equip. supplied by CyberLearning Technology, LLC. (Domenic Greco, Ph.D., President). Dr. Greco & Ms. Lindsay Greco trained staff in use of equipment & monitored Tx fidelity. Alan Pope, Ph.D. consulted during study development. I have met the Greco's and Dr. Pope, and all are excellent at what they do.

What is Neurofeedback (NF)? The research team defines Neurofeedback: Trains brain, via classical & operant conditioning, to change its physiological activity to improve performance by providing it w/ real-time video/audio info re its electrical activity (EEG). Rationale for Use: Attempts to modify certain EEG rhythms (brainwaves) thought to be associated w/ ADHD including ↑beta-rhythms, either sensorimotor (12-15 hertz [Hz])

2008 NIMH funding to explore feasibility of a randomized, double-blind, sham controlled pilot trial, & determine optimal session frequency, duration & explore efficacy of NF vs. sham-NF for a larger trial

Importance of Study

According to the authors, about 1/3 of children w/ ADHD don’t fully benefit from optimal established treatments and an unknown proportion won’t even consider most effective Tx (meds), so we need additional Txs.

Maximum benefit evident by 24 Txs as shown on tables/graphs of clinical & neuropsych. outcome variables for 40 Tx

This was a FEASIBILITY NOT AN EFFICACY STUDY looking at practical research issues of NF Tx of pediatric ADHD before applying for funds to examine a larger efficacy study

39 unmedicated 6-12 yr-olds rigorously diagnosed with DSM-IV:TR ADHD

Twice-randomized:
a)Active NF(n>24) vs. sham NF(n>12)
b) 2 vs. 3 X/wk Tx freq (>12 active, >6 sham NF)

40 Tx’s: @ Tx 24choice to stay with initial or change freq

NF = SmartBrain Technology:Sony PS & MS Xbox videogames; Interface modulates input to videogame hand-controller based on EEG

Goal to decrease theta increase beta via single CZ placement (top dead center over the sensory motor strip - a good "general" placement but not targeted to a subject).

34 subjects, or 87%, finished all 40 tx sessions.

Maximum benefit was shown at tx session 24, and was sustained through session 36.

Conclusion:

They successfully ran a study with a control group getting "sham feedback," which opens the door for a comprehensive "double-blind" study on the effectiveness of neurofeedback training. And while the study was not trying to determine the effectiveness of neurofeedback with ADHD, the results do justify spending the money on such as study.

Follow-up:

November, 2010 at the Atlanta CHADD Conference the seminar "EEG Neurofeedback for ADHD: Review of the Science..." was well received by all. Everyone is looking forward to a larger study that involves all of the interested parties from design to conclusions.

Fall, 2010, through Spring, 2011 sees weekly teleconferencing meetings discussing the goals and research design of such as study. The grant application is developed for a large, multi-site rendomized controlled study of neurofeedback training for ADHD in children and teens.

April, 2011 a letter of Intent is sent the NIMH regarding the proposed study.

June, 2011 NIMH response to the LOI

July, 2011 Revisions to LOI

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Task Switching and Attention Deficit Hyperactivity Disorder.

Author/s: Nicholas J. Cepeda Issue: June, 2000

The main goal of the present set of studies was to examine the efficiency of executive control processes and, more specifically, the control processes involved in task set inhibition and preparation to perform a new task in attention deficit hyperactivity disorder (ADHD) and non-ADHD children.

This was accomplished by having ADHD children, both on and off medication, and non-ADHD children perform the task-switching paradigm, which involves the performance of two simple tasks.

In nonswitch trials, an individual task is performed repeatedly for a number of trials. In switch trials, subjects must rapidly and accurately switch from one task to the other, either in a predictable or unpredictable sequence.

Switch costs are calculated by subtracting performance on the nonswitch trials from performance on the switch trials. These costs are assumed to reflect the executive control processes required for the coordination of multiple tasks.

ADHD children showed substantially larger switch costs than non-ADHD children. However, when on medication, the ADHD children's switch performance was equivalent to control children. In addition, medication was observed to improve the ADHD children's ability to inhibit inappropriate responses.

These data are discussed in terms of models of ADHD and cognition.

See the full article here on ADHD and Multi-tasking.

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Brain Scan Studies of ADHD and Stress in Children

As parents of ADHD kids know all too well, children with ADHD often have difficulty handling stress, or stressful situations. Now, a team of researchers in Australia may have found a biological reason why this is so.

ADHD Children Scanned

The researchers studied brain scans of 24 ADHD children (with hyperactivity) and found that the right parietal lobes in children with ADHD did not function as well as in children without ADHD. The right parietal lobes are associated with the development of coping strategies.

Prof Vance, who is based at Melbourne's Royal Children's Hospital, says these children will do anything to feel in control of their situation. They have negative, oppositional ways of relating, for instance, changing the rules of a game endlessly and arguing back. "This discovery has the real potential to improve treatment strategies for ADHD, to enable these children to better manage the demands of their family and school relationships," he said. "It cannot be assumed that ADHD behavior is the fault of bad parenting or lack or discipline."

Further studies into brain regions and key environmental factors are underway to add to this research, published in the journal Molecular Psychiatry.

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Naming Speed Performance and Stimulant Effects Indicate Effortful, Semantic Processing Deficits in Attention-Deficit/Hyperactivity Disorder.

Naming Speed Performance: ADHD, Reading Disorders, and Medications

This study investigated rapid automatized naming and effects of stimulant medication in school-age children with attention-deficit/hyperactivity disorder (ADHD) with and without concurrent reading disorder (RD).

Two ADHD groups (67 ADHD only; 21 ADHD + RD) and a control group of 27 healthy age-matched peers were compared on four variables: color naming speed, letter naming speed, phonologic decoding, and arithmetic computation. Discriminant function analysis (DFA) was conducted to predict group membership. The four variables loaded onto two discriminant functions with good specificity: phonologic decoding, letter naming speed, and arithmetic defined the first function; color naming speed defined the second function.

Both ADHD groups were significantly slower in color naming than controls, but did not differ from one another.

DFA correctly classified 96% of the control group, 91% of ADHD + RD, and 82% of ADHD only.

A subset of children in the ADHD groups participated subsequently in an acute, randomized, place bo-controlled, crossover trial with three single doses (10, 25, 20 mg) of methylphenidate.

Methylphenidate selectively improved color-naming speed but had no effect on the speed of naming letters or digits.

These findings challenge the tenet that naming speed deficits are specific to RD and implicate naming speed deficits associated with effortful semantic processing in ADHD, which are improved but not normalized by stimulant medication.

View this Article on ADHD.

Author/s: Rosemary Tannock Issue: June, 2000
Rosemary Tannock [1,2] Rhonda Martinussen [1] Jan Frijters [1]

Naming Speed Performance: ADHD, Reading Disorders, and Medications

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Behavioral and neuropsychological correlates of hyperactivity and inattention in Brazilian school children

Brito GN, Pereira CC, Santos-Morales TR
Dev Med Child Neurol 1999 Nov;41(11):732-9

Departamento de Pediatria, Instituto Fernandes Figueira, Fundacao Oswaldo Cruz, Brazil.

Attempts at subtyping attention-deficit-hyperactivity disorder (ADHD) along the hyperactivity dimension are considered controversial.

This study addresses this issue by dividing a non-clinical sample of Brazilian children (mean age, 9.4 years; SD, 2.9), who were attending a mainstream school in the Greater Rio de Janeiro area, into four behavioral domain groups (

• normal [NO, N=324],
• hyperactive/impulsive [HI, N=17],
• inattentive [IA, N=48],
• and combined [C, N=13])

on the basis of teacher ratings on an ADHD scale.

The groups did not differ in intellectual level as determined by the Human Figure Drawing test.

Comparisons were made between groups along the factorial dimensions extracted from the Composite Teacher Rating Scale, academic performance and neuropsychological measures were then performed.

Our data showed that IA and C children are less independent and more prone to socialization problems than NO children, and that HI and C children are less anxious and fearful than IA children.

Furthermore, the groups differed in academic and neuropsychological performance.

The results could be considered consistent with the hypothesis that ADD with hyperactivity (ADD/+) and ADD without hyperactivity (ADD/-) represent singular nosological entities.

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by Sonja Mak
European College of Neuropsychopharmacology

Attention deficit/hyperactivity disorder, ADHD, is one of the most common neuropsychiatric disorders of childhood. Worldwide, 3% of children are affected with the disorder. Key symptoms of ADHD include age-inappropriate hyperactive and impulsive behaviour and/or a reduced ability to focus attention. Clinically, three different ADHD subtypes are classified, a primarily inattentive subtype, a primarily hyperactive/impulsive subtype, and a combined subtype in which patients show deficits in both domains. At the level of the brain, small aberrations in both structure and activity of specific brain regions, as well as the connectivity between brain regions have been observed in children and adults with ADHD (Valera et al., 2007; Schneider et al., 2006; Makris et al., 2008; Pavuluri et al., 2009; Broyd et al., 2009).

Although ADHD has classically been viewed as a disorder of children, more than half of the patients carry symptoms, or even the full ADHD-diagnosis, into adulthood (Faraone et al., 2006). The prevalence of ADHD in adults lies between 1% and 4% (Kessler et al., 2006; Polanczyk et al., 2007; Kooij et al., 2005). Adult patients have difficulties in the social, educational and professional fields, such as developing or maintaining stable social relationships, completing educational programmes and holding down jobs. Untreated adults with ADHD often have chaotic life-styles: They may feel that it is impossible to get organised, or remember and keep appointments. Unfortunately, many adults who have the disorder are not aware of this. As symptoms in adults tend to be more varied than symptoms seen in children, health care professionals need to consider a wider range of symptoms when assessing adults for ADHD.

An expert calls "ADHD […] one of the costliest medical conditions in the US", the average loss of income for ADHD adults being $10,000 to $40,000 a year (see also Kessler et al., 2005; Kessler et al., 2006). In addition, patients are at increased risk of comorbidity, including aggression-related disorders and addiction. More than 60% of the adult patients have at least one additional psychiatric diagnosis. Substance abuse disorders are seen in 10% of the patients.

Treatments for ADHD include pharmacotherapy, various types of psychotherapy, education or training, or a combination of treatments. Currently available treatments focus on reducing the symptoms of ADHD and improving social functioning.

High heritability of adult ADHD

Converging evidence from multiple family and twin studies suggests that ADHD aetiology has a robust genetic component. Heritability estimates range from 60% (Biederman & Faraone, 2005). Heritability and genetic load of the adult form of ADHD appears even higher than that in children: whereas a sibling of a child with ADHD has a 3-fold increased risk for ADHD compared to control children, this risk-increase is 17-fold for a sibling of an adult ADHD patient (Faraone et al., 2000).

The high heritability of ADHD is likely due to multiple gene defects, all with a small effect; ADHD belongs to the multifactorial, i.e. complex disorders (Kuntsi et al., 2006). Due to the small effects of individual genetic risk factors, the identification of genes for ADHD has been very difficult. Up to now, only a small number of susceptibility genes have been found (Li et al., 2006; Franke et al., 2009), explaining no more than 5% of the genetic component of the disorder.

IMpACT: the largest clinical ADHD sample worldwide

So far, genetics research in ADHD has focused nearly exclusively on children with the disorder. However, as mentioned above, the genetic load of adults with ADHD is probably higher than that of children, which can facilitate the identification of risk genes for the disorder. Still, the involvement of multiple genes in one single patient, in combination with the small effects of individual genes, makes it necessary to investigate large samples of patients. For this reason, a group of researchers focusing on the genetics of ADHD in adults decided to pool their efforts in the International Multicentre persistent ADHD CollaboraTion, IMpACT.

Formed in 2007 and coordinated by Dr. Barbara Franke, IMpACT has the goal of performing and promoting high quality research in adult ADHD. IMpACT consists of research groups from 5 European countries and 2 groups from the USA. Each group contributes both clinical and genetic expertise to IMpACT. Together, the groups coordinate the largest clinical ADHD sample worldwide, consisting of more than 2700 adult patients and 3500 controls.

In 2008, IMpACT members consolidated their collaboration by starting up several collaborative projects, aimed at meta-analysis of existing genetic data, as well as replication of genetic findings of individual group members in the IMpACT sample. The first of these studies are to be published in 2009 (e.g. Ribases et al., 2009; Sanchez-Mora et al., 2009).

The goals for 2009 include the development of a uniform phenotyping protocol for the IMpACT member sites and the scientific community working on adult ADHD genetics, as well as setting up a combined database of phenotypic and genotypic information of the IMpACT sample.

From 2010, IMpACT will prioritise genome-wide association studies, as well as further genetic and clinical studies on adult ADHD.
Risk genes for ADHD

Meta-analysis of genetic data in IMpACT has, so far, focused mainly on established ADHD genes from studies in children. The gene encoding the dopamine transporter (DAT1), a regulator of signalling through the neurotransmitter dopamine in the brain, has been studied multiple times. Though results have been inconsistent for single genetic variants, a combination of genetic variations at two positions of the gene seems to increase ADHD risk in children. However, in a recent study of 1440 patients and 1769 controls in IMpACT a different combination of variants at the same two positions was found to increase the risk for the persistent, adult form of ADHD. This shows that age is an important factor to be taken into account in genetic association studies in ADHD, and might explain some of the discrepancies between the results of earlier studies (Cormand, Franke et al., presented at the ECNP Congress 2009).

Another strong candidate gene for ADHD, based on pharmacological data analysis of animal models and association studies, is the gene encoding Brain-Derived Neurotrophic Factor (BDNF). Studies investigating association of a genetic variant in this gene in children with ADHD and controls have, however, shown controversial results. In a high-powered association study in 1445 adult ADHD patients and 2247 controls from IMpACT no association between this genetic variant and adult ADHD was found. This confirms that the BDNF variant is not a risk factor for adult ADHD (Ribases et al., presented at the ECNP Congress 2009).

So far, risk genes for ADHD have primarily been derived from animal models and pharmacological studies. Recently, it has become possible to search for such genes on a genome-wide basis, without prior hypotheses about specific candidate pathways. This approach has delivered a first gene for ADHD in children, CDH13, encoding a cell-adhesion gene with a role in early brain development (Lasky-Su et al., 2008; Lesch et al., 2008). A preliminary analysis in IMpACT suggests that this gene also plays a role in the adult form of the disorder (presentation at the ECNP Congress 2009).

Additional genetic analyses, both from earlier candidate-gene research in children and from genome-wide association studies, are currently ongoing within IMpACT. With the adult form of ADHD being the most severe one, the findings of the IMpACT project, focusing on the genetics of ADHD in adults in the largest clinical ADHD sample worldwide, can be expected to guide future research in this challenging field.

Clinical implications
The genetic mechanisms involved in ADHD are being studied with considerable success by several centres worldwide. The International Multicenter persistent ADHD CollaboraTion, IMpACT, with its large sample of adult patients with ADHD, has become an important tool for the (re-)investigation of the role of previously suggested genetic risk factors for ADHD, and the mechanisms leading from gene to disease.

The large IMpACT sample will facilitate the identification of new genes for ADHD. For this reason, a genome-wide search for new risk genes should be carried out in this sample.

The findings of IMpACT will help to identify targets for the development of new and more effective treatments for ADHD.

In addition, these findings may contribute to the prediction of persistence of the disorder already in children, supporting disease prevention.
Conclusion

Attention deficit/hyperactivity disorder (ADHD) is not merely a child-psychiatric disorder that persists into young adulthood, but an important and unique manifestation of psychopathology across the lifespan (Kooij et al., 2005).

The majority of patients affected by ADHD in childhood carry ADHD symptoms, or even the full ADHD-diagnosis, into adulthood. Since adult ADHD is associated with social and professional problems and, consequently, considerable costs, efforts are needed to increase the detection and treatment of adult ADHD.

The recent expansion of knowledge in genetics, brain imaging, and behavioural research is leading to a better understanding of the causes of ADHD, and paving the way for strategies for the development of more effective treatments for all age groups affected by this disorder and the prevention of the progression of disease into adulthood.

Major breakthroughs are expected from the currently ongoing International Multicenter persistent ADHD CollaboraTion (IMpACT), which is investigating the largest clinical ADHD sample worldwide.

The identification of genetic risk factors for ADHD will help to identify targets for new and improved treatments for ADHD, and contribute to early disease prevention.

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References
Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet 2005;366:237-248

Broyd SJ, Demanuele C, Debener S, et al. Default-mode brain dysfunction in mental disorders: a systematic review. Neurosci Biobehav Rev 2009;33: 279-296

Faraone SV, Biederman J, Mick E. The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med 2006;36:159-165

Faraone SV, Biederman J, Monuteaux MC. Toward guidelines for pedigree selection in genetic studies of attention deficit hyperactivity disorder. Genet Epidemiol 2000;18:1-16

Franke B., Neale B., Faraone S.V. Genome-wide association studies in ADHD. Hum. Genet. 2009 Apr 22. [Epub ahead of print]

Kessler RC, Adler L, Ames M, et al. The prevalence and effects of adult attention deficit/hyperactivity disorder on work performance in a nationally representative sample of workers. J Occup Environ Med 2005;47:565-572

Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006;163:716-723

Kooij JJ, Buitelaar JK, van den Oord EJ, et al. Internal and external validity of attention-deficit hyperactivity disorder in a population-based sample of adults. Psychol Med 2005;35:817-827

Kuntsi J, Neale BM, Chen W, et al. The IMAGE project: methodological issues for the molecular genetic analysis of ADHD. Behav Brain Funct 2006;2:27

Lasky-Su J, Neale BM, Franke B, Anney RJ, et al. Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. Am J Med Genet B Neuropsychiatr Genet 2008;147B: 1345-1354

Lesch KP, Timmesfeld N, Renner TJ, et al. Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. J Neural Transm 2008;115:1573-1585

Li D, Sham PC, Owen MJ, He L. Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). Hum Mol Genet 2006;15:2276-2284

Makris N, Buka SL, Biederman J, et al. Attention and executive systems abnormalities in adults with childhood ADHD: A DT-MRI study of connections. Cereb Cortex 2008;18:1210-1220

Pavuluri MN, Yang S, Kamineni K, et al. Diffusion tensor imaging study of white matter fiber tracts in pediatric bipolar disorder and attention-deficit/hyperactivity disorder. Biol Psychiatry 2009;65:586-593

Polanczyk G, de Lima MS, Horta BL, et al. The worldwide prevalence of ADHD: a systematic review and meta-regression analysis. Am J Psychiatry 2007;164:942-948

Ribasés M, Bosch R, Hervás R, Ramos-Quiroga JA, Sánchez-Mora C, Bielsa C, Gastaminza X, Guijarro-Domingo S, Nogueira M, Gómez-Barros N, Kreiker S, Groß-Lesch S, Jacob CP, Lesch KP, Reif A, Johansson S, von Plessen K, Knappskog PM, Haavik J, Estivill X, Casas M, Bayés M, Cormand B. Biological Psychiatry, in press

Sánchez-Mora C, Ribasés M, Ramos-Quiroga JA, Casas M, Bosch R, Boreatti-Hümmer A, Heine M, Jacob CP, Lesch K-P, Fasmer OB, Knappskog PM, Kooij JJS, Kan C, Buitelaar JK, Mick E, Asherson P, Faraone SV, Franke B, Johansson S, Haavik J, Reif A, Bayés M, Cormand B. Meta-analysis of the brain-derived neurotrophic factor p.Val66Met in adult ADHD in four European populations. Am J Med Genet B Neuropsychiatr Genet., in press.

Schneider M, Retz W, Coogan A, Thome J, Rosler M. Anatomical and functional brain imaging in adult attention-deficit/hyperactivity disorder (ADHD) - a neurological view. Eur Arch Psychiatry Clin Neurosci 2006;256(Suppl 1):i32-i41

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Source:
Sonja Mak
European College of Neuropsychopharmacology http://www.ecnp.eu/emc.asp
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Tuning major gene variants conditioning human behavior: the anachronism of ADHD.

New findings suggest that attention deficit and hyperactivity disorder (ADHD) is the most common behavioral variant associated with a mental condition.

ADHD prevalence reaches figures of 18% in populations worldwide. Furthermore, genetic variants conferring susceptibility to develop ADHD are not rare but very frequent and eventually totally fixed in some populations.

These patterns of evolution can be associated with the fact that this behavioral trait had provided selective advantage. However, this behavioral trait is now under scrutiny because of new emerging social necessities.

Recent molecular and clinical evidence supports Thom Hartmann's Hunter-Farmer theory, reaffirming that ADHD might be an anachronic behavioral trait.

PMID: 17467976 [PubMed - as supplied by publisher]

* Arcos-Burgos M,
* Acosta MT.

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD

Advantages to ADHD : genetics

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Cerebrospinal fluid monoamine metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents.

Arch Gen Psychiatry 1990 May;47(5):419-26
Kruesi MJ, Rapoport JL, Hamburger S, Hibbs E, Potter WZ, Lenane M, Brown GL

National Institute of Mental Health, Child Psychiatry Branch, Bethesda, MD 20892.

Cerebrospinal Fluid 5-hydroxyindoleacetic Acid Levels in ADHD

Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid, a metabolite of serotonin, were measured in relation to aggression, impulsivity, and social functioning in 29 children and adolescents with disruptive behavior disorders.

The cerebrospinal fluid 5-hydroxyindoleacetic acid level was low compared with that of age-, sex-, and race-matched patients with obsessive-compulsive disorder.

Within the disruptive group, significant negative correlations with age-corrected 5-hydroxyindoleacetic acid level were seen for the child's report of aggression toward people and the expressed emotionality of the child toward his or her mother; other correlations of age-corrected 5-hydroxyindoleacetic acid level with measures of aggression were in the expected negative direction but did not reach statistical significance.

Impulsivity per se and socioenvironmental factors were not significantly related to cerebrospinal fluid 5-hydroxyindoleacetic acid concentration.

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Depressed Dopamine Activity in Caudate and Preliminary Evidence of Limbic Involvement in Adults With ADHD

ABSTRACT

Context Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder of childhood. There is considerable evidence that brain dopamine is involved in ADHD, but it is unclear whether dopamine activity is enhanced or depressed.

Objective To test the hypotheses that striatal dopamine activity is depressed in ADHD and that this contributes to symptoms of inattention.

Design Clinical (ADHD adult) and comparison (healthy control) subjects were scanned with positron emission tomography and raclopride labeled with carbon 11 (D2/D3 receptor radioligand sensitive to competition with endogenous dopamine) after placebo and after intravenous methylphenidate hydrochloride (stimulant that increases extracellular dopamine by blocking dopamine transporters). The difference in [11C]raclopride's specific binding between placebo and methylphenidate was used as marker of dopamine release. Symptoms were quantified using the Conners Adult ADHD Rating Scales.

Setting Outpatient setting.

Participants Nineteen adults with ADHD who had never received medication and 24 healthy controls.

Results With the placebo, D2/D3 receptor availability in left caudate was lower (P

Conclusions This study reveals depressed dopamine activity in caudate and preliminary evidence in limbic regions in adults with ADHD that was associated with inattention and with enhanced reinforcing responses to intravenous methylphenidate. This suggests that dopamine dysfunction is involved with symptoms of inattention but may also contribute to substance abuse comorbidity in ADHD.

Thank you to the Archives of General Psychiatry, August 2007. This is the Abstract. The entire article is made free to readers online at http://archpsyc.ama-assn.org/cgi/content/full/64/8/932

Nora D. Volkow, MD; Gene-Jack Wang, MD; Jeffrey Newcorn, MD; Frank Telang, MD; Mary V. Solanto, PhD; Joanna S. Fowler, PhD; Jean Logan, PhD; Yeming Ma, PhD; Kurt Schulz, PhD; Kith Pradhan, MS; Christopher Wong, MS; James M. Swanson, PhD

Arch Gen Psychiatry. 2007;64:932-940.

title: Depressed Dopamine Activity in Caudate and Preliminary Evidence of Limbic Involvement in Adults With ADHD

Back to "ADHD Research" index

Establishing an EEG Norm-Base for ADD v. non-ADD

Review of a journal article by Troy Janzen, Ken Graap, Stephan Stephanson, Wilma Marshall, and George Fitzsimmons
"Differences in Baseline EEG Measures for ADD and Normally Achieving Preadolescent Males"
Biofeedback and Self-Regulation, Vol. 20, No. 1, 1995, pp. 65-82.

Three well known tests (WISC-R, WRMT-R, WRAT-R) were administered to all subjects prior to the main part of the study, a series of cognitive tests performed while connected to a 19 lead EEG cap.

Findings: The most consistent finding was that ADD subjects have significantly higher theta amplitudes (p

The authors conclude that although the number of subjects was small, there were significant differences that could be observed. These findings form a starter set of data for additional efforts. Establishing an EEG Norm-Base for ADHD

We have several ADHD research studies on the functional neurology of ADHD, or how the brain of a person with ADHD functions differently than the brain of a person without ADHD. We have moved them all "up" into the main "research section" of the ADHD Information Library

Advances in genetic findings on attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common, childhood-onset neurodevelopmental disorder with adverse consequences during adult life. Family, twin and adoption studies show that genetic factors contribute to the aetiology of ADHD and that environmental factors also play a role. Family and twin studies have shown the importance of genetic influences on continuity in ADHD over time and in accounting for the co-occurrence of ADHD and conduct disorder problems.

In meta-analyses of molecular genetic studies, the 48-bp variable number tandem repeat (VNTR) variant in the dopamine D4 gene and the CA(n) microsatellite marker in the D5 receptor gene have been found to be repeatedly associated with ADHD.

Results from meta-analyses of the 480-bp VNTR in the dopamine transporter gene are mixed.

Several genetic studies have also identified genetic variants that are related to specific clinical and developmental features of ADHD.

In the next few years, a new generation of much larger-scale genetic studies should lead to the identification of further ADHD susceptibility genes. Such studies will also need to be integrated with other areas of neuroscience, clinical and epidemiological research to investigate how specific gene variants exert risk effects, interact with environmental factors and enable identification of the underlying causal mechanisms that lead to ADHD.

* Thapar A,
* Langley K,
* Owen MJ,
* O'donovan MC.

Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK.

PMID: 17506925 [PubMed - as supplied by publisher]
Genetics : Recent Findings on ADHD

Understanding comorbidity: A twin study of reading disability and attention-deficit/hyperactivity disorder.

A community sample of twins in which at least one member of each pair exhibited significant reading difficulties (99 monozygotic and 80 dizygotic pairs) or symptoms of attention-deficit/hyperactivity disorder (ADHD; 83 monozygotic and 78 dizygotic pairs) was used to test the etiology of comorbidity between reading disability (RD) and ADHD.

Univariate analyses revealed moderate to high heritability for all measures of reading difficulty and ADHD.

Subsequent bivariate analyses indicated that the relation between reading difficulties and inattention symptoms is primarily attributable to common genetic influences, whereas bivariate heritability estimates were not significant for hyperactivity-impulsivity and any of the reading measures.

Reading difficulties and ADHD symptoms were more highly heritable if the proband met criteria for both disorders versus RD or ADHD alone, suggesting that future molecular genetic analyses of comorbid RD + ADHD may facilitate the identification of susceptibility genes for RD, ADHD, and their comorbidity. (c) 2007 Wiley-Liss, Inc.

* Willcutt EG,
* Pennington BF,
* Olson RK,
* Defries JC.

University of Colorado at Boulder, Boulder, Colorado.

PMID: 17440942 [PubMed - as supplied by publisher]
Genetics Twin Study: ADHD and Reading Problems

Studies Examine Genetic Determinants of ADHD

ADHD Genetics. A special issue of American Journal of Medical Genetics (AJMG): Part B: Neuropsychiatric Genetics presents a comprehensive overview of the latest progress in genetic research of Attention Deficit/Hyperactivity Disorder (ADHD). The issue covers major trends in the field of complex psychiatric genetics, underscoring how genetic studies of ADHD have evolved, and what approaches are needed to uncover its genetic origins.

Press Release from Wiley, Boston, Mass. – January 07, 2009

ADHD is a complex condition with environmental and genetic causes. It is characterized by developmentally inappropriate levels of inattention, hyperactivity and impulsivity that has an onset in childhood. It is one of the most common psychiatric diseases, affecting between 8-12 percent of children worldwide. The drugs used to treat ADHD are highly effective, making ADHD one of the most treatable psychiatric disorders. However, despite the high efficacy of ADHD medications, these treatments are not curative and leave patients with residual disability. Because ADHD is also has one of the most heritable of psychiatric disorders, researchers have been searching for genes that underlie the disorder in the hopes that gene discovery will lead to better treatments for the disorder.

Among the many studies in the issue are two from the first genomewide association study of individual ADHD patients. The study examined more than 600,000 genetic markers in over 900 families from the largest genetic study of ADHD, the International ADHD Multicenter Genetics (IMAGE) project led by Stephen V. Faraone of SUNY Upstate Medical Center. The authors have made these data publicly available to researchers who are interested in pursuing further studies.

[Ed. note: Dr. Faraone has published about 200 research papers on ADHD, and is one of the most respected and cited researchers of ADHD and its genetic factors in the world.]

The studies found that one genetic marker may be associated with ADHD symptoms. The studies, suggests that many genes are involved in ADHD and that each of these have small effects. Thus, larger studies are needed to fully understand the genetic mechanisms underlying ADHD and whether these initial findings can be confirmed.

Another study, also led by Dr. Faraone, is the first genome-wide study of response to methylphenidate in ADHD children. Dr. Faraone and his colleagues, examined genetic markers across the entire human genome to search for genes that may someday be used to predict which children respond most favorably to the stimulant medications used to treat ADHD. It demonstrated that, although there are likely to be genetic factors that are associated with stimulant efficacy in children with ADHD, there are no single genes with a very large impact on treatment response.

“Previous efforts at understanding the role of candidate genes in the response to pharmacotherapy have been inconclusive,” says Eric Mick, the study’s first author. “There is a great need for larger more rigorous studies of genetic predictors of treatment response.”

Research was conducted, in part, through the Genetics Analysis Information Network (GAIN), a public-private partnership between the National Institutes of Health and the private sector with the goal of promoting genome mapping for various complex diseases.

Recent advances in these technologies have facilitated the cost-effective genotyping of hundreds of thousands of DNA markers. Genome-wide association studies (GWAS) hold great promise for identifying genetic variants for disease. GWAS have already been successful in identifying variants associated with many complex diseases including obesity, age-related macular degeneration, Type I and Type II diabetes, Crohn's disease and prostate cancer.

These studies are published in the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. Media wishing to receive a PDF copies of these articles may contact journalnews@bos.blackwellpublishing.net.

The first and senior authors of these papers are:

Eric Mick, the Director of Research for the Clinical and Research Program of Pediatric Psychopharmacology and Adult ADHD in the department of psychiatric at Massachusetts General Hospital. He can be reached for questions by contacting Sue McGreevey at (617) 724-2764 or smcgreevey@partners.org.

Jessica Lasky-Su, an Instructor at Channing Laboratories, Brigham and Women's Hospital and Harvard Medical School. She can be reached for questions by contacting Jessica Podlaski at (617) 534-1603.

Benjamin M. Neale, a visiting student at Massachusetts General Hospital; Broad Institute of Harvard and MIT; and the Institute of Psychiatry, King’s College London. He can be reached for questions by contacting Sue McGreevey at (617) 724-2764 or smcgreevey@partners.org.

Stephen V. Faraone is a Professor in the Departments of Psychiatry and Neuroscience & Physiology at SUNY Upstate Medical University and Director of Medical Genetics Research for the University. He can be reached for questions at faraones@upstate.edu.

Neuropsychiatric Genetics, Part B of the American Journal of Medical Genetics (AJMG), provides a forum for experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders. It is a resource for novel genetics studies of the heritable nature of psychiatric and other nervous system disorders, characterized at the molecular, cellular or behavior levels. Neuropsychiatric Genetics publishes eight times per year.

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Adoptive and Biological Families of Children and Adolescents With ADHD.

Objective: Using an adoption study design, the authors addressed the issue of genetics in attention-deficit hyperactivity disorder (ADHD).

Method: This study examined the rates of ADHD and associated disorders in the first-degree adoptive relatives of 25 adopted probands with ADHD and compared them with those of the first-degree biological relatives of 101 nonadopted probands with ADHD and 50 nonadopted, non-ADHD control probands.

Results: Six percent of the adoptive parents of adopted ADHD probands had ADHD compared with 18% of the biological parents of nonadopted ADHD probands and 3% of the biological parents of the control probands.

Conclusion: Results of this study lend support to the hypothesis that ADHD has a genetic component. J. Am. Acad. Child Adolesc. Psychiatry, 2000, 39(11):1432-1437. Key Words: adoption, attention-deficit hyperactivity disorder, family study.

Author/s: Susan Sprich
Issue: Nov, 2000

Etiology of Inattention and Hyperactivity/impulsivity in a Community Sample of Twins with Learning Difficulties.

A community sample of 373 8 to 18 year-old twin pairs in which at least one twin in each pair exhibited a history of learning difficulties was utilized to examine the etiology of inattention and hyperactivity/impulsivity (hyp/imp).

Symptoms of attention-deficit/hyperactivity disorder (ADHD) were assessed by the DSM-III Diagnostic Interview for Children and Adolescents. Inattention and hyp/imp composite scores were created based on results of a factor analysis.

Results indicated that extreme ADHD scores were almost entirely attributable to genetic influences across several increasingly extreme diagnostic cutoff scores.

Extreme inattention scores were also highly heritable whether or not the proband exhibited extreme hyp/imp.

In contrast, the heritability of extreme hyp/imp increased as a linear function of the number of inattention symptoms exhibited by the proband.

This finding suggests that extreme hyp/imp may be attributable to different etiological influences in individuals with and without extreme inatten tion. If this result can be replicated in other samples, it would provide evidence that the hyp/imp symptoms exhibited by individuals with Combined Type ADHD and Predominantly Hyp/Imp Type ADHD may be attributable to different etiological influences.

Author/s: Erik G. Willcutt
Issue: April, 2000

Erik G. Willcutt [1,3] Bruce F. Pennington [2] John C. DeFries [1]

http://www.findarticles.com/ articles on inattention, hyperactivity, impulsivity in ADHD

Genetics of Childhood Disorders: XX. ADHD

Is ADHD Genetically Heterogeneous?

Reviews of the literature leave no doubt that genes influence the etiology of attention-deficit/hyperactivity disorder (ADHD) (Faraone et al., 1998). Notably, twin studies show the heritability of ADHD to be about 0.80, indicating that the effect of genes is substantial.

These genetic epidemiological studies have motivated molecular genetic studies of ADHD that have produced intriguing but conflicting results (Faraone and Biederman, 1998).

Researchers have focused on genes in dopamine pathways because animal models, theoretical considerations, and the effectiveness of stimulant treatment implicate dopaminergic dysfunction in the pathophysiology of the disorder.

Two genes that have been intensively studied are the dopamine transporter gene (DAT) and the dopamine D4 receptor gene (DRD4). Some studies of these genes strongly suggest that they influence susceptibility to ADHD. There are, however, several negative studies for each gene.

The inconsistent results from molecular genetic studies could mean that rather than being a unitary disorder, ADHD comprises several disorders having different genetic and nongenetic etiologies.

Author/s: Stephen V. Faraone
Issue: Nov, 2000

Review of Neuroimaging Studies of Child and Adolescent Psychiatric Disorders From the Past 10 Years.

Objectives: To review recent neuroimaging studies of serious emotional disorders in youth and identify problems and promise of neuroimaging in clinical practice.

Method: Published reports from refereed journals are briefly described, critiqued, and synthesized into a summary of the findings to date.

Results:

• Childhood-onset schizophrenia shows progressive ventricular enlargement, reduction in total brain and thalamus volume, changes in temporal lobe structures, and reductions in frontal metabolism.
• Autistic disorder is associated with cerebellar changes, greater total brain and lateral ventricle volume, and asymmetry.
• The prefrontal cortex and the basal ganglia are consistently reported as abnormal in attention-deficit/hyperactivity disorder.
• Patients with anorexia nervosa show enlarged CSF spaces and reductions in gray and white matter that are only partially reversible with weight recovery.

Conclusions: Results from neuroimaging studies of childhood-onset psychiatric disorders suggest consistency in the structures found to be abnormal, but inconsistencies in the nature of these abnormalities. Although neuroimaging technology holds great promise for neurodevelopmental research, it is not yet a diagnostic instrument.

J. Am. Acad. Child Adolesc. Psychiatry 2000, 39(7):815-828.
(Statistical Data Included)

Author/s: Robert L. Hendren
Issue: July, 2000

ABSTRACT

ADD ADHD Neuropsychological deficits in adolescent-onset schizophrenia compared with attention deficit hyperactivity disorder.

OBJECTIVE: Impaired neuropsychological performance involving abstraction-flexibility, memory, motor function, and attention has frequently been reported in schizophrenia as well as in attention deficit hyperactivity disorder (ADHD).

This study represents an attempt to compare groups of adolescents with schizophrenia and ADHD on a comprehensive neuropsychological test battery. Such a comparison affords the opportunity to ascertain differences in the degree, profile, and specificity of impairments.

Am J Psychiatry 1999 Aug;156(8):1216-22
Oie M, Rund BR
National Centre for Child and Adolescent Psychiatry, University of Oslo, Norway.

Schizophrenia vs ADHD

Neuropsychological functioning of adults with attention deficit hyperactivity disorder.

The neuropsychological functioning of adults with Attention Deficit Hyperactivity Disorder (ADHD) was compared to that of healthy controls and individuals with mild psychiatric disorders including attentional complaints.

Thirty adults in each group were examined on the Conners' Continuous Performance Test (CPT) and measures of attention, executive function, psychomotor speed, and arithmetic skills.

The ADHD group performed lower than healthy controls on most measures.

However when compared to the psychiatric group, the performances of the ADHD group were not significantly lower on any of the measures.

J Clin Exp Neuropsychol 2000 Feb;22(1):115-24
Walker AJ, Shores EA, Trollor JN, Lee T, Sachdev PS
Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia.

Reduction of (3H)-imipramine binding sites on platelets of conduct-disordered children.

Neuropsychopharmacology 1987 Dec;1(1):55-62
Stoff DM, Pollock L, Vitiello B, Behar D, Bridger WH

Medical College of Pennsylvania, Eastern Pennsylvania Psychiatric Institute, Department of Psychiatry, Philadelphia.

Binding characteristics of tritiated imipramine on blood platelets were determined in daytime hospitalized prepubertal children who had mixed diagnoses of conduct disorder (CD) plus attention deficit disorder hyperactivity (ADHD) and in inpatient adolescents who had a history of aggressive behavior.

Physiological Differences in Conduct Disorder Children

The number of (3H)-imipramine maximal binding sites (Bmax) was significantly lower in the prepubertal patient group of CD plus ADDH; the dissociation constant (Kd) was not significantly different.

There were significant negative correlations between Bmax and the Externalizing or Aggressive factors of the Child Behavior Checklist when the CD plus ADDH prepubertal patients were combined with their matched controls and within the adolescent inpatient group.

We propose that a decreased platelet imipramine binding Bmax value, as an index of disturbed presynaptic serotonergic activity, is not specific to depression and may be used as a biologic marker for the lack of behavioral constraint in heterogeneous. populations of psychiatric patients.

Conduct Disorder Children

Attentional difficulties in hyperactive and conduct-disordered children: a processing deficit.

A random population sample of 1479 Chinese boys from Hong Kong was screened and diagnosed in a two-stage epidemiological study. Four groups, age 7-8, were distinguished: (1) a pure hyperactive group (HA), (2) a mixed hyperactive/conduct-disordered group (HA+CD), (3) a pure conduct-disordered group (CD), and (4) a normal control group (N).

On a visual search task, only the pure hyperactive (HA) children showed a specific processing deficit in performance.

• This confirms the diagnostic value of such a deficit for hyperactivity, differentiating it from conduct disorder.
• The failure to find a similar deficit in the HA+CD group raises questions concerning the clinical identity of these children.

Each group showed a performance decrement over time in the visual search task but the decrement did not differ between the four groups. This observation is not congruent with the reports of a short attention span in hyperactive children; explanations of this apparent contradiction are considered.

J Child Psychol Psychiatry 1994 Oct;35(7):1229-45
Leung PW, Connolly KJ
Department of Psychology,
Chinese University of Hong Kong, Shatin, New Territories.

Quantitative EEG and Auditory Event-Related Potentials in the Evaluation of Attention-Deficit/Hyperactivity Disorder: Effects of Methylphenidate and Implications for Neurofeedback Training

J. F. Lubar, M. O. Swartwood, J. N. Swartwood, D. L. Timmermann
University of Tennessee

Neurophysiological correlates of Attention Deficit Disorder with and without Hyperactivity (ADHD) and effects of methylphenidate are explored using electroencephalographic (EEG) and auditory eventrelated potentials (ERPs).

In the first of four studies, a database of ADHD individuals of varying ages and matched adolescent/adult controls is presented.

Study 2 compares controls and age-matched children with ADD, and children with ADHD on and off methylphenidate.

Study 3 examines habituation of the auditory ERPs of controls and children with ADHD both on and off methylphenidate.

The relationship between successful neurofeedback training and EEG changes is presented in Study 4.

Overall, these studies support a neurologic basis for ADHD and raise questions regarding the role of methylphenidate in modulating cortical processing.

Several important and controversial studies have been published in the past few months on ADHD, making the summer research reading all the more fun. Here are summaries of two summer studies for you:

August, 2007

Depressed Dopamine Activity in Caudate and Preliminary Evidence of Limbic Involvement in Adults With ADHD

Some very impressive researchers were involved in this study on ADHD, dopamine, and substance abuse. The researchers included Dr. Nora Volkow who is the Director of the National Institute on Drug Abuse, and Dr. James Swanson from U.C. Irvine. I’ve been a fan of Dr. Swanson’s work on ADHD treatment for many years.

This study concludes that ADHD is a real disease (ed. note: and not just something made up by drug companies to sell meds). ADHD is biologically caused and that dopamine production in individuals with ADHD is decreased, and that Ritalin increases dopamine production.

None of this is particularly new news, but the study is helpful to support this position, which we have held for about twenty years.

The study also reports that because of the lower dopamine levels in ADHD individuals there is a greater risk in the ADHD population for drug abuse, as “drugs of abuse increase dopamine brain function…”

The abstract of the article is available at the ADHD Information Library at http://newideas.net/adhd/adhd_research_5 .

Thank you to the Archives of General Psychiatry, August 2007.
The entire article is made free to readers online at
http://archpsyc.ama-assn.org/cgi/content/full/64/8/932

August, 2007

Gene Predicts Better Outcome as Cortex Normalizes in Teens with ADHD

The lead researcher in this study was Dr Philip Shaw from the NIMH Child Psychiatry Branch. He is an expert researcher on the human brain, especially children’s brains, and researches the structural brain differences in conditions as Schizophrenia and ADHD. Dr. Judith Rapoport was also involved in the study, and she is a long-time researcher in ADHD.

This study showed that there were structural differences in the brains of ADHD children, specifically that the brain areas that control paying attention were thinner in children with ADHD, especially those who carried a particular version of a gene. The good news was that for these particular children, as they reached adolescence, the right side of the cortex normalized in thickness, and performance improved.

So this study is both interested in the genetics of ADHD, and the structural differences in the ADHD brain (vs. non-ADHD). The study is available in full, thanks to the NIMH, at the ADHD Information Library.

There are several more studies from this summer that we will try to summarize for you in the next week or two.

Researcher see flaws in brain-imaging studies

Insight on the News, August 19, 2003
by Kelly Patricia O'Meara

A recent review by Jonathan Leo, professor of anatomy at the Western University of Health Sciences in Pomona, Calif., and professor David Cohen of the School of Social Work at Florida International University in Miami, dispels the myth of brain imaging as a way to diagnose ADHD. And it finds that the majority of studies dating back to 1978 failed, unaccountably, to consider a major variable the use of psychotropic drugs by participants in the studies.

ED: What's interesting is that MRI, PET scans, and other imaging technologies are never used in the diagnosis of ADHD, only in research on potential causes or structural differences. So why the authors should be dispelling "the myths of brain imaging as a way to diagnose ADHD" is beyond us, since they are not used this way."

Leo and Cohen's review, entitled "Broken Brains or Flawed Studies? A Critical Review of ADHD Neuroimaging Research," was published last month in the Journal of Mind and Behavior and looked at 33 of the most recent studies using computerized topography, magnetic resonance imaging (MRI), single photon emission computerized topography or positron emission topography on ADHD-diagnosed subjects.

Although 14 scientists contributed to the study, it is generally referred to as the "Castellanos study" after the lead scientist, child psychiatrist F. Xavier Castellanos. Ten years in the making and unknown millions spent, Castellanos and his team conducted 544 MRI scans of 291 subjects 152 ADHD-diagnosed patients and 139 control subjects (normal). The Castellanos results were that "on initial scan, patients with ADHD had significantly smaller brain volumes in all regions, even after adjustment for significant covariates."

The celebrated doctor further concluded that "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, not progressive and unrelated to stimulant treatment." In other words, kids diagnosed with ADHD had smaller brains than those kids in the "normal" control group, and brain size isn't due to drug use.

Read this article in full...

Effects of reward and response cost on response inhibition in AD/HD, disruptive, anxious, and normal children.

Author/s: Jaap Oosterlaan
Issue: June, 1998

Attention deficit/hyperactivity disorder (AD/HD) has been conceptualized as a disorder which arises from a deficit in the capability for response inhibition (e.g., Barkley, 1994, 1997; Douglas, 1989; Newman & Wallace, 1993; Pennington & Ozonoff, 1996; Quay, 1988a, 1988b, 1997; Wender, 1972). That is, a failure to suppress inappropriate responding has been postulated to underlie the inattentive, hyperactive, and impulsive behavior that characterizes AD/HD.

Recently, however, the primacy of the response inhibition deficit has been called into question (e.g., Sonuga-Barke, 1995). That is, the possibility exists that the impairment in response inhibition in fact is only one aspect of a more general dysfunction. For example, it has been suggested that poor response inhibition originates from a frontal lobe deficit (Barkley et al., 1992; Pennington & Ozonoff, 1996; Shue & Douglas, 1992) or a lag in the development of the cognitive functions (Barkley, 1997; Barkley et al., 1992; Shue & Douglas, 1992). In the present study, we examine the possibility that poor response inhibition in AD/HD children actually is one of the many manifestations of a disinclination to invest effort, or stated differently, reflects a motivational deficit.

Different lines of research seem to converge in indicating that AD/HD children do not have the same motivational set as normal children. One line of research, aimed at localizing possible deficits in the information processing system, suggests that AD/HD children do not expend the effort necessary to perform optimally (see for reviews, Sergeant & Van der Meere, 1990a, 1990b, 1994; Van der Meere, 1996).

A second line of research suggests that the performance of AD/HD children seems to rely more strongly on the presence of contingencies than the performance of normal children (e.g., Douglas, 1985, 1989; Haenlein & Caul, 1987; Newman & Wallace, 1993; Quay, 1988a, 1988b, 1997; Wender, 1972). Reward and Response Cost in ADHD

Using MRI to Examine Brain-Behavior Relationships in Males With Attention Deficit Disorder With Hyperactivity.

Objective: The relationship between neuropsychological measures of inhibition and sustained attention and structural brain differences in the regions of the caudate and the frontal region was examined in males with attention deficit disorder with hyperactivity (ADHD).

Children with ADHD were found to have reversed asymmetry of the head of the caudate, smaller volume of the left caudate head, and smaller volume of the white matter of the right frontal lobe.

Children with ADHD were found to score more poorly on measures of inhibition and sustained attention but not on measures of IQ, achievement, or motor speed.

Comparison of neuropsychological measures and brain structure measures indicated a significant relationship between reversed caudate asymmetry and measures of inhibition and externalizing behavior; i.e., children with reversed caudate asymmetry performed more poorly on measures of inhibition regardless of group membership.

Poorer performance on sustained attention tasks was related to smaller volume of the right-hemispheric white matter.

Author/s: Margaret Semrud-Clikeman
Issue: April, 2000

J. Am. Acad. Child Adolesc. Psychiatry, 2000, 39(4):477-484. Key Words: magnetic resonance imaging, attention-deficit hyperactivity disorder, neuropsychology, assessment.

http://www.findarticles.com/ has dozens of articles on this topic Brain - Behavior Relationships in ADHD

Subtle Brain Circuit Abnormalities Confirmed in ADHD

ADHD brain abnormalities. Subtle structural abnormalities in the brain circuit that inhibits thoughts have been confirmed in the first comprehensive brain imaging study of Attention Deficit Hyperactivity Disorder (ADHD).

Difficulty staying mentally focused is a primary symptom of ADHD, which affects about 5 percent of school age children.

Magnetic Resonance Imaging (MRI) scans of 57 boys with ADHD, aged 5-18, also revealed that their brains were more symmetrical than those of 55 age-matched controls. F. Xavier Castellanos, M.D., of the National Institute of Mental Health and colleagues report on their findings in the July issue of the Archives of General Psychiatry.

Three structures in the affected circuit on the right side of the brain -- prefrontal cortex, caudate nucleus and globus pallidus -- were smaller than normal in the boys with ADHD, when examined as a group.

The prefrontal cortex, located in the frontal lobe just behind the forehead, is believed to serve as the brain's command center. The caudate nucleus and globus pallidus, located near the middle of the brain, translate the commands into action. "If the prefrontal cortex is the steering wheel, the caudate and globus are the accelerator and brakes," explained Castellanos. "And it's this braking or inhibitory function that is likely impaired in ADHD." ADHD is thought to be rooted in an inability to inhibit thoughts. Finding smaller right hemisphere brain structures responsible for such "executive" functions strengthens support for this hypothesis.

The NIMH researchers also found that the entire right cerebral hemispheres in boys with ADHD were, on average, 5.2% smaller than those of controls.

EMBARGOED FOR RELEASE: JULY 15, 1996

http://www.nimh.nih.gov has dozens more studies like this on Structural Brain Circuit Abnormalities in ADHD

Structural Neurology of Attention Deficit Hyperactivity Disorder - ADHD

The Structural Differences include studies with MRIs, PET scans, and SPECT scans. They show subtle structural differences in these regions of the ADHD brain:

• prefrontal cortex - especially the smaller right anterior frontal cortex, and also less white matter in the right frontal lobes which cause problems with sustained or focused attention,
• caudate nucleus - asymmetries which cause problems with self-control,
• globus pallidus
• right hemisphere - the studies show that the right hemisphere of the ADD ADHD brain is, on average, 5% smaller than the control groups.

They also show differences in blood flow in certain parts of the brain, as well as chemical abnormalities in Attention Deficit Disorder subjects.

ADHD PET Scan

Zametkin's studies are enlightening in the structural differences in the ADHD brain. Brain scan images produced by positron emision tomography (PET) show differences between an adult with Attention deficit Hyperactivity Disorder (ADHD) (right) and an adult free of ADHD (left).

Source:

Alan Zametkin, M.D.
Section on Clinical Brain Imaging
Laboratory of Cerebral Metabolism
Division of Intramural Research Programs, NIMH 1990

Zametkin AJ, Nordahl TE, Gross M, et al. Cerebral glucose metabolism in adults with hyperactivity of childhood onset. New England Journal of Medicine, 1990; 323(20): 1361-6.

Several studies are included in this section on the Structural differences in the ADHD brain.