Are Kids Being Over Medicated?

Psychiatrists Say Schools Steer Parents To Over Medicate Kids

New York Times Syndicate
Judy Holland
October 02, 2000

WASHINGTON - Psychiatric leaders warned Congress Friday that too many educators are urging parents of problem children to give them prescription drugs rather than address their real problems at home or school.

Dr. Peter R. Breggin, director of the International Center for the Study of Psychiatry and Psychology, a nonprofit research group in Bethesda, Md., said school officials are pressing parents to give such children stimulant drugs such as Ritalin, Concerta, Metadate, Dexedrine and Adderall.

"Teachers, school psychologists and administrators commonly make dire threats about their inability to teach children without medicating them,'' Breggin told a panel of the House Committee on Education and the Workforce.

Behavioral and Neurological Correlation

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. ccsgnob@vm.uff.br

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.

Cerebrospinal Fluid 5-hydroxyindoleacetic Acid Levels in ADHD

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 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.

Changes in ADHD Treatment Services

Treatment Services for Children With ADHD: A National Perspective

Author/s: Kimberly Hoagwood
Issue: Feb, 2000

ABSTRACT

Objective: To summarize knowledge on treatment services for children and adolescents with attention-deficit hyperactivity disorder (ADHD), trends in services from 1989 to 1996, types of services provided, service mix, and barriers to care.

Method: A review of the literature and analyses from 2 national surveys of physician practices are presented.

Results: Major shifts have occurred in stimulant prescriptions since 1989, with prescriptions now comprising three fourths of all visits to physicians by children with ADHD.

Between 1989 and 1996, related services, such as health counseling, for children with ADHD increased 10-fold, and diagnostic services increased 3-fold. Provision of psychotherapy, however, decreased from 40% of pediatric visits to only 25% in the same time frame. Follow-up care also decreased from more than 90% of visits to only 75%.

Family practitioners were more likely than either pediatricians or psychiatrists to prescribe stimulants and less likely to use diagnostic services, provide mental health counseling, or recommend follow-up care.

About 50% of children with identified ADHD seen in real-world practice settings receive care that corresponds to guidelines of the American Academy of Child and Adolescent Psychiatry.

Physicians reported significant barriers to service provision for these children, including lack of pediatric specialists, insurance obstacles, and lengthy waiting lists.

Conclusions: The trends in treatment services and physician variations in service delivery point to major gaps between the research base and clinical practice.

Clinical variations may reflect training differences, unevenness in the availability of specialists and location of services, and changes in health care incentives.

J. Am. Acad. Child Adolesc. Psychiatry 2000, 39(2):198-206. Key Words: services, treatments, attention-deficit hyperactivity disorder.

http://www.findarticles.com/

Genetics of Methylphenidate Response

Association of the Dopamine Transporter Gene (DAT1) With Poor Methylphenidate Response

Author/s: Bertrand G. Winsberg
Issue: Dec, 1999

ABSTRACT

Objective: This study attempted to relate the alleles of the [D.sub.2] (DRD2), [D.sub.4] (DRD4), and dopamine transporter (DAT1) genes to the behavioral outcome of methylphenidate therapy.

Method: African-American children with attention-deficit hyperactivity disorder were treated with methylphenidate in doses not in excess of 60 mg/day.

The dosage was increased until behavioral change was achieved, using a decrement in scores of less than or equal to 1 on a commonly used rating scale or until the maximum tolerated dose was achieved.

Blood samples were obtained at that point, and genotypes for polymorphism at the respective genes were identified.

Results: Genotypes were then tested by [X.sup.2] to assess the significance of any association with drug response. Only the dopamine transporter gene was found to be significant.

Homozygosity of the 10-repeat allele was found to characterize nonresponse to methylphenidate therapy (p = .008).

Conclusions: While the results suggest that alleles of the dopamine transpor ter gene play a role in methyiphenidate response, replication in additional studies is needed.

J. Am. Acad. Child Adolesc. Psychiatry 1999, 38(12):1474-1 477. KeyWords: attention-deficit hyperactivity disorder, drug response, dopamine transporter, molecular genetics.

NIMH Research on Treatment for Attention Deficit Hyperactivity Disorder

ADHD: The Multimodal Treatment Study—Questions and Answers

Children with attention deficit hyperactivity disorder (ADHD), the most common of the psychiatric disorders that appear in childhood, are often the subject of great concern on the part of parents and teachers. Children with ADHD are unable to stay focused on a task, cannot sit still, act without thinking, and rarely finish anything. If untreated, the disorder can have long-term effects on a child's ability to make friends or do well at school or in other activities. Over time, children with ADHD may develop depression, lack of self-esteem, and other emotional problems.

Experts estimate that ADHD affects 3 to 5 percent of school-age children and two to three times as many boys as girls. Children with untreated ADHD have higher than normal rates of injury. ADHD frequently co-occurs with other problems, such as depression and anxiety disorders, conduct disorder, drug abuse, or antisocial behavior.

Although ADHD is relatively common, our knowledge of the problem is incomplete. Current ADHD treatment includes a mix of approaches, such as drug therapy, counseling, supportive services in schools and communities, and various combinations of the three. The medical literature offers many studies carried out over brief treatment periods (3 months or less), but a pressing question remains: what is the best kind of help we can offer children with ADHD over a longer term?

To answer this question, NIMH is sponsoring an ongoing, multisite, cooperative agreement treatment study of children with ADHD entitled The Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder. The first findings from this study, which were published in December 1999, provide important guidance for physicians and parents of children with ADHD and are discussed below. Ongoing follow-up reports will be published, with an additional 10-15 papers expected to be released in calendar year 2000.

Questions and Answers

Q. What is the Multimodal Treatment Study of Children with ADHD?

A. The Multimodal Treatment Study of Children with ADHD–"MTA" for short–brought together 18 nationally recognized authorities in ADHD at 6 different university medical centers and hospitals to evaluate the leading treatments for ADHD, including various forms of behavior therapy and medications. The study has included nearly 600 elementary school children, ages 7-9, randomly assigned to one of four treatment modes: (1) medication alone; (2) psychosocial/behavioral treatment alone; (3) a combination of both; or (4) routine community care.

Q. Why is this study important?

A. ADHD is a major public health problem of great interest to many parents, teachers, and health care providers. Up-to-date information concerning the long-term safety and comparative effectiveness of its treatments is urgently needed. While previous studies have examined the safety and compared the effectiveness of the two major forms of treatment, medication and behavior therapy, these studies generally have been limited to periods up to 4 months. The MTA study demonstrates for the first time the safety and relative effectiveness of these two treatments (including a behavioral therapy-only group), alone and in combination, for a time period up to 14 months, and compares these treatments to routine community care. The children involved in the study will be tracked into adolescence to document and evaluate long-term outcomes.

Q. What are the major findings of this study so far?

A. The MTA results published in December 1999 indicate that long-term combination treatments as well as medication-management alone are both significantly superior to intensive behavioral treatments and routine community treatments in reducing ADHD symptoms. The study also shows that these differential benefits extend as long as 14 months. In other areas of functioning (specifically anxiety symptoms, academic performance, oppositionality, parent-child relations, and social skills), the combined treatment approach was consistently superior to routine community care, whereas the single treatments (medication-only or behavioral treatment only) were not. In addition to the advantages provided by the combined treatment for several outcomes, this form of treatment allowed children to be successfully treated over the course of the study with somewhat lower doses of medication, compared to the medication-only group. These same findings were replicated across all six research sites, despite substantial differences among sites in their samples' sociodemographic characteristics. Therefore, the study's overall results appear to be applicable and generalizable to a wide range of children and families in need of treatment services for ADHD.

Q. Given the effectiveness of medication management, what is the role and need for behavioral therapy?

A. As noted in the NIH ADHD Consensus Conference in November 1998, several decades of research have amply demonstrated that behavioral therapies are quite effective. What the MTA study has demonstrated is that on average, carefully monitored medication management with monthly follow-up is more effective than intensive behavioral treatment for ADHD symptoms, for periods lasting as long as 14 months. All children tended to improve over the course of the study, but they differed in the relative amount of improvement, with the carefully done medication management approaches generally showing the greatest improvement. Nonetheless, children's responses varied enormously, and some children clearly did very well in each of the treatment groups. For some outcomes that are important in the daily functioning of these children (e.g., academic performance, familial relations), the combination of behavioral therapy and medication was necessary to produce improvements better than community care. Of note, families and teachers reported somewhat higher levels of consumer satisfaction for those treatments that included the behavioral therapy components. Therefore, medication alone is not necessarily the best treatment for every child, and families often need to pursue other treatments, either alone or in combination with medication.

Q. Which treatment is right for my child?

A. This is a critical question that must be answered by each family in consultation with their health care professional. For children with ADHD, no single treatment is the answer for every child; a number of factors appear to be involved in determining which treatments are best for which children. For example, even if a particular treatment might be effective in a given instance, the child may have unacceptable side effects or other life circumstances that might prevent that particular treatment from being used. Furthermore, findings indicate that children with other accompanying problems, such as co-occurring anxiety or high levels of family stressors, may do best with approaches that combine both treatment components, (i.e., medication management and intensive behavioral therapy). In developing suitable treatments for ADHD, each child's needs, personal and medical history, research findings, and other relevant factors need to be carefully considered.

Q. Why do many social skills improve with medication?

A. This question highlights one of the surprise findings of the study: although it has long been generally assumed that the development of new abilities in children with ADHD (e.g., social skills, enhanced cooperation with parents) often requires the explicit teaching of such skills, the MTA study findings suggest that many children can often acquire these abilities when given the opportunity. Children treated with effective medication management (either alone or in combination with intensive behavioral therapy) manifested substantially greater improvements in social skills and peer relations than children in the community comparison group after 14 months. This important finding indicates that symptoms of ADHD may interfere with their learning of specific social skills. It appears that medication management may benefit many children in areas not previously well known to be salient medication targets, in part by diminishing symptoms that had previously interfered with the child's social development.

Q. Why were the MTA medication treatments more effective than community treatments that also usually included medication?

A. There were substantial differences between the study-provided medication treatments and those provided in the community, differences mostly related to the quality and intensity of the medication management treatment. During the first month of treatment, special care was taken to find an optimal dose of medication for each child receiving the MTA medication treatment. After this period, these children were seen monthly for one-half hour at each visit. During the treatment visits, the MTA prescribing therapist spoke with the parent, met with the child, and sought to determine any concerns that the family might have regarding the medication or the child's ADHD-related difficulties. If the child was experiencing any difficulties, the MTA physician was encouraged to consider adjustments in the child's medication (rather than taking a "wait and see" approach). The goal was always to obtain such substantial benefit that there was "no room for improvement" compared with the functioning of children not suffering from ADHD. Close supervision also fostered early detection and response to any problematic side effects from medication, a process that may have facilitated efforts to help children remain on effective treatment. In addition, the MTA physicians sought input from the teacher on a monthly basis, and used this information to make any necessary adjustments in the child's treatment. While the physicians in the MTA medication-only group did not provide behavioral therapy, they did advise the parents when necessary concerning any problems the child may have been experiencing, and provided reading materials and additional information as requested. Physicians delivering the MTA medication treatments generally used 3 doses per day and somewhat higher doses of stimulant medications. In comparison, the community-treatment physician generally saw the children face-to-face only 1-2 times per year, and for shorter periods of time each visit. Furthermore, they did not have any interaction with the teachers, and prescribed lower doses and twice-daily stimulant medication.

Q. How were children selected for this study?

A. In all instances, the child's parents contacted the investigators to learn more about the study, after first hearing about it through local pediatricians, other health care providers, elementary school teachers, or radio/newspaper announcements. Children and parents were then carefully interviewed to learn more about the nature of the child's symptoms, and rule out the presence of other conditions or factors that may have given rise to the child's difficulties. In addition, extensive historical information was gathered and diagnostic interviews were conducted to establish whether or not the child exhibited the long-standing pattern of symptoms characteristic of ADHD across home, school, and peer settings. If children met full criteria for ADHD and study entry (and many did not), informed parental consent with child assent and school permission were received; the children and families then were eligible for study entry and randomization. Children who had behavior problems but not ADHD were not eligible for study participation.

Q. Where is this study taking place?

A. Research sites include:

* New York State Psychiatric Institute at Columbia University, New York, N.Y.
* Mount Sinai Medical Center, New York, N.Y.
* Duke University Medical Center, Durham, N.C.
* University of Pittsburgh, Pittsburgh, PA.
* Long Island Jewish Medical Center, New Hyde Park, N.Y.
* Montreal Children's Hospital, Montreal, Canada
* University of California at Berkeley, CA.
* University of California at Irvine, CA.

For More Information on Mental Disorders in Children, Contact:

Public Information and Communications Branch, NIMH
6001 Executive Boulevard, Room 8184, MSC 9663
Bethesda, MD 20892-9663
Phone: 301-443-4513
TTY: 301-443-8431
FAX: 301-443-4279
Mental Health FAX 4U: 301-443-5158
E-mail: nimhinfo@nih.gov
NIMH home page address:
http://www.nimh.nih.gov

March 2000

NIMH: Diagnosis and Treatment of ADHD

National Institutes of Health Consensus Development Conference Statement: Diagnosis and Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD).

Issue: Feb, 2000

ABSTRACT

Attention-deficit/hyperactivity disorder (ADHD) is a commonly diagnosed behavioral disorder of childhood that represents a costly major public health problem.

Despite progress, ADHD and its treatment have remained controversial, especially the use of psychostimulants for both short- and long-term treatment.

Although an independent diagnostic test for ADHD does not exist, there is evidence supporting the validity of the disorder.

Studies (primarily short-term, approximately 3 months), including randomized clinical trials, have established the efficacy of stimulants and psychosocial treatments for alleviating the symptoms of ADHD and associated aggressiveness and have indicated that stimulants are more effective than psychosocial therapies in treating these symptoms. Because of the lack of consistent improvement beyond the core symptoms and the paucity of long-term studies (beyond 14 months), there is a need for longer-term studies with drugs and behavioral modalities and their combination.

Although trials are under way, conclusive recommendations concerning treatment for the long term cannot be made at present. There are wide variations in the use of psychostimulants across communities and physicians, suggesting no consensus regarding which ADHD patients should be treated with psychostimulants, and thus the need for improved assessment, treatment, and follow-up.

Furthermore, the lack of insurance coverage, preventing the appropriate diagnosis and treatment of ADHD, and the lack of integration with educational services are substantial barriers and represent considerable long-term costs for society.

Finally, after years of clinical research and experience with ADHD, knowledge about the cause or causes of ADHD remain largely speculative.

Consequently, there are no documented strategies for the prevention of ADHD.

J. Am. Acad. Child Adolesc. Psychiatry, 2000, 39(2):182-193. Key Words: attention-deficit/hyperactivity disorder, diagnosis, treatment, psychostimulants, risks, barriers.

Physiological Differences in Platelets of Conduct Disorder Children

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.

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.

Reward and Response Cost in ADHD

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).

TOVA Test Useful in Diagnosis of ADHD

Diagnostic Issues and Attention Deficit Hyperactivity Disorder – ADD ADHD

Clinical utility of the test of variables of attention (TOVA) in the diagnosis of attention-deficit/hyperactivity disorder

Journal of Clinical Psychology
Volume 54, Issue 4, 1998. Pages: 461-476
Published Online: 6 Dec 1998

Ability of the Test of Variables of Attention (TOVA) to distinguish between referred children with attention-deficit/hyperactivity disorder (ADHD) and other (OTHER) clinical diagnoses were studied.

The ADHD group differed from the OTHER group on TOVA variables and most measures from the Revised Conners Teacher Rating Scale (RCTRS) and ADD-H Comprehensive Teacher's Rating Scale (ACTeRS).

The criteria of any one TOVA variable > 1.5 standard deviations from age and sex adjusted means correctly identified 80% of the sample with attention deficit disorders and 72% of the sample without attention deficit disorder.

Cases misclassified by teacher ratings were often correctly classified by the TOVA and conversely. The TOVA makes a unique and important contribution to diagnostic evaluations.

J Clin Psychol 54: 461-476, 1998.

http://www3.interscience.wiley.com/cgi-bin/abstract/31228/START

Benefits from EFA Supplementation in ADHD

Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD.

Sinn N, and Bryan J.

Commonwealth Scientific and Industrial Reasearch Organization Human Nutrition, Adelaide, South Australia.

METHODS: Various developmental problems including attention-deficit/hyperactivity disorder (ADHD) have been linked to biological deficiencies in polyunsaturated fatty acids (PUFAs). Additionally, there is evidence that symptoms may be reduced with PUFA supplementation.

This study investigated effects of supplementation with PUFAs on symptoms typically associated with ADHD. Because nutrients work synergistically, additional effects of micronutrient supplementation were also investigated.

A total of 132 Australian children aged 7 to 12 years with scores > or = 2 SD above the population average on the Conners ADHD Index participated in a randomized, placebo-controlled, double-blind intervention over 15 weeks, taking PUFAs alone, PUFAs + micronutrients, or placebo.

Due to unreturned questionnaires, data were only available for 104 children.

RESULTS: Significant medium to strong positive treatment effects were found on parent ratings of core ADHD symptoms, inattention, hyperactivity/impulsivity, on the Conners Parent Rating Scale (CPRS) in both PUFA treatment groups compared with the placebo group; no additional effects were found with the micronutrients.

After a one-way crossover to active supplements in all groups for a further 15 weeks, these results were replicated in the placebo group, and the treatment groups continued to show significant improvements on CPRS core symptoms. No significant effects were found on Conners Teacher Rating Scales.

CONCLUSION: These results add to preliminary findings that ADHD-related problems with inattention, hyperactivity, and impulsivity might respond to treatment with PUFAs and that improvements may continue with supplementation extending to 30 weeks.

Effects of Fatty Acids on ADHD Symptoms and LDs

A randomized double-blind, placebo-controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties.

Richardso AJ, and Puri BK.

University Department of Physiology, Oxford, England, UK.

The authors tested the prediction that relative deficiencies in highly unsaturated fatty acids (HUFAs) may underlie some of the behavioral and learning problems associated with attention-deficit/hyperactivity disorder (ADHD) by studying the effects of HUFA supplementation on ADHD-related symptoms in children with specific learning difficulties (mainly dyslexia) who also showed ADHD features.

Forty-one children aged 8-12 years with both specific learning difficulties and above-average ADHD ratings were randomly allocated to HUFA supplementation or placebo for 12 weeks.

At both baseline and follow-up, a range of behavioral and learning problems associated with ADHD was assessed using standardized parent rating scales.

At baseline, the groups did not differ, but after 12 weeks mean scores for cognitive problems and general behavior problems were significantly lower for the group treated with HUFA than for the placebo group; there were significant improvements from baseline on 7 out of 14 scales for active treatment, compared with none for placebo.

HUFA supplementation appears to reduce ADHD-related symptoms in children with specific learning difficulties.

Given the safety and tolerability of this simple treatment, results from this pilot study strongly support the case for further investigations.

PMID: 11817499 [PubMed - indexed for MEDLINE]

Essential Fatty Acid Metabolism ADHD

Essential fatty acid metabolism in boys with attention deficit-hyperactivity disorder.

Burgess, JR, et al.

American Journal of Clinical Nutrition 1995; 62;761-68.

Attention-deficit hyperactivity disorder (ADHD) is the term used to describe children who are inattentive, impulsive, and hyperactive. The cause is unknown and is thought to be multifactorial.

Based on the work of others, we hypothesized that some children with ADHD have altered fatty acid metabolism.

The present study found that 53 subjects with ADHD had significantly lower concentrations of key fatty acids in the plasma polar lipids (20:4n-6, 20:5n-3, and 22:6n-3) and in red blood cell total lipids (20:4n-6 and 22:4n-6) than did the 43 control subjects. Also, a subgroup of 21 subjects with ADHD exhibiting many symptoms of essential fatty acid (EFA) deficiency had significantly lower plasma concentrations of 20:4n-6 and 22:6n-3 than did 32 subjects with ADHD with few EFA-deficiency symptoms.

The data are discussed with respect to cause, but the precise reason for lower fatty acid concentrations in some children with ADHD is not clear.

Flax Seed Oil and Vitamin C with ADHD

Supplementation with flax oil and vitamin C improves the outcome of Attention Deficit Hyperactivity Disorder (ADHD).

* Joshi K,
* Lad S,
* Kale M,
* Patwardhan B,
* Mahadik SP,
* Patni B,
* Chaudhary A,
* Bhave S,
* Pandit A.

Interdisciplinary School of Health Sciences, University of Pune, Ganeshkhind, Pune-411007, Maharashtra, India.

Considerable clinical and experimental evidence now supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to a range of common developmental disorders including Attention Deficit Hyperactivity Disorder (ADHD).

This pilot study evaluates the effect of alpha linolenic acid (ALA)-rich nutritional supplementation in the form of flax oil and antioxidant emulsion on blood fatty acids composition and behavior in children with ADHD. Post-supplementation levels of RBC membrane fatty acids were significantly higher than pretreatment levels as well as the levels in control.

There was significant improvement in the symptoms of ADHD reflected by reduction in total hyperactivity scores of ADHD children derived from ADHD rating scale.

PMID: 16314082 [PubMed - indexed for MEDLINE]

Oxford-Durham Study: Fatty Acids ADHD and DCD

The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder.

* Richardson AJ,
* Montgomery P.

University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, United Kingdom.

BACKGROUND: Developmental coordination disorder (DCD) affects approximately 5% of school-aged children. In addition to the core deficits in motor function, this condition is associated commonly with difficulties in learning, behavior, and psychosocial adjustment that persist into adulthood.

Mounting evidence suggests that a relative lack of certain polyunsaturated fatty acids may contribute to related neurodevelopmental and psychiatric disorders such as dyslexia and attention-deficit/hyperactivity disorder. Given the current lack of effective, evidence-based treatment options for DCD, the use of fatty acid supplements merits investigation.

METHODS: A randomized, controlled trial of dietary supplementation with omega-3 and omega-6 fatty acids, compared with placebo, was conducted with 117 children with DCD (5-12 years of age). Treatment for 3 months in parallel groups was followed by a 1-way crossover from placebo to active treatment for an additional 3 months.

RESULTS: No effect of treatment on motor skills was apparent, but significant improvements for active treatment versus placebo were found in reading, spelling, and behavior over 3 months of treatment in parallel groups.

After the crossover, similar changes were seen in the placebo-active group, whereas children continuing with active treatment maintained or improved their progress.

CONCLUSIONS: Fatty acid supplementation may offer a safe efficacious treatment option for educational and behavioral problems among children with DCD.

Additional work is needed to investigate whether our inability to detect any improvement in motor skills reflects the measures used and to assess the durability of treatment effects on behavior and academic progress.

PMID: 15867048 [PubMed - indexed for MEDLINE]

Polyunsaturated Fatty Acids in ADHD

Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder.

Burgess, JR, et al.

American Journal of Clinical Nutrition 2000,Vol. 71, No. 1, 327-330.

Several previous studies indicated that some physical symptoms reported in ADHD are similar to symptoms observed in essential fatty acid (EFA) deficiency in animals and humans deprived of EFAs.

We reported previously that a subgroup of ADHD subjects reporting many symptoms indicative of EFA deficiency (L-ADHD) had significantly lower proportions of plasma arachidonic acid and docosahexaenoic acid than did ADHD subjects with few such symptoms or control subjects.

In another study using contrast analysis of the plasma polar lipid data, subjects with lower compositions of total n-3 fatty acids had significantly more behavioral problems, temper tantrums, and learning, health, and sleep problems than did those with high proportions of n-3 fatty acids.

The reasons for the lower proportions of long-chain polyunsaturated fatty acids (LCPUFAs) in these children are not clear; however, factors involving fatty acid intake, conversion of EFAs to LCPUFA products, and enhanced metabolism are discussed.

Primrose Oil Has Little Effect in this Study

The effects of essential fatty acid supplementation by Efamol in hyperactive children.

* Aman MG,
* Mitchell EA,
* Turbott SH.

Thirty-one children, selected for marked inattention and overactivity, were studied in a double-blind, placebo-controlled crossover study of essential fatty acid (EFA) supplementation.

Subjects received the active treatment and placebo conditions for 4 weeks each and were assessed on a variety of cognitive, motor, and standardized rating scale measures.

EFA supplementation (evening primrose oil; Efamol) resulted in significantly lower levels of palmitoleic acid (a nonessential fatty acid) and higher concentrations of dihomogammalinolenic acid, an EFA previously found to be deficient in some hyperactive children.

Supplementation was also associated with significant changes on two performance tasks and with significant improvement to parent ratings on the subscales designated as Attention Problem and Motor Excess of the Revised Behavior Problem Checklist.

However, a variety of eight other psychomotor performance tests and two standardized teacher rating scales failed to indicate treatment effects.

When the experiment-wise probability level was set at .05, only 2 of 42 variables showed treatment effects.

Baseline EFA concentrations appeared to be unrelated to treatment response. It was concluded that EFA supplementation, as employed here, produces minimal or no improvements in hyperactive children selected without regard to baseline EFA concentrations.

PMID: 3553274 [PubMed - indexed for MEDLINE]

ADHD and Multi-tasking

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 article here

Differences in Subjects Who Never Used Medication

Task-Specific Hypoactivation in Prefrontal and Temporoparietal Brain Regions During Motor Inhibition and Task Switching in Medication-Naive Children and Adolescents With Attention Deficit Hyperactivity Disorder

Anna B. Smith, Ph.D., Eric Taylor, M.D., Ph.D., Mick Brammer, Ph.D., Brian Toone, M.D. and Katya Rubia, Ph.D.

OBJECTIVE: A relatively small number of functional imaging studies of attention deficit hyperactivity disorder (ADHD) have shown abnormal prefrontal and striatal brain activation during tasks of motor response inhibition.

However, the potential confound of previous medication exposure has not yet been addressed, and no functional imaging study exists to date on medication-naive children and adolescents with ADHD.

The aim of this study was to investigate the neural substrates of a range of motor and cognitive inhibitory functions in a relatively large group of children and adolescents with ADHD who had never previously been exposed to medication.

METHOD: Nineteen boys with ADHD and 27 healthy age- and IQ-matched boys underwent functional MRI to compare brain activation during performance of tasks that assessed motor response inhibition (go/no go task), cognitive interference inhibition (motor Stroop task), and cognitive flexibility (switch task).

RESULTS: Boys with ADHD showed decreased activation in the left rostral mesial frontal cortex during the go/no go task and decreased activation in the bilateral prefrontal and temporal lobes and right parietal lobe during the switch task. No significant group differences were observed during motor Stroop task performance.

CONCLUSION: Abnormal brain activation was observed in medication-naive children and adolescents with ADHD during tasks involving motor inhibition and task switching, suggesting that hypoactivation in this patient group is unrelated to long-term stimulant exposure.

Furthermore, functional abnormalities are task-specific and extend from frontostriatal to parietal and temporal cortices.

EEG Norms for ADHD

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 < .05) for all sites at both baseline and while performing cognitive tasks. There were also differences in the ratios of theta to beta and theta to SMR for baseline and all tasks at all sites, but the differences were significant only for some tasks at the parietal sites. The raw beta and SMR amplitudes themselves were not significantly different between the two groups.

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.

Executive Function Differences in Adolescents with ADHD vs Oppositional Defiant Disorder

Do executive function deficits differentiate between adolescents with ADHD and oppositional defiant/conduct disorder?

A neuropsychological study using the Six Elements Test and Hayling Sentence Completion Test

J Abnorm Child Psychol 2000 Oct;28(5):403-14
Clark C, Prior M, Kinsella GJ
School of Psychological Science, La Trobe University, Victoria, Australia.
[Record supplied by publisher]

Two neuropsychological measures of executive functions--Six Elements Tests (SET) and Hayling Sentence Completion Test (HSCT)-were administered to 110 adolescents, aged 12-15 years.

Participants comprised four groups: Attention Deficit Hyperactivity Disorder (ADHD) only (n = 35). ADHD and Oppositional Defiant Disorder/Conduct Disorder (ODD/CD) (n = 38), ODD/CD only (n = 11), and a normal community control group (n = 26).

Results indicated that adolescents with ADHD performed significantly worse on both the SET and HSCT than those without ADHD, whether or not they also had ODD/CD.

The adolescents with ADHD and with comorbid ADHD and ODD/CD were significantly more impaired in their ability to generate strategies and to monitor their ongoing behavior compared with age-matched controls and adolescents with ODD/CD only.

It is argued that among adolescents with clinically significant levels of externalizing behavior problems, executive function deficits are specific to those with ADHD.

The findings support the sensitivity of these two relatively new tests of executive functions and their ecological validity in tapping into everyday situations, which are potentially problematic for individuals with ADHD.

Executive Functions and Developmental Psychopathology

Executive functions and developmental psychopathology.

J Child Psychol Psychiatry 1996 Jan;37(1):51-87
Pennington BF, Ozonoff S
Department of Psychology, University of Denver, CO 80208, USA.

In this paper, we consider the domain of executive functions (EFs) and their possible role in developmental psychopathologies.

We first consider general theoretical and measurement issues involved in studying EFs and then review studies of EFs in four developmental psychopathologies: attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), autism, and Tourette syndrome (TS).

Our review reveals that EF deficits are consistently found in both ADHD and autism but not in CD (without ADHD) or in TS.

Moreover, both the severity and profile of EF deficits appears to differ across ADHD and autism. Molar EF deficits are more severe in the latter than the former. In the few studies of more specific EF tasks, there are impairments in motor inhibition in ADHD but not in autism, whereas there are impairments in verbal working memory in autism but not ADHD. We close with a discussion of implications for future research.

Inhibitory Control Deficit in ADHD

Confirmation of an Inhibitory Control Deficit in Attention-Deficit/Hyperactivity Disorder.

Author/s: Russell Schachar
Issue: June, 2000

The objective of this study was to determine whether deficient inhibitory control distinguishes children with a diagnosis of attention-deficit/hyperactivity (ADHD) disorder, conduct disorder (CD), and comorbid ADHD + CD from normally developing children.

Participants were rigorously diagnosed children (age 7 to 12 years) with ADHD (N = 72), CD (N = 13) or ADHD + CD (N = 47) and 33 control children (NC). We studied inhibitory control using the stop-signal paradigm, a laboratory task that assessed the ability to inhibit an ongoing action.

The ADHD group had significantly impaired inhibitory control compared to NC, CD, and ADHD + CD children.

These results indicate that children with ADHD have deficient inhibition as measured in the stop-signal paradigm and that ADHD occurring in the presence of ADHD + CD may represent a phenocopy of CD rather than a variant of ADHD.

View full article here

Naming Speed Performance: ADHD, Reading Disorders, and Medications

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

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

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

Neuropsychiatric Comparison of Conduct Disorder to ADHD

Neuropsychiatric and neuropsychological findings in conduct disorder and attention-deficit hyperactivity disorder.

J Neuropsychiatry Clin Neurosci 1994 Summer;6(3):245-9
Aronowitz B, Liebowitz M, Hollander E, Fazzini E, Durlach-Misteli C, Frenkel M, Mosovich S, Garfinkel R, Saoud J, DelBene D, et al
Department of Psychiatry,
New York State Psychiatric Institute, New York.

Neuropsychiatric and neuropsychological evaluations were performed in a pilot study of adolescents with DSM-III-R disruptive behavior disorders, including conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD).

The following comparisons were made: 1) CD comorbid with ADHD vs. CD only; 2) all subjects with ADHD vs. all non-ADHD; and 3) all subjects with CD vs. all non-CD.

The CD + ADHD group had increased left-sided soft signs compared with the CD group.

CD + ADHD subjects significantly underperformed CD subjects on several executive functioning measures, with no differences on Verbal IQ subtests.

Results are discrepant with previous findings of deficient verbal functioning in delinquent populations.

Neuropsychological Deficits in Adolescent-onset Schizophrenia vs ADHD

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

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

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.

Neuropsychological Functioning of Adults with ADHD

Neuropsychological functioning of adults with attention deficit hyperactivity disorder.

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.

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.

Processing Deficits in ADHD and Conduct Disorder

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

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.

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.

Quantitative EEGs and Auditory ERPs in the Evaluation of ADHD

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 (AD/HD) and effects of methylphenidate are explored using electroencephalographic (EEG) and auditory eventrelated potentials (ERPs).

In the first of four studies, a database of AD/HD 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 AD/HD and raise questions regarding the role of methylphenidate in modulating cortical processing.

Stanford MRI Study on Brain Function in ADHD

Source: Stanford University
Date: November 24, 1998

Science Daily — Stanford neuro-scientists have found a clear difference in brain functioning between boys who have attention deficit disorder [ADHD] and those who do not, a step that could lead to better diagnosis of the most common developmental disorder of childhood.

Follow-up studies will be required before the results of this study on a small number of boys can lead to brain-based methods of diagnosis, caution the lead researchers, Research Associate Chandan Vaidya and Associate Professor John Gabrieli of Stanford's Department of Psychology.

Theirs is the first study, however, to show that Ritalin, the drug most commonly used to treat ADD, has different effects on the brains of people with and without ADD, and where those differences occur in the brain. The findings are reported in the Nov. 24 issue of the Proceedings of the National Academy of Sciences.

The study is also the first to use functional magnetic resonance imaging [FMRI] in the study of ADD. This imaging method can show brain differences in individual people, instead of in averages of differences of two groups. This is critical for diagnosis, which has to be established on an individual basis. Unlike methods used in other studies of ADD, FMRI does not require injection or inhalation of radioactive substances. It relies instead on naturally occurring changes in brain function, which makes it appropriate for research and clinical purposes for children.

Co-authors of the study are medical doctors Glenn Austin and Hugh Ridlehuber and school psychologist Gary Kirkorian of the Community/Academia Coalition in Los Altos, Calif. and Gary Glover and John Desmond of the Stanford Medical Center's Radiology Department.

The findings have drawn considerable attention from neuroscientists because "ADD is so widespread, so controversial and confusing, and these are among the few clear findings in that field," said Gabrieli, who heads the brain imaging laboratory where the research was done.

Attention deficit disorder, which often includes hyperactivity, is currently diagnosed on the basis of subjective observations of youngsters' behavior. If the new findings can be replicated, he said, it might be possible to make a biological diagnosis of the disorder by using FMRI. Since the common treatment for ADD is a prescription drug whose long-term effects on brain function are not known, parents and pediatricians most likely would welcome a more definitive way to diagnose the disorder.

Comparing the brain images later, researchers found a clear difference in the activation of neuronal tissue in two structures in the striatal region, which is known to be involved in motor control. The brain activation differences between the boys with ADD and those without were even more dramatic when the subjects were asked to perform the same task after taking the drug Ritalin. Ritalin is a stimulant medication used to temporarily relieve symptoms of ADD, such as inattention, impulsivity and hyperactivity.

"Both the normal kids and the ADD kids got better in their impulse control when they had taken the drug," Vaidya said. "Ritalin improved everyone's performance, but how it actually did it differed in the brains."

The boys with ADD showed more activity in the affected striatal structures (specifically known as the caudate and putamen) when taking the drug than when not. The healthy boys, in contrast, showed the reverse - less activity in those areas when taking the drug than when not.

"From past work with adults and children, some of which required injecting radioactive material, a consensus developed that it is the frontal striatal circuitry of the brain that is what's not right with this disorder," Vaidya said. "That is why we imaged this part of the brain, and our study confirmed that these structures are, indeed, important for ADD."

Ritalin primarily, but not exclusively, influences dopamine neurotransmission. The opposite effects of Ritalin on boys with ADD and boys without the disorder suggest that ADD involves atypical dopamine modulation in the striatum, she said.

The researchers caution that the study was conducted with a small group and needs to be replicated with girls as well as with more boys before they can be certain they have found a universal neurobiological marker for the disorder. They also reported that they tried the experiment on three other boys who had not been diagnosed with ADD but who had siblings with the diagnosis. Two of the three siblings of ADD boys showed some Ritalin enhancement of the striatum, as did their affected brothers.

"This would lend some support to the idea that ADD may involve atypical genetic influences on dopamine modulation," Vaidya said, but more studies would be necessary to establish a genetic influence.

Because of the widespread interest in ADD, the researchers also were careful to point out other limitations of their study. A fraction of people diagnosed with ADD have not responded to Ritalin treatment, and this study did not include such children, they said. It also did not attempt to investigate possible changes in brain activation that might occur with the drug over time. The ADD boys did show a different brain activation level when not on the drug, but all of them had been taking Ritalin previously as part of their ongoing treatment.

Despite these limitations, the study points to new directions for research into brain function that could improve individuals' performance.

"This is one of the few studies to examine brain function in children, and to further our knowledge about normal and abnormal brain development," Gabrieli said. "It suggests that FMRI is a powerful tool to examine brain and behavior in the context of both normal and abnormal development."

Currently, ADD impairs the function of an estimated 3 to 7 percent of youngsters in home and school, and the long-term consequences include lower educational and vocational accomplishments for them as adults as well as an increased risk for drug abuse and other risky behaviors.

The study was funded by a grant from the El Camino Hospital District Board in Mountain View, Calif.

Note: This story has been adapted from a news release issued by Stanford University.

Evolutionary Advatages to ADHD ?

Tuning major gene variants conditioning human behavior: the anachronism of ADHD.

* Arcos-Burgos M,
* Acosta MT.

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

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]

Genetics in ADHD Study with Adoptive Families

Adoptive and Biological Families of Children and Adolescents With ADHD.

Author/s: Susan Sprich
Issue: Nov, 2000

ABSTRACT

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.

Find dozens of articles on ADHD at http://www.findarticles.com/

Genetics: Dopamine Transporter Gene

Genetics of Childhood Disorders: XX. ADHD

Part 4: Is ADHD Genetically Heterogeneous?

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

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.

See more studies on this topic at FindArticles.com

Recent Findings on Genetics of ADHD

Advances in genetic findings on attention deficit hyperactivity disorder.

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

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

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.

PMID: 17506925 [PubMed - as supplied by publisher]

Twin Study: ADHD and Reading Problems

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

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

University of Colorado at Boulder, Boulder, Colorado.

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.

PMID: 17440942 [PubMed - as supplied by publisher]

Where Does Inattention Come From?

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

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

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

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.

http://www.findarticles.com/

Brain - Behavior Relationships in ADHD

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

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

ABSTRACT

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.

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 Circuit Abnormalities in ADHD

Subtle Brain Circuit Abnormalities Confirmed in ADHD

EMBARGOED FOR RELEASE: JULY 15, 1996

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.

http://www.nimh.nih.gov has dozens more studies like this.

Flaws in Some Brain Imaging Studies?

Researchers 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...

SEE this article on a STUDY on children who NEVER used medication. It has a different conclusion than the author's study above, and was not considered by the authors above.

Frontal Lobe Differences in ADHD

Atypical Frontal Brain Activation in ADHD: Preschool and Elementary School Boys and Girls.

(Statistical Data Included)

Author/s: Lioba Baving
Issue: Nov, 1999

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder that significantly hampers psychosocial adaptation (e.g., Biederman et al., 1996; Tannock, 1998).

Several findings point to the involvement of a right-sided frontostriatal dysfunction in ADHD symptoms.

An alerting network for maintaining a vigilant state is assumed to be localized in the right frontal lobe (Posner and Petersen, 1990). This hypothesis is supported by the fact that the development of attention in normal children correlated with magnetic resonance imaging (MRI)-derived morphometric measures of the anterior cingulate, particularly the right (Casey et al., 1992).

Adults and children with focal, especially frontal, right-hemispheric lesions display behavior problems comparable with those in children with ADHD, such as inattention, defective response inhibition, and impersistence (Heilman et al., 1991).

Findings of structural neuroimaging studies underscore the assumption of a right frontal deficit in ADHD. Using MRI, abnormal - though markedly diverging - findings in several brain regions (e.g., basal ganglia, corpus callosum) were reported in children with ADHD (Filipek, 1999; Tannock, 1998), but all studies examining the frontal region found the right anterior frontal cortex to be smaller than in nonADHD children (Casey et al., 1997; Castellanos et al., 1996; Filipek et al., 1997; Hynd et al., 1990).

Casey et al. (1997) correlated performance of ADHD children and control children in 3 response inhibition tasks with MRI-based anatomical measures of the prefrontal cortex and the basal ganglia. Significant negative correlations between task performance and volume of the prefrontal cortex and caudate nuclei emerged, predominantly in the right hemisphere, suggesting that the right frontostriatal circuitry is intimately involved in response inhibition.

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Neuroimaging Studies Review

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

(Statistical Data Included)

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

ABSTRACT

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.

Premature Birth and ADHD

Premature Or Low Birthweight Babies At Significantly Increased Risk Of Hyperactivity Disorder

Premature or low birthweight babies are up to three times as likely to become hyperactive, with low attention spans, suggests research published ahead of print in the Archives of Disease in Childhood.

The Danish research team compared the birth records of 834 children with confirmed HKD with those of 20,100 children with no mental disorders. All the children were born between 1980 and 1994.

Children born at between 34 and 36 weeks were around 70% more likely to develop the disorder than children born at term. Babies at born below 34 completed weeks were almost three times as likely to develop the disorder.

Low birthweight babies born at term were also at risk, the study showed.

Note: This story has been adapted from a news release issued by BMJ Specialty Journals.