for Generation Rescue
by Teresa Binstock
June 2008

ADHD: An Overview

Introduction

Prelude: In 2010, two studies linked ADHD with pesticides, which parallels a gene-finding linking autism and pesticides.

Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides
Bouchard MF, Bellinger DC, Wright RO, Weisskopf MG.
Pediatrics. 2010 Jun;125(6):e1270-7 here

Prenatal organochlorine exposure and behaviors associated with attention deficit hyperactivity disorder in school-aged children
Sagiv SK, Thurston SW, Bellinger DC, Tolbert PE, Altshul LM, Korrick SA.
Am J Epidemiol. 2010 Mar 1;171(5):593-601. here

Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions
D'Amelio M et al.
Mol Psychiatry. 2005 Nov;10(11):1006-16. here


Introduction
: This document's Table of Contents links to web pages with citations decribing aspects of ADHD and AD, ie, attention-deficit hyperactivity disorder and attention-deficit disorder.

In recent decades, voluminous data have been published in peer-reviewed journals; numerous websites offer information; and - perhaps most importantly - discussion groups are active  for parents of children with ADHD or AD and for adults with ADHD or AD. 
        Many studies focus upon genes and alleles which are etiologically significant in at least some cases of ADHD, whereas other researchers document environmental factors that impair attention or are associated with increased rates of ADHD. Studies emphasizing genes, environment, or the interplay of both domains are presented in this bibliography. The number and ubiquitousness of pollutants associated with AD and ADHD prompts a speculation: are many and perhaps most cases of AD and ADHD etiologically induced by environmental pollutants?


Subroups are important within AD and ADHD. Indeed, there is much inter-individual variation. For example, some individuals with childhood ADHD gradually have a lessening of symptoms sufficiently so that, as adults, these individuals no longer merit a diagnosis of ADHD.  Another observation described in medical literature is "age of onset" - ie, when did the individual's AD or ADHD begin? Or, begin to be significant?  Other important subgroups are determined by what additionally significant traits are present in an individual. This is known as "comorbidity".

An important concern in AD and ADHD focuses upon patterns of individuals' response to treatments, whether pharmacological or otherwise. Two webpages serve as preliminary guidelines regarding inter-individual responses to various treatments. 
        An ADHD website by Lewis Mehl-Madrona, M.D., Ph.D., and hosted by Healing-Arts.org summarily delineates a range of treatments and expected responses:
http://www.healing-arts.org/children/
        For more than 20 years, the Autism Research Institute has been compiling data derived from parents' reports about specific treatments, be they pharmaceuticals, diets, or supplements. If you visit these data, note the got-better/got-worse ratio for each specific treatment:
Parent Ratings of Various Interventions

The group or the individual: Many studies obtain insights as a result of considering groups of individuals - eg, with ADHD versus without ADHD.  However, whether as a child or as an adult, each person with AD or ADHD is an individual. A ramification is that what's true for many in the group being studied may not be true for all individuals. This kind of difference often occurs in regard to treatments. For instance, avoiding a particular food dye may help Johnny very much, whereas Billy's parents see virtually no difference when those same dyes are removed from Billy's diet. The notion "one size fits all" seldom applies to any given pharmaceutical or alternative treatment.

Etiologic Models: Genes and Environment: ADHD research includes a quest for understanding causes and for identifying etiologically significant factors. As previously mentioned, one model has long focused upon genetics. However, environmental factors (eg, mercury, aluminum, smoking during pregnancy) have been identified as increasing the likelihood of attention deficit (AD) and ADHD. Environmental pollutants may be especially and etiologically significant  for individuals having weak alleles in genes important for detoxification of intra-body pollutants. Furthermore, as the literature increasingly documents, some seemingly "cognitive genes" (eg, related to dopamine) have effects modified by environmental factors such as smoking.

A spectrum of pollutant-induced pathologies: In recent years, a number of studies have called attention to traits co-occurring among ADHD, PDD, and autism. Such findings (eg, 1-8) are  consistent with CDC findings in 1999, wherein a range of pathologies were associated with thimerosal injections during vaccinations.  The findings (1-8) are also consistent with the fact that AD, ADHD, and autism are associated with environmental pollutants such as mercury and arsenic (other url-pages in this collection).  A bell curve could be created, with the horizontal axis being severity/comorbidity of disorder - from neurotypical to adhd to PDD to autism, with the vertical axis being a combination of pollutant levels, nutritional impairments, and weak alleles. 

Reiersen et al offer important insights regarding DSM-IV criteria and experimental design:

       "DSM-IV does not allow ADHD to be diagnosed if symptoms occur only during the course of a PDD (American Psychiatric Association, 1994). Similarly, many neurobiological, genetic, and treatment studies of these disorders exclude participants with evidence of both disorders. Both of these practices may be inappropriate given the frequent co-occurrence of ADHD and PDD symptoms in clinical samples." (2)

       "The current study adds to existing literature by demonstrating that 1) autistic traits – measured quantitatively using the SRS – are elevated in children with ADHD ascertained from the general population, and 2) different ADHD subtypes are associated with markedly different levels of social impairment. (ibid)

       "...it appears that children with severe forms of ADHD, like children with autism, have clinically significant symptoms in all three autism symptom domains." (ibid)


Treating ADHD: Importantly for individuals, the success of prevention and/or treatment may be related to avoiding or reducing exposure to AD- and ADHD-associated factors such as smoking, lead, mercury, aluminum, etc. Furthermore, although some sections of webpages presented here mention treatments that may be relevant for specific individuals, working with a qualified health-care provider is recommended.


Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
Dxed with Asperger's


1. Co-occurrence of motor problems and autistic symptoms in attention-deficit/hyperactivity disorder

Reiersen AM, Constantino JN, Todd RD.
J Am Acad Child Adolesc Psychiatry. 2008 Jun;47(6):662-72.

OBJECTIVE: To investigate the relation between parent reports of motor problems and clinically significant autistic symptoms in children with and without attention-deficit/hyperactivity disorder (ADHD). METHOD: Subjects were male (n = 521) and female (n = 330) twins from an epidemiological study of ADHD, ages 7 to 19 years at assessment using the Child Behavior Checklist and semistructured psychiatric diagnostic interviews. Parent-rated Social Responsiveness Scale questionnaires were returned for 62% of 1,647 individuals who participated in interviews. After exclusion of subjects with incomplete data or evidence of mental retardation, 851 subjects (52%) were available for the present study analysis. Each subject was classified by DSM-IV ADHD subtype and assigned to one of seven population-defined ADHD subtypes based on latent class analysis of DSM-IV ADHD symptoms. Within each ADHD subtype, we examined the relation between Child Behavior Checklist motor problem endorsement and elevated autistic symptoms on the Social Responsiveness Scale. RESULTS: Motor problems and high levels of autistic traits were most common in individuals with combined-type ADHD. Within each of the clinically relevant DSM-IV and latent class ADHD subtypes, individuals with the combination of motor problems and ADHD were more likely to have high levels of autistic traits than those with ADHD alone. CONCLUSIONS: Children with the combination of ADHD and parent-reported motor coordination deficits have elevated levels of autistic symptoms. Targeted treatment and prevention interventions may be warranted. The exclusion criteria for DSM-IV ADHD should be revised to reflect these population-based findings.
    PMID: 18434922


2. Autistic traits in a population-based ADHD twin sample

Reiersen AM, Constantino JN, Volk HE, Todd RD.
J Child Psychol Psychiatry. 2007 May;48(5):464-72.

BACKGROUND: Most diagnostic nomenclatures do not allow for the concurrent diagnosis of autism and attention-deficit/hyperactivity disorder (ADHD). Clinic-based studies suggest autistic symptoms are common in children with ADHD, but such studies are prone to referral bias. This study assesses whether children with ADHD selected from the general twin population have elevated levels of autistic traits. METHODS: Nine hundred forty-six twins identified by Missouri birth records were assigned to DSM-IV ADHD diagnoses and seven population-derived ADHD subtypes defined through latent class analysis of DSM-IV ADHD symptoms. The Social Responsiveness Scale (SRS) was used as a quantitative measure of autistic traits. Linear regression was used to evaluate whether mean SRS scores differed between ADHD diagnostic groups. RESULTS: Mean SRS scores for DSM-IV predominantly inattentive subtype and combined subtype ADHD groups were significantly higher than for subjects without DSM-IV ADHD (p < .001, both comparisons). Five of the population-derived ADHD subtypes (talkative-impulsive, mild and severe inattentive, mild and severe combined) had significantly higher mean SRS scores compared to the latent class subtype with few ADHD symptoms (p < .001, all comparisons). DSM-IV combined subtype and the population-derived severe combined subtype had the highest mean total SRS scores and the highest mean scores for each of the three autism symptom domains, with a substantial proportion of individuals scoring in the clinically significant range. CONCLUSIONS: This study provides population-based evidence for clinically significant elevations of autistic traits in children meeting diagnostic criteria for ADHD. These results have implications for the design and interpretation of studies of both disorders.
    PMID: 17501727


3. The comorbidity of Pervasive Developmental Disorder and Attention Deficit Hyperactivity Disorder: results of a retrospective chart review

Goldstein S, Schwebach AJ.
J Autism Dev Disord. 2004 Jun;34(3):329-39.

OBJECTIVE: To determine if a sample of children meeting diagnostic criteria for a Pervasive Developmental Disorder (PDD) display symptoms and impairment related to Attention Deficit Hyperactivity Disorder (ADHD) sufficient to warrant a comorbid diagnosis of ADHD. Further, do children with PDD displaying such symptoms demonstrate more impairment in daily life activities than those children only having PDD? METHOD: A retrospective chart review was conducted on children (N = 57) diagnosed with the PDD's of Autism or PDD-Not Otherwise Specified (PDD-NOS), or ADHD. Comparative analysis of questionnaire and neuropsychological test data was completed to determine the severity of ADHD-like symptoms presenting among children with PDD. RESULTS: From the pool of subjects having PDD with sufficient data (N = 27), 7 or 26% met DSM-IV criteria for the combined type of ADHD. Nine or 33% met diagnostic criteria for the Inattentive Type of ADHD and 11 or 41% did not demonstrate a significant number of ADHD symptoms to warrant a comorbid diagnosis of ADHD. Results indicate that a subgroup of children with PDD displaying significant ADHD-like symptoms may in fact have ADHD thus warranting a comorbid diagnosis of ADHD. Current data did not suggest children with PDD and the combined type of ADHD demonstrated significantly more impairment in daily life functioning than those children only having PDD. However, this appeared likely the result of small sample size. The data, however, does indicate such children experience more difficulties in daily situations as rated by parents and teachers. CONCLUSION: These findings reinforce clinical observations indicating that some children with PDD may also experience an independent comorbid condition of ADHD, suggesting that a comorbid diagnosis of ADHD with PDD be considered in such cases. If further findings are replicated, the current exclusionary DSM-IV-TR criteria of making such a comorbid diagnosis should be re-considered.
   PMID: 15264500


4. Autism and attention deficit hyperactivity disorder: assessing attention and response control with the integrated visual and auditory continuous performance test

Corbett BA, Constantine LJ.
Child Neuropsychol. 2006 Aug;12(4-5):335-48.

Symptoms of attention deficit hyperactivity disorder (ADHD) have been widely reported in children with autism spectrum disorder (ASD). The current study investigated attention and response control in children with ASD, ADHD, and typical development using the Integrated Visual and Auditory Continuous Performance Test. Results indicate that many children with ASD show significant deficits in visual and auditory attention and greater deficits in impulsivity than children with ADHD or typical development. These findings suggest that many of the children with ASD demonstrate significant ADHD-like deficits. These findings are discussed in the context of symptoms, subtypes, and comorbidity.
   PMID: 16911977


5. Impact of comorbid autism spectrum disorders on stimulant response in children with attention deficit hyperactivity disorder: a retrospective and prospective effectiveness study

Santosh PJ, Baird G, Pityaratstian N, Tavare E, Gringras P.
Child Care Health Dev. 2006 Sep;32(5):575-83.

BACKGROUND: In the recent past, psychiatrists and paediatricians have avoided prescribing stimulant medication, such as methylphenidate and dexamphetamine to patients with autism spectrum disorders (ASD) because of both doubts about efficacy and concern that these medications make stereotypies worse. Recently, a number of small trials have suggested that methyphenidate does have a role in the management of hyperactivity in children with autistic spectrum disorders. METHODS: Children with ASD and attention deficit hyperactivity disorder (ADHD), and children with ADHD without ASD received standard treatment with methyphenidate from one specialist centre. A combination of standardized and novel outcome tools was used to allow both an exploratory retrospective study of 174 children and then a prospective study of a further 52 children to be carried out. RESULTS: After treatment with stimulants, the subjects in both groups showed statistically significant improvements in target symptoms of 'hyperactivity', 'impulsivity', 'inattention', 'oppositionality', 'aggression' and 'intermittent explosive rage'. The Clinical Global Impression-Improvement and efficacy index measures also improved in each group. In both the retrospective and the prospective studies, there was no statistically significant difference in the degree of improvements between each group. Importantly, neither tics nor repetitive behaviours worsened in either group. Children in the 'ADHD-only' group who were prescribed stimulants experienced significant 'nausea', 'giddiness', 'headaches' and 'sleep difficulties', whereas sleep difficulties were the only side effect that emerged in children in the ASD with ADHD group. CONCLUSIONS: Both studies presented here support previous findings from smaller studies that show children with autism and ADHD can respond as well to stimulants as children with ADHD alone. Although randomized controlled trials remain the gold standard for efficacy studies, systems like this that allow clinicians to continue rigorous and consistent monitoring for many years have a valuable role to play. Furthermore, such monitoring systems which now exist electronically can easily accumulate large data sets and reveal details about long-term effectiveness and long-term side effects of medication that are unlikely to be discovered in short-term trials.
    PMID: 16919137


6.  Attention-deficit hyperactivity disorder symptoms in a clinic sample of children and adolescents with pervasive developmental disorders

Lee DO, Ousley OY.
J Child Adolesc Psychopharmacol. 2006 Dec;16(6):737-46.

OBJECTIVES: The aims of this systematic chart review were to determine the frequency of attention-deficit/hyperactivity disorder (ADHD) in a clinic sample of children and adolescents with autism spectrum disorders (ASD), to compare ADHD symptoms in children with Autistic Disorder, Asperger's Disorder, and pervasive developmental disorders-not otherwise specified (PDD-NOS), to compare ADHD symptoms in individuals with and without ADHD-related chief complaints, and to determine the correlation between ADHD Rating Scale (ADHD RS) scores and age. METHOD: This systematic chart review examined data from children and adolescents who were consecutively referred to a university-based autism psychopharmacology program. All individuals were diagnosed by semistructured interview for ASD and ADHD, and ADHD symptoms were assessed using ADHD RS scores. RESULTS: Of 83 children, 78% fulfilled Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for ADHD and exceeded the 93rd percentile norm for the ADHD RS. Hyperactivity-impulsivity scores were significantly greater in individuals with autism than those with other ASDs. DSM-IV ADHD diagnosis was represented equally in individuals with and without ADHD as their chief complaints. ADHD RS hyperactivity-impulsivity and total scores were negatively correlated with age. CONCLUSION: ADHD symptoms are pervasive in clinically referred children and adolescents with ASD.
   PMID: 17201617


7. Autistic symptoms in children with attention deficit-hyperactivity disorder

Clark T, Feehan C, Tinline C, Vostanis P.
Eur Child Adolesc Psychiatry. 1999 Mar;8(1):50-5.

Children with the syndrome of disorders of attention, motor control and perception (DAMP) invariably fill diagnostic criteria for attention deficit hyperactivity disorder (ADHD) and commonly have symptoms of autistic spectrum disorders. This study estimates the rate of autistic symptoms in a sample of children with ADHD by using the parent-rated Autism Criteria Checklist. A high proportion of parents (between 65-80%) reported significant difficulties in social interaction (particularly in empathy and peer relationships), and communication (particularly in imaginative ability, nonverbal communication and maintaining conversation). The nature and relationship between ADHD and pervasive developmental disorders is considered, as well as implications for assessment, diagnosis and treatment.
   PMID: 10367741


8. Brief report: pervasive developmental disorder can evolve into ADHD: case illustrations

Fein D, Dixon P, Paul J, Levin H.
J Autism Dev Disord. 2005 Aug;35(4):525-34.

Despite prominent attentional symptoms in Pervasive Developmental Disorders (PDD) the relationship between PDD and Attention Deficit Hyperactivity Disorder (ADHD) has received little direct examination. In addition, outcome studies of children with PDD often focus on language, educational placement, or adaptive skills, but seldom on loss of the PDD diagnosis or change to another clinical syndrome. We present three cases in detail, and tabular data on eight more, that illustrate a clinical presentation in which prototypical cases of PDD evolve into clear-cut cases of ADHD from early to middle childhood.
   PMID: 16134038
 

Additional topics will be added from time to time

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April 17 2008