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PubMed2006

Effects of coexisting disorders on cognition and behavior in children with ADHD.

OBJECTIVE: To determine whether the presence of coexisting disorders affects memory, visual-motor skills, and daily functioning in children with ADHD. METHOD: Eighty-four boys and 18 girls (8 to 16 years old) participate in this study. Twenty children meet criteria for ADHD alone, 42 children for ADHD plus one other disorder, and 40 children for ADHD plus at least two other disorders (reading disability, developmental coordination disorder, oppositional defiant disorder, conduct disorder, anxiety, and depression). Children are assessed on memory and visual-motor skills. Parents complete measures of daily functioning. RESULTS: No significant group differences emerge for age, socioeconomic status, or IQ. Poorer performance on tests of memory and visual-motor skills, more prevalent behavioral problems, and more impairment in everyday functioning are associated with a higher number of coexisting disorders in children with ADHD. CONCLUSION: The presence of coexisting disorders has a significant influence on cognition and behavior of children with ADHD.

Activities of Daily Living↗

PubMed2006

The effect of polyphenolic extract from pine bark, Pycnogenol on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD).

UNLABELLED: Attention deficit hyperactivity disorder (ADHD) belongs to the neurodevelopmental disorders characterized by impulsivity, distractibility and hyperactivity. In the pathogenesis of ADHD genetic and non-genetic factors play an important role. It is assumed that one of non-genetic factors should be oxidative stress. Pycnogenol, an extract from the pine bark, consists of bioflavonoids, catechins, procyanidins and phenolic acids. Pycnogenol acts as powerful antioxidant, chelating agent; it stimulates the activities of some enzymes, like SOD, eNOS, and exhibits other biological activities. AIM: The aim of this randomized, double-blind, placebo-controlled trial was to investigate the influence of administered Pycnogenol or placebo on the level of reduced (GSH) and oxidized (GSSG) glutathione in children suffering from ADHD and on total antioxidant status (TAS). This is the first investigation of the redox glutathione state in relation to ADHD. RESULTS: One month of Pycnogenol administration (1 mg/kg body weight/day) caused a significant decrease in GSSG and a highly significant increase in GSH levels as well as improvement of GSH/GSSG ratio in comparison to a group of patients taking a placebo. TAS in children with ADHD was decreased in comparison with reference values. Pycnogenol administration normalizes TAS of ADHD children.

Adolescent↗

PubMed2006

A community assessment, open-label study of the safety, tolerability, and effectiveness of mixed amphetamine salts extended release in school-age children with ADHD.

OBJECTIVE: To assess the safety, tolerability, and effectiveness of mixed amphetamine salts extended release (MAS XR) in school-age children with attention-deficit/hyperactivity disorder (ADHD) treated in a community practice setting. METHODS: Children aged 6-12 years (N = 2968) with DSM-IV-defined ADHD entered a 9-week prospective, open-label, non-comparative study of MAS XR at 386 sites. For at least 2 weeks before enrollment, subjects with well-controlled ADHD received their consistent dose of previously prescribed psychostimulant. Subsequently, this regimen was converted to an equivalent once-daily dose of 10-, 20-, or 30-mg MAS XR, according to a conversion algorithm. Tolerability and safety were assessed based on reported treatment-emergent adverse events and observed changes in vital signs and body weight. Effectiveness was assessed using a parent-completed Conners' Global Index Scale (CGIS-P) measured 8 and 12 h postdose and a clinician-scored Clinical Global Impressions-Improvement (CGI-I) scale after 1, 3, and 7 weeks of treatment. The dose of study medication could be adjusted at weeks 1 and 3 to a maximum of 40 mg/day. Outcome analyses used an intent-to-treat methodology, with last observations carried forward. RESULTS: Statistically significant improvement in ADHD behavior 8 and 12 h postdose occurred during the first week of treatment and was maintained through study endpoint (p < 0.0001). Results of the investigator-rated CGI-I at weeks 1, 3, and 7 were consistent with the parent-rated CGIS-P results, indicating that MAS XR treatment significantly improved symptoms compared with the baseline stimulant regimen (p < 0.0001). The incidence of treatment-related adverse events was low, and most AEs were mild in intensity. CONCLUSION: MAS XR 10-40 mg is a safe and effective once-daily medication for treatment of children with ADHD in a community practice setting. ADHD symptoms may be further reduced by converting from current pharmacotherapy to an optimally titrated dose of MAS XR.

Amphetamines↗

PubMed2006

The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD).

BACKGROUND: ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. While dopamine release is decreased in SHR prefrontal cortex, norepinephrine concentrations are elevated. The noradrenergic system appears to be hyperactive as a result of impaired alpha-2A adrenoceptor regulation. Thus, the present study tested behavioral effects of the centrally acting alpha-2A adrenoceptor agonist guanfacine on SHR behavior. METHODS: The present study tested behavioral effects of guanfacine at doses of 0.075, 0.15, 0.30 and 0.60 mg base/kg i.p. in both male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. RESULTS: The striking impulsiveness, overactivity, and reduced sustained attention during baseline conditions in the SHR improved by treatment with guanfacine. The most pronounced improvement in SHR behavior was seen following the two highest doses (0.3 and 0.6 mg/kg) of guanfacine when SHR behaviors virtually normalized. The positive effects of the drug were most marked towards the end of the session. CONCLUSION: The results indicate that guanfacine improved poor noradrenergic modulation of neuronal circuits that involve the frontal lobes in an animal model of ADHD. The present results support the beneficial effects of guanfacine on ADHD behavior reported clinically and experimentally in primate models of frontal function. It is likely that guanfacine improved prefrontal functions in the SHR. It cannot be concluded, however, that the effects of the drug are mediated solely by norepinephrine.

Journal Article↗

PubMed2006

Serum level of semicarbazide-sensitive amine oxidase in children with ADHD.

BACKGROUND: The objective of this study was to analyze the extracellularly acting semicarbazide-sensitive amine oxidase (SSAO) serum levels in children with ADHD for the first time. SSAO is known to show deviations from normal in various somatic disorders and to interplay with the intracellularly active MAO. In humans two forms of SSAO a circulating form in plasma and a membrane-bound form are involved in monoaminergic metabolism. METHODS: We analyzed serum levels of SSAO in 27 children meeting ICD-10 criteria of Hyperkinetic Disorder (F90) or DSM-IV criteria of ADHD combined type by HPLC method and fluorimetric detection. A group of 42 healthy volunteers within the same age range (7.0 - 14.0 years) served as controls. RESULTS: No significant differences between children with ADHD (SSAO activity M = 773, SD = 217 mU/l) and healthy controls (SSAO activity M = 775, SD = 256 mU/l) in SSAO serum levels were found (F = 2.18; p > 0.14). Further, stimulant medication status had no influence on the result (F = 2.52; p > 0.11). CONCLUSION: There is no evidence for a deviation of SSAO serum activity in ADHD. Hence, extracellularly acting SSAO does not seem to be a promising factor for further research in ADHD. But progress in knowledge of its physiologic role and of the relationship between the membrane-bound and the circulating serum form may open new avenues for research on SSAO in ADHD.

Journal Article↗

PubMed2005

Delinquency, hyperactivity, and phonological awareness: a comparison of adolescents with ODD and ADHD.

The incidence of reading disabilities in children with attention deficit hyperactivity disorder (ADHD) has been found at a higher proportion than would be expected by chance. This study explored the relationship between reading problems-comprehension and phonological awareness, and externalizing behaviors-hyperactivity (ADHD), and oppositional defiant disorder (ODD). One hundred boys from Central Texas area alternative education schools between the ages of 11 and 15 were grouped by categories: ADHD-Combined Type (ADHD:C), ODD only, a combination of ADHD:C and ODD, and children without either ADHD or ODD. Results indicated that there were no significant differences among the four groups in terms of reading skills. However, findings suggest a significant negative linear relationship between hyperactivity and reading skills. Application of these findings is discussed.

Adolescent↗

PubMed2005

Selective effect of inhibition of literal or numerical irrelevant information in children with attention deficit hyperactivity disorder (ADHD) or arithmetic learning disorder (ALD).

This study investigated reasons why children with attention deficit hyperactivity disorder (ADHD) or arithmetic learning disorder (ALD) have difficulties in solving arithmetic word problems. In particular, the aim of this study was to verify whether these difficulties are due to a working memory deficit and defective inhibition of irrelevant information included in the problem wording. Furthermore, the study was geared to test whether children with ADHD or ALD have a specific disability in recalling and handling numerical or literal information. In an attempt to provide an answer to these questions, three groups of children were tested: children with ADHD, children with ALD, and a group of children achieving at normal levels. They were presented with a battery of arithmetic word problems containing irrelevant information (using either numerical or literal information). Children were asked to recall relevant information within the texts and then solve the problems. Children with ADHD recalled significantly more irrelevant literal information. Both children with ADHD and ALD recalled significantly more irrelevant numerical information. On the other hand, in the phase of problem solving, children with ADHD were more impaired by irrelevant literal information (which overloads memory), whereas children with ALD were more impaired by irrelevant numerical information (which may elicit the execution of wrong arithmetic procedures).

Achievement↗

PubMed2005

Implicit memory development in school-aged children with attention deficit hyperactivity disorder (ADHD): conceptual priming deficit?

Previous research has shown that children with attention deficit hyperactivity disorder (ADHD) often demonstrate performance deficits on effortful, strategic memory tasks, whereas relatively rote tasks of memory reveal no such deficit. Thus far, research in this domain has focused primarily on explicit memory. This study examined performance on multiple measures of implicit and explicit memory in children aged 7 to 14 years with and without ADHD. Memory for words and pictures was assessed at 15-min and 24-hr intervals. ADHD and non-ADHD groups performed similarly on tests of explicit memory (category-cued recall and recognition) and on perceptual aspects of implicit memory (word stem completion and picture fragment identification) as a function of age, retention interval, and stimulus format (i.e., picture or word). However, there was no evidence of priming on a conceptual implicit memory test (category exemplar generation) for boys with ADHD. This type of conceptual task, which is likely mediated by frontal systems, may indicate a unique memory deficit associated with ADHD.

Adolescent↗

PubMed1997

Diagnosing ADHD (predominantly inattentive and combined type subtypes): discriminant validity of the behavior assessment system for children and the achenbach parent and teacher rating scales.

Compared the effectiveness of discriminating attention deficit/hyperactivity disorder (ADHD) subtypes using the Parent Rating Scale (PRS) and Teacher Rating Scale (TRS) of the Behavior Assessment System for Children (BASC) and the Parent Report Form and Teacher Report Form (TRF) of the Achenbach Child Behavior Checklist (CBCL). To determine the extent to which these scales measured similar behaviors, Pearson Product-Moment Correlations were computed for the parent scales (PRS and CBCL) and for the teacher scales (TRS and TRF). Results indicated that correlations were significant for a number of scales. Discriminant analysis does not suggest a strong advantage of either measure in differentiating children with ADHD from those who do not meet criteria for ADHD, except for the BASC TRS which has better predictive ability for children who do not meet ADHD criteria. For subtypes of ADHD, and specifically the ADHD: Predominantly Inattentive subtype, however, results would favor the use of the BASC PRS and TRS.

Aggression↗

PubMed2001

Assessing ADHD across settings: contributions of behavioral assessment to categorical decision making.

Adapted methods of behavioral assessment to assess home and school functioning in a way that maps directly to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., [DSM-IV]; American Psychiatric Association, 1994). The study was conducted in a school-based sample with 5- to 12-year-old children referred to a school intervention team. A multigate set of procedures was used to assign children to one of 3 groups: attention deficit hyperactivity disorder (ADHD), inattentive group; ADHD, combined group; and a non-ADHD control group. The ADHD Rating Scale-IV was used to assess parent and teacher ratings of ADHD symptoms as delineated in DSM-IV. The findings suggest that the use of a fixed cutoff point (i.e., 6 or more symptoms), which is employed in the DSM-IV, is often not the best strategy for making diagnostic decisions. The optimal approach depends on whether diagnostic information is being provided by the parent or teacher and whether the purpose of assessment is to conduct a screening or a diagnostic evaluation. Also, the results indicate that a strategy that aggregates symptoms in the order in which they are accurate in predicting a diagnosis of ADHD is a more effective strategy than the approach used in DSM-IV, which aggregates any combination of a specific number of items. Implications for using methods of behavioral assessment to make diagnostic decisions using DSM-IV criteria are discussed.

Attention Deficit Disorder with Hyperactivity↗

PubMedDate not supplied

Improving guideline adherence for the diagnosis of ADHD in an ambulatory pediatric setting.

BACKGROUND: The American Academy of Pediatrics (AAP) has published clinical practice guidelines for the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD). However, implementation of guidelines has been notoriously difficult to achieve in the wider context of changing individual physicians' clinical practice. OBJECTIVE: Implement a formalized diagnostic protocol for ADHD and study whether this protocol improved adherence of pediatric residents and faculty to published guidelines for the diagnosis of ADHD. METHODS: Quasi-experimental retrospective record review of 63 pediatric patients evaluated for ADHD by pediatric residents and faculty in an outpatient pediatric clinic before (n = 25) and after (n = 38) implementation of a formal diagnostic process for ADHD. The key elements of the new diagnostic process include completion of a semistructured interview and mandatory rating scales for home and school. The published AAP guidelines include 1) documentation of Diagnostic and Statistical Manual for Mental Disorders (DSM) IV criteria; 2) evidence of core symptoms obtained directly from home and 3) from school; and 4) assessment for coexisting conditions. Adherence was assessed to each criterion individually (yes/no) and was summarized in a single score. RESULTS: Only 4% of clinicians and nurse practitioners diagnosing children in the before group adhered to all 4 AAP guidelines, compared to 82% in the after group (P < .001). Significant improvement was observed across each of the 4 criteria in the AAP guidelines. Moreover, the improvement in adherence to all 4 guidelines was noted for residents and faculty. CONCLUSION: A significant improvement in adherence to AAP guidelines was obtained for all providers through implementation of a structured diagnostic approach to ADHD.

Ambulatory Care↗

PubMed2005

Comorbidity between ADHD and symptoms of bipolar disorder in a community sample of children and adolescents.

The prevalence and frequency of comorbidity of possible bipolar disorder was examined with attention-deficit hyperactivity disorder (ADHD) in a nonreferred population of twins. Children and adolescents aged 7 to 18 years with a history of manic symptoms were identified from a population-based twin sample obtained from state birth records (n = 1610). The sample was enriched for ADHD; however, there was also a random control sample (n = 466), which allowed a look at the population prevalence of the disorder. Juveniles with threshold or below threshold manic episodes were further assessed for comorbidity with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) and population-defined ADHD subtypes (from latent class analysis) using Fisher's exact test. Nine juveniles who exhibited DSM-IV manic (n = 1), hypomanic (n = 2) or below threshold episodes (n = 6) were identified. The population prevalence of broadly defined mania in the random sample was 0.2%. The possible manic episodes showed significant comorbidity with population-defined severe combined and talkative ADHD subtypes. It can be concluded that there is a significant association of bipolar symptoms with two population-defined subtypes of ADHD. Episodes of possible bipolar disorders as defined by DSM-IV are uncommon in this nonreferred sample. Children and adolescents with ADHD appear to be only modestly at increased risk for bipolar disorders.

Adolescent↗

PubMed1992

Use of a verbal fluency measure in understanding and evaluating ADHD as an executive function disorder.

A primary characteristic of Attention Deficit Hyperactivity Disorder (ADHD) is an inability to establish and maintain sustained attention, which is speculated to reflect frontal lobe involvement. The Knight Verbal Fluency measure was administered to 19 ADHD inpatient boys and to a cohort group of 7 children who were matched for mean age, psychiatric diagnosis (depression), treatment facility, and examiner but were without the diagnosis of ADHD. Analysis indicated that ADHD children performed significantly lower than expected and lower than the similar non-ADHD children. These findings lend support to the hypothesis that frontal lobe dysfunction is involved in attentional process disorders and suggests the potential clinical usefulness in the diagnostic screening of ADHD children of a simply administered measure amenable to interpretation of frontal lobe function.

Adolescent↗

PubMed2003

Overflow movements predict impaired response inhibition in children with ADHD.

Neurologic models proposed to explain mechanisms underlying ADHD have emphasized deficits in response inhibition. Age-inappropriate overflow movements, e.g., mirror movements, are motor signs thought to reflect immaturity in cortical systems involved in automatically (unconsciously, without explicit effort) inhibiting extraneous movement. We investigated the hypothesis that the presence of excessive overflow movements would predict measures of conscious, effortful response inhibition (conflicting and contralateral motor response tests) in children with ADHD. 42 children with ADHD and 30 controls, ages 8 through 12 years, participated. Children with ADHD showed significantly more overflow movements than did controls and made more errors on the conflicting and contralateral motor response tests. Multiple linear regression analysis indicated that overflow movements predicted performance on measures of motor response inhibition. For one of those measures, the contralateral motor response test, there was a significant interaction with diagnosis, such that overflow predicted response inhibition in ADHD but not in controls. The findings suggest that overflow movements, which can be readily observed as part of clinical examination, are more evident in children with ADHD. Positive correlations between measures of overflow movements and measures of response inhibition suggest that closely associated neural mechanisms underlie these deficits and support hypotheses that age-inappropriate overflow reflects immaturity of cortical systems involved in automatic inhibition.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

The modulation of late component event related potentials by pre-stimulus EEG theta activity in ADHD.

Electroencephalography (EEG) and Event Related Potentials (ERPs) studies in ADHD have generally been studied separately. This study examined these measures simultaneously in 54 adolescent unmedicated ADHD males and age and gender matched normal controls during an auditory oddball paradigm. Compared with controls, ADHD patients showed increased pre-stimulus EEG Theta activity and post-stimulus reduced N200 amplitude, increased P200 amplitude and delayed N200 and P300 latencies evoked to target stimuli. Moreover, Theta activity was negatively correlated with N200 amplitude and positively correlated with P200, N200 and P300 latency in ADHD. There were no correlations in the control group. Pre-stimulus preparatory state increases in Theta activity in ADHD may underlie some of the reported disturbances in information processing reflected in ADHD.

Adolescent↗

PubMed2006

The adrenergic receptor alpha-2A gene (ADRA2A) and neuropsychological executive functions as putative endophenotypes for childhood ADHD.

There is resurgent interest in the psychiatric literature in endophenotypes, variables thought to more strongly reflect the effects of candidate genes than do manifest disorders. In a sample of 176 children with attention deficit hyperactivity disorder (ADHD) and 52 of their siblings, we examined the validity of several putative endophenotypes for ADHD that represent commonly used clinical measures of multiple cognitive/neuropsychological domains of executive functions (EFs). We review their distributional normality, their relations to ADHD symptoms in probands and unaffected siblings relative to nonADHD controls, and their correlation in siblings. We also tested theEF measures' associations with the ADRA2A gene and whether they mediated or moderated the associations between ADHD and ADRA2A. Several EF measures showed association with ADRA2A, as well as moderation, but not mediation, of its association with ADHD. Implications of the results for evaluating the validity and utility of putative endophenotype measures and for finding candidate gene effects on ADHD are discussed.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

Incorporating the management of ADHD into your practice. Can it be done?

BACKGROUND: Management of children with learning and behavioural disorders has traditionally been the precinct of specialist paediatricians, psychiatrists, psychologists and teaching professionals. Networks and teams have not generally included general practitioners. In Geraldton a professional network of health and educational professionals were of the view that learning disorders including attention deficit hyperactivity disorder (ADHD) frequently went unrecognised or misdiagnosed. In 1996 the National Health and Medical Research Council recommended use of the DSM-IV American Psychiatric Association diagnostic criteria for ADHD. A multimodal model of shared care was considered optimal. In 1999 the US National Institute of Mental Health's Multimodal Treatment Study of Children with ADHD was released. OBJECTIVE: To outline the development of a program to educate and support local professionals (doctors, teachers, psychologists, nurses, counsellors) in the management of behavioural disorders in which specific goals were to: build capacity for accurate diagnosis and management of children with learning and behavioural disorders facilitate via the Midwest Division of General Practice, a network of professionals to assess and manage learning disorders, including ADHD create a model of shared care with potential for application elsewhere formalise shared care/coprescriber arrangements for stimulant medications between GPs and specialists, including fast-tracking of medication develop school networks for early identification, referral and support of ADHD cases. DISCUSSION: Our creation of a strong professional network enabling a GP case manager role has been very successful. Multiple treatment successes have created much community goodwill toward the Midwest Division of General Practice and my private practice has changed forever with the inclusion of 200 ADHD families. Colleagues considering entering this area need to recognise the potential for disruption to both their practice and their personal lives. A well organised practice with firm boundaries for difficult cases is essential.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

Adult ADHD. Concluding thoughts.

This concluding paper raises some final questions and issues that the authors feel should receive more emphasis in future research on ADHD in adults. One significant problem for our field is the upward extension of child-based models and approaches without proper adaptation to adults. With adults differing patterns of comorbidity and symptom heterogeneity pose new conceptual, diagnostic, and treatment challenges. As an illustration, we review ten common presenting complaints in adults and their link to the underlying core ADHD deficits of hyperkinesis, inattention, and impulsivity. While these core symptoms are often overt problems in children, in adults subtler executive dysfunction appears. Even though the growing consensus is that ADHD is a disorder of executive functions (EF), the details of the EF/ADHD connection remain unclear and may be far more complex in adults. That complexity is mirrored in the widening anatomic representation of EF, extending beyond the frontal lobes into the subcortex and other nonfrontal regions. More research will be needed to follow the developmental trajectory of executive dysfunction in ADHD over the life cycle and tie this to the developmental neuropsychology of EF. Psychosocial context and nongenetic familial influence are also critical variables that need greater consideration when characterizing and measuring ADHD symptoms in adults. Finally, until we have reached consensus on adult subject selection, we may not be able to enhance diagnostic rigor or expand our conceptual framework for understanding the underlying pathophysiology of ADHD in adults.

Attention Deficit Disorder with Hyperactivity↗