Attention-deficit hyperactivity disorder and hyperkinetic disorder.
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Attention Deficit Disorder with Hyperactivity↗
Biomedical subjects
J M Swanson
Publications and source records attributed to J M Swanson.
Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach.
Previously in this journal, we reported an association of the dopamine D4 receptor gene (DRD4) and attention deficit hyperactivity disorder (ADHD). In a population-association (case-control) study of 39 children with a refined phenotype of ADHD and 39 ethnically matched controls, we observed an increased percentage of the 7 repeat allele (29% vs 12%) and the 7+ genotype (49% vs 21%) in the ADHD group compared to the control group. In a replication and an extension of our initial study, we recruited another sample of ADHD subjects and found percentages of the 7 repeat allele (28%) and the 7+ genotype (48%) consistent with our previous findings. We used a family-based approach to evaluate a predicted association of DRD4 and ADHD based on a test of allele transmission focused on the 7 repeat allele. We identified 52 families based on the diagnosis of the refined phenotype of ADHD in the proband and the availability of DNA from both biological parents as well as the proband. Haplotype relative risk (HRR) analysis was performed to test our a priori hypothesis and produced significant results (chi-square = 4.65, P < 0.035). This provides additional evidence that the DRD4 gene is associated with a refined phenotype of ADHD.
Alleles↗
Effect of reinforcement on facial responsivity and persistence in children with attention-deficit hyperactivity disorder.
Children with Attention Deficit-Hyperactivity Disorder (ADHD) may learn poorly under conditions of inconsistent (partial) reinforcement because they are easily frustrated and fail to develop persistence. To test this hypothesis, a nonsense word spelling task was used with 22 ADHD and 20 control children to investigate the effects of partial and continuous reinforcement on facial responsivity (frustration measure), words spelled correctly (learning performance measure), and persistence ratings. Partially reinforced ADHD children manifested higher levels of frustration in both acquisition and extinction than any other group and gave significantly lower persistence ratings across acquisition than partially reinforced control children. ADHD children spelled fewer words correctly than controls, regardless of reinforcement schedule. These findings suggest that partial reinforcement training develops persistence in normal but not ADHD children. The findings have theoretical implications for the etiology of ADHD as well as practical implications for designing behavior modification programs to treat ADHD.
Attention↗
How a regression artifact makes ICFs/MR look ineffective.
Based on a simple matched-control group quasi-experiment, Conroy (1996) concluded that small ICFs for persons with mental retardation have negative quality-of-life impacts. Our analysis of Conroy's design suggests, in contrast, that the reported effect is a pure regression artifact. The flaw in Conroy's design is selecting a control group on the basis of pretest matching. Although selecting a subsample of controls by matching on static characteristics such as age or gender can reduce the confounding influence of these variables, selection on the basis of pretest scores leads invariably to a large, spurious effect. The literature on this issue dates back a century, with warnings against pretest matching by Galton, Thorndike, McNemar, Stanley, Campbell, Cronbach, and Cook. We reviewed this historical literature and then used a Monte Carlo experiment to estimate the spurious effect that Conroy would observe from pretest matching alone. The magnitude of the artifact is as large as the quality-of-life reduction that Conroy attributed to the effects of living in an ICF. We discussed the methodological logic involved in matching and the broader policy issues raised by this evaluation.
Artifacts↗
Evaluation of individual subjects in the analog classroom setting: I. Examples of graphical and statistical procedures for within-subject ranking of responses to different delivery patterns of methylphenidate.
In this article, we describe graphical and statistical methods developed to evaluate the response patterns of individual children with attention deficit hyperactivity disorder (ADHD) to different conditions of treatment with stimulant medication. We used data from an investigation of drug delivery patterns to demonstrate these methods. Thirty-one children with ADHD participated in a double-blind crossover study of four conditions (three patterns of delivery of methylphenidate and a placebo control). In each condition, the children were evaluated across an 11-hour (7:00 a.m. to 6:00 p.m.) laboratory school day, and ratings of classroom behavior were obtained at regular intervals across the day. Graphical procedures were developed to display, for each individual, time courses of multiple measures of behavior taken across each double-blind test day. Expert clinicians judged these graphs and used this information to rank-order the test days from best to worst. A within-subject variant of Kendall's W was used to evaluate, for each subject, whether the rankings of these multidimensional graphs were reliable (concordant) across judges. A generalized kappa statistic was used to evaluate, for each condition, the reliability of the judges' rankings across subjects. Friedman's analysis of variance of ranks was used to evaluate, for the study, whether the conditions differed in terms of the average (consensus) rank assigned by the judges.
Attention Deficit Disorder with Hyperactivity↗
Evaluation of individual subjects in the analog classroom setting: II. Effects of dose of amphetamine (Adderall).
Multiple dependent variables were graphed for 29 subjects who participated in a double-blind evaluation of 4 doses of Adderall, plus positive (methylphenidate) and placebo control conditions. Five judges ranked the conditions for each subject, and analyses of individual subjects indicated that these rankings were concordant (reliable) across judges. Consensus rankings were assigned to each subject, and an analysis of these ranks showed that the conditions differed significantly. The choice of best conditions were judged to be across 3 doses of Adderall (10, 15, and 20 mg). This confirms the clinical impression of individual differences in optimal dose of stimulant medication. The methodological, graphical, and statistical methods presented in this article provide a systematic, reliable procedure for evaluating relative response of individuals to different doses of stimulant medication.
Amphetamine↗
Reliability and validity of the SKAMP rating scale in a laboratory school setting.
In children with attention deficit hyperactivity disorder (ADHD), the effects of methylphenidate were investigated in a pharmacodynamic comparison of placebo and the standard b.i.d. administration of methylphenidate. In each of these conditions, teachers completed ratings in classroom settings at times chosen to coincide with expected "peaks" and "troughs" of serum concentrations in the b.i.d. condition. Analyses of variance (ANOVAs) revealed the expected differences between the two conditions in the laboratory classroom setting using standard rating scales (Conners and the IOWA Conners) and a new rating scale (the SKAMP), which specifically measures the classroom manifestation of ADHD. The psychometric properties of the SKAMP were evaluated by calculating test-retest reliability and by calculating correlations with the standard rating scales to establish concurrent validity.
Attention Deficit Disorder with Hyperactivity↗
Analog classroom assessment of Adderall in children with ADHD.
OBJECTIVE: This was a randomized, double-blind, crossover study of 30 children with attention-deficit/hyperactivity disorder (ADHD) that evaluated the time course effects of four doses of Adderall (5, 10, 15, and 20 mg), an inactive control (placebo), and a positive control (clinical dose of methylphenidate). METHOD: For each treatment condition, a capsule was administered in the morning and assessments were performed in an analog classroom setting every 1.5 hours across the day. Subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measures were obtained for each classroom session, and these measures were used to evaluate time-response and dose response effects of Adderall. RESULTS: For doses of Adderall greater than 5 mg, significant time course effects were observed. Rapid improvements on teacher ratings and math performance were observed by 1.5 hours after administration, and these effects dissipated by the end of the day. The specific pattern of time course effects depended on dose: the time of peak effects and the duration of action increased with dose of Adderall. CONCLUSIONS: This documentation of efficacy in a controlled study supports the addition of Adderall to the armamentarium of psychotropic medications for the treatment of ADHD. The differences in time-response patterns of Adderall and methylphenidate may help tailor treatment to meet specific clinical needs of different children with ADHD.
Adolescent↗
National Institute of Mental Health Collaborative Multimodal Treatment Study of Children with ADHD (the MTA). Design challenges and choices.
The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first child multisite cooperative agreement treatment study of children conducted by the National Institute of Mental Health, Rockville, Md. It examines the long-term effectiveness of medication vs behavioral treatment vs both for treatment of ADHD and compares state-of-the-art treatment with routine community care. In a parallel-groups design, 576 children (age, 7-9 years) with ADHD (96 at each site) are thoroughly assessed and randomized to 4 conditions: (1) medication alone, (2) psychosocial treatment alone, (3) the combination of both, (4) or community comparison. The first 3 groups are treated for 14 months and all are reassessed periodically for 24 months. Designers met the following challenges: framing clinically relevant primary questions; defining the target population; choice, intensity, and integration and combination of treatments for fair comparisons; combining scientific controls and standardization with clinical flexibility; and implementing a controlled clinical trial in a nonclinical setting (school) controlled by others. Innovative solutions included extensive decision algorithms and manualized adaptations of treatments to specific needs.
Attention Deficit Disorder with Hyperactivity↗
Covert visual spatial attention in boys with attention deficit hyperactivity disorder: lateral effects, methylphenidate response and results for parents.
We report three related studies of covert visual spatial orienting in child attention deficit hyperactivity disorder (ADHD). In Study 1, we examined covert visual spatial orienting in ADHD and comparison boys, Study 2 comprised a dose-response study of methylphenidate for the ADHD group, and Study 3 was an investigation of biological and adoptive parents. In contrast with comparison subjects (n = 17). ADHD boys aged 6-12 (n = 27) showed both slower reaction times overall and within-condition (lateral) asymmetries in reaction times. Specifically, boys with ADHD reacted more slowly to uncued targets in the left visual field than in the right visual field. Responses to stimuli in the two visual fields were differentially affected by methylphenidate for the ADHD group. Medication equalized visual field responses to the uncued targets, resulting in a significant cue x dose x visual field interaction. Further, medication altered the relative cue responsivity in the two visual fields, resulting in a significant dose x visual field interaction for the Validity Effect. Biological parents of ADHD boys (n = 16) also showed slower reaction times to uncued left visual field targets than to right visual field targets; in addition they showed slower response to invalidity cued targets in the right visual field. These literal effects were not observed in adoptive parents of ADHD boys (n = 12) or biological parents of comparison boys (n = 14). Possible abnormal hemispheric asymmetry of attention functions in boys with ADHD and their biological parents is discussed.
Adoption↗
Lateralized attentional deficits in drug-free and medicated schizophrenic patients.
Performance on a cued reaction time (RT) task, theoretically linked to posterior and anterior neuroanatomical systems in the brain (Posner, M. I. et al., Science, 1988, 210, 1627-1631; Archives of General Psychiatry, 1988, 15, 811-821), was used to assess sensory orienting and maintenance of attention. In schizophrenic patients, Posner et al. found a lateralized abnormality in RT (longer RTs to uncued targets in the right visual field than in the left visual field), as did Maruff et al. (Neuropsychologia, 1995, 33, 1205-1223), but Strauss et al. (Journal of Psychiatric Research, 1991, 37, 139-146), among others, did not replicate this effect. However, the subjects in these studies differed in the percentage of schizophrenic patients taking neuroleptic medication at the time of testing and in the chronicity of the illness. In the present study, we used two groups of schizophrenic subjects to control for the use of neuroleptic medication. The lateralized abnormality in RT was observed in the drug-free group of schizophrenic subjects, but not in the group of drug-treated schizophrenic subjects.
Adolescent↗
Medication treatment strategies in the MTA Study: relevance to clinicians and researchers.
OBJECTIVE: Clinicians have difficulty applying drug research findings to clinical practice, because research protocols use methods different from those used in daily office practice settings. METHOD: To design a medication protocol for a multisite clinical trial involving 576 children with attention-deficit hyperactivity disorder (ADHD) while maintaining relevance to clinical practice, investigators from the NIMH Collaborative Multisite Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA study) developed novel medication strategies. These were designed to work either in a monomodal or multimodal format and to ensure standard approaches are used across diverse sites. Each child randomized to medication (projected N = 288) is individually titrated to his or her "best" methylphenidate dose and has individual ADHD symptoms monitored. Decision rules were developed to guide "best dose" selection, dose changes, medication changes, the management of side effects, and integration with psychosocial treatments. CONCLUSIONS: The MTA study uses a controlled method to standardize the identification of each child's "best" methylphenidate dose in a national, multisite cooperative treatment program. Although the titration protocol is complex, the study's individual dosing approach and algorithms for openly managing ADHD children's medication over time will be of interest to clinicians in office practice.
Adolescent↗
Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder.
Dopamine is believed to play a major role in the manifestation of attention deficit hyperactivity disorder (ADHD), which affects 3-6% of school-age children and shows evidence of familiarity. The dopamine D4 receptor, which is preferentially distributed in cortical and limbic regions of the brain, is currently of major interest because of the high degree of functionally relevant variability in its gene (DRD4), and the association of this gene with Novelty Seeking behavior. We examined the variability in the length of a region of DRD4 that contains a 48-bp repeat sequence in children with ADHD and controls matched for ethnicity. ADHD children differed from controls in that the 7-fold repeat form of DRD4 occurred significantly more frequently than in the control sample. This form of the receptor has previously been shown to mediate a blunted intracellular response to dopamine. Although ADHD is likely to be multifactorial in its etiology and its heritability is likely to be polygenetic, the present findings suggest that polymorphic variation in the gene encoding the D4 dopamine receptor may be a contributing factor in the expression of symptoms associated with ADHD.
Attention Deficit Disorder with Hyperactivity↗
More frequent diagnosis of attention deficit-hyperactivity disorder.
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Attention Deficit Disorder with Hyperactivity↗
Interaction of cytochrome c with cardiolipin: an infrared spectroscopic study.
The interactions of cytochrome c (cyt c) with cardiolipin, a major anionic phospholipid of mitochondrial membranes, and dioleoylphosphatidylglycerol (DOPG), have been compared by infrared (IR) spectroscopy. The Fourier self-deconvoluted IR spectra of the lipid carbonyl groups indicate that both cyt c3+ and cyt c2+ perturb and/or dehydrate the interfacial region of cardiolipin bilayers. Only a slight perturbation, if any, is observed in the interfacial region of DOPG bilayers. However, the phosphate head region of DOPG is perturbed by cyt c3+, which was not detected in cardiolipin. The results suggest that cytochrome c in both redox states can partially penetrate into cardiolipin but not into DOPG bilayers. The interaction of cyt c with cardiolipin and DOPG is mainly hydrophobic and electrostatic, respectively. The Fourier self-deconvoluted IR spectra in the amide I region reveal that ca. 10% of the cyt c3+ alpha-helix unfolds to random coil upon binding to cardiolipin bilayers. However, only very slight secondary structural changes, if any, were detected when cyt c3+ binds to DOPG bilayers.
Amides↗
NIMH collaborative multisite multimodal treatment study of children with ADHD: I. Background and rationale.
OBJECTIVE: The National Institute of Mental Health's recently initiated 5-year, multisite, multimodal treatment study of children with attention-deficit hyperactivity disorder (MTA) is the first major clinical trial in its history focused on a childhood mental disorder. This article reviews the major scientific and clinical bases for initiating the MTA. METHOD: A selective review of the literature is presented in the service of describing the estimated prevalence of ADHD among children and adolescents, its core clinical features, evidence concerning psychopharmacological and psychosocial treatment effects, and related research issues and trends leading to the development of the MTA. RESULTS: Despite decades of treatment research and clinical practice, there is an insufficient basis for answering the following manifold question: under what circumstances and with what child characteristics (comorbid conditions, gender, family history, home environment, age, nutritional/metabolic status, etc.) do which treatments or combinations of treatment (stimulants, behavior therapy, parent training, school-based intervention) have what impacts (improvement, stasis, deterioration) on what domains of child functioning (cognitive, academic, behavioral, neurophysiological, neuropsychological, peer relations, family relations), for how long (short versus long term), to what extent (effect sizes, normal versus pathological range), and why (processes underlying change)? CONCLUSIONS: The important scientific, clinical, and public health issues nested within this manifold question provide both the impetus and scaffolding for the MTA.
Adolescent↗
Pemoline effects on children with ADHD: a time-response by dose-response analysis on classroom measures.
OBJECTIVE: To evaluate the dose-response by time-response characteristics of pemoline (Cylert) on dependent measures of behavior and academic performance in a laboratory classroom. METHOD: After a 2-week baseline, a double-blind crossover design was used to compare placebo, 18.75 mg, 37.5 mg, 75 mg, and 112.5 mg of pemoline, q.a.m., with each dose administered for 1 week. Medication was given at 9:00 A.M., and performance was measured beginning immediately and beginning 2, 4, and 6 hours after ingestion. The dependent measures included number of math problems completed correctly, teacher-recorded rates of on-task behavior and noncompliance, and teacher ratings on an Abbreviated Conners Teacher Rating Scale. RESULTS: There were linear effects of medication, with pemoline doses greater than 18.75 mg having an effect beginning 2 hours after ingestion and lasting through the seventh hour after ingestion. CONCLUSIONS: Results are contrasted with widespread misbeliefs regarding pemoline's time course and efficacy.
Attention Deficit Disorder with Hyperactivity↗
A description of the gender differences in risk behaviors in young adults with genital herpes.
The purpose of this paper is to describe gender differences in risk behaviors--substance use and sexual behavior--in young adults with genital herpes. Two-hundred fifty-two young adults with genital herpes were recruited into the study via newspaper advertisements in a West Coast metropolitan area. As a part of a large randomized clinical trial, participants completed questionnaires measuring demographic characteristics and the risk behaviors of substance use and sexual behavior. Participants had a mean age of 27.1 years and were largely Caucasian, employed, college-educated, and heterosexual. Women were two years younger than men and had less income. Gender differences were found in both substance use and sexual behavior. Men were more likely to report current use of illicit drugs than were women. Men were also more likely to report a history of gonorrhea, and urethral discharge. Women reported initiating sex at an older age and having fewer sexual partners over their lifetimes than men. There were no gender differences in use of condoms or spermicides specifically to prevent transmission of genital herpes. Further study is needed of these young adults as they are at high risk for transmission of the disease and also for contracting other sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection. Sensitive interventions are needed with this high-risk population.
Adolescent↗