Personality Mediation of Genetic Effects on Attention-Deficit/Hyperactivity Disorder

Personality traits may be viable candidates for mediators of the relationship between genetic risk and ADHD. Participants were 578 children (331 boys; 320 children with ADHD) between the ages of six and 18. Parents and teachers completed a comprehensive, multi-stage diagnostic procedure to assess ADHD and comorbid disorders. Mother completed the California Q-Sort to assess child Big Five personality traits. Children provided buccal samples of DNA which were assayed for selected markers on DRD4, DAT1, and ADRA2A. An additive genetic risk composite was associated with ADHD symptoms and maladaptive personality traits; maladaptive personality traits were associated with ADHD symptoms. Low conscientiousness and high neuroticism partially mediated the relationship between genetic risk and ADHD symptoms. Mediation effects for conscientiousness were specific to inattentive symptoms; effects for neuroticism generalized to all disruptive behaviors. High neuroticism and low conscientiousness may be useful as early markers for children at risk for ADHD.     

Peer Rejection and Friendships in Children with Attention-Deficit/Hyperactivity Disorder: Contributions to Long-Term Outcomes

Even after evidence-based treatment, Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with poor long-term outcomes. These outcomes may be partly explained by difficulties in peer functioning, which are common among children with ADHD and which do not respond optimally to standard ADHD treatments. We examined whether peer rejection and lack of dyadic friendships experienced by children with ADHD after treatment contribute to long-term emotional and behavioral problems and global impairment, and whether having a reciprocal friend buffers the negative effects of peer rejection. Children with Combined type ADHD (N?=?300) enrolled in the Multimodal Treatment Study of Children with ADHD (MTA) were followed for 8 years. Peer rejection and dyadic friendships were measured with sociometric assessments after the active treatment period (14 or 24 months after baseline; M ages 9.7 and 10.5 years, respectively). Outcomes included delinquency, depression, anxiety, substance use, and general impairment at 6 and 8 years after baseline (Mean ages 14.9 and 16.8 years, respectively). With inclusion of key covariates, including demographics, symptoms of ADHD, ODD, and CD, and level of the outcome variable at 24 months, peer rejection predicted cigarette smoking, delinquency, anxiety, and global impairment at 6 years and global impairment at 8 years after baseline. Having a reciprocal friend was not, however, uniquely predictive of any outcomes and did not reduce the negative effects of peer rejection. Evaluating and addressing peer rejection in treatment planning may be necessary to improve long-term outcomes in children with ADHD.     

Attention-Deficit/Hyperactivity Disorder,Trait Impulsivity,and Externalizing Behavior in a Longitudinal Sample

Attention-deficit/hyperactivity disorder (ADHD) is highly comorbid with and predictive of externalizing behavior, yet is most often examined categorically, not dimensionally. We tested a recently proposed trait impulsivity model by dimensionally examining measures of childhood inattention and hyperactivity/impulsivity separately as predictors of later externalizing behavior in an all-female longitudinal sample of 228 young women. We also examined influences of parenting and peer relations, given the transactional nature and importance of environmental factors. We analyzed the relative contribution of hyperactive/impulsive (HI) and inattentive (IA) symptoms of girls with and without childhood-diagnosed ADHD (M age?=?9.5; 140 ADHD and 88 Comparison) to the development of externalizing behaviors in adolescence (M age?=?14.2) and early adulthood (M age?=?19.6). Authoritarian parenting was examined as a moderator and adolescent externalizing behavior as a mediator of the relation between childhood HI and later externalizing behavior. Childhood HI symptoms significantly predicted multiple externalizing behaviors in adolescence and early adulthood, after accounting for IA and covariates (ΔR ² ranged from 2.6 to 7.5 %). Mother’s authoritarian parenting moderated this relation. Adolescent externalizing behavior mediated the relation between childhood HI symptoms and early adult externalizing behavior. In no case did childhood IA significantly predict externalizing behavior after accounting for HI symptoms. Findings support a trait impulsivity model, as HI symptoms, but not IA symptoms, significantly predicted later externalizing behavior. Results support the importance of dimensional predictors of developmental trajectories. We discuss implications for assessment, intervention, and future research.     

Etiologic Subtypes of Attention-Deficit/Hyperactivity Disorder: Brain Imaging, Molecular Genetic and Environmental Factors and the Dopamine Hypothesis

Multiple theories of Attention-Deficit/Hyper- activity Disorder (ADHD) have been proposed, but one that has stood the test of time is the dopamine deficit theory. We review the narrow literature from recent brain imaging and molecular genetic studies that has improved our understanding of the role of dopamine in manifestation of symptoms of ADHD, performance deficits on neuropsychological tasks, and response to stimulant medication that constitutes the most common treatment of this disorder. First, we consider evidence of the presence of dopamine deficits based on the recent literature that (1) confirms abnormalities in dopamine-modulated frontal-striatal circuits, reflected by size (smaller-than-average components) and function (hypoactivation); (2) clarifies the agonist effects of stimulant medication on dopaminergic mechanisms at the synaptic and circuit level of analysis; and (3) challenges the most-widely accepted ADHD-related neural abnormality in the dopamine system (higher-than-normal dopamine transporter [DAT] density). Second, we discuss possible genetic etiologies of dopamine deficits based on recent molecular genetic literature, including (1) multiple replications that confirm the association of ADHD with candidate genes related to the dopamine receptor D4 (DRD4) and the DAT; (2) replication of differences in performance of neuropsychological tasks as a function of the DRD4 genotype; and (3) multiple genome-wide linkage scans that demonstrate the limitations of this method when applied to complex disorders but implicate additional genes that may contribute to the genetic basis of ADHD. Third, we review possible environmental etiologies of dopamine deficits based on recent studies of (1) toxic substances that may affect the dopamine system in early development and contribute substantially to the etiology of ADHD; (2) fetal adaptations in dopamine systems in response to stress that may alter early development with lasting effects, as proposed by the developmental origins of health and disease hypothesis; and (3) gene-environment interactions that may moderate selective damage or adaptation of dopamine neurons. Based on these reviews, we identify critical issues about etiologic subtypes of ADHD that may involve dopamine, discuss methods that could be used to address these issues, and review old and new theories that may direct research in this area in the future.     

Efficacy of Adderall for Attention-Deficit/Hyperactivity Disorder: a meta-analysis

Stimulant medication has, for many years, been the pharmacological treatment of choice for children and adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Several studies have shown Adderall , to be efficacious for measures of inattention, hyperactivity-impulsivity, aggression, disruptive behavior, and academic productivity. Although these studies provide useful information for clinicians treating ADHD children and adults, the variability in efficacy among the different types of measures used within each study has not been comprehensively examined. Thus, to provide a clearer picture of what conclusions can be drawn from these studies, we performed a meta-analysis. Data from the six available studies of standard release Adderall show it to be efficacious for symptoms of inattention, hyperactivity-impulsivity, and aggression, as well as global ratings. Its efficacy was significant for clinician, parent, and teacher ratings, and for both fixed- and best-dose designs.     

Cigarette Smoking Among Youth with Attention-Deficit/Hyperactivity Disorder: Clinical Phenomenology, Comorbidity, and Genetics

Cigarette smoking and other forms of tobacco use among children and adolescents is a significant public health concern. The negative consequences of prolonged exposure to such substances are numerous, and include higher prevalence rates of cardiopulmonary dysfunction and certain cancers, and may lead to other forms of drug use. Identifying subgroups of youth who may be at greater risk than others to develop a nicotine habit is an important step forward in preventing smoking initiation, and controlling tobacco use. One such subgroup is children with attention-deficit/hyperactivity disorder (ADHD). This is because the prevalence of smoking among these youngsters is nearly twice as high as it is among those who are unaffected with ADHD. However, the etiology of this association is not known. It is possible that a constellation of social, behavioral, and biological factors influences this process, resulting in higher prevalence rates. To further our understanding of this problem, we reviewed each of these factors in relationship to smoking and to ADHD. Using the primary care population as a model, we then discuss clinical research methods that may shed additional light on this topic, as well as the strengths and limitations of current smoking prevention and cessation options for ADHD-affected youth who are assessed and treated in medical settings.     

Time Perception: Modality and Duration Effects in Attention-Deficit/Hyperactivity Disorder (ADHD)

Time perception performance was systematically investigated in adolescents with and without attention-deficit/hyperactivity disorder (ADHD). Specifically, the effects of manipulating modality (auditory and visual) and length of duration (200 and 1000 ms) were examined. Forty-six adolescents with ADHD and 44 controls were administered four duration discrimination tasks and two control tasks, and a set of standardized measures. Participants with ADHD had higher thresholds than controls on all of the duration discrimination tasks, with the largest effect size obtained on the visual 1000 ms duration discrimination task. No group differences were observed on the control tasks. Visual–spatial memory was found to be a significant predictor of visual and auditory duration discrimination at longer intervals (1000 ms) in the ADHD sample, whereas auditory verbal working memory predicted auditory discrimination at longer intervals (1000 ms) in the control sample. These group differences suggest impairments in basic timing mechanisms in ADHD.     

Responses to methylphenidate in Attention-Deficit/Hyperactivity Disorder and normal children: update 2002

Since the positive effects of stimulants on disruptive behavior were described (Bradley & Bowen, 1941), further pediatric studyhas been limited almost exclusively to samples of hyperkinetic school-age children. Because these agents normally were viewed as arousing in their effects on the central nervous system, but were calming in their therapeutic effects on these children, stimulant effects on Attention Deficit Disorder (ADD) were interpreted as being 'paradoxical.' Investigation of effects in normal children and adolescents and in those with disorders unrelated to Attention-Deficit/Hyperactivity Disorder (ADHD), as well as in young adult samples, however, indicate that stimulants appear to have similar behavioral effects in normal and in hyperactive children. This brief report is an update (as of August 2002) on studies of stimulants in ADHD and normal children, with particular focus on MPH.     

Fundamental Movement Skills and Children with Attention-Deficit Hyperactivity Disorder: Peer Comparisons and Stimulant Effects

The purpose of this study was to compare the fundamental movement skills of 22 children with attention-deficit hyperactivity disorder (ADHD), from 6 to 12 years of age, to gender- and age-matched peers without ADHD and assess the effects of stimulant medication on the movement skill performance of the children with ADHD. Repeated measures analyses revealed significant skill differences between children with and without ADHD (p ≤ 0.001). Results from the stimulant medication trials indicated no significant effect of medication on the movement skill patterns of children with ADHD. It is concluded that children with ADHD may be at risk for developmental delays in movement skill performance. Potential factors underlying the movement skill difficulties are discussed, with suggestions for future research.     

Memory in Early Onset Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: Similarities and Differences

Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n?=?23), ADHD combined type (ADHD-C; n?=?26), BD?+?ADHD-C (n?=?15), and 68 healthy controls on memory tests (Digit span, Children's Verbal Learning Test-II). Further analyses were performed on subgroups of BD (BD-I, BD-II/BD-NOS, with and without previous psychotic symptoms). All clinical groups demonstrated some problems with free recall, but the BD subgroup with a history of psychotic symptoms had a more pervasive problem that also included recognition and semantic clustering. The ADHD-C groups demonstrated the lowest performance on working memory. These data suggest that children and adolescents with BD and previously psychotic symptoms may have inefficient encoding of verbal material, whereas memory problems in ADHD-C appear more characterized by impaired free recall.     

Paired-Associate Learning in Attention-Deficit/Hyperactivity Disorder as a Function of Hyperactivity-Impulsivity and Oppositional Defiant Disorder

A paired-associate learning (PAL) test was administered to 22 community volunteers without disruptive disorders and 197 children (7.5–13.5 years-old) presenting with the inattentive and combined subtypes of attention-deficit/hyperactivity disorder (ADHD) either in combination with or without oppositional defiant disorder (ODD). Participants were screened for learning disorders. In comparison to non-ADHD participants, children with ADHD achieved worse PAL and made errors rated as more acoustically and less semantically similar to the correct paired associates. These deficits were not related to hyperactivity–impulsivity or comorbid ODD. These results suggest that ADHD children are less competent at PAL and use less efficient learning strategies than their non-ADHD peers.     

Courtesy stigma in mothers of children with Attention-Deficit/Hyperactivity Disorder: a preliminary investigation

Mothers of children with Attention-Deficit/Hyperactivity Disorder face an increased risk for depression, anxiety, and social isolation. In addition to stress due to children's behavior, mothers of children with ADHD may also feel stigmatized by their children's diagnosis. Fifty-one mothers participated in a study to assess attitudes toward ADHD. Although mothers of children with ADHD expected that parents of children without ADHD would hold harsh views of the disorder, this was not generally the case. This difference between perception and the actual self-reported views of mothers of children without ADHD supports the idea that mothers feel stigmatized but suggests that increased awareness might help mothers of children with ADHD feel less isolated.     

Executive Function in Pediatric Bipolar Disorder and Attention-Deficit Hyperactivity Disorder: In Search of Distinct Phenotypic Profiles

Often, there is diagnostic confusion between bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD) in youth due to similar behavioral presentations. Both disorders have been implicated as having abnormal functioning in the prefrontal cortex; however, there may be subtle differences in the manner in which the prefrontal cortex functions in each disorder that could assist in their differentiation. Executive function is a construct thought to be a behavioral analogy to prefrontal cortex functioning. We provide a qualitative review of the literature on performance on executive function tasks for BD and ADHD in order to determine differences in task performance and neurocognitive profile. Our review found primary differences in executive function in the areas of interference control, working memory, planning, cognitive flexibility, and fluency. These differences may begin to establish a pediatric BD profile that provides a more objective means of differential diagnosis between BD and ADHD when they are not reliably distinguished by clinical diagnostic methods.     

A Comparison of Structural Brain Imaging Findings in Autism Spectrum Disorder and Attention-Deficit Hyperactivity Disorder

ASD and ADHD are regarded as distinct disorders in the current DSM-5. However, recent research and the RDoC initiative are recognizing considerable overlap in the clinical presentation of ASD, ADHD, and other neurodevelopmental disorders. In spite of numerous neuroimaging findings in ASD and ADHD, the extent to which either of the above views are supported remains equivocal. Here we compare structural MRI and DTI literature in ASD and ADHD. Our main findings reveal both distinct and shared neural features. Distinct expressions were in total brain volume (ASD: increased volume, ADHD: decreased volume), amygdala (ASD: overgrowth, ADHD: normal), and internal capsule (ASD: unclear, ADHD: reduced FA in DTI). Considerable overlap was noted in the corpus callosum and cerebellum (lower volume in structural MRI and decreased FA in DTI), and superior longitudinal fasciculus (reduced FA in DTI). In addition, we identify brain regions which have not been studied in depth and require more research. We discuss relationships between brain features and symptomatology. We conclude by addressing limitations of current neuroimaging research and offer approaches that account for clinical heterogeneity to better distinguish brain-behavior relationships.     

Components of Visual Search in Childhood-Onset Schizophrenia and Attention-Deficit/Hyperactivity Disorder

This study tested the hypotheses that visual search impairments in schizophrenia are due to a delay in initiation of search or a slow rate of serial search. We determined the specificity of these impairments by comparing children with schizophrenia to children with attention-deficit hyperactivity disorder (ADHD) and age-matched normal children. The hypotheses were tested within the framework of feature integration theory by administering children tasks tapping parallel and serial search. Search rate was estimated from the slope of the search functions, and duration of the initial stages of search from time to make the first saccade on each trial. As expected, manual response times were elevated in both clinical groups. Contrary to expectation, ADHD, but not schizophrenic, children were delayed in initiation of serial search. Finally, both groups showed a clear dissociation between intact parallel search rates and slowed serial search rates.     

Attention-Deficit/Hyperactivity Disorder and methylphenidate: a dose-response analysis and parent-child comparison of somatic complaints

The authors examined parent and child ratings of somatic complaints in 65 children with Attention-Deficit/Hyperactivity Disorder (ADHD) who received four doses (5 mg, 10 mg, 15 mg, 20 mg) of methylphenidate (MPH) in the context of a double-blind, placebo controlled, within-subject (crossover) experimental design. Results indicated that parent and child ratings of somatic complaints decreased in a linear fashion from baseline levels as a function of increasing MPH dose and showed minimal variation across MPH conditions. Statistical comparisons of specific somatic complaints indicated minimal agreement between parents and children in contrast to the nearly identical parent-child dose-response curves. The paradoxical findings of fewer somatic complaints associated with MPH, importance of obtaining children's perceptions of MPH treatment, and implications for measuring somatic complaints are discussed.