COMT and DAT1 polymorphisms moderate the indirect effect of parenting behavior on youth ADHD symptoms through neurocognitive functioning

Although gene × environment interactions contribute to youth attention-deficit/hyperactivity disorder (ADHD) symptoms, the pathways mediating these influences are unknown. We tested genetic moderation of indirect effects from parenting behavior to youth ADHD symptoms through multiple neurocognitive factors. Two hundred and twenty-nine youth with and without ADHD were assessed at baseline (Wave 1; ages 5–10) and at a 2-year follow-up (Wave 2; ages 7–13). At Wave 1, youth completed a neurocognitive battery including measures of response inhibition, visuospatial working memory, and fluid reasoning, and a standardized parent–child interaction task yielding observational measures of positive and negative parenting. At Wave 2, youth psychopathology was rated by parents and teachers using multiple methods (i.e., structured interview, rating scale). We employed moderated multiple mediation and compared conditional indirect effects across youth genotypes at two biologically plausible genetic loci. Controlling for parent ADHD symptoms as well as youth demographic factors and co-occurring externalizing symptoms, these genetic factors moderated the indirect effect from Wave 1 parenting to multi-method/informant Wave 2 ADHD symptoms through Wave 1 neurocognitive functioning. This preliminary study is the first to identify genetic moderation of mediated effects underlying ADHD symptoms and suggests that specific gene × parenting interactions may underlie neurocognitive functioning deficits and subsequent ADHD.     

Longitudinal Associations of Parental Emotion Socialization and Children’s Emotion Regulation: The Moderating Role of ADHD Symptomatology

Theory and research suggest that parents’ reactions to children’s emotions play a critical role in teaching children effective emotion regulation (ER) skills, but no studies have directly examined the role that parent emotion socialization plays in the development of ER in children with ADHD. Gaining insight into the causes of impaired ER, particularly in youth with ADHD who are known to have poor ER, has important theoretical and translational significance. The present study is the first to longitudinally examine whether emotion socialization predicts later physiological and adult-reported measures of ER in children with and without ADHD. It also sought to determine if these relations are moderated by ADHD symptoms. Participants were 61 children (31 girls, 30 boys; M = 10.67 years, SD = 1.28) with and without clinically significant ADHD symptoms. At Time 1, parent reports of emotion socialization and parent- and teacher-report of child ADHD symptoms were collected. At Time 2, child ER measures were collected based on parent- and teacher-report and physiological reactivity during an impossible puzzle and a social rejection task. Physiological measures included respiratory sinus arrhythmia and skin conductance level (SCL). Supportive parenting practices were associated with better parent-rated emotion regulation skills for all children and greater SCL reactivity for children with high ADHD symptoms. Non-supportive parenting reactions were associated with greater adult-rated emotional lability for children with high ADHD symptoms. Results highlight the importance of considering multiple aspects of ER, including physiological manifestations. Findings suggest that parents’ use of adaptive emotion socialization practices may serve as a protective factor for children’s ER development and may be particularly critical for youth with ADHD. Our findings support the use of interventions addressing parent emotion socialization to help foster better ER in children.     

Towards an understanding of unique and shared pathways in the psychopathophysiology of ADHD

Most attention deficit hyperactivity disorder (ADHD) research has compared cases with unaffected controls. This has led to many associations, but uncertainties about their specificity to ADHD in contrast with other disorders. We present a selective review of research, comparing ADHD with other disorders in neuropsychological, neurobiological and genetic correlates. So far, a specific pathophysiological pathway has not been identified. ADHD is probably not specifically associated with executive function deficits. It is possible, but not yet established, that ADHD symptoms may be more specifically associated with motivational abnormalities, motor organization and time perception. Recent findings indicating common genetic liabilities of ADHD and other conditions raise questions about diagnostic boundaries. In future research, the delineation of the pathophysiological mechanisms of ADHD needs to match cognitive, imaging and genetic techniques to the challenge of defining more homogenous clinical groups; multi-site collaborative projects are needed.     

Modeling Rater Disagreement for ADHD: Are Parents or Teachers Biased?

The present study is the first to utilize twin modeling to examine whether parent-teacher disagreement for ADHD ratings is due to parent or teacher bias, or due to raters observing different but valid ADHD behaviors. A joint analysis was conducted with 106 twin pairs, including twins selected for ADHD and control twin pairs. Total ADHD scores were analyzed using multiple rater models that estimate genetic and environmental contributions common to both raters and unique to each rater. Results suggest that 1) disagreement in ADHD ratings is strongly due to parents and teachers observing different ADHD behaviors, some of which is valid and some of which is due to bias, and 2) parents may be more biased than teachers in their ADHD ratings.     

DCD and ADHD: a genetic study of their shared aetiology

Previous studies have found that rates of attention deficit hyperactivity disorder (ADHD) and developmental coordination disorder (DCD) are very similar, both being approximately 7% in sample populations [Kadesj?, B., & Gillberg, C. (1999). Developmental coordination disorder in Swedish 7-year-old children. Journal of the American Academy of Child and Adolescent Psychiatry, 38, 820-828; Milberger, S., Faraone, S., Biederman, J., Testa, M., & Tsuang, M. (1996). New phenotype definition of attention deficit hyperactivity disorder in relatives for genetic analyses. American Journal of Medical Genetics, 67, 369-377]. The rate of comorbidity between the two has been found to be close to 50% [Barkley, R. (1990). Attention deficit hyperactivity disorder: A handbook for diagnosis and treatment. New York: Guilford Press]. Investigations into the comorbidity of the disorders points to a shared aetiology between them. The aim of the present investigation was to examine the extent to which the shared aetiology is due to common genetic factors to both disorders. We also investigated whether particular subtypes of each disorder were more linked than others. Mailed questionnaires were completed by parents (predominantly mothers) of 1285 twin pairs aged 5 and 16 years from the volunteer Australian Twin Registry (ATR). Included were a DSM-IV-based ADHD form, the alternative SWAN (Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour scale) and the Developmental Coordination Disorder Questionnaire (DCDQ). Statistical analyses including structural equation modelling were carried out to explore the genetic factors of both disorders. The modelling showed a strong shared additive genetic component between most subtypes of ADHD and DCD to the subtypes of the other disorder. Analyses comparing the two ADHD measures showed an overlap of the symptoms captured by each measure but also significant differences. The DCD-fine motor and ADHD-Inattentive were most strongly linked using the DSM-IV based scale. On the SWAN scale the results were similar but the general coordination scale was also very strongly linked. Implications for the use of different assessment tools are discussed.     

Does attention-deficit/hyperactivity disorder have a dimensional latent structure? A taxometric analysis

An understanding of the latent structure of attention-deficit/hyperactivity disorder (ADHD) is essential for developing causal models of this disorder. Although some researchers have presumed that ADHD is dimensional and others have assumed that it is taxonic, there has been relatively little research directly examining the latent structure of ADHD. The authors conducted a set of taxometric analyses using data from the NICHD Study of Early Child Care and Youth Development (ns between 667 and 1,078). The results revealed a dimensional latent structure across a variety of different analyses and sets of indicators for inattention, hyperactivity/impulsivity, and ADHD. Furthermore, analyses of correlations with associated features indicated that dimensional models demonstrated stronger validity coefficients with these criterion measures than dichotomous models. These findings jibe with recent research on the genetic basis of ADHD and with contemporary models of ADHD.     

The Effects of Childhood ADHD Symptoms on Early-onset Substance Use: A Swedish Twin Study

Research has documented that children and adolescents with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of substance use problems. Few studies, however, have focused on early-onset substance use. This study therefore investigated how the two symptom dimensions of ADHD (hyperactivity/impulsivity and inattention) are associated with early-onset substance use, the role of persistent ADHD for the association, and to what extent the association is influenced by genetic and environmental factors. Twins (1,480 pairs) in the Swedish Twin Study of Child and Adolescent Development were followed from childhood to adolescence. ADHD symptoms were measured at age 8–9 and age 13–14 via parent-report, whereas substance use was assessed at age 13–14 via self-report. Results revealed that hyperactive/impulsive symptoms predicted early-onset “sometimes” tobacco use (adjusted odds ratios, 1.12, for one symptom count), controlling for inattentive symptoms and conduct problem behaviors. There is no independent effect of inattentive symptoms on early-onset substance use. Children with persistent hyperactivity/impulsivity (defined as scoring above the 75th percentile at both time points) had a pronounced risk of both early-onset tobacco and alcohol use (adjusted odds ratios from 1.86 to 3.35, compared to the reference group). The associations between hyperactivity/impulsivity and early-onset substance use were primarily influenced by genetic factors. Our results indicated that hyperactivity/impulsivity, but not inattention, is an important early predictor for early-onset substance use, and a shared genetic susceptibility is suggested to explain this association.     

Exploring how symptoms of attention-deficit/hyperactivity disorder are related to reading and mathematics performance: general genes, general environments

Children with attention-deficit/hyperactivity disorder (ADHD) tend to perform more poorly on tests of reading and mathematical performance than their typical peers. Quantitative genetic analyses allow for a better understanding of the etiology of ADHD and reading and mathematics outcomes, by examining their common and unique genetic and environmental influences. Analyses were conducted on a sample 271 pairs of 10-year-old monozygotic and dizygotic twins drawn from the Western Reserve Reading and Mathematics Project. In general, the results suggested that the associations among ADHD symptoms, reading outcomes, and math outcomes were influenced by both general genetic and general shared-environment factors. The analyses also suggested significant independent genetic effects for ADHD symptoms. The results imply that differing etiological factors underlie the relationships among ADHD and reading and mathematics performance. It appears that both genetic and common family or school environments link ADHD with academic performance.     

Do Childhood Emotional Lability and ADHD Symptoms Have Shared Neuropsychological Roots?

Emotional Lability (EL) is a source of impairment in multiple mental disorders of children, including attention-deficit/hyperactivity disorder (ADHD). It has been proposed that the overlap between EL and ADHD symptoms is the result of common neuropsychological deficits. The aim of the present study was to test this hypothesis by using a multi-method approach. In a mixed sample of 61 children (49 community sample and 12 children with an ADHD diagnosis) aged between 8 and 12 years, we examined the relationship between parental reports of ADHD and EL, real-time children’s emotional expressions in an experimental context, children’s performance on neuropsychological tasks and parental ratings of neuropsychological functioning. Parental EL ratings were significantly predicted by task-based reaction time variability and by questionnaire measures of Self-Direction & Organization and Arousal Regulation. Parental EL ratings were also significantly related to both ADHD symptom dimensions. After controlling for shared neuropsychological factors, ADHD symptoms no longer predicted parental EL ratings. Neuropsychological task performance was not significantly related to real time emotional expressions. However, positive emotional expressions were significantly predicted by higher parental ratings of Cognition and negative emotional expressions by parental ratings of low Effort engagement – accounting for some of the correlation with ADHD symptoms. The current results highlight the plausible role of cognitive energetic processes in explaining the EL and ADHD symptom association.

     

More than off-task: Increased freely-moving thought in ADHD

Off-task thought has been found to occur at high rates and is related to impairment in ADHD. However, off-task thought is heterogenous and it remains unclear which specific dimensions of off-task thought are more prevalent in this disorder. It is therefore important to dissociate different aspects of off-task thought in order to better understand the mechanisms underlying impairment. The current study focused on the dimension of constrained (focused) to freely moving off-task thought. Self-report and neurophysiological measures during a computerized attention tasks provided convergent evidence that individuals with ADHD not only have more off-task thought than those without, but also engaged in a greater proportion of freely moving off-task thought than non-ADHD controls. Overall, this work demonstrated differences in both the quantity and type of off-task thought in adults with ADHD. It provides novel insight into both the phenomenology of off-task thought, as well as potential mechanisms underlying impairment in ADHD.     

Genetic Support for the Dual Nature of Attention Deficit Hyperactivity Disorder: Substantial Genetic Overlap Between the Inattentive and Hyperactive–impulsive Components

Objective Attention deficit hyperactivity disorder (ADHD) is a common, complex and highly heritable disorder, characterised by inattentive, impulsive and overactive behaviour. Evidence for the heritability of ADHD measures in twin population samples has come from the analysis of total scores that combine inattentive and hyperactive–impulsive symptoms subscales. This study investigated, in a community sample, the aetiology of ADHD-like traits and the aetiological overlap between the two dimensions that define the ADHD disorder. Materials and Methods Parents of 6,222 approximately 8-year-old twin pairs from the Twins Early Development Study (TEDS) population sample completed the two subscales of the Conners’ 18-item DSMIV checklist, a screening instrument for ADHD symptoms. Results Both subscales were highly heritable (hyperactive–impulsive: 88%; inattentive: 79%). Bivariate genetic modelling indicated substantial genetic overlap between the two components; however, there were significant independent genetic effects. Conclusions These findings suggest that many genes associated with the hyperactivity–impulsivity dimension will also be associated with the inattentive dimension but that there is significant genetic heterogeneity as well. These results provide genetic support for combining the two behavioural dimensions that define ADHD, but also suggest that some symptom-specific genes will also be identified. Correspondence and reprint requests to Gráinne McLoughlin, SGDP Centre, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, Tel: +44(0) 207-848-5261; Email: g.mcloughlin@iop.kcl.ac.uk.     

Genetic Influences on Anxiety in Children: What we’ve Learned and Where we’re Heading

Anxiety is a common problem, typically beginning early in life. This article explores reasons for individual differences in levels of anxiety among children, by reviewing the genetic literature. The plethora of research to date has demonstrated clearly that both genes and environmental influences play important roles in explaining differences in levels of anxiety of various types among children. This has encouraged researchers to search for specific genes and environmental influences upon anxiety. Despite important progress in identifying links between anxiety and specific genes—including associations between serotonin and dopamine genes and different symptoms of anxiety—overall, progress has been slow because multiple genes of small effect size are likely to influence anxiety. This article explains how the hunt for genes involved in anxiety is likely to benefit from genetically sensitive research, which examines the co-occurrence of symptoms; includes measures of the environment; and examines endophenotypes and risk pathways.     

Trajectories of Binge Drinking Behavior across Adolescence among Juvenile Offenders and the Role of ADHD for Predicting Development

Binge drinking has been linked to numerous health issues. Juvenile offenders may be at increased risk for binge drinking. ADHD has been demonstrated to be a predictor of substance use. The development of binge drinking behavior and the role of ADHD for predicting this development among this population has not yet been explored. This research uses group-based trajectory modeling to describe binge drinking development. Multinomial logistic regression is used to examine the role of ADHD for predicting development. Results indicate that an 8-group model fits the data and that ADHD predicts assignment to the High Chronic trajectory group.     

Measuring impulsivity in adolescents with serious substance and conduct problems

Adolescents with substance use and conduct disorders have high rates of aggression and attention deficit hyperactivity disorder (ADHD), all of which have been characterized in part by impulsivity. Developing measures that capture impulsivity behaviorally and correlate with self-reported impulsivity has been difficult. One promising behavioral measure, however, is a variant of the continuous performance test, the Immediate Memory Test/Delayed Memory Test (IMT/DMT). The authors showed significant group differences between adolescents in treatment for serious substance and conduct problems and community controls on impulsivity measures, both behavioral and self-report, as well as on aggression and problem behavior measures. Furthermore, the IMT/DMT correlated significantly with self-reported impulsivity. In summary, the IMT/DMT may be an effective behavioral measure of impulsivity in adolescents.     

Increased Intrasubject Variability in Boys with ADHD Across Tests of Motor and Cognitive Control

Increased intrasubject variability (ISV), or short-term, within-person fluctuations in behavioral performance is consistently found in Attention-Deficit/Hyperactivity Disorder (ADHD). ADHD is also associated with impairments in motor control, particularly in boys. The results of the few studies that have examined variability in self-generated motor output in children with ADHD have been inconsistent. The current study examined variability in motor control during a finger sequencing task among boys with and without ADHD as well as the relationship between intrasubject variability during motor and cognitive control tasks. Changes in performance over the course of the task and associations with ADHD symptom domains were also examined to elucidate the nature of impaired motor control in children with ADHD. Fifty-one boys (ages 8 to 12 years) participated in the study, including 28 boys with ADHD and 23 typically developing (TD) boys. Participants completed a finger sequencing task and a Go/No-Go task providing multiple measures of response speed and variability. Boys with ADHD were slower and more variable in both intertap interval on the finger sequencing task and reaction time on the Go/No-Go task, with measures of speed and variability correlated across the two tasks. For the entire cohort, the only unique predictor of parent ratings of hyperactive-impulsive symptoms was variability in intertap interval during finger sequencing, whereas inattentive symptoms were only predicted by reaction time variability on the Go/No-Go task. These findings suggest that inefficient motor control is implicated in the pathophysiology of ADHD, particularly in regards to developmentally inappropriate levels of hyperactivity and impulsivity.     

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.     

Variations in Anxiety and Depression as a Function of ADHD Subtypes Defined by DSM-IV: Do Subtype Differences Exist or Not?

Concerns have been raised about the ability of diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD) to distinguish subtypes that are clearly distinct from each other with regard to clinical correlates. One area of concern is that research regarding differences in anxiety and depression as a function of ADHD subtype has produced discrepant findings. This study was designed to systematically evaluate whether the ADHD subtypes differ with regard to level of internalizing symptoms. From a large pool of children referred to an ADHD center based in a pediatric hospital, children were differentiated into three groups: ADHD, Combined Type (ADHD/COM); ADHD, Inattentive Type (ADHD/I); and a non-ADHD, comparison group (COMP). Parent- and child-report measures using both dimensional and categorical methods were used to assess internalizing symptoms. The results indicated that children with ADHD/COM and ADHD/I had similar levels of anxiety and depression. Subtype differences related to parent-reported depression were accounted for by group differences in level of externalizing problems. The results were discussed with regard to their implications for refining the criteria used to differentiate children with ADHD into subtypes.     

Creative Thinking in Adolescents with Attention Deficit Hyperactivity Disorder (ADHD)

A widened attentional focus, that is typically associated with ADHD, has been postulated to be accompanied by enhanced creative ability. However, creativity has been only limitedly examined in ADHD. Performance across several creativity measures were investigated in three groups: adolescents with ADHD, those with conduct disorder, and a healthy control sample. The ADHD group exhibited selective cognitive advantages and disadvantages by demonstrating an enhanced ability in overcoming the constraining influence of examples, but a reduced capacity to generate a functional invention during an imagery task. These findings are interpreted with reference to inhibitory control mechanisms and the contextual modulation of creative cognition.     

Problems in Psychiatric Genetic Research: A Reply to Faraone and Biederman

This article examines evidence cited in favor of the operation of genetic factors in attention-deficit hyperactivity disorder (ADHD). Like other psychiatric conditions, a belief in the genetic basis of ADHD is derived from the results of family, twin, and adoption studies. Because family studies are widely believed to be confounded by environmental factors, primary emphasis is placed on twin and adoption studies. ADHD twin studies depend on the validity of the equal environment assumption (EEA), which holds that the environments of identical (MZ) and fraternal (DZ) twins are the same. Here it is argued that however the EEA is defined, it cannot be accepted. Therefore, the greater similarity or concordance of MZ twins when compared to DZ twins is plausibly explained by environmental factors. Adoption studies constitute a third method for investigating the role of genetic factors in ADHD. It is argued that these studies are greatly flawed by factors including non blinded diagnoses and the failure to study the biological relatives of adoptees. After an examination of the total weight of evidence in favor of a genetic basis or predisposition for ADHD, it is concluded that a role for genetic factors is not supported and that future research should be directed toward psychosocial causes     

Creative thinking in adolescents with attention deficit hyperactivity disorder (ADHD).

A widened attentional focus, that is typically associated with ADHD, has been postulated to be accompanied by enhanced creative ability. However, creativity has been only limitedly examined in ADHD. Performance across several creativity measures were investigated in three groups: adolescents with ADHD, those with conduct disorder, and a healthy control sample. The ADHD group exhibited selective cognitive advantages and disadvantages by demonstrating an enhanced ability in overcoming the constraining influence of examples, but a reduced capacity to generate a functional invention during an imagery task. These findings are interpreted with reference to inhibitory control mechanisms and the contextual modulation of creative cognition.