Heterogeneity Of Attention-deficit/hyperactivity Disorder Research Articles

Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a complex disorder that manifests variability in long-term outcomes and clinical presentations. The genetic contributions to such heterogeneity are not well understood. Here we show several genetic links to clinical heterogeneity in ADHD in a case-only study of 14,084 diagnosed individuals. First, we identify one genome-wide significant locus by comparing cases with ADHD and autism spectrum disorder (ASD) to cases with ADHD but not ASD. Second, we show that cases with ASD and ADHD, substance use disorder and ADHD, or first diagnosed with ADHD in adulthood have unique polygenic score (PGS) profiles that distinguish them from complementary case subgroups and controls. Finally, a PGS for an ASD diagnosis in ADHD cases predicted cognitive performance in an independent developmental cohort. Our approach uncovered evidence of genetic heterogeneity in ADHD, helping us to understand its etiology and providing a model for studies of other disorders.

The Relationship Between Emotion Dysregulation and Error Monitoring in Adolescents with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is emblematic of the limitations of existing diagnostic categories. One potential solution, consistent with the Research Domain Criteria (RDoC) initiative, is to interrogate psychological mechanisms at the behavioral and physiological level together to try and identify meaningful subgroups within existing categories. Such approaches provide a way to revise diagnostic boundaries and clarify individual variation in mechanisms. Here, we illustrate this approach to help resolve heterogeneity in ADHD using a combination of behaviorally-rated temperament measures from the Early Adolescent Temperament Questionnaire; cognitive performance on three difference conditions of an emotional go/no-go task; and electroencephalogram (EEG)-measured variation in multiple stages of error processing, including the error-related negativity (ERN) and positivity (Pe). In a large (N = 342), well-characterized sample of adolescents with ADHD, latent profile analysis identified two ADHD temperament subgroups: 1) emotionally regulated and 2) emotionally dysregulated (with high negative affect). Cognitive and EEG assessment in a subset of 272 adolescents (nADHD = 151) found that the emotionally dysregulated group showed distinct patterns of change in early neural response to errors (ERN) across emotional task conditions as compared to emotionally-regulated ADHD adolescents and typically-developing controls. Both ADHD groups showed blunted later response to errors (Pe) that was stable across emotional task conditions. Overall, neural response patterns identified important differences in how trait and state emotion interact to affect cognitive processing. Results highlight important temperament variation within ADHD that helps clarify its relationship to the ERN, one of the most prominent putative neural biomarkers for psychopathology.

Behavioral and brain functional characteristics of children with Attention-Deficit/Hyperactivity disorder and anxiety trait.

The current study aimed to explore the behavioral, daily-life executive functional, and brain functional connectivity patterns in children with attention-deficit/hyperactivity disorder (ADHD) and anxiety. A total of 246 children with non-comorbid ADHD and 91 healthy controls (HCs) participated in the current study, among whom 175 subjects went through resting-state functional magnetic resonance imaging (fMRI) scans. The ADHD participants were divided into two subgroups: ADHD with a high level of anxiety (ADHD + ANX) and ADHD with a low level of anxiety (ADHD-ANX). The Child Behavior Checklist (CBCL) and the Behavior Rating Inventory of Executive Function (BRIEF) were used to capture the behavioral and daily-life executive functional characteristics. Independent component analysis with dual regression models was applied to the fMRI data. All statistical models were estimated with age and sex as covariates. Compared with the ADHD-ANX group, the ADHD + ANX group showed more withdrawn, somatic, social, thought, attention, delinquent, and aggressive problems (all corrected p < 0.05). The ADHD + ANX group also displayed more impaired emotional control and working memory than the ADHD-ANX (all corrected p < 0.05). The ADHD-ANX group, but not the ADHD + ANX group, showed elevated functional connectivity within the default mode network compared with the HC group. The mean function connectivity within the default mode network significantly mediated the correlation between anxiety level and attention problems. In sum, anxiety in children with ADHD was associated with more social, emotional, and behavioral problems, more impaired daily-life executive function, and altered brain function. Our work provides important information on the heterogeneity of ADHD.

Clinical characteristics, neuroimaging findings, and neuropsychological functioning in attention-deficit hyperactivity disorder: Sex differences.

Recent clinical studies, in both children/adolescents and adults, have shown the extreme neuropsychological heterogeneity of attention-deficit hyperactivity disorder (ADHD): specific neuropsychological deficits have been found only in a minority of individuals, with no direct correlation between discrete cognitive performances and the trajectory of clinical symptoms. Deficits in specific neuropsychological functions may be common in ADHD, but nevertheless no cognitive or neuropsychological profile may fully explain the disorder. Sex differences in the ADHD presentation, both at a neuropsychological and clinical level, also contribute to this clinical and neuropsychological heterogeneity. At a neuropsychological level, females with ADHD may show greater working memory problems, poorer vocabulary skills and worse visual spatial reasoning. Structural and functional imaging study also show discrete differences across sex; however, the great majority of clinical studies mainly or exclusively include male participants with insufficient data to draw firm conclusions on sex differences within the disorder. Here, we report the recent literature data, discussing still open research questions about the clinical presentation, neuroimaging findings, and neuropsychological functioning in ADHD with a focus on the impact of sex differences-a deeper insight in these unresolved issues may have relevant clinical and therapeutic implications for tailored, effective, and long-lasting interventions.

The Greek Version of the Vanderbilt ADHD Diagnostic Parent Rating Scale for Follow-up Assessment in Prepubertal Children with ADHD

ABSTRACT Given the heterogeneity of Attention-Deficit Hyperactivity Disorder (ADHD), there is a constant need for proper diagnosis, employing more accurate, efficient, patient-friendly, and clinician-friendly tools. We developed a Greek version of the National Institute for Children’s Health Quality (NICHQ) Vanderbilt ADHD Diagnostic Parent Rating Scale (VADPRS) for follow-up assessment and examined its reliability and validity. A total of 100 schoolchildren (65 girls and 35 boys) between 7 and 12 years old with ADHD were included in the study. The internal consistency and test–retest reliability were examined via principal component analysis. Three-component structure in our study accounts for 74.63% of the tool’s variance. The questions’ loadings onto the factors and the internal reliability of the three factors were satisfactory. Finally, the reliability of all factors presented was found adequately high, confirming the high internal consistency of the items. Our results suggest that the Greek version of the VADPRS-follow-up may be used as an accurate psychometric instrument for the purposes of diagnosing ADHD. Furthermore, the combined use of the VADPRS-follow-up with other widely accepted tools, such as the ADHD Rating Scale-IV, may present clinical utility in collating parent information concerning the behavioural phenotype of their children.

Clarifying ADHD and Sluggish Cognitive Tempo Item Relations with Impairment: A Network Analysis.

Despite the pervasive nature of various forms of impairment associated with attention-deficit/hyperactivity disorder (ADHD), the precise nature of their associations with ADHD and related sluggish cognitive tempo (SCT), particularly at the heterogeneous item level, remains ambiguous. Using innovative network analysis techniques, we sought to identify and examine the concurrent validity of ADHD and SCT bridge items (i.e., those demonstrating the most robust relations with various forms of impairment) with respect to Overall, Home-School, and Community-Leisure impairment domains. Parents of a nationally representative sample of 1742 children (50.17% male) aged 6-17years completed rating scales of ADHD, SCT, and impairment. Assessment of Bridge Expected Influence suggested eight bridge items primarily from impulsive and Task Completion (i.e., overlapping SCT and inattentive) domains that demonstrated relations with impairment in school performance, completing chores at home, interacting with family members, following rules, and playing sports. Sum scores onlyincluding bridge items exhibited relations with Overall, Home-School, and Community-Leisure impairmentdomains comparable to that of sum scores including all items. Bridge impairment areas were generally consistent across "Childhood" (6-11years) and "Adolescence" (12-17years). Problems listening and slowness emerged as bridge items in Childhood, whereas difficulties following through on instructions, problems waiting one's turn, and social withdrawal emerged in Adolescence. Given the comparable validity of ADHD- and SCT-related bridge items versus all items, bridge items, together, may be the most efficient indicators of impairment. Further clarification is needed across development to inform personalized assessment and intervention protocols that account for item-level heterogeneity in ADHD, SCT, and impairment phenotypes.

Altered microRNA 5692b and microRNA let-7d expression levels in children and adolescents with attention deficit hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Its etiology is not clearly understood yet, but neurobiological, genetic and environmental factors are shown to play a role. The relationship between ADHD and miRNAs has been studied quite recently, and few studies have been conducted up to now. In this study, peripheral blood expression levels of miR-5692b, miR-let-7d, miR-124-3p, miR-4447 and miR-107 of 30 children and adolescents with combined type ADHD were compared to 30 healthy controls to understand the roles of these miRNAs in the ADHD etiopathogenesis. Compared to controls, levels of miR-5692b (p = 0.006) were found higher and levels of miR-let-7d (p = 0.017) were found lower in the ADHD group. There was no significant difference in terms of miR-124-3p, miR-4447, and miR-107 levels between the groups. In conclusion, our findings support other studies suggesting the importance of miRNAs in the pathogenesis of ADHD. Regarding the regulatory role of miRNAs in gene regulation, their contribution to etiopathogenesis and heterogeneity of ADHD should be investigated further.

Individual differences v. the average patient: mapping the heterogeneity in ADHD using normative models.

The present paper presents a fundamentally novel approach to model individual differences of persons with the same biologically heterogeneous mental disorder. Unlike prevalent case-control analyses, that assume a clear distinction between patient and control groups and thereby introducing the concept of an 'average patient', we describe each patient's biology individually, gaining insights into the different facets that characterize persistent attention-deficit/hyperactivity disorder (ADHD). Using a normative modeling approach, we mapped inter-individual differences in reference to normative structural brain changes across the lifespan to examine the degree to which case-control analyses disguise differences between individuals. At the level of the individual, deviations from the normative model were frequent in persistent ADHD. However, the overlap of more than 2% between participants with ADHD was only observed in few brain loci. On average, participants with ADHD showed significantly reduced gray matter in the cerebellum and hippocampus compared to healthy individuals. While the case-control differences were in line with the literature on ADHD, individuals with ADHD only marginally reflected these group differences. Case-control comparisons, disguise inter-individual differences in brain biology in individuals with persistent ADHD. The present results show that the 'average ADHD patient' has limited informative value, providing the first evidence for the necessity to explore different biological facets of ADHD at the level of the individual and practical means to achieve this end.

Large-scale brain functional network topology disruptions underlie symptom heterogeneity in children with attention-deficit/hyperactivity disorder.

Accumulating evidence suggests brain network dysfunction in attention-deficit/hyperactivity disorder (ADHD). Whether large-scale brain network connectivity patterns reflect clinical heterogeneity in ADHD remains to be fully understood. This study aimed to characterize the differential within- and between-network functional connectivity (FC) changes in children with ADHD combined (ADHD-C) or inattentive (ADHD-I) subtypes and their associations with ADHD symptoms. We studied the task-free functional magnetic resonance imaging (fMRI) data of 58 boys with ADHD and 28 demographically matched healthy controls. We measured within- and between-network connectivity of both low-level (sensorimotor) and high-level (cognitive) large-scale intrinsic connectivity networks and network modularity. We found that children with ADHD-C but not those with ADHD-I exhibited hyper-connectivity within the anterior default mode network (DMN) compared with controls. Additionally, children with ADHD-C had higher inter-network FC between the left executive control (ECN) and the salience (SN) networks, between subcortical and visual networks, and between the DMN and left auditory networks than controls, while children with ADHD-I did not show differences compared with controls. Similarly, children with ADHD-C but not ADHD-I showed lower network modularity compared with controls. Importantly, these observed abnormal inter-network connectivity and network modularity metrics were associated with Child Behavioral Checklist (CBCL) attention-deficit/hyperactivity problems and internalizing problems in children with ADHD. This study revealed relatively greater loss of brain functional network segregation in childhood ADHD combined subtype compared to the inattentive subtype, suggesting differential large-scale functional brain network topology phenotype underlying childhood ADHD heterogeneity.

Sluggish Cognitive Tempo Symptoms Contribute to Heterogeneity in Adult Attention-Deficit Hyperactivity Disorder.

Attention-deficit hyperactivity disorder (ADHD) persists into adulthood in over 50% of cases, although its associated symptom profiles, comorbid problems, and neuropsychological deficits change substantially across development. Sluggish cognitive tempo (SCT) symptoms may contribute to associations between ADHD and comorbid problems and may partially explain the substantial heterogeneity observed in its correlates. 349 adults aged 18-38 years (M = 23.2, SD = 4.5, 54.7% male, 61.03% with ADHD) completed a multi-informant diagnostic procedure and a comprehensive neuropsychological battery. Adults with ADHD (n = 213) were retained for analyses. Latent class analyses (LCA) revealed three profiles of SCT symptoms among those with ADHD, which we classified as minimal, moderate, or severe SCT. Multiple analysis of covariance (MANCOVA) revealed significant differences among these profiles, which remained when controlling for persistence of ADHD symptoms and sex. In general, adults with ADHD combined with SCT symptoms (moderate and severe) had significantly more symptoms of anxiety, depression, and persistent inattention, and had more severe professional and relational impairment compared to ADHD adults without SCT. Compared to those with moderate or minimal SCT symptoms, the severe SCT group had the most symptoms of depression and internalizing disorders, and the most impairment in the domain of daily responsibility. No significant differences based on externalizing symptoms emerged when controlling for sex and persistence of inattention symptoms, suggesting the moderate and severe SCT groups do not simply reflect more symptoms. Moreover, follow-up mediation analyses revealed that SCT might at least partially explain the heterogeneity in ADHD. Findings have implications for refinement of etiological conceptualization, assessment methods, and intervention strategies.

Parsing heterogeneity in attention-deficit hyperactivity disorder using EEG-based subgroups.

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous condition for which multiple efforts to characterize brain state differences are underway. The objective of this study was to identify distinct subgroups of resting electroencephalography (EEG) profiles among children with and without ADHD and subsequently provide extensive clinical characterization of the subgroups. Latent class analysis was used with resting state EEG recorded from a large sample of 781 children with and without ADHD (N=620 ADHD, N=161 Control), aged 6-18years old. Behavioral and cognitive characteristics of the latent classes were derived from semistructured diagnostic interviews, parent completed behavior rating scales, and cognitive test performance. A five-class solution was the best fit for the data, of which four classes had a defining spectral power elevation. The distribution of ADHD and control subjects was similar across classes suggesting there is no one resting state EEG profile for children with or without ADHD. Specific latent classes demonstrated distinct behavioral and cognitive profiles. Those with elevated slow-wave activity (i.e. delta and theta band) had higher levels of externalizing behaviors and cognitive deficits. Latent subgroups with elevated alpha and beta power had higher levels of internalizing behaviors, emotion dysregulation, and intact cognitive functioning. There is population-level heterogeneity in resting state EEG subgroups, which are associated with distinct behavioral and cognitive profiles. EEG measures may be more useful biomarkers of ADHD outcome or treatment response rather than diagnosis.

Catechol-O-methyltransferase polymorphism is associated with the cortico-cerebellar functional connectivity of executive function in children with attention-deficit/hyperactivity disorder

The cerebellum, although traditionally considered a motor structure, has been increasingly recognized to play a role in regulating executive function, the dysfunction of which is a factor in attention-deficit/hyperactivity disorder (ADHD). Additionally, catechol-O-methyltransferase (COMT) polymorphism has been reported to be associated with executive function. We examined whether the cortico-cerebellar executive function network is altered in children with ADHD and whether COMT polymorphism is associated with the altered network. Thirty-one children with ADHD and thirty age- and IQ-matched typically developing (TD) controls underwent resting-state functional MRI, and functional connectivity of executive function-related Crus I/II in the cerebellum was analysed. COMT Val158Met genotype data were also obtained from children with ADHD. Relative to TD controls, children with ADHD showed significantly lower functional connectivity of the right Crus I/II with the left dorsolateral prefrontal cortex. Additionally, the functional connectivity of children with ADHD was modulated by COMT polymorphism, with Met-carriers exhibiting significantly lower functional connectivity than the Val/Val genotype. These results suggest the existence of variations, such as ethnic differences, in COMT genetic effects on the cortico-cerebellar executive function network. These variations contribute to heterogeneity in ADHD. Further neuroimaging genetics study might lead to the development of fundamental therapies that target ADHD pathophysiology.

Heterogeneity in ADHD: Neurocognitive predictors of peer, family, and academic functioning

ABSTRACTChildhood attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in peer, family, and academic functioning. Although impairment is required for diagnosis, children with ADHD vary significantly in the areas in which they demonstrate clinically significant impairment. However, relatively little is known about the mechanisms and processes underlying these individual differences. The current study examined neurocognitive predictors of heterogeneity in peer, family, and academic functioning in a well-defined sample of 44 children with ADHD aged 8–13 years (M = 10.31, SD = 1.42; 31 boys, 13 girls; 81% Caucasian). Reliable change analysis indicated that 98% of the sample demonstrated objectively-defined impairment on at least one assessed outcome measure; 65% were impaired in two or all three areas of functioning. ADHD children with quantifiable deficits in academic success and family functioning performed worse on tests of working memory (d = 0.68 to 1.09), whereas children with impaired parent-reported social functioning demonstrated slower processing speed (d = 0.53). Dimensional analyses identified additional predictors of peer, family, and academic functioning. Working memory abilities were associated with individual differences in all three functional domains, processing speed predicted social functioning, and inhibitory control predicted family functioning. These results add to a growing literature implicating neurocognitive abilities not only in explaining behavioral differences between ADHD and non-ADHD groups, but also in the substantial heterogeneity in ecologically-valid functional outcomes associated with the disorder.

Attention-Deficit/Hyperactivity Disorder Symptoms Coincide With Altered Striatal Connectivity

BackgroundCorticostriatal network dysfunction in attention-deficit/hyperactivity disorder (ADHD) is generally investigated by comparing functional connectivity of the main striatal subregions (i.e., putamen, caudate, and nucleus accumbens) between an ADHD group and a control group. However, dimensional analyses based on continuous symptom measures might help to parse the high phenotypic heterogeneity in ADHD. Here, we focus on functional segregation of regions in the striatum and investigate corticostriatal networks using both categorical and dimensional measures of ADHD. MethodsWe computed whole-brain functional connectivity for six striatal subregions that resulted from a novel functional parcellation technique. We compared functional connectivity maps between adolescents with ADHD (n = 169) and healthy controls (n = 122), and investigated dimensional ADHD-related measures by relating striatal connectivity to ADHD symptom scores (N = 444). Finally, we examined whether altered connectivity of striatal subregions was related to motor and cognitive performance. ResultsWe observed no case-control differences in functional connectivity patterns of the six striatal networks. In contrast, inattention and hyperactivity/impulsivity symptom scores were associated with increases in functional connectivity in the networks of posterior putamen and ventral caudate. Increased connectivity of posterior putamen with motor cortex and cerebellum was associated with decreased motor performance. ConclusionsOur findings support hypotheses of corticostriatal network dysfunction in ADHD by demonstrating that dimensional symptom measures are associated with changes in functional connectivity. These changes were not detected by categorical ADHD versus control group analyses, which highlights the important contribution of dimensional analyses to investigating the neurobiology of ADHD.

Usefulness and Validity of Continuous Performance Tests in the Diagnosis of Attention-Deficit Hyperactivity Disorder Children.

Despite the popularity of continuous performance tests (CPT) in supporting the diagnostic procedure of attention-deficit hyperactivity disorder (ADHD), these measures are still controversial mainly due to limited sensitivity, specificity, and ecological validity. Thus, there continues to be a need for further validation of these objective attention measures. The purpose of this study was to evaluate the usefulness of a CPT that includes environmental distracting stimuli, in supporting the diagnosis of ADHD in children. Participants were 798 children aged 7-12 years (493 boys and 305 girls). The ADHD group included 339 children, whereas the control group included 459 children without ADHD. The study employed the MOXO-CPT, which incorporates visual and auditory stimuli serving as environmental distractors. Compared to their unaffected peers, children with ADHD received significantly lower scores in all 4 CPT indices: attention, timing, hyperactivity, and impulsivity. Specifically, ADHD children were less attended to the stimuli and performed fewer reactions on accurate timing. Furthermore, children with ADHD performed significantly more impulsive and hyperactive responses than controls. Receiver operating characteristic analysis revealed fair to excellent diagnostic ability of all CPT indices except impulsivity, which showed poor ability to distinguish ADHD children from controls. The test's total score yielded excellent diagnostic performance. MOXO-CPT consistently distinguished between children with ADHD and their unaffected peers, so that children with ADHD performed worse than controls in all study indices. Integration of CPT indices improves the diagnostic capacity of ADHD and may better reflect the complexity and heterogeneity of ADHD.

The effects of individual upper alpha neurofeedback in ADHD: an open-label pilot study.

Standardized neurofeedback (NF) protocols have been extensively evaluated in attention-deficit/hyperactivity disorder (ADHD). However, such protocols do not account for the large EEG heterogeneity in ADHD. Thus, individualized approaches have been suggested to improve the clinical outcome. In this direction, an open-label pilot study was designed to evaluate a NF protocol of relative upper alpha power enhancement in fronto-central sites. Upper alpha band was individually determined using the alpha peak frequency as an anchor point. 20 ADHD children underwent 18 training sessions. Clinical and neurophysiological variables were measured pre- and post-training. EEG was recorded pre- and post-training, and pre- and post-training trials within each session, in both eyes closed resting state and eyes open task-related activity. A power EEG analysis assessed long-term and within-session effects, in the trained parameter and in all the sensors in the (1-30) Hz spectral range. Learning curves over sessions were assessed as well. Parents rated a clinical improvement in children regarding inattention and hyperactivity/impulsivity. Neurophysiological tests showed an improvement in working memory, concentration and impulsivity (decreased number of commission errors in a continuous performance test). Relative and absolute upper alpha power showed long-term enhancement in task-related activity, and a positive learning curve over sessions. The analysis of within-session effects showed a power decrease ("rebound" effect) in task-related activity, with no significant effects during training trials. We conclude that the enhancement of the individual upper alpha power is effective in improving several measures of clinical outcome and cognitive performance in ADHD. This is the first NF study evaluating such a protocol in ADHD. A controlled evaluation seems warranted due to the positive results obtained in the current study.

Distinct neuropsychological profiles within ADHD: a latent class analysis of cognitive control, reward sensitivity and timing.

Multiple pathway models of attention deficit hyperactivity disorder (ADHD) suggest that this disorder is the behavioural expression of dysfunction in one of several separable brain systems. One such model focuses on the brain systems underlying cognitive control, timing and reward sensitivity. It predicts separable subgroups among individuals with ADHD, with performance deficits in only one of these domains. We used latent class analysis (LCA) to identify subgroups of individuals with ADHD based on their overall pattern of neuropsychological performance, rather than grouping them based on cut-off criteria. We hypothesized that we would find separable subgroups with deficits in cognitive control, timing and reward sensitivity respectively. Ninety-six subjects with ADHD (of any subtype) and 121 typically developing controls performed a battery assessing cognitive control, timing and reward sensitivity. LCA was used to identify subgroups of individuals with ADHD with a distinct neuropsychological profile. A similar analysis was performed for controls. Three subgroups represented 87% of subjects with ADHD. Two of our three hypothesized subgroups were identified, with poor cognitive control and timing. Two of the ADHD subgroups had similar profiles to control subgroups, whereas one subgroup had no equivalent in controls. Our findings support multiple pathway models of ADHD, as we were able to define separable subgroups with differing cognitive profiles. Furthermore, we found both quantitative and qualitative differences from controls, suggesting that ADHD may represent both categorical and dimensional differences. These results show that by addressing heterogeneity in ADHD, we can identify more homogeneous subsets of individuals to further investigate.

Resting electroencephalogram in attention deficit hyperactivity disorder: Developmental course and diagnostic value

This study investigated electroencephalographic (EEG) activity and its developmental course in attention deficit hyperactivity disorder (ADHD) throughout the lifespan, as well as the accuracy of EEG parameters in distinguishing ADHD patients from typically developing individuals. Three minutes eyes closed resting EEG was compared between 62 individuals with ADHD (36 children, 26 adults) and 55 typically developing individuals (30 children, 25 adults). EEG activity and maturation did not differ between individuals with ADHD and typically developing individuals. However, despite comparable developmental course between clinical groups, persistent elevated theta/beta ratio and reduced relative beta power were observed in the ADHD inattentive subtype compared to the ADHD combined subtype and controls across the lifespan. Therefore, a maturational deviation rather than a maturational delay may underlie a subgroup of ADHD. EEG based classification failed for ADHD but proved successful for age. These findings emphasize heterogeneity in ADHD throughout the lifespan and question clinical utility of conventional EEG approaches for diagnostic purposes in ADHD.

The Relationship Between ADHD Symptom Dimensions, Clinical Correlates, and Functional Impairments

To better understand how heterogeneity in attention-deficit hyperactivity disorder (ADHD) symptoms relates to heterogeneity in functional impairment domains in children with ADHD after accounting for demographic variables and comorbidities, in particular oppositionality and internalizing symptoms. Parents and teachers (n = 5663) rated child/adolescent impairments across impairment domains in the International Classification of Functioning, Disability and Health as well as symptoms of ADHD and comorbidities. Hierarchical regressions were conducted to assess the relationship between parent and teacher ratings of ADHD symptom domains and functional impairments after accounting for personal factors and comorbid disorders. Symptoms of inattention were the strongest predictors of ratings of academic (math, writing, and so on) functioning, while hyperactivity/impulsivity symptoms were the strongest predictor of classroom disruption even after accounting for the presence of learning disorders and oppositional symptoms. Symptoms of ADHD accounted for minimal variance in interpersonal functioning or participation in organized activities after controlling oppositional symptoms. The ADHD symptom domains demonstrate domain-specific relations with various ADHD-related functional impairments. In addition, the results highlight the role of oppositionality in interpersonal relationship difficulties and participation in organized activities.

Neuropsychological performance and attention-deficit hyperactivity disorder subtypes and symptom dimensions.

Characterization of clinical heterogeneity in attention-deficit hyperactivity disorder (ADHD) remains controversial. Neuropsychological and cognitive studies provide one type of validation data, but too often have considered only a narrow range of functional domains. The current study examined ADHD subtype and presentation differences across a broad range of neurocognitive domains in a large clinically characterized, community-recruited sample of 498 youth (213 control, 107 ADHD-primarily inattentive [ADHD-PI], 137 ADHD-combined [ADHD-C]), ages 6-17 years. Domains assessed included inhibition, working memory, arousal, processing speed, response variability, and temporal information processing. Youth with ADHD-C performed worse than youth with ADHD-PI in all domains, consistent with a severity model. Performance among a subgroup with a "restrictive inattentive" presentation indicated potential deficits in processing speed relative to other ADHD-PI youth, but no other effects. When all measures were included in the same model, cognitive control (executive functions, working memory, and memory span), arousal, and response variability each provided uniquely incremental statistical prediction of specific symptom dimensions and of subtype/presentation, but temporal information processing and processing speed did not. Results suggest the potential to consolidate multiple neurocognitive theories of ADHD, and that such consolidation will apply across putative clinical subtypes or presentations.