Hyperactive-impulsive Symptoms Research Articles

ADHD, chronotype, and circadian preference in a multi-site sample of college students.

Attention-deficit/hyperactivity disorder and an evening chronotype are both common among college students, and there is growing interest in understanding the possible link between attention-deficit/hyperactivity disorder and circadian function. However, mixed findings have been reported, and many of the existing studies have used small samples that were unable to examine chronotype across attention-deficit/hyperactivity disorder presentations. Participants were 4751 students (73% female; 80% White), aged 18-29 years (M = 19.28, SD = 1.50), from five universities who completed measures assessing attention-deficit/hyperactivity disorder, depressive and anxiety symptoms, as well as the Morningness-Eveningness Questionnaire to assess chronotype (categorical) and circadian preference (dimensional). Participants with either attention-deficit/hyperactivity disorder predominantly inattentive presentation or attention-deficit/hyperactivity disorder combined presentation had higher rates of being an evening type (47.2% and 41.5%, respectively) than participants without elevated attention-deficit/hyperactivity disorder (28.5%), and participants with attention-deficit/hyperactivity disorder predominantly inattentive presentation also had higher rates of being an evening type than participants with attention-deficit/hyperactivity disorder predominantly hyperactive-impulsive presentation (30.7%). Dimensional analyses indicated that attention-deficit/hyperactivity disorder inattentive symptoms were more strongly associated than hyperactive-impulsive symptoms with eveningness preference. Finally, greater eveningness preference strengthened the association between attention-deficit/hyperactivity disorder inattention and depressive symptoms but not anxiety symptoms. This is the largest study to document that college students with elevated attention-deficit/hyperactivity disorder symptoms are more likely to be evening types than other college students, and inattentive symptoms in particular are associated with later circadian preference.

Shared genetic etiology between ADHD, task-related behavioral measures and brain activation during response inhibition in a youth ADHD case–control study

Impaired response inhibition is commonly present in individuals with attention-deficit/hyperactivity disorder (ADHD) and their unaffected relatives, suggesting impaired response inhibition as a candidate endophenotype in ADHD. Therefore, we explored whether behavioral and neural correlates of response inhibition are related to polygenic risk scores for ADHD (PRS-ADHD). We obtained functional magnetic resonance imaging of neural activity and behavioral measures during a stop-signal task in the NeuroIMAGE cohort, where inattention and hyperactivity-impulsivity symptoms were assessed with the Conners Parent Rating Scales. Our sample consisted of 178 ADHD cases, 103 unaffected siblings, and 173 controls (total N = 454; 8–29 years), for whom genome-wide genotyping was available. PRS-ADHD was constructed using the PRSice-2 software. We found PRS-ADHD to be associated with ADHD symptom severity, a slower and more variable response to Go-stimuli, and altered brain activation during response inhibition in several regions of the bilateral fronto-striatal network. Mean reaction time and intra-individual reaction time variability mediated the association of PRS-ADHD with ADHD symptoms (total, inattention, hyperactivity-impulsivity), and activity in the left temporal pole and anterior parahippocampal gyrus during failed inhibition mediated the relationship of PRS-ADHD with hyperactivity-impulsivity. Our findings indicate that PRS-ADHD are related to ADHD severity on a spectrum of clinical, sub-threshold, and normal levels; more importantly, we show a shared genetic etiology of ADHD and behavioral and neural correlates of response inhibition. Given the modest sample size of our study, future studies with higher power are warranted to explore mediation effects, suggesting that genetic liability to ADHD may adversely affect attention regulation on the behavioral level and point to a possible response inhibition-related mechanistic pathway from PRS-ADHD to hyperactivity-impulsivity.

Disentangling the relationships between motor control and cognitive control in young children with symptoms of ADHD

ABSTRACT Children with ADHD experience difficulties with motor and cognitive control. However, the relationships between these symptoms are poorly understood. As a step toward improving treatment, this study investigated associations between specific aspects of motor control and cognitive control in children with varying levels of hyperactive-impulsive symptoms. A heterogeneous sample of 255 children of 4 to 10 years of age (median = 6.50, MAD = 1.36) completed a battery of tests probing motor generation, visuomotor fluency, visuomotor flexibility, cognitive inhibition, verbal and visuospatial working memory, and cognitive flexibility. Their caregivers were interviewed regarding their hyperactive-impulsive symptoms. 25.9% of the main sample met diagnostic criteria for ADHD. Multiple linear regression analysis was used to determine whether specific aspects of motor control were associated with specific aspects of cognitive control, and whether any associations were moderated by hyperactive-impulsive symptoms. Additionally, cognitive modeling (the drift diffusion model approximated with EZ-DM) was used to understand performance on a cognitive inhibition task. Visuomotor fluency was significantly associated with cognitive inhibition. Visuomotor flexibility was significantly associated with cognitive flexibility. There were no significant moderation effects. Cognitive modeling was inconclusive. In conclusion, the ability to fluently perform visually guided continuous movement is linked with the ability to inhibit the effects of distracting information. The ability to spontaneously use visual information to flexibly alter motor responses is related to the ability to cognitively shift from one frame of mind to another. These relationships appear to be quantitatively and qualitatively similar across the childhood hyperactive-impulsive continuum as rated by parents.

Identifying Symptoms of ADHD and Disruptive Behavior Disorders Most Strongly Associated with Functional Impairment in Children: A Symptom-Level Approach

To enhance the understanding of how symptoms of attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders such as oppositional defiant disorder (ODD), conduct disorder (CD), including callous-unemotional (CU) traits, differentially relate to functional impairment (FI). Participants were 474 German school-age children (age: M = 8.90, SD = 1.49, 81% male) registered for participation in the ESCAschool trial (ESCAschool: Evidence-based, Stepped Care of ADHD in school-aged children). Clinicians assessed the severity of individual symptoms and five FI domains specifically associated with ADHD symptoms or ODD/CD/CU symptoms using a semi-structured clinical interview. We conducted two multiple linear regression analyses, combined with relative importance analyses, to determine the impact of individual symptoms on global FI associated with ADHD and ODD/CD/CU symptoms. Next, we estimated two networks and identified the strongest associations of ADHD symptoms or ODD/CD/CU symptoms with the five FI domains. Symptoms varied substantially in their associations with global FI. The ADHD symptom Easily Distracted (15%) and ODD symptom Argues with Adults (10%) contributed most strongly to the total explained variance. FI related to academic performance, home life and family members, and psychological strain were most strongly associated with ADHD inattention symptoms, whereas FI related to relationships with adults and relationships with children and recreational activities were most strongly associated with hyperactivity-impulsivity symptoms. By comparison, the ODD/CD/CU symptoms most closely linked to FI domains originated from the ODD and CD dimensions. Our findings contribute to a growing body of literature on the importance of analyzing individual symptoms and highlight that symptom-based approaches can be clinically useful.

Methylphenidate dose–response in children with ADHD: evidence from a double-blind, randomized placebo-controlled titration trial

Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally increased doses are found to result in better symptom control; however, it remains unclear whether this pattern can be observed at the individual level, given the large heterogeneity in individual dose–response relationships and observed placebo responses. A double-blind, randomized, placebo-controlled cross-over trial was used to compare weekly treatment with placebo and 5, 10, 15 and 20 mg of MPH twice daily on parent and teacher ratings of child ADHD symptoms and side effects. Participants were 5–13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). MPH response was assessed at group and individual levels and predictors of individual dose–response curves were examined. Mixed model analysis showed positive linear dose–response curves at group level for parent and teacher rated ADHD symptoms and parent rated side effects, but not for teacher rated side effects. Teachers reported all dosages to improve ADHD symptoms compared to placebo, while parents only reported > 5 mg/dose as effective. At the individual level, most (73–88%) children, but not all, showed positive linear dose–response curves. Higher severity of hyperactive-impulsive symptoms and lower internalizing problems, lower weight, younger age and more positive opinions towards diagnosis and medication partly predicted steeper linear individual dose–response curves. Our study confirms that increased doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose–response relationship was found and increased doses did not lead to greater symptom improvement for all children. This trial was registered in the Netherlands trial register (# NL8121).

Yoga as an Adjunct Treatment for Attention Deficit Hyperactivity Disorder (ADHD)

IntroductionAttention Deficit Hyperactivity Disorder (ADHD) affects about 9.4% (6.4 million) children in the United States. Pharmacological treatment, including stimulants, is a known therapy for ADHD. However, its possible subtherapeutic effectiveness, residual symptoms, and adverse effects have prompted us to explore the current evidence of Yoga as an add-on therapy that has shown synergistic effects in recent studies.Objectives1) We aim to assess Yoga’s efficacy as an add-on treatment for ADHD.2) Assess the current evidence of Yoga as an add-on therapy for ADHD.MethodsWe searched PubMed, PubMed Central, Medline, Web of Science, and Biosis databases with the keywords “Attention Deficit Disorder with Hyperactivity” (MeSH) and “ADHD” in the context of “Yoga” (MeSH). Identified 4 relevant studies that were published until September 30, 2022.ResultsA study by Jensen et al. found improvement in impulsivity, hyperactivity, and restlessness in the ADHD with medications patient group after 20 Yoga sessions. Study utilized Conners’ Parents Rating Scales and found improvement in the Yoga group on Oppositional, Global Index Emotional Lability, Global Index Total, Global Index Restless/Impulsive, and ADHD Index scale, changes associated with the number of sessions (Jensen et al. J Atten Disord 2004; 7 205-216). In another study, children with ADHD showed significant improvement after 8 weeks of 16 Yoga sessions in accuracy rate and reaction time in the Visual Pursuit Test and Determination Test (Chou et al. Peer J 2017; 5 e2883). A nine-year-old male case showed improvement in inattentive and hyperactive-impulsive symptoms on Vanderbilt Assessment Scales from parents and teachers after 6 months of Yoga practice (Gunaseelan et al. Cureus 2021; 5, e2883). Another 6-week Yoga intervention randomized trial in pre-school ADHD children showed significant improvement in hyperactivity and inattention with fewer distractibility errors of omission and faster reaction time (Cohen et al. J Dev Behav Pediatr 2018; 39 200).ConclusionsThe results suggest that Yoga has beneficial effects as an adjunct treatment to pharmacotherapy in ADHD for reducing hyperactivity and inattentiveness. Additionally, studies indicate its effectiveness in managing stress, anxiety, energy levels, and impulse control by staying focused with the help of breath and mind control. To explore the full spectrum of benefits and effectiveness of Yoga as an add-on therapy for ADHD patients, we recommend robust well-design future studies.Disclosure of InterestNone Declared

ADHD symptoms and smoking outcomes in a randomized controlled trial of varenicline for adolescent and young adult tobacco cessation

BackgroundMost adult daily smokers try their first cigarette during adolescence. Attention-Deficit Hyperactivity Disorder (ADHD) in adolescents is associated with increased risk for cigarette smoking. The impact of ADHD symptoms on smoking cessation among adolescents has been less well-studied. The present secondary data analysis from a clinical trial of varenicline examined ADHD symptoms as a moderator of smoking cessation in adolescents and young adults. MethodsThe double-blind, placebo-controlled trial included treatment-seeking daily cigarette smokers ages 14 – 21 (N = 157) randomized to receive a 12-week course of varenicline or placebo, added to weekly smoking cessation counseling. At pre-treatment assessment, participants were administered a self-report measure of ADHD symptoms, the ADHD – Rating Scale (ADHD-RS). High (≥5) versus low (<5) and continuous ADHD-RS symptom counts in both hyperactive/impulsive (HI) and inattention (IA) domains were examined as predictors of smoking outcomes. ResultsParticipants with high IA symptoms at baseline were less likely to achieve 7-day point prevalence abstinence (PPA) at weekly visits (p = .001) during active treatment and end-of-treatment (p = .002) compared to those with low IA symptoms. In contrast, high HI symptoms did not predict differences in 7-day PPA or end-of-treatment abstinence versus low symptoms (p’s ≥ .07). These findings were not modified by varenicline versus placebo treatment assignment. ConclusionsADHD IA symptoms were associated with poorer cessation outcomes among adolescent smokers. These findings warrant additional investigation into how ADHD symptoms may be accounted for in smoking cessation interventions for adolescents and young adults.

Drinking Motives Mediate the Relation between Attention-Deficit/Hyperactivity Disorder Symptoms and Alcohol-Related Problems among College Students

Evidence demonstrates an association between symptoms of attention-deficit/hyperactivity disorder (ADHD) and alcohol outcomes, though mechanisms underlying relations are unclear. Given that drinking motives (coping-anxiety, coping-depression, enhancement, social, and conformity) appear to serve as a mediator through which other factors influence drinking behavior, the current multi-site study examined the relation between ADHD symptoms and alcohol outcomes through motives. Past-month drinkers completed online measures assessing ADHD symptoms, alcohol use and problems, and drinking motives. A multiple-mediator model found inattention symptoms were: 1) positively associated with coping-depression, which positively related to alcohol use, which positively related to alcohol problems; 2) positively associated with enhancement motives, which positively related to use, which positively related to problems; and 3) positively associated with coping-anxiety, which negatively related to use, which positively related to problems. No indirect relations via motives were found for hyperactive-impulsive symptoms. Findings highlight unique associations depending on ADHD symptoms and specific drinking motives.

Attention-deficit/hyperactivity disorder and white matter microstructure: the importance of dimensional analyses and sex differences.

Attention-deficit/hyperactive disorder (ADHD) has substantial heterogeneity in clinical presentation. A potentially important clue may be variation in brain microstructure. Using fractional anisotropy (FA), previous studies have produced equivocal results in relation to ADHD. This may be due to insufficient consideration of possible sex differences and ADHD's multi-componential nature. Using whole-brain analyses, we investigated the association between FA and both ADHD diagnosis and ADHD symptom domains in a well-characterized, ADHD (n = 234; 32% female youth) and non-ADHD (n = 177; 52% female youth), case-control cohort (ages 7-12). Sex-specific effects were tested. No ADHD group differences were found using categorical assessment of ADHD without consideration of moderators. However, dimensional analyses found total symptoms were associated with higher FA in the superior corona radiata. Further, inattention symptoms were associated with higher FA in the corpus callosum and ansa lenticularis, and lower FA in the superior longitudinal fasciculus, after control for overlap with hyperactivity-impulsivity. Hyperactivity-impulsivity symptoms were associated with higher FA in the superior longitudinal fasciculus, and lower FA in the superior cerebellar peduncles, after control for overlap with inattention. Meanwhile, both categorical and dimensional analyses revealed ADHD-by-sex interactions (voxel-wise p < 0.01). Girls with ADHD had higher FA, but boys with ADHD had lower FA (or no effect), compared to their same-sex peers, in the bilateral anterior corona radiata. Further, higher ADHD symptom severity was associated with higher FA in girls, but lower FA in boys, in the anterior and posterior corona radiata and cerebral peduncles. ADHD symptom domains appear to be differentially related to white matter microstructure, highlighting the multi-componential nature of the disorder. Further, sex differences will be crucial to consider in future studies characterizing ADHD-related differences in white matter microstructure.

A Counting Stroop Functional Magnetic Resonance Imaging Study on the Effects of ORADUR-Methylphenidate in Drug-Naive Children with Attention-Deficit/Hyperactivity Disorder.

Objective: Methylphenidate is effective in reducing the clinical symptoms of patients with attention-deficit/hyperactivity disorder (ADHD). ORADUR®-methylphenidate is a new extended-release preparation of methylphenidate. This study aimed at identifying brain regions with activation changes and their correlations with neuropsychological functions after treatment with ORADUR-methylphenidate in children with ADHD. Methods: We recruited drug-naive children with ADHD and age- and sex-matched typically developing (TD) children. They were all scanned with the functional magnetic resonance imaging (fMRI) during the counting Stroop task at baseline, and those with ADHD had the second fMRI assessment after 8-week treatment with ORADUR-methylphenidate. The Rapid Visual Information Processing (RVP) and Conners' Continuous Performance Test (CCPT) were used to assess the attention performance of the ADHD (before and after treatment) and TD groups. Results: ORADUR-methylphenidate significantly decreased inattention (Cohen d = 2.17) and hyperactivity-impulsivity (Cohen d = 0.98) symptoms. We found less activation in the right inferior frontal gyrus (rIFG) in the pre-treatment ADHD children than TD children and greater treatment-induced activation in the dorsal anterior cingulate cortex (dACC) and the right dorsolateral prefrontal cortex (rDLPFC). There was no significant difference between the post-treatment ADHD and TD groups. However, the treatment-related activations in the dACC, rDLPFC, and rIFG were significantly correlated with CCPT and RVP measures. Conclusions: Our findings indicated that ORADUR-methylphenidate increased brain activations in the dACC, rDLPFC, and rIFG in children with ADHD, associated with improved focused attention, reduced impulsivity, and enhanced inhibition control. Activities of these brain regions might be biomarkers for the treatment effectiveness of methylphenidate for ADHD. Clinical Trials Registration: ClinicalTrials.gov number, NCT02450890.

The moderating role of sex and self-, teacher-, and father-reported ADHD hyperactivity-impulsivity symptoms, on the association between early adolescent internalizing symptoms and substance use

AimsInternalizing symptoms are theorized to lead to substance use (SU) via a tendency to use substances to cope with or self-medicate negative feelings and emotions; however, empirically, this association is mixed, pointing to the existence of moderating factors. The present study aimed to examine how self-, teacher-, and father-reported attention-deficit/hyperactivity disorder hyperactivity-impulsivity symptoms (ADHD-HI) and sex, moderated the association between self-reported internalizing symptoms and SU, in early adolescence. MethodsCross-sectional data obtained at 13 years of age, drawn from the Quebec Longitudinal Study of Child Development (N = 1,424; 53 % female). Alcohol, cigarette, and cannabis use, and internalizing and ADHD-HI symptoms were assessed. ResultsThere was a significant three-way interaction between internalizing, ADHD-HI, and sex, for cigarette use, with Bayes factor (BF) indicating very strong evidence for an effect (BF = 48.40). While the three-way interaction for cannabis use did not reach statistical significance (self-report: p <.066; father-report: p <.053), BF indicated substantial evidence for an effect (self-report: BF = 3.54; father-report: BF = 9.08). Further analyses revealed internalizing was associated with cigarette and cannabis use only among females with high ADHD-HI symptoms (cigarette use: β = 0.15, SE = 0.04, 95 %CI [0.07, 0.22]; cannabis use (self-reported ADHD-HI): β = 0.14, SE = 0.06, 95 %CI [0.04, 0.25]; cannabis use (father-reported ADHD-HI): β = 0.21, SE = 0.10, 95 %CI [0.01, 0.41]). ConclusionsFindings aid in clarifying the inconsistent relationship between internalizing symptoms and SU among adolescent females by underscoring the moderating role of ADHD-HI. Further, findings also support a growing body of literature which highlights the need for both self- and adult-informants (i.e., teacher and parent) in assessing ADHD-HI symptoms in females.

Attention-deficit/hyperactivity disorder from preschool to school age: change and stability of parent and teacher reports

Identifying attention-deficit/hyperactivity disorder (ADHD) in pre-schoolers may improve their development if treated, but it is unclear whether ADHD symptoms from this age are stable enough to merit treatment. We aimed to investigate the stability of parent- and teacher-reported ADHD symptoms and ADHD classified above the diagnostic symptom thresholds, including for hyperactivity-impulsivity (HI), inattention and combined presentations from age 3 to 8 years. This study is part of the longitudinal, population-based Norwegian Mother, Father and Child Cohort Study. At child age 3 years, parents were interviewed and teachers rated ADHD symptoms. At age 8 years, parents (n = 783) and teachers (n = 335) reported ADHD symptoms by the Child Symptom Inventory-4. We found a significant reduction in the mean number of parent-reported ADHD and HI symptoms from age 3 to 8 years, but otherwise similar mean numbers. Parent-reported ADHD symptoms were moderately correlated between ages, while correlations were low for teachers. A total of 77/108 (71%) of the children classified with parent-reported HI presentation at age 3 years were no longer classified within any ADHD presentation at age 8 years, the only clear trend across time for either informant. There was a low to moderate parent–teacher-agreement in the number of reported symptoms, and very low informant agreement for the classified ADHD presentations. Overall, clinicians should exercise caution in communicating concern about HI symptoms in preschool children. Age 3 years may be too early to apply the ADHD diagnostic symptom criteria, especially if parents and teachers are required to agree.

Associations among ADHD symptoms, ODD symptoms, and borderline personality features: A network analysis.

Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are common childhood syndromes that exhibit a high degree of comorbidity. Both ADHD and ODD symptoms in childhood predict higher levels of borderline personality features (BPF) later in development. Yet ADHD, ODD, and BPF each consist of a heterogeneous group of symptoms, and symptom-level associations between these groups remain unclear. The present study examined symptom-level associations, as well as sex differences in symptom-level associations, among ADHD, ODD, and BPF using network analysis. Caregivers of 962 children between the ages of 5 and 12 completed rating scales of ADHD, ODD, and BPF. Assessment of Bridge Expected Influence indicated a number of bridge symptoms linking ADHD to ODD; these bridge symptoms were primarily from the hyperactive-impulsive (rather than the inattentive) dimension of ADHD (e.g., blurts out answers, leaves seat, runs excessively). A smaller number of bridge symptoms were identified linking ADHD and ODD to BPF, and these bridge symptoms were different for girls versus boys. Overall, several ADHD hyperactive-impulsive symptoms were related to the BPF item gets in trouble for doing things without thinking, and the ODD item touchy/easily annoyed was related to the BPF item goes back and forth between different feelings. Moreover, whereas we observed stronger links between ODD antagonistic symptoms (e.g., blames others) and BPF among girls, we observed stronger links between ODD oppositional symptoms (e.g., defies/refuses to comply) and BPF among boys. Taken together, results provide a more nuanced, symptom-level understanding of the overlap among ADHD, ODD, and BPF.

Temperament Dimensions and Awakening Cortisol Levels in Attention-Deficit/Hyperactivity Disorder.

ObjectiveTo investigate whether temperament dimensions, Effortful Control (EC), Surgency-Extraversion (SE), and Negative Affectivity (NA), are associated with attention-deficit/hyperactivity disorder (ADHD) and how they relate to awakening cortisol levels, as a proxy measure of peripheral arousal.MethodsParent-rated temperament and saliva samples were collected from 55 children with ADHD and 65 age-matched controls.ResultsCompared to controls, youths with ADHD showed lower EC, higher NA, and lower awakening cortisol levels but did not differ in SE. Similar findings emerged in dimensional analyses linking temperament traits to inattention and hyperactivity-impulsivity symptoms. The results remained unchanged when controlling for the presence of co-occurring opposition-defiance and anxiety traits, as well as medication status. Temperament dimensions were not associated with cortisol levels.ConclusionsPoor temperamental emotional and cognitive self-regulation showed significant associations with ADHD but did not appear to be linked to the under-arousal typically seen in ADHD.

Review: Which components of behavioral parent and teacher training work for children with ADHD? - a metaregression analysis on child behavioral outcomes.

This metaregression analysis examined which behavioral techniques that are commonly used in behavioral parent and teacher training programs for children with attention-deficit/hyperactivity disorder (ADHD) were related to program effectiveness on children's behavioral outcomes. We included 32 randomized controlled trials (N = 2594 children) investigating behavioral parent training, teacher training, or a combination, in children with ADHD under 18 years. Outcomes were symptom counts of total ADHD, inattention, and hyperactivity-impulsivity and behavioral problems. The dosage of techniques was extracted from the intervention manuals. Metaregression was used to assess which techniques and intervention characteristics (setting, delivery method, duration, and home-school collaboration) were associated with intervention effectiveness. Higher dosage of psycho-education for parents was associated with smaller effects on behavioral problems and, only in case of parent training, also with smaller effects on ADHD symptoms. Higher dosage of teaching parents/teachers to use negative consequences was associated with larger effects on behavioral problems. Individual training compared with group training was associated with larger effects on ADHD and hyperactivity-impulsivity symptoms. This study provides first insights into the specific techniques that are essential in behavioral parent and teacher training programs for children with ADHD. This knowledge can eventually be used to improve and tailor interventions.

Multimodal treatment efficacy differs in dependence of core symptom profiles in adult Attention-Deficit/Hyperactivity Disorder: An analysis of the randomized controlled COMPAS trial

There is broad consensus that to improve the treatment of adult Attention-Deficit/Hyperactivity Disorder (ADHD), the various therapy options need to be tailored more precisely to the individual patient's needs and specific symptoms. This post-hoc analysis evaluates the multimodal effects of first-line medication (methylphenidate [MPH] vs placebo [PLB]) and psychotherapeutic (group psychotherapy [GPT] vs clinical management [CM]) treatments on the ADHD core symptoms inattention, hyperactivity and impulsivity. For the two-by-two factorial, observer-blinded, multicenter, randomized controlled Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS; ISRCTN54096201), 419 outpatients with ADHD were considered for analysis. ADHD symptoms were assessed by blind observer-rated and patient-rated Conners Adult ADHD Rating Scales before treatment (T1), 13 weeks (T2) and 26 weeks (T3) after T1, at treatment completion after 52 weeks (T4), and at follow-up (130 weeks, T5). MPH was superior to PLB in improving symptoms of inattention at almost all endpoints (observer-rated T2, T3, T4, T5; patient-rated T2, T3, T4), while a significant decrease in hyperactivity and impulsivity was at first found after 6 months of treatment. CM compared to GPT decreased inattention and impulsivity in the early treatment phase only (observer-rated T2, patient-rated T2, T3). In conclusion, while MPH seems to have a direct and sustained effect on inattention, premature medication discontinuation should particularly be avoided in patients with hyperactive-impulsive symptoms. Also, especially in high inattention and/or impulsivity presentations, initial individual patient management might be beneficial. Consequently, considering individual core symptom profiles may enhance the efficacy of treatments in adult ADHD.

Affective-cognitive-behavioral heterogeneity of Attention-Deficit/Hyperactivity Disorder (ADHD): Emotional dysregulation as a sentinel symptom differentiating “ADHD-simplex” and “ADHD-complex” syndromes?

BackgroundCurrent DSM and ICD classifications of Attention-Deficit/Hyperactivity Disorder (ADHD) exclude emotional dysregulation (ED) in their diagnostic criteria, despite ED symptoms frequently co-occurring in ADHD and likely sharing common neurobiological substrates. In this study, we examined whether consideration of ED symptoms could delineate more informative “ADHD+ED” subphenotypes. Method4106 children with ADHD were recruited. ED and inattentive (IA) and hyperactive/impulsive (HI) symptoms were profiled using latent class analyses (LCA). The derived latent class (LC) subphenotypes were evaluated and validated in relation to comorbidity patterns, executive functions, and functional impairments. ResultsFive LC subphenotypes with ED symptoms were identified: IA/HI + ED profile (LC1); HI + ED profile (LC2); IA + ED profile (LC3); IA/HI profile (LC4); and IA profile (LC5). Cross-validation of the LCA model using support vector machine analysis confirmed 83% accuracy. ED positive (ED+ve) subphenotypes were associated with higher rates of oppositional defiant disorder, mood disorders, anxiety disorders, as well as more severe autistic traits and sluggish cognitive tempo symptoms. Higher rates of ecological executive functioning impairments (BRIEF ratings) were found among ED+ve subphenotypes (though no differences were detected by laboratory-based measures). Functional impairments were also more severe among participants with ED+ve subphenotypes. LimitationsThe data for our LCA were cross-sectional and based primarily on parent ratings. ConclusionOur classification model has parcellated IA, HI, and ED symptoms into novel informative subphenotypes. These classifications provide preliminary evidence that ED symptoms could serve as sentinel features to identify a potential “ADHD-complex” syndrome, which demarcates a more pervasive condition of greater severity, complexity, and impairment.

Peer feedback decreases impulsive choice in adolescents with and without attention-deficit/hyperactivity disorder.

Impulsivity is a core feature of attention-deficit/hyperactivity disorder (ADHD). Previous work using the delay discounting task to assess impulsivity reveals that adolescents with ADHD tend to prefer a smaller-immediate reward over a larger-delayed reward, and this relates to problematic choices in daily life. To gain a better understanding of daily decision-making in adolescence, it is important to examine the social context, as peers have a major influence on decisions. Peer influence often has a negative connotation, but also provides an opportunity to promote positive outcomes. To date, it is unclear if peers affect impulsive decision-making in adolescents with ADHD, for better or for worse. The aim of this preregistered study was to examine the effect of peer feedback on impulsive choice in male adolescents with and without ADHD (ages 13-23; N=113). We utilized an adapted delay discounting task that was administered alone, in a social condition, and alone again. In the social condition, adolescents received either (between-subjects) manipulated impulsive or non-impulsive peer feedback. Impulsive peer feedback consisted of likes for choosing the smaller immediate reward, whereas non-impulsive peers endorsed choosing the larger delayed reward. Preregistered analyses showed that non-impulsive peer feedback resulted in decreased impulsive choice, whereas impulsive peer feedback did not alter decision-making in adolescents with and without ADHD. Explorative analyses of inattention and hyperactivity-impulsivity symptoms in the total sample, irrespective of diagnosis, showed that lower hyperactivity-impulsivity and more inattention symptoms were associated with increased susceptibility to non-impulsive peer feedback. Together, these findings indicate that peers may provide an opportunity to decrease impulsivity and emphasize individual differences in susceptibility to non-impulsive peer feedback related to inattention and hyperactivity-impulsivity. Therefore, peer feedback may be a promising component in behavioral peer-supported interventions in adolescents with ADHD.

Altered White-matter Tract Property in Adults with Attention-deficit Hyperactivity Disorder

Although altered microstructure properties of white-matter tracts have been reported in children with attention-deficit/hyperactivity disorder (ADHD), findings from relatively few adult ADHD studies are inconsistent. This study aims to examine microstructural property over the whole brain in adults with ADHD and explore structural connectivities. Sixty-four medication-naïve adults with ADHD and 81 healthy adults received diffusion spectrum imaging. Generalized fractional anisotropy (GFA), an index indicating microstructural property, was calculated stepwise among 76 white-matter tracts. With the threshold-free clustering weighted method, the segments with the largest group difference were selected, and mean GFA (mGFA) values were calculated. Adults with ADHD had increased mGFA values in the segments located in the left frontal aslant tract, the right inferior longitudinal fasciculus, and the left perpendicular fasciculus, and reduced mGFA values in the segments located in the right superior longitudinal fasciculus (SLF) I, the left SLF II, the right frontostriatal tracts from dorsolateral prefrontal cortex and the ventrolateral prefrontal cortex, the right medial lemniscus, the right inferior thalamic radiation to the auditory cortex, and the callosal fibers. Additionally, the mGFA value of the right SLF I segment was associated with hyperactivity-impulsivity symptoms. Our findings suggest that white-matter tracts with altered microstructure properties are located within the attention networks, fronto-striato-thalamocortical regions, and those associated with attention and visual perception in adults with ADHD.

Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis

BackgroundVariation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 – 34 years), and using the more physiologically informative fixel-based analysis (FBA). MethodsData were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. ResultsClinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax = 1.092, standardized effect[SE] = 0.044, pFWE = 0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax = 3.775, SE = 0.051, pFWE = 0.019). ConclusionsAberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory.