Attention-deficit/hyperactivity Disorder Rating Scale Research Articles

Reliability and Validity of the Korean Version of the Parental Stress Scale for Children With Attention-Deficit/Hyperactivity Disorder

ObjectiveThis study standardizes the Parental Stress Scale (PSS) for Republic of Korean parents of children with attention-deficit/hyperactivity disorder (ADHD) and verifies its reliability and validity. MethodsData from 160 parents of children with ADHD who completed the following self-reported questionnaires were analyzed: the Korean ADHD Rating Scales, the Patient Health Questionnaire-9, the State–Trait Anxiety Inventory, the PSS, and the Global Assessment of Recent Stress Scale. All scale items were measured for reliability and validity, and the appropriate factors for measuring stress in Korean parents with ADHD children were extracted. ResultsExploratory and confirmatory factor analyses derived two sub-factors and 11 items. Goodness of fit was confirmed, and the scale was deemed suitable for explaining stress in parents of children with ADHD. ConclusionIn this study, the validity and reliability of the K-PSS-ADHD were investigated. We expect that the K-PSS-ADHD will be used as a basis for future studies on stress in parents of children with ADHD.

Differences in Attention Skill between Children with ADHD and Typically Developing Children in Indonesian Primary Schools

Background: Attention Deficit Hyperactivity Disorder (ADHD) is the most common neuropsychological developmental disorder in children. ADHD is characterized by inattention, overactivity, and impulsivity. However, the attention skill is not clearly studied in children with ADHD in Indonesia. Objective: The aim of the present study was to investigate the differences in attention skill between children with ADHD and typically developing children (TD), and identify the differences between ADHD subtypes at primary schools in Bandung city Indonesia in terms of the parameter of attention. Methods: This study used the quantitative method. The population of this study was children with ADHD and typically developing (TD) school-age children. The data sampling technique was purposive sampling, consisting of 30 children as a group of ADHD children and 30 children as a group of TD children. The instrument to collect data was Wechsler Intelligence Scale for Children (WISC), Indonesian ADHD Rating Scale (IARS), and The D2 test of attention. The analysis method used t-test and SPSS V.24 for Windows. Results: This study showed significant differences in attention skill performance between children with ADHD and TD children in the variables including the total number of tasks completed, omission, commission, error rate, total amount minus errors or selective attention skill, fluctuation rate and concentration performance. There have been observed significant differences between ADHD subtypes in terms of total number, omission, commission, error rate, total amount minus errors or selective attention skill, and concentration performance. Conclusion: Children with ADHD were found to have lower results than typically developing children in terms of attention skill, inhibiting control, and ability in performance accuracy. Children with ADHD-C subtypes were found to have more inattentive tendencies, hyperactive, and impulsive compared to ADHD-I and ADHD-H. ADHD-C subtype showed more deficits than ADHD-I and ADHD-H in response inhibition and accuracy of performance.

Hyperactivity and Inattention in Young Patients Born With an Atrial Septal or Ventricular Septal Defect.

Background: Patients with congenital heart defects have a well-established risk of neuropsychiatric comorbidities. Inattention and hyperactivity are three to four times more frequent in children with complex congenital heart defects. We have previously shown a higher burden of overall attention deficit/hyperactivity disorder (ADHD) symptoms in adults with simple congenital heart defects as well. However, it is unknown whether the higher burden of ADHD symptoms is mainly driven by hyperactivity, inattention, or both.Methods: The participants [simple congenital heart defect = 80 (26.6 years old), controls = 36 (25.3 years old)] and a close relative for each (n = 107) responded to the long version of the Conners' Adults ADHD Rating Scales questionnaire. Our primary and secondary outcomes are mean T-scores in the ADHD scores and symptom sub-scores.Results: Patients with simple congenital heart defects reported a higher mean T-score at all three DSM-IV ADHD scores (ADHD—combined: 52.8 vs. 44.9, p = 0.007, ADHD—inattention: 55.5 vs. 46.4, p = 0.002, and ADHD—hyperactivity: 49.4 vs. 44.0, p = 0.03) and in all four ADHD symptom sub-scores (inattention/memory problems: 50.3 vs. 44.2, p = 0.001, hyperactivity/restlessness: 49.7 vs. 45.9, p = 0.03, impulsivity/emotional lability: 50.0 vs. 41.3, p = 0.001, and self-esteem problems: 53.8 vs. 46.3, p = 0.003). The results were maintained after the removal of outliers (incongruent responses), albeit the hyperactivity/restlessness ADHD symptom sub-score lost significance. Self- and informant ratings differed significantly on the ADHD—inattention score for the congenital heart defect group, where informants rated the ADHD—inattention scores better than the congenital heart defect patients rated themselves.Conclusions: Patients with a simple congenital heart defect have a higher symptom burden across all ADHD scores and all symptom sub-scores. The higher burden of ADHD is driven by both inattention and hyperactivity symptoms, though the inattention symptoms seem more prominent. Close relatives were less aware of the inattention symptoms than the congenital heart defect patients themselves. Routine screening for ADHD symptoms may be warranted to facilitate adequate help and guidance as these symptoms are easily overlooked.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03871881.

The Implementation of CBT to Reduce Hyperactive Behaviors among Adolescents with ADHD

Adolescents with ADHD need serious handling to reduce their hyperactive Behavior. One strategy that is alleged to reduce this behavior is by implementing Cognitive Behavior Therapy (CBT). The purpose of this study was to determine the effect of the implementation of CBT and to analyze the effectiveness of CBT in reducing hyperactive behavior of adolescents with ADHD in Inclusive Junior High Schools. The implementation of this research used a pre-experimental research design with the One Group Pre-Test Post-Test research design by using the Vanderbilt ADHD Rating Scale behavior check instrument which is adopted by considering Indonesian language and culture. The subjects in this study were 3 adolescents with ADHD who had a level of activity representing the mild, moderate, and severe levels. The time used was 5 meeting sessions with a time allocation of 2 x 30 minutes for each meeting. The results showed that there is an effect of the implementation of CBT in reducing the hyperactive behavior of adolescents with ADHD at Inclusive Junior High School.

Influence of Atomoxetine on Relationship Between ADHD Symptoms and Prefrontal Cortex Activity During Task Execution in Adult Patients.

Objective: We conducted this non-randomized prospective interventional study to clarify the relationship between improved attention-deficit hyperactivity disorder (ADHD) symptoms and regional brain activity.Methods: Thirty-one adult patients underwent near-infrared spectroscopy examinations during a go/no-go task, both before and 8 weeks after atomoxetine administration.Results: Clinical symptoms, neuropsychological results of the go/no-go task, and bilateral lateral prefrontal activity significantly changed. A positive correlation was observed between right dorsolateral prefrontal cortex activity and Conners’ Adult ADHD Rating Scales scores. Before atomoxetine administration, no correlations between prefrontal cortex activity and clinical symptoms were observed in all cases. When participants were divided into atomoxetine-responder and non-responder groups, a positive correlation was observed between prefrontal cortex activity and clinical symptoms in the non-responder group before treatment but not in the responder group, suggesting that non-responders can activate the prefrontal cortex without atomoxetine.Conclusions: Individuals with increased ADHD symptoms appear to recruit the right dorsolateral prefrontal cortex more strongly to perform the same task than those with fewer symptoms. In clinical settings, individuals with severe symptoms are often observed to perform more difficultly when performing the tasks which individuals with mild symptoms can perform easily. The atomoxetine-responder group was unable to properly activate the right dorsolateral prefrontal cortex when necessary, and the oral administration of atomoxetine enabled these patients to activate this region. In brain imaging studies of heterogeneous syndromes such as ADHD, the analytical strategy used in this study, involving drug-responsivity grouping, may effectively increase the signal-to-noise ratio.

Suicidal ideation and executive functioning in pediatric cancer.

Neurocognitive impairments and psychological distress are among the most common difficulties experienced by children treated for cancer. Elevated rates of suicidal ideation (SI) are documented among cancer survivors, and a link between neurocognitive deficits and SI is evident, yet the relationship between SI and pediatric cancer-related neurocognitive effects has not yet been studied. Participants were 166 pediatric cancer patients (57.8% Brain Tumor, 31.3% leukemia, 10.8% other cancers) aged 6-23 (M=11.57, SD=3.82; 45.8% female) referred for neuropsychological surveillance. SI prevalence was measured by parent, teacher, or patient endorsement of self-harm related items on informant-report measures (e.g., the Child Behavior Checklist). Executive functioning (Behavior Rating Inventory of Executive Function), ADHD symptoms (ADHD Rating Scale), and performance-based measures were compared between those with SI and those without. 17.5% of pediatric cancer patients experienced SI, of which 44.7% had self-endorsement only, 58.5% parent-endorsement only, 20.6% teacher-endorsement only, and 24.1% had two endorsements. Those with SI had significantly greater impairments in global executive composite scores by both parent- and teacher-report (ps<0.05). Parents of children with SI endorsed significantly more inattention symptoms (M=6.10, SD=15.48) than those without SI (M=50.56, SD=8.70; p<0.01), but hyperactivity symptoms did not differ. Intellectual and executive function performance did not differ between those with and without SI (ps>0.1). An elevated number of children treated for cancer experience SI and related neurocognitive problems. Screening for SI and further assessment of the connection between executive functioning and SI in pediatric cancer populations is needed.

Correlation between brain function and ADHD symptom changes in children with ADHD following a few-foods diet: an open-label intervention trial

Research into the effect of nutrition on attention-deficit hyperactivity disorder (ADHD) in children has shown that the few-foods diet (FFD) substantially decreases ADHD symptoms in 60% of children. However, the underlying mechanism is unknown. In this open-label nutritional intervention study we investigated whether behavioural changes after following an FFD are associated with changes in brain function during inhibitory control in 79 boys with ADHD, aged 8–10 years. Parents completed the ADHD Rating Scale before (t1) and after the FFD (t2). Functional magnetic resonance imaging (fMRI) scans were acquired during a stop-signal task at t1 and t2, and initial subject-level analyses were done blinded for ARS scores. Fifty (63%) participants were diet responders, showing a decrease of ADHD symptoms of at least 40%. Fifty-three children had fMRI scans of sufficient quality for further analysis. Region-of-interest analyses demonstrated that brain activation in regions implicated in the stop-signal task was not associated with ADHD symptom change. However, whole-brain analyses revealed a correlation between ADHD symptom decrease and increased precuneus activation (pFWE(cluster) = 0.015 for StopSuccess > Go trials and pFWE(cluster) < 0.001 for StopSuccess > StopFail trials). These results provide evidence for a neurocognitive mechanism underlying the efficacy of a few-foods diet in children with ADHD.

Pilot study of a mobile application-based intervention to induce changes in neural activity in the frontal region and behaviors in children with attention deficit hyperactivity disorder and/or intellectual disability

Children with neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) and intellectual disability (ID), need early intervention and continuous treatment. We aimed to investigate the feasibility and acceptability of mobile application-based interventions in children with ADHD and ID in supporting attention and cognitive function. Twenty-six children with ADHD and/or ID with attention and cognition difficulties were recruited. Participants completed a 12-week mobile application-based intervention. To assess whether digital intervention improved attention and cognitive function, we used the Comprehensive Attention Test (CAT), Cambridge Neuropsychological Tests Automated Battery (CANTAB), and electroencephalography (EEG) to examine direct changes in children's behavior and neural activity. Clinicians and parents assessed changes using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Korean version of the ADHD Rating Scale (K-ARS), Clinical Global Impression-Improvement Scale, and parental questionnaires. The intervention induced changes in neural activities on EEG and behavior but there were no significant changes in CAT and CANTAB results. Relative theta and alpha power were significantly lower post-intervention in the eyes-open (EO) condition of EEG recording and these changes were mainly observed in the frontal regions of the brain. Parental reports using the BRIEF-2 and K-ARS noted significant improvements in executive function, attention, and hyperactivity-impulsivity. In addition, the clinical impression improved in 60% of participants. These results provide evidence that a mobile application-based intervention has the benefit of supporting children with ADHD and/or ID. Digital intervention could change neural activity and improve children's attention and cognitive function. Given our findings, we suggested that mobile application-based digital therapeutics may have great potential for helping children with neurodevelopmental disorders who need continuous treatment.

Neonatal hypoxic-ischaemic encephalopathy: Motor impairment beyond cerebral palsy

Research investigating neuromotor function in the absence of cerebral palsy (CP) for children who had neonatal HIE is limited.To investigate school-age neurological and neuromotor function, and correlations with attention, neonatal Magnetic Resonance Imaging (MRI), and neuromotor assessments at toddler age.Twenty-seven children with neonatal HIE without CP who underwent hypothermia treatment and a comparison group of 20 children were assessed at age 5-7 years for Minor Neurological Dysfunction (MND; simplified Touwen), motor skills (Movement Assessment Battery for Children-2; MABC-2), parental concern over motor function (MABC Checklist), general cognition (Wechsler Preschool and Primary Scale of Intelligence-IV, WPPSI), and attention (DuPaul ADHD Rating Scale). Neurological examination and motor development, using Bayley-3 scales, at age 24-months was extracted from the clinical database. Clinical neonatal MRI was assessed for hypoxic-ischaemic injury.In the HIE group, MND was more prevalent (p = 0.026) and M-ABC performance (total score p = 0.006; balance subtest p = 0.008) was worse; parents were more concerned about children's motor function (p = 0.011). HIE group inattention scores were higher (p = 0.032), which correlated with lower MABC-2 scores (rs = -0.590, p = 0.004). Neurological examination at 24-months correlated with MND (rs = 0.437, p = 0.033); Bayley-3 motor scores did not correlate with M-ABC-2 scores (rs = 368, p = 0.133). Neonatal MRI findings were not associated with school-age MND (rs = 0.140, p = 0.523) or MABC-2 (rs = 0.300, p = 0.165).Children with neonatal HIE, without CP, treated with hypothermia may be more likely to develop MND and motor difficulties than typically developing peers. Inattention may contribute to motor performance. In the absence of CP, neonatal MRI and toddler age assessment of motor development have limited predictive value for school-age outcome. Since this was an exploratory study with a small sample size, findings should be confirmed by a definite larger study.

Outcomes of a 12-week ecologically valid observational study of first treatment with methylphenidate in a representative clinical sample of drug naïve children with ADHD.

Randomized placebo-controlled trials have reported efficacy of methylphenidate (MPH) for Attention-deficit/hyperactivity disorder (ADHD); however, selection biases due to strict entry criteria may limit the generalizability of the findings. Few ecologically valid studies have investigated effectiveness of MPH in representative clinical populations of children. This independently funded study aims to describe treatment responses and their predictors during the first 12 weeks of MPH treatment using repeated measurements of symptoms and adverse reactions (ARs) to treatment in 207 children recently diagnosed with ADHD. The children were consecutively included from the Child and Adolescent Mental Health Centre, Mental Health Services, The Capital Region of Denmark. The children (mean age, 9.6 years [range 7-12], 75.4% males) were titrated with MPH, based on weekly assessments of symptoms (18-item ADHD-rating scale scores, ADHD-RS-C) and ARs. At study-end 187 (90.8%) children reached a mean end-dose of 1.0 mg/kg/day. A normalisation/borderline normalisation on ADHD-RS-C was achieved for 168 (81.2%) children on the Inattention and/or the Hyperactivity-Impulsivity subscale in week 12, and 31 (15.0%) children were nonresponders, which was defined as absence of normalisation/borderline normalisation (n = 19) or discontinuation due to ARs (n = 12), and eight (3.8%) children dropped out from follow-up. Nonresponders were characterised by more severe symptoms of Hyperactivity-Impulsivity and global impairment before the treatment. ARs were few; the most prominent were appetite reduction and weight loss. A decrease in AR-like symptoms during the treatment period questions the validity of currently available standard instruments designed to measure ARs of MPH. This ecologically valid observational study supports prior randomized placebo-controlled trials; 81.2% of the children responded favourably in multiple domains with few harmful effects to carefully titrated MPH. Clinical trial registration: ClinicalTrials.gov with registration number NCT04366609.

Efficacy and Safety of a Long-Acting Multilayer-Release Methylphenidate Formulation (PRC-063) in the Treatment of Adolescent Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Clinical Trial with a 6-Month Open-Label Extension.

Objectives: To study the safety and efficacy of the long-acting methylphenidate formulation PRC-063 in adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: Adolescents 12 to ≤17 years who met Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for ADHD and had a baseline ADHD Rating Scale DSM-5 (ADHD-5-RS) score ≥24 participated in a randomized, double-blind, placebo-controlled, fixed-dose, parallel-group study. Participants were randomized 1:1:1:1:1 to receive placebo or one of four doses of PRC-063 once daily for 4 weeks. The primary endpoint was change from baseline in least-squares mean clinician-rated ADHD-5-RS total score for PRC-063 (all doses combined) versus placebo. Other efficacy assessments included Conners third Edition: Self-Report (C3SR) and Clinical Global Impression-Improvement (CGI-I). A subset of double-blind study participants entered a subsequent open-label, dose-optimized study. Safety outcomes in both studies included treatment-emergent adverse events (TEAEs). Results: Three hundred fifty-four participants were included in the primary analysis. The least-squares mean change from baseline in ADHD-5-RS total score was -15.17 for PRC-063 versus -10.98 for placebo (least-squares mean difference -4.2, p = 0.0067). For individual PRC-063 doses, improvements in ADHD-5-RS total score versus placebo were significant for 45 mg (p = 0.0155) and 70 mg (p = 0.0401), but not for 25 or 85 mg. A significant improvement for PRC-063 versus placebo was recorded for C3SR Inattention (p = 0.0168), but not for the other C3SR subscales. About 52.7% of participants randomized to PRC-063 were responders based on CGI-I versus 32.4% of those randomized to placebo (p = 0.0004). Further improvements in ADHD symptoms based on ADHD-5-RS were observed from 1 month through 6 months of open-label treatment (p < 0.0001). There were two serious adverse events (both during the open-label study), one of which (aggressive behavior) was assessed as related to study drug. The only TEAEs that occurred in >10% of participants during double-blind treatment were decreased appetite (20.1%) and headache (15.0%). Most TEAEs were of mild or moderate severity. Conclusion: PRC-063 significantly improved ADHD symptomatology in adolescents. It was generally well tolerated, with an AE profile consistent with other long-acting stimulants. NCT02139111 and NCT02168127.

EFFICACY OF LONG-TERM TREATMENT WITH VILOXAZINE EXTENDED-RELEASE CAPSULES (QELBREE™) IN CHILDREN AND ADOLESCENTS WITH ADHD: AN OPEN-LABEL EXTENSION STUDY

Viloxazine extended-release capsules (viloxazine ER; Qelbree™) is a novel nonstimulant recently approved for the treatment of ADHD in children and adolescents based on results from 3 pivotal Phase 3 trials. Here, we report efficacy results of the ADHD Rating Scale, 5th Edition (ADHD-RS-5) and Clinical Global Impression-Improvement (CGI-I) assessed during the long-term open-label extension (OLE) safety study of viloxazine ER. The change from baseline (pivotal; CFB) in ADHD-RS-5 Total score, 50% ADHD-RS-5 Responder Rate (percentage of subjects with a ≥50% reduction in their CFB ADHD-RS-5 Total score), and CGI-I Responder Rate (percentage of subjects with a CGI-I score of 1 or 2) were analyzed by visit from pivotal to last visit in an OLE trial. Subjects were grouped based on pivotal trial treatment assignment (pivotal-placebo or pivotal-viloxazine ER). In the OLE trial, subjects aged 6-11 years were dosed at 100 mg/day or titrated up (100 mg/day/week) to optimal dose at or below 400 mg/day, and subjects aged 12-17 years were dosed at 100 mg/day or titrated up (100 or 200 mg/day/week) to optimal dose at or below 600 mg/day. Of the 1170 subjects who completed a pivotal trial, 1100 subjects were dosed in the OLE (323 pivotal-placebo and 777 pivotal-viloxazine ER). The median dose of viloxazine ER was 300 mg in children aged 6-11 years and 400 mg in adolescents aged 12-17 years. ADHD symptoms improved in the first month and continued improving over time during OLE in both pivotal-placebo and pivotal-viloxazine ER subjects. The mean (±SD) CFB in ADHD-RS-5 Total score at last visit during OLE was significantly improved in the pivotal-viloxazine ER group (–19.3 ± 13.22; p < 0.0001) and in the pivotal-placebo group (–18.0 ± 13.17; p < 0.0001). For both groups, ADHD-RS-5 and CGI-I responder rates were above 50% within the first 3 months, remained above 65% after 3 months, and remained above 75% after 18 months of treatment. ADHD symptoms significantly improved and the number of subjects experiencing a clinically meaningful improvement increased over time during long-term viloxazine ER treatment. These data indicate that viloxazine ER treatment can provide sustained efficacy, further improve ADHD symptoms, and increase the responder rates even after 8 weeks of treatment.

5.22 Improving the Predictive Value of Self-Report in Adult ADHD Diagnosis

A limited number of studies have assessed the predictive value of self-report questionnaires and items in diagnosing and/or screening for adult ADHD. Recently, for example, a shortened version of the World Health Organization ADHD Screening Scale was developed by selecting items that, taken together, are most predictive of diagnosis. Here, we aim to compare the diagnostic value of multiple self-report and other-report questionnaires commonly used in adult ADHD evaluation and draw on all of these questionnaires to identify a set of items that are mutually most predictive. Analyses drew on a large cohort of adult patients evaluated for ADHD within the Duke University Health System between 2008 and 2019. Each patient completed a subset of the following self-report questionnaires as part of their evaluation: the Barkley Adult ADHD Rating Scale (BAARS) self- and other-report; the Conners’ Adult ADHD Rating Scale (CAARS) self- and other-report; the Conners’ Adult ADHD Diagnostic Interview for DSM-IV Part 1 (CAADID-1); and an additional ADHD screening scale developed at Duke University (DSS). Diagnoses were based on the consensus of a team of ADHD specialists. Predictive models were developed based on: 1) each self-report scale in isolation; and 2) all self-report scales, taken together. Model selection and evaluation were conducted using nested cross-validation, and performance was evaluated using the area under the receiver operating characteristic curve (AUROC). Among the individual questionnaires, prediction performance was highest for the DSS self-report (AUROC = 0.80) followed by the DSS other-report (AUROC = 0.75), CAARS self-report (AUROC = 0.68), BAARS other-report (AUROC = 0.66), and CAADID-1 (AUROC = 0.66). However, combining all available items led to an average prediction performance of AUROC = 0.65 and revealed that the CAADID-1 and CAARS self-report were most predictive across the entire cohort. Moreover, the predictive values of individual items were ranked. Self- and other-report questionnaires used in adult ADHD evaluation vary substantially in their predictive value, and the predictive value of a set of items selected from multiple scales is projected to be higher than that of any individual questionnaire.

18.4 IMAGING THE TREATMENT OF ADHD

ADHD is one of the most common mental health disorders affecting children. Psychostimulants are a first-line treatment for ADHD, but common side effects often result in discontinuation. Moreover, the long-term efficacy of psychostimulants remains unclear. Identifying the neural mechanisms by which psychostimulants attenuate ADHD symptoms may guide the development of more refined and tolerable therapeutics. In this work, we aim to identify causal effects of psychostimulants on brain connectivity in individuals with ADHD and their relationship with symptom improvement. In a 12-week, randomized, placebo-controlled trial of lisdexamfetamine (LDEX), 49 out of 58 eligible participants (12.6 [5.7] years; 33 [67%] males; 25 LDEX and 24 placebo) completed both pre– and post–randomized controlled trial MRI scanning with adequate data quality. The primary clinical outcome measures are T scores on ADHD symptom scales assessed with the Conners’ Parent Rating Scale and the Conners’ Adult ADHD Rating Scale. Treatment effects on striatal and thalamic functional connectivity (FC) are identified using both static (time-averaged) and dynamic (time-varying) measures and then correlated with symptom improvement. We also examined whether treatment-induced connectivity changes acted on connections that differed between those with ADHD and healthy controls (HCs). An HC group (n = 46) matched on age and sex was included for comparison. Analyses were then repeated in independent samples from the ABCD study (n = 103) and the New York University ADHD-200 Consortium cohort (n = 213). We found that LDEX resulted in increasing static and decreasing dynamic FC. However, there were only dynamic mediated therapeutic effects of LDEX. Additionally, at baseline, dynamic FC was elevated in unmedicated-ADHD participants relative to HCs. Independent samples yielded similar findings: ADHD was associated with increased dynamic FC, and psychostimulants with reduced dynamic FC. We found that changes in dynamic, not static, FC accounted for therapeutic effects of psychostimulants. Altered dynamic FC may represent a reliable target for new ADHD interventions aimed at stabilizing network dynamics.

14.2 FEASIBILITY, ACCEPTABILITY, AND EFFECTIVENESS OF A NEW COGNITIVE-BEHAVIORAL INTERVENTION FOR COLLEGE STUDENTS WITH ADHD

This study assessed the feasibility, acceptability, and effectiveness of a group CBT intervention to enhance executive function (EF) in college students with ADHD. The treatment addressed time-awareness, distractibility, procrastination, poor planning, failure to complete academic tasks in a timely and effective manner, and the negative automatic thoughts that engender anxiety/depression and further impair academic functioning. Home exercise facilitated practice of the strategies between sessions. The intervention was delivered in 12 weekly 2-hour sessions at a major university in the Netherlands. Two parallel-group series each enrolled 9 undergraduate or graduate students meeting rigorous DSM-5 criteria for ADHD, who comprised the sample. Outcome measures included a clinician-administered structured interview of ADHD symptoms (Adult Investigator Symptom Rating Scale, AISRS), as well as self-report measures of inattentive symptoms (Conners Adult ADHD Rating Scales, CAARS), executive functions (Barkley Deficits in Executive Function Scale, BDEFS), and learning and study skills (Learning and Study Strategies Inventory, LASSI). Students rated program components on a scale from 0 (“not helpful”) to 3 (“very helpful”). Fifteen students (83%) attended 9 or more sessions. There were no study dropouts. Overall program helpfulness was rated as 2.27. The following strategies received the highest mean ratings: planner use (2.83), breaking down aversive tasks into smaller parts (2.56), and identifying (2.22) and challenging (2.00) negative automatic thoughts. Repeated measures analyses of change from pre- to posttreatment yielded improvement in clinician-rated inattentive symptoms (AISRS) (frequency: 6.78 vs 4.22, p = 0.000; effect size (ES) = 0.646), and self-ratings (CAARS) of inattentive symptoms (t scores = 80.22 vs 70.28, p = 0.000; ES = 0.640). Also significantly improved were scores on the BDEFS subscales of Self-Management to Time, Organization, and Total Executive Function, as well as the LASSI subscale of Concentration. Results support the feasibility, acceptability, and effectiveness of a CBT program in reducing inattentive symptoms and enhancing EFs in college students with ADHD and warrant examination in a randomized controlled trial.

A post hoc analysis of the effect of viloxazine extended-release capsules on learning and school problems in children and adolescents with attention-deficit/hyperactivity disorder

Improvement in attention-deficit/hyperactivity disorder (ADHD) symptoms vs. placebo was reported in a series of pediatric clinical trials of viloxazine extended-release capsules (viloxazine ER; Qelbree™). This post hoc analysis of those studies evaluated the effect of viloxazine ER on learning and school problems (LSPs). We used data from four Phase 3 placebo-controlled trials of 100–600 mg/day viloxazine ER (N = 1354; 6–17 years of age). LSPs were evaluated using the School domain of the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P-S) and the Learning Problems content scale of the Conners 3rd Edition-Parent Short Form (C3PS-LP) at baseline and end of study (≥ Week 6). ADHD symptoms were assessed weekly using the ADHD Rating Scale 5th Edition. The analyses were performed using the general linear mixed model with participant as a random effect. The responder analyses were performed using the Chi-square test. Viloxazine ER demonstrated significantly greater improvements in WFIRS-P-S (p < 0.0001) and C3PS-LP (p = 0.0113) scores vs. placebo. The response rate for the WFIRS-P-S was significantly greater for viloxazine ER vs. placebo (p = 0.001), and the number needed to treat (NNT) was 10.3 (effect size 0.7). Conversely, response rates for C3PS-LP did not differ between groups (p = 0.9069). In addition to ADHD symptoms improvement demonstrated in previous studies, viloxazine ER significantly reduced LSPs in pediatric subjects with ADHD. The responder analyses and NNT estimates indicate that a substantial number of children and adolescents with ADHD treated with viloxazine ER improved in clinically assessed LSPs.

Executive Function Outcome of Treatment with Viloxazine Extended-Release Capsules in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Post-Hoc Analysis of Four Randomized Clinical Trials.

AimThe aim of this study was to evaluate the effect of viloxazine extended-release capsules (viloxazine ER; Qelbree™) on executive function deficits (EFDs) in pediatric subjects (6–17 years of age) with attention-deficit/hyperactivity disorder (ADHD).MethodsData from four phase III placebo-controlled trials of 100–600 mg/day viloxazine ER (6–8 weeks of treatment) were used to evaluate the change from baseline (CFB) in the Conners 3rd Edition Parent Short Form—Executive Function (C3PS-EF) content scale T-score. Subjects were defined as EFD responders if they had C3PS-EF T-score > 70 at baseline and < 65 at end of study. ADHD symptoms were assessed with ADHD Rating Scale 5th Edition (ADHD-RS-5). Subjects were defined as ADHD symptom responders if they had a ≥ 50% reduction in CFB ADHD-RS-5 Total score at Week 6. The number needed to treat (NNT) and Cohen’s d effect sizes were estimated for EFD and ADHD symptoms.ResultsA total of 1154 subjects were included in the analysis. Statistically significant improvements in EFDs were observed with viloxazine ER versus placebo (p = 0.0002). There were 52.5% of EFD or ADHD symptom responders in the viloxazine ER treatment group and 35.4% in the placebo group (p < 0.0001). The NNT was 5.8. The Cohen’s d effect size for EFD and ADHD symptoms was 0.31.ConclusionConsistent with the efficacy of viloxazine ER demonstrated in pivotal trials, viloxazine ER significantly reduced EFDs in subjects with ADHD. Moreover, a substantial proportion of subjects treated with viloxazine ER had large improvements in EFDs, ADHD symptoms, or both.Clinical Trial Registration NumbersNCT03247530, NCT03247517, NCT03247543, NCT03247556.

Hyperactive/impulsive symptoms and autistic trait in institutionalized children with maltreatment experience.

The present study examined how maltreatment experience was associated with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) symptoms in children under institutional care. The key caregivers of children and adolescents aged 6 to 18 years who were under institutional care in Nagano prefecture, Japan were asked to answer the background questionnaire, ADHD-Rating Scale, and the Japanese children's version of the Autism-Spectrum Quotient. A total of 378 valid responses were obtained, of which 222 reported maltreatment experience prior to institutionalization. Both hyperactive/impulsive and inattentive scores were significantly higher in the maltreated group. Maltreatment experience was significantly associated with the presence of hyperactive/impulsive symptoms (p=0.003) and inattentive symptoms (p=0.027). Particularly, those who had experienced physical abuse were significantly more likely to have hyperactive/impulsive symptoms (p=0.012) and autistic trait (p=0.002). Thorough assessment of neurodevelopmental symptoms should be performed when placing children with maltreatment experience into institutional care.

A-155 The Relationship between Parent-Reported Inattention Symptoms and Intra-Individual Variability in Neuropsychological Performance in Male Children and Adolescents

Abstract Objective While previous research has demonstrated that males show greater intra-individual variability (IIV) in neuropsychological performance than females (Roalf et al., 2014), previous studies have not investigated how IIV relates to psychological factors in each gender. This study examined the relationship between psychological symptoms (i.e., depression, anxiety and inattention) and IIV in male and female pediatric samples. Method Participants included 135 male and 210 female individuals between the ages of 6 and 17 from Nathan Kline Institute’s Rockland Project. Participants endorsing a medical diagnosis associated with cognitive impairment (e.g., brain injury; n = 19) were excluded. The four psychological variables included T-scores from the Children’s Depression Inventory (CDI) total to measure depression, the Multidimensional Anxiety Scale for Children (MASC) to measure anxiety, Conners ADHD Rating Scale - Parent to measure parent-ratings of inattention, and the Conners ADHD Rating Scale – Youth to measure self-rated inattention. IIV scores for accuracy were calculated from 10 subtests from the Penn Computerized Neurocognitive Battery. Results In male participants, a regression analysis predicting IIV accuracy scores revealed that the four psychological variables together accounted for 7% of the variance in IIV accuracy scores. Conners Parent Inattention T-scores significantly predicted IIV accuracy scores in males (β = 0.19, p 0.16). In an analogous regression analysis with female participants, psychological symptoms did not significantly predict IIV accuracy scores. Conclusions Results indicated that inattention reported by parents predicted IIV accuracy for male children and adolescents in a community sample.

The effect of epigenome-wide DNA methylation on the association between prenatal exposure to air pollution and childhood attention-deficit hyperactivity disorder

BACKGROUND AND AIM: Prenatal exposure to air pollution including particulate matter (PM), NO2, and SO2, has been linked with attention deficit hyperactivity disorder (ADHD) in children. Epigenetic influence has been suggested to have a role in the association between exposure to air pollution and ADHD. We aimed to investigate the epigenetic effects on the association between prenatal air pollution exposure and ADHD symptoms in children. METHODS: Whole blood samples of 60 children were obtained at age 2 and 6 years repeatedly and genome-wide DNA methylation was analyzed using the Illumina Infinium Human Methylation BeadChip 450K. After quality control, a total of 256,864 CpG sites were analyzed for their association with prenatal PM10, PM2.5, NO2, and SO2 exposure in the first, second, and third trimesters of pregnancy, respectively. CpG sites associated with prenatal air pollution exposure were studied in relation to ADHD rating scale (ARS) scores at ages 6 and 8. We aimed to investigate the epigenetic effects on the association between prenatal air pollution exposure and ADHD symptoms in children. RESULTS:DNA methylation levels at the 6 CpG sites at age 2 were associated with prenatal SO2 exposure levels at the third trimester: CpG sites located in GP1BB, ATP2C2, GNB4, GRIA1, RPE, INPP5D. Among these, 1 IQR increase in the methylation of cg14130977 (GP1BB) and cg16698748 (ATP2C2) at age 2 was associated with a 0.11 (95% confidence interval (CI) 0.41, 0.83) and 0.12 (95% CI 0.3, 0.76) increase in ARS at age 6, respectively. cg21656520 (RPE) and cg22331159 (INPP5D) showed similar results. CONCLUSIONS:Changes in DNA methylation levels at the CpG sites associated with prenatal SO2 exposure led to increases in ARS scores, suggesting that epigenetic mechanisms underly the effects of prenatal exposure to air pollution on ADHD symptoms in children. KEYWORDS: prenatal, sulfur dioxide, SO2, DNA methylation, ADHD, epigenome-wide association study, epigenetics