Attention-deficit/hyperactivity disorder (ADHD) affects up to 10

Objective: To characterize the size and course of placebo response in attention-deficit/hyperactivity disorder (ADHD), with informant and moderator effects, and illustrate its importance by comparison to Multimodal Treatment Study of ADHD (MTA) 3-month data. Methods: In two randomized clinical trials parents and teachers rated DSM-IV ADHD symptoms (Sx) on pill placebo at baseline (BL), 8, 12, and 16 weeks for 57 children age 5-12 with ADHD (25 inattentive, 32 combined type) and on an intense 12-week nonmedical control condition (NMCC) for 27 children age 6-12. Results: Parent- and teacher-rated placebo effects peaked at 12 and 8 weeks, respectively. Changes from BL are significant (p = 0.001) by parent and teacher on inattentive Sx (d = .60, .56 for pill placebo; d = 1.48, .51 for NMCC) and on hyperactive/impulsive Sx by parent (d = 0.48 pill; d = 1.26 NMCC). Teacher-rated hyperactive/impulsive show greater placebo effect September-January than February-May (p = 0.017). Teacher-rated inattentive Sx shows a significant (p = 0.033) interaction of season*subtype. Compared to placebo data, MTA treatments show significant benefit (p = 0.000) at 3 months on both inattentive and HYP/IMP symptoms for medication management and combination groups but not for behavioral treatment (Beh) or community comparison groups, except for teacher-rated HYP/IMP for Beh (p = 0.002). Conclusions: Parent/teacher ratings show a medium placebo effect for pill placebo and a large effect (d > 1.2) by parent for intense, complex NMCC, suggesting that parent-rated placebo response depends on the complexity/intensity of the control condition. Raters agree on inattentive but diverge on HYP/IMP Sx. Teachers' perceptions of HYP/IMP severity change by season. Pill placebo data indirectly support the 3-month efficacy of two MTA treatments, combination and medication management.

IntroductionAccurately diagnosing mental disorders is required for determining therapeutic or preventative interventions. Individuals with intellectual disabilities (ID) are often disenfranchised from the diagnostic process due to a lack of accessible measures; proxy reporting by caregivers often takes precedence. The original Diagnostic Interview for Adolescents and Adults with ID: An interview schedule of mental disorders (DIAAID) includes 15 direct-report interviews for individuals ages 14-24 and 24 informant interviews. We describe the collaborative process used to extend the DIAAID to adults beyond school-age.MethodThe DIAAID content, response options, and visual supports were examined and modified for relevance to adults beyond age 24. A learning module and two additional informant interviews were developed. Cognitive testing was conducted.ResultsThe age-extended DIAAID includes 15 direct-report and 26 proxy interviews.ConclusionThe process used to extend the age-range of the DIAAID may be useful to investigators developing direct-report instruments for individuals with ID.

Objectives: Although ADHD has its roots in childhood, significant symptoms persist into adulthood for more than half of individuals. Adults with ADHD are heterogeneous in terms of symptom presentations, impairment domains, and relative strengths. Consequently, it is essential to better understand the diverse self-perceptions and experiences of adults with ADHD; qualitative methods are a valuable complement to quantitative work in this area. Our aim is to provide a scoping review of qualitative studies on adults with ADHD to articulate the current status of the field and establish future research directions.Method: We review 41 studies, separating findings into four subpopulations: (1) adults with childhood ADHD, (2) college students with ADHD, (3) adults diagnosed with ADHD in adulthood, and (4) other studies (unspecified age of diagnosis).Results: Qualitative research on all four subgroups identifies recurring themes: substance use, decisions about medication for ADHD, perceived domains of impairment, factors that promote or hinder success, and concerns about identity and stigma. Notably, the relative emphasis of each theme varies as a function of sample type. Specifically, qualitative research among adults with a childhood ADHD diagnosis focuses principally on substance use and treatment desistance, whereas studies of individuals diagnosed with ADHD as adults often examine emotional responses to receiving the diagnosis. For college students with ADHD, themes frequently relate to struggles with the increased independence demanded by post-secondary educational environments and the adoption of accommodations or coping strategies. For future studies of adult ADHD, we highlight key domains for which mixed-methods strategies will be critical: (a) similarities and differences between multiple reporters of functioning, (b) willingness to receive treatment, (c) women, (d) participants from diverse racial and ethnic groups, and (e) middle age and older adults.Conclusion: In all, we highlight the value of qualitative and mixed-methods approaches to ensure that research captures the beliefs, intentions, experiences, emotions, and self-perspectives of people with ADHD.

Micronutrients have demonstrated promise in managing inattention and emotional dysregulation in children with attention-deficit/hyperactivity disorder (ADHD). One plausible pathway by which micronutrients improve symptoms is the gut microbiome. This study examines changes in fecal microbial composition and diversity after micronutrient supplementation in children with ADHD (N = 44) and highlights potential mechanisms responsible for the behavioral improvement, as determined by blinded clinician-rated global improvement response to micronutrients. Participants represent a sub-group of the Micronutrients for ADHD in Youth (MADDY) study, a double blind randomized controlled trial in which participants received micronutrients or placebo for 8 weeks, followed by an 8-week open extension. Stool samples collected at baseline, week 8, and week 16 were analyzed using 16S rRNA amplicon sequencing targeting the V4 hypervariable region. Pairwise compositional analyses investigated changes in fecal microbial composition between micronutrients versus placebo and responders versus non-responders. A significant change in microbial evenness, as measured by alpha diversity, and beta-diversity, as measured by Bray-Curtis, was observed following micronutrients supplementation. The phylum Actinobacteriota decreased in the micronutrients group compared to placebo. Two butyrate-producing bacterial families: Rikenellaceae and Oscillospiraceae, exhibited a significant increase in change following micronutrients between responders versus non-responders. These findings suggest that micronutrients modulated the composition of the fecal microbiota and identified specific bacterial changes associated with micronutrient responders.

Objectives/Background: Multiple factors influence symptom severity in Attention Deficit/Hyperactivity Disorder (ADHD). We examined four of these: diet, sleep hygiene, exercise, and lighting, in the International Collaborative ADHD Neurofeedback (ICAN) randomized clinical trial, which found large significant improvement with both active neurofeedback and control condition without treatment difference. Methods: A total of 142 participants aged 7-10 had breakfast and lunch intake and exercise recorded at each neurofeedback session. Parents completed the Children's Sleep Habits Questionnaire (CSHQ). Parents and teachers rated inattention on Conners3. Lifestyle changes were correlated with inattention changes. Results: At baseline, CSHQ correlated with parent-rated inattention (r = 0.17, p = 0.04), and length of sleep correlated with teacher-rated inattention (r = 0.20, p = 0.03). From baseline to treatment end food group variety (p = 0.029, d = 0.22) and sleep problems (p < 0.0001, d = -0.49) improved significantly, exercise time and protein intake marginally (p = 0.06 - 0.08). Parent-rated inattention improvement correlated with CSHQ improvement (Rho = 0.26, p = 0.002) and marginally with protein intake increase (Rho = 0.18, p = 0.06). The three components of the light-emitting-diode (LED)-induced circadian pathway hypothesis were significant. Conclusions: Most measures improved, but few significantly. How much they impact classroom attention remains unclear. Although parent ratings of inattention improvement correlated with sleep problems improvement, composited parent/teacher ratings (primary outcome) did not. The circadian pathway hypothesis associated with LED lighting was supported. These findings warrant further studies examining the role sleep hygiene can play in improving ADHD symptoms. Meanwhile, attention to sleep hygiene seems appropriate in any treatment plan for ADHD.

Introduction: Essential oils have been touted to benefit children with autism spectrum disorder (ASD) in a multitude of ways. However, the lack of empirical evidence makes it difficult to accept this claim. We tested the feasibility of conducting a large randomized clinical crossover trial of an essential oils blend in children with ASD and evaluated its safety and efficacy for improving quality of life. Methods: Children ages 3-9 with ASD were randomized to a crossover study of ReconnectTM, an essential oils blend, versus a control. Outcomes were the Pediatric Quality of Life Inventory, Parent-Rated Anxiety Scale for ASD, Children's Sleep Habits Questionnaire, and laboratory safety tests. Inflammatory cytokines and other labs were explored. Mixed-effects analyses were applied. Results: Twenty-six participants evaluated as intent-to-treat population. Seventeen completed both conditions (61 %). Outcomes improved, but between-treatment differences in the crossover were nonsignificant (p = .33-.16). At first treatment endpoint, anxiety decreased significantly more with active than control (p = .015, d=1.01). Adverse events and hematological/hepatic/ renal tests revealed no significant differences. C-reactive protein and interleukin-6 (IL-6) revealed no inflammation. Conclusion: Recruitment was feasible, adherence was high, first-condition retention was high (92.7 %). Retention in second condition was low (65.4 %). A large crossover is not feasible. Anxiety results suggest further study in a randomized controlled trial with a parallel-groups design. ReconnectTM appears safe.

Attention deficit hyperactivity disorder is a prevalent syndrome that costs billions of dollars annually. Finding meaningful interventions based upon predictive baseline EEG values can reduce uncertainty in symptom remediation. This study aims to deepen the understanding of ADHD neurophysiology and contribute to the development of personalized approaches in its treatment. This study retrospectively assessed EEG connectivity of participants in the International Collaborative ADHD Neurofeedback (ICAN) randomized controlled trial (7-10YO, N = 83) of theta/beta ratio neurofeedback (TBR-NFB). Using machine learning, it examined the relationship between inattention improvement on the Conners' Teacher and Parent Rating Scales (CTPRS) and specific baseline frequency connections within networks relevant to ADHD to find predictors of clinical improvement. Analyses were also performed considering specific comorbidities, slow cognitive tempo, ADHD presentation, pre-to-post network changes, and treatment group. Dysregulation in the ventral and dorsal attention networks, and delta and hibeta frequency bands throughout all networks were the strongest baseline connectivity predictors of clinical improvement on the CTPRS. The connectivity patterns predicting improvement differed significantly between active NFB and control. Other findings included predictors of improvements in EEG connectivity dysregulations, demographics, and connectivity patterns of comorbidity. Machine learning algorithms identified EEG features in connectivity, network, and frequency to assess when considering ADHD interventions. There was evidence, albeit weak, that the EEG features we studied predicted improvement with the ICAN TBR-NFB protocol. When considering interventions for ADHD symptoms, a multi-channel EEG evaluation that focuses on specific brain connectivity patterns may offer insight into treatment choice.

BACKGROUND:Many children with attention-deficit/hyperactivity disorder (ADHD) demonstrate impairment in social skills. However, ADHD rarely occurs in isolation, with approximately one-third of children with ADHD having one additional disorder, and another third having two or three comorbidities. Few studies have considered the global and specific patterns of social skill performance based on comorbidity status. METHOD:Using a large dataset containing 1400 carefully phenotyped children with ADHD (ages 7-12; 28% girls) in the United States and Canada, we characterized social skill deficit profiles associated with the presence of internalizing comorbidity (depression and/or anxiety), externalizing comorbidity (oppositional defiant or conduct disorder), and both internalizing + externalizing comorbidities. All children had parent and teacher ratings of social skills on a consistent measure, and we took a nuanced approach that considered both global social skills and specific subdomains of skills. RESULTS:Parent ratings indicated main and interaction effects of each comorbidity on lower social skill performance in a varied pattern. Both comorbidities were associated with poorer global social skills, responsibility, and self-control. In addition, internalizing was associated with poorer assertion, while externalizing was associated with poorer communication, cooperation, and empathy. Interaction effects suggested that the impact of externalizing overshadowed internalizing for poor responsibility and self-control; however, internalizing comorbidity attenuated the negative association between externalizing comorbidity and empathy. On teacher ratings, only externalizing comorbidity was associated with poorer global social skills, communication, cooperation, assertion, responsibility, empathy, and self-control. In addition, girls and younger children tended to have poorer global social skills (using a gender-normed standard score), while girls and older children showed better specific social skills (using a raw, not gender-normed score). CONCLUSION:Children with ADHD and these comorbidities had poorer social skills relative to children with ADHD only, as perceived by parents and teachers. There also may be different social skill profiles depending on the comorbid condition and informant. These findings may inform more personalized social skill interventions for children with ADHD.

This study analyzed data from the Micronutrients for ADHD in Youth (MADDY) 8-week RCT to identify moderators of treatment response to multinutrients, i.e., patient characteristics likely to predict optimal benefit based on the Clinical Global Impression-Improvement (CGI-I)- scale. Classification tree analysis investigated demographic and clinical history variables as potential moderators of treatment response. Effect sizes (ES) with confidence intervals (CI) were generated using bivariate analysis of risk difference of proportions derived from the classification tree between-treatment effects stratified by the moderator variable. The classification tree showed a higher response rate among multinutrient–treated children (n = 70) with university-educated parents compared to those with parents with less than a university education (64

BACKGROUND:ADHD is associated with oxidative stress (OS), possibly stemming from deficiencies in essential nutrients. Previous randomized controlled trials (RCTs), including Micronutrients for ADHD in Youth (MADDY), demonstrated improved symptoms in response to treatment with multinutrients compared to placebo. It remains unknown whether multinutrient supplementation influences antioxidant status and OS, and if these factors contributed to improvements observed in children with ADHD in the MADDY RCT. OBJECTIVES:Utilizing samples from the MADDY RCT, (1) compare the change in antioxidant (AO) and OS biomarkers after 8 weeks of multinutrient supplementation vs placebo, and (2) evaluate these biomarkers at baseline, and their change after 8 weeks, as moderators/mediators of treatment response. METHODS:Activity of glutathione peroxidase (GPx) and glutathione reductase (GR) enzymes, plus oxidative stress index (OSI) based on ratio of reactive oxygen metabolites (ROM) to biological antioxidant potential (BAP), were measured in plasma at baseline and week 8. Differences between groups were determined using two-sample t-test or Mann-Whitney U-test. Logistic regression models assessed AO/OS biomarkers for mediation/moderation of treatment response. RESULTS:Plasma from 77 children (aged 9.9 ± 1.7 years; 71% male) treated with multinutrients (n = 45) or placebo (n = 32) was analyzed. After 8 weeks, ROM decreased with multinutrients and increased with placebo (-14.3 vs. +26.8 Carratelli units, p = .017); but no significant differences in OSI, BAP, GPx, and GR between groups. None of the baseline AO/OS biomarker levels were moderators of treatment response. Eight-week change in both OSI and ROM trended toward mediation of treatment response (OR = 0.00058, 95% CI [0.000, 2.30], p = .078 and OR = 0.985, 95% CI [0.968, 1.002], p = 0.086, respectively) but did not reach significance. CONCLUSIONS:Eight weeks of multinutrient supplementation in children with ADHD reduced ROM without significant change in antioxidant status, suggesting decrease in oxidative stress. Given the preliminary signals associating a decrease in OS with symptom improvement following multinutrient supplementation, future research is warranted to understand OS in ADHD pathogenesis. CLINICAL TRIAL REGISTRY:NCT03252522.

In this issue of the Journal, Reed and colleagues1 explore the intersection of 2 important public health problems: overweight/obesity and attention-deficit/ hyperactivity disorder (ADHD), both having a high population prevalence and tending to start in childhood. They analyzed data cross-sectionally and longitudinally from a UK birth cohort of 7,908 youth, including 442 with ADHD by either actual diagnosis or parent-rated threshold score. This epidemiologic ADHD prevalence was comparable to those in other countries, although the actual diagnosis rate was lower. They added a cross-lagged longitudinal perspective to previous reports showing a small association of obesity with ADHD, especially in adults. Their clinically important findings include the following. (1) Both disorders are associated with slightly lower birth weight, presumably reflecting a generally less favorable gestation. (2) The shift from underweight to overweight for those with ADHD occurred in preschool years, at 3 to 5 years of age. (3) ADHD symptom severity predicted overweight: for girls, "higher ADHD symptoms at ages 7, 11, and 14 predicted higher body mass index (BMI) at 11, 14, and 17, respectively." For boys, higher ADHD symptoms at age 11 predicted higher BMI at 14 years. (4) Girls had earlier onset of obesity/overweight (not necessarily a higher rate than boys with ADHD). These have numerous clinical and research implications cutting across many areas of inquiry.

Objectives: Children with attention-deficit/hyperactivity disorder (ADHD) have an elevated oxidative stress which may lead to neuroinflammation and impaired sleep quality. This study examined the association of micronutrients (from dietary intake and plasma levels), involved in oxidative balance, with subjective sleep quality in children with ADHD. Methods: This cross-sectional study analyzed baseline micronutrients data (n=134 for dietary intake, n=77 for plasma levels) from a randomized controlled trial investigating multinutrient supplementation for ADHD in children ages 6-12 years (the MADDY RCT). Dietary intake of vitamins (A, C, D, E) and minerals (Cu, Fe, Mg, Mn, Zn) was assessed by Vioscreen food frequency questionnaire completed by parents. Plasma mineral levels were measured by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Sleep quality was assessed using parent- and child-rated Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance survey, where higher t-score indicates worse sleep. Linear regression models determined the relationships between variables, controlling for confounders. Exploratory sensitivity analyses focused on a subset with poor sleep quality (PROMIS t-score >60). Results: Participants were 71% male, mean age 9.7± 1.69 yrs. Sleep disturbance was respectively reported in 59% and 49% of participants by parent- and child-rated t-scores. After adjusting for age, BMI, and location, dietary intake of Cu (β=4.52, p=0.019), Mg (β=0.018, p=0.017), Mn (β=1.40, p=0.018), and Zn (β=0.35, p=0.041) were correlated with worse parent-rated sleep quality. There was no significant association between plasma mineral levels and sleep quality (parent- or child-rated). Sensitivity analysis showed that Zn level was associated with worse parent-rated sleep quality (β=0.02, p=0.03). Conclusions: Our study produced unexpected findings where higher dietary mineral intakes were associated with poorer sleep outcomes. Future studies with larger sample sizes will be helpful to further explain these relationships among children with ADHD. Funding Sources: Foundation for Excellence in Mental Health Care, Gratis Foundation, CTSA award #s UL1TR002733, UL1TR002369.

OBJECTIVE To examine cognitive effects of neurofeedback (NF) for attention-deficit hyperactivity disorder (ADHD) as a secondary outcome of a randomized clinical trial. METHOD In a double-blind randomized clinical trial (NCT02251743), 133 7-10-year olds with ADHD received either 38 sessions of NF (n = 78) or control treatment (n = 55) and performed an integrated visual and auditory continuous performance test at baseline, mid- and end-treatment. We used the diffusion decision model to decompose integrated visual and auditory continuous performance test performance at each assessment into cognitive components: efficiency of integrating stimulus information (v), context sensitivity (cv), response cautiousness (a), response bias (z/a), and nondecision time for perceptual encoding and response execution (Ter). Based on prior findings, we tested whether the components known to be deficient improved with NF and explored whether other cognitive components improved using linear mixed modeling. RESULTS Before NF, children with ADHD showed main deficits in integrating stimulus information (v), which led to less accurate and slower responses than healthy controls (p = .008). The NF group showed significantly more improvement in integrating auditory stimulus information (v) than control treatment (significant group-by-time-by-modality effect: p = .044). CONCLUSIONS NF seems to improve v, deficient in ADHD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

IntroductionYoung people with intellectual disabilities (ID) are at an increased risk for experiencing mental health issues compared to their peers without disabilities. Further, there are limited resources available to help accurately assess mental health disorders and that are accessible for adolescents with ID.MethodThis paper describes the iterative development and pilot testing of the Diagnostic Interview for Adolescents and Adults with Intellectual Disabilities (DIAAID). The authors utilized Evidence Center Design and Universal Design principals to develop the DIAAID; a multi-informant diagnostic interview.ResultsThe DIAAID development resulted in the creation of 15 adolescents disorder interviews and 24 caregiver disorder interviews. Preliminary results suggest that the DIAAID is a feasible and accessible diagnostic interview for adolescents with ID and their caregivers.DiscussionLessons learned from DIAAID implementation and future areas research are discussed.

Objectives: Recent studies report a fluctuating course of attention-deficit/ hyperactivity disorder (ADHD) across development characterized by intermittent periods of remission and recurrence. In the Multimodal Treatment of ADHD (MTA) study, we investigated fluctuating ADHD including clinical expression over time, childhood predictors, and between- and within-person associations with factors hypothesized as relevant to remission and recurrence. Methods: Children with DSM-5 ADHD, combined type (N = 483), participating in the MTA adult follow-up were assessed 9 times from baseline (mean age = 8.46) to 16-year follow-up (mean age = 25.12). The fluctuating subgroup (63.8% of sample) was compared to other MTA subgroups on variables of interest over time. Results: The fluctuating subgroup experienced multiple fluctuations over 16 years (mean = 3.58, SD = 1.36) with a 6- to 7-symptom within-person difference between peaks and troughs. Remission periods typically first occurred in adolescence and were associated with higher environmental demands (both between- and within-person), particularly at younger ages. Compared to other groups, the fluctuating subgroup demonstrated moderate clinical severity. In contrast, the stable persistent group (10.8%) was specifically associated with early and lasting risk for mood disorders, substance use problems in adolescence/ young adulthood, low medication utilization, and poorer response to childhood treatment. Protective factors were detected in the recovery group (9.1%; very low parental psychopathology) and the partial remission group (15.6%; higher rates of comorbid anxiety). Conclusions: In the absence of specific risk or protective factors, individuals with ADHD demonstrated meaningful within-individual fluctuations across development. Clinicians should communicate this expectation and monitor fluctuations to trigger as-needed return to care. During remission periods, individuals with ADHD successfully manage increased demands and responsibilities. Trial Registration: ClinicalTrials.gov identifier: NCT00000388.