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Contains fulltext : 240648.pdf (Publisher’s version ) (Open Access) Impulsive and risky decision-making peaks in adolescence, and is consistently associated with the neurodevelopmental disorder Attention-Deficit/Hyperactivity Disorder (ADHD), regardless of age. In this brief review, we demonstrate the similarity of theoretical models explaining impulsive and risky decision-making that originate in two relatively distinct literatures (i.e. on adolescence and on ADHD). We summarize research thus far and conclude that the presence of ADHD during adolescence further exacerbates the tendency that is already present in adolescents to make impulsive and risky decisions. We also conclude that much is still unknown about the developmental trajectories of individuals with ADHD with regard to impulsive and risky decision-making, and we therefore provide several hypotheses that warrant further longitudinal research. 7 p.

Objective To evaluate which early neurocognitive and behavioral precursors are associated with the development of attention-deficit/hyperactivity disorder (ADHD) and whether these are currently targeted in early interventions. Method We conducted 2 systematic reviews and meta-analyses of empirical studies to examine the following: (1) early-life (0−5 years) neurocognitive and behavioral precursors associated with familial likelihood for ADHD, an early ADHD diagnosis/elevated ADHD symptoms, and/or the presence of later-childhood ADHD; and (2) interventions delivered to children aged 0 to 5 years targeting the identified precursors or measuring these as outcomes. Standardized mean differences (Hedges’ g) and pre-post-treatment change scores (SMD) were computed. Results A total of 149 studies (165,095 participants) investigating 8 neurocognitive and behavioral domains met inclusion criteria for part 1. Multi-level random-effects meta-analyses on 136 studies revealed significant associations between ADHD and poorer cognitive (g = −0.46 [95% CIs: −0.59, −0.33]), motor (g = −0.35 [CIs: −0.48, −0.21]) and language (g = −0.43 [CIs: −0.66, −0.19]) development, social (g = 0.23 [CIs: 0.03, 0.43]) and emotional (g = 0.46 [CIs: 0.33, 0.58]) difficulties, early regulatory (g = 0.30 [CIs: 0.18, 0.43]) and sleep (g = 0.29 [CIs: 0.14, 0.44]) problems, sensory atypicalities (g = 0.52 [CIs: 0.16, 0.88]), elevated activity levels (g = 0.54 [CIs: 0.37, 0.72]), and executive function difficulties (g = 0.34 [CIs: 0.05, 0.64] to −0.87 [CIs: −1.35, −0.40]). A total of 32 trials (28 randomized, 4 nonrandomized, 3,848 participants) testing early interventions that targeted the identified precursors met inclusion criteria for part 2. Multi-level random-effects meta-analyses on 22 studies revealed significant intervention-related improvements in ADHD symptoms (SMD = 0.43 [CIs: 0.22, 0.64]) and working memory (SMD = 0.37 [CIs: 0.06, 0.69]). Conclusion Children aged 0 to 5 years with current or later-emerging ADHD are likely to experience difficulties in multiple neurocognitive/behavioral functions. Early interventions show some effectiveness in reducing ADHD symptoms, but their effects on neurocognitive/behavioral difficulties require further study.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with an estimated heritability of around 70%. Although the largest genome-wide association study (GWAS) meta-analysis on ADHD identified independent loci conferring risk to the disorder, the molecular mechanisms underlying the genetic basis of the disorder remain to be elucidated. To explore ADHD biology, we ran a two-step transcriptome profiling in peripheral blood mononuclear cells (PBMCs) of 143 ADHD subjects and 169 healthy controls. Through this exploratory study we found eight differentially expressed genes in ADHD. These results highlight promising candidate genes and gene pathways for ADHD and support the use of peripheral tissues to assess gene expression signatures for ADHD. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

BackgroundA variety of DNA-based methods have been applied to identify genetic markers of attention deficit hyperactivity disorder (ADHD), but the connection to RNA-based gene expression has not been fully exploited.MethodsUsing well defined cohorts of discordant, monozygotic twins from the Michigan State University Twin Registry, and case-controlled ADHD cases in adolescents, the present studies utilized advanced single molecule RNA sequencing to identify expressed changes in whole blood RNA in ADHD. Multiple analytical strategies were employed to narrow differentially expressed RNA targets to a small set of potential biomarkers of ADHD.ResultsRNA markers common to both the discordant twin study and case-controlled subjects further narrowed the putative targets, some of which had been previously associated with ADHD at the DNA level. The potential role of several differentially expressed genes, including ABCB5, RGS2, GAK, GIT1 and 3 members of the galactose metabolism pathway (GALE, GALT, GALK1) are substantiated by prior associations to ADHD and by established mechanistic connections to molecular pathways relevant to ADHD and behavioral control.ConclusionsThe convergence of DNA, RNA, and metabolic data suggests these may be promising targets for diagnostics and therapeutics in ADHD.

Objectives: In two studies of adult attention-deficit/hyperactivity disorder (ADHD), SHP465 mixed amphetamine salts (MAS) extended-release significantly reduced ADHD-Rating Scale, 4th Edition total score (ADHD-RS-IV-TS) versus placebo (PBO). This report describes post hoc analyses of SHP465 MAS treatment response and remission rates from those studies. Methods: Adults with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision–defined ADHD were randomized to SHP465 MAS (12.5–75 mg) or PBO in a 7-week dose-optimization study and to SHP465 MAS (25, 50, or 75 mg) or PBO in a 6-week fixed-dose study. Response was examined using three definitions (definition 1: ≥30% ADHD-RS-IV-TS reduction + Clinical Global Impressions-Improvement [CGI-I] rating of 1 or 2; definition 2: ≥50% ADHD-RS-IV-TS reduction + CGI-I rating of 1 or 2; definition 3: ADHD-RS-IV-TS ≤18). Remission was defined as ADHD-RS-IV-TS ≤12. The Kaplan–Meier analyses assessed time to response or remission. Results: The intent-to-treat populations included 136 SHP465 MAS and 132 PBO participants in the dose-optimization study and 302 SHP465 MAS and 103 PBO participants in the fixed-dose study. Percentages of participants meeting response criteria (SHP465 MAS vs. PBO) at the final treatment week in the dose-optimization and fixed-dose studies, respectively, were 66.0% versus 31.6% and 72.7% versus 28.3% (definition 1); 47.9% versus 27.6% and 60.6% versus 16.7% (definition 2); and 54.3% versus 30.3% and 52.6% versus 18.3% (definition 3). The remission criterion (SHP465 MAS vs. PBO) at the final treatment week was met by 37.2% versus 19.7% of participants in the dose-optimization study and 39.7% versus 10.0% of participants in the fixed-dose study. Times to response and remission favored SHP465 MAS over PBO in both studies (all nominal log-rank p

The current meta-analysis summarizes relevant literature on earlier (P100, N100, P200, N200, ERN/Ne) versus later (P300, Pe, CNV) cognitive Event-Related Potential (ERP) differences between children, adolescents, and adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and without ADHD (non-ADHD). Furthermore, the heterogeneity in previous research is addressed by analyzing potentially relevant demographic and methodological moderators (age group, IQ, medication, comorbidity, task, cognitive function, modality, inter-stimulus-interval, number of electrodes). Via database search 52 relevant articles were identified including n = 1576 ADHD and n = 1794 non-ADHD. Using multilevel-models, pooled effect sizes were calculated. For earlier components, individuals with ADHD showed shorter Go-P100-latencies than non-ADHD. For later ERPs, individuals with ADHD showed smaller Cue-P300-amplitudes, longer Go-P300-latencies, smaller NoGo-P300-amplitudes, longer NoGo-P300-latencies, smaller CNV-amplitudes, and smaller Pe-amplitudes. The substantial heterogeneity identified for most of the ERP components could be explained by the demographic and methodological moderators of interest. This meta-analysis identified relevant moderate group differences (−0.32, Neuroscience & Biobehavioral Reviews, 112, ISSN:0149-7634, ISSN:1873-7528

Neuroimaging research seeks to identify biomarkers to improve the diagnosis, prognosis, and treatment of attention-deficit/hyperactivity disorder (ADHD), although clinical translation of findings remains distant. Resting-state functional magnetic resonance imaging (R-fMRI) is increasingly being used to characterize functional connectivity in the brain. Despite mixed results to date and multiple methodological challenges, dominant hypotheses implicate hyperconnectivity across brain networks in patients with ADHD, which could be the target of pharmacological treatments. We describe the experience and results of the Clínica Universidad de Navarra (Spain) Metilfenidato (CUNMET) pilot study. CUNMET tested the feasibility of identifying R-fMRI markers of clinical response in children with ADHD undergoing naturalistical pharmacological treatments. We analyzed cross-sectional data from 56 patients with ADHD (18 treated with methylphenidate, 18 treated with lisdexamfetamine, and 20 treatment-naive patients). Standard preprocessing and statistical analyses with attention to control for head motion and correction for multiple comparisons were performed. The only results that survived correction were noted in contrasts of children who responded clinically to lisdexamfetamine after long-term treatment vs. treatment-naive patients. In these children, we observed stronger negative correlations (anticorrelations) across nodes in six brain networks, which is consistent with higher across-network functional segregation in patients treated with lisdexamfetamine, i.e., less inter-network interference than in treatment-naive patients. We also note the lessons learned, which could help those pursuing clinically relevant multidisciplinary research in ADHD en route to eventual personalized medicine. To advance reproducible open science, our report is accompanied with links providing access to our data and analytic scripts.

Sleep disturbances are common among children with attention-deficit/hyperactivity disorder (ADHD). While pharmacological treatment has increased dramatically, parents often prefer non-pharmacological interventions. Research on experiences of weighted blankets and their effect in sleep improvement is scarce. The aim of this study was to explore parents’ experiences of weighted blankets for children with ADHD and sleep problems, and the impact on their children’s sleep. The explorative design was based on qualitative content analysis. Interviews were conducted with a purposeful sample of 24 parents of children with ADHD and sleep problems, after completing a sleep intervention with weighted blankets for 16 weeks. Parents reported that children sleeping with weighted blankets: (1) achieved satisfactory sleep, including improved sleep onset latency, sleep continuity, and sleep routines; (2) achieved overall well-being, including improved relaxation and reduced anxiety; and (3) mastered everyday life, including improved balance in life, family function, and participation in school and leisure activities. This study brings forward novel aspects of the effects of improved sleep among children with ADHD. The findings contribute to the understanding of potential positive effects of an intervention with weighted blankets critical for clinical practice to improve sleep, well-being, and everyday life of children with ADHD and their families.

Background: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may be a risk factor for neurodevelopmental deficits and disorders, but evidence is inconsistent. Objectives: We investigated whether prenatal exposure to PFAS were associated with childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). Methods: This study was based on the Norwegian Mother, Father and Child Cohort Study and included n = 821 ADHD cases, n = 400 ASD cases and n = 980 controls. Diagnostic cases were identified by linkage with the Norwegian Patient Registry. In addition, we used data from the Medical Birth Registry of Norway. The study included the following PFAS measured in maternal plasma sampled mid-pregnancy: Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonate (PFOS). Relationships between individual PFAS and ADHD or ASD diagnoses were examined using multivariable adjusted logistic regression models. We also tested for possible non-linear exposure-outcome associations. Further, we investigated the PFAS mixture associations with ASD and ADHD diagnoses using a quantile-based g-computation approach. Results: Odds of ASD was significantly elevated in PFOA quartile 2 [OR = 1.71 (95% CI: 1.20, 2.45)] compared to quartile 1, and PFOA appeared to have a non-linear, inverted U-shaped dose-response relationship with ASD. PFOA was also associated with increased odds of ADHD, mainly in quartile 2 [OR = 1.54 (95% CI: 1.16, 2.04)] compared to quartile 1, and displayed a non-linear relationship in the restricted cubic spline model. Several PFAS (PFUnDA, PFDA, and PFOS) were inversely associated with odds of ADHD and/or ASD. Some of the associations were modified by child sex and maternal education. The overall PFAS mixture was inversely associated with ASD [OR = 0.76 (95% CI: 0.64, 0.90)] as well as the carboxylate mixture [OR = 0.79 (95% CI: 0.68, 0.93)] and the sulfonate mixture [OR = 0.84 (95% CI: 0.73, 0.96)]. Conclusion: Prenatal exposure to PFOA was associated with increased risk of ASD and ADHD in children. For some PFAS, as well as their mixtures, there were inverse associations with ASD and/or ADHD. However, the inverse associations reported herein should not be interpreted as protective effects, but rather that there could be some unresolved confounding for these relationships. The epidemiologic literature linking PFAS exposures with neurodevelopmental outcomes is still inconclusive, suggesting the need for more research to elucidate the neurotoxicological potential of PFAS during early development.

Attention-Deficit/Hyperactivity Disorder (ADHD) in children is associated with several adverse family characteristics, such as higher parenting stress, more conflicted parent-child relationships, lower parental competence, and higher levels of parental psychopathology. Hence, children with ADHD more often grow up under suboptimal circumstances, which may impact the development of their attachment representations. Here, we investigated whether children with ADHD have more insecure and disorganized attachment representations than their typically developing peers, and which factors could explain this association. We included 104 children between 4 and 11 years old, 74 with ADHD (without Conduct Disorder) and 30 typically developing control children. Children completed a state-of-the-art story stem task to assess their attachment representation, and we measured parents' expressed emotion (as an index of parent-child relationship quality), parents' perceived sense of competence, parental education levels, and parent-rated ODD symptoms of the child. We found that, after controlling for multiple comparisons, children with ADHD had less secure and more ambivalent and disorganized attachment representations relative to their typically developing peers. These group differences were independent of comorbid ODD and parental education levels. There were no group differences on avoidant attachment representations. Explorative analyses within the ADHD group showed that attachment representations were not related to parent-child relationship quality, perceived parenting competence, parental education levels, and comorbid ODD symptoms. We conclude that children with ADHD disproportionately often have attachment problems. Although this conclusion is important, treatment implications of this co-occurrence are yet unclear as research on ADHD and attachment is still in its infancy. ispartof: Brain Sciences vol:11 issue:11 pages:1-13 ispartof: location:Switzerland status: published

The universal donning of masks during the coronavirus disease 2019 pandemic led to a decreased ability to read people’s facial expressions. In this context, it is prudent to think about how diagnoses can be missed or worsened by the practice of mandatory masking. Here, we report the case of an adolescent white male who presented with new-onset agitation, akathisia, and orofacial dyskinesia in the context of chronic stimulant use for the treatment of attention-deficit hyperactivity disorder and antipsychotic use for oppositional defiant disorder.

Background Prenatal exposure to toxic metals or variations in maternal levels of essential elements during pregnancy may be a risk factor for neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring. Objectives We investigated whether maternal levels of toxic metals and essential elements measured in mid-pregnancy, individually and as mixtures, were associated with childhood diagnosis of ADHD or ASD. Methods This study is based on the Norwegian Mother, Father and Child Cohort Study and included 705 ADHD cases, 397 ASD cases and 1034 controls. Cases were identified through linkage with the Norwegian Patient Registry. Maternal concentrations of 11 metals/elements were measured in blood at week 17 of gestation; cadmium; cesium; cobalt; copper; lead; magnesium; manganese; selenium; zinc; total arsenic; and total mercury. Multivariable adjusted logistic regression models were used to examine associations between quartile levels of individual metals/elements and outcomes. We also investigated non-linear associations using restricted cubic spline models. The joint effects of the metal/element mixture on ASD and ADHD diagnoses were estimated using a quantile-based g-computation approach. Results For ASD, we identified positive associations (increased risks) in the second quartile of arsenic [OR = 1.77 (CI: 1.26, 2.49)] and the fourth quartiles of cadmium and manganese [OR = 1.57 (CI: 1.07 2.31); OR = 1.84 (CI: 1.30, 2.59)], respectively. In addition, there were negative associations between cesium, copper, mercury, and zinc and ASD. For ADHD, we found increased risk in the fourth quartiles of cadmium and magnesium [OR = 1.59 (CI: 1.15, 2.18); [OR = 1.42 (CI: 1.06, 1.91)]. There were also some negative associations, among others with mercury. In addition, we identified non-linear associations between ASD and arsenic, mercury, magnesium, and lead, and between ADHD and arsenic, copper, manganese, and mercury. There were no significant findings in the mixture approach analyses. Conclusion Results from the present study show several associations between levels of metals and elements during gestation and ASD and ADHD in children. The most notable ones involved arsenic, cadmium, copper, mercury, manganese, magnesium, and lead. Our results suggest that even population levels of these compounds may have negative impacts on neurodevelopment. As we observed mainly similarities among the metals’ and elements’ impact on ASD and ADHD, it could be that the two disorders share some neurochemical and neurodevelopmental pathways. The results warrant further investigation and replication, as well as studies of combined effects of metals/elements and mechanistic underpinnings.

Parents of children with ADHD experience several difficulties while raising their children and report lower levels of knowledge about their children’s life and behaviors. A recent study found that low levels of parental knowledge mediated the association between ADHD symptoms and risk-taking behavior (RTB) in adolescents. The current study aimed to investigate this previous finding further by replicating it, by taking peer influence into account as additional social factor of importance and by extending it and also investigate the role of parental knowledge in the association between ADHD symptoms and homework problems. Three studies were performed: study 1 (N=234) replicated previous work on parental knowledge mediating the association between ADHD symptoms and RTB, study 2 (pre-registered, N=313) added peer influence, and study 3 (pre-registered, N=315) assessed whether parental knowledge mediated the association between ADHD symptoms and homework behavior. Parental knowledge consistently mediated the association between ADHD symptoms on one hand and RTB and homework problems on the other, and also predicted stronger resistance to peer influence. Because parental knowledge was repeatedly linked to ADHD-related problems, it seems promising to include parental knowledge in treatment of ADHD-related problems in adolescents, by improving the parent-child relationship. Future studies should test more directly how improvement of the parent-child relationship can be used to optimize parental knowledge, which in its turn reduces ADHD-related problems. Electronic supplementary material The online version of this article (10.1007/s00787-020-01579-4) contains supplementary material, which is available to authorized users.

Sluggish cognitive tempo (SCT) is a cluster of attentional symptoms characterized by slow information processing and behavior, distractibility, mental confusion, absent-mindedness, and hypoactivity. The present study aimed to compare early and late selective attention in the information processing speed of adults with SCT to those with attention-deficit/hyperactivity disorder (ADHD) and adults without any attentional problems. The participants were screened using Barkley Adult ADHD Rating Scale-IV and divided into the following groups: SCT (N = 24), ADHD (N = 24), and controls (N = 25). All participants completed the irrelevant distractor task measuring early and late selective attention under load condition (low vs. high) and distractor condition (no-distractor vs. distractor). The inefficiency index was calculated by subtracting the reaction time of no-distractor condition of correct trials from the reaction time of distractor condition to control the impact of accuracy. Upon analysis, the SCT group showed a lower efficiency compared to the ADHD group under high load, while the ADHD group showed lower efficiency under low load than high load. This meant that the ADHD group had increased efficiency of selective attention with higher load, while the SCT group had low efficiency of selective attention even under high loads. These results suggest that the symptoms of “slow” or “distracted” in SCT could be attributed to the reduced speed and efficiency of selective attention in early information processing and the problem can be pronounced in situations with distractors. The results of the study imply that the attention-deficit-like symptoms shown in those with SCT and ADHD can be distinguished in specific stage of information processing.

Objectives Few studies have focused on the participation of children with attention-deficit/hyperactivity disorder (ADHD) in daily routine and leisure activities. This study aimed to compare the participation, support and barriers for children with ADHD at home pre-COVID-19 and during the COVID-19 outbreak. Methods The study included 55 children with ADHD aged 6–11 years. Participation frequency, involvement, desire for change, supports and barriers at home were assessed using the Participation and Environment Measure for Children and Youth (PEM-CY). Results During the COVID-19 pandemic compared with the pre-COVID-19 period, the mean frequency of participation of children with ADHD in computer and video games (5.8% vs 5%, respectively), socialising with other people (7% vs 6.2%) and household chores (5.5% vs 4.6%) was shown to be significantly higher (p

Attention deficit/hyperactivity disorder (ADHD) is one of the most frequent neurodevelopmental disorders in childhood and adolescence. Choosing the right treatment is critical to controlling and improving symptoms. An innovative ADHD treatment is neurofeedback (NF) that trains participants to self-regulate brain activity. The aim of the study was to analyze the effects of NF interventions in children with ADHD. A systematic review was carried out in the CINAHL, Medline (PubMed), Proquest, and Scopus databases, following the PRISMA recommendations. Nine articles were found. The NF improved behavior, allowed greater control of impulsivity, and increased sustained attention. In addition, it improved motor control, bimanual coordination and was associated with a reduction in theta waves. NF combined with other interventions such as medication, physical activity, behavioral therapy training, or attention training with brain–computer interaction, reduced primary ADHD symptoms. Furthermore, more randomized controlled trials would be necessary to determine the significant effects.

Although sleep problems are common in children with ADHD, their extent, preceding risk factors, and the association between neurocognitive performance and neurobiological processes in sleep and ADHD, are still largely unknown. We examined sleep variables in school-aged children with ADHD, addressing their intra-individual variability (IIV) and considering potential precursor symptoms as well as the chronotype. Additionally, in a subgroup of our sample, we investigated associations with neurobehavioral functioning (n = 44). A total of 57 children (6–12 years) with (n = 24) and without ADHD (n = 33) were recruited in one center of the large ESCAlife study to wear actigraphs for two weeks. Actigraphy-derived dependent variables, including IIV, were analyzed using linear mixed models in order to find differences between the groups. A stepwise regression model was used to investigate neuropsychological function. Overall, children with ADHD showed longer sleep onset latency (SOL), higher IIV in SOL, more movements during sleep, lower sleep efficiency, and a slightly larger sleep deficit on school days compared with free days. No group differences were observed for chronotype or sleep onset time. Sleep problems in infancy predicted later SOL and the total number of movements during sleep in children with and without ADHD. No additional effect of sleep problems, beyond ADHD symptom severity, on neuropsychological functioning was found. This study highlights the importance of screening children with ADHD for current and early childhood sleep disturbances in order to prevent long-term sleep problems and offer individualized treatments. Future studies with larger sample sizes should examine possible biological markers to improve our understanding of the underlying mechanisms., Brain Sciences, 11 (12)

Attention-deficit/hyperactivity disorder (ADHD) is associated with disrupted emotional processes including impaired regulation of approach behavior and positive affect, irritability, and anger. Enhanced reactivity to emotional cues may be an underlying process. Pupil dilation is an indirect index of arousal, modulated by the autonomic nervous system and activity in the locus coeruleus-noradrenergic system. In the current study, pupil dilation was recorded while 8- to 12- year old children (n = 71, 26 with a diagnosis of ADHD and 45 typically developing), viewed images of emotional faces. Parent-rated hyperactive/impulsive symptoms were uniquely linked to higher pupil dilation to happy, but not fearful, angry, or neutral faces. This was not explained by comorbid externalizing symptoms. Together, these results suggest that hyperactive/impulsive symptoms are associated with hyperresponsiveness to approach-related emotional cues across a wide range of symptom severity.

Recent debates in the literature discuss commonalities between Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) at multiple levels of putative causal networks. This debate requires systematic comparisons between these disorders that have been studied in isolation in the past, employing potential markers of each disorder to be investigated in tandem. The present study, choose superior local processing, typical to ASD, and increased Intra-Subject Variability (ISV), typical to ADHD, for a head-to-head comparison of the two disorders, while also considering the comorbid cases. It directly examined groups of participants aged 10–13 years with ADHD, ASD with (ASD+) or without (ASD−) comorbid ADHD and a typically developing (TD) group (total N = 85). A visual search task consisting of an array of paired words was designed. The participants needed to find the specific pair of words, where the first word in the pair was the cue word. This visual search task was selected to compare these groups on overall search performance and trial-to-trial variability of search performance (i.e., ISV). Additionally, scanpath analysis was also carried out using Recurrence Quantification Analysis (RQA) and the Multi-Match Model. Results show that only the ASD− group exhibited superior search performance; whereas, only the groups with ADHD symptoms showed increased ISV. These findings point towards a double dissociation between ASD and ADHD, and argue against an overlap between ASD and ADHD.

High-dose use of benzodiazepines (BZDs) and Z-drugs was found to be associated with adult attention deficit/hyperactivity disorder (ADHD) and multidomain cognitive deficits, but the interplay between these factors and its effect on quality of life (QoL) is unclear. We explored (a) whether cognitive dysfunction differs in high-dose BZD/Z-drug users with and without adult ADHD and (b) the impact of cognitive deficits and adult ADHD on QoL in this substance-use disorder (SUD). From January 2015 to December 2019, we recruited 207 high-dose BZD/Z-drug users seeking treatment. We assessed the presence of adult ADHD with a screening tool, which was validated in SUD patients, and collected demographic, clinical and QoL data from the 76 included patients. A neuropsychological battery explored five cognitive domains. We found that: (a) screening for adult ADHD was frequently positive; (b) Short Form-36 (SF-36), a self-administered QoL questionnaire, was worse than the general population and worse in patients positive (ADHD+) vs. those negative (ADHD−) to ADHD screening tool; (c) executive function was significantly worse in ADHD+ than ADHD− patients; (d) some SF-36 dimensions were negatively influenced by executive dysfunction; (e) multivariate analysis showed an interplay between adult ADHD and cognitive dysfunction in worsening QoL. We documented a complex interplay between adult ADHD, cognitive dysfunction and QoL in high-dose BZD/Z-drug users. Assessing adult ADHD, neuropsychological measures and QoL may offer a full scenario of these patients, who are frequently impaired in everyday activities. Future research should explore whether pharmacological treatment might improve cognitive dysfunction and QoL in this SUD.

BackgroundMaintaining the therapeutic care of psychiatric patients during the first wave of the COVID-19 pandemic in Switzerland required changes to the way in which sessions were conducted, such as telepsychiatric interventions or the use of face masks during on-site sessions. While little is known about how face masks affect the therapeutic experience of patients and therapists, the effectiveness of telepsychiatry is well documented for several psychiatric disorders. However, research on the benefits of telepsychiatry in adult patients with attention-deficit/hyperactivity disorder (ADHD) remains scarce. This seems problematic since the symptoms typically associated with ADHD, such as attention problems and distractibility, may lessen the utility of telepsychiatry for this particular group. The present study’s aim was to explore how adult patients with ADHD and their therapists experienced therapy sessions during the COVID-19 pandemic in three different settings: face-to-face with the therapist wearing a face mask, via telephone, or via videoconferencing.MethodsIn this exploratory, quantitatively driven mixed-method study (quantitative questionnaire data and qualitative data from open-ended responses), we assessed patients’ evaluation of the session, their treatment satisfaction, and patients’ and therapists’ ratings of therapeutic alliance. We also collected qualitative comments on both sides’ experience of the session. Overall, 97 therapist and 66 patient questionnaires were completed. Results are reported for theN= 60 cases for which data from both parties were available. Sequential multiple regressions adjusted for therapist and number of sessions were used for the main quantitative analyses.ResultsTelepsychiatric sessions were rated as significantly less deep than face-to-face sessions, an effect that was mainly driven by lower ratings in the videoconferencing group and, as suggested by further analyses, may decline over time. No other statistically significant differences were observed. Elements that were mentioned as facilitating or complicating a session differed markedly between patients and therapists.ConclusionsBoth settings, on-site with the therapist wearing a face mask and telepsychiatric, seem to be valid options to continue treatment of adults with ADHD during a situation such as the COVID-19 pandemic. Aspects such as patient preference, session content, and therapeutic methods may be useful to identify the most suitable modality.

A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-alpha-2,3-sialyltransferase (ST3GAL5), leads to severe neuropathology, including epilepsy and metabolic abnormalities. Disruption of ganglioside production by this enzyme may also have a role in the development of neuropsychiatric disorders. ST3Gal5 knock-out (St3gal5−/−) mice lack a-, b-, and c-series gangliosides, but exhibit no overt neuropathology, possibly owing to the production of compensatory 0-series glycosphingolipids. Here, we sought to investigate the possibility that St3gal5−/− mice might exhibit attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In addition, we evaluated potential metabolic and electroencephalogram (EEG) abnormalities. St3gal5−/− mice were subjected to behavioural testing, glucose tolerance tests, and the levels of expression of brain and peripheral A and B isoforms of the insulin receptor (IR) were measured. We found that St3gal5−/− mice exhibit locomotor hyperactivity, impulsivity, neophobia, and anxiety-like behavior. The genotype also altered blood glucose levels and glucose tolerance. A sex bias was consistently found in relation to body mass and peripheral IR expression. Analysis of the EEG revealed an increase in amplitude in St3gal5−/− mice. Together, St3gal5−/− mice exhibit ADHD-like behaviours, altered metabolic and EEG measures providing a useful platform for better understanding of the contribution of brain gangliosides to ADHD and associated comorbidities.

Objective: Our objective was to examine developmental trajectories of co-occurring psychopathology symptoms from childhood to young adulthood in individuals with Attention-Deficit/Hyperactivity Disorder (ADHD), individuals with Autism Spectrum Disorder (ASD), and typically developing (TD) individuals.Method: We assessed co-occurring psychopathology symptoms in 61 individuals with ADHD, 26 with ASD, and 40 TD individuals at baseline (T1; Mage = 11.72, 64% boys), 2-year follow up (T2; Mage = 13.77), and 10-year follow up (T3; Mage = 21.35). We analyzed trajectories of internalizing behaviors, externalizing behaviors, and total problems with linear mixed models.Results: From T1 to T3, the ADHD group displayed a small decline in internalizing behaviors (d = −0.49) and large declines in externalizing behaviors (d = −0.78) and total problems (d = −0.71). The ASD group displayed large declines in internalizing behaviors (d = −0.79), externalizing behaviors (d = −0.80), and total problems (d = −0.89). From T1 to T2, the decline in externalizing behaviors and total problems were significantly smaller in the ADHD group compared with the ASD group. The ADHD and the ASD group displayed more co-occurring symptoms compared with the TD group at T3.Conclusion: Individuals with ADHD and ASD, respectively, displayed declines in co-occurring symptoms from childhood to young adulthood. Individuals with ASD displayed an earlier decline compared with individuals with ADHD. Compared with TD individuals, individuals with ADHD and ASD, respectively, continued to display elevated levels of co-occurring symptoms in young adulthood.

Objectives: In a previous pivotal study of children and adolescents (aged 6–17 years) with attention-deficit/hyperactivity disorder (ADHD), dose-optimized SHP465 mixed amphetamine salts (MAS) extended-release (12.5–25 mg once daily) was superior to placebo in reducing ADHD symptoms. This study evaluated the efficacy, tolerability, and safety of 6.25 mg SHP465 MAS once daily (one-half the lowest approved dose for adolescents and adults) versus placebo in children aged 6–12 years with ADHD. Methods: Children (aged 6–12 years) with Diagnostic and Statistical Manual of Mental Disorders, Fifth edition—defined ADHD; baseline ADHD-Rating Scale, Fifth Edition, Child, Home Version total scores (ADHD-RS-5-HV-TS) ≥28; and baseline Clinical Global Impressions-Severity scores ≥4 were eligible. Participants received 6.25 mg SHP465 MAS once daily or placebo for 4 weeks. The primary (ADHD-RS-5-HV-TS change from baseline at week 4) and key secondary (Clinical Global Impressions-Improvement [CGI-I] score at week 4) efficacy end points were assessed using linear mixed-effects models for repeated measures. Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital sign changes. Results: Of 89 randomized participants, 83 completed the study (placebo, n = 41; SHP465 MAS, n = 42). At week 4, the least squares mean (95% confidence interval) treatment differences (SHP465 MAS-placebo) were not statistically significant for ADHD-RS-5-HV-TS change (−1.9 [−6.8 to 3.1], p = 0.451; effect size [ES] = 0.17) or CGI-I score (−0.1 [−0.5 to 0.3], nominal p = 0.597; ES = 0.12). The percentage of participants reporting TEAEs was 16.3% with placebo and 24.4% with SHP465 MAS. The most frequently reported TEAEs (placebo; SHP465 MAS) were headache (7.0%; 4.4%) and decreased appetite (4.7%; 2.2%). Minimal increases in blood pressure were observed with SHP465 MAS at the final on-treatment assessment. Conclusions: SHP465 MAS 6.25 mg once daily (one-half the lowest dose approved for adolescents and adults) was well tolerated in children aged 6–12 years but was not superior to placebo in reducing ADHD symptoms, suggesting that this dose of SHP465 MAS was subtherapeutic in this age group. The Clinical Trial Registration number: NCT03325881.

sBackgroundThe aim of this study was to investigate the association between adult ADHD screening scores and hospitalization due to pedestrian injuries in a sample of Iranian pedestrians.MethodsThrough a case-control study, a case population of 177 pedestrians injured by the vehicles in road traffic crashes were compared with 177 controls who lacked a record of intentional or unintentional injuries enrolled from various wards of Imam Reza University Hospital which is a specialty teaching hospital located in the same city with similar referral level. The cases and controls had an age range of 18–65 years and were matched on gender and age. ADHD symptom profile was assessed using the Persian Self-report Screening Version of the Conner’s Adult ADHD Rating Scales (CAARS-S:SV). The association of ADHD screening score and pedestrian injuries was investigated using multiple binary logistic regression to investigate the independent effect of ADHD index score on belonging to case group. Both crude and adjusted odds ratios were reported.ResultsMen comprised 86.4% of the study subjects. The crude odds ratios for all the four ADHD subscales to be associated with pedestrian injuries were 1.05, 1.08, and 1.04 for the subscales A (attention deficit), B (hyperactivity/impulsiveness) and ADHD index respectively. However, the association for subscale A was not statistically significant with a borderlinep-value. The final multivariate analysis showed that variables associated with pedestrian injuries in the road traffic crashes were ADHD Index score (OR = 1.06, 95% CI: 1.01–1.12); economic status (including household income and expenditure capacity); educational level and total walking time per 24 h.ConclusionsAdult ADHD screening score can predict pedestrian injuries leading to hospitalization independently from sex, age, economic status, educational level and pedestrian exposure to traffic environment (average walking time).

Adolescents with ADHD demonstrate increased risk-taking behavior (RTB) like substance abuse and dangerous traffic conduct. RTB in adolescence is more likely under peer influence. The current investigation (1) tests the hypothesis that adolescents with ADHD are particularly susceptible to such influence and (2) tests whether groups differed in autonomic reactivity to peer influence. Adolescent boys between 12 and 19 years with (n = 81) and without (n = 99) ADHD performed the Balloon Analogue Risk Task twice. In the peer condition, a highly credible virtual peer manipulation that encouraged risk taking was added, in the solo condition this was absent. Autonomic reactivity was indexed by heart rate (HR), pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA). All adolescents engaged in more risk taking in the peer condition relative to solo condition. Autonomic differences between groups were only found on PEP: a stronger sympathetic response to peer influence was observed in typically developing adolescents relative to adolescents with ADHD. Increased physiological stress (as indexed by PEP) in the peer relative to the solo condition predicted peer-induced risk taking in all adolescents. We conclude that susceptibility to peer influence is not exaggerated in ADHD but rather reflects a general tendency of adolescents. As adolescents experiencing peer influence as stressful are most susceptible to peer influence, we suggest that increasing resistance to peer influence may be an important treatment aim for these adolescents specifically. Electronic supplementary material The online version of this article (10.1007/s10802-020-00666-z) contains supplementary material, which is available to authorized users.

Publisher's version (útgefin grein), Background There is evidence to suggest that the broad discrepancy in the ratio of males to females with diagnosed ADHD is due, at least in part, to lack of recognition and/or referral bias in females. Studies suggest that females with ADHD present with differences in their profile of symptoms, comorbidity and associated functioning compared with males. This consensus aims to provide a better understanding of females with ADHD in order to improve recognition and referral. Comprehensive assessment and appropriate treatment is hoped to enhance longer-term clinical outcomes and patient wellbeing for females with ADHD. Methods The United Kingdom ADHD Partnership hosted a meeting of experts to discuss symptom presentation, triggers for referral, assessment, treatment and multi-agency liaison for females with ADHD across the lifespan. Results A consensus was reached offering practical guidance to support medical and mental health practitioners working with females with ADHD. The potential challenges of working with this patient group were identified, as well as specific barriers that may hinder recognition. These included symptomatic differences, gender biases, comorbidities and the compensatory strategies that may mask or overshadow underlying symptoms of ADHD. Furthermore, we determined the broader needs of these patients and considered how multi-agency liaison may provide the support to meet them. Conclusions This practical approach based upon expert consensus will inform effective identification, treatment and support of girls and women with ADHD. It is important to move away from the prevalent perspective that ADHD is a behavioural disorder and attend to the more subtle and/or internalised presentation that is common in females. It is essential to adopt a lifespan model of care to support the complex transitions experienced by females that occur in parallel to change in clinical presentation and social circumstances. Treatment with pharmacological and psychological interventions is expected to have a positive impact leading to increased productivity, decreased resource utilization and most importantly, improved long-term outcomes for girls and women., The meeting was funded by the UK ADHD Partnership (UKAP), who has been in receipt of unrestricted educational donations from Takeda. Takeda had no influence or involvement in determining the topic and arrangements of the day, the consensus process and outcomes, or writing the final manuscript. Other than reimbursement of travel expenses to attend the meeting, none of the authors received any financial compensation for attending the meeting or writing the manuscript, aside from CS who received funds for medical writing assistance., "Peer Reviewed"

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder of childhood. Although abnormalities in several brain regions and disturbances of the catecholaminergic pathway have been demonstrated, the pathophysiology of ADHD is not completely understood, but as a multifactorial disorder, has been associated with an increase in oxidative stress and neuroinflammation. This review presents an overview of factors that increase oxidative stress and neuroinflammation. The imbalance between oxidants and antioxidants and also the treatment with medications are two factors that can increase oxidative damage, whereas the comorbidity between ADHD and inflammatory disorders, altered immune response, genetic and environmental associations, and polymorphisms in inflammatory-related genes can increase neuroinflammation. Evidence of an association with these factors has become valuable for research on ADHD. Such evidence opens up new intervention routes for the use of natural products as antioxidants that could have potential as a treatment against oxidative stress and neuroinflammation in ADHD.

Neurofeedback training (NFT) provides strategies for children with ADHD to achieve changes on the neurophysiological and behavioral level to attenuate ADHD symptoms. We assume self-efficacy (an “active attitude”), a core variable in successful NFT. In a randomized, double-blind controlled study, we investigated the impact of a “placebo instruction” on the EEG-regulation performance during two sessions of Theta-Beta-NFT in children with ADHD (age 8–12 years). Children receiving the information “this might be a placebo-training” showed inferior neuroregulation (n = 10) compared to children receiving a standard instruction (n = 12). Results of our pilot study are discussed in view of factors necessary for a valid training (ensuring maximal self-efficacy in the participants) and the fidelity of placebo-controlled trials in NFT-research. Electronic supplementary material The online version of this article (10.1007/s00702-020-02193-z) contains supplementary material, which is available to authorized users.

Actigraphy, an objective measure of motor activity, reliably indexes increased movement levels in attention-deficit/hyperactivity disorder (ADHD) and may be useful for diagnosis and treatment-monitoring. However, actigraphy has not been examined in complex neurodevelopmental conditions. This study used actigraphy to objectively measure movement levels in individuals with a complex neurodevelopmental genetic disorder, tuberous sclerosis (TSC). Thirty participants with TSC (11–21 years, 20 females, IQ = 35–108) underwent brief (approximately 1 h) daytime actigraph assessment during two settings: movie viewing and cognitive testing. Multiple linear regressions were used to test associations between movement measurements and parent-rated ADHD symptoms. Correlations were used to examine associations between actigraph measures and parent-rated ADHD symptoms and other characteristics of TSC (symptoms of autism spectrum disorder (ASD), intellectual ability (IQ), epilepsy severity, cortical tuber count). Higher movement levels during movies were associated with higher parent-rated ADHD symptoms. Higher ADHD symptoms and actigraph-measured movement levels during movies were positively associated with ASD symptoms and negatively associated with IQ. Inter-individual variability of movement during movies was not associated with parent-rated hyperactivity or IQ but was negatively associated with ASD symptoms. There were no associations with tuber count or epilepsy. Our findings suggest that actigraph-measured movement provides a useful correlate of ADHD in TSC.

Adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) demonstrate increased levels of real-life risk-taking behavior like substance abuse and reckless behavior in traffic, which potentially originates in decision-making deficits. Using experimental gambling tasks, the current study investigated three potential underlying mechanisms: (1) risky vs. suboptimal decision making, (2) the complexity of decision-making strategies and (3) the influence of feedback. Participants were 181 male adolescents (81 ADHD, 100 Typically Developing (TD); Mage = 15.1 years). First, we addressed a common confound in many gambling tasks by disentangling risk seeking from suboptimal decision making, and found that ADHD-related decision-making deficits do not originate in increased risk seeking but in suboptimal decision making. Second, we assessed decision-making strategies with a Bayesian latent mixture analysis and found that ADHD-related decision-making deficits are characterized by the use of less complex strategies. That is, adolescent boys with ADHD, relative to TD adolescent boys, less often adopted strategies in which all characteristics relevant to make an optimal decision were integrated. Third, we administered two gambling task conditions with feedback in which adolescents experience the outcomes of their decisions and found that adolescents with ADHD performed worse relative to TD adolescents on both conditions. Altogether, this set of studies demonstrated consistent decision-making deficits in adolescent boys with ADHD: The use of less complex decision-making strategies may cause suboptimal decision making, both in situations with and without direct feedback on performance.

Background Nearly half of all mental health disorders develop prior to the age of 15. Early assessments, diagnosis, and treatment are critical to shortening single episodes of care, reducing possible comorbidity and long-term disability. In Norway, approximately 20% of all children and adolescents are experiencing mental health problems. To address this, health officials in Norway have called for the integration of innovative approaches. A clinical decision support system (CDSS) is an innovative, computer-based program that provides health professionals with clinical decision support as they care for patients. CDSS use standardized clinical guidelines and big data to provide guidance and recommendations to clinicians in real-time. IDDEAS (Individualised Digital DEcision Assist System) is a CDSS for diagnosis and treatment of child and adolescent mental health disorders. The aim of IDDEAS is to enhance quality, competency, and efficiency in child and adolescent mental health services (CAMHS). Methods/design IDDEAS is a mixed-methods innovation and research project, which consists of four stages: 1) Assessment of Needs and Preparation of IDDEAS; 2) The Development of IDDEAS CDSS Model; 3) The Evaluation of the IDDEAS CDSS; and, 4) Implementation & Dissemination. Both qualitative and quantitative methods will be used for the evaluation of IDDEAS CDSS model. Child and adolescent psychologists and psychiatrists (n = 30) will evaluate the IDDEAS` usability, acceptability and relevance for diagnosis and treatment of attention-deficit/hyperactivity disorder. Discussion The IDDEAS CDSS model is the first guidelines and data-driven CDSS to improve efficiency of diagnosis and treatment of child and adolescent mental health disorders in Norway. Ultimately, IDDEAS will help to improve patient health outcomes and prevent long-term adverse outcomes by providing each patient with evidence-based, customized clinical care. © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Background In recent years, the existence of possible developmental pathways from childhood Attention-Deficit/Hyperactivity Disorder (ADHD) to adult Borderline Personality Disorder (BPD) has been suggested. The existence of common genetic factors has been described but there is little evidence on the role of environmental factors in the possible transition from one disorder to another throughout life. The main goal of this work is to review the literature about the existing evidence on childhood traumas as factors that mediate the risk of developing BPD in children with ADHD. Methods A literature search was conducted using PubMed, Science Direct and PsychInfo databases. Criteria included studies of BPD and ADHD relationships and childhood traumas as environmental influences from epidemiological or clinical samples. Results The review only identified 4 studies that matched the search criteria. All studies retrospectively analyzed childhood traumas, and adult patients with BPD, with or without comorbid ADHD, were the most frequently mentioned. The analyzed evidence reinforces the relationship between the number of childhood traumas and higher clinical severity. Three of these analyzed studies describe an increased the risk of children with ADHD who report emotional and sexual traumatic experiences to develop BPD in adulthood. Conclusions The experience of traumatic childhood events, especially those of an emotional type, may have a mediating effect of an increased risk of developing adult BPD in childhood ADHD patients. However, to consider them as risk factors, more studies, and especially longitudinal studies, are necessary to clarify the probable transactional process between the two disorders. Evidence from these studies may be helpful to develop early intervention programs to reduce the functional impairment associated with the two disorders.

Background Many adolescents in special education are affected by anxiety in addition to their behavioral problems. Anxiety leads to substantial long-term problems and may underlie disruptive behaviors in the classroom as a result of the individual’s inability to tolerate anxiety-provoking situations. Thus, interventions in special needs schools that help adolescents cope with anxiety and, in turn, diminish disruptive classroom behaviors are needed. Objective This study aimed to evaluate the effect of a virtual reality biofeedback game, DEEP, on daily levels of state-anxiety and disruptive classroom behavior in a clinical sample. In addition, the study also aimed to examine the duration of the calm or relaxed state after playing DEEP. Methods A total of 8 adolescents attending a special secondary school for students with behavioral and psychiatric problems participated in a single-case experimental ABAB study. Over a 4-week period, participants completed 6 DEEP sessions. In addition, momentary assessments (ie, 3 times a day) of self-reported state-anxiety and teacher-reported classroom behavior were collected throughout all A and B phases. Results From analyzing the individual profiles, it was found that 6 participants showed reductions in anxiety, and 5 participants showed reductions in disruptive classroom behaviors after the introduction of DEEP. On a group level, results showed a small but significant reduction of anxiety (d=–0.29) and a small, nonsignificant reduction of disruptive classroom behavior (d=−0.16) on days when participants played DEEP. Moreover, it was found that the calm or relaxed state of participants after playing DEEP lasted for about 2 hours on average. Conclusions This study demonstrates the potential of the game, DEEP, as an intervention for anxiety and disruptive classroom behavior in a special school setting. Future research is needed to fully optimize and personalize DEEP as an intervention for the heterogeneous special school population.

Objective: To evaluate the relationship between symptom and functional improvement and remission in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) enrolled in an 11-week open-label dose-optimization phase of an methylphenidate extended release (MPH-MLR) pivotal study. Methods: Assessments included the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P) and ADHD Rating Scale, Fourth Edition (ADHD-RS-IV). Definitions included the following: symptom improvement (≥30% decrease in ADHD-RS-IV total score); symptom remission (ADHD-RS-IV total score ≤18); functional improvement (decrease in WFIRS-P total score ≥0.25 [minimally important difference]); and functional remission (WFIRS-P total score ≤0.65). Results: Two hundred children completed the open-label phase. At initial assessment, functional impairment was evident across all WFIRS-P domains and similar between children and adolescents. Those who were treatment naive had more functional impairment (WFIRS-P total: 0.82 vs. 0.70, p = 0.02). Significant improvements in all WFIRS-P domains were noted at open-label end (p

With increasing numbers of children being diagnosed with neurodevelopmental disorders (NDDs) attention has been drawn to these children’s physical health. We aimed to identify the prevalence of defined physical problems (epilepsy, migraine, asthma, cancer, diabetes, psoriasis, lactose intolerance, celiac disease, diarrhea, constipation, daytime enuresis, encopresis) in a nationwide population of 9- and 12-year-old twins subdivided into those with and without indications of NDDs. Parents of 28,058 twins participated in a well-validated telephone interview regarding their children’s mental health and answered questions about their physical problems. The results indicate a high rate of physical problems in children with NDDs, particularly in those with indications of the presence of combinations of several NDDs. Electronic supplementary material The online version of this article (10.1007/s10803-018-3697-4) contains supplementary material, which is available to authorized users.

Background Addictive-like behaviors (e.g., hoarding and shopping) may be the result of the cumulative effects of dopaminergic and other neurotransmitter genetic variants as well as elevated stress levels. We, therefore, propose that dopamine homeostasis may be the preferred goal in combating such challenging and unwanted behaviors, when simple dopaminergic activation through potent agonists may not provide any resolution. Case presentation C.J. is a 38-year-old, single, female, living with her mother. She has a history of substance use disorder as well as attention deficit hyperactivity disorder, inattentive type. She had been stable on buprenorphine/naloxone combination and amphetamine, dextroamphetamine mixed salts for many years when unexpectedly she lost her job for oversleeping and not calling into work. KB200z (a pro-dopamine compound) was added to her regimen for complaints of low drive and motivation. After taking this nutraceutical for 4 weeks, she noticed a marked improvement in her mental status and many behaviors. She noted that her shopping and hoarding addictions had appreciably decreased. Furthermore, her lifelong history of terrifying lucid dreams was eliminated. Finally, she felt more in control; her locus of control shifted from external to more internal. Discussion The hypothesis is that C.J.'s reported, behavioral, and psychological benefits resulted from the pro-dopamine-regulating effect of KB220Z across the brain reward system. Conclusions This effect, we surmise, could be the result of a new dopamine balance, across C.J.'s brain reward system. Dopamine homeostasis is an effect of KB220Z seen in both animal and human placebo-controlled fMRI experiments.

Adhesion G protein-coupled receptor L3 (ADGRL3, LPHN3) has putative roles in neuronal migration and synapse function. Various polymorphisms in ADGRL3 have been linked with an increased risk of attention deficit/hyperactivity disorder (ADHD). In this study, we examined the characteristics of Adgrl3-deficient mice in multiple behavioural domains related to ADHD: locomotive activity, impulsivity, gait, visuospatial and recognition memory, sociability, anxiety-like behaviour and aggression. Additionally, we investigated the effect of Adgrl3-depletion at the transcriptomic level by RNA-sequencing three ADHD-relevant brain regions: prefrontal cortex (PFC), hippocampus and striatum.Adgrl3(-/-) mice show increased locomotive activity across all tests and subtle gait abnormalities. These mice also show impairments across spatial memory and learning domains, alongside increased levels of impulsivity and sociability with decreased aggression. However, these alterations were absent in Adgrl3(-/-) mice. Across all brain regions tested, the numbers of genes found to exhibit differential expression was relatively small, indicating a specific pathway of action, rather than a broad neurobiological perturbation. Gene-set analysis of differential expression in the PFC detected a number of ADHD-relevant pathways including dopaminergic synapses as well as cocaine and amphetamine addiction. The Slc6a3 gene coding for the dopamine transporter was the most dysregulated gene in the PFC. Unexpectedly, several neurohormone/peptides which are typically only expressed in the hypothamalus were found to be dysregulated in the striatum. Our study further validates Adgrl3 constitutive knockout mice as an experimental model of ADHD while providing neuroanatomical targets for future studies involving ADGRL3 modified models.This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity'.

Adaptive behavior requires the adjustment of one's behavioral repertoire to situational demands. The learning of situationally appropriate choice behavior can be operationalized as a task of Conditional Discrimination Learning (CDL). CDL requires the acquisition of hierarchical reinforcement relations, which may pose a particular challenge for children with Attention Deficit Hyperactivity Disorder (ADHD), particularly in light of documented deficits in short-term/working memory and delay aversion in ADHD. Using an arbitrary Delayed Matching-To-Sample task, we investigated whether children with ADHD (N = 46), relative to Typically Developing children (TD, N = 55), show a deficit in CDL under different choice delays (0, 8, and 16 seconds) and whether these differences are mediated by short-term/working memory capacity and/or delay aversion. Children with ADHD demonstrated poorer CDL than TD children under 8 and 16-second delays. Non-delayed CDL performance did not differ between groups. CDL differences were not mediated by short-term/working memory performance or delay aversion. Moreover, CDL performance under an 8-second delay was a better predictor of clinical status than short-term/working memory performance or delay aversion. CDL, under conditions of delay, is impaired in children with ADHD. This may lead to difficulties discriminating between different situational demands and adapting behavior according to the prevailing reward contingencies or expectations. ispartof: Journal of Clinical Medicine vol:8 issue:9 ispartof: location:Switzerland status: Published online

This study explored (1) whether growth mixture modelling (GMM) could identify different trajectories of learning efficiency during a working memory (WM) training programme for young children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD), compared with a typically developing (TD) control group, and (2) if learning trajectories and outcomes were different for simple and complex training tasks. Children completed simple visuospatial short-term memory (VSSTM) and complex visuospatial WM (VSWM) tasks for 15 minutes a day, 5 days a week and for 8 weeks. Parent-reported executive functioning, and children’s WM and attention control, educational achievement, and IQ were measured prior to (T1), immediately following (T2) and three months after training (T3). GMM analysis showed that WM training was represented as one learning curve, and there was no difference for the trajectories of the ADHD and TD groups. The learning trajectory for the VSSTM tasks across groups was represented as one learning curve and for the VSWM tasks there were three learning curves. Learning for the VSSTM tasks and for most children in the VSWM tasks was characterized by an inverted-U shape, indicating that training was effective for up to 15 sessions, was stable and declined thereafter, highlighting an optimal training timeframe. For the VSWM tasks, the two remaining groups showed either a U-shaped or a high inverted U-shaped trajectory, with the latter group achieving the highest T1T2 change score (i.e., children showed a lower starting point and the most gain in terms of learning and post-training performance). There were no broader benefits of training at post-test or follow-up. Further research should explore who would benefit most from intensive cognitive training, as well as the potential benefits for mental health and well-being. Keywords. WM training, learning trajectories, young children, Attention-Deficit/Hyperactivity Disorder (ADHD), Growth Mixture Modelling (GMM).

The delay aversion hypothesis argues that the tendency for impulsive choice (preference for smaller sooner over larger later rewards) is motivated by the escape of negative affective states associated with delay. This model predicts that individuals with ADHD find the imposition of delay before an outcome or event especially aversive and its escape reinforcing. Consistent with this, fMRI studies show that ADHD is associated with amygdala hyper-sensitivity to cues of delay. However, evidence that delay escape is reinforcing is lacking. Here we extend fMRI research by using electrophysiological methods to study the reinforcing properties of delay-escape in ADHD. Thirty controls and 25 adolescents with ADHD aged 10–15 years performed the Escape Delay Incentive (EDI) task- in which pre-target cues indicated three conditions: i) CERTAIN DELAY: delay would follow a response irrespective of response speed ii) CONDITIONAL DELAY: delay would only follow if the response was too slow and iii) NO DELAY: delay would follow the response whatever the speed. We focused on the Contingent Negative Variation (CNV), a cue-evoked marker of motivated response preparation, across two time windows (CNV1 and CNV2). We took measures of parent, teacher and self-rated ADHD symptoms, task performance (RT) and self-rated delay aversion. We isolated CNV components and compared these between ADHD and controls. Adolescents with ADHD displayed a larger CNV2 to the CONDITIONAL DELAY than the CERTAIN DELAY cues compared to controls. However, this effect was not mirrored at the performance level and was unrelated to self-reported delay aversion. Our study provides the first ERP evidence that delay escape differentially reinforcers neural activation of attention preparation in ADHD cases. Future studies should examine the impact of varying cognitive load on task EDI performance., Highlights • Individuals with ADHD find cues predicting the imposition of delay aversive but evidence that delay escape is reinforcing is lacking • We used the Escape-Delay Incentive Task to isolate the CNV, reflecting motivated attention preparation to escape delay cues • Adolescents with ADHD displayed larger CNV2 to cues signalling the possibility to escape delay • Results provide the first ERP evidence of the reinforcing value of delay escape in ADHD

Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.

Background/objective: Sluggish Cognitive Tempo (SCT) is an attentional disorder characterized by the symptoms of slowness in behavior or thinking, a lack of en.ergy, difficulty initiating and sustaining effort, daydreaming, and drowsiness. The aim of the present study was to investigate the distinctive attentional characteristics of SCT as compared to Attention-Deficit/Hyperactivity Disorder (ADHD). Method: A total of 110 adults were recruited and divided into four groups: SCT+ADHD, SCT, ADHD, and healthy controls. The Revised version of Attention Networks Test was used to investigate each group’s attentional profile. Results: The results revealed that the two SCT groups (SCT+ADHD and SCT) showed a significantly weaker orienting network due to the problems of engaging and disengaging attention than the other two groups. Additionally, the two ADHD groups (SCT+ADHD and ADHD) showed a significantly weaker executive control network than the other two groups. Conclusions: The findings demonstrate an attentional distinction between the SCT and the ADHD groups with a greater dysfunction in the orienting network in the SCT group as compared to the ADHD group. Furthermore, a greater executive control dysfunction was observed in the ADHD group as compared to the SCT group.

Employing a large sample of children from Dutch regular elementary schools, this study assessed the contributing and discriminating values of reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD) to two types of phonological processing skills, phonemic awareness (PA) and rapid automatized naming (RAN). A second objective was to investigate whether comorbidity of RD and ADHD should be considered as an additive phenomenon as to RAN and PA. A total of 1,262 children, aged 8 to 13 years, were classified as RD ( n = 121), ADHD ( n = 17), comorbid (RD+ADHD; n = 16), or control ( n = 1,108). Phonological processing was assessed by standardized tests of PA and RAN. Disability groups were compared to each other and contrasted to the control group. Although results indicate substantial effects for all three disability groups on both types of phonological processing, and the RAN/PA compound measure in particular, effect sizes were considerably larger for the RD groups, as compared to the ADHD-only group. Theoretical and practical implications are discussed.

ADHD has been associated with various forms of risky real life decision making, for example risky driving, unsafe sex and substance abuse. However, results from laboratory studies on decision making deficits in ADHD have been inconsistent, probably because of between study differences. We therefore performed a meta-regression analysis in which 37 studies (n ADHD = 1175; n Control = 1222) were included, containing 52 effect sizes. The overall analysis yielded a small to medium effect size (standardized mean difference = .36, p < .001, 95% CI [.22, .51]), indicating that groups with ADHD showed more risky decision making than control groups. There was a trend for a moderating influence of co-morbid Disruptive Behavior Disorders (DBD): studies including more participants with co-morbid DBD had larger effect sizes. No moderating influence of co-morbid internalizing disorders, age or task explicitness was found. These results indicate that ADHD is related to increased risky decision making in laboratory settings, which tended to be more pronounced if ADHD is accompanied by DBD. We therefore argue that risky decision making should have a more prominent role in research on the neuropsychological and -biological mechanisms of ADHD, which can be useful in ADHD assessment and intervention.

Introduction: Recent research has highlighted an increased rate of co-morbidity between the neurodevelopmental-behavioral disorder of attention deficit hyperactivity disorder (ADHD) and a variety of psychiatric disorders, such as mood disorders or bipolar disorder (BD). The etiology and clinical course of BD are considered to be determined by both genetic and environmental factors, either aggravating or improving. Aim: This follow-up study of an adolescent aimed to clarify the co-morbidity between ADHD and BD. We also discuss the controversies surrounding the two diagnoses in younger populations and describe several aspects of concern regarding diagnosis, differential diagnosis, therapeutic planning/intervention, and prognosis. Methods: Reporting of a two-year follow-up study of a bipolar 15-year-old female patient with a previous diagnosis of ADHD during childhood. Results: Despite the occurrence of major risk factors, such as early onset and positive family history, the patient’s condition rapidly remitted with medication, without relapse and/or rehospitalization during the following two years, due to the stability of her cooperation, and support of a stable and caring familial environment. Early diagnosis of BD and differential diagnoses of ADHD are considered crucial protective factors leading to an appropriate planning of treatment. In addition, parental involvement and empathic attitude towards the patient supported the latter to cooperate and comply with the treatment, enhancing positive outcomes and stability. Conclusions: Research is required into the reliability and validity of diagnostic protocols and criteria for BD in children and adolescents, and also into the development of individualized therapeutic planning.