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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.

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.

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 characterized by inattention, hyperactivity and impulsivity. A dearth of studies have investigated psychosexuality in this population, often with few (predominantly male) participants. We recruited individuals with and without ADHD via an anonymous online survey distributed electronically by ADHD support organizations and social media. We investigated sexual history; interests and practices; and relationships. Of 1392 respondents, we classified an ‘ADHD’ group (n = 541; 30.5% male) and compared them to individuals of similar ages without ADHD, (‘Other’ group; n = 851; 37.6% male). The ADHD group (both males and females) had a significantly higher preference for same-sex or either-sex partners; and higher rates of electronic sexual exchanges, masturbation, and sexually transmitted diseases. They were more adventurous in sexual interests and practices and substantially less satisfied with their partners, both sexually and generally. Within the ADHD group, significant sex differences emerged: females had younger onset of sexual activities, used contraception less frequently, had more sexual partners and practiced more infidelity. Sexual interests differed between the sexes, but females more commonly acted on them, whereas males did not. Findings suggest both sexes engage in risky sexual behaviors, perhaps driven by impulsivity, but risk is substantially greater for females with ADHD.

Attention-Deficit/Hyperactivity Disorder (ADHD) is consistently associated with a host of social problems, such as victimization and difficulties in maintaining close friendships. These problems are not limited to offline relations but also manifest in the online social world, as previous research shows that ADHD is associated with problematic use of social media. Given the ubiquitous nature of social media, the goal of the current review is to understand why adolescents with ADHD demonstrate more problematic social media use than their typically developing peers. To this end, we provide a narrative review on the evidence for the link between ADHD and social media use, and consequently present an integrative framework, which encompasses neurobiological mechanisms (i.e., imbalance theory of brain development and dual pathway model of ADHD) and social mechanisms, including influences from peers and parents. We conclude that empirical work shows most consistent evidence for the link between problematic social media use and ADHD (symptoms), while intensity of social media use is also associated with several other behaviors and outcomes. Finally, we hypothesize how existing interventions for ADHD may work on the identified mechanisms and provide at-hand clinical recommendations for therapists working with adolescents with ADHD who exhibit problematic social media use.

Investigating the relationship between attention-deficit/hyperactivity disorder (ADHD) symptoms and impulsivity will benefit our understanding of the concept of problematic pornography use (PPU), and revealing predisposing and malleable moderators of PPU will be beneficial for its prevention and intervention. The current study not only aimed to observe these relationships, but also explored the potential moderating role of physical exercise in the general population. A total of 600 Chinese adults (Mage = 32.31, SDage = 12.40, 39.8% women) were recruited and completed an online survey. The results showed that participants with regular exercise scored lower than those without exercise on ADHD, impulsivity, and PPU (all ps < 0.001). Using latent moderated structural equations (LMS), the findings revealed that the relationship between ADHD symptoms and PPU was mediated by impulsivity, and physical exercise moderated this relationship (B = −0.14, p = 0.048). Specifically, when individuals’ physical exercise was higher than 0.84 standard deviations above the mean, the positive predictive effect of impulsivity on PPU was not significant. These findings indicate the important role of impulsivity in the relationship between ADHD and PPU, and physical exercise could be a meaningful component of interventions among individuals experiencing PPU.

Disruptive behaviour disorders can affect between 1 and 11% of children. Without adequate intervention, children with disruptive behaviour and their families experience social, emotional, and occupational impacts (e.g., depression, self-harm, lower academic achievement, family stress). We have yet to clearly understand the causal factors that underlie disruptive behaviour. Inhibitory control problems are a common aetiological factor associated with Attention-Deficit/Hyperactivity Disorder (ADHD), a disorder that is commonly comorbid with disruptive behaviours. What remains unclear is whether inhibitory control problems are present in disruptive behaviour disorders, such as Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD), independent of ADHD symptomatology. Determining the role of inhibitory control in ODD/CD is challenging for two reasons: 1) high comorbidity between ODD/CD and ADHD, and 2) theoretical issues in how we conceptualise inhibitory control, which is part of executive functioning. This thesis presents three papers aiming to clarify some of these issues: 1) A systematic review and meta-analysis of 25 studies examined the presence of inhibitory control problems in children with ODD/CD compared to clinical and healthy controls. Results revealed that children with ODD/CD had more difficulties with inhibitory control problems than healthy controls. Children with ODD/CD also presented with similar inhibitory control problems and ADHD symptomatology to children with ADHD. Given that inhibitory control problems are similar across clinical groups, transdiagnostic formulations of disruptive behaviour in diagnosis and treatment were discussed. 2) Based on the findings of the review, the associations between disruptive behaviours (measured by conduct problems and aggression) and inhibitory control in a community sample of 148 school aged children were explored. Another aim of this study was to understand the relationship between inhibitory control and callous-unemotional traits (CU traits) on disruptive behaviour to further extend our understanding of risk factors. Results indicated that caregivers who rated their children as having more inhibitory control problems also rated their children as more aggressive and as having more conduct problems, even after controlling for ADHD symptoms. Further, inhibitory control exacerbated the effect of CU traits on conduct problems, but not aggression. The results of this study identified unique relationships between inhibitory control and CU traits on disruptive behaviour, laying the groundwork for future studies to explore their role in the aetiology of disruptive behaviours. 3) Across studies, the challenges inherent in the executive function literature appeared to limit our understanding of inhibitory control. These challenges were explored by a critical review of the executive dysfunction literature. Results highlighted that a divergence of theoretical frameworks has negatively impacted upon operationalisation, measurement, and translation of research results on executive function into clinical practice. The development of clinical guidelines for executive dysfunction was recommended as a next step in bridging the research-practice gap, with a focus on the inclusion of key stakeholders (i.e., health professionals and consumers) in the process. The results of this thesis have key implications for the conceptualisation of disruptive behaviours from a dimensional perspective, specifically that inhibitory control difficulties are likely to play a critical aetiological role in disruptive behaviour. Inhibitory control difficulties, which cut across disorders, may be an important consideration in complementary approaches to intervention and future iterations of diagnostic manuals. Further, this thesis highlights the need for consensus within the executive function research, to provide clarity on theoretical underpinnings and allow for more meaningful results which can inform better care for consumers.

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

We examined perceived stress and sleep problems in adolescent ADHD and whether this varies as a function of ADHD presentation and sex. Further, we mapped structural associations between ADHD symptoms, comorbid symptoms, perceived stress, and sleep problems. Participants were 306 adolescents aged 13–19 years (66.8% females, 193 had an ADHD diagnosis, 113 were controls). Parents rated ADHD symptoms, all other constructs were self-rated. Adolescents with ADHD had elevated levels of perceived stress and sleep problems. Girls with ADHD reported the highest levels of perceived stress. Emotional symptoms mediated the effect of inattention whereas conduct problems mediated the effect of hyperactivity/impulsivity on stress and sleep. Perceived stress and sleep problems should be considered when mapping ADHD-related problems. Comorbid symptoms are potential intervention targets that may increase treatment response.

Children with developmental disabilities (DDs) have sensory modulation disorders that interrelate school performance. Virtual reality (VR) has demonstrated the potential to become a neuropsychological assessment modality. This study was conducted to explore the feasibility of the VR classroom for assessing their characteristics of gaze, school performance, and interoception. School-aged children were assigned to the DD group or control group. A VR classroom was designed to evaluate their gaze patterns to distracting events. Interoception was assessed using the Heart Rate Perception test and the Multidimensional Assessment of Interoceptive Awareness (MAIA). The DD group had a significantly longer gaze duration on the virtual teacher during 30–45 s of the VR classroom event (p < 0.05). The mean score of the quiz and the Heart Rate Perception test showed a significant tendency to be lower than the children of the control group. The DD group scored significantly lower in six of eight subscales of the MAIA. These results showed the potential of VR classroom to evaluate the difference of sensory modulation between school-aged children with DDs and typically developed children. Future research is necessary to investigate the validity of the VR environment used in this study.

Attention-deficit/hyperactivity disorder (ADHD) is associated with impaired social interaction. Other’s eyes are important for understanding the social world. Here, we examined concurrent and longitudinal links between attention to other’s eyes and symptoms of ADHD and comorbid externalizing and internalizing symptoms. Eighty-two 8 to 13-year-old children (40% with ADHD) participated. The latency to a first gaze shift to and away from the eye region of human faces, when primed to look at either the eyes or the mouth, was recorded with eye tracking. Parents rated ADHD, externalizing and internalizing symptoms at the time of testing and at 2-year follow-up. The results show that longer looking at the eyes before reorienting was specifically associated with concurrent and future symptoms of inattention, even when accounting for comorbid symptoms. We conclude that the temporal microstructure of attention to other’s eyes is altered in children with symptoms of ADHD, which may contribute to social impairments.

Attention-deficit/hyperactivity disorder (ADHD), though now classified in the Diagnostic and Statistical Manual (DSM-5) as a neurodevelopmental disorder, has been framed in myriad ways over the last century. Regardless of framing, however, the diagnostic category has consistently occupied a contentious space in public discourse and medical systems alike. Even though current research in clinical psychology estimates that ADHD is likely underdiagnosed and undertreated, particularly among women, debates which question the legitimacy and prevalence of the disorder continue to persist. The last two years have witnessed a pushback to underdiagnosis with assistance from an unlikely source: social media. Platforms like Instagram and TikTok have seen increasing amounts of content produced on the disorder, with particularly profound consequences for women. Significantly, women have taken to these platforms to share experiences with the disorder, spreading awareness of the differences in symptom presentations for women and illuminating the paradox of being diagnosed with a neurodevelopmental disorder in adulthood. Using qualitative data collected from Zoom interviews, social media posts, and comment sections, I seek to elucidate the dual phenomenon of late diagnoses of ADHD in women and the proliferation of ADHD content online. I ask: what becomes of those who are not the center of the DSM’s gaze? And how does one form reality in the biomedical periphery? In answering these questions, I evaluate how women reorient themselves after the rupture caused by a “late” diagnosis and interrogate the role of social media to understand how women find their bearings in the wake of a late diagnosis.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent condition with onset in childhood and in many cases persisting into adulthood. Even though an increasing number of studies have investigated the efficacy of pharmacotherapy in the management of adult ADHD, few authors have tried to identify the biological predictors of treatment response. Objectives: To summarize the available data about the biological markers of treatment response in adults affected by ADHD. Methods: A search on the main biomedical and psychological archives (PubMed, Embase, Scopus, and PsycINFO) was performed. Manuscripts in English, published up to May 2022 and having the biological predictors of treatment response in adults with ADHD as their main topic, were included. Results: A total of 3855 articles was screened. Twenty-two articles were finally included. Most of the manuscripts studied neuroimaging and electrophysiological factors as potential predictors of treatment response in adult ADHD patients. No reliable markers were identified until now. Promising findings on this topic regard genetic polymorphisms in snap receptor (SNARE) proteins and default mode network-striatum connectivity. Conclusions: Even though some biological markers seem promising for the prediction of treatment response in adults affected by ADHD, further studies are needed to confirm the available data in the context of precision medicine.

Attention-deficit/hyperactivity disorder (ADHD), a neuropsychiatric condition characterized by inattention, hyperactivity, and impulsivity, afflicts 5% of children worldwide. Each ADHD patient presents with individual cognitive and motivational peculiarities. Furthermore, choice of appropriate therapy is still up to clinicians, who express somewhat qualitative advice on whether a child is being successfully cured or not: it would be more appropriate to use an objective biomarker to indicate whether a treatment led to benefits or not. The aim of our work is to search for such clinical biomarkers. We recruited 60 ADHD kids; psychopathological scales were administered at recruitment and after six weeks of therapy. Out of such a cohort of ADHD children, we rigorously extracted two specific subgroups; regardless of the initial severity of their disease, we compared those who obtained the largest improvement (ΔCGAS > 5) vs. those who were still characterized by a severe condition (CGAS < 40). After such a therapy, methylation levels of DNA extracted from buccal swabs were measured in the 5′-UTR of the DAT1 gene. CpGs 3 and 5 displayed, in relation to the other CpGs, a particular symmetrical pattern; for “improving” ADHD children, they were methylated together with CpG 2 and CpG 6; instead, for “severe” ADHD children, they accompanied a methylated CpG 1. These specific patterns of methylation could be used as objective molecular biomarkers of successful cures, establishing if a certain therapy is akin to a given patient (personalized medicine). Present data support the use of post-therapy molecular data obtained with non-invasive techniques.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, where differences are often present relating to the performance of motor skills. Our previous work elucidated unique event-related potential patterns of neural activity in those with ADHD when performing visuomotor and force-matching motor paradigms. The purpose of the current study was to identify whether there were unique neural sources related to somatosensory function and motor performance in those with ADHD. Source localization (sLORETA) software identified areas where neural activity differed between those with ADHD and neurotypical controls when performing a visuomotor tracing task and force-matching task. Median nerve somatosensory evoked potentials (SEPs) were elicited, while whole-head electroencephalography (EEG) was performed. sLORETA localized greater neural activity post-FMT in those with ADHD, when compared with their baseline activity (p < 0.05). Specifically, greater activity was exhibited in BA 31, precuneus, parietal lobe (MNI coordinates: X = −5, Y = −75, and Z = 20) at 156 ms post stimulation. No significant differences were found for any other comparisons. Increased activity within BA 31 in those with ADHD at post-FMT measures may reflect increased activation within the default mode network (DMN) or attentional changes, suggesting a unique neural response to the sensory processing of force and proprioceptive afferent input in those with ADHD when performing motor skills. This may have important functional implications for motor tasks dependent on similar proprioceptive afferent input.

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.

Yoga has been shown to play a role in reducing the symptoms associated with the inattentive and hyperactive-impulsive forms of attention-deficit/hyperactivity disorder (ADHD). The medical history and clinical findings for a nine-year-old patient presenting with difficulty paying attention and impulsive speech and actions at home and school are presented. After the diagnosis of combination type ADHD by assessment of DSM-5 criteria, both at home and school and through parent and teacher evaluations using National Institute for Children’s Health Quality (NICHQ) Vanderbilt Assessment Scales, the patient initiated a yoga training regimen. Six months after initiating the yoga training regimen, follow-up parent and teacher questionnaires revealed improvement in both the inattentive and hyperactive-impulsive symptoms. Literature sourced from the PubMed database to explore the efficacy of yoga for ADHD was used to support the research hypothesis that a structured yoga training regimen improves the symptoms associated with the inattentive and hyperactive-impulsive forms of ADHD, and thus, yoga is recommended as a management technique for individuals with ADHD.

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

Genome wide association meta-analysis identified ST3GAL3, a gene encoding the beta-galactosidase-alpha-2,3-sialyltransferase-III, as a risk gene for attention-deficit/hyperactivity disorder (ADHD). Although loss-of-function mutations in ST3GAL3 are implicated in non-syndromic autosomal recessive intellectual disability (NSARID) and West syndrome, the impact of ST3GAL3 haploinsufficiency on brain function and the pathophysiology of neurodevelopmental disorders (NDDs), such as ADHD, is unknown. Since St3gal3 null mutant mice display severe developmental delay and neurological deficits, we investigated the effects of partial inactivation of St3gal3 in heterozygous (HET) knockout (St3gal3±) mice on behavior as well as expression of markers linked to myelination processes and sialylation pathways. Our results reveal that male St3gal3 HET mice display cognitive deficits, while female HET animals show increased activity, as well as increased cognitive control, compared to their wildtype littermates. In addition, we observed subtle alterations in the expression of several markers implicated in oligodendrogenesis, myelin formation, and protein sialylation as well as cell adhesion/synaptic target glycoproteins of ST3GAL3 in a brain region- and/or sex-specific manner. Taken together, our findings indicate that haploinsufficiency of ST3GAL3 results in a sex-dependent alteration of cognition, behavior and markers of brain plasticity.

This study characterizes a large sample of adults with attention-deficit/hyperactivity disorder (ADHD) and healthy controls regarding their task performance and neurophysiology; cross-sectionally and longitudinally. Self-reported symptoms, behavioral measures, and event-related potentials from a classical cued Go/NoGo task were used to outline the symptom burden, executive function deficits and neurophysiological features, and the associations between these domains. The study participants (N = 210 ADHD, N = 158 controls, age: 18–62 years) were assessed five (ADHD) or three (controls) times over two years. We describe cross-sectional and longitudinal group differences, and associations between symptom burden, and behavioral and event-related potential (ERP) components variables by latent growth curve models, including random slopes and intercepts. The ADHD group showed increased reaction time variability, increased commission and omission errors, and attenuated cueP3, CNV, N2d, and P3d amplitudes. We observed a decrease in self-reported symptoms in the ADHD group over the two years. The behavioral measures (reaction time variability, number of omission, and commission errors) did not change over time, whereas the cueP3, P3d, and N2d amplitude attenuated in both groups. There was no evidence for a robust association between symptom burden and behavioral or ERP measures. The changes in the ERP components with stable task performance, potentially indicate more efficient neuronal processing over the two years. Whether the lack of association between symptom burden and behavioral or ERP measures might be due to the low reliability of the ADHD assessment criteria, or the inappropriateness of the objective measures cannot be inferred.

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 Chronic Tic Disorder (CTD), Obsessive–Compulsive Disorder (OCD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are complex neuropsychiatric disorders that frequently co-occur. The aim of this study was to examine WISC-IV performance of a clinical cohort of children with CTD, OCD and/or ADHD. Methods N = 185 children aged 6 to 17 years from Germany with CTD, OCD and/or ADHD were examined with the WISC-IV that comprises four index scores (VCI: Verbal Comprehension Index, PRI: Perceptual Reasoning Index, WMI: Working Memory Index, PSI: Processing Speed Index) and a Full Scale Intelligence Quotient (FSIQ). WISC-IV profiles of children with CTD-only, OCD-only, ADHD-only, CTD+ADHD, CTD+OCD and CTD+OCD+ADHD were compared with the WISC-IV norm (N = 1650, M = 100 and SD = 15) and among each other. Results Unpaired t-tests revealed that children with ADHD-only showed significant lower PSI scores, whereas children with CTD-only and OCD-only had significant higher VCI scores as compared to the German WISC-IV norm. One-way ANOVA revealed that children with ADHD-only showed significant lower WMI scores as compared to children with CTD+OCD. Conclusions We were able to confirm previous evidence on WISC-IV profiles in ADHD in a German clinical sample and contribute new findings on cognitive performance in children with (non-)comorbid CTD and OCD that have to be seen in light of the study’s limitations.

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.

Traballo Fin de Grao en Medicina. Curso 2020-2021 Justificación: El Metilfenidato es el tratamiento farmacológico de elección para el Trastorno por Déficit de Atención e Hiperactividad (TDAH), un trastorno del neurodesarrollo que interfiere de manera significativa con el funcionamiento normal del paciente. Múltiples estudios avalan que, independientemente de las comorbilidades, el TDAH presenta alteraciones en el procesamiento sensorial. Con el fin de lograr una mejor individualización terapéutica, este trabajo busca encontrar posibles biomarcadores farmacogenéticos y su relación con el perfil sensorial en pacientes diagnosticados de TDAH a tratamiento con Metilfenidato. Objetivos: Primero, una revisión sistemática relacionada con el perfil sensorial de pacientes diagnosticados de TDAH a tratamiento con Metilfenidato. Segundo, una revisión sistemática de biomarcadores farmacogenéticos que permitan explicar la eficacia y/o efectos adversos relacionados con el perfil sensorial en pacientes con TDAH a tratamiento con Metilfenidato. Materiales y métodos: Siguiendo la guía PRISMA, se llevaron a cabo dos revisiones sistemáticas de todos los artículos publicados entre 2000 y 2020 usando como bases de datos Pubmed, Web of Science, PsycInfo y Scopus. Resultados: Seis artículos cumplieron los criterios establecidos para la primera revisión, que tenía como objetivo estudiar el perfil sensorial en pacientes diagnosticados de TDAH a tratamiento con Metilfenidato. Dos versaban sobre el olfato, uno sobre el dolor y tres sobre el sistema vestibular. Ningún artículo cumplió los criterios de la segunda revisión sobre biomarcadores farmacogenéticos. Conclusiones: Niños y adolescentes con TDAH presentan alteraciones en el procesamiento olfativo y doloroso y peor control postural. Independientemente del dominio afectado, el Metilfenidato tiende a la normalización de las alteraciones sensoriales. No existen estudios sobre farmacogenética en población con TDAH europea que relacionen el perfil sensorial con el Metilfenidato Xustificación: O Metilfenidato é o tratamento farmacolóxico de elección para o tratamento do Trastorno por Déficit de Atención e Hiperactividade (TDAH), un trastorno do neurodesenvolvemento que interfire de maneira importante co funcionamento normal do paciente. Múltiples estudios avalan que, independentemente das comorbilidades, o TDAH presenta alteracións no procesamento sensorial. Co fin de lograr unha mellor individualización terapéutica, este traballo busca atopar posibles marcadores farmacoxenéticos e a súa relación co perfil sensorial en pacientes diagnosticados de TDAH a tratamento con Metilfenidato. Obxectivos: Primeiro, unha revisión sistemática relacionada co perfil sensorial de pacientes TDAH a tratamento con Metilfenidato. Segundo, unha revisión sistemática de biomarcadores farmacoxenéticos que permitan explicar a eficacia e /ou efectos adversos relacionados co perfil sensorial en pacientes diagnosticados de TDAH a tratamento con Metilfenidato. Materiais e métodos: Seguindo a guía PRISMA, leváronse a cabo dúas revisións sistemáticas de todos os artigos publicados entre 2000 e 2020 usando como bases de datos Pubmed, Web of Science, PyscInfo e Scopus. Resultados: Seis artigos cumpriron os criterios establecidos para a primeira revisión que tiña como obxectivo estudar o perfil sensorial en pacientes TDAH a tratamento con Metilfenidato. Dous versaban sobre o olfacto, un sobre a dor e tres sobre o sistema vestibular. Ningún artigo cumpriu os criterios da segunda revisión sobre biomacardores farmacoxenéticos. Conclusións: Nenos e adolescentes con TDAH presentan alteracións no procesamento olfativo e doloroso e peor control postural. Independentemente do dominio afecto, o Metilfendiato tende á normalización das alteracións sensoriais. Non existen estudos sobre farmacoxenética en población con TDAH europea que relacionen o perfil sensorial co Metilfenidato Introduction: Methylphenidate is the treatment of choice for Attention-Deficit/Hyperactivity Disorder (ADHD), a neurodevelopmental disorder that interferes significatly with the normal functioning of the patient. Multiple studies support that, regardless of comorbidities, ADHD shows impairments in sensory processing. Therefore, this work seeks to find pharmacogenetic biomarkers and their association with the sensory profile in ADHD patients under treatment with Methylphenidate in order to achieve a better therapeutic management. Objectives: First, a systematic review related to sensory profile of ADHD patients receiving Methylphenidate. Second, a systematic review of pharmacogenetic biomarkers that can explain the efficacy and/or adverse effects related to the sensory profile in ADHD patients receiving Methylphenidate. Methods: Following PRISMA guidelines, two systematic reviews of all published articles between 2000 and 2020 were carried out using Pubmed, Web of Science, PyscInfo and Scopus as databases. Results: Six articles met the criteria established for the first review that aimed to study the sensory profile in ADHD patients receiving Methylphenidate. Two articles were about smell, one about pain and three about vestibular system. No articles met the criteria of the second review about pharmacogenetic biomarkers. Conclusions: ADHD Children and adolescents show alterations in olfactory and painful processing and worse postural control. Regardless of the domain affected, Methylphenidate tends to normalize sensory alterations. There are no studies on genetics in the European ADHD population that relate sensory profile to Methylphenidate

Introduction: Experimental models of neuropsychiatric disorders, for example, ADHD, are used to mimic specific phenotypic traits of a complex human disorder. However, it remains unresolved to what extent the animal phenotype reflects the specific human trait. The null mutant mouse of the serotonin-synthesizing tryptophan hydroxylase-2 (Tph2(-/-)) gene has been proposed as experimental model for ADHD with high face validity for impulsive, aggressive, and anxious behaviors. To validate this ADHD-like model, we examined the Tph2(-/-) phenotype in humans when considering allelic variation of TPH2 function ("reverse phenotyping").Methods: 58 participants (6 females, 8-18 years) were examined, of whom 32 were diagnosed with ADHD. All participants were phenotyped for impulsivity, aggression, and anxiety using questionnaires, behavioral tests, and MRI scanning while performing the 4-choice serial reaction time task. Additionally, participants were genotyped for the TPH2 G-703T (rs4570625) polymorphism. To analyze the relation between TPH2 G-703T variants and the impulsive/aggressive/anxious phenotype, mediation analyses were performed using behavioral and MRI data as potential mediators.Results: We found that the relation between TPH2 G-703T and aggression as part of the reverse Tph2(-)/(-) phenotype was mediated by structure and function of the right middle and inferior frontal gyrus.Conclusion: At the example of trait aggression, our results support the assumption that the Tph2 null mutant mouse reflects the TPH2 G-703T-dependent phenotype in humans. Additionally, we conclude that "reverse phenotyping" is a promising method to validate experimental models and human findings for refined analysis of disease mechanisms.

Introduction Experimental models of neuropsychiatric disorders, for example, ADHD, are used to mimic specific phenotypic traits of a complex human disorder. However, it remains unresolved to what extent the animal phenotype reflects the specific human trait. The null mutant mouse of the serotonin‐synthesizing tryptophan hydroxylase‐2 (Tph2 ‐/‐) gene has been proposed as experimental model for ADHD with high face validity for impulsive, aggressive, and anxious behaviors. To validate this ADHD‐like model, we examined the Tph2‐/‐ phenotype in humans when considering allelic variation of TPH2 function (“reverse phenotyping”). Methods 58 participants (6 females, 8–18 years) were examined, of whom 32 were diagnosed with ADHD. All participants were phenotyped for impulsivity, aggression, and anxiety using questionnaires, behavioral tests, and MRI scanning while performing the 4‐choice serial reaction time task. Additionally, participants were genotyped for the TPH2 G‐703T (rs4570625) polymorphism. To analyze the relation between TPH2 G‐703T variants and the impulsive/aggressive/anxious phenotype, mediation analyses were performed using behavioral and MRI data as potential mediators. Results We found that the relation between TPH2 G‐703T and aggression as part of the reverse Tph2‐/‐ phenotype was mediated by structure and function of the right middle and inferior frontal gyrus. Conclusion At the example of trait aggression, our results support the assumption that the Tph2 null mutant mouse reflects the TPH2 G‐703T‐dependent phenotype in humans. Additionally, we conclude that “reverse phenotyping” is a promising method to validate experimental models and human findings for refined analysis of disease mechanisms., The Tph2‐/‐ mouse has been proposed as an experimental model for ADHD. Translation of an animal phenotype into humans to examine its face validity (reverse phenotyping). Phenotyping included impulsivity, aggression, and anxiety, reflecting comorbid conditions of ADHD. Use of the RDoC approach to address phenotype dimensions in an isolated manner.

Introduction: Experimental models of neuropsychiatric disorders, for example, ADHD, are used to mimic specific phenotypic traits of a complex human disorder. However, it remains unresolved to what extent the animal phenotype reflects the specific human trait. The null mutant mouse of the serotonin-synthesizing tryptophan hydroxylase-2 (Tph2(-/-)) gene has been proposed as experimental model for ADHD with high face validity for impulsive, aggressive, and anxious behaviors. To validate this ADHD-like model, we examined the Tph2(-/-) phenotype in humans when considering allelic variation of TPH2 function ("reverse phenotyping").Methods: 58 participants (6 females, 8-18 years) were examined, of whom 32 were diagnosed with ADHD. All participants were phenotyped for impulsivity, aggression, and anxiety using questionnaires, behavioral tests, and MRI scanning while performing the 4-choice serial reaction time task. Additionally, participants were genotyped for the TPH2 G-703T (rs4570625) polymorphism. To analyze the relation between TPH2 G-703T variants and the impulsive/aggressive/anxious phenotype, mediation analyses were performed using behavioral and MRI data as potential mediators.Results: We found that the relation between TPH2 G-703T and aggression as part of the reverse Tph2(-)/(-) phenotype was mediated by structure and function of the right middle and inferior frontal gyrus.Conclusion: At the example of trait aggression, our results support the assumption that the Tph2 null mutant mouse reflects the TPH2 G-703T-dependent phenotype in humans. Additionally, we conclude that "reverse phenotyping" is a promising method to validate experimental models and human findings for refined analysis of disease mechanisms.

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.

Genome wide association meta-analysis identified ST3GAL3, a gene encoding the beta-galactosidase-alpha-2,3-sialyltransferase-III, as a risk gene for attention-deficit/hyperactivity disorder (ADHD). Although loss-of-function mutations in ST3GAL3 are implicated in non-syndromic autosomal recessive intellectual disability (NSARID) and West syndrome, the impact of ST3GAL3 haploinsufficiency on brain function and the pathophysiology of neurodevelopmental disorders (NDDs), such as ADHD, is unknown. Since St3gal3 null mutant mice display severe developmental delay and neurological deficits, we investigated the effects of partial inactivation of St3gal3 in heterozygous (HET) knockout (St3gal3±) mice on behavior as well as expression of markers linked to myelination processes and sialylation pathways. Our results reveal that male St3gal3 HET mice display cognitive deficits, while female HET animals show increased activity, as well as increased cognitive control, compared to their wildtype littermates. In addition, we observed subtle alterations in the expression of several markers implicated in oligodendrogenesis, myelin formation, and protein sialylation as well as cell adhesion/synaptic target glycoproteins of ST3GAL3 in a brain region- and/or sex-specific manner. Taken together, our findings indicate that haploinsufficiency of ST3GAL3 results in a sex-dependent alteration of cognition, behavior and markers of brain plasticity.

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.

Neurophysiological measures of preparation and attention are often atypical in ADHD. Still, replicated findings that these measures predict which patients improve after Neurofeedback (NF), reveal neurophysiological specificity, and reflect ADHD-severity are limited. Methods We analyzed children’s preparatory (CNV) and attentional (Cue-P3) brain activity and behavioral performance during a cued Continuous Performance Task (CPT) before and after slow cortical potential (SCP)-NF or semi-active control treatment (electromyogram biofeedback). Mixed-effects models were performed with 103 participants at baseline and 77 were assessed for pre-post comparisons focusing on clinical outcome prediction, specific neurophysiological effects of NF, and associations with ADHD-severity. Results Attentional and preparatory brain activity and performance were non-specifically reduced after treatment. Preparatory activity in the SCP-NF group increased with clinical improvement. Several performance and brain activity measures predicted non-specific treatment outcome. Conclusion Specific neurophysiological effects after SCP-NF were limited to increased neural preparation associated with improvement on ADHD-subscales, but several performance and neurophysiological measures of attention predicted treatment outcome and reflected symptom severity in ADHD. The results may help to optimize treatment., Biological Psychology, 165, ISSN:0301-0511, ISSN:1873-6246

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., Brain Sciences, 11 (2)

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.

La aplicación de terapias alternativas enfocadas en dispositivos tecnológicos para el tratamiento del TDAH es una buena estrategia para el mejor aprendizaje de niños de edad escolar, ayudándolos a obtener mejoría en su capacidad de concentración con el fin de llevar a cabo sus actividades diarias de buena manera. En este artículo se presenta el desarrollo de un dispositivo basado en la lectura de señales cerebrales para mejorar la concentración. El dispositivo presenta una interfaz de usuario con 3 retos programados que representan los 3 niveles de dificultad para tratar el TDAH de forma progresiva. Se realiza el procesamiento de las señales emitiditas por el lector cerebral para obtener señales entendibles para el sistema y realizar el control de dispositivos de salida. Mediante las pruebas de funcionamiento los niños diagnosticados con TDAH obtuvieron un 20 % más de mejoría en concentración comparado a los datos iniciales antes de los retos. The application of alternative therapies focused on technological devices for the treatment of ADHD (Attention-Deficit/Hyperactivity Disorder) is the right way for school-age children's learning and motivation, improving their ability to concentrate on carrying out their daily and school activities properly. This article presents the development of tool to support therapies on ADHD subjects. The device was developed based on reading brain signals to improve concentration levels for those who use it. It features a user interface with 3 programmed challenges representing the 3 existing difficulty levels: easy, moderate, and challenging to treat ADHD progressively. Through signal processing, all the raw signals emitted by the brain reader are transformed into signals that can be understood by the system and, in this way, assign a range of the extracted signal for the control of output devices. Thanks to the results obtained after the performance tests, children diagnosed with ADHD obtained a 20% more improvement in concentration compared to the initial data before the challenges.

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.

Increased Intra-Subject Variability (ISV) is a candidate endophenotype of ADHD. ISV's relationship with response speed is highly relevant for ADHD as patients are highly variable but typically no slower than controls. This brief report addresses the relationship between variability and speed by employing dimensional analyses for differentiated performance measures, with a particular focus on the ex-Gaussian measures, across relevant ADHD studies and in young healthy adults (N = 70). For both patients with ADHD and healthy adults, we found that reaction time standard deviation and mean reaction time were strongly correlated, thus failing to dissociate, but ex-Gaussian tau (tau) shared only little variance with Gaussian mu (mu), thus dissociating slow responses (tau) from response speed or-if given-slow responding (mu). Our results highlight the utility of employing the ex-Gaussian measures to disentangle ISV and speed, particularly for ADHD data as patients make more slow responses but are not overall slower than typical controls.