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Coping with academic demands can be challenging for university students with Attention-Deficit/Hyperactivity Disorder (ADHD). Treatment can help them cope and prevent related mental health issues. The present study aimed to investigate the feasibility of a randomized controlled trial for group Cognitive Behavioural Therapy (CBT), including the use of an app for CBT homework assignments, and to explore the effects of CBT for university students with ADHD. University students (n = 36) participated in the first phase of the study, involving the design of an app to present CBT homework assignments, by evaluating prototypes of the app along with the development team. In the second phase, a pre- vs. post-test design was used. Students with ADHD (n = 7) were offered manual-based CBT once a week for 6 weeks using the app or a paper manual to do the homework, as preferred. University students who took part in the development of the app noted that they would rather use the app than a printed manual. On the other hand, participants in the CBT feasibility study preferred doing homework on paper rather than using the developed app. They all found group CBT and the key elements in the CBT manual helpful. The findings suggest that providing group CBT for university students with ADHD through 6 sessions is feasible and assessing its effects in a randomized controlled trial (RCT) is feasible. Such treatment might improve coping with ADHD symptoms and related mental health issues. Further studies on the development of an app supporting CBT are needed. Trial registration Registry name: Cognitive Behavioural Therapy for University Students with Attention-deficit Hyperactivity Disorder (ADHD). URL: https://register.clinicaltrials.gov. Registration number: NCT 04714866. [ABSTRACT FROM AUTHOR]

The genetic architecture of neurodevelopmental disorders is largely polygenic, non-specific, and pleiotropic. This complex genetic architecture makes the search for specific etiological mechanisms that contribute to neurodevelopmental risk more challenging. Monogenic disorders provide an opportunity to focus in on how well-articulated signaling pathways contribute to risk for neurodevelopmental outcomes. This paper will focus on neurofibromatosis type 1 (NF1), a rare monogenic disorder that is associated with varied neurodevelopmental outcomes. Specifically, this paper will provide a brief overview of NF1 and its phenotypic associations with autism spectrum disorder, attention-deficit/hyperactivity disorder, and specific learning disorders, describe how variation within the NF1 gene increases risk for neurodevelopmental disorders via altered Ras signaling, and provide future directions for NF1 research to help elucidate the genetic architecture of neurodevelopmental disorders in the general population. [ABSTRACT FROM AUTHOR]

Although earlier research has shown that individual differences on the spectrum of attention deficit hyperactivity disorder (ADHD) are highly heritable, emerging evidence suggests that symptoms are associated with complex interactions between genes and environmental influences. This study investigated whether a genetic predisposition [Note that the term 'genetic predisposition' was used in this manuscript to refer to an estimate based on twin modeling (an individual's score on the latent trait that resembles additive genetic influences) in the particular population being examined.] for the symptom dimensions hyperactivity and inattention determines the extent to which unique-environmental influences explain variability in these symptoms. To this purpose, we analysed a sample drawn from the Twins Early Development Study (TEDS) that consisted of item-level scores of 2168 16-year-old twin pairs who completed both the Strengths and Difficulties Questionnaire (SDQ; Goodman, in J Child Psychol Psychiatry 38:581–586, 1997) and the Strength and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN; Swanson, in Paper presented at the meeting of the American Psychological Association, Los Angeles, 1981) questionnaire. To maximize the psychometric information to measure ADHD symptoms, psychometric analyses were performed to investigate whether the items from the two questionnaires could be combined to form two longer subscales. In the estimation of genotype-environment interaction, we corrected for error variance heterogeneity in the measurement of ADHD symptoms through the application of item response theory (IRT) measurement models. A positive interaction was found for both hyperactivity (e.g., β 1 = 2.20 with 95% highest posterior density interval equal to [1.79;2.65] and effect size equal to 3.00) and inattention (e.g., β 1 = 2.16 with 95% highest posterior density interval equal to [1.56;2.79] and effect size equal to 3.07). These results indicate that unique-environmental influences were more important in creating individual differences in both hyperactivity and inattention for twins with a genetic predisposition for these symptoms than for twins without such a predisposition. [ABSTRACT FROM AUTHOR]

This paper extends the understanding of the relation between ADHD and reading comprehension, through examining how this relation differs depending on the quantile an individual falls in for each. Samples from three twin projects around the United States were used (Florida Twin Project, Colorado component of International Longitudinal Twin Study of Early Reading Development, & Western Reserve Reading and Math Projects). Phenotypic analysis using quantile regression showed relations between ADHD related behaviors and reading comprehension to be stronger in the lower quantiles of reading comprehension in two of three samples. A new method was developed extending this analysis into the bivariate genetic space. Results of this quantile genetic analysis revealed that overlapping common environmental influences accounted for a larger proportion of variance in the lower quantiles of these variables in two of three samples. Finally, in all three samples the phenotypic relation was strongest when shared environmental influences accounted for a larger proportion of the overall variance. [ABSTRACT FROM AUTHOR]

Children diagnosed with attention deficit hyperactivity disorder (ADHD) experience a variety of difficulties related to three primary symptoms: hyperactivity, inattention and impulsivity. The most common type of ADHD has a combination of all three symptom areas. These core symptoms may negatively impact the academic and social performance of children throughout their school life. The AHA (ADHD-Augmented) project focused specifically on the impact of digital technologies' intervention on literacy skills of children that participated in the pilot study and were diagnosed with ADHD prior to the intervention. Existing research has shown that augmented reality (AR) can improve academic outcomes by stimulating pupils' attention. AHA project aimed at implementing an evidence-based intervention to improve ADHD children's reading and spelling abilities through the enhancement of an existing literacy programme with AR functionality. The present paper reports preliminary findings of the pilot study aimed at evaluating the effectiveness of the AHA system in promoting the acquisition of literacy skills in a sample of children diagnosed with ADHD compared to the literacy programme as usual. Background information on the main characteristics and difficulties related to the teaching and learning process associated with children diagnosed with ADHD are first introduced; the design and methodology of the AHA project intervention are also described. The preliminary findings have shown that AHA project succeeded in delivering an AR solution within an existing online literacy programme, which integrates a set of specific technologies and supports interactive educational content, services, assessment, and feedback. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

The absence of a common understanding of attention plagues current research on the topic. Combining the findings from three domains of research on attention, this paper presents a univocal account that fits normal use of the term as well as its many associated phenomena: attention is a process of mental selection that is within the control of the subject. The role of the subject is often excluded from naturalized accounts, but this paper will be an exception to that rule. The paper aims to show how we might reinstate the subject into the act of attention, endorsing the ordinary notion that attention is a direction of the mind by the subject, rather than a mere occurrence or happening. To do so, it lays out the best work of phenomenology, psychology, and neuroscience on specifying the ordinary notion of attention and, in finding them individually wanting, combines them into a unified view that avoids the problems of each. In this way the paper presents a 'how possible' account of the ordinary notion of attention, wherein attention is enacted by a subject. [ABSTRACT FROM AUTHOR]

Comorbidity between neurodevelopmental disorders is common, especially between autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). This study aimed to detect overlapped sensory processing alterations in a sample of children and adolescents diagnosed with both ASD and ADHD. A collection of 42 standard and 8 proposed machine learning classifiers, 22 feature selection methods and 19 unbalanced classification strategies were applied on the 6 standard question groups of the Sensory Profile-2 questionnaire. The relatively low performance achieved by state-of-the-art classifiers led us to propose the feature population sum classifier, a probabilistic method based on class and feature value populations, designed for datasets where features are discrete numeric answers to questions in a questionnaire. The proposed method achieves the best kappa and accuracy, 60% and 82.5%, respectively, reaching 68% and 86.5% combined with backward sequential feature selection, with false positive and negative rates below 15%. Since the SP2 questionnaire can be filled by parents for children from three years, our prediction can alert the clinicians with an early diagnosis in order to apply early interventions. [ABSTRACT FROM AUTHOR]

Problem: Attention deficit hyperactivity disorder (ADHD) is the most commonly found neurodevelopmental condition among children with an estimated 2.5% to 9% global prevalence. While ADHD has been regarded as a lifelong condition, its early diagnosis elevates the probability of recovery and normal life for children. Despite clinical diagnosis being the primary one, substantial developments in ADHD diagnosis have been made during the past decade. Aim: Several imaging-based technologies and approaches have been presented in the existing literature including magnetic resonance imaging (MRI) and functional MRI (fMRI). In addition, the deployment of machine learning and deep learning models has paved the way for automated diagnosis of ADHD which increases both accuracy and robustness of ADHD detection. A comprehensive and systematic literature review (SLR) of imaging technologies and machine learning approaches is highly desired to comprehend the current status of such approaches concerning their potential and challenges to outline future directions. Although a substantial body of literature exists on imaging-based ADHD diagnosis, comprehensive SRL on such approaches is scarce. This SLR aims to provide a comprehensive overview of imaging-based ADHD diagnosis with emphasis on machine learning approaches, reveals their pros and cons, and provides potential future research directions thereby contributing to the scientific community to accelerate further research for ADHD diagnosis. Methods: This SRL focuses on analyzing recently published studies between 2010 and 2023. For this purpose, preferred reporting items for systematic review and meta-analyses (PRISMA) approach is performed in this study. Five eminent academic databases Web of Science, ACM, Springerlink, Elsevier, and PubMed are selected for article search. The SLR follows a systematic methodology comprising article search, selection based on inclusion and exclusion criteria, and rigorous assessment for categorization. Results: It is found that MRI and fMRI are the dominant approaches integrated with machine learning models for ADHD detection and function near-infrared spectroscopy is also adopted by a few studies. Predominantly, the ATHENA preprocessing approach is used to preprocess MRI data before model training. Due to the public availability of the ADHD-200 dataset, it is widely used in the existing literature while a few studies utilized their self-collected datasets. Machine learning models are the choice of the majority of the studies, particularly, the support vector machines model has been widely used for ADHD detection. Feature fusion is observed to be a better choice for obtaining more accurate results. Conclusion: Machine learning and deep learning models provide automated ADHD detection with better accuracy and robustness, however, such models are not generalizable and their performance varies concerning the locality of data used for experiments. In addition, the heterogeneity of data collection from various devices is a challenge, and the use of a standard device may provide better solutions. The lack of labeled data also adds difficulties to training models. Besides the use of MRI and fMRI, other novel technologies should be explored for better ADHD detection performance. [ABSTRACT FROM AUTHOR]

Air pollution stands as an environmental risk to child mental health, with proven relationships hitherto observed only in urban areas. Understanding the impact of pollution in rural settings is equally crucial. The novelty of this article lies in the study of the relationship between air pollution and behavioural and developmental disorders, attention deficit hyperactivity disorder (ADHD), anxiety, and eating disorders in children below 15 living in a rural area. The methodology combines spatio-temporal models, Bayesian inference and Compositional Data (CoDa), that make it possible to study areas with few pollution monitoring stations. Exposure to nitrogen dioxide (NO2), ozone (O3), and sulphur dioxide (SO2) is related to behavioural and development disorders, anxiety is related to particulate matter (PM10), O3 and SO2, and overall pollution is associated to ADHD and eating disorders. To sum up, like their urban counterparts, rural children are also subject to mental health risks related to air pollution, and the combination of spatio-temporal models, Bayesian inference and CoDa make it possible to relate mental health problems to pollutant concentrations in rural settings with few monitoring stations. Certain limitations persist related to misclassification of exposure to air pollutants and to the covariables available in the data sources used. [ABSTRACT FROM AUTHOR]

Children with attention-deficit hyperactivity disorder (ADHD) have difficulties in social interactions. Studying brain activity during social interactions is difficult with conventional artificial stimuli. This pioneering study examined the neural correlates of social perception in children with ADHD and matched controls using naturalistic stimuli. We presented 20 children with ADHD and 20 age-and-sex-matched controls with tailored movies featuring high- or low-level social interactions while recording electroencephalographic signals. Both groups exhibited synchronized gamma-band oscillations, but controls demonstrated greater inter-subject correlations. Additionally, the difference in inter-subject correlations between high- and low-interaction movies was significantly larger in controls compared to ADHD patients. Between 55 and 75 Hz comparing viewing high interaction movies with low interaction moves, controls had a significantly larger weighting in the right parietal lobe, while ADHD patients had a significantly smaller weighting in the left occipital lobe. These findings reveal distinct spatiotemporal neural signatures in social interaction processing among children with ADHD and controls using naturalistic stimuli. These neural markers offer potential for group differentiation and assessing intervention efficacy, advancing our understanding ADHD-related social interaction mechanisms. [ABSTRACT FROM AUTHOR]

Children born to parents with fewer years of education are more likely to have depression, anxiety, and attention-deficit hyperactivity disorder (ADHD), but it is unclear to what extent these associations are causal. We estimated the effect of parents' educational attainment on children's depressive, anxiety, and ADHD traits at age 8 years, in a sample of 40,879 Norwegian children born in 1998–2009 and their parents. We used within-family Mendelian randomization, which employs genetic variants as instrumental variables, and controlled for direct genetic effects by adjusting for children's polygenic indexes. We found little evidence that mothers' or fathers' educational attainment independently affected children's depressive, anxiety, or ADHD traits. However, children's own polygenic scores for educational attainment were independently and negatively associated with these traits. Results suggest that differences in these traits according to parents' education may reflect direct genetic effects more than genetic nurture. Consequences of social disadvantage for children's mental health may however be more visible in samples with more socioeconomic variation, or contexts with larger socioeconomic disparities than present-day Norway. Further research is required in populations with more educational and economic inequality and in other age groups. [ABSTRACT FROM AUTHOR]

Research demonstrates the important role of genetic factors in attention-deficit/hyperactivity disorder (ADHD). DNA sequencing of families provides a powerful approach for identifying de novo (spontaneous) variants, leading to the discovery of hundreds of clinically informative risk genes for other childhood neurodevelopmental disorders. This approach has yet to be extensively leveraged in ADHD. We conduct whole-exome DNA sequencing in 152 families, comprising a child with ADHD and both biological parents, and demonstrate a significant enrichment of rare and ultra-rare de novo gene-damaging mutations in ADHD cases compared to unaffected controls. Combining these results with a large independent case-control DNA sequencing cohort (3206 ADHD cases and 5002 controls), we identify lysine demethylase 5B (KDM5B) as a high-confidence risk gene for ADHD and estimate that 1057 genes contribute to ADHD risk. Using our list of genes harboring ultra-rare de novo damaging variants, we show that these genes overlap with previously reported risk genes for other neuropsychiatric conditions and are enriched in several canonical biological pathways, suggesting early neurodevelopmental underpinnings of ADHD. This work provides insight into the biology of ADHD and demonstrates the discovery potential of DNA sequencing in larger parent-child trio cohorts. Here, whole-exome DNA sequencing study of parent-child trios shows a significant enrichment of rare and ultra-rare de novo gene-damaging mutations in children with ADHD compared to unaffected controls and identifies KDM5B as a high-confidence risk gene. [ABSTRACT FROM AUTHOR]

Across vertebrates, adaptive behaviors, like feeding and avoiding predators, are linked to lateralized brain function. The presence of the behavioral manifestations of these biases are associated with increased task success. Additionally, when an individual's direction of bias aligns with the majority of the population, it is linked to social advantages. However, it remains unclear if behavioral biases in humans correlate with the same advantages. This large-scale study (N = 313–1661, analyses dependent) examines whether the strength and alignment of behavioral biases associate with cognitive and social benefits respectively in humans. To remain aligned with the animal literature, we evaluate motor-sensory biases linked to motor-sequencing and emotion detection to assess lateralization. Results reveal that moderate hand lateralization is positively associated with task success and task success is, in turn, associated with language fluency, possibly representing a cascade effect. Additionally, like other vertebrates, the majority of our human sample possess a 'standard' laterality profile (right hand bias, left visual bias). A 'reversed' profile is rare by comparison, and associates higher self-reported social difficulties and increased rate of autism and/or attention deficit hyperactivity disorder. We highlight the importance of employing a comparative theoretical framing to illuminate how and why different laterization profiles associate with diverging social and cognitive phenotypes. [ABSTRACT FROM AUTHOR]

Human endogenous retroviruses (HERVs) are repetitive elements previously implicated in major psychiatric conditions, but their role in aetiology remains unclear. Here, we perform specialised transcriptome-wide association studies that consider HERV expression quantified to precise genomic locations, using RNA sequencing and genetic data from 792 post-mortem brain samples. In Europeans, we identify 1238 HERVs with expression regulated in cis, of which 26 represent expression signals associated with psychiatric disorders, with ten being conditionally independent from neighbouring expression signals. Of these, five are additionally significant in fine-mapping analyses and thus are considered high confidence risk HERVs. These include two HERV expression signatures specific to schizophrenia risk, one shared between schizophrenia and bipolar disorder, and one specific to major depressive disorder. No robust signatures are identified for autism spectrum conditions or attention deficit hyperactivity disorder in Europeans, or for any psychiatric trait in other ancestries, although this is likely a result of relatively limited statistical power. Ultimately, our study highlights extensive HERV expression and regulation in the adult cortex, including in association with psychiatric disorder risk, therefore providing a rationale for exploring neurological HERV expression in complex neuropsychiatric traits. Duarte et al. report that common genetic variants linked to psychiatric disorders influence the regulation of ancient retroviruses integrated into the genome. This suggests ancient viruses acquired millions of years ago may have shaped modern human brain function. [ABSTRACT FROM AUTHOR]

Today, diagnosis of attention deficit hyperactivity disorder (ADHD) still primarily relies on a series of subjective evaluations that highly rely on a doctor's experiences and intuitions from diagnostic interviews and observed behavior measures. An accurate and objective diagnosis of ADHD is still a challenge and leaves much to be desired. Many children and adults are inappropriately labeled with ADHD conditions, whereas many are left undiagnosed and untreated. Recent advances in neuroimaging studies have enabled us to search for both structural (e.g., cortical thickness, brain volume) and functional (functional connectivity) abnormalities that can potentially be used as new biomarkers of ADHD. However, structural and functional characteristics of neuroimaging data, especially magnetic resonance imaging (MRI), usually generate a large number of features. With a limited sample size, traditional machine learning techniques can be problematic to discover the true characteristic features of ADHD due to the significant issues of overfitting, computational burden, and interpretability of the model. There is an urgent need of efficient approaches to identify meaningful discriminative variables from a higher dimensional feature space when sample size is small compared with the number of features. To tackle this problem, this paper proposes a novel integrated feature ranking and selection framework that utilizes normalized brain cortical thickness features extracted from MRI data to discriminate ADHD subjects against healthy controls. The proposed framework combines information theoretic criteria and the least absolute shrinkage and selection operator (Lasso) method into a two-step feature selection process which is capable of selecting a sparse model while preserving the most informative features. The experimental results showed that the proposed framework generated the highest/comparable ADHD prediction accuracy compared with the state-of-the-art feature selection approaches with minimum number of features in the final model. The selected regions of interest in our model were consistent with recent brain-behavior studies of ADHD development, and thus confirmed the validity of the selected features by the proposed approach. [ABSTRACT FROM AUTHOR]

We analyze networks of functional correlations between brain regions to identify changes in their structure caused by Attention Deficit Hyperactivity Disorder (adhd). We express the task for finding changes as a network anomaly detection problem on temporal networks. We propose the use of a curvature measure based on the Forman–Ricci curvature, which expresses higher-order correlations among two connected nodes. Our theoretical result on comparing this Forman–Ricci curvature with another well-known notion of network curvature, namely the Ollivier–Ricci curvature, lends further justification to the assertions that these two notions of network curvatures are not well correlated and therefore one of these curvature measures cannot be used as an universal substitute for the other measure. Our experimental results indicate nine critical edges whose curvature differs dramatically in brains of adhd patients compared to healthy brains. The importance of these edges is supported by existing neuroscience evidence. We demonstrate that comparative analysis of curvature identifies changes that more traditional approaches, for example analysis of edge weights, would not be able to identify. [ABSTRACT FROM AUTHOR]

Background: Overactivity is prevalent in several rare genetic neurodevelopmental syndromes, including Smith-Magenis syndrome, Angelman syndrome, and tuberous sclerosis complex, although has been predominantly assessed using questionnaire techniques. Threats to the precision and validity of questionnaire data may undermine existing insights into this behaviour. Previous research indicates objective measures, namely actigraphy, can effectively differentiate non-overactive children from those with attention-deficit hyperactivity disorder. This study is the first to examine the sensitivity of actigraphy to overactivity across rare genetic syndromes associated with intellectual disability, through comparisons with typically-developing peers and questionnaire overactivity estimates. Methods: A secondary analysis of actigraphy data and overactivity estimates from The Activity Questionnaire (TAQ) was conducted for children aged 4-15 years with Smith-Magenis syndrome (N=20), Angelman syndrome (N=26), tuberous sclerosis complex (N=16), and typically-developing children (N=61). Actigraphy data were summarized using the M10 non-parametric circadian rhythm variable, and 24-hour activity profiles were modelled via functional linear modelling. Associations between actigraphy data and TAQ overactivity estimates were explored. Differences in actigraphy-defined activity were also examined between syndrome and typically-developing groups, and between children with high and low TAQ overactivity scores within syndromes. Results: M10 and TAQ overactivity scores were strongly positively correlated for children with Angelman syndrome and Smith-Magenis syndrome. M10 did not substantially differ between the syndrome and typically-developing groups. Higher early morning activity and lower evening activity was observed across all syndrome groups relative to typically-developing peers. High and low TAQ group comparisons revealed syndrome-specific profiles of overactivity, persisting throughout the day in Angelman syndrome, occurring during the early morning and early afternoon in Smith-Magenis syndrome, and manifesting briefly in the evening in tuberous sclerosis complex. Discussion: These findings provide some support for the sensitivity of actigraphy to overactivity in children with rare genetic syndromes, and offer syndrome-specific temporal descriptions of overactivity. The findings advance existing descriptions of overactivity, provided by questionnaire techniques, in children with rare genetic syndromes and have implications for the measurement of overactivity. Future studies should examine the impact of syndrome-related characteristics on actigraphy-defined activity and overactivity estimates from actigraphy and questionnaire techniques. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA) plays a crucial role in the central nervous system as an inhibitory neurotransmitter. Imbalances of this neurotransmitter are associated with neurological diseases, such as Alzheimer's and Parkinson's disease, and psychological disorders, including anxiety, depression, and stress. Since GABA has long been believed to not cross the blood–brain barrier, the effects of circulating GABA on the brain are neglected. However, emerging evidence has demonstrated that changes in both circulating and brain levels of GABA are associated with changes in gut microbiota composition and that changes in GABA levels and microbiota composition play a role in modulating mental health. This recent research has raised the possibility that GABA may be a potent mediator of the gut–brain axis. This review article will cover up-to-date information about GABA-producing microorganisms isolated from human gut and food sources, explanation why those microorganisms produce GABA, food factors inducing gut–GABA production, evidence suggesting GABA as a mediator linking between gut microbiota and mental health, including anxiety, depression, stress, epilepsy, autism spectrum disorder, and attention deficit hyperactivity disorder, and novel information regarding homocarnosine-a predominant brain peptide that is a putative downstream mediator of GABA in regulating brain functions. This review will help us to understand how the gut microbiota and GABA-homocarnosine metabolism play a significant role in brain functions. Nonetheless, it could support further research on the use of GABA production-inducing microorganisms and food factors as agents to treat neurological and psychological disorders. [ABSTRACT FROM AUTHOR]

Organisms must regulate their behavior flexibly in the face of environmental challenges. Failure can lead to a host of maladaptive behavioral traits associated with a range of neuropsychiatric disorders, including attention deficit hyperactivity disorder, autism, and substance use disorders. This maladaptive dysregulation of behavior is influenced by genetic and environmental factors. For example, environmental enrichment produces beneficial neurobehavioral effects in animal models of such disorders. The present study determined the effects of environmental enrichment on a range of measures related to behavioral regulation using a large cohort of male, outbred heterogeneous stock (HS) rats as subjects. Subjects were reared from late adolescence onwards either in pairs in standard housing with minimal enrichment (n = 200) or in groups of 16 in a highly enriched environment consisting of a large multi-level cage filled with toys, running wheels, and shelters (n = 64). Rats were subjected to a battery of tests, including: (i) locomotor response to novelty, (ii) light reinforcement, (iii) social reinforcement, (iv) reaction time, (v) a patch-depletion foraging test, (vi) Pavlovian conditioned approach, (vii) conditioned reinforcement, and (viii) cocaine conditioned cue preference. Results indicated that rats housed in the enriched environment were able to filter out irrelevant stimuli more effectively and thereby regulate their behavior more efficiently than standard-housing rats. The dramatic impact of environmental enrichment suggests that behavioral studies using standard housing conditions may not generalize to more complex environments that may be more ethologically relevant. [ABSTRACT FROM AUTHOR]

With the growing concern for the issues and problems associated with static testing, dynamic assessment (DA) has been recently receiving increased attention as an alternative in educational settings. The present single case study attempted to investigate the potential of interactionist dynamic assessment in developing an Attention Deficit Hyperactivity Disorder (ADHD) L2 learner's reading competence and selective attention. A 13-year-old female EFL learner with the combined type of ADHD voluntarily participated in this study. During the DA sessions, the learner read some short passages and answered the questions through mediations emerging from the interactions between the mediator and the learner. The qualitative analysis of DA protocols led to the development of an inventory of different forms of implicit and explicit mediations. Moreover, the quantitative analysis of the data showed that DA contributed to the learner's reading comprehension and some congruent parameters of selective attention. The results of the present study call for teachers', policymakers', and material developers' increasing attention to the mediations required to assist ADHD L2 learner's independence from the mediator, which demonstrates self-regulation. [ABSTRACT FROM AUTHOR]

Background: To assess the effectiveness, safety, and tolerability of anti-Alzheimer agents (memantine, galantamine, rivastigmine, and donepezil) in controlling ADHD symptoms in children, adolescents, and adults. Methods: Following the PRISMA guideline, clinical trials assessing the potency of anti-Alzheimer medications in managing ADHD symptoms were imported from PubMed, Web of Science, and Scopus (until February 2023). Screening stages were conducted by two independent researchers. Two independent researchers also extracted data from clinical trials reporting the outcomes as the reduction in scores of ADHD questionnaires. The risk of bias within the included studies was assessed using the Cochrane Collaboration tool, while the certainty of outcomes was evaluated based on the GRADE criteria. Results: Of the initial 1597 studies, 11 studies were included. No studies were available for rivastigmine, and only a single study was conducted for galantamine. The results of the other two medications had a slight inconsistency. While both memantine and donepezil were reported to be effective in several studies, they were reported to be ineffective in some other studies. Side effects were mostly reduced appetite and headache. The tolerability of memantine, donepezil, and galantamine was all convincing. Conclusions: While galantamine did not demonstrate a promising efficacy in ADHD, memantine and donepezil showed effectiveness. However, future studies are needed to confirm their efficacy in ADHD since there was some inconsistency. [ABSTRACT FROM AUTHOR]

Members of the lay public are turning increasingly to the internet to answer health-related questions. Some authors suggest that the widespread availability of online health information has dislodged medical knowledge from its traditional institutional base and enabled a growing role for alternative or previously unrecognized health perspectives and 'lay health expertise'. Others have argued, however, that the organization of information retrieved from influential search engines, particularly Google, has merely intensified mainstream perspectives because of the growing consolidation of the internet with traditional, commercial media sources. In this paper we describe an analysis of 'first page' results retrieved through Google searches about several common health concerns, each of which has been the subject of controversy as a result of uncertain aetiology, diagnoses, outcomes and/or contested approaches to treatment. Our findings suggest that the online search tactics used by most lay health information seekers produce sources of information that, for the most part, reflect mainstream biomedical discourses, often linked to commercial interests, rather than a plurality of voices that offer a variety of perspectives and resources. We discuss the implications for health-interested internet searchers who fail to look beyond the 'first page'. [ABSTRACT FROM AUTHOR]

Attention deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders with a worldwide prevalence around 4–5% in children and 1–4% in adults. Although ADHD is highly heritable and familial risk may contribute most strongly to the persistent form of the disorder, there are few studies on the genetics of ADHD in adults. In this paper, we present the first results of the International Multicentre Persistent ADHD Genetics CollaboraTion (IMpACT) that has been set up with the goal of performing research into the genetics of persistent ADHD. In this study, we carried out a combined analysis as well as a meta-analysis of the association of the SLC6A3/DAT1 gene with persistent ADHD in 1440 patients and 1769 controls from IMpACT and an earlier report. DAT1, encoding the dopamine transporter, is one of the most frequently studied genes in ADHD, though results have been inconsistent. A variable number tandem repeat polymorphism (VNTR) in the 3′-untranslated region (UTR) of the gene and, more recently, a haplotype of this VNTR with another VNTR in intron 8 have been the target of most studies. Although the 10/10 genotype of the 3′-UTR VNTR and the 10-6 haplotype of the two VNTRs are thought to be risk factors for ADHD in children, we found the 9/9 genotype and the 9-6 haplotype associated with persistent ADHD. In conclusion, a differential association of DAT1 with ADHD in children and in adults might help explain the inconsistencies observed in earlier association studies. However, the data might also imply that DAT1 has a modulatory rather than causative role in ADHD. [ABSTRACT FROM AUTHOR]

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Attention-deficit/hyperactivity disorder, ADHD, is a common and highly heritable neuropsychiatric disorder that is seen in children and adults. Although heritability is estimated at around 76%, it has been hard to find genes underlying the disorder. ADHD is a multifactorial disorder, in which many genes, all with a small effect, are thought to cause the disorder in the presence of unfavorable environmental conditions. Whole genome linkage analyses have not yet lead to the identification of genes for ADHD, and results of candidate gene-based association studies have been able to explain only a tiny part of the genetic contribution to disease, either. A novel way of performing hypothesis-free analysis of the genome suitable for the identification of disease risk genes of considerably smaller effect is the genome-wide association study (GWAS). So far, five GWAS have been performed on the diagnosis of ADHD and related phenotypes. Four of these are based on a sample set of 958 parent-child trio's collected as part of the International Multicentre ADHD Genetics (IMAGE) study and genotyped with funds from the Genetic Association Information Network (GAIN). The other is a pooled GWAS including adult patients with ADHD and controls. None of the papers reports any associations that are formally genome-wide significant after correction for multiple testing. There is also very limited overlap between studies, apart from an association with CDH13, which is reported in three of the studies. Little evidence supports an important role for the 'classic' ADHD genes, with possible exceptions for SLC9A9, NOS1 and CNR1. There is extensive overlap with findings from other psychiatric disorders. Though not genome-wide significant, findings from the individual studies converge to paint an interesting picture: whereas little evidence--as yet--points to a direct involvement of neurotransmitters (at least the classic dopaminergic, noradrenergic and serotonergic pathways) or regulators of neurotransmission, some suggestions are found for involvement of 'new' neurotransmission and cell-cell communication systems. A potential involvement of potassium channel subunits and regulators warrants further investigation. More basic processes also seem involved in ADHD, like cell division, adhesion (especially via cadherin and integrin systems), neuronal migration, and neuronal plasticity, as well as related transcription, cell polarity and extracellular matrix regulation, and cytoskeletal remodeling processes. In conclusion, the GWAS performed so far in ADHD, though far from conclusive, provide a first glimpse at genes for the disorder. Many more (much larger studies) will be needed. For this, collaboration between researchers as well as standardized protocols for phenotyping and DNA-collection will become increasingly important. [ABSTRACT FROM AUTHOR]

This paper outlines methodological challenges encountered in producing an independent economic evaluation for the National Institute for Health and Clinical Excellence (NICE) to inform its technology appraisal process. The analysis used to highlight these challenges is a recent evaluation of pharmacological treatments for attention deficit hyperactivity disorder (ADHD). The NICE reference case for economic evaluation is compared with the methods necessary to complete an evaluation given the evidence base for ADHD. The primary analysis deviated from NICE methods guidelines most noticeably in the time horizon. Identifying appropriate utility data was challenging, and the results were sensitive to the values used. Issues found in this evaluation are common to many technology appraisals. Although challenging to undertake, economic evaluation in disease areas such as ADHD has great potential to add value, making the limitations of the data explicit, combining available evidence in a systematic and transparent framework and identifying future research needs. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are more common in boys than girls. In this paper, we investigated whether the prevalence differences are attributable to measurement bias. In addition, we examined sex differences in the genetic and environmental influences on variation in these behaviors. Teachers completed the Conners Teacher Rating Scale-Revised:Short version (CTRS-R:S) in a sample of 800 male and 851 female 7-year-old Dutch twins. No sex differences in the factor structure of the CTRS-R:S were found, implying the absence of measurement bias. The heritabilities for both ADHD and ODD were high and were the same in boys and girls. However, partly different genes are expressed in boys and girls. [ABSTRACT FROM AUTHOR]

This paper examines the role of Working Memory (WM) in developmental reading problems, considering: 1) The operationalization of WM; 2) The unique contribution of WM to reading; 3) Domain-general or -specific explanations of decoding and reading comprehension deficits; and 4) The capacity of WM constructs to distinguish between reading disabilities and attention-deficit/hyperactivity disorder (ADHD). It is concluded that: 1) Significant problems operationalizing working memory measures remain; 2) No clear unique role for WM is evident in longitudinal studies of reading acquisition; 3) Existing evidence concerning the domain-specificity or generality of WM problems is hard to interpret given problems in identification and sampling of poor readers and operationalization of WM constructs; 4) Further work is required to specify the nature of WM problems in samples of poor readers, as distinct from other co-occurring problems such as ADHD. Additional research is suggested to address these issues more fully. [ABSTRACT FROM AUTHOR]

Recent animal research suggests that brain-derived neurotrophic factor ( BDNF), may mediate response to different environmental stimuli. In this paper, we evaluated the possible role of BDNF as a moderator of attention deficit hyperactivity disorder (ADHD) in the context of different socioeconomic classes. We genotyped ten single nucleotide polymorphisms (SNPs) in and around BDNF in 229 families and evaluate whether there are SNP-by-socioeconomic status (SES) interactions for attention deficit hyperactivity. We developed three quantitative phenotypes for ADHD from nine inattentive and nine hyperactive-impulsive symptoms that were used in SNP-by-SES interaction analyses using a new methodology implemented in the computer program PBAT. Findings were adjusted for multiple comparisons using the false discovery rate. We found multiple significant SNP-by-SES interactions using the inattentive symptom count. This study suggests that different SES classes may modify the effect of the functional variant(s) in and around BDNF to have an impact on the number of ADHD symptom counts that are observed. The two exons within BDNF represent potential functional variants that may be causing the observed associations. [ABSTRACT FROM AUTHOR]

The synaptosomal-associated protein of 25 kDa gene (SNAP25) has been suggested as a genetic susceptibility factor in attention-deficit hyperactivity disorder (ADHD) based on the mouse strain coloboma. This strain is hemizygous for the SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but not to methylphenidate. Previously, we reported association of SNAP25 and ADHD using two polymorphisms. To further investigate this gene, we screened the exons for DNA variation and genotyped ten additional polymorphisms in an expanded sample of families from Toronto and a second sample of families collected in Irvine, CA. Significant results were observed in the Toronto sample for four markers, although not in the Irvine sample. The paper discusses the possible influence of the selection criteria on these differential results. The Irvine sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25. Our findings continue to support SNAP25 in the susceptibility to ADHD.Molecular Psychiatry (2005) 10, 998–1005. doi:10.1038/sj.mp.4001722; published online 9 August 2005 [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed disorders in school-aged children and is usually treated with stimulant medications, including methylphenidate (MPH; Ritalin®, Ritalin-LA®, Concerta®, Metadate®, or Focalin®) and other drug compounds (e.g., Adderall®, Adderall-XR®, or Dexedrine). Assessment of school behavior and performance is a critical component in determining the safety and efficacy of these medications. This paper reviews methodological issues in assessing drug effects in school settings by considering features of the independent variable (the medication), the dependent variables (the endpoints selected for assessment), and the design (the structure of the assessment). In addition, we consider recent conceptual advances in understanding the behavioral mechanisms of action of drugs used to treat ADHD that may influence the structure and interpretation of medication assessments. [ABSTRACT FROM AUTHOR]

Attention-deficit hyperactivity disorder (ADHD) is the most common childhood psychiatric disorder, affecting 5–10% of school-age children. Although the biological basis of this disorder is unknown, twin and family studies provide strong evidence that ADHD has a genetic basis involving multiple genes. A previous study found an association between ADHD and two polymorphisms in the 3' untranslated region (UTR) of SNAP-25, a gene encoding a synaptic vesicle docking protein known to play a role in the hyperactivity observed in the Coloboma mouse strain. In this paper, we test biased transmission of the 3' UTR SNAP-25 haplotype using a larger ADHD sample of 113 families with 207 affected children. Using the transmission disequilibrium test (TDT), we found a trend consistent with biased transmission of the TC haplotype of SNAP-25 in all transmissions and detected a significant distortion (P = 0.027) when paternal transmissions were evaluated. Molecular Psychiatry (2003) 8, 309–315. doi:10.1038/sj.mp.4001247. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to assess the effectiveness of serotonin-norepinephrine reuptake inhibitors (SNRIs) in managing ADHD symptoms compared to placebo, stimulants, or compared as pre- and post-treatment. Methods: Clinical trials assessing the potency of SNRIs in treating ADHD patients were imported from PubMed, Web of Science, and Scopus (until February 2023). Data were extracted by two independent researchers. Random- and fixed- effect meta-analysis was performed to pool the data. Publication bias and study heterogeneity were assessed. The Cochrane Collaboration tool was utilized to determine the risk of bias. The certainty of outcomes was evaluated by the Grade criteria. Results: Of the initial 830 studies, 13 were finally imported after two screening stages which two separate researchers carried out. The pooled standardized mean difference (95% CI) of reducing the score of different ADHD questionnaires (showing reduction in total inattentive and hyperactivity/impulsivity symptoms) by SNRIs, venlafaxine, and duloxetine were − 2.20 [− 3.00, − 1.40], − 1.86 [− 2.69, − 1.02], − 2.65 [− 3.35, − 1.96], respectively. While the most reported side effects were nausea, abdominal pain, and sedation, all studies reported that side effects were not serious and were well tolerated. Outcomes for the effectiveness of venlafaxine and duloxetine got high and moderate certainty, respectively. Conclusions: Duloxetine and venlafaxine can be administered to treat symptoms of ADHD while being well tolerated. It seems that duloxetine is more potent in reducing ADHD symptoms. It can also be concluded that venlafaxine is more effective in females, and is more effective on inattentive symptoms of ADHD rather than hyperactive symptoms. [ABSTRACT FROM AUTHOR]

To examine the relationship between adverse childhood experiences (ACEs) and Attention-deficit Hyperactivity Disorder (ADHD) among college students. We investigated the association between ACEs and ADHD symptoms among French college students enrolled in the i-Share cohort using multivariate logistic regression models. The sample comprised of 1062 participants with a mean age of 20.3 (SD = 2.3) of which 30.6% had no ACEs exposure, 29.6% had 1 ACE, 19.2% had 2 ACEs, and 20.6% had ≥ 3 ACEs. After controlling for potential confounders, every increase in ACE exposure heightened the risk of ADHD symptoms with the respective adjusted Odds Ratios and 95% confidence intervals: 1 ACE: 2.1 (0.7–6.3) / 2 ACEs: 4.5 (2.6–12.8)/ ≥ 3 ACEs: 5.2 (1.8–14.8). Estimates for ADHD symptoms were higher with sexual abuse, emotional and physical neglect, and bullying. Findings suggest that ACEs heighten the risk for developing ADHD symptoms among college students and bear important implications for prevention and clinical practice. [ABSTRACT FROM AUTHOR]

Although the pharmacological therapy of ADHD has been widely studied, little has been done to compare the different therapeutic approaches (e.g., drug therapy vs. psychological treatments) and even less has been done to compare the outcome of the therapy between centers. This multicenter observational study aims to assess between-center variation in functional outcome of ADHD patients one year after the diagnosis, according to the treatment received. We used the Regional ADHD Registry data on 1429 patients enrolled in 16 ADHD centers in the 2011–2022 period. To evaluate the effectiveness of the therapy we used a generalized linear mixed model with the center as the random effect, including patient condition at diagnosis and center characteristics, weighting by the inverse of the propensity score of the treatment received by the patient. Between-center variation was expressed as the relative difference in odds-ratios between the observed and the expected number of patients whose condition improved, using the Clinical Global Impressions—Improvement Scale (CGI-I), and the relative 95% CI. Patients who received combined treatment were significantly more likely to improve compared to other treatment groups (65.5% vs 54.4% for methylphenidate alone, 53.4% for psychological treatment alone, or 40.5% for no therapy). Adjusted for patients and center characteristics, the log-odds ratio ranged from 0.85 (0.29–1.55 95% CI) to − 0.64 (− 1.17–− 0.18 95% CI). The mean expected probability of improvement after one year of therapy for an average patient with ADHD for each center was 47.7% in a center at the 25th percentile and 61.2% in a center at the 75th percentile of the outcome distribution after adjustments. The wide between-center variation in patient functional improvement one year after the diagnosis of ADHD could be largely explained by center-specific therapeutic approaches or attitudes. More careful and stringent work is needed to reduce differences in responses between centers, as could formal and periodic audit programs within and between centers. [ABSTRACT FROM AUTHOR]

Childhood anxiety and depressive symptoms may be influenced by symptoms of attention deficit/hyperactivity disorder (ADHD). We investigated whether parent- and teacher-reported anxiety, depressive and ADHD symptoms at age 3 years predicted anxiety disorders and/or depression in children with and without ADHD at age 8 years. This study is part of the longitudinal, population-based Norwegian Mother, Father and Child Cohort Study. Parents of 3-year-olds were interviewed, and preschool teachers rated symptoms of anxiety disorders, depression and ADHD. At age 8 years (n = 783), Child Symptom Inventory-4 was used to identify children who fulfilled the diagnostic criteria for anxiety disorders and/or depression (hereinafter: Anx/Dep), and ADHD. Univariable and multivariable logistic regression analyses were used. In the univariable analyses, parent-reported anxiety, depressive and ADHD symptoms, and teacher-reported anxiety symptoms at age 3 years all significantly predicted subsequent Anx/Dep. In the multivariable analyses, including co-occurring symptoms at age 3 years and ADHD at 8 years, parent-reported anxiety and depressive symptoms remained significant predictors of subsequent Anx/Dep. At age 3 years, regardless of ADHD symptoms being present, asking parents about anxiety and depressive symptoms, and teachers about anxiety symptoms, may be important to identify children at risk for school-age anxiety disorders and/or depression. [ABSTRACT FROM AUTHOR]

Background: Attention-Deficit / Hyperactivity Disorder (ADHD) is prevalent at a higher rate in correctional settings than in the general population. Treatment of ADHD in this environment is challenging as stimulants, the most common treatment for ADHD, require cautious prescribing in the context of frequent substance use disorders (SUD) and diversion in the institutional setting. In addition, both pharmacological and non-pharmacological treatment approaches require significant staff resources. The aim of this scoping review is to map and summarize all literature addressing treatment of ADHD specifically in correctional settings, synthesize the evidence supporting various approaches, and highlight areas for future research. Due to the limited number of primary research studies addressing this question directly, we chose a scoping review methodology that would allow us to explore what kinds of studies and literature exist and include all types of articles directly related to our question. Results: Five-hundred sixty-five relevant articles were screened. Thirty-two articles were included in the final review. Eleven of the articles reported primary research. Five of these articles were based on three randomized controlled trials. Among randomized controlled trials on the effect of stimulants, inclusion criteria, outcome measures and effectiveness varied widely. Non-male and non-white populations were under-represented. Among review articles and recommendations opinion was inconsistent, with some recommending stimulants as first-line treatment and others recommending they be avoided altogether. The effect of non-stimulant medications was examined in 2 small studies. The only non-pharmacological treatment examined was dialectical behavior therapy, and only feasibility was reported. Four articles provided practice recommendations from consensus or expert opinion. Two of these recommended stimulants as first-line treatment, and two recommended stimulants as treatment of last resort. Conclusions: We found a diverse but shallow literature addressing our research question. Primary research in the corrections setting is limited and varies in inclusion criteria, outcomes studied, and effectiveness. Recommendations on treatment are inconsistent. Future research should address methods of diagnosis, the role of non-stimulants, non-pharmacological interventions, non-male and non-white people who are incarcerated (PWAI), and effects of treatment method on patients, staff and other PWAI. Better research and guidance on treating ADHD has potential to improve health of PWAI, the institutional environment, and resource utilization. [ABSTRACT FROM AUTHOR]

The predictive performance of polygenic scores (PGS) is largely dependent on the number of samples available to train the PGS. Increasing the sample size for a specific phenotype is expensive and takes time, but this sample size can be effectively increased by using genetically correlated phenotypes. We propose a framework to generate multi-PGS from thousands of publicly available genome-wide association studies (GWAS) with no need to individually select the most relevant ones. In this study, the multi-PGS framework increases prediction accuracy over single PGS for all included psychiatric disorders and other available outcomes, with prediction R2 increases of up to 9-fold for attention-deficit/hyperactivity disorder compared to a single PGS. We also generate multi-PGS for phenotypes without an existing GWAS and for case-case predictions. We benchmark the multi-PGS framework against other methods and highlight its potential application to new emerging biobanks. Polygenic scores (PGS) have high potential for clinical use but are currently underpowered for many applications. Here, the authors develop an approach that leverages an agnostic library of hundreds of PGS to increase prediction of complex diseases and other traits. This multi-PGS framework is ideal for emerging biobank data. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21566-w [ABSTRACT FROM AUTHOR]

Functional impairments in cognition are frequently thought to be a feature of individuals with depression or anxiety. However, documented impairments are both broad and inconsistent, with little known about when they emerge, whether they are causes or effects of affective symptoms, or whether specific cognitive systems are implicated. Here, we show, in the adolescent ABCD cohort (N = 11,876), that attention dysregulation is a robust factor underlying wide-ranging cognitive task impairments seen in adolescents with moderate to severe anxiety or low mood. We stratified individuals high in DSM-oriented depression or anxiety symptomology, and low in attention deficit hyperactivity disorder (ADHD), as well as vice versa – demonstrating that those high in depression or anxiety dimensions but low in ADHD symptoms not only exhibited normal task performance across several commonly studied cognitive paradigms, but out-performed controls in several domains, as well as in those low in both dimensions. Similarly, we showed that there were no associations between psychopathological dimensions and performance on an extensive cognitive battery after controlling for attention dysregulation. Further, corroborating previous research, the co-occurrence of attention dysregulation was associated with a wide range of other adverse outcomes, psychopathological features, and executive functioning (EF) impairments. To assess how attention dysregulation relates to and generates diverse psychopathology, we performed confirmatory and exploratory network analysis with different analytic approaches using Gaussian Graphical Models and Directed Acyclic Graphs to examine interactions between ADHD, anxiety, low mood, oppositional defiant disorder (ODD), social relationships, and cognition. Confirmatory centrality analysis indicated that features of attention dysregulation were indeed central and robustly connected to a wide range of psychopathological traits across different categories, scales, and time points. Exploratory network analysis indicated potentially important bridging traits and socioenvironmental influences in the relationships between ADHD symptoms and mood/anxiety disorders. Trait perfectionism was uniquely associated with both better cognitive performance and broad psychopathological dimensions. This work suggests that attentional dysregulation may moderate the breadth of EF, fluid, and crystalized cognitive task outcomes seen in adolescents with anxiety and low mood, and may be central to disparate pathological features, and thus a target for attenuating wide-ranging negative developmental outcomes. [ABSTRACT FROM AUTHOR]

Background: Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic associations implicated by rare recurrent copy number variations (CNVs). Both of these NDDs have been shown to share similar biological etiologies as well as genetic pleiotropy. Methods: Platforms aimed at investigating genetic-based associations, such as high-density microarray technologies, have been groundbreaking techniques in the field of complex diseases, aimed at elucidating the underlying disease biology. Previous studies have uncovered CNVs associated with genes within shared candidate genomic networks, including glutamate receptor genes, across multiple different NDDs. To examine shared biological pathways across two of the most common NDDs, we investigated CNVs across 15,689 individuals with ADHD (n = 7920), ASD (n = 4318), or both (n = 3,416), as well as 19,993 controls. Cases and controls were matched by genotype array (i.e., Illumina array versions). Three case–control association studies each calculated and compared the observed vs. expected frequency of CNVs across individual genes, loci, pathways, and gene networks. Quality control measures of confidence in CNV-calling, prior to association analyses, included visual inspection of genotype and hybridization intensity. Results: Here, we report results from CNV analysis in search for individual genes, loci, pathways, and gene networks. To extend our previous observations implicating a key role of the metabotropic glutamate receptor (mGluR) network in both ADHD and autism, we exhaustively queried patients with ASD and/or ADHD for CNVs associated with the 273 genomic regions of interest within the mGluR gene network (genes with one or two degrees protein–protein interaction with mGluR 1–8 genes). Among CNVs in mGluR network genes, we uncovered CNTN4 deletions enriched in NDD cases (P = 3.22E − 26, OR = 2.49). Additionally, we uncovered PRLHR deletions in 40 ADHD cases and 12 controls (P = 5.26E − 13, OR = 8.45) as well as clinically diagnostic relevant 22q11.2 duplications and 16p11.2 duplications in 23 ADHD + ASD cases and 9 controls (P = 4.08E − 13, OR = 15.05) and 22q11.2 duplications in 34 ADHD + ASD cases and 51 controls (P = 9.21E − 9, OR = 3.93); those control samples were not with previous 22qDS diagnosis in their EHR records. Conclusion: Together, these results suggest that disruption in neuronal cell-adhesion pathways confers significant risk to NDDs and showcase that rare recurrent CNVs in CNTN4, 22q11.2, and 16p11.2 are overrepresented in NDDs that constitute patients predominantly suffering from ADHD and ASD. Trial registration: ClinicalTrials.gov Identifier: NCT02286817 First Posted: 10 November 14, ClinicalTrials.gov Identifier: NCT02777931 first posted: 19 May 2016, ClinicalTrials.gov Identifier: NCT03006367 first posted: 30 December 2016, ClinicalTrials.gov Identifier: NCT02895906 first posted: 12 September 2016. [ABSTRACT FROM AUTHOR]

Carriers of a premutation allele (PM) in the FMR1 gene are at risk of developing a number of Fragile X premutation asssociated disorders (FXPAC), including Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), Fragile X-associated Primary Ovarian Insufficiency (FXPOI), and Fragile X-associated neuropsychiatric disorders (FXAND). We have recently reported somatic CGG allele expansion in female PM; however, its clinical significance remains unclear. The aim of this study was to examine the potential clinical association between somatic FMR1 allele instability and PM associated disorders. Participants comprised of 424 female PM carriers age 0.3– 90 years. FMR1 molecular measures and clinical information on the presence of medical conditions, were determined for all subjects for primary analysis. Two sub-groups of participants (age ≥ 25, N = 377 and age ≥ 50, N = 134) were used in the analysis related to presence of FXPOI and FXTAS, respectively. Among all participants (N = 424), the degree of instability (expansion) was significantly higher (median 2.5 vs 2.0, P = 0.026) in participants with a diagnosis of attention deficit hyperactivity disorder (ADHD) compared to those without. FMR1 mRNA expression was significantly higher in subjects with any psychiatric disorder diagnosis (P = 0.0017); specifically, in those with ADHD (P = 0.009), and with depression (P = 0.025). Somatic FMR1 expansion was associated with the presence of ADHD in female PM and FMR1 mRNA levels were associated with the presence of mental health disorders. The findings of our research are innovative as they suggest a potential role of the CGG expansion in the clinical phenotype of PM and may potentially guide clinical prognosis and management. [ABSTRACT FROM AUTHOR]

Attention-Deficit/Hyperactivity Disorder (ADHD) is young children's most common mental health disorder. We aim to provide causal estimates of the differential costs for the non-adult population with ADHD. We used longitudinal administrative data covering the non-adult population over five years and different healthcare providers (general practitioners, hospitalisations and emergency departments, visits to mental healthcare centres—day-care or hospitals) of 1,101,215 individuals in Catalonia (Spain). We also include the consumption of pharmaceuticals and cognitive therapies. We instrumented ADHD diagnosis by the probability of being diagnosed by the most visited healthcare provider based on individual monthly visits to the provider in which this visit was related to ADHD and the density of professionals in the different mental health providers. After using matching procedures to include a proper control group, we estimated two-part and finite mixture models. Our results indicate that ADHD children and adolescents displayed 610€ higher annual health direct costs compared to not diagnosed counterparts. We provide average costs disentangling the sample by age boundaries, gender, and comorbidities to offer values for cost-effective analyses and incremental costs after diagnosis, which is around 400€. A significant differential annual direct health cost for the non-adult population with ADHD is determined, which will be helpful for cost-effectiveness analysis and complete cost-of-illness studies. [ABSTRACT FROM AUTHOR]

Chronic pain and attention-deficit hyperactivity disorder (ADHD) frequently coexist. However, the common pathology is still unclear. Attenuated noradrenergic endogenous analgesia can produce acute pain chronification, and dysfunction of noradrenergic systems in the nervous system is relevant to ADHD symptoms. Noxious stimuli-induced analgesia (NSIA) is measured to estimate noradrenergic endogenous analgesia in spontaneously hypertensive rats (SHR) as an ADHD model and control. Recovery of pain-related behaviors after paw incision was assessed. Contributions of noradrenergic systems were examined by in vivo microdialysis and immunohistochemistry. The SHR showed attenuated NSIA and needed a more extended period for recovery from acute pain. These results suggest ADHD patients exhibit acute pain chronification due to pre-existing attenuated noradrenergic endogenous analgesia. Immunohistochemistry suggests abnormal noradrenaline turnover and downregulation of the target receptor (alpha2a adrenoceptor). Standard ADHD treatment with atomoxetine restored NSIA and shortened the duration of hypersensitivity after the surgery in the SHR. NSIA protocol activated the locus coeruleus, the origin of spinal noradrenaline, of both strains, but only the control exhibited an increase in spinal noradrenaline. This result suggests dysfunction in the noradrenaline-releasing process and can be recognized as a novel mechanism of attenuation of noradrenergic endogenous analgesia. [ABSTRACT FROM AUTHOR]

Several risk factors of children's mental health issues have been identified during the pandemic of COronaVIrus Disease first appeared in 2019 (COVID-19). This study aims to fill the knowledge gap regarding the association between parents' and children's mental health issues during the COVID-19 school closure in France. We conducted a cross-sectional analysis of data collected in the SAPRIS-ELFE study during the COVID-19 pandemic in France. Using multinomial logistic regressions, we estimated associations between parents' and children's mental health issues. Symptoms of anxiety were assessed by the General Anxiety Disorder-7 (GAD-7) and depression by the Patient Health Questionnaire-9 (PHQ-9) for the parents. Hyperactivity/inattention and emotional symptoms in children were assessed by the Strengths and Difficulties Questionnaire (SDQ). The sample included 3496 children aged 8 to 9 years, of whom 50.0% were girls. During the school closure, 7.1% of responding parents had moderate to severe levels of anxiety and 6.7% had moderate to severe levels of depression. A total of 11.8% of the children had an abnormal hyperactivity/inattention score and 6.6% had an abnormal emotional symptoms score. In multivariate regression models, parental moderate to severe level of anxiety and moderate to severe level of depression were associated with abnormal hyperactivity-inattention score (adjusted Odds Ratio (aOR) 3.31; 95% Confidence Interval (CI) 2.33–4.70 and aOR 4.65; 95% CI 3.27–6.59, respectively) and abnormal emotional symptoms score in children (aOR 3.58; 95% CI 2.33–5.49 and aOR 3.78; 95 CI 2.47–5.78 respectively). Children whose parents have symptoms of anxiety and/or depression have an increased likelihood of symptoms of hyperactivity/inattention and emotional symptoms during school closures in France due to COVID-19. Our findings suggest that public health initiatives should target parents and children to limit the impact of such crises on their mental health issues. [ABSTRACT FROM AUTHOR]

Pain often occurs in parallel with neuropsychiatric disorders. However, the underlying mechanisms and potential causality have not been well studied. We collected the genome-wide association study (GWAS) summary statistics of 26 common pain and neuropsychiatric disorders with sample size ranging from 17,310 to 482,730 in European population. The genetic correlation between pair of pain and neuropsychiatric disorders, as well as the relevant cell types were investigated by linkage disequilibrium (LD) score regression analyses. Then, transcriptome-wide association study (TWAS) was applied to identify the potential shared genes by integrating the gene expression information and GWAS. In addition, Mendelian randomization (MR) analyses were conducted to infer the potential causality between pain and neuropsychiatric disorders. Among the 169 pairwise pain and neuropsychiatric disorders, 55 pairs showed positive correlations (median rg = 0.43) and 9 pairs showed negative correlations (median rg = −0.31). Using MR analyses, 26 likely causal associations were identified, including that neuroticism and insomnia were risk factors for most of short-term pain, and multisite chronic pain was risk factor for neuroticism, insomnia, major depressive disorder and attention deficit/hyperactivity disorder, and vice versa. The signals of pain and neuropsychiatric disorders tended to be enriched in the functional regions of cell types from central nervous system (CNS). A total of 19 genes shared in at least one pain and neuropsychiatric disorder pair were identified by TWAS, including AMT, NCOA6, and UNC45A, which involved in glycine degradation, insulin secretion, and cell proliferation, respectively. Our findings provided the evidence of shared genetic structure, causality and potential shared pathogenic mechanisms between pain and neuropsychiatric disorders, and enhanced our understanding of the comorbidities of pain and neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that early motor impairments are a common feature of autism. Thus, scalable, quantitative methods for measuring motor behavior in young autistic children are needed. This work presents an engaging and scalable assessment of visual-motor abilities based on a bubble-popping game administered on a tablet. Participants are 233 children ranging from 1.5 to 10 years of age (147 neurotypical children and 86 children diagnosed with autism spectrum disorder [autistic], of which 32 are also diagnosed with co-occurring attention-deficit/hyperactivity disorder [autistic+ADHD]). Computer vision analyses are used to extract several game-based touch features, which are compared across autistic, autistic+ADHD, and neurotypical participants. Results show that younger (1.5-3 years) autistic children pop the bubbles at a lower rate, and their ability to touch the bubble's center is less accurate compared to neurotypical children. When they pop a bubble, their finger lingers for a longer period, and they show more variability in their performance. In older children (3-10-years), consistent with previous research, the presence of co-occurring ADHD is associated with greater motor impairment, reflected in lower accuracy and more variable performance. Several motor features are correlated with standardized assessments of fine motor and cognitive abilities, as evaluated by an independent clinical assessment. These results highlight the potential of touch-based games as an efficient and scalable approach for assessing children's visual-motor skills, which can be part of a broader screening tool for identifying early signs associated with autism. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) is a common cognitive disorder affecting children. ADHD can interfere with educational, social, and emotional development, so early detection is essential for obtaining proper care. Standard ADHD diagnostic protocols rely heavily on subjective assessments of perceived behavior. An objective diagnostic measure would be a welcome development and potentially aid in accurately and efficiently diagnosing ADHD. Analysis of pupillary dynamics has been proposed as a promising alternative method of detecting affected individuals effectively. This study proposes a method based on the self-similarity of pupillary dynamics and assesses its strength as a potential diagnostic biomarker. Localized discriminatory features are developed in the wavelet domain and selected via a rolling window method to build classifiers. The application on a task-based pupil diameter time series dataset of children aged 10–12 years shows that the proposed method achieves greater than 78% accuracy in detecting ADHD. Comparing with a recent approach that constructs features in the original data domain, the proposed wavelet-based classifier achieves more accurate ADHD classification with fewer features. The findings suggest that the proposed diagnostic procedure involving interpretable wavelet-based self-similarity features of pupil diameter data can potentially aid in improving the efficacy of ADHD diagnosis. [ABSTRACT FROM AUTHOR]

Previous genetically informed studies have uncovered likely causal relationships between mental health problems and self-harm but resulting causal estimates may be biased due to unmediated pleiotropy. By fitting Mendelian Randomization - Direction of Causation (MR-DoC) models that explicitly model pleiotropy, we investigated the effect of four quantitatively measured mental health problems - major depressive disorder (MDD), schizophrenia, attention-deficit hyperactivity disorder (ADHD), and insomnia, on non-suicidal self-harm (NSSH) and suicidal self-harm (SSH), separately. We used data of 12,723 twins (56.6% females) in the Twins Early Development Study. Besides substantial pleiotropy, we found effects from child-rated depressive symptoms to both NSSH (β = 0.194, 95% CIs: 0.131, 0.257) and SSH (β = 0.210, 95% CIs: 0.125, 0.295). Similarly, effects flowed from parent-rated depressive symptoms to NSSH (β = 0.092, 95% CIs: 0.004, 0.181) and SSH (β = 0.165, 95% CIs: 0.051, 0.281). We did not find evidence of aetiological difference between NSSH and SSH. [ABSTRACT FROM AUTHOR]