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The Test of Everyday Attention for Children (TEA-Ch) is a reliable neuropsychological assessment of attention control in children. Methylphenidate (MPH) is an effective treatment to improve attentional difficulties in children with attention deficit/hyperactivity disorder (ADHD). Previous studies investigating the effects of MPH on attention performance of children with ADHD have produced mixed results and prior MPH usage may have confounded these results. No previous study has tested the effects of MPH on the entire TEA-Ch battery. This study investigated the effects of MPH on attention performance using the entire TEA-Ch in 51 medication-naïve children with ADHD compared with 35 nonmedicated typically developing children. All children were tested at baseline and after 6 weeks: The children with ADHD were medication-naïve at baseline, received MPH for 6 weeks and were tested whilst on medication at the second testing session. A beneficial effect of MPH administration was found on at least one subtest of each of the three forms of attention (selective, sustained, and attentional control) assessed by the TEA-Ch, independent of practice effects. MPH aided performance on the TEA-Ch tasks that were inherently nonarousing and that might require top-down control of attention. It is recommended that the TEA-Ch measures—Sky Search Count (selective attention),Score! (sustained attention), Creature Counting Time Taken for older children (attentional control), and Same Worlds (attentional control) be prioritized for use in future pharmacological studies using MPH. [ABSTRACT FROM PUBLISHER]

Response inhibition, comprising action cancellation and action restraint, and error awareness are executive functions of considerable clinical relevance to neuropsychiatric disorders. Nevertheless, our understanding of their underlying catecholamine mechanisms, particularly regarding dopamine, is limited. Here, we used the dopamine D2 agonist cabergoline to study its ability to improve inhibitory control and modulate awareness of performance errors. A randomized, double-blind, placebo-controlled, crossover design with a single dose of cabergoline (1.25 mg) and placebo (dextrose) was employed in 25 healthy participants. They each performed the stop-signal task, a well-validated measure of action cancellation, and the Error Awareness Task, a go/no-go measure of action restraint and error awareness, under each drug condition. Cabergoline was able to selectively reduce stop-signal RT, compared with placebo, indicative of enhanced action cancellation ( p < .05). This enhancement occurred without concomitant changes in overall response speed or RT variability and was not seen for errors of commission on the Error Awareness Task. Awareness of performance errors on the go/no-go task was, however, significantly improved by cabergoline compared with placebo ( p < .05). Our results contribute to growing evidence for the dopaminergic control of distinct aspects of human executive ability, namely, action cancellation and error awareness. The findings may aid the development of new, or the repurposing of existing, pharmacotherapy that targets the cognitive dysfunction of psychiatric and neurological disorders. They also provide further evidence that specific cognitive paradigms have correspondingly specific neurochemical bases. [ABSTRACT FROM AUTHOR]

Background: The Coloboma mouse carries a ∼2 cM deletion encompassing the SNAP25 gene and has a hyperactive phenotype similar to that of ADHD. Such mice are 3 fold more active compared to their control littermates. Genetic association studies support a role for allelic variants of the human SNAP25 gene in predisposing to ADHD. Methods/Principal Findings: We performed association analysis across the SNAP25 gene in 1,107 individuals (339 ADHD trios). To assess the functional relevance of the SNAP25-ADHD associated allele, we performed quantitative PCR on post-mortem tissue derived from the inferior frontal gyrus of 89 unaffected adults. Significant associations with the A allele of SNP rs362990 (χ2 = 10, p-corrected = 0.019, OR = 1.5) and three marker haplotypes (rs6108461, rs362990 and rs362998) were observed. Furthermore, a significant additive decrease in the expression of the SNAP25 transcript as a function of the risk allele was also observed. This effect was detected at the haplotype level, where increasing copies of the ADHD-associated haplotype reduced the expression of the transcript. Conclusions: Our data show that DNA variation at SNAP25 confers risk to ADHD and reduces the expression of the transcript in a region of the brain that is critical for the regulation of attention and inhibition. [ABSTRACT FROM AUTHOR]

Pharmacological evidence suggests the importance of noradrenergic and other monoaminergic neurotransmitters in the aetiology and treatment of attention deficit hyperactivity disorder (ADHD). Until recently, the genes of the noradrenergic pathway were not intensively investigated in ADHD compared to dopaminergic and serotonergic candidates. In this study, 91 SNP markers of 14 noradrenergic genes (an average density of one SNP per 4.5 kbp) were examined in ADHD samples from Ireland and Australia. Although suggestive evidence of association (nominal p ≤ 0.05) with the genes SLC6A2, ADRA1A, ADRA1B and ADRA2B was observed, none remained significant after permutation adjustments. In contrast, haplotype analyses demonstrated a significant association between ADHD and a SLC6A2 haplotype comprising the markers rs36009, rs1800887, rs8049681, rs2242447 and rs9930182 (χ = 9.39, p-corrected = 0.019, OR = 1.51). A rare ADRA1B haplotype made of six SNPs (rs2030373, rs6884105, rs756275, rs6892282, rs6888306 and rs13162302) was also associated (χ = 7.79, p-corrected = 0.042 OR = 2.74) with the disorder. These findings provide evidence of a contribution of the noradrenaline system to the genetic aetiology of ADHD. The observed haplotype association signals may be driven by as yet unidentified functional risk variants in or around the associated regions. Functional genomic analysis is warranted to determine the biological mechanism of the observed association. [ABSTRACT FROM AUTHOR]

The impulsive behavior that is often characteristic of adolescence may reflect underlying neurodevelopmental processes. Moreover, impulsivity is a multi-dimensional construct, and it is plausible that distinct brain networks contribute to its different cognitive, clinical and behavioral aspects. As these networks have not yet been described, we identified distinct cortical and subcortical networks underlying successful inhibitions and inhibition failures in a large sample (n = 1,896) of 14-year-old adolescents. Different networks were associated with drug use (n = 1,593) and attention-deficit hyperactivity disorder symptoms (n = 342). Hypofunctioning of a specific orbitofrontal cortical network was associated with likelihood of initiating drug use in early adolescence. Right inferior frontal activity was related to the speed of the inhibition process (n = 826) and use of illegal substances and associated with genetic variation in a norepinephrine transporter gene (n = 819). Our results indicate that both neural endophenotypes and genetic variation give rise to the various manifestations of impulsive behavior. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate a possible association between norepinephrine genes and cardiovascular side effects of the Osmotic Controlled-Release Oral Delivery System–methylphenidate (OROS-MPH) in Korean children with attention-deficit/hyperactivity disorder (ADHD). One hundred and one children with ADHD (8.7 ± 1.7 years) were recruited from child psychiatric centers at six university hospitals in South Korea. All participants were drug-naive ADHD children treated with OROS-MPH for 12 weeks. During the treatment period the investigators titrated the OROS-MPH dosage on the basis of symptom severity and side effects. Resting heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were examined before and after treatment. The percentage change score (post-treatment – pretreatment/pretreatment × 100) of each parameter was calculated. Genotyping of SLC6A2 −3081(A/T) and G1287A, and alpha-2A-adrenergic receptor (ADRA2A) MspI and DraI polymorphisms was performed. Clinically significant changes were not found in cardiovascular monitoring during the course of treatment. An increase of HR after OROS-MPH treatment was found to be statistically significant (t = 3.54, p = 0.001). Changes in SBP and DBP were not significant and no specific change was found in the ECGs. However, an additive regression analysis demonstrated a significant association between SLC6A2 −3081(A/T) and percentage change in HR post-treatment (p = 0.01) after controlling for age, gender, dosage of MPH and response and baseline pulse rate. Children with ADHD having the T/T genotype of SLC6A2 showed a 12.5% increase in HR compared to baseline, whereas children with the A/T or A/A genotype showed a 3.5% and 2.5% increase after OROS-MPH treatment, respectively. There was also a significant association between the ADRA2A MspI genotype and percentage change of DBP post-treatment after controlling for age, gender, dosage of MPH and response and baseline DBP (p = 0.009). Children with ADHD having the C/C genotype of ADRA2A MspI showed an 18.5% increase in DBP compared to baseline, but children with the G/G or G/C genotype showed a 0.2% decrease after OROS-MPH treatment. The overall cardiovascular effects of OROS-MPH were modest. However, our findings show a positive association between norepinephrine-related gene polymorphisms and cardiovascular response induced by MPH in Korean children with ADHD. Consideration must be given to such children oradults with specific norepinephrine-related genotypes, especially if they show significant changes in HR or DBP after OROS-MPH administration. [ABSTRACT FROM PUBLISHER]

The extent to which changes in brain activity can foreshadow human error is uncertain yet has important theoretical and practical implications. The present study examined the temporal dynamics of electrocortical signals preceding a lapse of sustained attention. Twenty-one participants performed a continuous temporal expectancy task, which involved continuously monitoring a stream of regularly alternating patterned stimuli to detect a rarely occurring target stimulus whose duration was 40% longer. The stimulus stream flickered at a rate of 25 Hz to elicit a steady-state visual-evoked potential (SSVEP), which served as a continuous measure of basic visual processing. Increasing activity in the band (8 -14 Hz) was found beginning ∼20 s before a missed target. This was followed by decreases in the amplitude of two event-related components over a short pretarget time frame: the frontal P3 (3- 4 s) and contingent-negative variation (during the target interval). In contrast, SSVEP amplitude before hits and misses was closely matched, suggesting that the efficacy of ongoing basic visual processing was unaffected. Our results show that the specific neural signatures of attentional lapses are registered in the EEG up to 20 s before an error. [ABSTRACT FROM AUTHOR]

To document possible motor disturbance in schizophrenia, we examined the ability to use advance information (or cues) to plan movements in a sequential button pressing task in 12 Clozapine medicated patients. Programming of movements under various cues revealed that patients with schizophrenia, relative to controls, initiated movements slower to the right than left, providing possible evidence for right hemineglect (left hemisphere dysfunction). Additionally, patients with schizophrenia had difficulty in the initiation of movements in the absence of a cue, suggesting internal cue generation difficulty for movement related to some form of fronto-striatal disturbance. Motor abnormalities were predominantly observed at the level of movement initiation, but not execution, contrary to basal ganglia disorders such as Parkinson's and Huntington's disease. [ABSTRACT FROM AUTHOR]

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

Background: Autistic traits are often reported to be elevated in children diagnosed with attention‐deficit/hyperactivity disorder (ADHD). However, the distribution of subclinical autistic traits in children with ADHD has not yet been established; knowing this may have important implications for diagnostic and intervention processes. The present study proposes a preliminary model of the distribution of parent‐reported ADHD and subclinical autistic traits in two independent samples of Australian children with and without an ADHD diagnosis. Methods: Factor mixture modelling was applied to Autism Quotient and Conners' Parent Rating Scale – Revised responses from parents of Australian children aged 6–15 years who participated in one of two independent studies. Results: A 2‐factor, 2‐class factor mixture model with class varying factor variances and intercepts demonstrated the best fit to the data in both discovery and replication samples. The factors corresponded to the latent constructs of 'autism' and 'ADHD', respectively. Class 1 was characterised by low levels of both ADHD and autistic traits. Class 2 was characterised by high levels of ADHD traits and low‐to‐moderate levels of autistic traits. The classes were largely separated along diagnostic boundaries. The largest effect size for differences between classes on the Autism Quotient was on the Social Communication subscale. Conclusions: Our findings support the conceptualisation of ADHD as a continuum, whilst confirming the utility of current categorical diagnostic criteria. Results suggest that subclinical autistic traits, particularly in the social communication domain, are unevenly distributed across children with clinically significant levels of ADHD traits. These traits might be profitably screened for in assessments of children with high ADHD symptoms and may also represent useful targets for intervention. [ABSTRACT FROM AUTHOR]

Objective: Reward‐based eating drives are putative mechanisms of uncontrolled eating implicated in obesity and disordered eating (e.g., binge eating). Uncovering the genetic and environmental contributions to reward‐related eating, and their genetic correlation with BMI, could shed light on key mechanisms underlying eating and weight‐related disorders. Method: We conducted a classical twin study to examine how much variance in uncontrolled eating phenotypes and body mass index (BMI) was explained by genetic factors, and the extent that these phenotypes shared common genetic factors. 353 monozygotic twins and 128 dizygotic twins completed the Reward‐based Eating Drive 13 scale, which measures three distinct uncontrolled eating phenotypes (loss of control over eating, preoccupation with thoughts about food, and lack of satiety), and a demographic questionnaire which included height and weight for BMI calculation. We estimated additive genetic (A), common environmental (C), and unique environmental (E) factors for each phenotype, as well as their genetic correlations, with a multivariate ACE model. A common pathway model also estimated whether genetic variance in the uncontrolled eating phenotypes was better explained by a common latent uncontrolled eating factor. Results: There were moderate genetic correlations between uncontrolled eating phenotypes and BMI (.26–.41). Variance from the uncontrolled eating phenotypes was also best explained by a common latent uncontrolled eating factor that was explained by additive genetic factors (52%). Discussion: These results suggest that uncontrolled eating phenotypes are heritable traits that also share genetic variance with BMI. This has implications for understanding the cognitive mechanisms that underpin obesity and disordered eating. Public Significance: Our study clarifies the degree to which uncontrolled eating phenotypes and BMI are influenced by shared genetics and shows that vulnerability to uncontrolled eating traits is impacted by common genetic factors. [ABSTRACT FROM AUTHOR]

Background: Despite the known benefits of accurate and timely diagnosis for children with attention-deficit hyperactivity disorder and autism spectrum disorders (autism), for some children this goal is not always achieved. Existing research has explored diagnostic delay for autism and attention-deficit hyperactivity disorder only, and when attention-deficit hyperactivity disorder and autism co-occur, autism has been the focus. No study has directly compared age at diagnosis and diagnostic delay for males and females across attention-deficit hyperactivity disorder, autism and specifically, attention-deficit hyperactivity disorder + autism. Methods: Australian caregivers (N = 677) of children with attention-deficit hyperactivity disorder, autism or attention-deficit hyperactivity disorder + autism were recruited via social media (n = 594) and the Monash Autism and ADHD Genetics and Neurodevelopment Project (n = 83). Caregivers reported on their child's diagnostic process. Diagnostic delay was the mean difference between general initial developmental concerns and the child's attention-deficit hyperactivity disorder and autism diagnosis. Results: Children with autism were significantly younger at autism diagnosis than the attention-deficit hyperactivity disorder + autism group (ηp2 = 0.06), whereas children with attention-deficit hyperactivity disorder were significantly older at attention-deficit hyperactivity disorder diagnosis than the attention-deficit hyperactivity disorder + autism group (ηp2 = 0.01). Delay to attention-deficit hyperactivity disorder and autism diagnosis was significantly longer in the attention-deficit hyperactivity disorder + autism group compared to attention-deficit hyperactivity disorder (ηp2 = 0.02) and autism (η2 = 0.04) only. Delay to autism diagnosis for females with autism (η2 = 0.06) and attention-deficit hyperactivity disorder + autism (η2 = 0.04) was longer compared to males. Conclusions: Having attention-deficit hyperactivity disorder + autism and being female were associated with longer delays to diagnosis. The reasons for these delays and possible adverse effects on outcomes require further study. [ABSTRACT FROM AUTHOR]

Objective: The Strengths and Difficulties Questionnaire is a widely used screening tool for emotional and behavioural problems in children. Recent quantitative analyses have raised concerns regarding its structural validity in Aboriginal and Torres Strait Islander communities. This paper aims to extend upon existing findings by analysing the factor structure of both the parent- and teacher-reported Strengths and Difficulties Questionnaire in this population across a broader age range than in previous studies. Methods: Participants were the caregivers and teachers of 1624 Aboriginal and Torres Strait Islander children (820 male, 804 female) aged 2–15 years from Waves 2–11 of the Longitudinal Study of Indigenous Children. The majority of children were Aboriginal living in major cities and inner regional areas. Internal consistency was estimated with McDonald's Omega. Exploratory structural equation modelling was conducted to investigate the factor structure of the parent-reported and teacher-reported versions of the Strengths and Difficulties Questionnaire. Results: Responses from teachers demonstrated higher internal consistency than responses from parents, which was unacceptably low across most age groups. The purported five-factor structure of the Strengths and Difficulties Questionnaire failed to be replicated across both parent- and teacher-reported questionnaires. The results of bifactor and hierarchical exploratory structural equation models also failed to approximate the higher-order summary scales. These results indicate that the Strengths and Difficulties Questionnaire subscales and summary scores do not provide a valid index of emotional and behavioural problems in Aboriginal and Torres Strait Islander children. Conclusion: The Strengths and Difficulties Questionnaire should not be used with Aboriginal and Torres Strait Islander children. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has markedly impacted functioning for children and adolescents including those with attention-deficit/hyperactivity disorder (ADHD). We explored home learning difficulties (HLD) during COVID-19 restrictions in Australian children (aged 5–17) with ADHD, aiming to: (1) describe home learning experiences, and (2) examine associations between child anxiety (i.e., concurrent anxiety symptoms and pre-existing anxiety disorder status) and HLD. Baseline data from the longitudinal ADHD COVID-19 Survey were used (n = 122). Parents reported on school factors and HLD; pre-existing anxiety and co-occurring difficulties; anxiety, ADHD, and oppositional symptoms; demographics; and medications. Parents retrospectively reported more children often looked forward to school pre-pandemic, than during the pandemic. Anxiety symptoms, but not pre-existing anxiety disorder status, were associated with HLD after accounting for covariates. ADHD inattention symptoms were also associated with HLD. Results support recommendations to continue pre-pandemic supports to assist with ADHD symptoms during home learning, and strategies/supports for families are discussed. [ABSTRACT FROM AUTHOR]

Older adults exposed to enriched environments (EEs) maintain relatively higher levels of cognitive function, even in the face of compromised markers of brain health. Response speed (RS) is often used as a simple proxy to measure the preservation of global cognitive function in older adults. However, it is unknown which specific selection, decision, and/or motor processes provide the most specific indices of neurocognitive health. Here, using a simple decision task with electroencephalography (EEG), we found that the efficiency with which an individual accumulates sensory evidence was a critical determinant of the extent to which RS was preserved in older adults (63% female, 37% male). Moreover, the mitigating influence of EE on age-related RS declines was most pronounced when evidence accumulation rates were shallowest. These results suggest that the phenomenon of cognitive reserve, whereby high EE individuals can better tolerate suboptimal brain health to facilitate the preservation of cognitive function, is not just applicable to neuroanatomical indicators of brain aging but can be observed in markers of neurophysiology. Our results suggest that EEG metrics of evidence accumulation may index neurocognitive vulnerability of the aging brain. [ABSTRACT FROM AUTHOR]

Objective: Understanding the unmet needs of healthcare consumers with attention‐deficit/hyperactivity disorder (ADHD) (individuals with ADHD and their caregivers) provides critical insight into gaps in services, education and research that require focus and funding to improve outcomes. This review examines the unmet needs of ADHD consumers from a consumer perspective. Methods: A standardised search protocol identified peer‐reviewed studies published between December 2011 and December 2021 focusing on consumer‐identified needs relating to ADHD clinical care or research priorities. Results: 1,624 articles were screened with 23 studies that reviewed examining the needs of ADHD consumers from Europe, the U.K., Hong Kong, Iran, Australia, the U.S.A. and Canada. Consumer‐identified needs related to: treatment that goes beyond medication (12 studies); improved ADHD‐related education/training (17 studies); improved access to clinical services, carer support and financial assistance (14 studies); school accommodations/support (6 studies); and ongoing treatment efficacy research (1 study). Conclusion: ADHD consumers have substantial unmet needs in clinical, psychosocial and research contexts. Recommendations to address these needs include: improving access to and quality of multimodal care provision; incorporating recovery principles into care provision; fostering ADHD health literacy; and increasing consumer participation in research, service development and ADHD‐related training/education. [ABSTRACT FROM AUTHOR]