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ADHD is the most common neurodevelopmental disorder presenting to child and adolescent mental health, paediatric, and primary care services. Timely and effective interventions to address core ADHD symptoms and co-occurring problems are a high priority for healthcare and society more widely. While much research has reported on the benefits and adverse effects of different interventions for ADHD, these individual research reports and the reviews, meta-analyses and guidelines summarizing their findings are sometimes inconsistent and difficult to interpret. We have summarized the current evidence and identified several methodological issues and gaps in the current evidence that we believe are important for clinicians to consider when evaluating the evidence and making treatment decisions. These include understanding potential impact of bias such as inadequate blinding and selection bias on study outcomes; the relative lack of high-quality data comparing different treatments and assessing long-term effectiveness, adverse effects and safety for both pharmacological and non-pharmacological treatments; and the problems associated with observational studies, including those based on large national registries and comparing treatments with each other. We highlight key similarities across current international clinical guidelines and discuss the reasons for divergence where these occur. We discuss the integration of these different perspective into a framework for person/family-centered evidence-based practice approach to care that aims to achieve optimal outcomes that prioritize individual strengths and impairments, as well as the personal treatment targets of children and their families. Finally, we consider how access to care for this common and impairing disorder can be improved in different healthcare systems., European Child & Adolescent Psychiatry, 32 (8), ISSN:1435-165X, ISSN:1018-8827

BackgroundPrevious studies have reported brain structure abnormalities in conduct disorder (CD), but it is unclear whether these neuroanatomical alterations mediate the effects of familial (genetic and environmental) risk for CD. We investigated brain structure in adolescents with CD and their unaffected relatives (URs) to identify neuroanatomical markers of familial risk for CD.MethodsForty-one adolescents with CD, 24 URs of CD probands, and 38 healthy controls (aged 12–18), underwent structural magnetic resonance imaging. We performed surface-based morphometry analyses, testing for group differences in cortical volume, thickness, surface area, and folding. We also assessed the volume of key subcortical structures.ResultsThe CD and UR groups both displayed structural alterations (lower surface area and folding) in left inferior parietal cortex compared with controls. In contrast, CD participants showed lower insula and pars opercularis volume than controls, and lower surface area and folding in these regions than controls and URs. The URs showed greater folding in rostral anterior cingulate and inferior temporal cortex than controls and greater medial orbitofrontal folding than CD participants. The surface area and volume differences were not significant when controlling for attention-deficit/hyperactivity disorder comorbidity. There were no group differences in subcortical volumes.ConclusionsThese findings suggest that alterations in inferior parietal cortical structure partly mediate the effects of familial risk for CD. These structural changes merit investigation as candidate endophenotypes for CD. Neuroanatomical changes in medial orbitofrontal and anterior cingulate cortex differentiated between URs and the other groups, potentially reflecting neural mechanisms of resilience to CD.

This study investigated the factor structure of attention-deficit/hyperactivity disorder (ADHD) by comparing the fit of a single-factor model, a correlated model with two or three factors, and a bifactor model with one general and two or three specific factors. Different three-factor solutions that varied with regard to the specification of the item “talks excessively” as impulsivity or hyperactivity were also tested. Parent ratings on the ADHD-Rating Scale (ADHD-RS-IV) were collected in a sample of 2044 schoolchildren (1st to 3rd grade) from the general population and in a clinical sample of 165 children and adolescents with ADHD referred to a public regional child and adolescent psychiatric hospital. Confirmatory factor analyses found a satisfactory fit for most models in both samples. However, a correlated three-factor model where “talks excessively” was included as an indicator of impulsivity and especially the bifactor version of this model with one general and three specific factors fit the data slightly better in the general population. In the clinical sample, a number of models performed equally well (the same version of the correlated three-factor model and all the bifactor models). Overall, the factor structure of ADHD seems to be better characterized by a bifactor model with a strong general factor and two or three weaker specific factors. Due to the strong general factor, we suggest emphasizing the ADHD-RS-IV total score rather than the subscale scores in clinical practice.

OBJECTIVE: This study investigated whether improvements in working memory, reaction time, lapses of attention, interference control, academic motivation, and perceived competence mediated effects of methylphenidate on math performance.METHOD: Sixty-three children (ADHD diagnosis; methylphenidate treatment; age 8-13; IQ > 70) were randomly allocated to a 7-day methylphenidate or placebo treatment in this double-blind placebo-controlled crossover study and compared with 67 controls. Data were collected at schools and analyzed using mixed-model analysis. Methylphenidate was hypothesized to improve all measures; all measures were evaluated as potential mediators of methylphenidate-related math improvements.RESULTS: Controls mostly outperformed the ADHD group. Methylphenidate did not affect measures of cognitive functioning ( p = .082-.641) or academic motivation ( p = .199-.865). Methylphenidate improved parent ratings of their child's self-perceived competence ( p < .01), which mediated methylphenidate efficacy on math productivity.CONCLUSION: These results question the necessity of improvements in specific cognitive and motivational deficits associated with ADHD for medication-related academic improvement. They also stimulate further study of perceived competence as a mediator.

Digital health interventions (DHIs) have frequently been highlighted as one way to respond to increasing levels of mental health problems in children and young people. Whilst many are developed to address existing mental health problems, there is also potential for DHIs to address prevention and early intervention. However, there are currently limitations in the design and reporting of the development, evaluation and implementation of preventive DHIs that can limit their adoption into real-world practice. This scoping review aimed to examine existing evidence-based DHI interventions and review how well the research literature described factors that researchers need to include in their study designs and reports to support real-world implementation. A search was conducted for relevant publications published from 2013 onwards. Twenty-one different interventions were identified from 30 publications, which took a universal (n = 12), selective (n = 3) and indicative (n = 15) approach to preventing poor mental health. Most interventions targeted adolescents, with only two studies including children aged ≤10 years. There was limited reporting of user co-design involvement in intervention development. Barriers and facilitators to implementation varied across the delivery settings, and only a minority reported financial costs involved in delivering the intervention. This review found that while there are continued attempts to design and evaluate DHIs for children and young people, there are several points of concern. More research is needed with younger children and those from poorer and underserved backgrounds. Co-design processes with children and young people should be recognised and reported as a necessary component within DHI research as they are an important factor in the design and development of interventions, and underpin successful adoption and implementation. Reporting the type and level of human support provided as part of the intervention is also important in enabling the sustained use and implementation of DHIs.

Objective: To explore the burden associated with childhood ADHD in a large observational study. Methods: We recruited familes with at least one child (6-18 years) with ADHD via 15 NHS trusts in the UK, and collected data from all family members. We made careful adjustments to ensure a like-for-like comparison with two different control groups, and explored the impact of controlling for a positive parental/carer ADHD screen, employment, and relationship status. Results: We found significant negative impacts of childhood ADHD on parents’/carers’ hours and quality of sleep, satisfaction with leisure time, and health-related quality of life (measured by the EuroQol-5D [EQ-5D]). We found a decrement in life satisfaction, mental well-being (as measured by the Short–Warwick Edinburgh Mental Well-Being Scale [S-WEMWBS]), and satisfaction with intimate relationships, but this was not always robust across the different control groups. We did not find any decrement in satisfaction with health, self-reported health status, or satisfaction with income. Conclusion: The study quantifies the impact on the health and well-being of parents living with a child with ADHD using a survey of families attending ADHD clinics in the United Kingdom.

Aim: This study examined the direct and indirect associations between childhood psychopathology symptoms, screen use, media multitasking and participation in non-digital recreation. Methods: Psychopathology symptoms, media use, media multitasking, participation in sports, social clubs and reading/games were reported by 520 parents about their 3- to 11-year-old children. The data were analysed using structural equation modelling. Results: There were bidirectional negative associations between sports participation and emotional problems (β = −0.16, P

Academic impairment in individuals with attention-deficit/hyperactivity disorder (ADHD) is in part due to reduced motivation for academic tasks, which is likely to vary as a function of task characteristics. The current study employed a new questionnaire—the Child and Adolescent Motivational Profile (CHAMP)—to examine; (1) which task characteristic participants with ADHD perceive as most motivating relative to typically developing peers (TDP) and (2) whether these differences mediate academic functioning. 34 participants with ADHD and 435 TDP (8–16 years) completed the CHAMP. Academic achievement (grade point average) and self-reported positive/negative classroom experiences were recorded. No task characteristics were rated higher in terms of their motivational salience in the ADHD group than in the control sample. Marked/graded, Socially evaluated, Collaborative, Requiring focus and Cognitively challenging task characteristics were rated significantly lower by the ADHD group than controls. The lower rating of Socially evaluated was explained by comorbid ODD symptoms. Cognitively challenging was rated as particularly unmotivating by individuals with ADHD. ADHD was associated with a decreased GPA and a more negative classroom experience. The associations between ADHD and GPA/negative classroom experience were both partially mediated by scores on the Cognitively Challenging scale. For children and adolescents with ADHD tasks that are cognitively challenging were not particularly motivating. To increase task motivation, and improve academic performance of individuals with ADHD, it may be important to include rewarded task elements as they are appraised as particularly motivating by these individuals and this appraisal was similar to that of TDP.

Background: Using data from the English & Romanian Adoptees (ERA) study, we recently reported that early timelimited exposure to severe institutional deprivation is associated with early-onset and persistent neurodevelopmental problems and later-onset emotional problems. Here, we examine possible reasons for the late emergence of emotional problems in this cohort. Our main focus is on testing a developmental cascade mediated via the functional impact of early-appearing neurodevelopmental problems on late adolescent functioning. We also explore a second putative pathway via sensitization to stress. Methods: The ERA study includes 165 Romanian individuals who spent their early lives in grossly depriving institutions and were subsequently adopted into UK families, along with 52 UK adoptees with no history of deprivation. Age six years symptoms of neurodevelopmental problems and age 15 anxiety/depression symptoms were assessed via parental reports. Young adult symptoms of depression and anxiety were assessed by both parent and self-reports; young adults also completed measures of stress reactivity, exposure to adverse life events, and functioning in work and interpersonal relationships. Results: The path between early institutional deprivation and adult emotional problems was mediated via the impact of early neurodevelopmental problems on unemployment and poor friendship functioning during the transition to adulthood. The findings with regard to early deprivation, later life stress reactivity, and emotional problems were inconclusive. Conclusions: Our analysis suggests that the risk for adult depression and anxiety following extreme institutional deprivation is explained through the effects of early neurodevelopmental problems on later social and vocational functioning. Future research should more fully examine the role of stress susceptibility in this model. Keywords: Institutional deprivation; depression; anxiety; emotional problems; developmental cascades; neurodevelopmental problems; longitudinal; prospective; natural experiment.

Background: A diagnosis of attention-deficit/hyperactivity disorder (ADHD) requires the presence of impairment alongside symptoms above a specific frequency and severity threshold. However, the question of whether that symptom threshold represents anything more than an arbitrary cutoff on a continuum of impairment requires further empirical study. Therefore, we present the first study investigating if the relationship between ADHD symptom severity and functional impairment is nonlinear in a way that suggests a discrete, nonarbitrary symptom level threshold associated with a marked step increase in impairment. Methods: Parent reports on the ADHD-Rating Scale (ADHD-RS-IV), the Weiss Functional Impairment Rating Scale (WFIRS-P), and the Strengths and Difficulties Questionnaire were collected in a general population sample of 1st, 2nd, and 3rd graders (N = 1,914–2,044). Results: Piecewise linear regression analyses and nonlinear regression modeling both demonstrated that the relationship between symptom severity (ADHD-RS-IV total score) and impairment (WFIRS-P mean score) was characterized by a gradual linear increase in impairment with higher symptom severity and no apparent step increase or changing rate of increase in impairment at a certain high ADHD-RS-IV total score level. Controlling for socioeconomic status, sex, and co-occurring conduct and emotional symptoms did not alter these results, though comorbid symptoms had a significant effect on impairment. Conclusions: There was no clear evidence for a discrete, nonarbitrary symptom severity threshold with regard to impairment. The results highlight the continued need to consider both symptoms and impairment in the diagnosis of ADHD.

Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551

Background: Children with ADHD are reported to have sleep problems and neuropsychological deficits, but studies examining a potential association between the two are scarce and the use of varying methodology can complicate conclusions. Participants: A clinical sample of 59 medication-naïve children with ADHD between the ages of 6 and 14 years (71% male). Methods: Children underwent polysomnography and multiple sleep latency test, and parent rated sleep habits on the Children’s Sleep Habits Questionnaire. Children also completed an extensive neuropsychological battery of executive function and delay aversion tasks, and parents and teachers rated executive function behavior on the Behavior Rating Inventory of Executive Function. Linear regression analyses were conducted with each of the neuropsychological outcomes included as the outcome variable and the sleep parameters as the predictor variables. Results: The correlations between sleep and neuropsychological outcomes were generally modest, but some sleep parameters (primarily sleep stages and sleep latencies) were associated with objectively and subjectively measured executive function and delay aversion. Conclusions: Using objective and subjective gold standard assessment procedures this study supports a (modest) association between sleep and neuropsychological function in children with ADHD.

The use of lockdown to slow the spread of COVID-19 has been unprecedented in its scale, scope and duration despite early predictions that such a measure would have a negative impact on the mental health and well-being of many young people and their families. From a developmental psychopathology perspective both direct and indirect effects of lockdown-related harms to young people's mental health were predictable: Direct effects, for instance, being due to the negative psychological impact of social isolation and confinement on children; Indirect effects being exerted via negative impacts on family and parent mental health and wellbeing. That these effects would vary from person-to-person was also predicted from this perspective; with vulnerable individuals with pre-existing conditions and those living in high-risk settings being at particular risk. The presumption has been that such negative effects, if they do occur, would be time limited and that everything would return to normal once lockdowns ended. But this is not necessarily the case. In this editorial we ask whether lockdowns could have long-term effects on young people's mental health and then briefly outline three putative mechanisms through which such long-term effects might occur.

Autism is associated with complex and diverse needs that vary from individual to individual. Those affected, and their families, often require specialist care and support. These involve educational and clinical skills which are demanding to implement effectively, and costly, in terms of time and money, to deliver. Early screening and intervention approaches, which can improve outcomes, sometimes dramatically, require government prioritisation of investment. A coordinated, evidence-based approach to screening and support is critical for ensuring that individuals with autism thrive. Autism is, of course, a global phenomenon. Whilst its meaning and significance will inevitably vary from one culture to the next, epidemiological studies report similar presentations and rates across all nations and ethnic/racial groupings. Indeed, the provision of effective services to support people with autism is recognised as a universal human right and a global health priority (Divan et al., this issue). However, although the care needs of people with autism are largely similar across the nations of the world, they will inevitably involve a disproportionate call on the finances of less wealthy nations - and a nation's ability to meet the needs of people with autism is inevitably constrained by their financial circumstances. Countries with limited resources have very difficult choices to make between competing calls for investment that impact their ability to prioritise services for people with autism. Here we explore the implications of these constraints and the best way to address them in the light of the review by Divan et al.

Background Identifying low‐cost and easy to implement measures of infant markers of later psychopathology may improve targeting of early intervention for prevention. Because of their early manifestation, relative stability and overlap with constructs central to affect‐based dimensions of child and adolescent psychopathology, negative emotionality and self‐regulation have been the focus of this research. We conducted a meta‐analysis of longitudinal studies examining the prospective association between infant temperament measured with parent ratings and child/adolescent psychopathology. Methods A systematic literature search for prospective longitudinal studies, which included measures of questionnaire‐assessed infant temperament (negative emotionality, self‐regulation, behavioural inhibition, surgency/extraversion, activity level) and symptoms of child or adolescent mental health (externalising, internalising) and neurodevelopmental problems (attention deficit/hyperactivity disorder [ADHD], autism spectrum disorder [ASD]), was conducted. Standardised estimates of association were calculated and pooled in meta‐analyses. Results Twenty‐five studies (n = 28,425) met inclusion criteria. Small associations were seen between psychopathology aggregated across all domains and infant negative emotionality (r = .15; p < .001) and self‐regulation (r = −.19; p = .007). Effects were also significant but weaker for behavioural inhibition (r = .10; p = .027) and activity level (r = .08; p = .016). Surgency/extraversion was not significantly associated with psychopathology in general (r = −.04; p = .094); however, it was negatively associated with ASD (r = −.10, p = .015). Significant correlations were observed with some outcomes isomorphic with predictors, internalising problems and behavioural inhibition (r = .10; p = .013), ADHD symptoms and activity level (r = .19; p = .009). Conclusion Questionnaire‐based assessments of infant negative emotionality may have transdiagnostic potential to contribute to a risk index of later childhood psychopathology. Behavioural inhibition, surgency/extraversion and activity ratings may provide more specific predictive power. More data from prospective studies are required before the potential of self‐regulation and surgency/extraversion can be properly gauged.

Recent magnetic resonance imaging (MRI) studies implicate structural alterations of amygdala, a brain region responsible for processing and experiencing negative emotions, in adolescents with attention-deficit/hyperactivity disorder (ADHD). Here we examined ADHD-related structural correlates of amygdala functional activity elicited during a functional MRI task designed to test behavioural and brain responses to the imposition of delay - an event known to both elicit amygdala hyperactivation and aversity in ADHD.Structural MRI scans from 28 right-handed male adolescents with combined type ADHD and 32 age-matched controls were analysed. Regional grey matter volumes of ADHD and control participants (ADHD was associated with significantly reduced volumes in bilateral amygdala, parahippocampal and temporal gyrus (We provide the first evidence of the functional significance of reduced amygdala volumes in adolescents with ADHD by highlighting its relation to delay-induced brain activity that is linked to delay aversion.

Increased reaction time variability (RTV) is one of the most replicable behavioral correlates of attention-deficit/hyperactivity disorder (ADHD). However, this may not be specific to ADHD but a more general marker of psychopathology. Here we compare RT variability in individuals with ADHD and those with other childhood internalizing and externalizing conditions both in terms of standard (i.e., the standard deviation of reaction time) and alternative indices that capture low-frequency oscillatory patterns in RT variations over time thought to mark periodic lapses of attention in ADHD. A total of 667 participants (6-12 years old) were classified into non-overlapping diagnostic groups consisting of children with fear disorders (n = 91), distress disorders (n = 56), ADHD (n = 103), oppositional defiant or conduct disorder (ODD/CD; n = 40) and typically developing controls (TDC; n = 377). We used a simple two-choice reaction time task to measure reaction time. The strength of oscillations in RTs across the session was extracted using spectral analyses. Higher RTV was present in ADHD compared to all other disorder groups, effects that were equally strong across all frequency bands. Interestingly, we found that lower RTV to characterize ODD/CD relative to TDC, a finding that was more pronounced at lower frequencies. In general, our data support RTV as a specific marker of ADHD. RT variation across time in ADHD did not show periodicity in a specific frequency band, not supporting that ADHD RTV is the product of spontaneous periodic lapses of attention. Low-frequency oscillations may be particularly useful to differentiate ODD/CD from TDC.

Antipsychotic medications are used in a wide range of mental health and neurodevelopmental conditions in children and adolescents. Their efficacy and tolerability with long-term use have not been clearly established. We aimed to conduct a systematic review and meta-analysis to evaluate the long-term use of antipsychotics in children and adolescents. All relevant double-blind randomized control trials (RCTs), on any antipsychotic used for 12 weeks or longer in any mental health/neurodevelopmental condition in this age group, were included. We evaluated several efficacy and tolerability measures. Meta-analysis was performed for adverse events. Seven RCTs were identified (n = 939, age = 5-17 years), four on aripiprazole and three on risperidone. All studies reported symptomatic/functional improvements or more time before discontinuation with antipsychotics compared to placebo. Weight gain was identified as a significant side effect with antipsychotics. Serum prolactin was reduced with aripiprazole and increased with risperidone, and abdominal pain/discomfort, respiratory tract infections, were more common with Aripiprazole compared to placebo. Musculoskeletal pain may be more common with aripiprazole compared to placebo. Use of antipsychotics for 12 weeks or longer may be associated with symptomatic/functional improvements, but may be associated with additional side effects compared to short-term treatment. Further research in this population is needed.

Since the beginning of the COVID-19 pandemic in early 2020, many governments have implemented national or regional lockdowns to slow the spread of infection. The widely anticipated negative impact these interventions would have on families, including on their mental health, were not included in decision models. The purpose of this editorial is, therefore, to stimulate debate by considering some of the barriers that have stopped governments setting the benefits of lockdown against, in particular, mental health costs during this process and so to make possible a more balanced approach going forward. First, evidence that lockdown causes mental health problems needs to be stronger. Natural experimental studies will play an essential role in providing such evidence. Second, innovative health economic approaches that allow the costs and benefits of lockdown to be compared directly are required. Third, we need to develop public health information strategies that allow more nuanced and complex messages that balance lockdown's costs and benefits to be communicated. These steps should be accompanied by a major public consultation/engagement campaign aimed at strengthening the publics' understanding of science and exploring beliefs about how to strike the appropriate balance between costs and benefits in public health intervention decisions.

Objectives The COVID-19 related lockdowns and distancing measures have presented families with unprecedented challenges. A UK-wide cohort study tracking changes in families’ mental health since early lockdown (Co-SPACE) found a significant rise in primary school-aged children’s behaviour problems and associated family-related stress. Three-quarters of parents in Co-SPACE also reported wanting extra support. In SPARKLE, we will examine whether providing Co-SPACE families with a smartphone application delivering information and parenting support, Parent Positive, can reverse the negative effects of the pandemic on children and parents. The efficacy on child and parent outcomes and cost-effectiveness of Parent Positive will be examined. We will also test whether the effects are moderated by pre-existing levels of child conduct problems and usage of Parent Positive. Exploratory analyses will examine whether other baseline characteristics or lockdown circumstances moderate the effects of Parent Positive. Trial design SPARKLE is a two-arm superiority parallel group randomised controlled trial embedded in an existing large UK-wide self-selected community cohort – Co-SPACE. Those who consent to SPARKLE will be randomised 1:1 to either Parent Positive or Follow-up As Usual (FAU). Participants Co-SPACE (a UK-wide longitudinal cohort study) parents aged ≥18 who have children aged 4-10 years will be eligible for SPARKLE. Intervention and comparator Parent Positive: is a digital public health intervention that can be delivered rapidly at scale to support parents in managing their children’s behaviour to reduce conduct problems and levels of family conflict, which were exacerbated during the first lockdown, and which may increase further in future months as families need to cope with continuous uncertainty and further disruption to their daily lives. Co-designed with parents and based on decades of parenting research, Parent Positive consists of three elements: (i) Parenting Boosters: where advice, delivered in the form of narrated animations, videos, graphics and text is provided to help parents with eight common parenting challenges; (ii) Parenting Exchange: a facilitated parent-to-parent communication and peer support platform and; (iii) Parent Resources: giving access to carefully selected high-quality, evidence-based online parenting resources. Follow-up as Usual: FAU was selected as a comparator because the public health nature meant that an active comparator was not appropriate due to the pragmatic, rapid implementation of the trial. Individuals randomised to FAU will receive no intervention for the first two months while the data for baseline (T1), T2 and T3 are collected. They will then be given full access to the app until 30th November 2021. Main outcomes Outcome measures will be collected remotely through Qualtrics according to the Co-SPACE schedule at baseline (T1), which will be the Co-SPACE survey data obtained immediately prior to randomisation, and then at one month (T2) and two months (T3) post-randomisation. Measures will be collected to assess group differences in child and parent outcomes, costs and service utilisation, and adverse events. Usage of Parent Positive will also be tracked. The primary outcome is parent-reported child conduct problems at one-month post-randomisation measured using the Strengths and Difficulties Questionnaire conduct problems subscale. Randomisation Enrolled participants will be allocated to Parent Positive or FAU at the ratio of 1:1 by simple randomisation using the Randomizer function within the Qualtrics programme. Neither blocking nor stratification will be used. Blinding (masking) It is not possible to blind parents enrolled in the study and Qualtrics will automatically inform parents of their group allocation. Blinded members of the research team and the senior statistician will not be given access to the Qualtrics system or the data in order to remain blinded until after the analysis is complete. We do not anticipate any serious harms associated with taking part in the intervention, therefore there will be no need to unblind any blinded staff during the study. The junior statistician will be unblinded throughout. Numbers to be randomised (sample size) A total of 616 will be recruited into the trial with 308 consenting parents randomised to each treatment arm. Trial status V1.0; 15.03.2021. Not yet recruiting. Anticipated start date: 1st April 2021. Anticipated end date for recruitment: 31st July 2021. Trial registration Clinicaltrial.gov: NCT04786080. The trial was prospectively registered on 8 March 2021. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Background Consistent research findings indicate that parents and teachers observe genuinely different Attention Deficit/Hyperactivity Disorder (ADHD) behaviours in their respective settings. Objective To evaluate the utility of information provided by teacher informant assessments (INFAs) of ADHD symptoms, and the implications of aggregation algorithms in combing parents’ information, i.e. using ‘or-rule’ (endorsement by either one informant) versus ‘and-rule’ (endorsement by both informants). Method Teacher ratings on Conners scales and clinical data from parental accounts on 1383 probands and their siblings from the IMAGE study were analysed. The psychometric properties of teacher and combined ratings using the item response theory model (IRT) are presented. Kappa coefficients, intraclass correlations and linear regression were employed. Results First, teacher endorsement of symptoms is located in a narrow part of the trait continuum close to the average levels. Symptoms exhibit comparable perception in the measurement of the trait(s) with similar discrimination ability and information (reliability). Second, the IRT properties of the ‘or-rule’ ratings are predominantly influenced by parent-INFAs; and the ‘and-rule’ ratings predominantly by teacher-INFAs ratings. Third, parent-teacher INFAs agreement was low, both for individual items (κ = 0.01–0.15) and for dimensional scores (r = 0.12–0.16). The ‘or-rule’ captured milder expressions of ADHD symptoms, whereas the ‘and-rule’ indexed greater severity of ADHD. Conclusions Parent and teacher-INFAs provide different kinds of information, while both are useful. Teacher-INFA and the ‘and-rule’ provide a more accurate index of severity than an additive symptom count. Parent-INFA and the ‘or-rule’ are more sensitive for detecting cases with milder ADHD.

Contains fulltext : 231767.pdf (Publisher’s version ) (Closed access) BACKGROUND: Methylphenidate (MPH) is an efficacious treatment for ADHD but concerns have been raised about potential adverse effects of extended treatment on growth. OBJECTIVES: To systematically review the literature, up to December 2018, conducting a meta-analysis of association of long-term (> six months) MPH exposure with height, weight and timing of puberty. RESULTS: Eighteen studies (ADHD n = 4868) were included in the meta-analysis. MPH was associated with consistent statistically significant pre-post difference for both height (SMD = 0.27, 95% CI 0.16-0.38, p < 0.0001) and weight (SMD = 0.33, 95% CI 0.22-0.44, p < 0.0001) Z scores, with prominent impact on weight during the first 12 months and on height within the first 24-30 months. No significant effects of dose, formulation, age and drug-naïve condition as clinical moderators were found. Data on timing of puberty are currently limited. CONCLUSIONS: Long-term treatment with MPH can result in reduction in height and weight. However, effect sizes are small with possible minimal clinical impact. Long-term prospective studies may help to clarify the underlying biological drivers and specific mediators and moderators.

Objective School-age children with attention-deficit/hyperactivity disorder (ADHD) have reduced health-related quality of life (HRQoL), but it is unclear whether this is also true for preschool children. It is unknown whether parent training (PT) improves HRQoL. This study compared HRQoL in preschool children with ADHD with age-matched children from the general population; examined whether PT improves HRQoL; and tested if treatment-related changes in HRQoL were mediated by improvements in ADHD, parent efficacy, and family stress. Method Parents of 164 children age 3–7 years with an ADHD diagnosis participated in a randomized controlled trial comparing the New Forest Parenting Programme and treatment as usual. Measures of HRQoL, ADHD, parent efficacy, and family stress were completed at baseline, posttreatment, and 36-week follow-up. Child baseline HRQoL was compared with 2 general population-based reference groups. PT effects were analyzed using linear models and mediation analyses. Results Preschoolers with ADHD had lower HRQoL than the reference groups. The New Forest Parenting Programme, but not treatment as usual, was associated with improvement in psychosocial HRQoL at posttreatment (change 2.28, 95% CI [0.78, 3.77]) and at 36-week follow-up (change 2.05, 95% CI [0.56, 3.54]). This difference between treatment arms was not statistically significant. Parent efficacy and family stress scores at posttreatment significantly mediated improvements in HRQoL at 36-week follow-up; ADHD scores at posttreatment did not. Conclusion ADHD negatively impacts HRQoL in early childhood. PT for ADHD has the potential to improve HRQoL independently of its effects on ADHD symptoms. Clinical trial registration information A Controlled Study of Parent Training in the Treatment of ADHD in Young Children (D’SNAPP); http://clinicaltrial.gov/ ; NCT01684644.

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

Functional magnetic resonance imaging studies have reported a diminished response in the brain's reward circuits to contingent cues predicting future monetary gain in adolescents with attention-deficit/hyperactivity disorder (ADHD). The situation with regard to monetary loss is less clear, despite recognition that both positive and negative consequences impact ADHD behaviour. Here, we employ a new Escape Monetary Loss Incentive task in an MRI scanner, which allows the differentiation of contingency and valence effects during loss avoidance, to examine ADHD-related alterations in monetary loss processing. There was no evidence of atypical processing of contingent or non-contingent monetary loss cues in ADHD - either in terms of ratings of emotional and motivational significance or brain responses. This suggests that the ability to process contingencies between performance and negative outcomes is intact in ADHD and that individuals with ADHD are no more (or less) sensitive to negative outcomes than controls. This latter finding stands in stark contrast to recent evidence from a similar task of atypical emotion network recruitment (e.g. amygdala) in ADHD individuals to cues predicting another negative event, the imposition of delay, suggesting marked specificity in the way they respond to negative events. ispartof: SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE vol:17 issue:5 pages:482-492 ispartof: location:England status: published

The rapid expansion of access to, and engagement with, the Internet and digital technology over the past 15 or so years has transformed the social, educational and therapeutic space occupied by children and young people in contemporary society in remarkable ways. First, it has created previously unimaginable opportunities for learning and development and personal exploration and growth. Second, it seems that the very same qualities and characteristics of the Internet that make these positive contributions possible, such as its immediacy, portability, intimacy, unconstrained reach and lack of supervision and regulation of content, has opened children and young people up to a range of serious social, intellectual and mental health risks. Finally, over and above these 'effects', the digital space is increasingly successfully being harnessed for the identification and treatment of mental health problems. Accordingly, the Internet is not so much a double-, as a triple-edged sword, with regard to children’s mental health.

BackgroundInstitutional deprivation in early childhood is associated with neuropsychological deficits in adolescence. Using 20-year follow-up data from a unique natural experiment – the large-scale adoption of children exposed to extreme deprivation in Romanian institutions in the 1980s –we examined, for the first time, whether such deficits are still present in adulthood and whether they are associated with deprivation-related symptoms of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).MethodsAdult neuropsychological functioning was assessed across five domains (inhibitory control, emotion recognition, decision-making, prospective memory and IQ) in 70 previously institutionalized adoptees (mean age = 25.3, 50% female) and 22 non-deprived UK adoptees (comparison group, mean age = 24.6, 41% female). ADHD and ASD symptoms were assessed using parent-completed questionnaires.ResultsEarly institutionalization was associated with impaired performance on all tasks in adulthood. Prospective memory deficits persisted after controlling for IQ. ADHD and ASD symptoms were positively correlated. After controlling for ASD symptoms, ADHD symptoms remained associated with deficits in IQ, prospective memory, proactive inhibition, decision-making quality and emotion recognition. ASD symptoms were not independently associated with neuropsychological deficits when accounting for their overlap with ADHD symptoms. Multiple regression analysis revealed that the link between childhood deprivation and adult ADHD symptoms was statistically explained by deprivation-related differences in adult IQ and prospective memory.ConclusionsThese results represent some of the most compelling evidence to date of the enduring power of early, time-limited childhood adversity to impair long-term neuropsychological functioning across the lifespan – effects that are linked specifically to deprivation-related adult ADHD symptoms.

Introduction Symptoms of attention-deficit hyperactivity disorder (ADHD) and conduct problems have been associated with heightened temporal discounting of reward value resulting in a preference for immediate over delayed outcomes. We examined the cross-sectional relationship between future preference (including intertemporal choice) and prospection (the ability to bring to mind and imagine the experience of future personally-relevant events and outcomes) in adolescents with a range of ADHD symptoms and aggressive behaviour. Methods A combination of behavioural tasks and self-reports measured intertemporal decision making, individual differences in preference for future outcomes and experience of prospection in a convenience sample of English adolescents aged 11–17 (n = 64, 43.8% males). Parents rated symptoms of ADHD and aggression. Results & Conclusions: Factor analysis identified two factors: “Future Preference” and “Prospection”. Significant negative bivariate correlations were found between ADHD and the scores of both factors and between aggression and Future Preference. A path model confirmed the independent significant association of ADHD with both factors but not with aggression. There was no evidence that Prospection was associated with Future Preference or that it reduced the associations between ADHD symptoms and Future Preference. These results provide further evidence that ADHD is associated with a tendency to prefer immediate over future outcomes. The same association with aggression seemed to be driven by the overlap with ADHD symptoms. We provide some of the first evidence that individuals with high ADHD symptoms have difficulty in prospecting about future episodes. However, this is unrelated to their preference for future outcomes.

Significance Millions of children worldwide live in nonfamilial institutions. We studied impact on adult brain structure of a particularly severe but time-limited form of institutional deprivation in early life experienced by children who were subsequently adopted into nurturing families. Institutional deprivation was associated with lower total brain volume in a dose-dependent way. Regionally specific effects were seen in medial prefrontal, inferior frontal, and inferior temporal areas. Deprivation-related alterations in total brain volume were associated with lower intelligence quotient and more attention deficit/hyperactivity disorder symptoms; alterations in temporal volume seemed compensatory, as they were associated with fewer attention deficit/hyperactivity disorder symptoms. We provide evidence that early childhood deprivation is related to alterations in adult brain structure, despite environmental enrichment in intervening years., Early childhood deprivation is associated with higher rates of neurodevelopmental and mental disorders in adulthood. The impact of childhood deprivation on the adult brain and the extent to which structural changes underpin these effects are currently unknown. To investigate these questions, we utilized MRI data collected from young adults who were exposed to severe deprivation in early childhood in the Romanian orphanages of the Ceaușescu era and then, subsequently adopted by UK families; 67 Romanian adoptees (with between 3 and 41 mo of deprivation) were compared with 21 nondeprived UK adoptees. Romanian adoptees had substantially smaller total brain volumes (TBVs) than nondeprived adoptees (8.6% reduction), and TBV was strongly negatively associated with deprivation duration. This effect persisted after covarying for potential environmental and genetic confounds. In whole-brain analyses, deprived adoptees showed lower right inferior frontal surface area and volume but greater right inferior temporal lobe thickness, surface area, and volume than the nondeprived adoptees. Right medial prefrontal volume and surface area were positively associated with deprivation duration. No deprivation-related effects were observed in limbic regions. Global reductions in TBV statistically mediated the observed relationship between institutionalization and both lower intelligence quotient (IQ) and higher levels of attention deficit/hyperactivity disorder symptoms. The deprivation-related increase in right inferior temporal volume seemed to be compensatory, as it was associated with lower levels of attention deficit/hyperactivity disorder symptoms. We provide compelling evidence that time-limited severe deprivation in the first years of life is related to alterations in adult brain structure, despite extended enrichment in adoptive homes in the intervening years.

ispartof: Lancet Child and Adolescent Health vol:4 issue:6 pages:1-2 ispartof: location:England status: Published online

BackgroundPrevious studies of conduct disorder (CD) have reported structural and functional alterations in the limbic system. However, the white matter tracts that connect limbic regions have not been comprehensively studied. The uncinate fasciculus (UF), a tract connecting limbic to prefrontal regions, has been implicated in CD. However, CD-related alterations in other limbic tracts, such as the cingulum and the fornix, have not been investigated. Furthermore, few studies have examined the influence of sex and none have been adequately powered to test whether the relationship between CD and structural connectivity differs by sex. We examined whether adolescent males and females with CD exhibit differences in structural connectivity compared with typically developing controls.MethodsWe acquired diffusion-weighted magnetic resonance imaging data from 101 adolescents with CD (52 females) and 99 controls (50 females). Data were processed for deterministic spherical deconvolution tractography. Virtual dissections of the UF, the three subdivisions of the cingulum [retrosplenial cingulum (RSC), parahippocampal and subgenual cingulum], and the fornix were performed and measures of fractional anisotropy (FA) and hindrance-modulated orientational anisotropy (HMOA) were analysed.ResultsThe CD group had lower FA and HMOA in the right RSC tract relative to controls. Importantly, these effects were moderated by sex – males with CD significantly lower FA compared to male controls, whereas CD and control females did not differ.ConclusionsOur results highlight the importance of considering sex when studying the neurobiological basis of CD. Sex differences in RSC connectivity may contribute to sex differences in the clinical presentation of CD.

Impulsivity is a core feature of attention-deficit hyperactivity disorder (ADHD). It has been conceptualized in a number of different ways. In the current article, we examine how the new concept of "waiting impulsivity", which refers to premature responding before a scheduled target appears, adds to our understanding of impulsivity in ADHD. Sixty children (8-12 years old; 30 ADHD; 30 typically developing controls) completed the 4-choice serial reaction time task, a measure of waiting impulsivity, alongside tasks measuring inhibitory control and temporal discounting and questionnaires measuring behavioral disorder symptoms, delay aversion, and various aspects of impulsivity. A multiple logistic regression model was used to explore the contribution of the primary task outcomes to predict group membership. Children with ADHD displayed more waiting impulsivity and less inhibitory control; they did not differ in temporal discounting. There was no correlation between waiting impulsivity and inhibitory control. Waiting impulsivity was correlated with parent-reported ratings of hyperactivity/impulsivity, inattention, oppositional defiant disorder (ODD), and conduct disorder (CD) and with self-reported delay aversion ratings. Only waiting impulsivity was a significant predictor of ADHD status. In conclusion, waiting impulsivity is distinct from inhibitory control deficits and predicts ADHD status independently of it. Future research needs to examine the relationship with delay aversion and ODD/CD more thoroughly.

The search for objective biological tests, sufficiently reliable, and predictive enough to be diagnostic of psychiatric disorders, continues apace – yet their discovery remains a distant dream. It seems increasingly unlikely that current diagnostic structures and concepts map biologically in a straight forward way – with heterogeneity within, and sharing across, existing diagnostic boundaries being the biological rule rather than the exception. Indeed, it now appears that the science of biological psychiatry is more likely to redraw those boundaries than it is to confirm and mark them (Sonuga‐Barke, Journal of Child Psychology and Psychiatry, 2016, 57, 1). Clinical identification of childhood psychiatric disorders therefore remains, for the foreseeable future at least, an exercise in regulated social perception – reliant on the fallible and subjective judgements of parents, teachers and clinicians. Social perception of this sort is an active and motivated process and therefore prone, like all social perception, to bias and distortions – both systematic and idiosyncratic. Progress has certainly been made over the last 50 years in reducing such judgement bias by, for instance filtering perceptions through the lens of standardised instruments (questionnaires and interviews) with carefully operationalised items and a degree of reliability and validity. However, such instruments often play only a peripheral role in actual diagnostic encounters and when they are used, there is still sufficient ambiguity to leave open plenty of room for interpretation. When we acknowledge that psychiatric diagnoses are social constructions – we are not saying that symptoms of inattention, impulsivity and hyperactivity are not real or do not cluster together in meaningful ways or that they do not cause real distress and disability but that their interpretation and meaning are often informed by social constructs such as ethnic or gender norms and stereotypes (Meyer, Stevenson, & Sonuga‐Barke, Journal of Attention Disorders, 2019).

As in life generally, so in scholarly publishing, the turn of the year inevitably encourages editors to reflect soberly and take honest stock of the progress their journals have made over the previous 12 months. In this frame of mind, my own thoughts turned to our beloved Journal of Child Psychology and Psychiatry. Of course I say ours because we who currently work at the journal, know it actually belongs to you, the world-wide community of child and adolescent psychologists and psychiatrists: We are only its stewards. We hold it in trust for the whole field. We understand the important role that it has served, in shaping the field of scientific child psychology and psychiatry. We know it has a special place in both your intellectual and working lives. We are aware how important it is to you that the journal continues, on your behalf, to help drive the promotion of science-driven and evidence-based solutions to the great, and, in some aspects, growing, burden of suffering imposed by childhood mental and neuro-developmental disorders. It is vital that we have your confidence that we do this in a transparent and fair way - without fear or favour - not letting our own preconceptions, prejudices or vested interests influence the content of what we publish - unless it is our prejudice towards, and vested interest in, finding out 'the truth of the matter'. We are acutely aware of the responsibility that all this places on our shoulders - a yoke we feel privileged to bear.

© 2017, The Author(s). Altered decision making processes and excessive risk-seeking behaviours are key features of conduct disorder (CD). Previous studies have provided compelling evidence of abnormally increased preference for risky options, higher sensitivity to rewards, as well as blunted responsiveness to aversive outcomes in adolescents with CD. However, most studies published to date have focused on males only; thus, it is not known whether females with CD show similar alterations in decision making. The current study investigated potential sex differences in decision making and risk-seeking behaviours in adolescents with CD. Forty-nine adolescents with CD (23 females) and 51 control subjects (27 females), aged 11-18 years, performed a computerised task assessing decision making under risk—the Risky Choice Task. Participants made a series of decisions between two gamble options that varied in terms of their expected values and probability of gains and losses. This enabled the participants’ risk preferences to be determined. Taking the sample as a whole, adolescents with CD exhibited increased risk-seeking behaviours compared to healthy controls. However, we found a trend towards a sex-by-group interaction, suggesting that these effects may vary by sex. Follow-up analyses showed that males with CD made significantly more risky choices than their typically developing counterparts, while females with CD did not differ from typically developing females in their risk-seeking behaviours. Our results provide preliminary evidence that sex may moderate the relationship between CD and alterations in risk attitudes and reward processing, indicating that there may be sex differences in the developmental pathways and neuropsychological deficits that lead to CD. European Commission’s Seventh Framework Programme for research, technological development and demonstration (FP7/2007-2013) under Grant Agreement no. 602407 (FemNAT-CD).

BACKGROUND: Although numerous studies report positive effects of methylphenidate on academic performance, the mechanism behind these improvements remains unclear. This study investigates the effects of methylphenidate on academic performance in children with attention-deficit/hyperactivity disorder (ADHD) and the mediating and moderating influence of ADHD severity, academic performance, and ADHD symptom improvement.METHODS: Sixty-three children with ADHD participated in a double-blind placebo-controlled crossover study comparing the effects of long-acting methylphenidate and placebo. Dependent variables were math, reading, and spelling performance. The ADHD group performance was compared with a group of 67 typically developing children.RESULTS: Methylphenidate improved math productivity and accuracy in children with ADHD. The effect of methylphenidate on math productivity was partly explained by parent-rated symptom improvement, with greater efficacy for children showing more symptom improvement. Further, children showing below-average math performance while on placebo profited more from methylphenidate than children showing above-average math performance.CONCLUSIONS: The results from this study indicate positive effects of methylphenidate on academic performance, although these were limited to math abilities. In light of these results, expectations of parents, teachers, and treating physicians about the immediate effects of methylphenidate on academic improvement should be tempered. Moreover, our results implicate that positive effects of methylphenidate on math performance are in part due directly to effects on math ability and in part due to reductions in ADHD symptoms.

Background: Suboptimal decision making in the face of risk (DMR) in children with ADHD may be mediated by deficits in a number of different neuropsychological processes. We investigated DMR in children with ADHD using the Cambridge Gambling Task (CGT) to distinguish difficulties in adjusting to changing probabilities of choice outcomes (so called risk adjustment) from general risk proneness, and to distinguish these two processes from delay aversion (the tendency to choose the least delayed option) and impairments in the ability to reflect on choice options. Based on previous research we predicted that suboptimal performance on this task in children with ADHD would be primarily due to problems with risk adjustment and delay aversion rather than general risk proneness. Method: Drug naïve children with ADHD (n = 36), 8 to 12 years, and an age-matched group of typically developing children (n = 34) performed the CGT. Results: As predicted children with ADHD were not more prone to making risky choices (i.e., risk proneness). However, they had difficulty adjusting to changing risk levels and were more delay aversive – with these two effects being correlated. Conclusions: Our findings add to the growing body of evidence that children with ADHD do not favor risk taking per se when performing gambling tasks, but rather may lack the cognitive skills or motivational style to appraise changing patterns of risk effectively.

IMPORTANCE: Patients with attention-deficit/hyperactivity disorder (ADHD) are at an increased risk of attempting suicide. Stimulants, such as methylphenidate hydrochloride, are the most common treatment for ADHD, but the association between their therapeutic use and suicide is unclear. OBJECTIVE: To investigate the association between methylphenidate and the risk of suicide attempts. DESIGN, SETTING, AND PARTICIPANTS: A population-based, electronic medical records database from the Hong Kong Clinical Data Analysis & Reporting System was used to identify 25 629 individuals aged 6 to 25 years who were treated with methylphenidate between January 1, 2001, and December 31, 2015. Those who had attempted suicide were included in the analysis. A self-controlled case series design was used to control for time-invariant characteristics of the patients. MAIN OUTCOMES AND MEASURES: Relative incidence of suicide attempt during periods when patients were exposed to methylphenidate compared with nonexposed periods. RESULTS: Among 25 629 patients with methylphenidate prescriptions, 154 had their first recorded suicide attempt within the study period; of these individuals, 111 (72.1%) were male; mean (SD) age at baseline was 7.15 (2.19) years. The overall incidence of suicide attempts during methylphenidate treatment was 9.27 per 10 000 patient-years. An increased risk of suicide attempts was detected during the 90-day period before methylphenidate was initiated, with an incidence rate ratio (IRR) of 6.55 (95% CI, 3.37-12.72). The IRR remained elevated during the first 90 days of treatment (IRR, 3.91; 95% CI, 1.62-9.42) before returning to baseline levels during ongoing treatment (IRR, 1.35; 95% CI, 0.77-2.38). When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of suicide attempts was not elevated (IRR, 0.78; 95% CI, 0.26-2.35). CONCLUSIONS AND RELEVANCE: The incidence of suicide attempts was higher in the period immediately before the start of methylphenidate treatment. The risk remained elevated immediately after the start of methylphenidate treatment and returned to baseline levels during continuation of methylphenidate treatment. The observed higher risk of suicide attempts before treatment may reflect emerging psychiatric symptoms that trigger medical consultations that result in a decision to begin ADHD treatment. Therefore, this study's results do not support a causal association between methylphenidate treatment and suicide attempts., link_to_OA_fulltext

Background It has been hypothesized that resting state cardiac vagal activity (CVA) - an indicator of parasympathetic nervous system activity - is a specific psychophysiological marker of executive control function. Here, we propose an alternative hypothesis - that CVA is associated with early stage attention orientation, promoting the flexible uptake of new information, on which the later operation of such executive control functions depends. We therefore predicted that CVA would predict the interaction between orienting and executive control. This was tested using the revised version of the Attention Network Test (ANT-R) that was developed to distinguish between orienting and executive attention during a stimulus conflict task. Methods Healthy adults (N = 48) performed the ANT-R and their resting CVA was measured over a 5 min period using ECG recordings. Results Multiple regression analyses indicated that, when other factors were controlled for, CVA was more strongly associated with the interaction between the orienting and executive control terms than with either factor individually. Conclusion Higher levels of CVA are specifically implicated in the modulation of executive control by intrinsic orientation operating at early stages of conflict detection. These initial findings of higher CVA on orienting attention in conflict detection need to be replicated in larger samples.

Objective: ADHD has been linked to higher engagement in risky behaviors in circumscribed domains such as dangerous driving, substance abuse, and gambling. This study tests whether ADHD is associated with a pervasive tendency to engage in risky behavior across a spectrum of activities and domains, and whether this tendency is driven by comorbid disorders. Method: A sample of 97 adults with ADHD and 103 typically developing controls completed a self-report questionnaire measuring the likelihood and frequency of engaging in a broad range of risky behaviors. ADHD, comorbid psychiatric disorders, and demographic variables were extensively assessed using standardized instruments. Results: Participants with ADHD reported a pervasive tendency to engage in risky behaviors across multiple activities. This tendency was associated with ADHD over and above the contribution of comorbid psychiatric disorders. Conclusion: These results suggest that ADHD is uniquely linked to a pervasive pattern of engagement in risky behaviors.

ObjectivesThis study aims to ascertain whether the differences of prevalence and severity of attention deficit hyperactivity disorder (ADHD) are true or whether children are perceived and rated differently by parent and teacher informant assessments (INFAs) according to gender, age, and co‐occurring disorders, even at equal levels of latent ADHD traits.MethodsUse of latent trait models (for binary responses) to evaluate measurement invariance in children with ADHD and their siblings from the International Multicenter ADHD Gene data.ResultsSubstantial measurement noninvariance between parent and teacher INFAs was detected for seven out of nine inattention (IA) and six out of nine hyperactivity/impulsivity (HI) items; the correlations between parent and teacher INFAs for six IA and four HI items were not significantly different from zero, which suggests that parent and teacher INFAs are essentially rating different kinds of behaviours expressed in different settings, instead of measurement bias. However, age and gender did not affect substantially the endorsement probability of either IA or HI symptom criteria, regardless of INFA. For co‐occurring disorders, teacher INFA ratings were largely unaffected by co‐morbidity; conversely, parental endorsement of HI symptoms is substantially influenced by co‐occurring oppositional defiant disorder.ConclusionsOur findings suggest general robustness of Diagnostic and Statistical Manual of Mental Disorders ADHD diagnostic items in relation to age and gender. Further research on classroom presentations is needed.

Altres ajuts: VR has served on the speakers for Eli Lilly, Rubio, and Shire in the last 5 years. She has received travel awards from Eli Lilly and Co. and Shire for participating in psychiatric meetings. The ADHD Program has received unrestricted educational and research support from Eli Lilly and Co., Janssen-Cilag, Shire, Rovi, Psious, and Laboratorios Rubió in the past 2 years. MC received travel awards for taking part in psychiatric meetings from Shire. CF received travel awards for taking part in psychiatric meetings from Shire and Lundbeck. GEM received travel awards for taking part in psychiatric meetings from Shire. EJSS-B received speaker fees, consultancy, research funding, and conference support from Shire Pharma. Consultancy from Neurotech Solutions, Copenhagen University and Berhanderling, Skolerne & KU Leuven. Book royalties from OUP and Jessica Kingsley. Financial support-Arhus University and Ghent University for visiting Professorship. Editor-in-Chief JCPP-supported by a buy-out of time to University of Southampton and personal Honorarium. King's College London received payments for work conducted by PA: consultancy for Shire, Eli Lilly, Novartis, and Lundbeck; educational and/or research awards from Shire, Eli Lilly, Novartis, Vifor Pharma, GW Pharma, and QbTech; speaker at events sponsored by Shire, Eli Lilly, Janssen-Cilag, and Novartis. JKB has been in the past 3 years a consultant to/member of advisory board of and/or speaker for Shire, Roche, Medice, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. In the past year, SVF received income, potential income, travel expenses continuing education support and/or research support from Tris, Otsuka, Arbor, Ironshore, Shire, Akili Interactive Labs, Enzymotec, Sunovion, Supernus, and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is principal investigator of www.adhdinadults.com. JK has given talks at educational events sponsored by Medice; all funds are received by King's College London and used for studies of ADHD. HL has served as a speaker for Evolan Pharma and Shire and has received research grants from Shire; all outside the submitted work. K-PL served as a speaker for Eli Lilly and received research support from Medice, and travel support from Shire, all outside the submitted work. LAR reported receiving honoraria, serving on the speakers' bureau/advisory board, and/or acting as a consultant for Eli Lilly, Janssen-Cilag, Novartis, and Shire in the last 3 years; receiving authorship royalties from Oxford Press and ArtMed; and receiving travel awards from Shire for his participation in the 2015 WFADHD meetings and from Novartis to take part of the 2016 AACAP meeting. The ADHD and juvenile bipolar disorder outpatient programs chaired by him received unrestricted educational and research support from the following pharmaceutical companies in the last 3 years: Janssen-Cilag, Novartis, and Shire. MC has received travel grants and research support from Eli Lilly and Co., Janssen-Cilag, Shire, and Lundbeck and served as consultant for Eli Lilly and Co., Janssen-Cilag, Shire, and Lundbeck. BF has received educational speaking fees from Medice and Shire. JAR-Q was on the speakers' bureau and/or acted as consultant for Eli Lilly, Janssen-Cilag, Novartis, Shire, Lundbeck, Almirall, Braingaze, Sincrolab, Medice, and Rubió in the last 5 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubió, Shire, Medice, and Eli- Lilly. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 5 years: Eli Lilly, Lundbeck, Janssen- Cilag, Actelion, Shire, Ferrer, Oryzon, Roche, Psious, and Rubió. The other authors have nothing to disclose. All members of the 23andMe Research Team are current or former employees of 23andMe, Inc. and hold stock or stock options in 23andMe. Authors of the ADHD Working group of the PGC that participated in this study: Catharina A. Hartman, Ziarih Hawi, Jennifer Crosbie, Sandra Loo, Josephine Elia, Russell Schachar, Christie Burton, Ted Reichborn-Kjennerud, Aribert Rothenberger, Søren Dalsgaard, Irwin Waldman, Mark Bellgrove, Hakon Hakonarson, Johannes Hebebrand, Anke Hinney, and Robert Oades have nothing to disclose. Joseph Biederman 2019-2020: he received research support from Genentech, Headspace Inc., Lundbeck AS, Neurocentria Inc, Pfizer Pharmaceuticals, Roche TCRC Inc., Shire Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., and Tris. He was a consultant for Akili, Avekshan, Jazz Pharma, and Shire/Takeda. Through MGH CTNI, he participated in a scientific advisory board for Supernus. Dr Biederman's program has received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Bracket Global, Ingenix, Prophase, Shire, Sunovion, and Theravance; these royalties were paid to the Department of Psychiatry at MGH. Tobias Banaschewski served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm. He received conference support or speaker's fee by Lilly, Medice, and Shire. He received royalties from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. James McGough is an expert testimony for Eli Lilly; DSMB for Sunovion. Benjamin Neale is a member of the scientific advisory board at Deep Genomics and consultant for Camp4 Therapeutics, Takeda Pharmaceutical, and Biogen. Ole Andreas Andreassen received speaker's honorarium from Lundbeck, and is a consultant for HealthLytix. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 602805 (Aggressotype) as well as from the European Union H2020 Programme (H2020/2014-2020). The work was also supported by the ECNP Network "ADHD across the Lifespan" (https://www.ecnp.eu/research-innovation/ECNP-networks/List-ECNP-Networks/ADHD.aspx). Over the course of this investigation, PR is a recipient of a pre-doctoral fellowship from the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), Generalitat de Catalunya, Spain. The iPSYCH project is funded by the Lundbeck Foundation (grant nos. R102-A9118 and R155-2014-1724) and the universities, and university hospitals of Aarhus and Copenhagen. ADB and NRM's work is also supported by the EU's Horizon 2020 programme. Data handling and analysis was supported by NIMH (1U01MH109514-01 to Michael O'Donovan and ADB). CSM is a recipient of a Sara Borrell contract from the Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad, Spain. K-PL and his team are supported by the Deutsche Forschungsgemeinschaft (DFG: CRU 125, CRC TRR 58 A1/A5, no. 44541416), ERA-Net NEURON/RESPOND, no. 01EW1602B, ERA-Net NEURON/DECODE, no. 01EW1902, and 5-100 Russian Academic Excellence Project. JH thanks Stiftelsen K.G. Jebsen, University of Bergen, the Western Norwegian Health Authorities (Helse Vest). HL thanks the Swedish research council. BC received financial support from the Spanish "Ministerio de Economía y Competitividad" and AGAUR. MSA is a recipient of a contract from the Biomedical Network Research Center on Mental Health (CIBERSAM), Madrid, Spain. MR is a recipient of a Miguel de Servet contract from the Instituto de Salud Carlos III, Spain. The research leading to these results has received funding from the Instituto de Salud Carlos III , and cofinanced by the European Regional Development Fund (ERDF), from the Pla estratègic de recerca i innovació en salut (PERIS); Generalitat de Catalunya, from "la Marató de TV3" (092330/31) and from the Agència de Gestió d'Ajuts Universitaris i de Recerca-AGAUR, Generalitat de Catalunya. ES's work is supported by a personal Hypatia grant from the Radboud University Medical Center. MH received a Veni grant from of the Netherlands Organization for Scientific Research (NWO, grant number 91619115). The NeuroIMAGE study was supported by NIH Grant R01MH62873 (to SVF), NWO Large Investment Grant 1750102007010 (to JKB), ZonMW grant 60-60600-97-193, NWO grants 056-13-015 and 433-09-242, and matching grants from Radboud University Nijmegen Medical Center, University Medical Center Groningen and Accare, and Vrije Universiteit Amsterdam. Organization for Scientific Research (NWO; grant 016-130-669). BF and MK's work is supported by the Dutch National Science Agenda (NWA) for the NeurolabNL project (grant 400-17-602). This paper represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. BF received additional funding from a personal Vici grant of the Dutch. Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.

Contains fulltext : 202907.pdf (Publisher’s version ) (Open Access) OBJECTIVE:: Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with a complex pathophysiology. Intracranial volume (ICV) and volumes of the nucleus accumbens, amygdala, caudate nucleus, hippocampus, and putamen are smaller in people with ADHD compared with healthy individuals. The authors investigated the overlap between common genetic variation associated with ADHD risk and these brain volume measures to identify underlying biological processes contributing to the disorder. METHODS:: The authors combined genome-wide association results from the largest available studies of ADHD (N=55,374) and brain volumes (N=11,221-24,704), using a set of complementary methods to investigate overlap at the level of global common variant genetic architecture and at the single variant level. RESULTS:: Analyses revealed a significant negative genetic correlation between ADHD and ICV (rg=-0.22). Meta-analysis of single variants revealed two significant loci of interest associated with both ADHD risk and ICV; four additional loci were identified for ADHD and volumes of the amygdala, caudate nucleus, and putamen. Exploratory gene-based and gene-set analyses in the ADHD-ICV meta-analytic data showed association with variation in neurite outgrowth-related genes. CONCLUSIONS:: This is the first genome-wide study to show significant genetic overlap between brain volume measures and ADHD, both on the global and the single variant level. Variants linked to smaller ICV were associated with increased ADHD risk. These findings can help us develop new hypotheses about biological mechanisms by which brain structure alterations may be involved in ADHD disease etiology.

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

Background: Attention-deficit/hyperactivity disorder (ADHD) is presumed to involve mental effort application difficulties. To test this assumption, we manipulated task difficulty and measured behavioral, as well as subjective and psychophysiological indices of effort.Methods: Fifteen adolescent ADHD boys and 16 controls performed two tasks. First, subjective estimates and behavioral and pupillary measures of effort were recorded across five levels of N-back task difficulties. Second, effort discounting was assessed. In the latter, participants made repeated choices between performing a difficult N-back task for a high reward versus an easier N-back task for a smaller reward.Results: Increasing task difficulty led to similar deteriorations in performance for both groups – although ADHD participants performed more poorly at all difficulty levels than controls. While ADHD and control participants rated the tasks equally difficult and discounted effort similarly, those with ADHD displayed slightly different pupil dilation patterns with increasing task difficulty.Conclusion: The behavioral results did not provide evidence for mental effort problems in adolescent boys with ADHD. The subtle physiological effects, however, suggest that adolescents with ADHD may allocate effort in a different way than controls.

Science is not a linear process of accumulating knowledge. To the contrary, progress in understanding is most likely to occur, especially in less 'mature' disciplines, when healthy debate between opposing points of view create a dialectic in which thesis and antithesis force a new synthesis. In developmental psychopathology, such tension between opposing schools of thought continue to play a vital role in driving discovery across a wide range of topics.

Biases in emotion processing have been identified in both conduct disorder (CD) and anxiety disorders (ADs). Given the significant comorbidity between these conditions, it is important to examine whether individuals with comorbid CD+ADs display a combination of the biases observed in the non-comorbid versions of these disorders or their own distinctive pattern. We measured attentional biases and vigilance towards, and disengagement from, angry, fearful and happy faces in adolescents with CD-only (n = 31), ADs-only (n = 23), comorbid CD+ADs (n = 20) and controls (n = 30), using standard (500 ms) and masked, brief (17 ms) presentation versions of a visual-probe task. Adolescents with ADs displayed faster reaction times to happy, compared to fearful or angry, faces (irrespective of probe position). In addition to having longer reaction times in general, the CD-only and ADs-only groups showed decreased vigilance towards, and delayed disengagement from, emotional faces compared to the comorbid CD+ADs and control groups. These results suggest that CD and ADs interact in terms of their effects on vigilance and disengagement, such that attentional biases are attenuated, rather than exacerbated, in individuals with comorbid CD+ADs.