Psychometric properties of the Chinese version of the Quick Delay Questionnaire (C-QDQ) and ecological characteristics of reward-delay impulsivity of adults with ADHD.

BACKGROUND: The Quick Delay Questionnaire (QDQ) is a short questionnaire designed to assess delay-related difficulties in adults. This study aimed to examine the reliability and validity of the Chinese version of the QDQ (C-QDQ) in Chinese adults, and explore the ecological characteristics of delay-related impulsivity in Chinese adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Data was collected from 302 adults, including ADHD (n = 209) and healthy controls (HCs) (n = 93). All participants completed the C-QDQ. The convergent validity, internal consistency, retest reliability and confirmatory factor analysis (CFA) of the C-QDQ were analyzed. The correlations between C-QDQ and two laboratory measures of delay-related difficulties and Barratt Impulsiveness Scale-11 (BIS-11), the comparison of C-QDQ scores between ADHD subgroups and HCs were also analyzed. RESULTS: The Cronbach's α of C-QDQ was between 0.83 and 0.89. The intraclass correlation coefficient of C-QDQ was between 0.80 and 0.83. The results of CFA of C-QDQ favoured the original two-factor model (delay aversion and delay discounting). Significant positive associations were found between C-QDQ scores and BIS-11 total score and performance on the laboratory measure of delay-related difficulties. Participants with ADHD had higher C-QDQ scores than HCs, and female ADHD reported higher scores on delay discounting subscale than male. ADHD-combined type (ADHD-C) reported higher scores on delay aversion subscale than ADHD-inattention type (ADHD-I). CONCLUSION: The C-QDQ is a valid and reliable tool to measure delay-related responses that appears to have clinical utility. It can present the delay-related impulsivity of patients with ADHD. Compared to HCs, the level of reward-delay impulsivity was higher in ADHD.

Commentary: Health anxiety in youth during 'COVID' - some thoughts prompted by Rask et al. (2024).

Researchers continue to count the short- and longer-term mental health costs for children and adolescents of the COVID-19 pandemic and the associated exceptional restrictions imposed by governments on their lives in an attempt to control the pandemic and its impacts. Despite being at low risk of serious physical illness from COVID-19 themselves, some studies have reported a decline in the mental health of many young people during the pandemic. Some have suggested that this could even create a risk for long-term morbidity. In this commentary, we reflect on the excellent article by Rask and colleagues on paediatric health anxiety and consider key research gaps for the field in general and for the specific challenges and questions posed by the COVID-19 pandemic and its legacy.

Participatory translational science of neurodivergence: model for attention-deficit/hyperactivity disorder and autism research.

BACKGROUND: There are increasing calls for neurodivergent peoples' involvement in research into neurodevelopmental conditions. So far, however, this has tended to be achieved only through membership of external patient and public involvement (PPI) panels. The Regulating Emotions - Strengthening Adolescent Resilience (RE-STAR) programme is building a new participatory model of translational research that places young people with diagnoses of attention-deficit hyperactivity disorder (ADHD) and autism at the heart of the research team so that they can contribute to shaping and delivering its research plan. AIMS: To outline the principles on which the RE-STAR participatory model is based and describe its practical implementation and benefits, especially concerning the central role of members of the Youth Researcher Panel (Y-RPers). METHOD: The model presented is a culmination of a 24-month process during which Y-RPers moved from advisors to co-researchers integrated within RE-STAR. It is shaped by the principles of co-intentionality. The account here was agreed following multiple iterative cycles of collaborative discussion between academic researchers, Y-RPers and other stakeholders. RESULTS: Based on our collective reflections we offer general guidance on how to effectively integrate young people with diagnoses of ADHD and/or autism into the core of the translational research process. We also describe the specific theoretical, methodological and analytical benefits of Y-RPer involvement in RE-STAR. CONCLUSIONS: Although in its infancy, RE-STAR has demonstrated the model's potential to enrich translational science in a way that can change our understanding of the relationship between autism, ADHD and mental health. When appropriately adapted we believe the model can be applied to other types of neurodivergence and/or mental health conditions.

The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents: Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project.

OBJECTIVE: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age. METHOD: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age. RESULTS: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable. CONCLUSION: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.

Methylphenidate and Sleep Difficulties in Children and Adolescents With ADHD: Results From the 2-Year Naturalistic Pharmacovigilance ADDUCE Study.

OBJECTIVE: Short-term RCTs have demonstrated that MPH-treatment significantly reduces ADHD-symptoms, but is also associated with adverse events, including sleep problems. However, data on long-term effects of MPH on sleep remain limited. METHODS: We performed a 2-year naturalistic prospective pharmacovigilance multicentre study. Participants were recruited into three groups: ADHD patients intending to start MPH-treatment (MPH-group), those not intending to use ADHD-medication (no-MPH-group), and a non-ADHD control-group. Sleep problems were assessed with the Children's-Sleep-Habits-Questionnaire (CSHQ). RESULTS: 1,410 participants were enrolled. Baseline mean CSHQ-total-sleep-scores could be considered clinically significant for the MPH-group and the no-MPH-group, but not for controls. The only group to show a significant increase in any aspect of sleep from baseline to 24-months was the control-group. Comparing the MPH- to the no-MPH-group no differences in total-sleep-score changes were found. CONCLUSION: Our findings support that sleep-problems are common in ADHD, but don't suggest significant negative long-term effects of MPH on sleep.

Is Attention-Deficit/Hyperactivity Disorder (ADHD) a Dimension or a Category? What Does the Relationship Between ADHD Traits and Psychosocial Quality of Life Tell Us?

OBJECTIVE: The question of whether attention-deficit/hyperactivity disorder (ADHD) is a discrete category or a continuous dimension remains clinically relevant. We report the first examination of this question from the viewpoint of the relationship between ADHD traits and psychosocial quality of life (QoL), and whether the level of QoL declines markedly around a certain high ADHD trait range suggestive of a categorical boundary. METHODS: Parents/caregivers of 1,967 schoolchildren aged 6 to 11 from the general population completed the Pediatric Quality of Life Inventory and the ADHD-Rating Scale IV. Piecewise linear and non-linear regression analyses were performed. RESULTS: No evidence for a non-linear association or an abrupt change in the rate of decrease in QoL was observed in the high end of the ADHD traits continuum. Instead, the relationship was consistent with linearity. CONCLUSION: Psychosocial QoL gradually declines in a linear manner as ADHD trait levels increase providing further support for a dimensional model.

Paradigm 'flipping' to reinvigorate translational science: Outlining a neurodevelopmental science framework from a 'neurodiversity' perspective.

For the most part the science of neuro-developmental conditions, such as autism and ADHD, is conducted within a framework defined by a paradigm that assumes that these expressions of neuro-developmental variation are disorders resulting from brain dysfunction. the translational goal being to identify, then target, the source of such dysfunction to reduce disorder and resolve impairment. By shifting this perspective to one that defines such conditions as divergence in thought and action underpinned by brain atypicality, the neurodiversity paradigm offers a fresh scientific vision shaped by a new translational imperative. It shifts the focus of enquiry to understanding the way environments shape experience to either stifle or promote the well-being and development of neurodivergent people. It also encourages the fullest possible participation of neurodivergent people in the scientific process. Together these two elements provide a platform for a new translational science of neurodevelopment.

Remote Recruitment Strategy and Structured E-Parenting Support (STEPS) App: Feasibility and Usability Study.

BACKGROUND: The Structured E-Parenting Support (STEPS) app provides support for parents of children with elevated hyperactivity, impulsivity, inattention, and conduct problems who are awaiting clinical assessment. STEPS will be evaluated in a randomized controlled trial (RCT) within the Online Parent Training for the Initial Management of ADHD Referrals (OPTIMA) research program in the United Kingdom. Phase 1 of the OPTIMA tested the feasibility of participants' recruitment and the app's usability. OBJECTIVE: This study aimed to adapt a digital routine clinical monitoring system, myHealthE, for research purposes to facilitate waitlist recruitment; test using remote methods to screen and identify participants quickly and systematically; pilot the acceptability of the recruitment and assessment protocol; and explore the usability of STEPS. METHODS: myHealthE was adapted to screen patients' data. Parents' and clinicians' feedback on myHealthE was collected, and information governance reviews were conducted in clinical services planning to host the RCT. Potential participants for the observational feasibility study were identified from new referrals using myHealthE and non-myHealthE methods. Descriptive statistics were used to summarize the demographic and outcome variables. We estimated whether the recruitment rate would meet the planned RCT sample size requirement (n=352). In addition to the feasibility study participants, another group of parents was recruited to assess the STEPS usability. They completed the adapted System Usability Scale and responded to open-ended questions about the app, which were coded using the Enlight quality construct template. RESULTS: Overall, 124 potential participants were identified as eligible: 121 (97.6%) via myHealthE and 3 (2.4%) via non-myHealthE methods. In total, 107 parents were contacted, and 48 (44.9%) consented and were asked if, hypothetically, they would be willing to participate in the OPTIMA RCT. Of the 28 feasibility study participants who provided demographic data, 21 (75%) identified as White. Their children had an average age of 8.4 (SD 1.7) years and 65% (31/48) were male. During the primary recruitment period (June to July 2021) when 45 participants had consented, 38 (84%) participants agreed hypothetically to take part in the RCT (rate of 19/mo, 95% CI 13.5-26.1), meeting the stop-go criterion of 18 participants per month to proceed with the RCT. All parents were satisfied or very satisfied with the study procedures. Parents (n=12) recruited to assess STEPS' usability described it as easy to navigate and use and as having an attractive combination of colors and visual design. They described the content as useful, pitched at the right level, and sensitively presented. Suggested improvements included adding captions to videos or making the recorded reflections editable. CONCLUSIONS: Remote recruitment and study procedures for testing a parenting intervention app are feasible and acceptable for parents. The parents felt that STEPS was a useful and easy-to-use digital parenting support tool. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s40814-021-00959-0.

The Effectiveness and Cost-Effectiveness of a Universal Digital Parenting Intervention Designed and Implemented During the COVID-19 Pandemic: Evidence From a Rapid-Implementation Randomized Controlled Trial Within a Cohort.

BACKGROUND: Children's conduct and emotional problems increased during the COVID-19 pandemic. OBJECTIVE: We tested whether a smartphone parenting support app, Parent Positive, developed specifically for this purpose, reversed these effects in a cost-effective way. Parent Positive includes 3 zones. Parenting Boosters (zone 1) provided content adapted from standard face-to-face parent training programs to tackle 8 specific challenges identified by parents and parenting experts as particularly relevant for parents during the pandemic. The Parenting Exchange (zone 2) was a parent-to-parent and parent-to-expert communication forum. Parenting Resources (zone 3) provided access to existing high-quality web-based resources on a range of additional topics of value to parents (eg, neurodevelopmental problems, diet, and sleep). METHODS: Supporting Parents And Kids Through Lockdown Experiences (SPARKLE), a randomized controlled trial, was embedded in the UK-wide COVID-19: Supporting Parents, Adolescents and Children during Epidemics (Co-SPACE) longitudinal study on families' mental health during the pandemic. Parents of children aged 4 to 10 years were randomized 1:1 to Parent Positive or follow-up as usual (FAU) between May 19, 2021, and July 26, 2021. Parent Positive provided advice on common parenting challenges and evidence-based web-based resources and facilitated parent-to-parent and expert-to-parent support. Child conduct and emotional problems and family well-being were measured before randomization (T1) and at 1 (T2) and 2 (T3) months after randomization. Service use, costs, and adverse events were measured, along with app use and satisfaction. The primary outcome was T2 parent-reported child conduct problems, which were analyzed using linear mixed regression models. RESULTS: A total of 320 participants were randomized to Parent Positive, and 326 were randomized to FAU. The primary outcome analysis included 79.3% (512/646) of the participants (dropout: 84/320, 26% on Parent Positive and 50/326, 15% on FAU). There were no statistically significant intervention effects on conduct problems at either T2 (standardized effect=-0.01) or T3 (secondary outcome; standardized effect=-0.09) and no moderation by baseline conduct problems. Significant intervention-related reductions in emotional problems were observed at T2 and T3 (secondary outcomes; standardized effect=-0.13 in both cases). Parent Positive, relative to FAU, was associated with more parental worries at T3 (standardized effect=0.14). Few intervention-attributable adverse events were reported. Parent Positive was cost-effective once 4 outliers with extremely high health care costs were excluded. CONCLUSIONS: Parent Positive reduced child emotional problems and was cost-effective compared with FAU once outliers were removed. Although small when considered against targeted therapeutic interventions, the size of these effects was in line with trials of nontargeted universal mental health interventions. This highlights the public health potential of Parent Positive if implemented at the community level. Nevertheless, caution is required before making such an interpretation, and the findings need to be replicated in large-scale, whole-community studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04786080; https://clinicaltrials.gov/ct2/show/NCT04786080.

Computerized cognitive training in attention-deficit/hyperactivity disorder (ADHD): a meta-analysis of randomized controlled trials with blinded and objective outcomes.

This meta-analysis investigated the effects of computerized cognitive training (CCT) on clinical, neuropsychological and academic outcomes in individuals with attention-deficit/hyperactivity disorder (ADHD). The authors searched PubMed, Ovid, and Web of Science until 19th January 2022 for parallel-arm randomized controlled trials (RCTs) using CCT in individuals with ADHD. Random-effects meta-analyses pooled standardized mean differences (SMD) between CCT and comparator arms. RCT quality was assessed with the Cochrane Risk of Bias 2.0 tool (PROSPERO: CRD42021229279). Thirty-six RCTs were meta-analysed, 17 of which evaluated working memory training (WMT). Analysis of outcomes measured immediately post-treatment and judged to be "probably blinded" (PBLIND; trial n = 14) showed no effect on ADHD total (SMD = 0.12, 95%CI[-0.01 to -0.25]) or hyperactivity/impulsivity symptoms (SMD = 0.12, 95%[-0.03 to-0.28]). These findings remained when analyses were restricted to trials (n: 5-13) with children/adolescents, low medication exposure, semi-active controls, or WMT or multiple process training. There was a small improvement in inattention symptoms (SMD = 0.17, 95%CI[0.02-0.31]), which remained when trials were restricted to semi-active controls (SMD = 0.20, 95%CI[0.04-0.37]), and doubled in size when assessed in the intervention delivery setting (n = 5, SMD = 0.40, 95%CI[0.09-0.71]), suggesting a setting-specific effect. CCT improved WM (verbal: n = 15, SMD = 0.38, 95%CI[0.24-0.53]; visual-spatial: n = 9, SMD = 0.49, 95%CI[0.31-0.67]), but not other neuropsychological (e.g., attention, inhibition) or academic outcomes (e.g., reading, arithmetic; analysed n: 5-15). Longer-term improvement (at ~6-months) in verbal WM, reading comprehension, and ratings of executive functions were observed but relevant trials were limited in number (n: 5-7). There was no evidence that multi-process training was superior to working memory training. In sum, CCT led to shorter-term improvements in WM, with some evidence that verbal WM effects persisted in the longer-term. Clinical effects were limited to small, setting specific, short-term effects on inattention symptoms.

Long-term safety of methylphenidate in children and adolescents with ADHD: 2-year outcomes of the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study.

BACKGROUND: Methylphenidate is the most frequently prescribed medication for the treatment of ADHD in children and adolescents in many countries. Although many randomised controlled trials support short-term efficacy, tolerability, and safety, data on long-term safety and tolerability are scarce. The aim of this study was to investigate the safety of methylphenidate over a 2-year period in relation to growth and development, psychiatric health, neurological health, and cardiovascular function in children and adolescents. METHODS: We conducted a naturalistic, longitudinal, controlled study as part of the ADDUCE research programme in 27 European child and adolescent mental health centres in the UK, Germany, Switzerland, Italy, and Hungary. Participants aged 6-17 years were recruited into three cohorts: medication-naive ADHD patients who intended to start methylphenidate treatment (methylphenidate group), medication-naive ADHD patients who did not intend to start any ADHD medication (no-methylphenidate group), and a control group without ADHD. Children with ADHD diagnosed by a qualified clinician according to the DSM-IV criteria and, in the control group, children who scored less than 1·5 on average on the Swanson, Nolan, and Pelham IV rating scale for ADHD items, and whose hyperactivity score on the parent-rated Strengths and Difficulties Questionnaire was within the normal range (<6) were eligible for inclusion. Participants were excluded if they had previously taken any ADHD medications but remained eligible if they had previously taken or were currently taking other psychotropic drugs. The primary outcome was height velocity (height velocity SD score; estimated from at least two consecutive height measurements, and normalised with reference to the mean and SD of a population of the same age and sex). FINDINGS: Between Feb 01, 2012, and Jan 31, 2016, 1410 participants were enrolled (756 in methylphenidate group, 391 in no-methylphenidate group, and 263 in control group). 1070 (76·3%) participants were male, 332 (23·7%) were female, and for eight gender was unknown. The average age for the cohort was 9·28 years (SD 2·78; IQR 7-11). 1312 (93·0%) of 1410 participants were White. The methylphenidate and no-methylphenidate groups differed in ADHD symptom severity and other characteristics. After controlling for the effects of these variables using propensity scores, there was little evidence of an effect on growth (24 months height velocity SD score difference -0·07 (95% CI -0·18 to 0·04; p=0·20) or increased risk of psychiatric or neurological adverse events in the methylphenidate group compared with the no-methylphenidate group. Pulse rate and systolic and diastolic blood pressure were higher in the methylphenidate group compared with the no-methylphenidate group after 24 months of treatment. No serious adverse events were reported during the study. INTERPRETATION: Our results suggest that long-term treatment with methylphenidate for 2 years is safe. There was no evidence to support the hypothesis that methylphenidate treatment leads to reductions in growth. Methylphenidate-related pulse and blood pressure changes, although relatively small, require regular monitoring. FUNDING: EU Seventh Framework Programme.

The adult outcome of childhood quasi-autism arising following extreme institutional deprivation.

BACKGROUND: Rutter and colleagues' seminal observation that extended early life exposure to extreme institutional deprivation can result in what he termed quasi-autism (QA), informed both our understanding of the effects of adversity on development and the nature of autism. Here we provide the first detailed analysis of the adult outcomes of the group of institutionally deprived-then-adopted children identified as displaying QA. METHODS: Twenty-six adult adoptees identified with QA in childhood (Childhood QA+) were compared to 75 adoptees who experienced extended institutional deprivation (>6 months) but no QA (Childhood QA-), and 116 adoptees exposed to Low/No institutional deprivation. The outcomes were child-to-adult developmental trajectories of neuro-developmental symptoms (autism, attention-deficit/hyperactivity disorder (ADHD), disinhibited social engagement (DSE) and cognitive impairment), adult functioning, life satisfaction and mental health. RESULTS: Childhood QA+ was associated with elevated and persistent trajectories of broad-based autism-related difficulties, ADHD and DSE symptoms and low IQ, as well as adult mental health difficulties and functional impairment, including high rates of low educational attainment and unemployment. Life satisfaction and self-esteem were unaffected. Autism-related communication problems, in particular, predicted negative adult outcomes. Childhood QA+ was still associated with poor outcomes even when ADHD, DSE and IQ were controlled. CONCLUSIONS: Early and time-limited institutional deprivation has a critical impact on adult functioning, in part via its association with an early established and persistent variant of autism, especially related to communication difficulties. Apparent similarities and differences to non-deprivation related autism are discussed.

Inhibitory deficits and symptoms of attention-deficit hyperactivity disorder: How are they related to effortful control?

Separate studies with clinical and community-based samples have identified an association between symptoms of attention-deficit hyperactivity disorder (ADHD) and inhibitory control deficits and ADHD and weak effortful control. We tested whether differences in effortful control explained the associations between ADHD symptoms and inhibitory control deficits, controlling for conduct problems. In a community sample, parents rated ADHD symptoms, conduct problems, effortful control, surgency and negative affect in 77 4-7-year-olds (47 girls), who performed an inhibitory control task. ADHD symptoms, deficient inhibitory control and low effortful control were correlated. Controlling for conduct problems, path analysis showed the ADHD symptoms - inhibitory control link was mediated statistically by effortful control. This focuses attention on cognitive-energetic factors associated with ADHD-related executive deficits.

Neuroanatomical markers of familial risk in adolescents with conduct disorder and their unaffected relatives.

BACKGROUND: Previous 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. METHODS: Forty-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. RESULTS: The 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. CONCLUSIONS: These 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.

Parent Training for ADHD: No Generalization of Effects From Clinical to Neuropsychological Outcomes in a Randomized Controlled Trial.

OBJECTIVE: We examined whether neuropsychological function in ADHD can be improved by the New Forest Parenting Programme (NFPP), that combines standard parenting strategies with self-regulatory skills training, or predict ADHD and quality of life (QoL) treatment effects. METHOD: Participants were 93 medication-naive preschool children with ADHD (3-7 years) randomized to either NFPP (n = 49) or treatment as usual (TAU; n = 44) in a recent randomized trial. Laboratory measures of executive function, reaction time variability, and delay of gratification were collected along with parent ratings of ADHD and QoL at baseline and post treatment. Ratings were collected again at 3-month follow-up. RESULTS: NFPP did not improve neuropsychological function (compared to TAU), and baseline neuropsychological function did not predict treatment-related ADHD or QoL effects. CONCLUSION: Although NFPP includes a neuropsychological training element and has been shown to improve several clinical outcomes, it did not improve the neuropsychological functions it targets.

Annual Research Review: Perspectives on progress in ADHD science - from characterization to cause.

The science of attention-deficit/hyperactivity disorder (ADHD) is motivated by a translational goal - the discovery and exploitation of knowledge about the nature of ADHD to the benefit of those individuals whose lives it affects. Over the past fifty years, scientific research has made enormous strides in characterizing the ADHD condition and in understanding its correlates and causes. However, the translation of these scientific insights into clinical benefits has been limited. In this review, we provide a selective and focused survey of the scientific field of ADHD, providing our personal perspectives on what constitutes the scientific consensus, important new leads to be highlighted, and the key outstanding questions to be addressed going forward. We cover two broad domains - clinical characterization and, risk factors, causal processes and neuro-biological pathways. Part one focuses on the developmental course of ADHD, co-occurring characteristics and conditions, and the functional impact of living with ADHD - including impairment, quality of life, and stigma. In part two, we explore genetic and environmental influences and putative mediating brain processes. In the final section, we reflect on the future of the ADHD construct in the light of cross-cutting scientific themes and recent conceptual reformulations that cast ADHD traits as part of a broader spectrum of neurodivergence.

Editorial: 'Safety in numbers'? Big data discovery strategies in neuro-developmental science - contributions and caveats.

In the last 10 years, we have seen a shift toward the use of big data hypothesis-free discovery strategies in studies of neuro-development and mental health. In this editorial, I discuss the reasons for their popularity, their potential contribution as well as some limitations and pitfalls. I conclude with a call for methodological pluralism where big data approaches are strategically integrated into cycles of hypothesis generation and testing.

Online Parent Training for The Initial Management of ADHD referrals (OPTIMA): the protocol for a randomised controlled trial of a digital parenting intervention implemented to support parents and children on a treatment waitlist.

BACKGROUND: Children referred for attention-deficit/hyperactivity disorder (ADHD) often present with a broader pattern of conduct problems including oppositionality and defiance. This combination can be extremely stressful to parents, lower parents' self-esteem and negatively impact family life. The National Institute for Health and Care Excellence (NICE) recommends that families receive support as soon as possible after their referral. However, as clinical services are overstretched, and traditional in-person parenting intervention programmes are expensive, families often must wait times a long time prior to receiving this vital input. To address this, we have created a digital parenting programme called STEPS. It is delivered as a mobile phone app providing a set of tools and resources that can be easily accessed at parents' convenience. This study aims to evaluate the clinical and cost-effectiveness of STEPS in supporting parents of children with high levels of hyperactivity/impulsivity, inattention and conduct problems, who are waiting to be assessed by specialist children's clinical services. METHODS: Online Parent Training for The Initial Management of ADHD referrals (OPTIMA) is a two-arm superiority parallel randomised controlled trial with an internal pilot study. We aim to recruit 352 parents and their children, who have been accepted onto a waitlist in Child and Adolescent Mental Health Services or similar child health services. Parents who consent will be randomised 1:1 to either the STEPS or wait-as-usual (WAU) group. The trial will be conducted remotely (online and telephone) with measures taken at baseline and 3, 6, 9 and 12 months post-randomisation. The primary objective is to evaluate whether STEPS reduces the severity of children's oppositional and defiant behaviour, as rated by parents, measured at 3 months post-randomisation compared to WAU. DISCUSSION: Digital solutions, such as mobile phone apps, have potential for delivering psychological support for parents of children with clinical-level needs in a timely and inexpensive manner. This trial will provide data on the clinical and cost-effectiveness of the STEPS app, which could support the implementation of this scalable parenting intervention programme into standard clinical care and, ultimately, improve the outcomes for families of children referred to specialist child and adolescent health services. TRIAL REGISTRATION: ISRCTN 16523503. Prospectively registered on 18 November 2021. https://www.isrctn.com/ISRCTN16523503.

A Prospective Study of the Impact of Severe Childhood Deprivation on Brain White Matter in Adult Adoptees: Widespread Localized Reductions in Volume But Unaffected Microstructural Organization.

Early childhood neglect can impact brain development across the lifespan. Using voxel-based approaches we recently reported that severe and time-limited institutional deprivation in early childhood was linked to substantial reductions in total brain volume in adulthood, >20 years later. Here, we extend this analysis to explore deprivation-related regional white matter volume and microstructural organization using diffusion-based techniques. A combination of tensor-based morphometry (TBM) analysis and tractography was conducted on diffusion-weighted imaging (DWI) data from 59 young adults who spent between 3 and 41 months in the severely depriving Romanian institutions of the 1980s before being adopted into United Kingdom families, and 20 nondeprived age-matched United Kingdom controls. Independent of total volume, institutional deprivation was associated with smaller volumes in localized regions across a range of white matter tracts including (1) long-ranging association fibers such as bilateral inferior longitudinal fasciculus (ILF), bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculi (SLFs), and left arcuate fasciculus; (2) tracts of the limbic circuitry including fornix and cingulum; and (3) projection fibers with the corticospinal tract particularly affected. Tractographic analysis found no evidence of altered microstructural organization of any tract in terms of hindrance modulated orientational anisotropy (HMOA), fractional anisotropy (FA), or mean diffusivity (MD). We provide further evidence for the effects of early neglect on brain development and their persistence in adulthood despite many years of environmental enrichment associated with successful adoption. Localized white matter effects appear limited to volumetric changes with microstructural organization unaffected.