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ObjectiveMost young autistic children display emotional and behavioral problems (EBPs). There is evidence that behavioral parenting interventions (BPIs) reduce these. The COVID-19 pandemic and associated lockdowns can be seen as a natural experiment to test the longer-term effect of BPIs under conditions of increased uncertainty.MethodOpportunistic follow-up (n = 49) of a pilot randomized controlled trial (RCT) cohort (n = 62 autistic children aged 6-11 years; originally randomized to a 12-week group BPI [Predictive Parenting; n = 31] or an attention control [Psychoeducation; n = 31]) was conducted during COVID-19−related lockdowns. Measures of parent-reported child irritability and parenting stress were collected at 3 time points (baseline: mean age = 6.7 years; primary endpoint: mean age = 7.1 years, ∼5 months after randomization; and COVID-19 follow-up: mean age = 8.8 years, ∼2 years after randomization). We tested the magnitude of intervention effects using point estimates of differences in child irritability and parenting stress between arms at primary endpoint and COVID-19 follow-up, covarying for baseline scores. We used area under the curve (AUC) analyses to obtain overall estimates of the average intervention effect across all 3 timepoints. Semi-structured qualitative interviews were conducted with a subsample of parents (n = 18).ResultsA small but significant intervention effect was found from baseline to COVID-19 follow-up in favor of Predictive Parenting on parent-reported child irritability (d = −0.33, 95% CI = −0.65, −0.01) and parenting stress (d = −0.31, 95% CI = −0.59, −0.03). No overall mean intervention effect for these measures as estimated by the AUC analyses (which takes into account the nonsignificant effect at primary endpoint) was found. Interview feedback on the both interventions was positive, and parents reported using strategies from Predictive Parenting during COVID-19−related restrictions.ConclusionThis opportunistic follow-up study at a time of stress indicates the need for careful consideration of how and when to measure the effects of BPIs in autistic child populations. Future trials should consider both the most appropriate endpoint and in what context effects may be more likely to be seen.Clinical trial registration informationAutism Spectrum Treatment and Resilience (ASTAR); https://www.isrctn.com; 91411078.

Introduction: The use of benzodiazepines and/or z-drugs in women of childbearing age has increased. Objective: The aim of the study was to evaluate whether gestational benzodiazepine and/or z-drug exposure is associated with adverse birth and neurodevelopmental outcomes. Methods: A population-based cohort including mother-child pairs from 2001 to 2018 in Hong Kong was analysed to compare gestationally exposed and nonexposed children on the risk of preterm birth, small for gestational age, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) through logistic/Cox proportional hazards regression with a 95% confidence interval (CI). Sibling-matched analyses and negative control analyses were applied. Results: When comparing gestationally exposed with gestationally nonexposed children, the weighted odds ratio (wOR) was 1.10 (95% CI = 0.97–1.25) for preterm birth and 1.03 (95% CI = 0.76–1.39) for small for gestational age, while the weighted hazard ratio (wHR) was 1.40 (95% CI = 1.13–1.73) for ASD and 1.15 (95% CI = 0.94–1.40) for ADHD. Sibling-matched analyses showed no association between gestationally exposed children and their gestationally nonexposed siblings for all outcomes (preterm birth: wOR = 0.84, 95% CI = 0.66–1.06; small for gestational age: wOR = 1.02, 95% CI = 0.50–2.09; ASD: wHR = 1.10, 95% CI = 0.70–1.72; ADHD: wHR = 1.04, 95% CI = 0.57–1.90). Similarly, no significant differences were observed when comparing children whose mothers took benzodiazepines and/or z-drugs during pregnancy to children whose mothers took benzodiazepines and/or z-drugs before but not during pregnancy for all outcomes. Conclusions: The findings do not support a causal relationship between gestational benzodiazepines and/or z-drugs exposure and preterm birth, small for gestational age, ASD, or ADHD. Clinicians and pregnant women should carefully balance the known risks of benzodiazepines and/or z-drugs use against those of untreated anxiety and sleep problems.

Contains fulltext : 290864.pdf (Publisher’s version ) (Open Access) 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. 01 april 2023

BackgroundAlthough autism and callous-unemotional (CU) traits are distinct conditions, both are associated with difficulties in emotion recognition. However, it is unknown whether the emotion recognition difficulties characteristic of autism and CU traits are driven by comparable underpinning mechanisms.MethodsWe tested whether cueing to the eyes improved emotion recognition in relation to autistic and CU traits in a heterogeneous sample of children enhanced for social, emotional and behavioural difficulties. Participants were 171 (n = 75 male) children aged 10–16 years with and without a diagnosis of autism (n = 99 autistic), who completed assessments of emotion recognition with and without cueing to the eyes. Parents completed the assessment of autistic and CU traits.ResultsAssociations between autistic and CU traits and emotion recognition accuracy were dependent upon gaze cueing. CU traits were associated with an overall decrease in emotion recognition in the uncued condition, but better fear recognition when cued to the eyes. Conversely, autistic traits were associated with decreased emotion recognition in the cued condition only, and no interactions between autistic traits and emotion were found.ConclusionsThe differential effect of cueing to the eyes in autistic and CU traits suggests different mechanisms underpin emotion recognition abilities. Results suggest interventions designed to promote looking to the eyes may be beneficial for children with CU traits, but not for children with autistic characteristics. Future developmental studies of autism and CU characteristics are required to better understand how different pathways lead to overlapping socio-cognitive profiles.

Despite the high prevalence of mental health difficulties in autistic youth, little is known about the patterns of developmental continuity and change in psychiatric symptoms between childhood and adolescence. Using a stratified community-derived sample of autistic youth (n = 101; 57 males, 44 females), within (homotypic) and between (heterotypic) domain associations between psychiatric symptoms in childhood to adolescence were tested as well as whether any continuities were moderated by sex, IQ, autism symptom severity, social economic status, or parental mental health.Autistic youth were assessed for emotional, behavioral, and attention-deficit/hyperactivity disorder (ADHD) symptoms in childhood (age 4-9 years) and adolescence (age 13-17 years) using parental diagnostic interview. Unadjusted and adjusted (accounting for the co-occurrence of psychiatric symptoms in childhood) weighted models tested homotypic and heterotypic associations between symptoms in childhood and adolescence. Moderation of significant pathways was tested using multigroup analysis.Adolescent psychiatric symptoms all were predicted by symptoms of their childhood counterparts (emotional symptoms incidence rate ratio [IRR] = 1.06, 95% CI = 1.02-1.10, p .01; behavioral symptoms IRR = 1.38, 95% CI = 1.21-1.59, p .01; ADHD symptoms IRR = 1.11, 95% CI = 1.05-1.19, p .01); the only heterotypic pathway that remained significant in adjusted analyses was from childhood emotional symptoms to adolescent ADHD symptoms (IRR = 1.04, 95% CI = 1.01-1.07, p = .02). Sex moderated the homotypic ADHD symptoms pathway; associations were significant in female participants only. Child IQ moderated the homotypic behavioral symptoms pathway; the association was stronger in youth with IQ 70.Results from this community-based sample suggest that psychiatric symptoms in autistic youth exhibit substantial developmental continuity and thus highlight the importance of early screening and intervention. Sex and IQ may be important factors to consider when predicting likelihood of stability of ADHD and behavioral symptoms.

The Goldacre review, published in April, 2022, 1 is a landmark evaluation of the use, availability, and safety of National Health Service (NHS) data across all four nations of the UK. The review underscores the necessary role of data in driving health-care improvement and innovation, and the potential risks inherent in using data routinely contributed by health service users. The review recommends a radical overhaul in NHS data curation, access, and analysis, and, crucially, argues that substantial new resources must be marshalled to make this aspiration a reality.

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

Objective This systematic review and meta-analysis aimed to determine the accuracies of a broad range of screening tools for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, and to compare the diagnostic accuracy of tools between population-based and clinical/high-risk samples, and across reporters. Method MEDLINE, PsycINFO, EMBASE, and PubMed were searched up until February 20, 2020, with no language restrictions. Studies reporting diagnostic accuracy of a screening tool against a diagnosis of ADHD in children and adolescents

Autism spectrum disorder (ASD) often co-occurs with attention-deficit/hyperactivity disorder (ADHD) and people with these conditions have frontostriatal functional atypicality during motor inhibition. We compared the neural and neurocognitive correlates of motor inhibition and performance monitoring in young adult males with “pure” and combined presentations with age-and sex-matched typically developing controls, to explore shared or disorder-specific atypicality. Males aged 20–27 years with typical development (TD; n = 22), ASD (n = 21), combined diagnoses ASD + ADHD (n = 23), and ADHD (n = 25) were compared using a modified tracking fMRI stop-signal task that measures motor inhibition and performance monitoring while controlling for selective attention. In addition, they performed a behavioural go/no-go task outside the scanner. While groups did not differ behaviourally during successful stop trials, the ASD + ADHD group relative to other groups had underactivation in typical performance monitoring regions of bilateral anterior insula/inferior frontal gyrus, right posterior thalamus, and right middle temporal gyrus/hippocampus during failed inhibition, which was associated with increased stop-signal reaction time. In the behavioural go/no-go task, both ADHD groups, with and without ASD, had significantly lower motor inhibition performance compared to TD controls. In conclusion, only young adult males with ASD + ADHD had neurofunctional atypicality in brain regions associated with performance monitoring, while inhibition difficulties on go/no-go task performance was shared with ADHD. The suggests that young people with ASD + ADHD are most severely impaired during motor inhibition tasks compared to ASD and ADHD but do not reflect a combination of the difficulties associated with the pure disorders.

In this issue of the Journal, Cherkasova et al.

Autistic people experience high rates of co-occurring psychiatric diagnoses. Current prevalence estimates vary considerably due to an over-reliance on clinical cohorts and the longitudinal stability of diagnoses from childhood into adolescence is poorly understood. This study aims to provide prevalence rates of co-occurring DSM-5 psychiatric diagnosis for autistic adolescence and investigate, for the first time, the stability of diagnoses from childhood. Using a longitudinal stratified sample of autistic youth (N = 77; 13–17 years; 60% male), selected from a larger community-derived sample of those with pre-existing autism diagnoses (N = 277) weighted prevalence estimates of emotional (anxiety, depression), behavioural (oppositional and conduct disorders) and ADHD diagnoses were calculated based on semi-structured psychiatric interview. Prediction of adolescent psychiatric diagnosis based on childhood diagnostic status, sex, childhood IQ (both assessed at age 4–10 years) was tested. Emotional and behavioural disorders in adolescence were particularly prevalent, and significantly predicted by childhood disorder status. Attention-deficit/hyperactivity-disorder (ADHD) was prevalent but not predicted by childhood ADHD diagnosis. Neither sex nor childhood IQ predicted diagnostic outcomes. Autistic youth have high levels of co-occurring psychiatric conditions, which are broadly persistent across childhood and adolescence. Emotional disorders are particularly prevalent and remain persistent from childhood to adolescence. Greater diagnostic variability was found for ADHD with more adolescents moving across diagnostic thresholds.

Contains fulltext : 235396.pdf (Publisher’s version ) (Open Access) In the last decade there has been a revolution in terms of genetic findings in neurodevelopmental disorders (NDDs), with many discoveries critical for understanding their aetiology and pathophysiology. Clinical trials in single-gene disorders such as fragile X syndrome highlight the challenges of investigating new drug targets in NDDs. Incorporating a developmental perspective into the process of drug development for NDDs could help to overcome some of the current difficulties in identifying and testing new treatments. This paper provides a summary of the proceedings of the 'New Frontiers Meeting' on neurodevelopmental disorders organised by the European College of Neuropsychopharmacology in conjunction with the Innovative Medicines Initiative-sponsored AIMS-2-TRIALS consortium. It brought together experts in developmental genetics, autism, NDDs, and clinical trials from academia and industry, regulators, patient and family associations, and other stakeholders. The meeting sought to provide a platform for focused communication on scientific insights, challenges, and methodologies that might be applicable to the development of CNS treatments from a neurodevelopmental perspective. Multidisciplinary translational consortia to develop basic and clinical research in parallel could be pivotal to advance knowledge in the field. Although implementation of clinical trials for NDDs in paediatric populations is widely acknowledged as essential, safety concerns should guide each aspect of their design. Industry and academia should join forces to improve knowledge of the biology of brain development, identify the optimal timing of interventions, and translate these findings into new drugs, allowing for the needs of users and families, with support from regulatory agencies.

Objective: Anxiety disorders are among the most common co-occurring conditions in autism spectrum disorder (ASD). Despite their prevalence and impact, there are no randomized controlled trials (RCTs) aimed at evaluating the efficacy of selective serotonin reuptake inhibitors (SSRIs) for anxiolysis in this population, who may have a different biological basis for anxiety. Methods: Secondary analyses of the STAART double-blind, placebo-controlled RCT of citalopram in children with ASD examined whether citalopram reduced anxiety measured on the parent-reported Child and Adolescent Symptom Inventory-4 (CASI-4) as the primary outcome. An intention-To-Treat analysis involving all 149 participants used multiple imputations for missing data and included baseline stratification factors of age group and site, among others. We prespecified as clinically significant a 33% reduction in anxiety in citalopram versus placebo, coinciding with 80% power. We tested whether communicative ability on the Vineland Communication score moderated treatment effect and explored whether initial anxiety was associated with greater adverse events, which could impact on dose titration and achieving optimal dose. Results: Both groups showed substantial reduction in anxiety. Citalopram was associated with a nonsignificant 16.5% greater reduction (observed coefficient =-0.181, bootstrap standard error = 0.126, p = 0.151, confidence interval =-0.428 to 0.066). Anxiety reports were significantly lower in children with reduced communicative ability, but communicative ability did not moderate the treatment effect (interaction p = 0.294). Initial anxiety levels were not associated with increased adverse effects (interaction ps 0.162-0.954). Conclusion: Citalopram did not statistically significantly improve anxiety in children with ASD. Clinicians should be cautious in their use of SSRIs for this indication. There remains a need for well-powered clinical trials testing the efficacy of SSRIs among autistic children with anxiety disorders.

Research suggests an increased prevalence of callous-unemotional (CU) traits in children with autism spectrum disorder (ASD), and a similar impairment in fear recognition to that reported in non-ASD populations. However, past work has used measures not specifically designed to measure CU traits and has not examined whether decreased attention to the eyes reported in non-ASD populations is also present in individuals with ASD. The current paper uses a measure specifically designed to measure CU traits to estimate prevalence in a large community-based ASD sample. Parents of 189 adolescents with ASD completed questionnaires assessing CU traits, and emotional and behavioral problems. A subset of participants completed a novel emotion recognition task (n = 46). Accuracy, reaction time, total looking time, and number of fixations to the eyes and mouth were measured. Twenty-two percent of youth with ASD scored above a cut-off expected to identify the top 6% of CU scores. CU traits were associated with longer reaction times to identify fear and fewer fixations to the eyes relative to the mouth during the viewing of fearful faces. No associations were found with accuracy or total looking time. Results suggest the mechanisms that underpin CU traits may be similar between ASD and non-ASD populations.

BackgroundPeople with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have abnormalities in frontal, temporal, parietal and striato-thalamic networks. It is unclear to what extent these abnormalities are distinctive or shared. This comparative meta-analysis aimed to identify the most consistent disorder-differentiating and shared structural and functional abnormalities.MethodsSystematic literature search was conducted for whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies of cognitive control comparing people with ASD or ADHD with typically developing controls. Regional gray matter volume (GMV) and fMRI abnormalities during cognitive control were compared in the overall sample and in age-, sex- and IQ-matched subgroups with seed-based d mapping meta-analytic methods.ResultsEighty-six independent VBM (1533 ADHD and 1295 controls; 1445 ASD and 1477 controls) and 60 fMRI datasets (1001 ADHD and 1004 controls; 335 ASD and 353 controls) were identified. The VBM meta-analyses revealed ADHD-differentiating decreased ventromedial orbitofrontal (z = 2.22, p < 0.0001) but ASD-differentiating increased bilateral temporal and right dorsolateral prefrontal GMV (zs ⩾ 1.64, ps ⩽ 0.002). The fMRI meta-analyses of cognitive control revealed ASD-differentiating medial prefrontal underactivation but overactivation in bilateral ventrolateral prefrontal cortices and precuneus (zs ⩾ 1.04, ps ⩽ 0.003). During motor response inhibition specifically, ADHD relative to ASD showed right inferior fronto-striatal underactivation (zs ⩾ 1.14, ps ⩽ 0.003) but shared right anterior insula underactivation.ConclusionsPeople with ADHD and ASD have mostly distinct structural abnormalities, with enlarged fronto-temporal GMV in ASD and reduced orbitofrontal GMV in ADHD; and mostly distinct functional abnormalities, which were more pronounced in ASD.

BackgroundThe COVID-19 pandemic necessitated the adoption of telemental health (TMH). Pre-pandemic, clinicians had voiced many TMH concerns, but these had not been investigated with respect to autism spectrum disorder (ASD) even with it being known that there are distinct ASD-associated challenges for in-person mental health interventions.MethodA convenience sample of (n = 55) clinicians completed an online survey regarding their perspectives of adopting TMH interventions in ASD, with closed- and open-answered questions. Quantitative and qualitative data were analysed descriptively/inferentially and via Content Analysis, respectively.ResultsMultiple clinicians endorsed each TMH challenges/barrier previously identified as concerns in the non-ASD literature. However, overall levels of concern over challenges/barriers were low, and challenges were more likely to be predicted than experienced and considered to be case/presentation specific. Challenges that were considered ASD-specific included the exacerbation of those associated with in-person delivery in ASD, alongside difficulties with trust and appropriate remote social behaviour. On average, clinicians indicated a preference for 50% TMH interventions post-pandemic. Clinicians’ perceived technological competence and extent of professional experience with ASD were not significantly associated with levels of concern, nor number of experienced challenges, with TMH interventions in ASD.ConclusionIn support of the existing TMH literature, challenges/barriers were more likely to be predicted than experienced and were considered to be case/presentation-specific, though this may be more variable in ASD owing to the well-established marked heterogeneity in this population. Remote provision of interventions exacerbated in-person ASD-associated challenges, as predicted, but clinician-level factors appeared not to impact TMH perceptions.

Objective: To examine the feasibility and preliminary efficacy of a group behavioral parenting intervention for emotional and behavioral problems (EBPs) in young autistic children. Method: This was a feasibility pilot randomized controlled trial comparing a 12-week group behavioral parenting intervention (Predictive Parenting) to an attention control (Psychoeducation). Parents of 62 autistic children 4 to 8 years of age were randomized to Predictive Parenting (n = 31) or Psychoeducation (n = 31). The primary outcome was a blinded observational measure of child behaviors that challenge. Secondary outcomes were observed child compliance and parenting behaviors; parent- and teacher-reported child EBPs; self-reported parenting practices, stress, self-efficacy, and well-being. Cost-effectiveness was also explored. Results: Recruitment, retention, completion of measures, treatment fidelity, and parental satisfaction were high for both interventions. There was no group difference in primary outcome: mean log of rate 0.18 lower (d, 90% CI = −0.44 to 0.08) in Predictive Parenting. Differences in rates of child compliance (0.44, 90% CI = 0.11 to 0.77), facilitative parenting (0.63, 90% CI = 0.33 to 0.92) and parent-defined target symptom change (−0.59, 90% CI −0.17 to −1.00) favored Predictive Parenting. There were no differences on other measures. Predictive Parenting was more expensive than Psychoeducation, with a low probability of being more cost-effective. Conclusion: Feasibility was demonstrated. There was no evidence from this pilot trial that Predictive Parenting resulted in reductions in child EBPs beyond those seen following Psychoeducation; in addition, the effect size was small, and it was more expensive. However, it showed superiority for child compliance and facilitative parenting with moderate effect sizes. Future, definitive studies should evaluate whether augmented or extended intervention would lead to larger improvements. Clinical trial registration information: Autism Spectrum Treatment and Resilience (ASTAR); https://www.isrctn.com/ISRCTN91411078.

This systematic review (Prospero Registration Number: CRD42019142910) aimed to narratively synthesise technology-aided assessments and treatments of anxiety in individuals with autism spectrum disorder (ASD) for the first time. Sixteen studies were identified: 5 assessment studies and 11 treatment studies. Assessment studies targeted state anxiety using ecological momentary assessment, wearables, or computerised tasks. Treatment studies targeted specific fears/phobias using electronic screen media or transdiagnostic anxiety using telemedicine. Broadly, results indicated technology-aided assessments and treatments may be feasible and effective at targeting anxiety in ASD, except treatments involving social scripts or peer modelling. Assessment results further indicated that state anxiety in ASD has a distinct psychophysiological signature and is evoked by idiosyncratic triggers. However, larger scale studies with representative samples are needed.

Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a broad range of pharmacological interventions for emotional dysregulation and irritability in ASD and predictors of response.Following a preregistered protocol (PROSPERO: CRD42021235779), we systematically searched multiple databases until January 1, 2021. We included placebo-controlled randomized controlled trials (RCTs) and evaluated the efficacy of pharmacological interventions and predictors of response for emotional dysregulation and irritability. We assessed heterogeneity using Q statistics and publication bias. We conducted subanalyses and meta-regressions to identify predictors of response. The primary effect size was the standardized mean difference. Quality of studies was assessed using the Cochrane Risk of Bias Tool (RoB2).A total of 2,856 individuals with ASD in 45 studies were included, among which 26.7% of RCTs had a high risk of bias. Compared to placebo, antipsychotics (standardized mean difference = 1.028, 95% CI = 0.824-1.232) and medications used to treat attention-deficit/hyperactivity disorder (ADHD) (0.471, 0.061-0.881) were significantly better than placebo in improving emotional dysregulation and irritability, whereas evidence of efficacy was not found for other drug classes (p.05). Within individual medications, evidence of efficacy was found for aripiprazole (1.179, 0.838-1.520) and risperidone (1.074, 0.818-1.331). Increased rates of comorbid epilepsy (β = -0.049, p = .026) were associated with a lower efficacy.Some pharmacological interventions (particularly risperidone and aripiprazole) have proved efficacy for short-term treatment of emotional dysregulation and irritability in ASD and should be considered within a multimodal treatment plan, taking into account also the tolerability profile and families' preferences.

Over the last year, the coronavirus disease 2019 (COVID-19) pandemic has resulted in profound disruptions across the globe, with school closures, social isolation, job loss, illness, and death affecting the lives of children and families in myriad ways. In an Editors' Note in our June 2020 issue, 1 our senior editorial team described this Journal's role in advancing knowledge in child and adolescent mental health during the pandemic and outlined areas we identified as important for science and practice in our field. Since then, the Journal has published articles on the impacts of the pandemic on child and adolescent mental health and service systems, 2-5 which are available in a special collection accessible through the Journal's website. 6 Alongside many opinion papers, the pace of publication of empirical research in this area is rapidly expanding, covering important issues such as increased frequency of mental health symptoms among children and adolescents 3,5,7-10 and changes in patterns of clinical service use such as emergency department visits. 11-14 As the Senior Editors prepared that Editors’ Note, they were acutely aware that the priorities that they identified were broad and generated by only a small group of scientists and clinicians. Although this had the advantage of enabling us to get this information out to readers quickly, we decided that a more systematic approach to developing recommendations for research priorities would be of greater long-term value. We were particularly influenced by the efforts of the partnership between the UK Academy of Medical Scientists and a UK mental health research charity (MQ: Transforming Mental Health) to detail COVID-19−related research priorities for “Mental Health Science” that was published online by Holmes et al. in The Lancet Psychiatry in April 2020. 15 Consistent with its focus on mental health research across the lifespan, several recommendations highlighted child development and children's mental health. However, a more detailed assessment of research priorities related to child and adolescent mental health was beyond the scope of that paper. Furthermore, the publication of that position paper preceded the death of George Floyd at the hands of Minneapolis police on May 25, 2020, which re-energized efforts to acknowledge and to address racism and healthcare disparities in the United States and many other countries. To build upon the JAACAP Editors’ Note 1 and the work of Holmes et al., 15 we conducted an international survey of professionals—practitioners and researchers—working on child and adolescent development and pediatric mental health to identify concerns about the impact of the pandemic on children, adolescents, and their families, as well as what is helping families navigate these impacts, and the specific research topics that are of greatest importance.

Background: Social anxiety is common in autistic adolescents. While emerging evidence indicates the importance of several mechanisms (including intolerance of uncertainty (IU), alexithymia and sensory processing) for maintaining anxiety, limited research has explored how these factors are associated with social anxiety in autistic adolescents. Methods: We investigated whether IU, emotional and sensory processing are related to social anxiety in autistic and neurotypical adolescents, gathering experimental and questionnaire data from 61 autistic and 62 neurotypical 11- to 17-year-olds recruited to have similarly high levels of anxiety. Results: In autistic and neurotypical adolescents matched for social anxiety, similar significant associations were observed between social anxiety and IU, alexithymia, maladaptive emotion regulation, sensory hypersensitivity and interoceptive sensibility. Taking a dimensional approach, we found that child- and parent-reported IU, alexithymia and sensory hypersensitivity mediated the relationship between autistic traits and social anxiety symptoms in the combined group of adolescents. Conclusions: Our findings indicate that similar correlates of social anxiety are evident in autistic and neurotypical youths experiencing social anxiety and further our understanding of mechanisms that may contribute towards social anxiety in both groups.

Theory of mind (ToM) or mentalizing difficulties is reported in attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), but the mechanism underpinning these apparently shared deficits is relatively unknown. Eighty-three young adult males, 19 with ASD alone, 21 with ADHD alone, 18 with dual diagnosis of ASD and ADHD, and 25 typically developing (TD) controls completed the functional magnetic resonance imaging version of the Frith-Happé animated-triangle ToM task. We compared neural function during ToM with two non-ToM conditions, random and goal directed motions, using whole-brain and region-of-interest analysis of brain activation and functional connectivity analyses. The groups showed comparable ToM task performance. All three clinical groups lacked local connectivity increase shown by TD controls during ToM in the right temporoparietal cortex, a key mentalizing region, with a differentially increased activation pattern in both ASD and comorbid groups relative to ADHD. Both ASD groups also showed reduced connectivity between right inferior lateral prefrontal and posterior cingulate cortices that could reflect an atypical information transmission to the mentalizing network. In contrast, with mentalizing both ADHD groups showed decreasing connectivity between the medial prefrontal and left temporoparietal cortices when compared to TD controls. Therefore, despite the complex pattern of atypical brain function underpinning ToM across the three disorders, some neurofunctional abnormalities during ToM are associated with ASD and appeared differentiable from those associated with ADHD, with the comorbid group displaying combined abnormalities found in each condition.

Highlights • No association between gestational diabetes and common mental disorders prior to and during pregnancy. • One of the largest cohort studies in multi-ethnic UK population of 12,239 women with 13,539 pregnancies. • No increase in risk observed with increasing levels of hyperglycaemia used as a continuous measure. • Reassuring findings for women with GDM and/or CMD., Background anxiety and depression are common in women with gestational diabetes but it is not clear whether they are more likely to precede the onset of gestational diabetes or to co-occur with it. Our aims were to compare the strength of association between common mental disorders of anxiety and depression (i) before pregnancy and (ii) during pregnancy in women with and without gestational diabetes. Methods the sample comprised 12,239 women with 13,539 pregnancies from the UK's Born in Bradford cohort. Gestational diabetes was diagnosed by oral glucose tolerance test (OGTT). Indicators of common mental disorders were obtained from linked primary care records. Multivariable robust Poisson and logistic regression were employed. Multiple imputation by chained equations was implemented to handle missing data. Models were adjusted for maternal age, ethnicity, education and obstetric complications. Analyses of common mental disorders during pregnancy were additionally adjusted for maternal smoking, pre-pregnancy BMI, multiple pregnancy and common mental disorders prior to pregnancy. Results there was no evidence for an association between common mental disorders prior to pregnancy and gestational diabetes (adjusted RR 0.96; 95% CI 0.80,1.15) or between gestational diabetes and common mental disorders during pregnancy (adjusted OR 0.91; 95% CI 0.73,1.12). Limitations high levels of deprivation and multi-ethnic composition of the cohort may limit generalisability of these findings to other populations. Conclusions routine primary care records did not identify an increased risk of gestational diabetes in women with common mental disorders prior to pregnancy or of gestational diabetes in women with common mental disorders during pregnancy.

BACKGROUND: Patient-reported outcome measures (PROMs) are important tools to inform patients, clinicians and policy-makers about clinical need and the effectiveness of any given treatment. Consistent PROM use can promote early symptom detection, help identify unexpected treatment responses and improve therapeutic engagement. Very few studies have examined associations between patient characteristics and PROM data collection.METHODS: We used the electronic mental health records for 28,382 children and young people (aged 4-17 years) accessing Child and Adolescent Mental Health Services (CAMHS) across four South London boroughs between the 1st of January 2008 to the 1st of October 2017. We examined the completion rates of the caregiver Strengths and Difficulties Questionnaire (SDQ), a ubiquitous PROM for CAMHS at baseline and 6-month follow-up.RESULTS AND CONCLUSIONS: SDQs were present for approximately 40% (n = 11,212) of the sample at baseline, and from these, only 8% (n = 928) had a follow-up SDQ. Patterns of unequal PROM collection by sociodemographic factors were identified: males were more likely (aOR 1.07, 95% CI 1.01-1.13), whilst older age (aOR 0.87, 95% CI 0.87-0.88), Black (aOR 0.79 95% CI 0.74-0.84) and Asian ethnicity (aOR 0.75 95% CI 0.66-0.86) relative to White ethnicity, and residence within the most deprived neighbourhood (aOR 0.87 95% CI 0.80-0.94) were less likely to have a record of baseline SDQ. Similar results were found in the sub-group (n = 11,212) with follow-up SDQ collection. Our findings indicate systematic differences in the currently available PROMS data and highlights which groups require increased focus if we are to gain equitable PROM collection. We need to ensure representative PROM collection for all individuals accessing treatment, regardless of ethnic or socioeconomic background; biased data have adverse ramifications for policy and service level decision-making.

One in seven children with an impairing mental health disorder has intellectual disability (ID). Despite the ubiquity of ID, many clinicians are less confident in the assessment and management of mental disorders in youth with ID. Key to determining how to modify these is a good understanding of the child's developmental/cognitive strengths and weaknesses. There is very limited evidence for mental health interventions specific to children with ID. In this context, NICE guidelines generally recommend the same interventions identified for typically developing children. However, psychological interventions should be adapted for developmental level and communication ability. Medication should be selected carefully taking account of co-existing conditions, drug interactions and the greater sensitivity to adverse effects in this population. Assessment and intervention should always take account of the child's wider context, including education. There is little evidence regarding the best service models in relation to efficacy and efficiency, but the high prevalence of ID amongst youth with mental health problems suggests that all mental health professionals should have competence in working with youth with milder levels of ID.

ObjectiveFor the first time, we use a longitudinal population-based autism cohort to chart the trajectories of cognition and autism symptoms from childhood to early adulthood and identify features that predict the level of function and change with development.MethodLatent growth curve models were fitted to data from the Special Needs and Autism Project cohort at three time points: 12, 16, and 23 years. Outcome measures were IQ and parent-reported Social Responsiveness Scale autism symptoms. Of the 158 participants with an autism spectrum disorder at 12 years, 126 (80%) were reassessed at 23 years. Child, family, and contextual characteristics obtained at 12 years predicted intercept and slope of the trajectories.ResultsBoth trajectories showed considerable variability. IQ increased significantly by a mean of 7.48 points from 12 to 23 years, whereas autism symptoms remained unchanged. In multivariate analysis, full-scale IQ was predicted by initial language level and school type (mainstream/specialist). Participants with a history of early language regression showed significantly greater IQ gains. Autism symptoms were predicted by Social Communication Questionnaire scores (lifetime version) and emotional and behavioral problems. Participants attending mainstream schools showed significantly fewer autism disorder symptoms at 23 years than those in specialist settings; this finding was robust to propensity score analysis for confounding.ConclusionOur findings suggest continued cognitive increments for many people with autism across the adolescent period, but a lack of improvement in autism symptoms. Our finding of school influences on autism symptoms requires replication in other cohorts and settings before drawing any implications for mechanisms or policy.

It has been suggested that the structure of psychiatric phenomena can be reduced to a few symptom dimensions. These proposals, mainly based on epidemiological samples, may not apply to clinical populations. We tested the structure of psychiatric symptoms across two pediatric clinical samples from England (N = 8434) and Norway (N = 5866). Confirmatory factor analyses of the parent-reported Strengths and Difficulties Questionnaire (SDQ) evaluated the relative fit of several models, including a first-order model, a second-order model with the widely-established broad symptom dimensions of internalizing-externalizing, and two bi-factor models capturing a general psychopathology factor. Predictive value of the SDQ subscales for psychiatric disorders was examined. A first-order five-factor solution better fit the data. The expected SDQ subscale(s) related best to the corresponding psychiatric diagnosis. In pediatric clinical samples, a granular approach to psychiatric symptoms where several dimensions are considered seems to fit the data better than models based on lumping symptoms into internalizing/externalizing dimensions. Electronic supplementary material The online version of this article (10.1007/s10578-017-0777-1) contains supplementary material, which is available to authorized users.

Contains fulltext : 204809.pdf (Publisher’s version ) (Closed access) Although pharmacological therapies are recommended as a key component in the treatment of attention-deficit hyperactivity disorder, their use continues to prompt intense debate. Despite considerable research efforts, several gaps in the knowledge base and several questions over the quality of evidence exist. Particular issues surrounding pharmacological treatments include uncertainties about long-term effectiveness and safety, safety profiles in adults, and the comparative effectiveness of different medications. In this Review, we focus on four key methodological issues for future research: (1) the use of appropriate trial designs; the need for (2) outcome measures targeting effectiveness beyond symptom control and (3) safety outcome measures; and (4) the application of clinical and administrative research databases to assess real-world outcomes. Potential solutions include increased use of randomised placebo-controlled withdrawal trials and large pharmacoepidemiological studies that use electronic health-care records on the long-term effectiveness and safety of medications. Pragmatic head-to-head randomised trials would also provide direct evidence on comparative effectiveness and safety profiles.

Published online at: DOI: 10.1016/S2215-0366(18)30396-1 This is an Open Access article under the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). Copyright © 2018 Elsevier Ltd. All rights reserved.

© 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: The benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD) remain controversial, and guidelines are inconsistent on which medications are preferred across different age groups. We aimed to estimate the comparative efficacy and tolerability of oral medications for ADHD in children, adolescents, and adults. Methods: We did a literature search for published and unpublished double-blind randomised controlled trials comparing amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo. We systematically contacted study authors and drug manufacturers for additional information. Primary outcomes were efficacy (change in severity of ADHD core symptoms based on teachers' and clinicians' ratings) and tolerability (proportion of patients who dropped out of studies because of side-effects) at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. We estimated summary odds ratios (ORs) and standardised mean differences (SMDs) using pairwise and network meta-analysis with random effects. We assessed the risk of bias of individual studies with the Cochrane risk of bias tool and confidence of estimates with the Grading of Recommendations Assessment, Development, and Evaluation approach for network meta-analyses. This study is registered with PROSPERO, number CRD42014008976. Findings: 133 double-blind randomised controlled trials (81 in children and adolescents, 51 in adults, and one in both) were included. The analysis of efficacy closest to 12 weeks was based on 10 068 children and adolescents and 8131 adults; the analysis of tolerability was based on 11 018 children and adolescents and 5362 adults. The confidence of estimates varied from high or moderate (for some comparisons) to low or very low (for most indirect comparisons). For ADHD core symptoms rated by clinicians in children and adolescents closest to 12 weeks, all included drugs were superior to placebo (eg, SMD −1·02, 95% CI −1·19 to −0·85 for amphetamines, −0·78, −0·93 to −0·62 for methylphenidate, −0·56, −0·66 to −0·45 for atomoxetine). By contrast, for available comparisons based on teachers' ratings, only methylphenidate (SMD −0·82, 95% CI −1·16 to −0·48) and modafinil (−0·76, −1·15 to −0·37) were more efficacious than placebo. In adults (clinicians' ratings), amphetamines (SMD −0·79, 95% CI −0·99 to −0·58), methylphenidate (−0·49, −0·64 to −0·35), bupropion (−0·46, −0·85 to −0·07), and atomoxetine (−0·45, −0·58 to −0·32), but not modafinil (0·16, −0·28 to 0·59), were better than placebo. With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36–3·89) and adults (3·26, 1·54–6·92); guanfacine was inferior to placebo in children and adolescents only (2·64, 1·20–5·81); and atomoxetine (2·33, 1·28–4·25), methylphenidate (2·39, 1·40–4·08), and modafinil (4·01, 1·42–11·33) were less well tolerated than placebo in adults only. In head-to-head comparisons, only differences in efficacy (clinicians' ratings) were found, favouring amphetamines over modafinil, atomoxetine, and methylphenidate in both children and adolescents (SMDs −0·46 to −0·24) and adults (−0·94 to −0·29). We did not find sufficient data for the 26-week and 52-week timepoints. Interpretation: Our findings represent the most comprehensive available evidence base to inform patients, families, clinicians, guideline developers, and policymakers on the choice of ADHD medications across age groups. Taking into account both efficacy and safety, evidence from this meta-analysis supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred first-choice medications for the short-term treatment of ADHD. New research should be funded urgently to assess long-term effects of these drugs. Funding: Stichting Eunethydis (European Network for Hyperkinetic Disorders), and the UK National Institute for Health Research Oxford Health Biomedical Research Centre.

This issue of the Journal includes two articles summarizing the evidence from clinical trials aimed at improving symptoms of autism. French and Kennedy (Journal of Child Psychology and Psychiatry, 2018, xx, xxxx) systematically review randomized controlled trials (RCTs) aimed at an "early intervention" and focus on trials including children with or at risk of autism under age 6 years. Although no type of intervention were excluded from their review, none of the included 48 RCTs employed pharmacological modalities and the overwhelming majority tested psychological/behavioural interventions aimed at modifying aspects of observed behaviours that are abnormal in children with autism. Using the standard Cochrane tool for evaluating risk of bias, French and Kennedy conclude that many RCTs are of low quality, which throws into question the reliance that should be placed on the findings.

Background Many young people with autism spectrum disorder (ASD) experience emotional and behavioural problems. However, the causes of these co-occurring difficulties are not well understood. Perceptual processing atypicalities are also often reported in individuals with ASD, but how these relate to co-occurring emotional and behavioural problems remains unclear, and few studies have used objective measurement of perceptual processing. Methods Event-related potentials (ERPs) were recorded in response to both standard and deviant stimuli (which varied in pitch) in an auditory oddball paradigm in adolescents (mean age of 13.56 years, SD = 1.12, range = 11.40–15.70) with ASD (n = 43) with a wide range of IQ (mean IQ of 84.14, SD = 24.24, range 27–129). Response to deviant as compared to standard stimuli (as indexed by the mismatch negativity (MMN)) and response to repeated presentations of standard stimuli (habituation) were measured. Multivariate regression tested the association between neural indices of perceptual processing and co-occurring emotional and behavioural problems. Results Greater sensitivity to changes in pitch in incoming auditory information (discrimination), as indexed by increased MMN amplitude, was associated with higher levels of parent-rated behaviour problems. MMN amplitude also showed a trend positive correlation with parent-rated sensory hyper-sensitivity. Conversely, greater habituation at the later N2 component was associated with higher levels of emotional problems. Upon more detailed analyses, this appeared to be driven by a selectively greater ERP response to the first (but not the second or third) standard stimuli that followed deviant stimuli. A similar pattern of association was found with other measures of anxiety. All results remained in covariation analyses controlling for age, sex and IQ, although the association between MMN amplitude and behaviour problems became non-significant when controlling for ASD severity. Conclusions Findings suggest that alterations in mechanisms of perceptual processing and discrimination may be important for understanding co-occurring emotional and behavioural problems in young people with ASD. Electronic supplementary material The online version of this article (10.1186/s13229-018-0236-2) contains supplementary material, which is available to authorized users.

An expert review of the aetiology, assessment, and treatment of autism spectrum disorder, and recommendations for diagnosis, management and service provision was coordinated by the British Association for Psychopharmacology, and evidence graded. The aetiology of autism spectrum disorder involves genetic and environmental contributions, and implicates a number of brain systems, in particular the gamma-aminobutyric acid, serotonergic and glutamatergic systems. The presentation of autism spectrum disorder varies widely and co-occurring health problems (in particular epilepsy, sleep disorders, anxiety, depression, attention deficit/hyperactivity disorder and irritability) are common. We did not recommend the routine use of any pharmacological treatment for the core symptoms of autism spectrum disorder. In children, melatonin may be useful to treat sleep problems, dopamine blockers for irritability, and methylphenidate, atomoxetine and guanfacine for attention deficit/hyperactivity disorder. The evidence for use of medication in adults is limited and recommendations are largely based on extrapolations from studies in children and patients without autism spectrum disorder. We discuss the conditions for considering and evaluating a trial of medication treatment, when non-pharmacological interventions should be considered, and make recommendations on service delivery. Finally, we identify key gaps and limitations in the current evidence base and make recommendations for future research and the design of clinical trials.

Item does not contain fulltext A recent Cochrane review assessed the efficacy of methylphenidate for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. Notwithstanding the moderate-to-large effect sizes for ADHD symptom reduction found in the meta-analysis, the authors concluded that the quality of the evidence is low and therefore the true magnitude of these effects remains uncertain. We identified a number of major concerns with the review, in the domains of study inclusion, approaches to quality assessment and interpretation of data relating to serious adverse events as well as of the clinical implications of the reported effects. We also found errors in the extraction of data used to estimate the effect size of the primary outcome. Considering all the shortcomings, the conclusion in the Cochrane review that the status of the evidence is uncertain is misplaced. Professionals, parents and patients should refer to previous reviews and existing guidelines, which include methylphenidate as one of the safe and efficacious treatment strategies for ADHD.

Background: Behavioural interventions are recommended for use with children and young people with ADHD, however specific guidance for their implementation based on the best available evidence is currently lacking. Methods: This review used an explicit question and answer format to address issues of clinical concern, based on expert interpretation of the evidence with precedence given to meta-analyses of randomised controlled trials. Results: On the basis of current evidence that takes into account whether outcomes are blinded, behavioural intervention cannot be supported as a front-line treatment for core ADHD symptoms. There is however, evidence from measures that are probably blinded that these interventions benefit parenting practices and improve conduct problems which commonly co-occur with ADHD, and are often the main reason for referral. Initial positive results have also been found in relation to parental knowledge, children’s emotional, social and academic functioning – although most studies have not used blinded outcomes. Generic as well as specialised ADHD parent training approaches - delivered either individually or in groups – have reported beneficial effects. High quality training, supervision of therapists and practice with the child, may improve outcomes but further evidence is required. Evidence for who benefits the most from behavioural interventions is scant. There is no evidence to limit behavioural treatments to parents with parenting difficulties or children with conduct problems. There are positive effects of additive school based intervention for the inattentive subtype. Targeting parental depression may enhance the effects of behavioural interventions. Conclusion: Parent training is an important part of the multi-modal treatment of children with ADHD which improves parenting, reduces levels of oppositional and non-compliant behaviours and may improve other aspects of functioning. However, blinded evidence does not support it as a specific treatment for core ADHD symptoms. More research is required to understand how to optimise treatment effectiveness either in general or for individual patients and explore potential barriers to treatment uptake and engagement. In terms of selecting which intervention formats to use it seems important to acknowledge and respond to parental treatment preferences. ispartof: Journal of Child Psychology and Psychiatry vol:59 issue:9 pages:932-947 ispartof: location:England status: published

Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. Electronic supplementary material The online version of this article (doi:10.1186/s13229-017-0146-8) contains supplementary material, which is available to authorized users.

In a sample of children and adolescents with first-episode psychosis, we investigated whether multiple treatment failure (MTF, defined as the initiation of a third trial of novel antipsychotic due to nonadherence, adverse effects, or insufficient response) was associated with comorbid autism spectrum disorders.Data were from the electronic health records of 638 children (51% male) aged from 10 to 17 years with first-episode psychosis (per ICD-10 criteria) from January 1, 2008, to November 1, 2014, referred to mental health services in South London, United Kingdom; data were extracted using the Clinical Record Interactive Search (CRIS) system. The effect of autism spectrum disorder comorbidity on the development of MTF during a 5-year period was modeled using Cox regression.There were 124 cases of MTF prior to the age of 18 (19.4% of the sample). Comorbid autism spectrum disorders were significantly associated with MTF (adjusted hazard ratio = 1.99; 95% CI, 1.19-3.31; P = .008) after controlling for a range of potential confounders. Other factors significantly associated with MTF included higher age at first presentation (P = .001), black ethnicity (P = .03), and frequency of clinical contact (P.001). No significant association between other comorbid neurodevelopmental disorders (hyperkinetic disorder or intellectual disability) and MTF was found.Children with first-episode psychosis and comorbid autism spectrum disorders at first presentation are less likely to have a beneficial response to antipsychotics.

Dr. Micoulaud-Franchi et al. raise concerns relating to our 2016 meta-analysis1 of neurofeedback as a treatment for attention-deficit/hyperactivity disorder (ADHD). It is encouraging that Dr. Micoulaud-Franchi et al. agree with us that there is “an urgent need to conduct future research that associates both high quality of [randomized controlled trial] RCT and high quality of [electroencephalography] EEG-neurofeedback sessions.” Consistent with this, we wrote, “Future efforts should focus on implementing standard neurofeedback protocols, ensuring learning, and optimizing clinically relevant transfer.”1(p444) This is in line with the significant advantage for neurofeedback demonstrated in our additional preliminary analysis of the few studies meeting such standards.

Objective There is evidence that parental psychiatric disorders are associated with offspring psychiatric disorder. Very few small studies have investigated the effect of maternal eating disorders on offspring psychopathology throughout childhood and early adolescence. We aimed to investigate psychiatric disorders at age 7, 10, and 13 years in offspring of women with eating disorders prior to pregnancy and investigate the relative contribution of other psychiatric disorders. Method Women (N = 12,035) from a large population-based longitudinal cohort: the Avon Longitudinal Study of Parents and Children (ALSPAC). A brief prepregnancy psychiatric history was obtained at enrollment to determine exposure. Offspring psychiatric disorder was measured using the developmental and well-being assessment at ages 7, 10, and 13. Results Maternal eating disorders were associated with a psychiatric diagnosis in the offspring at age 7 and 10, particularly emotional disorders (Odds ratio = 1.9, 95%CI: 1.1–2.8). Maternal psychiatric disorders other than eating disorders predicted psychiatric diagnoses across ages, and acted in an additive fashion with maternal eating disorders. Discussion Maternal eating disorders together with comorbid psychopathology increase risk for psychiatric disorders in childhood and early adolescence, in particular for emotional disorders. This has important implications for prevention and future research. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:385–393)

Objective: Nonpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments.Method: Using a common systematic search and a rigorous coding and data extraction strategy across domains, the authors searched electronic databases to identify published randomized controlled trials that involved individuals who were diagnosed with ADHD (or who met a validated cutoff on a recognized rating scale) and that included an ADHD outcome.Results: Fifty-four of the 2,904 nonduplicate screened records were included in the analyses. Two different analyses were performed. When the outcome measure was based on ADHD assessments by raters closest to the therapeutic setting, all dietary (standardized mean differences=0.21-0.48) and psychological (standardized mean differences=0.40-0.64) treatments produced statistically significant effects. However, when the best probably blinded assessment was employed, effects remained significant for free fatty acid supplementation (standardized mean difference=0.16) and artificial food color exclusion (standardized mean difference=0.42) but were substantially attenuated to nonsignificant levels for other treatments.Conclusions: Free fatty acid supplementation produced small but significant reductions in ADHD symptoms even with probably blinded assessments, although the clinical significance of these effects remains to be determined. Artificial food color exclusion produced larger effects but often in individuals selected for food sensitivities. Better evidence for efficacy from blinded assessments is required for behavioral interventions, neurofeedback, cognitive training, and restricted elimination diets before they can be supported as treatments for core ADHD symptoms.

OBJECTIVE: We performed meta-analyses of randomized controlled trials to examine the effects of neurofeedback on attention-deficit/hyperactivity disorder (ADHD) symptoms and neuropsychological deficits in children and adolescents with ADHD. METHOD: We searched PubMed, Ovid, Web of Science, ERIC, and CINAHAL through August 30, 2015. Random-effects models were employed. Studies were evaluated with the Cochrane Risk of Bias tool. RESULTS: We included 13 trials (520 participants with ADHD). Significant effects were found on ADHD symptoms rated by assessors most proximal to the treatment setting, that is, the least blinded outcome measure (standardized mean difference [SMD]: ADHD total symptoms = 0.35, 95% CI = 0.11-0.59; inattention = 0.36, 95% CI = 0.09-0.63; hyperactivity/impulsivity = 0.26, 95% CI = 0.08-0.43). Effects were not significant when probably blinded ratings were the outcome or in trials with active/sham controls. Results were similar when only frequency band training trials, the most common neurofeedback approach, were analyzed separately. Effects on laboratory measures of inhibition (SMD = 0.30, 95% CI = -0.10 to 0.70) and attention (SMD = 0.13, 95% CI = -0.09 to 0.36) were not significant. Only 4 studies directly assessed whether learning occurred after neurofeedback training. The risk of bias was unclear for many Cochrane Risk of Bias domains in most studies. CONCLUSION: Evidence from well-controlled trials with probably blinded outcomes currently fails to support neurofeedback as an effective treatment for ADHD. Future efforts should focus on implementing standard neurofeedback protocols, ensuring learning, and optimizing clinically relevant transfer. ispartof: Journal of the American Academy of Child & Adolescent Psychiatry vol:55 issue:6 pages:444-455 ispartof: location:United States status: published

Background: Psychiatric problems are common in autism spectrum disorders (ASDs), but the reasons are poorly understood. We use a longitudinal population-representative cohort to examine for the first time the persistence of psychiatric problems and to identify risk factors for their occurrence and stability. Methods: Eighty-one 16-year olds (75 male, six female), initially seen at 12 years, were re-assessed using the parent-report Strengths and Difficulties Questionnaire (SDQ). Child, family and contextual characteristics from age 12 were tested as risk factors for psychopathology. Results: Prevalence rates varied depending on whether general population or ASD-specific SDQ cut-offs were used. While the former suggested a decrease in psychiatric problems over time, the ASD-specific cut-offs showed no significant differences. With the exception of ADHD, the ASD-specific cut-offs identified a smaller proportion of individuals as ‘affected’ than did the general population cut-offs. There was longitudinal domain specificity, with parent correlations ranging from 0.50 to 0.58 and teacher SDQ reports at age 12 correlating 0.33–0.53 with parent reports at 16 years. In examining the role of risk factors, lower IQ and adaptive functioning predicted higher hyperactivity and total difficulties scores. Greater emotional problems at 16 were predicted by poorer maternal mental health, family-based deprivation and lower social class. Improvement from 12 to 16 years in conduct problems was predicted by greater neighbourhood deprivation and special school attendance. Conclusions: This is the first longitudinal study of other psychiatric symptoms in ASD. Additional psychiatric problems in ASD are persistent and domain-specific from childhood to adolescence. The finding that age-related reduction in SDQ symptoms does not apply when ASD-specific cut-offs are used requires further evaluation using diagnostic measures. Only a few of the expected risk factor-psychopathology predictions expected from general population studies were found, raising the possibility that the causes of psychopathology in ASD differ from those in the general population.

Introduction: Severe mood dysregulation and problems (SMP) in otherwise typically developing youth are recognized as an important mental health problem with a distinct set of clinical features, family history and neurocognitive characteristics. SMP in people with autism spectrum disorders (ASDs) have not previously been explored. Method: We studied a longitudinal, population-based cohort of adolescents with ASD in which we collected parent-reported symptoms of SMP that included rage, low and labile mood and depressive thoughts. Ninety-one adolescents with ASD provided data at age 16 years, of whom 79 had additional data from age 12. We studied whether SMP have similar correlates to those seen in typically developing youth. Results: Severe mood problems were associated with current (parent-rated) and earlier (parent- and teacher-rated) emotional problems. The number of prior psychiatric diagnoses increased the risk of subsequent SMP. Intellectual ability and adaptive functioning did not predict to SMP. Maternal mental health problems rated at 12 and 16 years were associated with SMP. Autism severity as rated by parents was associated with SMP, but the relationship did not hold for clinician ratings of autistic symptoms or diagnosis. SMP were associated with difficulty in identifying the facial expression of surprise, but not with performance recognizing other emotions. Relationships between SMP and tests of executive function (card sort and trail making) were not significant after controlling for IQ. Conclusions: This is the first study of the behavioural and cognitive correlates of severe mood problems in ASD. As in typically developing youth, SMP in adolescents with ASD are related to other affective symptoms and maternal mental health problems. Previously reported links to deficits in emotion recognition and cognitive flexibility were not found in the current sample. Further research is warranted using categorical and validated measures of SMP.

Children with an autism spectrum disorder (ASD) may be vulnerable to social isolation and bullying. We measured the friendship, fighting/bullying and victimization experiences of 10–12-year-old children with an ASD (N = 100) using parent, teacher and child self-report. Parent and teacher reports were compared to an IQ-matched group of children with special educational needs (SEN) without ASD (N = 80) and UK population data. Parents and teachers reported a lower prevalence of friendships compared to population norms and to children with SEN without an ASD. Parents but not teachers reported higher levels of victimization than the SEN group. Half of the children with an ASD reported having friendships that involved mutuality. By teacher report children with an ASD who were less socially impaired in mainstream school experienced higher levels of victimization than more socially impaired children; whereas for more socially impaired children victimization did not vary by school placement. Strategies are required to support and improve the social interaction skills of children with an ASD, to enable them to develop and maintain meaningful peer friendships and avoid victimization.

Background: Attention deficit hyperactivity disorder is increased in children with intellectual disability. Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks. Method: One hundred and twenty two drug-free children aged 7-15 with hyperkinetic disorder and IQ 30-69 were recruited to a double-blind, placebo-controlled trial that randomized participants using minimization by probability, stratified by referral source and IQ level in a one to one ratio. Methylphenidate was compared with placebo. Dose titration comprised at least 1 week each of low (0.5 mg/kg/day), medium (1.0 mg/kg/day) and high dose (1.5 mg/kg/day). Parent and teacher Attention deficit hyperactivity disorder (ADHD) index of the Conners Rating Scale-Short Version at 16 weeks provided the primary outcome measures. Clinical response was determined with the Clinical Global Impressions scale (CGI-I). Adverse effects were evaluated by a parent-rated questionnaire, weight, pulse and blood pressure. Analyses were by intention to treat. Trial registration: ISRCTN 68384912. Results: Methylphenidate was superior to placebo with effect sizes of 0.39 [95% confidence intervals (CIs) 0.09, 0.70] and 0.52 (95% CIs 0.23, 0.82) for the parent and teacher Conners ADHD index. Four (7%) children on placebo versus 24 (40%) of those on methylphenidate were judged improved or much improved on the CGI. IQ and autistic symptoms did not affect treatment efficacy. Active medication was associated with sleep difficulty, loss of appetite and weight loss but there were no significant differences in pulse or blood pressure. Conclusions: Optimal dosing of methylphenidate is practical and effective in some children with hyperkinetic disorder and intellectual disability. Adverse effects typical of methylphenidate were seen and medication use may require close monitoring in this vulnerable group. © 2012 Association for Child and Adolescent Mental Health.

Objective: We used multi-level modelling of sibling-pair data to disentangle the influence of proband-specific and more general family influences on maternal expressed emotion (MEE) toward children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: MEE was measured using the Five Minute Speech Sample (FMSS) for 60 sibling pairs (aged 5 through 17 years) each comprising one proband with ADHD and one child without ADHD. Questionnaire measures were used to assess child and adolescent conduct and emotional problems and maternal depression and ADHD. Multi-level models partitioned the effects of five MEE components (initial statement [IS], relationship [REL], warmth [WAR], critical comments [CC], and positive comments [PC]) into proband-specific and general family effects. Results: Significant proband-specific effects were confirmed for all MEE components, with higher levels of MEE expressed toward probands with ADHD than siblings without ADHD. For REL, PC, and CC, this effect was explained by comorbid child conduct problems rather than ADHD. Only low WAR was associated with child ADHD itself. Furthermore, only low WAR was related to variations in more general family characteristics, especially levels of maternal depression. Conclusions: MEE toward children with ADHD was influenced by proband-specific factors. For most components, these were driven by comorbid symptoms of conduct problems rather than ADHD itself. WAR was different; it was influenced by both child-specific and more general characteristics of the family. Further studies utilising a longitudinal design are required to establish the direction of causation and extend our understanding of the relationship between EE components and ADHD. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(10):1042-1053.

Background: Maternal eating disorders (ED) have been shown to increase the risk of feeding difficulties in the offspring. Very few studies, however, have investigated whether the effect of a maternal ED on childhood feeding is a direct effect or whether it can be ascribed to other child or maternal factors. We aimed to determine the role of maternal anxiety and depression in mediating the risk for feeding difficulties in infants of women with ED. Methods: A prospective study comparing women with lifetime ED (441) and without any lifetime psychiatric disorder (10,461) and their infants from the Avon Longitudinal Study of Parents and Children (ALSPAC). We investigated the effect of: maternal anxiety and depression in late pregnancy (32 weeks) and the post-partum (8 weeks), child temperament and developmental status on infant feeding difficulties at 1 and 6 months. We also investigated the effect of active pregnancy ED symptoms. We tested 3 models and their fit to the data using structured equation modelling: a direct effect model, a fully mediational model and an integrated (partial meditational) model. Results: The integrated model including a direct effect of maternal lifetime ED on infant feeding and a mediational path via maternal distress (a latent variable combining anxiety and depression) fitted the data best. This also applied to maternal pregnancy ED symptoms. Feeding difficulties in turn increased maternal distress over time. Conclusions: Lifetime ED and active pregnancy ED increase the risk for infant feeding difficulties and do so via maternal distress (i.e., depression and anxiety). This has important implications for prevention and early intervention in relation to infant feeding difficulties, as well as for future research in the field.