Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother-child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD.

Association between prenatal antipsychotic exposure and the risk of attention-deficit/hyperactivity disorder and autism spectrum disorder: a systematic review and meta-analysis.

The paucity of evidence regarding the safety of gestational antipsychotic exposure has led to treatment discontinuation in pregnant women with severe mental health conditions. This systematic review and meta-analysis aimed to summarise the current evidence on the association between gestational antipsychotic exposure and attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children (Study protocol registered in PROSPERO:CRD42022311354). Five studies included in our meta-analysis with around 8.6 million pregnancy episodes in nine different countries/regions. Results from our meta-analysis indicate that the heightened risks of ASD and ADHD in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relationship with the antipsychotic exposure during pregnancy. The results underscore the importance of meticulously monitoring the neurodevelopment of children born to mothers with mental illnesses, which can facilitate early interventions and provide requisite support.

Co-designing behavioural activation for depression for autistic adolescents: A case series.

Autistic youth are at high risk of depression, but there are few psychological interventions that have been specifically designed for use with this population. Behavioural activation (BA) is a particularly promising approach for autistic adolescents, having an established evidence-base for the treatment of depression in non-autistic people, and with a strong focus on behavioural, rather than cognitive change, which is a challenge for some autistic people. In this study, we worked with autistic adolescents and clinicians to co-design a BA-informed intervention to be delivered in an online format. We then conducted a pilot case-series with seven autistic adolescents with depression. Our focus was on establishing the acceptability and feasibility of the intervention but clinical outcomes on both self- and parent-reported symptoms of depression and anxiety are also presented. Our results indicate the intervention to be acceptable and feasible for autistic adolescents, with six out of seven participants being retained to the end of the intervention. Qualitative feedback indicated that all participants found the intervention a positive experience and would recommend it to others. Similarly, all participants found the online format acceptable, with 64% preferring this format to face-to-face therapy. Qualitative feedback and suggestions for refinement will also be discussed.

Autistic youth are at high risk of depression, but there are few psychological interventions that have been specifically designed for use with this population. Behavioural activation (BA) is a particularly promising approach for autistic adolescents, which has been used previously with non-autistic people. BA-focusses on improving mood through increasing engagement in positive activities and is well suited to being adapted to meet the needs of autistic youth. In this study, we worked with autistic adolescents and clinicians to co-design a BA-informed intervention to be delivered in an online format. We then conducted a pilot case-series with seven autistic adolescents with depression. Our focus was on establishing the acceptability (can participants complete the intervention) and feasibility (can this be done again on a larger scale) of the intervention. Our results indicated that the intervention was acceptable and feasible for autistic adolescents, with six out of seven participants being retained to the end of the intervention. Feedback from young people and their parents indicated that all participants both found the intervention a positive experience and would recommend it to others. Similarly, all participants found the online format acceptable, with 64% preferring this format to face-to-face therapy. Qualitative feedback and suggestions for refinement will also be discussed.

No association between alexithymia and emotion recognition or theory of mind in a sample of adolescents enhanced for autistic traits.

LAY ABSTRACT: Alexithymia is a sub-clinical condition characterised by difficulties identifying and describing one's own emotions, which is found in many, but not all autistic people. The alexithymia hypothesis suggests that certain aspects of socio-cognitive functioning typically attributed to autism, namely difficulties in emotion recognition, might be better explained by often co-occurring alexithymia. It is important to understand what is specific to autism and what is due to other co-occurring characteristics to develop appropriate support for autistic people. However, most research on this topic has been conducted in adults, which limits our knowledge about the relevance of this theory to younger autistic populations. This study tested whether difficulties in emotion recognition and theory of mind traditionally associated with autism might be better explained by alexithymia in a sample of adolescents with and without a diagnosis of autism. Results found that difficulties in emotion recognition and theory of mind were both associated with autistic traits, and this was not accounted for by individual differences in levels of alexithymia. This research suggests that more work is needed to understand the applicability of the alexithymia hypothesis in younger populations, but that at least in adolescents and when using parent-report measures, alexithymia may not account for emotion recognition or theory of mind difficulties associated with autistic traits.

Systematic Review and Meta-Analysis: Clinical Utility of Continuous Performance Tests for the Identification of Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: We aimed to quantify the clinical utility of continuous performance tests (CPTs) for the diagnosis of attention-deficit/hyperactivity disorder (ADHD) compared to a clinical diagnosis in children and adolescents. METHOD: Four databases (MEDLINE, PsycINFO, EMBASE, and PubMed) were screened until January 2023. Risk of bias of included results was judged with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We statistically pooled the area under the curve, the sensitivity, and the specificity of 3 commonly used CPTs subscales: omission/inattention, commission/impulsivity, and total number of errors/ADHD subscales (PROSPERO registration: CRD42020168091). RESULTS: A total of 19 studies using commercially available CPTs were identified. Results from up to 835 control individuals and 819 cases were combined in the summary receiver operating characteristic (ROC) curve analyses (sensitivity and specificity pooling), and up to 996 cases and 1,083 control individuals in the area under the curve (AUC) analyses. Clinical utility as measured by AUCs could be considered as barely acceptable (between 0.7 and 0.8) for the most part, with the best results for the total/ADHD score, followed by omissions/inattention, and poorest for commission/impulsivity scores. A similar pattern was found when pooling sensitivity and specificity: 0.75 (95% CI = 0.66-0.82) and 0.71 (0.62-0.78) for the total/ADHD score; 0.63 (0.49-0.75) and 0.74 (0.65-0.81) for omissions; and 0.59 (0.38-0.77) and 0.66 (CI = 0.50-0.78) for commissions. CONCLUSION: At the clinical level, CPTs as a stand-alone tool have only a modest to moderate ability to differentiate ADHD from non-ADHD samples. Hence, they should be used only within a more comprehensive diagnostic process. STUDY PREREGISTRATION INFORMATION: A systematic review of screening tools for ADHD in children and adolescents; https://www.crd.york.ac.uk/prospero/; CRD42020168091.

Psychopharmacology in children and adolescents: unmet needs and opportunities.

Psychopharmacological treatment is an important component of the multimodal intervention approach to treating mental health conditions in children and adolescents. Currently, there are many unmet needs but also opportunities, alongside possible risks to consider, regarding the pharmacological treatment of mental health conditions in children and adolescents. In this Position Paper, we highlight and address these unmet needs and opportunities, including the perspectives of clinicians and researchers from the European College of Neuropsychopharmacology-Child and Adolescent Network, alongside those of experts by lived experience from national and international associations, via a survey involving 644 participants from 13 countries, and of regulators, through representation from the European Medicines Agency. We present and discuss the evidence base for medications currently used for mental disorders in children and adolescents, medications in the pipeline, opportunities in the development of novel medications, crucial priorities for the conduct of future clinical studies, challenges and opportunities in terms of the regulatory and legislative framework, and innovations in the way research is conducted, reported, and promoted.

Testing the social motivation theory of autism: the role of co-occurring anxiety.

BACKGROUND: The Social Motivation Theory proposes that social reward processing differences underlie autism. However, low social motivation has also been linked to higher anxiety. Given the co-occurrence between autism and anxiety, it is possible that anxiety drives the association between social motivation and autistic characteristics. This study tests the mechanisms underlying the association between social motivation and autistic traits. METHODS: Participants were 165 adolescents (71 male), aged 10-16 years, from the Mapping profiles of cognition, motivation and attention in childhood (C-MAPS) study, enriched for autistic traits (70 participants with an autism diagnosis, 37 male). Participants completed a battery of online experimental tasks, including a Choose-a-Movie social motivation task and social cognition measures (theory of mind; emotion recognition), alongside parent-reported child anxiety and autistic traits. RESULTS: Higher social motivation was significantly associated with lower autistic traits (ß = -.26, p < .001). Controlling for social cognition did not change the association between social motivation and autistic traits. Controlling for anxiety did significantly reduce the strength of the association (unstandardized coefficient change: p = .003), although social motivation remained associated with autistic traits (ß = -.16, p = .004). Post hoc analyses demonstrated differential sex-effects: The association between social motivation and autistic traits was significant only in the females (ß = -.38, p < .001), as was the attenuation by anxiety (unstandardized coefficient change: p < .001). CONCLUSIONS: The association between social motivation and autistic traits could be partially attributed to co-occurring anxiety. Sex-specific effects found in females may be due to environmental factors such as increased social demands in adolescent female relationships. Results are consistent with self-report by autistic individuals who do not identify as having reduced social motivation.

Moving from development to implementation of digital innovations within the NHS: myHealthE, a remote monitoring system for tracking patient outcomes in child and adolescent mental health services.

Objective: This paper aims to report our experience of developing, implementing, and evaluating myHealthE (MHE), a digital innovation for Child and Adolescents Mental Health Services (CAMHS), which automates the remote collection and reporting of Patient-Reported Outcome Measures (PROMs) into National Health Services (NHS) electronic healthcare records. Methods: We describe the logistical and governance issues encountered in developing the MHE interface with patient-identifiable information, and the steps taken to overcome these development barriers. We describe the application's architecture and hosting environment to enable its operability within the NHS, as well as the capabilities needed within the technical team to bridge the gap between academic development and NHS operational teams. Results: We present evidence on the feasibility and acceptability of this system within clinical services and the process of iterative development, highlighting additional functions that were incorporated to increase system utility. Conclusion: This article provides a framework with which to plan, develop, and implement automated PROM collection from remote devices back to NHS infrastructure. The challenges and solutions described in this paper will be pertinent to other digital health innovation researchers aspiring to deploy interoperable systems within NHS clinical systems.

Practitioner Review: Clinical utility of the QbTest for the assessment and diagnosis of attention-deficit/hyperactivity disorder - a systematic review and meta-analysis.

BACKGROUND: Several computerised cognitive tests (e.g. continuous performance test) have been developed to support the clinical assessment of attention-deficit/hyperactivity disorder (ADHD). Here, we appraised the evidence-base underpinning the use of one of these tests - the QbTest - in clinical practice, by conducting a systematic review and meta-analysis investigating its accuracy and clinical utility. METHODS: Based on a preregistered protocol (CRD42022377671), we searched PubMed, Medline, Ovid Embase, APA PsycINFO and Web of Science on 15th August 2022, with no language/type of document restrictions. We included studies reporting accuracy measures (e.g. sensitivity, specificity, or Area under the Receiver Operating Characteristics Curve, AUC) for QbTest in discriminating between people with and without DSM/ICD ADHD diagnosis. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). A generic inverse variance meta-analysis was conducted on AUC scores. Pooled sensitivity and specificity were calculated using a random-effects bivariate model in R. RESULTS: We included 15 studies (2,058 participants; 48.6% with ADHD). QbTest Total scores showed acceptable, rather than good, sensitivity (0.78 [95% confidence interval: 0.69; 0.85]) and specificity (0.70 [0.57; 0.81]), while subscales showed low-to-moderate sensitivity (ranging from 0.48 [0.35; 0.61] to 0.65 [0.52; 0.75]) and moderate-to-good specificity (from 0.65 [0.48; 0.78] to 0.83 [0.60; 0.94]). Pooled AUC scores suggested moderate-to-acceptable discriminative ability (Q-Total: 0.72 [0.57; 0.87]; Q-Activity: 0.67 [0.58; 0.77); Q-Inattention: 0.66 [0.59; 0.72]; Q-Impulsivity: 0.59 [0.53; 0.64]). CONCLUSIONS: When used on their own, QbTest scores available to clinicians are not sufficiently accurate in discriminating between ADHD and non-ADHD clinical cases. Therefore, the QbTest should not be used as stand-alone screening or diagnostic tool, or as a triage system for accepting individuals on the waiting-list for clinical services. However, when used as an adjunct to support a full clinical assessment, QbTest can produce efficiencies in the assessment pathway and reduce the time to diagnosis.

Child educational progress in Born in Bradford pregnancies affected by gestational diabetes and also exposed to maternal common mental disorders.

Gestational diabetes and the maternal mental disorders of anxiety and depression have been implicated in adverse offspring neuro-behavioural outcomes but these exposures have only been studied in isolation. 1051 children whose mothers were diagnosed with gestational diabetes in UK's Born in Bradford cohort had linkage to maternal primary care records, providing diagnostic and treatment codes for depression and anxiety. Education record linkage provided results of the Early Years Foundation Stage Profile from the first year of school, aged five. Risk of not attaining a 'Good level of development' was analysed using multivariable Poisson regression within a generalised estimating equation framework. Multiple imputation was implemented for missing data. There was limited evidence of increased risk of failure to attain a 'good level of development' in those additionally exposed to maternal mental disorders (adjusted RR 1.21; 95% CI 0.94, 1.55). However, there was more evidence in children of Pakistani maternal ethnicity (adjusted RR 1.36; 95% CI 1.04, 1.77) than White British; this may have been driven by English not being the primary language spoken in the home. Therefore there may be groups with GDM in whom it is particularly important to optimise both maternal physical and mental health to improve child outcomes.

Screening for Attention Deficit Hyperactivity Disorder in Young Autistic Adults: The Diagnostic Accuracy of Three Commonly Used Questionnaires.

OBJECTIVE: Attention Deficit Hyperactivity Disorder (ADHD) is a common co-occurring condition in autistic individuals. ADHD is sometimes first recognised in young adulthood because ADHD symptoms may be misattributed to autism due to superficial overlap in presentation and diagnostic overshadowing. It should be investigated whether ADHD questionnaires are accurate in screening symptoms in young adults with autism. The current study examined this. METHODS: Participants were autistic young adults (N = 119) who took part in the Special Needs and Autism Project (SNAP), a population-based cohort. ADHD research diagnoses were obtained through the parent-informed Young Adult Psychiatric Assessment. Parents and young adults (self-report sample N = 71) completed ADHD questionnaires (Aberrant Behavior Checklist hyperactivity/non-compliance subscale, Conners Adult ADHD Rating Scales ADHD Index, and Strengths and Difficulties Questionnaire ADHD subscale). Receiver operating characteristic analyses were conducted to explore if the questionnaires discriminated ADHD cases from non-cases. To assess whether results varied by intellectual functioning, subgroup analyses were completed for those with an IQ ≥ 70 vs. <70. RESULTS: Weighted ADHD rates were high. Overall although the measures were performing at or close to adequate levels (area under the curve was 0.66 to 0.79 for parent-report and 0.70 to 0.65 for self-report), no single measure met adequate thresholds for sensitivity and specificity simultaneously. Tool performance was not different for those with an IQ ≥ 70 vs. <70. CONCLUSION: No single measure reported adequate performance for distinguishing ADHD from non-ADHD cases in this sample of young autistic adults. Use of current thresholds may lead to under-diagnosis.

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.

Molehill Mountain feasibility study: Protocol for a non-randomised pilot trial of a novel app-based anxiety intervention for autistic people.

Up to 50% of autistic people experience co-occurring anxiety, which significantly impacts their quality of life. Consequently, developing new interventions (and/ or adapting existing ones) that improve anxiety has been indicated as a priority for clinical research and practice by the autistic community. Despite this, there are very few effective, evidence-based therapies available to autistic people that target anxiety; and those that are available (e.g., autism adapted Cognitive Behavioural Therapy; CBT) can be challenging to access. Thus, the current study will provide an early-stage proof of concept for the feasibility and acceptability of a novel app-based therapeutic approach that has been developed with, and adapted for, autistic people to support them in managing anxiety using UK National Institute for Health and Care Excellence (NICE) recommended adapted CBT approaches. This paper describes the design and methodology of an ethically approved (22/LO/0291) ongoing non-randomised pilot trial that aims to enrol approximately 100 participants aged ≥16-years with an existing autism diagnosis and mild-to-severe self-reported anxiety symptoms (trial registration NCT05302167). Participants will be invited to engage with a self-guided app-based intervention-'Molehill Mountain'. Primary (Generalised Anxiety Disorder Assessment, Hospital Anxiety and Depression Scale) and secondary outcomes (medication/ service use and Goal Attainment Scaling) will be assessed at baseline (Week 2 +/- 2), endpoint (Week 15 +/- 2) and three follow-ups (Weeks 24, 32 and 41 +/- 4). Participants will also be invited to complete an app acceptability survey/ interview at the study endpoint. Analyses will address: 1) app acceptability/ useability and feasibility (via survey/ interview and app usage data); and 2) target population, performance of outcome measures and ideal timing/ duration of intervention (via primary/ secondary outcome measures and survey/ interview)-with both objectives further informed by a dedicated stakeholder advisory group. The evidence from this study will inform the future optimisation and implementation of Molehill Mountain in a randomised-controlled trial, to provide a novel tool that can be accessed easily by autistic adults and may improve mental health outcomes.

Exploring cognitive, behavioral and autistic trait network topology in very preterm and term-born children.

Introduction: Compared to full-term (FT) born peers, children who were born very preterm (VPT; <32 weeks' gestation) are likely to display more cognitive and behavioral difficulties, including inattention, anxiety and socio-communication problems. In the published literature, such difficulties tend to be studied independently, thus failing to account for how different aspects of child development interact. The current study aimed to investigate children's cognitive and behavioral outcomes as interconnected, dynamically related facets of development that influence one another. Methods: Participants were 93 VPT and 55 FT children (median age 8.79 years). IQ was evaluated with the Wechsler Intelligence Scale for Children-4th edition (WISC-IV), autism spectrum condition (ASC) traits with the social responsiveness scale-2nd edition (SRS-2), behavioral and emotional problems with the strengths and difficulties questionnaire (SDQ), temperament with the temperament in middle childhood questionnaire (TMCQ) and executive function with the behavior rating inventory of executive functioning (BRIEF-2). Outcome measures were studied in VPT and FT children using Network Analysis, a method that graphically represents partial correlations between variables and yields information on each variable's propensity to form a bridge between other variables. Results: VPT and FT children exhibited marked topological differences. Bridges (i.e., the variables most connected to others) in the VPT group network were: conduct problems and difficulties with organizing and ordering their environment. In the FT group network, the most important bridges were: difficulties with initiating a task or activity and prosocial behaviors, and greater emotional problems, such as lower mood. Discussion: These findings highlight the importance of targeting different aspects of development to support VPT and FT children in person-based interventions.

Attention-deficit/hyperactivity disorder medication consumption in 64 countries and regions from 2015 to 2019: a longitudinal study.

Background: Timely recognition and appropriate treatment of attention-deficit/hyperactivity disorder (ADHD) are essential to enhance long-term outcomes of individuals with ADHD. This study aimed to evaluate the multinational trends and patterns of ADHD medication consumption. Methods: In this longitudinal trend study, we used pharmaceutical sales data of ADHD medication from the IQVIA-Multinational Integrated Data Analysis System between 2015 and 2019, covering 64 countries across the world. Consumption rates of ADHD medication were expressed as defined daily dose per 1000 child and adolescent inhabitants (aged 5-19) per day (DDD/TID). Linear mixed models were used to estimate the multinational, regional, and income level trend changes. Findings: The results showed that multinational ADHD medication consumption increased by +9.72% (95% confidence interval [CI], +6.25%, +13.31%) per year, from 1.19 DDD/TID in 2015 to 1.43 DDD/TID in 2019 across the 64 countries with marked differences between geographical locations. When stratified by countries' income levels, increases in ADHD medication consumption were observed in high-income countries but not in middle-income countries. In 2019, the pooled consumption rates of ADHD medication were 6.39 DDD/TID (95% CI, 4.63, 8.84) in high-income countries, 0.37 DDD/TID (95% CI, 0.23, 0.58) in upper-middle-income countries and 0.02 DDD/TID (95% CI, 0.01, 0.05) in lower-middle-income countries. Interpretation: Current ADHD prevalence estimates and rates of ADHD medication consumption in most middle-income countries are lower than the global epidemiological prevalence. It is therefore imperative to evaluate the potential barriers to diagnosis and treatment in these countries to minimise the risk of negative outcomes from undiagnosed and untreated ADHD. Funding: This project was funded by a grant from the Hong Kong Research Grants Council Collaborative Research Fund (project number C7009-19G).

Reduced inferior fronto-insular-thalamic activation during failed inhibition in young adults with combined ASD and ADHD compared to typically developing and pure disorder groups.

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.

The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications.

We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010-08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.

Maternal Benzodiazepines and Z-Drugs Use during Pregnancy and Adverse Birth and Neurodevelopmental Outcomes in Offspring: A Population-Based Cohort Study.

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.

Factors associated with mental health symptoms among UK autistic children and young people and their parents during the COVID-19 pandemic.

LAY ABSTRACT: What is already known about the topic: The COVID-19 pandemic and the associated restrictions impacted all of society. There is emerging evidence showing a range of impacts on autistic children and young people and their families. Further research that looks at how individuals coped during the pandemic while considering how they were doing before the pandemic is needed.What this paper adds: This article explores whether how well autistic youth were doing before the pandemic influenced how they coped during the pandemic. It also looked at how well their parents were doing during the pandemic and whether any pre-pandemic factors influenced how they coped. Samples of both primary-school-aged autistic children and autistic teenagers and their parents were surveyed to answer these questions. More engagement and enjoyment in education provision during the pandemic and getting outside more were linked with better child and parental mental health during the pandemic. More attention deficit hyperactivity disorder before the pandemic was linked with more attention deficit hyperactivity disorder and behavioural problems during the pandemic in primary-school-aged autistic children, and more emotional problems during the pandemic in autistic teenagers. Parents with more mental health problems during the pandemic had more mental health problems before the pandemic.Implications for practice, research or policy: Encouraging engagement and enjoyment in education and promoting physical exercise are key intervention targets. Ensuring access to attention deficit hyperactivity disorder medication and support is important, especially if this is managed jointly across school and home.