Search

The aim of this study was to evaluate the effectiveness of a three-hour psychoeducation group in improving understanding of non-epileptic seizures (NES), health outcomes and quality of life in young people with NES.Multi-session psychoeducational groups for adults with NES have reported improved psychosocial functioning and reduced NES compared to those who do not receive psychoeducational interventions. To date there have been no studies in young people examining the effects of a single session of psychoeducation.15 young people with NES and their families attended a psychoeducation group within a specialist hospital following a multidisciplinary assessment. The group's effectiveness was evaluated in terms of perceptions of seizure controllability, seizure severity, the management of the condition and health-related quality of life measures.A significant decrease in accident and emergency (AE) visits and ambulance call outs was observed following the psychoeducation group. Young people additionally reported increased knowledge of NES and ability to cope with the condition which was maintained at 6-week follow-up. Significant reduction in NES occurrence or quality of life was not observed.Significant reduction in AE attendance and ambulance use was found following group psychoeducation and improvements in psychosocial functioning and knowledge about NES. Group psychoeducation has the potential to increase child and parental understanding of NES and reduce inappropriate healthcare usage.

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies., This research was funded by National Institute of Mental Health (NIMH) grant R01MH092293 (to GAH and JAT) and NJCTS (New Jersey Center for Tourette Syndrome and Associated Disorders; to GAH and JAT). This work was also supported by grants from the Judah Foundation, the Tourette Association of America, National Institute of Health (NIH) Grants NS40024, NS016648, MH079489, MH073250, the American Recovery and Re-investment Act (ARRA) Grants NS040024-07S1; NS16648-29S1; NS040024-09S1; MH092289; MH092290; MH092291; MH092292; R01MH092293; MH092513; MH092516; MH092520; MH071507; MH079489; MH079487; MH079488; and MH079494. Dr. Mir has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña and the Jaques and Gloria Gossweiler Foundation. Dr. Morer has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d’Innovacio (DIUE) 2009SGR1119. Dr. Münchau has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1 and FOR 2698). This study was also supported by a Grant from the National Institute for Environmental Health Science (R01 ES021462).

Funder: NIHR Great Ormond Street Hospital Biomedical Research Centre, BACKGROUND: To update and internally validate a model to predict children and young people (CYP) most likely to experience long COVID (i.e. at least one impairing symptom) 3 months after SARS-CoV-2 PCR testing and to determine whether the impact of predictors differed by SARS-CoV-2 status. METHODS: Data from a nationally matched cohort of SARS-CoV-2 test-positive and test-negative CYP aged 11-17 years was used. The main outcome measure, long COVID, was defined as one or more impairing symptoms 3 months after PCR testing. Potential pre-specified predictors included SARS-CoV-2 status, sex, age, ethnicity, deprivation, quality of life/functioning (five EQ-5D-Y items), physical and mental health and loneliness (prior to testing) and number of symptoms at testing. The model was developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping and the final model was adjusted for overfitting. RESULTS: A total of 7139 (3246 test-positives, 3893 test-negatives) completing a questionnaire 3 months post-test were included. 25.2% (817/3246) of SARS-CoV-2 PCR-positives and 18.5% (719/3893) of SARS-CoV-2 PCR-negatives had one or more impairing symptoms 3 months post-test. The final model contained SARS-CoV-2 status, number of symptoms at testing, sex, age, ethnicity, physical and mental health, loneliness and four EQ-5D-Y items before testing. Internal validation showed minimal overfitting with excellent calibration and discrimination measures (optimism-adjusted calibration slope: 0.96575; C-statistic: 0.83130). CONCLUSIONS: We updated a risk prediction equation to identify those most at risk of long COVID 3 months after a SARS-CoV-2 PCR test which could serve as a useful triage and management tool for CYP during the ongoing pandemic. External validation is required before large-scale implementation.

Background There is little understanding of the mental health impact for young people with long-term physical health conditions and mental health professionals’ experiences of supporting them during COVID-19. This service evaluation aimed to conduct a survey of the psychological services provided by mental health professionals in a paediatric hospital in relation to COVID-19. Method Clinical psychologists and assistant psychologists ( n = 76) across the hospital were asked to complete a survey, asking about their perceptions of COVID-19’s impact on patients and families and experiences of providing support during COVID-19. Open-ended survey questions were analysed qualitatively using framework analysis. Results Respondents described perceived impacts on patients and families around social isolation, school closure, family relationships, physical health, mental health, treatments and social support. Respondents’ experiences of providing mental health support during COVID-19 highlighted themes around providing remote/virtual support, workload and facilitators and barriers to their work. Conclusions Mental health professionals surveyed reported a complex mental health landscape in young people with long-term physical health conditions and their families during COVID-19. Service-wide involvement is needed to facilitate changes to support vital adaptations to remote/virtual working. Research on the mental health of young people with long-term physical health conditions and staff experiences of providing support is warranted.

This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3–16 years) with CTD (n = 327); first-degree relatives (3–10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27–3.42, p p = 0.01) and was inversely associated with ADHD symptom severity (β = − 2.52, 95% CI − 4.16–0.88, p

Background There is clear evidence that tic disorders (TDs) are associated with psychosocial stress as well as emotional and behavioral problems. Studies have shown that individuals with TDs have higher acute physiological stress responses to external, single stressors (as reflected by saliva cortisol). The aim of the present study was to examine a physiological marker of longer-term stress (as reflected by hair cortisol concentration) in children and adolescents with TDs and unaffected siblings of individuals with TDs. Methods Two samples of a European cohort were included in this study. In the COURSE sample, 412 children and adolescents aged 3–16 years with a chronic TD including Tourette syndrome according to DSM IV-TR criteria were included. The ONSET sample included 131 3–10 years old siblings of individuals with TDs, who themselves had no tics. Differences in hair cortisol concentration (HCC) between the two samples were examined. Within the COURSE sample, relations of HCC with tic severity and perceived psychosocial stress as well as potential effects and interaction effects of comorbid emotional and behavioral problems and psychotropic medication on HCC were investigated. Results There were no differences in HCC between the two samples. In participants with TDs, there were no associations between HCC and tic severity or perceived psychosocial stress. No main effects of sex, psychotropic medication status and comorbid emotional and behavioral problems on HCC were found in participants with TDs. Conclusion A link between HCC and TDs is not supported by the present results.

Objective A lack of universal definitions for response and remission in pediatric obsessive-compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children’s Yale−Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes. Method A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references; 42 randomized controlled clinical trials were considered eligible, and 21 provided data for inclusion (N 1,234). Scores of ≤2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A 2-stage, random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively. Results The CY-BOCS had sufficient discriminative ability to determine response (AUC = 0.89) and remission (AUC = 0.92). The optimal cutoff for response was a ≥35% reduction from baseline to posttreatment (sensitivity = 83.9, 95% CI = 83.7−84.1; specificity = 81.7, 95% CI = 81.5−81.9). The optimal cutoff for remission was a posttreatment raw score of ≤12 (sensitivity = 82.0, 95% CI = 81.8−82.2; specificity = 84.6, 95% CI = 84.4−84.8). Conclusion Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD randomized controlled clinical trials. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD.

BackgroundChildren and young people with long-term physical conditions have significantly elevated mental health needs. Transdiagnostic, brief psychological interventions have the potential to increase access to evidence-based psychological treatments for patients who attend health services primarily for physical health needs.ObjectiveA non-randomised study was conducted to assess the impact of brief, transdiagnostic psychological interventions in children and young people presenting at a drop-in mental health centre in the reception area of a paediatric hospital.Methods186 participants attending a transdiagnostic mental health drop-in centre were allocated to assessment and psychological intervention based on a clinical decision-making algorithm. Interventions included signposting, guided self-help based on a modular psychological treatment and referral to the hospital’s paediatric psychology service. The primary transdiagnostic mental health outcome measure was the parent-reported Strengths and Difficulties Questionnaire (SDQ), which was given at baseline and 6 months post-baseline.FindingsThere was a significant positive impact of attending the drop-in mental health centre on the SDQ (Cohen’s d=0.22) and on the secondary outcome measure of Paediatric Quality of life (Cohen’s d=0.55).ConclusionsA mental health drop-in centre offering brief, transdiagnostic assessment and treatment may reduce emotional and behavioural symptoms and improve quality of life in children and young people with mental health needs in the context of long-term physical conditions. A randomised controlled trial to investigate the specificity of any effects is warranted.Clinical implicationsDrop-in centres for mental health needs may increase access and have beneficial effects for children and young people with physical conditions.

Family accommodation (FA) refers to the participation of family members in obsessive-compulsive disorder (OCD) rituals. Most studies have focused on maternal accommodation; consequently, little is known about fathers’ accommodation of OCD. The current study aims to extend the existing literature by examining maternal versus paternal accommodation of OCD symptoms. The sample consisted of 209 children with OCD (Mean [M] age = 14.1 years) and their parents (NMothers = 209, NFathers = 209) who had completed the Family Accommodation Scale- Parent Report (FAS-PR). Paired t-test and chi-square analyses were used to compare FA of OCD symptoms between mothers and fathers. Linear regression was used to examine correlates of maternal and paternal FA and its impact on treatment outcomes. Mothers reported significantly higher levels of daily FA than fathers. Correlates of maternal and paternal accommodation included OCD symptom severity, emotional and behavioral difficulties, and parent psychopathology. Both maternal and paternal FA significantly predicted worse treatment outcomes. Both mothers and fathers accommodate child OCD symptoms with high frequency, and in similar ways. Although mothers accommodate to a greater extent than fathers, both maternal and paternal involvement in rituals are a significant predictor of the child’s treatment response. Results emphasise the need to consider the whole family system, including fathers, in understanding and treating OCD in children. Electronic supplementary material The online version of this article (10.1007/s10802-020-00678-9) contains supplementary material, which is available to authorized users.

AIM To investigate the association between circulating anti-dopamine D2 receptor (D2R) autoantibodies and the exacerbation of tics in children with chronic tic disorders (CTDs). METHOD One hundred and thirty-seven children with CTDs (108 males, 29 females; mean age [SD] 10y 0mo [2y 7mo], range 4-16y) were recruited over 18 months. Patients were assessed at baseline, at tic exacerbation, and at 2 months after exacerbation. Serum anti-D2R antibodies were evaluated using a cell-based assay and blinded immunofluorescence microscopy scoring was performed by two raters. The association between visit type and presence of anti-D2R antibodies was measured with McNemar's test and repeated-measure logistic regression models, adjusting for potential demographic and clinical confounders. RESULTS At exacerbation, 11 (8%) participants became anti-D2R-positive ('early peri-exacerbation seroconverters'), and nine (6.6%) became anti-D2R-positive at post-exacerbation ('late peri-exacerbation seroconverters'). The anti-D2R antibodies were significantly associated with exacerbations when compared to baseline (McNemar's odds ratio=11, p=0.003) and conditional logistic regression confirmed this association (Z=3.49, p

There are potent evidence-based psychological treatments for youth with mental health needs, yet they are rarely implemented in clinical practice, especially for youth with mental health disorders in the context of chronic physical illness such as epilepsy. Implementation science, the study of the translation of research into practice, can promote the uptake of existing effective interventions in routine clinical practice and aid the sustainable integration of psychological treatments with routine health care. The aim of this report was to use four implementation science methods to develop a version of an existing effective psychological treatment for mental health disorders [the Modular Approach to Treatment of Children with Anxiety, Depression or Conduct Problems (MATCH-ADTC)] for use within paediatric epilepsy services: (a) literature search; (b) iterative focus groups underpinned by normalisation process theory; (c) Plan–Do–Study–Act methods; and (d) qualitative patient interviews. Findings: Three modifications were deemed necessary to facilitate implementation in children with both mental health disorders and epilepsy. These were (a) a universal brief psychoeducational component addressing the relationship between epilepsy and mental health; (b) supplementary, conditionally activated interventions addressing stigma, parental mental health and the transition to adulthood; and (c) additional training and supervision. The intervention needed relatively little alteration for implementation in paediatric epilepsy services. The modified treatment reflected the scientific literature and the views of clinicians and service users. The multi-method approach used in this report can serve as a model for implementation of evidence-based psychological treatments for children with mental health needs in the context of other chronic illnesses.

(1) To identify patient reported outcome measures (PROMs) which have been used to screen and assess mental health symptoms in studies of youth with skin disease. (2) To critically appraise their evidence base in this population.A systematic literature search was conducted within PubMed and PsycINFO combining search terms for pediatric populations, dermatology, screening and assessment tools, and psychological and psychiatric conditions, to identify PROMs which screened or assessed for mental health symptoms in youth with skin disease. PROMs which had undergone validation within this population were assessed for quality and evidence base using the COSMIN risk of bias tool.One hundred eleven PROMs which assess mental health symptoms in studies of youth with skin disease were identified. These included generic mental health scales which are extensively validated in different populations. Only one PROM, the "Skin Picking Scale-Revised" has undergone specific validation in youth with skin disease. This showed poor quality of evidence for content validity and therefore cannot be recommended.There is an urgent need to identify mental health problems early and treat proactively to improve outcomes in youth with skin disease. This review highlights the current lack of consensus around the best way to assess our patients. It is likely that existing generic mental health methods and PROMS will be appropriate for our needs. More work is required to examine the utility, feasibility, and acceptability of existing generic, validated mental health screening tools in youth with skin disease.

Background: We describe post-COVID symptomatology in a non-hospitalised, national sample of adolescents aged 11-17 years with PCR-confirmed SARS-CoV-2 infection compared with matched adolescents with negative PCR status. Methods: In this national cohort study, adolescents aged 11-17 years from the Public Health England database who tested positive for SARS-CoV-2 between January and March, 2021, were matched by month of test, age, sex, and geographical region to adolescents who tested negative. 3 months after testing, a subsample of adolescents were contacted to complete a detailed questionnaire, which collected data on demographics and their physical and mental health at the time of PCR testing (retrospectively) and at the time of completing the questionnaire (prospectively). We compared symptoms between the test-postive and test-negative groups, and used latent class analysis to assess whether and how physical symptoms at baseline and at 3 months clustered among participants. This study is registered with the ISRCTN registry (ISRCTN 34804192). Findings: 23 048 adolescents who tested positive and 27 798 adolescents who tested negative between Jan 1, 2021, and March 31, 2021, were contacted, and 6804 adolescents (3065 who tested positive and 3739 who tested negative) completed the questionnaire (response rate 13·4%). At PCR testing, 1084 (35·4%) who tested positive and 309 (8·3%) who tested negative were symptomatic and 936 (30·5%) from the test-positive group and 231 (6·2%) from the test-negative group had three or more symptoms. 3 months after testing, 2038 (66·5%) who tested positive and 1993 (53·3%) who tested negative had any symptoms, and 928 (30·3%) from the test-positive group and 603 (16·2%) from the test-negative group had three or more symptoms. At 3 months after testing, the most common symptoms among the test-positive group were tiredness (1196 [39·0%]), headache (710 [23·2%]), and shortness of breath (717 [23·4%]), and among the test-negative group were tiredness (911 [24·4%]), headache (530 [14·2%]), and other (unspecified; 590 [15·8%]). Latent class analysis identified two classes, characterised by few or multiple symptoms. The estimated probability of being in the multiple symptom class was 29·6% (95% CI 27·4-31·7) for the test-positive group and 19·3% (17·7-21·0) for the test-negative group (risk ratio 1·53; 95% CI 1·35-1·70). The multiple symptoms class was more frequent among those with positive PCR results than negative results, in girls than boys, in adolescents aged 15-17 years than those aged 11-14 years, and in those with lower pretest physical and mental health. Interpretation: Adolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clusters of symptoms. The multiple and varied symptoms show that a multicomponent intervention will be required, and that mental and physical health symptoms occur concurrently, reflecting their close relationship. Funding: UK Department of Health and Social Care, in their capacity as the National Institute for Health Research, and UK Research and Innovation. Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Tic disorders have a strong male predominance, with a male-to-female ratio of 4:1 in Tourette syndrome (TS) and 2:1 in persistent tic disorders. In other neurodevelopmental conditions, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), the disparity in sex distribution has been partially related to differences in symptom presentation between males and females. In tic disorders, however, little research has been conducted on this topic, probably due to the limited access to large samples with a significant proportion of females. The aim of this study was to describe sex differences in the clinical presentation of tic disorders in children and adolescents in one of the largest pediatric samples with TS/persistent tic disorders (n = 709, 23.3% females) recruited as part of the European Multicenter Tics in Children Study (EMTICS). Validated measures assessed the severity of tics and comorbid psychiatric symptoms. Using mixed-effect models, we found that sex had a significant influence on the severity of tics, ADHD symptoms, ASD symptoms, and emotional problems. Males had more severe symptoms than females, except for emotional problems. We also observed a statistically significant interaction between sex and age on the severity of tics and compulsions, with females showing higher symptom severity with increasing age than males. These findings indicate that the clinical presentation of TS/persistent tic disorders varies with sex. Males seem to exhibit a more noticeable pattern of clinical symptoms at a younger age that may contribute to their earlier detection in comparison to females.

Background and aimClinical centres have seen an increase in tic-like movements during the COVID-19 pandemic. A series of children and adolescents are described.MethodsA retrospective chart review of 34 consecutive paediatric patients presenting with sudden onset tic-like movements, seen over 6 months.Results94% of patients were female, with an average age of sudden onset or increase of tic-like movements of 13.7 years. 44% had a previous diagnosis of tics, and 47% initially presented to an emergency department. Comorbid psychiatric and neurodevelopmental disorders were reported in 91% with 68% reporting anxiety.ConclusionWe highlight a dramatic presentation of sudden onset functional tic-like movements in predominantly female adolescents to help inform identification and management. There is need to research the neurobiological underpinnings and environmental exacerbating factors leading to these presentations and to explore effective therapeutic strategies.

Background Paediatric patients being treated for long-term physical health conditions (LTCs) have elevated mental health needs. However, mental health services in the community are difficult to access in the usual course of care for these patients. The Lucy Project – a self-referral drop-in access point—was a program to address this gap by enrolling patients for low-intensity psychological interventions during their treatment for LTCs. In this paper, we evaluate the cost-effectiveness of the Lucy Project. Methods Using a pre-post design, we evaluate the cost-effectiveness of the intervention by calculating the base-case incremental cost-effectiveness ratio (ICER) using outcomes data and expenses recorded by project staff. The target population was paediatric patients enrolled in the program with an average age of 9 years, treated over a time horizon of 6 months. Outcome data were collected via the Paediatric Quality of Life Inventory, which was converted to health utility scores using an instrument found in the literature. The QALYs were estimated using these health utility scores and the length of the intervention. We calculate a second, practical-case incremental cost-effectiveness ratio using streamlined costing figures with maximum capacity patient enrolment within a one-year time horizon, and capturing lessons learned post-trial. Results The base-case model showed an ICER of £21,220/Quality Adjusted Life Years (QALY) gained, while the practical model showed an ICER of £4,359/QALY gained. The practical model suggests the intervention garners significant gains in quality of life at an average cost of £309 per patient. Sensitivity analyses reveal use of staff time was the greatest determinant of the ICER, and the intervention is cost-effective 75% of the time in the base-case model, and 94% of the time in the practical-case model at a cost-effectiveness threshold of £20,000/QALY gained. Conclusions We find the base-case intervention improves patient outcomes and can be considered cost-effective according to the National Institute for Health and Care Excellence (NICE) threshold of £20,000—£30,000/QALY gained, and the practical-case intervention is roughly four times as cost-effective as the base-case. We recommend future studies incorporate a control group to corroborate the effect size of the intervention.

BACKGROUND: Children and young people with long term physical health conditions are at increased risk of experiencing mental health and wellbeing difficulties. However, there is a lack of research that explores the experiences of, and attitudes towards interventions aiming to improve their mental health and wellbeing. This systematic review seeks to address this gap in the literature by exploring what children and young people with long term conditions, their caregivers and health practitioners perceive to be important aspects of interventions aiming to improve their mental health and wellbeing. // METHODS: An information specialist searched five academic databases using pre-defined criteria for qualitative evaluations of interventions aiming to improve the mental health or wellbeing of children with long term physical conditions. Reviewers also performed supplementary citation and grey literature searches. Two reviewers independently screened titles, abstracts and full texts which met the inclusion criteria and conducted data extraction and quality assessment. Meta-ethnography was used to synthesise the findings. // RESULTS: Screening identified 60 relevant articles. We identified five overarching constructs through the synthesis: i) Getting In and Staying In, ii) Therapeutic Foundation, iii) Social Support, iv) A Hopeful Alternative and v) Empowerment. The line of argument which links these constructs together indicates that when interventions can provide an environment that allows young people to share their experiences and build empathetic relationships; it can enable participants to access social support and increase feelings of hope and empowerment. // CONCLUSION: These findings may provide a framework to inform the development of mental health interventions for this population, and evaluate existing interventions which already include some of the components or processes identified by this research. Further research is needed to establish which of the constructs identified by the line of argument are most effective in improving the mental wellbeing of young people living with long term conditions.

Although mental health difficulties can severely complicate the lives of children and young people (CYP) with long-term physical conditions (LTCs), there is a lack of evidence about the effectiveness of interventions to treat them.To evaluate the clinical effectiveness and cost-effectiveness of interventions aiming to improve the mental health of CYP with LTCs (review 1) and explore the factors that may enhance or limit their delivery (review 2).For review 1, 13 electronic databases were searched, including MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Science Citation Index. For review 2, MEDLINE, PsycINFO and CINAHL were searched. Supplementary searches, author contact and grey literature searches were also conducted.The first systematic review sought randomised controlled trials (RCTs) and economic evaluations of interventions to improve elevated symptoms of mental ill health in CYP with LTCs. Effect sizes for each outcome were calculated post intervention (Cohen'sReview 1 synthesised 25 RCTs evaluating 11 types of intervention, sampling 12 different LTCs. Tentative evidence from seven studies suggests that cognitive-behavioural therapy interventions could improve the mental health of CYP with certain LTCs. Intervention-LTC dyads were diverse, with few opportunities to meta-analyse. No economic evaluations were located. Review 2 synthesised 57 studies evaluating 21 types of intervention. Most studies were of individuals with cancer, a human immunodeficiency virus (HIV) infection or mixed LTCs. Interventions often aimed to improve broader mental health and well-being, rather than symptoms of mental health disorder. The metaethnography identified five main constructs, described in an explanatory line of argument model of the experience of interventions. Nine overarching synthesis categories emerged from the integrated evidence, raising implications for future research.Review 1 conclusions were limited by the lack of evidence about intervention effectiveness. No relevant economic evaluations were located. There were no UK studies included in review 1, limiting the applicability of findings. The mental health status of participants in review 2 was usually unknown, limiting comparability with review 1. The different evidence identified by the two systematic reviews challenged the overarching synthesis.There is a relatively small amount of comparable evidence for the effectiveness of interventions for the mental health of CYP with LTCs. Qualitative evidence provided insight into the experiences that intervention deliverers and recipients valued. Future research should evaluate potentially effective intervention components in high-quality RCTs integrating process evaluations. End-user involvement enriched the project.This study is registered as PROSPERO CRD42011001716.The National Institute for Health Research (NIHR) Health Technology Assessment programme and the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.Many children and young people with a long-term physical health condition also experience feelings of depression, anxiety and other mental health issues that affect their day-to-day life, their family and others around them. This review investigates whether or not interventions (treatments, strategies and resources) can help children and young people with their mental health. The study also reviewed studies that explored the attitudes and experiences of those involved in receiving or delivering similar interventions. The study found 25 publications that evaluated 11 different types of interventions, including cognitive–behavioural therapy (seven studies) and music therapy (one study). There were some positive effects for the strategies tested on both mental health and other outcomes, but, because the studies were often small, exact effects were uncertain. Many of the studies were not very well designed or carried out and differences between research designs meant that it was hard to compare different studies. The study found 57 publications that explored experiences of interventions. Analysis suggested that it is important that strategies involve building good relationships and are delivered in what feels like a safe space. Participants in studies tended to like interventions that provided social support and helped them feel better about living with a long-term physical condition. Successful interventions were viewed as accessible and engaging. These studies were often conducted well, but they focused on the range of interventions rather than the review evaluating how well interventions work. There are many gaps in the research carried out so far. Some long-term conditions affecting children and young people have not been the subject of studies of mental health interventions, and some important outcomes, such as school attendance and self-care, have not been assessed. More carefully designed UK research consulting children and young people, parents and practitioners is needed before it can be clear what works for children with particular physical conditions to help their mental health, and why.

To evaluate neuropsychiatric comorbidities in children and adolescents with hypothalamic hamartoma.We retrospectively analysed case notes for all individuals with hypothalamic hamartoma referred to Great Ormond Street Hospital, London, between 2000 and 2016. In addition, a systematic review aiming to identify all previous paediatric case series was performed. Psychiatric symptoms, demographics, physical comorbidities, and cognitive functioning were recorded for all cases where possible. Analyses were performed to determine which factors were associated with psychopathology and potential mechanisms investigated.Forty-six cases were included in the case series (28 males, 18 females; mean age at assessment 11y 8mo [1y 11mo-16y 11mo, SD 4y 0mo]). Twenty-nine papers representing data from 264 cases met inclusion criteria for the systematic review. Overall, at least 50% of cases presented with psychopathology. Epilepsy, intellectual disability, and male sex were associated with externalizing disorders (attention-deficit/hyperactivity disorder, conduct and oppositional defiance disorders, and rage attacks). Intellectual disability mediated the effects of epilepsy on externalizing psychopathology. No factors were associated with internalizing disorders (anxiety and depressive disorders), although these were not well reported.Psychiatric comorbidities are highly prevalent in the presentation of paediatric hypothalamic hamartoma. The aetiology of psychopathology comprises a range of interacting biological and psychosocial factors with particular influence from epilepsy. Further research is required to achieve an evidence base for treatment.Over half of children with hypothalamic hamartoma present with psychiatric comorbidity. Externalizing and internalizing disorders are present in approximately 60% and 30% of children with hypothalamic hamartomas respectively. Epilepsy and male sex are associated with externalizing psychopathology. Intellectual disability mediates the association between epilepsy and externalizing symptoms. No clear associations are evident for internalizing disorders or precocious puberty.PERFIL NEUROPSIQUIÁTRICO DEL HAMARTOMA HIPOTALÁMICO EN PEDIATRÍA: REVISIÓN SISTEMÁTICA Y SERIE DE CASOS: OBJETIVO: Evaluar las comorbilidades neuropsiquiátricas en niños y adolescentes con hamartoma hipotalámico. MÉTODO: En este estudio analizamos retrospectivamente las notas de los casos de todos los individuos con hamartoma hipotalámicos referidos al Great Ormond Street Hospital, London, entre el 2000 y 2016. Además, realizamos una revisión bibliográfica sistemática dirigida a identificar la serie de casos pediátricos. Síntomas psiquiátricos, demográfico, comorbilidades físicas y funcionamiento cognitivo fueron recolectados en todos los casos posibles.Se efectuaron análisis para determinar qué factores se asociaron con psicopatología y se investigaron mecanismos potenciales. RESULTADOS: En total 46 casos fueron incluidos en la serie de casos (28 masculinos, 18 femeninos, media de edad a la evaluación 11 años y 8 meses, DS 4 años y 0 mes). La revisión bibliográfica identifico 29 artículos describiendo 264 casos que reunieron criterios de inclusión para la extracción de datos. En total, al menos 50% de casos presentaban psicopatología. Epilepsia, discapacidad intelectual, y sexo masculino fueron asociados con desórdenes externos (déficit de atención con hiperactividad, desórdenes conductuales y oposicional desafiante, ataques de furia). Ningún factor fue asociado con la internalización de desórdenes neuropsiquiátricos (desórdenes de ansiedad y depresión), aunque éstos no fueron bien reportados. INTERPRETACIÓN: Las comorbilidades psiquiátricas son altamente prevalentes en la presentación del hamartoma hipotalámico pediátrico. La etiología de la psicopatología comprende un rango de interacciones biológicas y factores psicosociales con particular influencia de la epilepsia. Se requiere más información de investigación para reunir evidencia científica que guie el tratamiento.PERFIL NEUROPSIQUIÁTRICO DO HAMARTOMA HIPOTALÂMICO PEDIÁTRICO: REVISÃO SISTEMÁTICA E SÉRIE DE CASOS: OBJETIVO: Avaliar comorbidades neuropsiquiátricas em crianças e adolescentes com hamartoma hipotalâmico. MÉTODO: Nós analisamos retrospectivamente os registros de casos de todos os indivíduos encaminhados para o Hospital Great Ormond Street, Londres, entre 2000 e 2016. Além disso, uma revisão sistemática visando identificar todos os casos pediátricos prévios foi realizada. Sintomas psiquiátricos, dados demográficos, comorbidades físicas, e funcionamento cognitivo foram registrados para todos os casos em que foi possível. Análises foram realizadas para determinar quais fatores se associavam com psicopatologia e potenciais mecanismos foram investigados. RESULTADOS: Quarenta e seis casos foram incluídos na série de casos (28 do sexo masculino, 18 do sexo feminino; média de idade na avaliação 11a 8m (1a 11m-16a 11m, DP 4a 0m). Vinte e nove artigos representando dados de 264 casos atenderam aos critérios de inclusão para a revisão sistemática. No total, pelo menos 50% dos casos apresentaram psicopatologia. Epilepsia, deficiência intelectual, e sexo masculino eram associados com desordens externalizantes (transtorno de déficit de atenção e hiperatividade, transtornos de conduta e de desafio oposicional, e ataques de raiva). A deficiência intelectual mediou os efeitos da epilepsia e da psicopatologia externalizante. Nenhum fator foi associado com transtornos internalizantes (ansiedade e transtornos depressivos), embora estes não tenham sido bem reportados. INTERPRETAÇÃO: Comorbidades psiquiátricas são altamente prevalentes na apresentação do hamartoma hipotalâmico pediátrico. A etiologia da psicopatologia envolve uma variedade de fatores biológicos e psicossociais que interagem, com particular influência da epilepsia. Mais pesquisas são necessárias para se atingir uma base de evidências para o tratamento.

EMTICS Collaborative Group., Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive–compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3–10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3–16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host’s immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders., This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under Grant agreement no. 278367. Schrag was supported by the National Institute for Health Research UCLH Biomedical Research Centre, and Müller, Burger, Schnell and Weidinger by Stiftung Immunität und Seele. This research was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London (Heyman); partially sponsored by GSK Vaccines (Margarit, Bartolini); and Deutsche Forschungsgemeinschaft (DFG): projects 1692/3-1, 4-1 (Münchau).

Objectives The primary aim of this qualitative study was to explore the views of health professionals, with little previous clinical mental health training, of an adapted modular cognitive-behavioral intervention (MATCH-ADTC) for common mental health problems in children and young people with epilepsy. Methods Healthcare Professionals (HCPs) and their supervisors were interviewed at the start (n = 23) and end (n = 15) of the six-month training period. The interviews were transcribed verbatim and analyzed using thematic analysis. Results Three higher order themes with sub-themes were identified: (1) strengths of the MATCH-ADTC content and manual; (2) expectations of the treatment; and (3) improving practice with MATCH-ADTC. Overall impressions of the training and treatment were largely positive, with HCPs viewing MATCH-ADTC as an acceptable treatment for the families that they worked with. HCPs highlighted some challenges in delivering an integrated service, particularly relating to the time commitment involved and their own confidence in delivering the intervention, as many participants did not have a mental health background. Conclusions The findings suggested that the intervention and training was acceptable to HCPs working in pediatric epilepsy services, and confidence grew over the six-month training period. Further research is needed to understand how to best train, supervise, and support HCPs in pediatric epilepsy services to deliver mental health treatments.

Behavioural difficulties impact greatly upon quality of life for children with chronic illness and their families but are often not identified or adequately treated, possibly due to the separation of physical and mental health services. This case study describes the content and outcomes of guided self-help teletherapy for behavioural difficulties in a child with epilepsy and complex needs using an evidence-based behavioural parenting protocol delivered within a paediatric hospital setting. Behavioural difficulties and progress towards the family’s self-identified goals were monitored at each session. Validated measures of mental health and quality of life in children were completed before and after intervention and satisfaction was measured at the end of treatment. Measures demonstrated clear progress towards the family’s goals and reduction in weekly ratings of behavioural difficulties. This case demonstrates that a guided self-help teletherapy approach delivered from within the paediatric setting may be one way of meeting unmet need.

Background Mental health disorders in the context of long-term conditions in children and young people are currently overlooked and undertreated. Evidence-based psychological treatments for common childhood mental health disorders (anxiety, depression and disruptive behaviour disorders) have not been systematically evaluated in young people with epilepsy despite their high prevalence in this population. The aim of this multi-site randomised controlled trial is to determine the clinical and cost-effectiveness of adding a modular psychological intervention to usual care for the mental health disorders in comparison to assessment-enhanced usual care alone. Methods In total, 334 participants aged 3–18 years attending epilepsy services will be screened for mental health disorders with the Strengths and Difficulties Questionnaire (SDQ) and the diagnostic Development and Wellbeing Assessment (DAWBA). Those identified as having a mental health disorder and consenting to the trial will be randomised to either receive up to 22 sessions of the modular psychological intervention (MATCH-ADTC) delivered over the telephone over 6 months by non-mental health professionals in addition to usual care or to assessment-enhanced usual care alone. Outcomes will be measured at baseline, 6 months and 12 months post-randomisation. It is hypothesised that MATCH-ADTC plus usual care will be superior to assessment-enhanced usual care in improving emotional and behavioural symptoms. The primary outcome is the SDQ reported by parents at 6 months. Secondary outcomes include parent-reported mental health measures such as the Revised Children’s Anxiety and Depression Scale, quality of life measures such as the Paediatric Quality of Life Inventory and physical health measures such as the Hague Seizure Severity Scale. Outcome assessors will be blinded to group assignment. Qualitative process evaluations and a health economic evaluation will also be completed. Discussion This trial aims to determine whether a systematic and integrated approach to the identification and treatment of mental health disorders in children and young people with epilepsy is clinically and cost-effective. The findings will contribute to policies and practice with regard to addressing mental health needs in children and young people with other long-term conditions. Trial registration ISRCTN ISRCTN57823197. Registered on 25 February 2019.

Tsetsos, Fotis et al., Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS., This research is co-financed by Greece and the European Union (European Social Fund—ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Reinforcement of Postdoctoral Researchers - 2nd Cycle” (MIS-5033021), implemented by the State Scholarships Foundation (IKY). L.K.D. was supported by grants from the National Institutes of Health including U54MD010722-04, R01NS102371, R01MH113362, U01HG009086, R01MH118223, DP2HD98859, R01DC16977, R01NS105746, R56MH120736, R21HG010652, and RM1HG009034.

Background: Children with Tourette syndrome (TS) often have comorbid disorders, particularly attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). While subtle premorbid symptoms have been described in various psychiatric disorders, the presence of clinical precursors that may exist before the onset of tics is unknown. This longitudinal study aimed to find clinical precursors of tics by assessing a range of clinical characteristics prior to tic onset in comparison with children without onset of tics.Methods: A sample of 187 3- to 10-year-old first-degree unaffected relatives of children with TS were followed up to 7 years in the European Multicentre Tics in Children Study (EMTICS). We investigated whether clinical characteristics assessed at baseline predicted tic onset, comparing 126 children without tic onset to 61 children who developed tics. We used the least absolute shrinkage and selection operator (LASSO) method, a penalised logistic regression approach. We also explored sex differences and repeated our analyses in an age- and sex-matched subsample.Results: Children with tic onset were more frequently male (beta = -0.36), had higher baseline severity of conduct problems (beta = 0.23), autism spectrum disorder symptoms (ASD; beta = 0.08), compulsions (beta = 0.02) and emotional problems (beta = 0.03) compared to children without tic onset. Conduct and ASD problems were male-specific predictors, whereas severity of compulsions and oppositional (beta = 0.39) and emotional problems were female-specific predictors.Conclusion: This study supports the presence of clinical precursors prior to tic onset and highlights the need of sex-specific monitoring of children at risk of developing tics. This may aid in the earlier detection of tics, particularly in females. We moreover found that tics most often persisted one year after tic onset, in contrast to the common belief that tics are mostly transient.

The coronavirus pandemic has highlighted the need for remote technologies to be used in child and adolescent mental health services. With the UK being placed in lockdown one week before a scheduled 'face-to-face' low-intensity CBT training day due to COVID-19, there was a need for rapid adaptations to be made to the content, structure and format of a training day for practitioners in mental health services, to suit the online environment. The content covered the core areas of low-intensity CBT in children and adolescents. Findings showed that the one-day low-intensity training day increased knowledge and understanding in all key areas measured, and was positively received, providing further evidence for the effectiveness and acceptability of remote delivery. Given discussed benefits of remote delivery, as well as rapid developments in technologies helping to address some of the challenges raised, going forward, remote delivery could continue to be beneficial for increasing access to much needed evidence-based interventions.

ObjectiveTo determine rates of psychiatric comorbidity in a clinical sample of childhood movement disorders (MDs).DesignCohort study.SettingTertiary children’s hospital MD clinics in Sydney, Australia and London, UK.PatientsCases were children with tic MDs (n=158) and non-tic MDs (n=102), including 66 children with dystonia. Comparison was made with emergency department controls (n=100), neurology controls with peripheral neuropathy or epilepsy (n=37), and community controls (n=10 438).InterventionsOn-line development and well-being assessment which was additionally clinically rated by experienced child psychiatrists.Main outcome measuresDiagnostic schedule and manual of mental disorders-5 criteria for psychiatric diagnoses.ResultsPsychiatric comorbidity in the non-tic MD cohort (39.2%) was comparable to the tic cohort (41.8%) (not significant). Psychiatric comorbidity in the non-tic MD cohort was greater than the emergency control group (18%, pConclusionsPsychiatric comorbidity is common in non-tic MDs such as dystonia. These psychiatric comorbidities appear to be under-recognised and undertreated.

This study provides a preliminary exploration of factors which differentially predict treatment response to telephone-delivered cognitive behavioural therapy (TCBT) compared to face-to-face CBT (CBT) in a randomised non-inferiority controlled trial of 72 children (aged 11–18 years) with obsessive–compulsive disorder (OCD). Potential moderator variables, their interaction with treatment group (CBT, TCBT) and baseline levels of OCD severity were entered into separate regression models where the primary outcome measure was the post-intervention Children’s Yale–Brown Obsessive–Compulsive Scale total score (CYBOCS). Separate regressions were also used to test associations between predictors and outcome controlling for pretreatment CYBOCS. Only pretreatment level of parent-rated child peer problems moderated the effects of the two interventions on CYBOCS severity at post-treatment. After controlling for baseline CYBOCS, only family accommodation rated by mothers predicted poorer outcomes in both groups. While CBT and TCBT may be equally effective for adolescents with OCD, the current results tentatively suggest that higher baseline level of peer problems strengthened the response to therapy for youth receiving TCBT and the predictor analyses reinforce the importance of directly addressing family accommodation during CBT for paediatric OCD regardless of delivery mode. Limitations of the current findings and directions for future work are discussed.

SUMMARY We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk., In Brief Wang et al. expand their earlier exome-sequencing work in TD, adding 291 trios and conducting combined analyses suggesting de novo variants carry more risk in individuals with unaffected parents, establishing de novo structural variants as risk factors, identifying CELSR3 as a risk gene, and implicating cell polarity in pathogenesis., Graphical Abstract

ObjectiveWe aimed to test the feasibility of using an online parent-completed diagnostic assessment for detecting common mental health disorders in children attending neurology clinics. The assessment does not require intervention by a mental health professional or additional time in the clinic appointment.SettingTwo parallel and related screening studies were undertaken: Study 1: Tertiary paediatric neurology clinics. Study 2: Secondary and tertiary paediatric neurology clinics.PatientsStudy 1: 406 Young people aged 7–18 attending paediatric neurology clinics. Study 2: 225 Young people aged 3–18 attending paediatric epilepsy clinics.InterventionsParents completed online versions of the Strengths and Difficulties Questionnaire (SDQ) and Development and Well-being Assessment (DAWBA).Main outcome measuresWe investigated: the willingness of families to complete the measures, proportion identified as having mental health disorders, time taken to complete the measures and acceptability to families and clinicians.ResultsThe mean total difficulties score of those that had completed the SDQ fell in the ‘high’ and ‘very high’ ranges. 60% and 70% of the DAWBAS completed met criteria for at least one DSM-IV disorder in study 1 and 2 respectively. 98% of the parents reported that the screening methods used were acceptable.

Objective Children with neurological conditions such as epilepsy are at high risk of developing mental health disorders. Guided self-help can be used to increase access to psychological therapies. When developing and evaluating interventions, it is important to obtain the views of service-users about their acceptability. A telephone-guided self-help intervention was used to treat common mental health difficulties in children and young people with neurological conditions. The intervention was not adapted in content to account for chronic illness. This study therefore reports on qualitative interviews with participants to determine the acceptability of the intervention. Methods Semi-structured interviews were conducted with 27 participants (25 parents and 2 young people) who had undertaken a telephone-delivered guided self-help intervention for common mental health difficulties in the context of a paediatric neurological condition. Transcripts were analysed thematically using the framework approach. Results Thirteen themes were extracted, organised into three main domains, which covered: the practicalities of telephone guided self-help treatment; the outcomes of the intervention; and the extent to which adaptation was needed for chronic illness. Most families found the intervention helpful in working towards their specific goals and noticed changes for the child and/or parents and family. Conclusions Participants had a positive experience of the intervention and the majority of parents found the standard intervention with individualised goals sufficient to meet the young person's mental health needs.

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent–child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case–control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive–compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes. Electronic supplementary material The online version of this article (doi:10.1007/s00406-017-0808-8) contains supplementary material, which is available to authorized users.

IntroductionThere is uncertainty surrounding the diagnosis, prevalence, phenotype, duration and treatment of Long COVID. This study aims to (A) describe the clinical phenotype of post-COVID symptomatology in children and young people (CYP) with laboratory-confirmed SARS-CoV-2 infection compared with test-negative controls, (B) produce an operational definition of Long COVID in CYP, and (C) establish its prevalence in CYP.Methods and analysisA cohort study of SARS-CoV-2-positive CYP aged 11–17 years compared with age, sex and geographically matched SARS-CoV-2 test-negative CYP. CYP aged 11–17 testing positive and negative for SARS-CoV-2 infection will be identified and contacted 3, 6, 12 and 24 months after the test date. Consenting CYP will complete an online questionnaire. We initially planned to recruit 3000 test positives and 3000 test negatives but have since extended our target. Data visualisation techniques will be used to examine trajectories over time for symptoms and variables measured repeatedly, separately by original test status. Summary measures of fatigue and mental health dimensions will be generated using dimension reduction methods such as latent variables/latent class/principal component analysis methods. Cross-tabulation of collected and derived variables against test status and discriminant analysis will help operationalise preliminary definitions of Long COVID.Ethics and disseminationResearch Ethics Committee approval granted. Data will be stored in secure Public Health England servers or University College London’s Data Safe Haven. Risks of harm will be minimised by providing information on where to seek support. Results will be published on a preprint server followed by journal publication, with reuse of articles under a CC BY licence. Data will be published with protection against identification when there are small frequencies involved.Trial registration numberISRCTN34804192; Pre-results.

Psychiatric symptoms are an increasingly recognised feature of movement disorders. Recent identification of causative genes and autoantibodies has allowed detailed analysis of aetiologically homogenous subgroups, thereby enabling determination of the spectrum of psychiatric symptoms in these disorders.\ud \ud This review evaluates the incidence and type of psychiatric symptoms encountered in patients with movement disorders. A broad spectrum of psychiatric symptoms was identified across all subtypes of movement disorder, with depression, generalised anxiety disorder and obsessive-compulsive disorder being most common. Psychosis, schizophrenia and attention deficit hyperactivity disorder were also identified, with the psychiatric symptoms often predating onset of the motor disorder.\ud \ud The high incidence of psychiatric symptoms across such a wide range of movement disorders suggests a degree of common or overlapping pathogenic mechanisms. Our review demonstrates the need for increased clinical awareness of such co-morbidities, which should facilitate early neuropsychiatric intervention and allied specialist treatment for patients.

Contains fulltext : 174490.pdf (Publisher’s version ) (Open Access) Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response. 10 p.

ObjectiveThis study aimed to conduct a randomised pilot trial to assess the feasibility of a randomised controlled trial (RCT) to investigate the effect of telephone-guided self-help for the treatment of mental health difficulties in children with neurological conditions.DesignPreliminary RCT. The primary outcome measure was the Strengths and Difficulties Questionnaire.SettingNeurology clinics in a national tertiary paediatric hospital.PatientsYoung people attending neurology clinics who met criteria for mental health difficulties according to the Development and Wellbeing Assessment.Interventions12 weeks of telephone-guided self-help based on a modular approach to psychological therapy for children delivered to children and/or their parents (n=17; eight males; mean age 12.04 years, SD=3.34) or a waiting list for telephone-guided self-help with no additional intervention over 12 weeks (n=17; nine males; mean age 10.53 years, SD=3.14).Results124 participants completed the DAWBA, and 34 children and young people were entered into the trial. 65% of those randomised to the intervention arm completed the full intervention, and the intervention was acceptable to those completing it. However, there were significant problems related to lack of data completion (38% data loss for primary outcome measure), choice of control comparator and outcome measures. Due to significant loss of data at follow-up, the effect size findings are considered unreliable.ConclusionsFurther feasibility work should be conducted to improve data completeness before progression to a definitive trial of guided self-help for mental health problems in children with neurological conditions can be recommended.Trial registration numberISRCTN21184717.

Functional symptom disorders—often termed ‘medically unexplained symptoms’—are being increasingly recognised as a major source of distress, confusion and—not least—cost. The 2016 Kings Fund report—‘Bringing Together Physical and Mental Health’—estimated that the National Health Service in England spends about 3 billion pounds per year on this group of conditions in adults and children. Though published studies have revealed the importance of recognising and treating functional symptoms in adults, the literature in children is sparse. Raper and colleagues in this issue add significantly to our knowledge by reporting on a 20-year experience, in their centre, of children with functional neurological disorder (FND).1 FND, also known as conversion disorder, refers to a spectrum of neurological symptoms which have no established neurological cause and are assumed psychological in origin. Adult patients with FND are reported to have disappointing rates of recovery, but this long-term follow-up study highlights the emerging optimism for outcomes in children. Less than a quarter of those followed long term appeared to experience persistent severe functional symptoms in adult life. Notably and unusually the reporting hospital has been accurately diagnosing and coding functional neurological symptoms reliably and routinely over the last 20 years. Precise recording and communication of the diagnosis of these patients seems to have become embedded in the culture of the setting for this study and is likely to be key to recovery. For progress to be made, this practice needs to be widely adopted nationally and internationally. The positive endorsement of a FND diagnosis …

A subset of patients with obsessive-compulsive disorder (OCD) present with symptoms that indicate risk. In some cases of OCD, risk is only apparent, merely reflecting the content of obsessional fears which are never acted upon (e.g. intrusive thoughts of harming others). In contrast, genuine risk can arise in OCD as an unintended consequence of engaging in compulsions or avoidance (e.g. skin damage caused by washing with bleach). In both situations, risk can cause confusion among clinicians regarding diagnosis and /or hinder access to appropriate treatment. The current article adds to the small existing literature on risk in OCD by presenting case examples illustrating different types of risk in the context of pediatric OCD, along with a discussion of their implications for management. The cases highlight that it is crucial that risk in OCD is considered carefully within the context of the phenomenology of the disorder. In many cases, treatment should follow the usual OCD treatment protocols and both apparent and genuine risk resolve with successful treatment of the OCD. In some cases, there may be a need to actively manage genuine risk. In these instances, it is essential that risk management is carefully integrated into a program of evidence-based treatment for OCD.

Purpose Non-epileptic seizures are paroxysmal events which to an observer resemble epileptic seizures. Proposed risk factors incorporate biopsychosocial aspects including factors in the affected individual. Unexpectedly high rates of autism spectrum disorder (ASD) occurred in the clinical population reported here. Although elevated levels of psychiatric co-morbidity are known to be present in patients with NES, ASD has only been previously described in a single case report. Methods This case series captures rates of ASD in 59 children and young people who were referred to a specialist paediatric mental health service at Great Ormond Street Hospital, London, UK for assessment and treatment of non-epileptic seizures between 2012 and 2016. Results 10/59 (16.9%) of the children and young people with non-epileptic seizures also had ASD, with 5/10 (50%) of these undiagnosed with ASD before referral. Children and young people with ASD were significantly more likely to have tics or attention-deficit hyperactivity disorder than those without ASD. Conclusion ASD may be a common co-morbidity in non-epileptic seizures. Careful clinical assessment with consideration of ASD traits is therefore important in the non-epileptic seizures population. It is beneficial to diagnose ASD early as its presence is likely to require a modified approach to assessment and treatment of non-epileptic seizures. Study of the development of non-epileptic seizures in ASD may suggest hypotheses for the pathogenesis of non-epileptic seizures in the wider population.

The EMTICS collaborative group: Anastasiou, Zacharias; Apter, Alan; Baglioni, Valentina; Bartolini, Erika; Benaroya-Milshtein, Noa; Bodmer, Benjamin; Bognar, Emese; Burger', Bianka; Buttiglione, Maura; Cardona, Francesco; Vela, Marta Correa; Creti, Roberta; Dietrich, Andrea; Debes, Nanette M.; Efstratiou, Androulla; Ferro, Maria Cristina; Fremer, Carolin; Garcia-Delgar, Blanca; Gariup, Maria; Georgitsi, Marianthi; Gulisano, Mariangela; Hagen, Annelieke; Hagstrom, Julie; Hedderly, Tammy J.; Heyman, Isobel; Hoekstra, Pieter J.; Huyser, Chaim; Imperi, Monica; Karagiannidis, Iordanis; Laviola, Giovanni; Macri, Simone; Madruga-Garrido, Marcos; Margarit, Immaculada; Marotta, Anna; Martino, Davide; Meier, Ute C.; Mir, Pablo; Mo, Natalie; More, Astrid; Mueller-Vahl, Kirsten; Muenchau, Alexander; Nagy, Peter; Neri, Valeria; Openneer, Thafra J. C.; Orefici, Graziella; Paschou, Peristera; Pellico, Alessandra; Petruzzelli, Onofrio; Porcelli, Cesare; Redondo, Marina; Rizzo, Renata; Roazzi, Paolo; Roessner, Veit; Ruhrman, Daphna; Schnell, Jaana M. L.; Schrag, Anette; Schutze, Gregor A.; Schwarz, Markus J.; Silvestri, Paola Rosaria; Skov, Liselotte; Steinberg, Tamar; Stober, Sara; Tallon, Marco; Tarnok, Zsanett, In Tourette Syndrome (TS) a role for autoantibodies directed against neuronal proteins has long been suspected, but so far results are still inconsistent. The aim of this study was to look for antibodies to specific or undefined neuronal proteins that could be involved in the aetiology of the disease. Sera from children with Tourette Syndrome or another chronic tic disorder (TS/TD), collected as part of the longitudinal European Multicenter Tics in Children Study, were investigated. Participants included 30 siblings of patients with TS/TD prior to developing tics (preclinical stage) and the same children after the first tic onset (onset), and 158 patients in the chronic phase undergoing an acute relapse (exacerbation). Presence of antibodies binding to rodent brain tissue was assessed by immunohistology on rat brain sections and by immunofluorescent staining of live hippocampal neurons. Live cell-based assays were used to screen for antibodies to NMDAR, CASPR2, LGI1, AMPAR and GABAAR. Immunohistology indicated evidence of antibodies reactive with brain tissue, binding mainly to the hippocampus, the basal ganglia or the cerebellum in 26/218 (12%), with 8% of the preclinical or onset sera binding to the dentate gyrus/CA3 region or cerebellum. Only two individuals (one pre-clinical, one chronic) had antibodies binding the NMDAR and the binding was only weakly positive. No other specific antibodies were detected. Despite some immunoreactivity towards neuronal antigens on brain tissue, this was not mirrored by antibodies binding to live neurons, suggesting the presence of non-specific antibodies or those that bind non-pathogenic intracellular epitopes. NMDAR or the other neuronal surface antibodies tested were very infrequent in these patients. The evidence for pathogenic antibodies that could be causative of TS is weak.

Objective Adult research investigating the link between alexithymia and medically unexplained symptoms (MUS) has found a significant relationship between increased alexithymia and MUS. This difficulty in expressing emotions is likely to begin in childhood so the objective of this paper is to present a quantitative review of studies focussing on the association between MUS and alexithymia in children. Methods Databases were searched with predefined terms relating to alexithymia and MUS in children (0–17 years). Two reviewers independently assessed abstracts, extracted data and undertook quality analyses. Systematic review methods were used in accordance with Cochrane guidelines. Results Ten studies met the criteria for inclusion in the review. Seven of the eight studies which focused on a comparison between children with MUS and healthy controls, found higher levels of self-reported alexithymia in the children with MUS. However, in the two studies where children were asked to complete tasks that objectively measure alexithymia, significant differences were not found. Results of studies comparing alexithymia in children with MUS and children with medical/psychiatric controls were inconsistent; there was some evidence of increased anxiety and depression in young people with alexithymia and MUS but inconsistency of measures across studies makes drawing conclusions difficult. Conclusion There is preliminary evidence that children with MUS have significantly higher levels of alexithymia than controls based on self-report measures; however, this finding was not replicated in objective tasks of alexithymia. Future studies should include validated tasks that objectively measure emotion recognition abilities and focus on possible mediating factors such as neurodevelopmental and mental health difficulties.

Objective The objective was to systematically review studies that have focused on behavioral and emotional functioning before (baseline) and after (follow-up) pediatric epilepsy surgery. Methods The systematic review was carried out according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and EMBASE were searched from inception. Findings are described with respect to (1) changes in behavior and emotions between baseline and follow-up, (2) factors associated with changes in behavior and emotions, and (3) impact of study quality on findings. Results Fifteen studies met inclusion criteria. The majority of studies employed parent report screening checklists. In these studies, scores were reported to have significantly improved at follow-up on at least one domain in seven studies and not to have changed significantly in two studies. In no studies was a deterioration in behavior noted. In studies that used Diagnostic and Statistical Manual of Mental Disorders (DSM) clinical diagnoses, no significant change was noted in the numbers of children diagnosed at baseline and at follow-up. In total, 21 children lost diagnoses, whereas 16 children developed new diagnoses. A better seizure outcome was associated with improvements in behavioral-emotional functioning at follow-up in three of the four studies where it was considered. In terms of study quality, none of the studies was rated as strong (ie, had no weak ratings on a quality assessment tool). Significance There is some evidence of improvement in emotional and behavioral functioning after epilepsy surgery. However, this is confined to scores on parent-reported screening measures of emotional and behavioral symptoms and not clinical diagnoses. Future research should focus on including responses from multiple respondents (child, parent, teacher) when using screening instruments, but also diagnostic interviews. There is a need for long-term follow-up (beyond 2 years) with sufficiently large sample sizes including data from nonsurgery controls to understand factors associated with changes in functioning postsurgery.

Contains fulltext : 209315.pdf (Publisher’s version ) (Closed access) The apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has been administered can account for this "declining effect". We also investigated the association between DCS administration characteristics and treatment outcome to find optimal dosing parameters. We conducted a secondary analysis of individual participant data obtained from 1047 participants in 21 studies testing the efficacy of DCS-augmented exposure treatments. Different outcome measures in different studies were harmonized to a 0-100 scale. Intent-to-treat analyses showed that, in participants randomized to DCS augmentation (n = 523), fewer DCS doses, later timing of DCS dose, and lower baseline severity appear to account for this decline effect. More DCS doses were related to better outcomes, but this advantage leveled-off at nine doses. Administering DCS more than 60 minutes before exposures was also related to better outcomes. These predictors were not significant in the placebo arm (n = 521). Results suggested that optimal DCS administration could increase pre-to-follow-up DCS effect size by 50%. In conclusion, the apparent declining effectiveness of DCS over time may be accounted for by how it has been administered. Optimal DCS administration may substantially improve outcomes. Registration: The analysis plan for this manuscript was registered on Open Science Framework (https://osf.io/c39p8/). 8 p.

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

Background Fatigue is a disabling, poorly understood symptom in children and adolescents with multiple sclerosis (caMS), for which effective treatments are lacking. In paediatric Chronic Fatigue Syndrome (CFS), effective psychological interventions have been developed based on psychosocial factors associated with fatigue. This study aimed to identify potentially modifiable factors of fatigue in caMS by comparing caMS, adolescents with CFS, healthy adolescents and their parents on measures of fatigue, psychosocial factors, and neurocognitive functioning. Methods 175 participants including 30 caMS (15 fatigued, 15 non-fatigued), 30 adolescents with CFS, 30 healthy controls, and their parents were compared on measures of self- and parent-reported fatigue, adolescent and parent cognitive behavioural responses to symptoms, sleep, psychological difficulties, parental distress and objectively measured neurocognitive functioning. Results Fatigue severity, functional impairment and cognitive behavioural responses to symptoms were equivalent in fatigued caMS and adolescents with CFS, and were significantly higher than in healthy controls and non-fatigued caMS. Neurocognitive functioning was impaired in both caMS groups, but was normal in adolescents with CFS and healthy controls. No between-group differences were identified in adolescent sleep behaviour or psychological difficulties. Parents of all illness groups had more unhelpful cognitions than parents of healthy controls. Psychological distress was elevated in parents of both fatigued groups. Conclusions Fifty percent of caMS reported clinically significant fatigue. Similarities between adolescent and parent cognitive behavioural factors in fatigued caMS and adolescents with CFS suggest important potential targets for intervention. Both fatigued and non-fatigued caMS had cognitive difficulties, suggesting that fatigue may need targeted intervention.

Purpose To describe clinical experiences of paediatric non-epileptic seizures (NES) among doctors attending a UK child and adolescent psychiatry conference. Methods Sixty-six participants completed a semi-structured bespoke questionnaire. Results are reported using descriptive statistics. Results Two-thirds of respondents regarded the best name for the disorder to be "non-epileptic seizures". Although most doctors saw new cases each year, two-thirds described their own service as poorly equipped to manage NES. Anti-epileptic drugs (AEDs) were commonly still being taken by children without epilepsy 6 months after their diagnosis. Preferred treatment approaches included supportive case management and cognitive behavioural therapy. Joint working with paediatrics and liaison with schools were seen as important. Conclusion Despite many clinicians having experience of the disorder, NES seemed to occupy a neglected status, often falling between paediatrics and child mental health, with inadequately defined care pathways leading to sub-optimal treatment. Re-configuration of services to prioritise liaison with paediatrics and education may support development of effective treatment, thus maximising health, social and educational opportunities for young people and their families.

Background Mental and physical health treatment should be delivered together for children and young people with epilepsy. Training healthcare professionals (HCPs) in epilepsy services to deliver mental health interventions is an important way to facilitate integrated care. Objective To determine the feasibility of remotely delivered assessment and psychological treatment for mental health difficulties delivered by HCPs in pediatric epilepsy clinics with limited formal training in psychological interventions. We hypothesized that it would be (i) feasible to train HCPs to deliver the psychological intervention and (ii) that participants receiving the psychological therapy would report reductions in symptoms of mental health difficulties including anxiety, depression, and behavior difficulties and improve quality of life. Methods Thirty-four children and young people with epilepsy who had impairing symptoms of a common mental health difficulty (anxiety, depression, disruptive behavior, and/or trauma) were allocated to receive 6 months of a modular cognitive behavioral intervention delivered by a HCP with limited formal psychological therapy experience. Thirteen HCPs were trained in delivery of the intervention. Healthcare professional competence was assessed in a two-stage process. Parent-reported measures of mental health symptoms and quality of life were completed at baseline and following the intervention. Paired t-tests were used to analyze changes in symptoms over time. Results All thirteen HCPs who participated in the training were considered competent in therapeutic delivery by the end of the training period. Twenty-three patients completed pre- and post-intervention measures and were included in the analysis. There were statistically significant improvements in: symptoms of mental health problems (p = 0.01; Cohen’s d = 0.62), total impact of mental health problems (p = 0.03; Cohen’s d = 0.52), anxiety and depression symptoms (p = 0.02; Cohen’s d = 0.57) and quality of life (p = 0.01; Cohen’s d = 0.57). Conclusion A modular cognitive behavioral treatment delivered over the telephone by HCPs with limited experience of psychological therapy was feasible and effective in treating mental health problems in children and young people with epilepsy. Health-related Quality of Life also improved over the duration of treatment. A randomized controlled trial (RCT) is needed to demonstrate efficacy of the intervention.