Tackle your Tics, a brief intensive group-based exposure treatment for young people with tics: results of a randomised controlled trial.

Tics can have a serious impact on the quality of life of children and their families. Behavioural therapy is an evidence-based first line treatment for tic disorders. This randomised controlled trial studied the efficacy of a brief, condensed group-based programme for children with tics (Dutch Trial Registry NL8052, 27 September 2019). Tackle your Tics is a four-day group treatment, including exposure and response prevention and supporting components, delivered by therapists and 'experts by experience'. We collected outcome measures at baseline (T1), directly post-treatment (T2), and at three- and 6-months follow-up (T3, T4) including tic severity (primary outcome measure), tic-related impairment, quality of life, tic-related cognitions, emotional/behavioural functioning, family functioning, treatment satisfaction and adherence. Outcomes directly post-treatment improved in both the treatment group (n = 52) and waiting list (n = 54), but showed no statistically significant differences between the conditions (differential change over time T1-T2) on tic severity (Yale Global Tic Severity Scale), quality of life (Gilles de la Tourette Syndrome Quality of Life Scale), tic-related cognitions and family functioning. At longer term (T3), again no between-group difference was found on tic severity, but tic-related impairment, quality of life and emotional/behavioural functioning significantly improved in the treatment group compared to the waiting list. Mean treatment satisfaction scores were favourable for both children and parents. Directly posttreatment, Tackle your Tics showed no superior effect compared to waiting list. However, on longer term this brief four-day group treatment was effective in improving tic-related impairment, quality of life and emotional/behavioural functioning.

Training is not enough: child and adolescent psychiatry clinicians' impressions of telepsychiatry during the first COVID-19 related lockdown.

To ensure the continuity of care during the COVID-19 pandemic, clinicians in Child and Adolescent Psychiatry (CAP) were forced to immediately adapt in-person treatment into remote treatment. This study aimed to examine the effects of pre-COVID-19 training in- and use of telepsychiatry on CAP clinicians' impressions of telepsychiatry during the first two weeks of the Dutch COVID-19 related lockdown, providing a first insight into the preparations necessary for the implementation and provision of telepsychiatry during emergency situations. All clinicians employed by five specialized CAP centres across the Netherlands were invited to fill in a questionnaire that was specifically developed to study CAP clinicians' impressions of telepsychiatry during the COVID-19 pandemic. A total of 1065 clinicians gave informed consent and participated in the study. A significant association was found between pre-COVID-19 training and/or use of telepsychiatry and CAP clinicians' impressions of telepsychiatry. By far, the most favourable impressions were reported by participants that were both trained and made use of telepsychiatry before the pandemic. Participants with either training or use separately reported only slightly more favourable impressions than participants without any previous training or use. The expertise required to provide telepsychiatry is not one-and-the-same as the expertise that is honed through face-to-face consultation. The findings of this study strongly suggest that, separately, both training and (clinical) practice fail to sufficiently support CAP clinicians in the implementation and provision of telepsychiatry. It is therefore recommended that training and (clinical) practice are provided in conjunction.

Long-term methylphenidate exposure and 24-hours blood pressure and left ventricular mass in adolescents and young adults with attention deficit hyperactivity disorder.

Young people with attention deficit hyperactivity disorder (ADHD) are now being treated with psychostimulant medication for longer than was previously the case and are increasingly likely to remain on methylphenidate into adolescence and adulthood. This study was designed to determine whether the long-term use of methylphenidate (MPH, immediate release or extended release) increases blood pressure and left ventricular mass (LVM) identified by echocardiography in adolescents and young adults with ADHD aged 12-25 years. In a five-site cross-sectional design two groups were compared for 24- hour blood pressure and heart rate (HR) registrations and LVM: 1) adolescents and young adults with ADHD who had been treated with MPH for > 2 years (N=162, age mean (SD) 15.6 (3.0)), and 2) adolescents and young adults with ADHD who had never been treated with methylphenidate (N=71, age mean 17.4 (4.2)). The analyses were controlled for propensity scores derived from age, sex, height, weight, and 19 relevant background variables. A blood pressure indicative of hypertension (>95th percentile) was observed in 12.2% (95% confidence interval 7.3 - 18.9%) of the participants in the MPH treated group and in 9.6% (95%CI 3.2 - 21.0%) of the MPH naïve group, with overlapping intervals. The 24-hour recorded systolic blood pressure (SBP) and HR were significantly higher during daytime in medicated individuals with ADHD than in those with unmedicated ADHD, but were similar in both groups during the night. 24-hour diastolic blood pressure (DBP) did not differ between both groups during either daytime or at night. LVM, corrected for body-surface area (LVMBSA), also did not differ between the two groups (p=0.20, controlling for confounders). Further, MPH daily dose and duration of treatment were unrelated to LVMBSA, SBP, and DBP. Long-term MPH use in adolescents and young adults with ADHD is associated with small but significant increases of SBP and HR during daytime. Given the current sample size, the proportions of hypertension do not differ significantly between MPH treated and MPH-naïve individuals with ADHD. Future studies with larger samples, longer treatment duration, and/or with within-subject designs are necessary. The results do, however, further support recommendations that highlight the importance of monitoring blood pressure and HR during MPH treatment.

Tackle your Tics: pilot findings of a brief, intensive group-based exposure therapy program for children with tic disorders.

Tourette syndrome (TS) and other chronic tic disorders (CTD) are prevalent neurodevelopmental disorders, which can have a huge burden on families and society. Behavioral treatment is a first-line intervention for tic disorders. Despite demonstrated efficacy, tic reduction and utilization rates of behavioral treatment remain relatively low. Patient associations point to an urgent need for easy-to-undergo treatments that focus both on tic reduction and improvement of quality of life. To enhance treatment outcome and overcome treatment barriers, this pilot study's aim was to investigate the feasibility and preliminary results of a brief, intensive group-based treatment. Tackle your Tics is a 4-day intensive and comprehensive group-based program for children and adolescents (9-17 years) with a tic disorder, consisting of exposure and response prevention (ERP) treatment and additional supporting components, such as coping strategies, relaxing activities and parent support. Assessments were performed pre- and post-treatment and at 2 months follow-up, to test outcomes on tic severity and quality of life, and explore premonitory urges, emotional and behavioral functioning and treatment satisfaction (N = 14, of whom 13 completed the treatment). Parents and children rated this treatment positive on a treatment satisfaction questionnaire. On tic severity (Yale Global Tic Severity Scale) and quality of life (Gilles de la Tourette Syndrome Quality of Life Scale for children and adolescents), improvements between pre-treatment and follow-up were found. Intensive ERP in group format is promising as a feasible treatment to improve both tic severity as well as quality of life. Larger controlled trials are needed to establish its effectiveness.

Exposure to challenging behaviours and burnout symptoms among care staff: the role of psychological resources.

BACKGROUND: Staff supporting individuals with intellectual disabilities are at risk of burnout symptoms. Evidence suggests an association between exposure to challenging behaviours of individuals with intellectual disabilities and burnout symptoms of staff, but the protective role of staff psychological resources in this relation has been understudied. METHOD: We investigated the association between exposure to challenging behaviours and burnout symptoms of staff and the direct and moderating effects of several psychological resources. Staff (N = 1271) completed an online survey concerning burnout symptoms (subscale Emotional Exhaustion of the Maslach Burnout Inventory), exposure to challenging behaviours and a range of potential psychological resources. We examined main and moderating effects with multilevel analyses. In order to control for the multiple comparisons, P values corrected for false discovery rate (PFDR ) were reported. RESULTS: We found a direct relation between exposure to challenging behaviours and increased levels of burnout symptoms in staff (b = .15, t(670) = 4.466, PFDR  < .0001). Perceived supervisor social support (b = -.97, t(627) = -7.562, PFDR  < .0001), staff self-efficacy (b = -.23, t(673) = -3.583, PFDR  < .0001), resilience (b = -.19, t(668) = -2.086, PFDR  < .05) and extraversion (b = -.20, t(674) = -3.514, PFDR  < .05) were associated with reduced burnout symptoms. None of the proposed psychological resources moderated the association between exposure to challenging behaviours and burnout symptoms of staff. CONCLUSIONS: Of the psychological resources found to be associated with reduced risk of burnout symptoms, staff self-efficacy and access of staff to supervisor social support seem to be the factors that can be influenced best. These factors thus may be of importance in reducing the risk of developing burnout symptoms and improving staff well-being, even though the current study was not designed to demonstrate causal relations between psychological resources and burnout symptoms.

Non-pharmacological interventions for challenging behaviours of adults with intellectual disabilities: A meta-analysis.

BACKGROUND: Non-pharmacological interventions are recommended for the treatment of challenging behaviours in individuals with intellectual disabilities by clinical guidelines. However, evidence for their effectiveness is ambiguous. The aim of the current meta-analysis is to update the existing evidence, to investigate long-term outcome, and to examine whether intervention type, delivery mode, and study design were associated with differences in effectiveness. METHOD: An electronic search was conducted using the databases Medline, Eric, PsychINFO and Cinahl. Studies with experimental or quasi-experimental designs were included. We performed an overall random-effect meta-analysis and subgroup analyses. RESULTS: We found a significant moderate overall effect of non-pharmacological interventions on challenging behaviours (d = 0.573, 95% CI [0.352-0.795]), and this effect appears to be longlasting. Interventions combining mindfulness and behavioural techniques showed to be more effective than other interventions. However, this result should be interpreted with care due to possible overestimation of the subgroup analysis. No differences in effectiveness were found across assessment times, delivery modes or study designs. CONCLUSIONS: Non-pharmacological interventions appear to be moderately effective on the short and long term in reducing challenging behaviours in adults with intellectual disabilities.

[Dilemmas in discontinuation of antipsychotic drug use in people with intellectual disabilities]. / Dilemma's bij afbouw van anti-psychoticagebruik bij mensen met een verstandelijke beperking.

BACKGROUND: The prevalence of antipsychotic drug use in people with intellectual disability (id) is high and largely off-label for challenging behaviour (cb), while evidence for their efficacy lacks. Side-effects frequently occur. Guidelines recommend appropriate psychotropic drug use by monitoring of effects and side-effects and discontinuing off-label use for cb. However, they are insufficiently adhered to. Discontinuation often fails due to behavioural worsening by largely unknown causes.
AIM: To offer an overview of results of off-label antipsychotic drug discontinuation and determinants for success or failure.
METHOD: Literature search in Medline, embase and Psycinfo.
RESULTS: Prospective open-label studies show that discontinuation in selected populations is possible in 33-40% and in placebo-controlled studies in 55-82%. Challenging behaviours, as measured with a standardized scale, mostly remained similar in those who succeeded as well as in those who failed to discontinue. Health problems, extrapyramidal symptoms, higher antipsychotic drug dosage, more severe cb, autism and male gender in participants, negative emotions towards cb, less knowledge on psychotropic drugs and male gender of support professional were related to less chance of successful discontinuation.
CONCLUSION: To improve results of antipsychotic drug discontinuation, proper diagnostics of underlying causes for cb, involvement of all stakeholders and enhancement of treatment opportunities for psychopathology in people with id are needed. Integrative care and knowledge development of id- and mental health care may be helpful.

Psychosocial risk factors for suicidality in children and adolescents.

Suicidality in childhood and adolescence is of increasing concern. The aim of this paper was to review the published literature identifying key psychosocial risk factors for suicidality in the paediatric population. A systematic two-step search was carried out following the PRISMA statement guidelines, using the terms 'suicidality, suicide, and self-harm' combined with terms 'infant, child, adolescent' according to the US National Library of Medicine and the National Institutes of Health classification of ages. Forty-four studies were included in the qualitative synthesis. The review identified three main factors that appear to increase the risk of suicidality: psychological factors (depression, anxiety, previous suicide attempt, drug and alcohol use, and other comorbid psychiatric disorders); stressful life events (family problems and peer conflicts); and personality traits (such as neuroticism and impulsivity). The evidence highlights the complexity of suicidality and points towards an interaction of factors contributing to suicidal behaviour. More information is needed to understand the complex relationship between risk factors for suicidality. Prospective studies with adequate sample sizes are needed to investigate these multiple variables of risk concurrently and over time.

Development and psychometric properties of the "Suicidality: Treatment Occurring in Paediatrics (STOP) Risk and Resilience Factors Scales" in adolescents.

Suicidality in the child and adolescent population is a major public health concern. There is, however, a lack of developmentally sensitive valid and reliable instruments that can capture data on risk, and clinical and psychosocial mediators of suicidality in young people. In this study, we aimed to develop and assess the validity of instruments evaluating the psychosocial risk and protective factors for suicidal behaviours in the adolescent population. In Phase 1, based on a systematic literature review of suicidality, focus groups, and expert panel advice, the risk factors and protective factors (resilience factors) were identified and the adolescent, parent, and clinician versions of the STOP-Suicidality Risk Factors Scale (STOP-SRiFS) and the Resilience Factors Scale (STOP-SReFS) were developed. Phase 2 involved instrument validation and comprised of two samples (Sample 1 and 2). Sample 1 consisted of 87 adolescents, their parents/carers, and clinicians from the various participating centres, and Sample 2 consisted of three sub-samples: adolescents (n = 259) who completed STOP-SRiFS and/or the STOP-SReFS scales, parents (n = 213) who completed one or both of the scales, and the clinicians who completed the scales (n = 254). The STOP-SRiFS demonstrated a good construct validity-the Cronbach Alpha for the adolescent (α = 0.864), parent (α = 0.842), and clinician (α = 0.722) versions of the scale. Test-retest reliability, inter-rater reliability, and content validity were good for all three versions of the STOP-SRiFS. The sub-scales generated using Exploratory Factor Analysis (EFA) were the (1) anxiety and depression risk, (2) substance misuse risk, (3) interpersonal risk, (4) chronic risk, and (5) risk due to life events. For the STOP-SRiFS, statistically significant correlations were found between the Columbia-Suicide Severity Rating Scale (C-SSRS) total score and the adolescent, parent, and clinical versions of the STOP-SRiFS sub-scale scores. The STOP-SRiFS showed good psychometric properties. This study demonstrated a good construct validity for the STOP-SReFS-the Cronbach Alpha for the three versions were good (adolescent: α = 0.775; parent: α = 0.808; α = clinician: 0.808). EFA for the adolescent version of the STOP-SReFS, which consists of 9 resilience factors domains, generated two factors (1) interpersonal resilience and (2) cognitive resilience. The STOP-SReFS Cognitive Resilience sub-scale for the adolescent was negatively correlated (r = - 0.275) with the C-SSRS total score, showing that there was lower suicidality in those with greater Cognitive Resilience. The STOP-SReFS Interpersonal resilience sub-scale correlations were all negative, but none of them were significantly different to the C-SSRS total scores for either the adolescent, parent, or clinician versions of the scales. This is not surprising, because the items in this sub-scale capture a much larger time-scale, compared to the C-SSRS rating period. The STOP-SReFS showed good psychometric properties. The STOP-SRiFS and STOP-SReFS are instruments that can be used in future studies about suicidality in children and adolescents.

Is risperidone effective in reducing challenging behaviours in individuals with intellectual disabilities after 1 year or longer use? A placebo-controlled, randomised, double-blind discontinuation study.

BACKGROUND: Many people with intellectual disabilities use risperidone long term for the management of challenging behaviours, despite its limited proof of effectiveness and its clear association with adverse events. Therefore, this study aimed to investigate the effectiveness of ongoing treatment with risperidone in reducing challenging behaviours versus controlled discontinuation on behaviour and health parameters. METHOD: This was a placebo-controlled, double-blind, randomised discontinuation trial of risperidone. In the discontinuation group, risperidone was gradually replaced by a placebo over 14 weeks, while the control group maintained their existing dosage. Eight weeks after discontinuation, behaviour (as measured by the 'Aberrant Behavior Checklist') and health parameters (dyskinesia, akathisia, parkinsonism, weight, waist circumference, sedation and laboratory outcomes) were compared in both groups. RESULTS: A total of 25 participants were included in the trial, of which 11 were randomised into the discontinuation group and 14 were randomised into the continued treatment group. In the discontinuation group, 82% completely withdrew from risperidone. There was no significant change in irritability, compared with the continuation group, although there was a Group*Time effects on stereotypical behaviour in favour of the continuation group. Significant Group*Time effects were also found for weight, waist, body mass index, prolactin levels and testosterone levels, with beneficial effects for the discontinuation group. CONCLUSION: Discontinuation of long-term risperidone for reducing challenging behaviours is possible, without an increase in irritability. Discontinuation of risperidone may have beneficial effects on weight, waist circumference, prolactin levels and testosterone levels. The study suffered from difficulties in achieving the required sample size, which affected study power and generalizability.

A Potential Role for the STXBP5-AS1 Gene in Adult ADHD Symptoms.

We aimed to detect Attention-deficit/hyperactivity (ADHD) risk-conferring genes in adults. In children, ADHD is characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity and may persists into adulthood. Childhood and adulthood ADHD are heritable, and are thought to represent the clinical extreme of a continuous distribution of ADHD symptoms in the general population. We aimed to leverage the power of studies of quantitative ADHD symptoms in adults who were genotyped. Within the SAGA (Study of ADHD trait genetics in adults) consortium, we estimated the single nucleotide polymorphism (SNP)-based heritability of quantitative self-reported ADHD symptoms and carried out a genome-wide association meta-analysis in nine adult population-based and case-only cohorts of adults. A total of n = 14,689 individuals were included. In two of the SAGA cohorts we found a significant SNP-based heritability for self-rated ADHD symptom scores of respectively 15% (n = 3656) and 30% (n = 1841). The top hit of the genome-wide meta-analysis (SNP rs12661753; p-value = 3.02 × 10-7) was present in the long non-coding RNA gene STXBP5-AS1. This association was also observed in a meta-analysis of childhood ADHD symptom scores in eight population-based pediatric cohorts from the Early Genetics and Lifecourse Epidemiology (EAGLE) ADHD consortium (n = 14,776). Genome-wide meta-analysis of the SAGA and EAGLE data (n = 29,465) increased the strength of the association with the SNP rs12661753. In human HEK293 cells, expression of STXBP5-AS1 enhanced the expression of a reporter construct of STXBP5, a gene known to be involved in "SNAP" (Soluble NSF attachment protein) Receptor" (SNARE) complex formation. In mouse strains featuring different levels of impulsivity, transcript levels in the prefrontal cortex of the mouse ortholog Gm28905 strongly correlated negatively with motor impulsivity as measured in the five choice serial reaction time task (r2 = - 0.61; p = 0.004). Our results are consistent with an effect of the STXBP5-AS1 gene on ADHD symptom scores distribution and point to a possible biological mechanism, other than antisense RNA inhibition, involved in ADHD-related impulsivity levels.

The Course of Neurocognitive Functioning and Prediction of Behavioral Outcome of ADHD Affected and Unaffected Siblings.

Longitudinal studies on the course of neurocognitive functioning of children with ADHD and their unaffected siblings are scarce. Also, it is unclear to what extent that course is related to ADHD outcomes. A carefully phenotyped large sample of 838 Caucasian participants (ADHD-combined type: n = 339, unaffected siblings: n = 271, controls: n = 228; mean age at baseline = 11.4 years, mean age at follow-up = 17.3 years, SD = 3.2) was used to investigate differences in the course of neurocognitive functioning of ADHD affected and unaffected siblings versus controls, and to investigate the relationship between neurocognitive change and ADHD outcomes. At baseline, an aggregated measure of overall neurocognitive functioning and eight neurocognitive measures of working memory, timing (speed/variability), motor control, and intelligence were investigated. Outcomes at follow-up were dimensional measures of ADHD symptom severity and the Kiddie-Global Assessment Scale (K-GAS) for overall functioning. At follow up, affected and unaffected siblings trended to, or fully caught up with performance levels of controls on four (44.4%) and five (55.6%) of the nine dependent variables, respectively. In contrast, performance in remaining key neurocognitive measures (i.e. verbal working memory, variability in responding) remained impaired at follow-up. Change in neurocognitive functioning was not related to ADHD outcomes. Our results question the etiological link between neurocognitive deficits and ADHD outcomes in adolescents and young adults.

Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder.

Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology.

Physicians' reasons not to discontinue long-term used off-label antipsychotic drugs in people with intellectual disability.

BACKGROUND: People with intellectual disability (ID) frequently use antipsychotic drugs on an off-label base, often for many years. Physicians' decisions to discontinue these drugs not only depend on patient characteristics, like the presence of mental or behavioural disorders, but also on environmental factors, such as inappropriate living circumstances, and on attitudes, knowledge and beliefs of staff, clients and their representatives towards the effects of antipsychotic drug use. In this study, we therefore investigated the influence of participant and setting-related factors on decisions of physicians not to discontinue off-label prescribed antipsychotics. METHODS: The study took place in living facilities of six service providers for people with ID spread over the Netherlands and staffed with support professionals, nurses, behavioural scientist and physicians and was part of an antipsychotics discontinuation trial. ID physicians had to decide whether the off-label use of antipsychotics could be discontinued. Medical and pharmaceutical records were used to establish the prevalence of antipsychotic drug use in the study population, along with duration of use and whether the use was off-label. Reasons of physicians not to discontinue the prescription of antipsychotics in those participants who used off-label antipsychotics for more than a year were collected and categorised as related to participant or setting characteristics, including lack of consent to discontinue, and staff members, participants or their legal representatives. RESULTS: Of the 3299 clients of the service providers, 977 used one or more antipsychotic drugs. The prevalence of antipsychotic drug use was 30%. Reasons for use were in 5% of cases, a chronic psychotic disorder classified according to Diagnostic System Mental Disorders, Fourth Edition, criteria, in 25%, present or past (suspected) non-schizophrenia-related psychotic symptoms and in 69%, challenging behaviours. Overall, physicians were willing to discontinue their prescriptions in 51% of cases, varying from 22% to 87% per service provider. The odds for decisions of physicians to discontinue off-label prescriptions varied from 0.19 to 13.95 per service provider. The variables 'a living situation with care and support' and 'challenging behaviour' were associated with a higher chance of discontinuation. The main reasons for decisions not to discontinue were concerns for symptoms of restlessness, the presence of an autism spectrum disorder, previously unsuccessful attempts to discontinue and objections against discontinuation of legal representatives. Reasons for physicians' decisions not to discontinue the off-label use of antipsychotics varied largely between the service providers. CONCLUSIONS: The prevalence of antipsychotic drug use for off-label indications in people with ID remains high. The results of this study indicate that there is a large variation in clinical practice of physicians regarding discontinuation of long-term antipsychotic drug prescriptions, which may be partially related to environmental factors as setting culture and attitudes of staff towards off-label antipsychotic drug use in persons with ID.

Predicting attention-deficit/hyperactivity disorder severity from psychosocial stress and stress-response genes: a random forest regression approach.

Identifying genetic variants contributing to attention-deficit/hyperactivity disorder (ADHD) is complicated by the involvement of numerous common genetic variants with small effects, interacting with each other as well as with environmental factors, such as stress exposure. Random forest regression is well suited to explore this complexity, as it allows for the analysis of many predictors simultaneously, taking into account any higher-order interactions among them. Using random forest regression, we predicted ADHD severity, measured by Conners' Parent Rating Scales, from 686 adolescents and young adults (of which 281 were diagnosed with ADHD). The analysis included 17 374 single-nucleotide polymorphisms (SNPs) across 29 genes previously linked to hypothalamic-pituitary-adrenal (HPA) axis activity, together with information on exposure to 24 individual long-term difficulties or stressful life events. The model explained 12.5% of variance in ADHD severity. The most important SNP, which also showed the strongest interaction with stress exposure, was located in a region regulating the expression of telomerase reverse transcriptase (TERT). Other high-ranking SNPs were found in or near NPSR1, ESR1, GABRA6, PER3, NR3C2 and DRD4. Chronic stressors were more influential than single, severe, life events. Top hits were partly shared with conduct problems. We conclude that random forest regression may be used to investigate how multiple genetic and environmental factors jointly contribute to ADHD. It is able to implicate novel SNPs of interest, interacting with stress exposure, and may explain inconsistent findings in ADHD genetics. This exploratory approach may be best combined with more hypothesis-driven research; top predictors and their interactions with one another should be replicated in independent samples.

Development and psychometric properties of the Suicidality: Treatment Occurring in Paediatrics (STOP) Suicidality Assessment Scale (STOP-SAS) in children and adolescents.

BACKGROUND: To create a self-reported, internet-based questionnaire for the assessment of suicide risk in children and adolescents. METHODS: As part of the EU project 'Suicidality: Treatment Occurring in Paediatrics' (STOP project), we developed web-based Patient Reported Outcome Measures (PROMs) for children and adolescents and for proxy reports by parents and clinicians in order to assess suicidality. Based on a literature review, expert panels and focus groups of patients, we developed the items of the STOP Suicidality Assessment Scale (STOP-SAS) in Spanish and English, translated it into four more languages, and optimized it for web-based presentation using the HealthTrackerTM platform. Of the total 19 questions developed for the STOP-SAS, four questions that assess low-level suicidality were identified as screening questions (three of them for use with children, and all four for use with adolescents, parents and clinicians). A total of 395 adolescents, 110 children, 637 parents and 716 clinicians completed the questionnaire using the HealthTrackerTM, allowing us to evaluate the internal consistency and convergent validity of the STOP-SAS with the clinician-rated Columbia Suicide Severity Rating Scale (C-SSRS). Validity was also assessed with the receiver operating characteristic (ROC) area of the STOP-SAS with the C-SSRS. RESULTS: The STOP-SAS comprises 19 items in its adolescent, parent, and clinician versions, and 14 items in its children's version. Good internal consistency was found for adolescents (Cronbach's alpha: 0.965), children (Cronbach's alpha: 0.922), parents (Cronbach's alpha: 0.951) and clinicians (Cronbach's alpha: 0.955) versions. A strong correlation was found between the STOP-SAS and the C-SSRS for adolescents (r:0.670), parents (r:0.548), clinicians (r:0.863) and children (r:0.654). The ROC area was good for clinicians' (0.917), adolescents' (0.834) and parents' (0.756) versions but only fair (0.683) for children's version. CONCLUSIONS: The STOP-SAS is a comprehensive, web-based PROM developed on the HealthTrackerTM platform, and co-designed for use by adolescents, children, parents and clinicians. It allows the evaluation of aspects of suicidality and shows good reliability and validity.

An explorative study of school performance and antipsychotic medication.

BACKGROUND: Antipsychotic therapy can reduce severe symptoms of psychiatric disorders, however, data on school performance among children on such treatment are lacking. The objective was to explore school performance among children using antipsychotic drugs at the end of primary education. METHODS: A cross-sectional study was conducted using the University Groningen pharmacy database linked to academic achievement scores at the end of primary school (Dutch Cito-test) obtained from Statistics Netherlands. Mean Cito-test scores and standard deviations were obtained for children on antipsychotic therapy and reference children, and statistically compared using analyses of covariance. In addition, differences in subgroups as boys versus girls, ethnicity, household income, and late starters (start date within 12 months of the Cito-test) versus early starters (start date > 12 months before the Cito-test) were tested. RESULTS: In all, data from 7994 children could be linked to Cito-test scores. At the time of the Cito-test, 45 (0.6 %) were on treatment with antipsychotics. Children using antipsychotics scored on average 3.6 points lower than the reference peer group (534.5 ± 9.5). Scores were different across gender and levels of household income (p < 0.05). Scores of early starters were significantly higher than starters within 12 months (533.7 ± 1.7 vs. 524.1 ± 2.6). CONCLUSION: This first exploration showed that children on antipsychotic treatment have lower school performance compared to the reference peer group at the end of primary school. This was most noticeable for girls, but early starters were less affected than later starters. Due to the observational cross-sectional nature of this study, no causality can be inferred, but the results indicate that school performance should be closely monitored and causes of underperformance despite treatment warrants more research.

Interplay between stress response genes associated with attention-deficit hyperactivity disorder and brain volume.

The glucocorticoid receptor plays a pivotal role in the brain's response to stress; a haplotype of functional polymorphisms in the NR3C1 gene encoding this receptor has been associated with attention-deficit hyperactivity disorder (ADHD). The serotonin transporter (5-HTT) gene polymorphism 5-HTTLPR is known to influence the relation between stress exposure and ADHD severity, which may be partly because of its reported effects on glucocorticoid levels. We therefore investigated if NR3C1 moderates the relation of stress exposure with ADHD severity and brain structure, and the potential role of 5-HTTLPR. Neuroimaging, genetic and stress exposure questionnaire data were available for 539 adolescents and young adults participating in the multicenter ADHD cohort study NeuroIMAGE (average age: 17.2 years). We estimated the effects of genetic variation in NR3C1 and 5-HTT, stress exposure and their interactions on ADHD symptom count and gray matter volume. We found that individuals carrying the ADHD risk haplotype of NR3C1 showed significantly more positive relation between stress exposure and ADHD severity than non-carriers. This gene-environment interaction was significantly stronger for 5-HTTLPR L-allele homozygotes than for S-allele carriers. These two- and three-way interactions were reflected in the gray matter volume of the cerebellum, parahippocampal gyrus, intracalcarine cortex and angular gyrus. Our findings illustrate how genetic variation in the stress response pathway may influence the effects of stress exposure on ADHD severity and brain structure. The reported interplay between NR3C1 and 5-HTT may further explain some of the heterogeneity between studies regarding the role of these genes and hypothalamic-pituitary-adrenal axis activity in ADHD.

Adolescent behavioral and neural reward sensitivity: a test of the differential susceptibility theory.

Little is known about the causes of individual differences in reward sensitivity. We investigated gene-environment interactions (GxE) on behavioral and neural measures of reward sensitivity, in light of the differential susceptibility theory. This theory states that individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments. Reward responses were assessed during a monetary incentive delay task in 178 participants with and 265 without attention-deficit/hyperactivity disorder (ADHD), from N=261 families. We examined interactions between variants in candidate plasticity genes (DAT1, 5-HTT and DRD4) and social environments (maternal expressed emotion and peer affiliation). HTTLPR short allele carriers showed the least reward speeding when exposed to high positive peer affiliation, but the most when faced with low positive peer affiliation or low maternal warmth. DAT1 10-repeat homozygotes displayed similar GxE patterns toward maternal warmth on general task performance. At the neural level, DRD4 7-repeat carriers showed the least striatal activation during reward anticipation when exposed to high maternal warmth, but the most when exposed to low warmth. Findings were independent of ADHD severity. Our results partially confirm the differential susceptibility theory and indicate the importance of positive social environments in reward sensitivity and general task performance for persons with specific genotypes.