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BACKGROUND: Methylphenidate is the most frequently prescribed medication for the treatment of ADHD in children and adolescents in many countries. Although many randomised controlled trials support short-term efficacy, tolerability, and safety, data on long-term safety and tolerability are scarce. The aim of this study was to investigate the safety of methylphenidate over a 2-year period in relation to growth and development, psychiatric health, neurological health, and cardiovascular function in children and adolescents. METHODS: We conducted a naturalistic, longitudinal, controlled study as part of the ADDUCE research programme in 27 European child and adolescent mental health centres in the UK, Germany, Switzerland, Italy, and Hungary. Participants aged 6-17 years were recruited into three cohorts: medication-naive ADHD patients who intended to start methylphenidate treatment (methylphenidate group), medication-naive ADHD patients who did not intend to start any ADHD medication (no-methylphenidate group), and a control group without ADHD. Children with ADHD diagnosed by a qualified clinician according to the DSM-IV criteria and, in the control group, children who scored less than 1·5 on average on the Swanson, Nolan, and Pelham IV rating scale for ADHD items, and whose hyperactivity score on the parent-rated Strengths and Difficulties Questionnaire was within the normal range (

European neuropsychopharmacology : ENP 64, 63-71 (2022). doi:10.1016/j.euroneuro.2022.09.001, Published by Elsevier, Amsterdam

ADHD is the most common neurodevelopmental disorder presenting to child and adolescent mental health, paediatric, and primary care services. Timely and effective interventions to address core ADHD symptoms and co-occurring problems are a high priority for healthcare and society more widely. While much research has reported on the benefits and adverse effects of different interventions for ADHD, these individual research reports and the reviews, meta-analyses and guidelines summarizing their findings are sometimes inconsistent and difficult to interpret. We have summarized the current evidence and identified several methodological issues and gaps in the current evidence that we believe are important for clinicians to consider when evaluating the evidence and making treatment decisions. These include understanding potential impact of bias such as inadequate blinding and selection bias on study outcomes; the relative lack of high-quality data comparing different treatments and assessing long-term effectiveness, adverse effects and safety for both pharmacological and non-pharmacological treatments; and the problems associated with observational studies, including those based on large national registries and comparing treatments with each other. We highlight key similarities across current international clinical guidelines and discuss the reasons for divergence where these occur. We discuss the integration of these different perspective into a framework for person/family-centered evidence-based practice approach to care that aims to achieve optimal outcomes that prioritize individual strengths and impairments, as well as the personal treatment targets of children and their families. Finally, we consider how access to care for this common and impairing disorder can be improved in different healthcare systems., European Child & Adolescent Psychiatry, 32 (8), ISSN:1435-165X, ISSN:1018-8827

INTRODUCTION: Maternal postnatal mental health problems may negatively impact child development. Postpartum research has mainly focused on the impact of maternal depression and anxiety due to their high prevalence (13-25 % and 10-18 %, respectively). However, maternal childbirth-related PTSD (CB-PTSD) could be another important risk factor in child development (estimated prevalence: 4.7 %). OBJECTIVE: We investigated whether maternal CB-PTSD (symptoms) are associated with a negative mother-child relationship and/or child developmental outcome for children aged 0-5 years. Furthermore, we examined whether maternal trauma-focused therapy can positively impact mother and child outcomes. METHODS: We performed a systematic review by searching three databases (Embase, Medline, PsycInfo). Search terms involved: 'birth or delivery modes', 'PTSD psychological trauma', and 'child development or child behavior'. Two independent reviewers evaluated all eligible papers. RESULTS: Thirty-five papers (30 samples) were included and qualitatively reported. Results suggest a negative association of maternal CB-PTSD (symptoms) with mother-infant attachment and child behavior. However, confounding factors may explain this association. The evidence on associations with breastfeeding, sleeping, socio-emotional development, and weight gain is insufficient. Research investigating the effect of maternal trauma-focused therapy on a child's outcome is scarce, contradictory, and of low quality. CONCLUSION: This systematic review suggests that maternal CB-PTSD may be associated with an increased number of problems in mother-infant attachment and child behavior, but other domains remain scarcely investigated and methodologic issues are present (cross-sectional study design, influence of confounding variables, sample representativeness, diversity in assessment tools). Our results support a multidisciplinary approach to providing early prevention and screening of the maternal mental health state.

Restrictions related to the COVID-19 pandemic may have significantly impacted adolescents’ sleep, possibly even more so in adolescents with attention-deficit/hyperactivity disorder (ADHD). The current study examines the sleep of adolescents without ADHD (TD) and a homogeneous group of adolescents with ADHD and comorbid sleep problems using a multi-method objective and subjective assessment of sleep outcomes, during few and multiple COVID-19 restrictions. Four groups (2 TD and 2 ADHD) of in total 100 adolescents (50 TD and 50 ADHD) were included. One ADHD group was tested during numerous COVID-19 restrictions, the other during few. The same was done with the two TD groups. All participants were between 13 and 17 years old. Three two-way MANCOVAs were implemented with ADHD diagnosis and level of COVID-19 restrictions as independent and sleep outcomes (sleep hygiene, sleep deprivation, and objective and subjective total sleep time (TST) and sleep onset latency (SOL)) as dependent variables. As expected, adolescents with ADHD and comorbid sleep problems had significantly more subjective and objective sleep problems. Additionally, COVID-19 restrictions were related to sleep outcomes in both TD and ADHD groups, with both objective TST and subjective SOL being shorter when there were numerous COVID-19 restrictions. However, the shorter SOL was only found in the ADHD group. COVID-19 restrictions are related to sleep in adolescents, and more so in the ADHD group. Future research should focus on mechanisms underlying these relations.

OBJECTIVES: This study aimed to describe the differences and similarities in the reaction of the healthcare worker involved in a patient safety incident or during the COVID-19 pandemic. We also compared the differences in support they need. METHODS: A secondary data analysis was performed based on 2 cross-sectional survey studies. One study evaluated the impact of patient safety incidents on healthcare professionals, and the other evaluated the impact of COVID-19. Measurements on mental health reactions and an evaluation of the experienced support system were compared between 883 doctors and 1970 nurses working in different hospitals. RESULTS: Anxiety, difficulties concentrating, doubting knowledge and skills, feeling on their own, feeling unhappy and dejected, feeling uncertain in team, flashbacks, hypervigilance, sleep deprivation, stress and wanting to quit profession were statistically higher in the COVID-19-related groups. Second victims tend to speak about it with their own/close colleagues, whereas healthcare workers working during the COVID-19 pandemic talk more often to their partner and friends. Only a small number talked to a psychologist, but the number who needed to talk to a psychologist but did not is higher than the number who did talk to a psychologist or used professional support in all 5 groups. CONCLUSIONS: The impact of the COVID-19 pandemic on the mental health of healthcare workers is larger than after being involved in a patient safety incident. There is the need for an adequate support system, and the mental health of all healthcare workers needs to be considered. Partners and friend play a more important role in the support experienced during the COVID-19 pandemic, and there is an important need for professional help. ispartof: Journal Of Patient Safety vol:18 issue:7 pages:717-721 ispartof: location:United States status: published

IntroductionAdolescents with attention deficit hyperactivity disorder (ADHD) experience a more disrupted sleep and more sleep problems compared with typically developing adolescents. This is particularly concerning, because disrupted sleep is related to worsened clinical, neurocognitive and functional outcomes and leads to increased ADHD symptom impairment. Due to the specific difficulties adolescents with ADHD experience, a tailored sleep treatment is needed. Therefore, our lab developed a cognitive behavioural treatment—Sleep IntervEntion as Sympom Treatment for ADHD (SIESTA)—that integrates sleep training with motivational interviewing, and planning/organisational skills training with the aim of improving sleep problems in adolescents with ADHD.Methods and analysisA randomised, controlled, investigator-blinded monocentre trial is used to test whether SIESTA in combination with treatment as usual (TAU) for ADHD results in greater improvement in sleep problems than TAU only. Adolescents (aged 13–17 years) with ADHD and sleep problems are included. They complete measurements before treatment (pre-test), approximately 7 weeks after the pre-test (post-test), and approximately 3 months after the post-test (follow-up). The assessment includes questionnaires filled out by adolescents, parents and teachers. Additionally, sleep is assessed by actigraphy and sleep diaries at all time-points. Primary outcomes include objectively and subjectively measured sleep architecture (specified as total sleep time, sleep onset latency, sleep efficiency and number of awakenings), subjectively measured sleep problems and sleep hygiene. Secondary outcomes include ADHD symptoms, comorbidities and functional outcomes. To analyse the data, a linear mixed effects model will be used with an intent-to-treat approach.Ethics and disseminationThe study activities, informed consent and assent forms have been approved by the Ethical Committee Research UZ/KU Leuven (study ID S64197). If proven effective, the intervention will be implemented throughout Flanders. Therefore, an advisory board consisting of societal partners in healthcare is appointed at the start of the project, giving advice throughout the project and assistance with implementation afterwards.Trial registration numberNCT04723719.

Academic impairment in individuals with attention-deficit/hyperactivity disorder (ADHD) is in part due to reduced motivation for academic tasks, which is likely to vary as a function of task characteristics. The current study employed a new questionnaire—the Child and Adolescent Motivational Profile (CHAMP)—to examine; (1) which task characteristic participants with ADHD perceive as most motivating relative to typically developing peers (TDP) and (2) whether these differences mediate academic functioning. 34 participants with ADHD and 435 TDP (8–16 years) completed the CHAMP. Academic achievement (grade point average) and self-reported positive/negative classroom experiences were recorded. No task characteristics were rated higher in terms of their motivational salience in the ADHD group than in the control sample. Marked/graded, Socially evaluated, Collaborative, Requiring focus and Cognitively challenging task characteristics were rated significantly lower by the ADHD group than controls. The lower rating of Socially evaluated was explained by comorbid ODD symptoms. Cognitively challenging was rated as particularly unmotivating by individuals with ADHD. ADHD was associated with a decreased GPA and a more negative classroom experience. The associations between ADHD and GPA/negative classroom experience were both partially mediated by scores on the Cognitively Challenging scale. For children and adolescents with ADHD tasks that are cognitively challenging were not particularly motivating. To increase task motivation, and improve academic performance of individuals with ADHD, it may be important to include rewarded task elements as they are appraised as particularly motivating by these individuals and this appraisal was similar to that of TDP.

Objective: Motivation is what moves us to act, what engages us in goal-directed behavior. The Self Determination Theory (SDT) is a motivational framework conceptualizing motivation—or internal motives—as a continuum of motivation qualities fueled by satisfaction of the three basic psychological needs Autonomy, Relatedness, and Competence. ADHD has been associated with motivational alterations that contribute to academic difficulties. However, ADHD theories and research are mainly focused on the effects of reinforcement on behavior, with little attention for the broader definition of motivation, that is, internal motives. Therefore, the main objective here was to introduce the SDT as theoretical framework within which we can develop relevant research questions about motivation in the field of ADHD. Method: To this end, we (i) present the SDT as a comprehensive motivational framework, and (ii) describe current motivation-related ADHD theories and research. Results: Based on this, we suggest how SDT can be used as a guiding framework in generating relevant research questions that can help broaden our understanding of the role motivation plays in individuals with ADHD. Conclusion: We conclude that ADHD research on motivation would benefit from (i) including internal motives as potential key mediators in the relation between environmental factors and behavior/symptoms; (ii) studying potential negative effects of external reinforcers intrinsic motivation, affect, and well-being. Finally, we conclude that this framework carries value for further development of clinical interventions for those with ADHD.

OBJECTIVE: Although instrumental learning deficits are, among other deficits, assumed to contribute to attention-deficit/hyperactivity disorder (ADHD), no comprehensive systematic review of instrumental learning deficits in ADHD exists. This review examines differences between ADHD and typically developing (TD) children in basic instrumental learning and the effects of reinforcement form, magnitude, schedule, and complexity, as well as effects of medication, on instrumental learning in children with ADHD. METHOD: A systematic search of PubMed, PsyINFO, CINAHL, EMBASE+EMBASE CLASSIC, ERIC, and Web of Science was conducted for articles up to March 16, 2020. Experimental studies comparing instrumental learning between groups (ADHD versus TD) or a manipulation of reinforcement/medication within an ADHD sample were included. Quality of studies was assessed with an adapted version of the Hombrados and Waddington criteria to assess risk of bias in (quasi-) experimental studies. RESULTS: A total of 19 studies from among 3,384 non-duplicate screened articles were included. No difference in basic instrumental learning was found between children with ADHD and TD children, nor effects of form or magnitude of reinforcement. Results regarding reinforcement schedule and reversal learning were mixed, but children with ADHD seemed to show deficits in conditional discrimination learning compared to TD children. Methylphenidate improved instrumental learning in children with ADHD. Quality assessment showed poor quality of studies with respect to sample sizes and outcome and missing data reporting. CONCLUSION: The review identified very few and highly heterogenous studies, with inconsistent findings. No clear deficit was found in instrumental learning under laboratory conditions. Children with ADHD do show deficits in complex forms of learning, that is, conditional discrimination learning. Clearly more research is needed, using more similar task designs and manipulations. ispartof: Journal Of The American Academy Of Child And Adolescent Psychiatry vol:60 issue:11 pages:1367-1381 ispartof: location:United States status: published

Recent magnetic resonance imaging (MRI) studies implicate structural alterations of amygdala, a brain region responsible for processing and experiencing negative emotions, in adolescents with attention-deficit/hyperactivity disorder (ADHD). Here we examined ADHD-related structural correlates of amygdala functional activity elicited during a functional MRI task designed to test behavioural and brain responses to the imposition of delay - an event known to both elicit amygdala hyperactivation and aversity in ADHD.Structural MRI scans from 28 right-handed male adolescents with combined type ADHD and 32 age-matched controls were analysed. Regional grey matter volumes of ADHD and control participants (ADHD was associated with significantly reduced volumes in bilateral amygdala, parahippocampal and temporal gyrus (We provide the first evidence of the functional significance of reduced amygdala volumes in adolescents with ADHD by highlighting its relation to delay-induced brain activity that is linked to delay aversion.

Contains fulltext : 231767.pdf (Publisher’s version ) (Closed access) BACKGROUND: Methylphenidate (MPH) is an efficacious treatment for ADHD but concerns have been raised about potential adverse effects of extended treatment on growth. OBJECTIVES: To systematically review the literature, up to December 2018, conducting a meta-analysis of association of long-term (> six months) MPH exposure with height, weight and timing of puberty. RESULTS: Eighteen studies (ADHD n = 4868) were included in the meta-analysis. MPH was associated with consistent statistically significant pre-post difference for both height (SMD = 0.27, 95% CI 0.16-0.38, p < 0.0001) and weight (SMD = 0.33, 95% CI 0.22-0.44, p < 0.0001) Z scores, with prominent impact on weight during the first 12 months and on height within the first 24-30 months. No significant effects of dose, formulation, age and drug-naïve condition as clinical moderators were found. Data on timing of puberty are currently limited. CONCLUSIONS: Long-term treatment with MPH can result in reduction in height and weight. However, effect sizes are small with possible minimal clinical impact. Long-term prospective studies may help to clarify the underlying biological drivers and specific mediators and moderators.

Functional magnetic resonance imaging studies have reported a diminished response in the brain's reward circuits to contingent cues predicting future monetary gain in adolescents with attention-deficit/hyperactivity disorder (ADHD). The situation with regard to monetary loss is less clear, despite recognition that both positive and negative consequences impact ADHD behaviour. Here, we employ a new Escape Monetary Loss Incentive task in an MRI scanner, which allows the differentiation of contingency and valence effects during loss avoidance, to examine ADHD-related alterations in monetary loss processing. There was no evidence of atypical processing of contingent or non-contingent monetary loss cues in ADHD - either in terms of ratings of emotional and motivational significance or brain responses. This suggests that the ability to process contingencies between performance and negative outcomes is intact in ADHD and that individuals with ADHD are no more (or less) sensitive to negative outcomes than controls. This latter finding stands in stark contrast to recent evidence from a similar task of atypical emotion network recruitment (e.g. amygdala) in ADHD individuals to cues predicting another negative event, the imposition of delay, suggesting marked specificity in the way they respond to negative events. ispartof: SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE vol:17 issue:5 pages:482-492 ispartof: location:England status: published

ispartof: Lancet Child and Adolescent Health vol:4 issue:6 pages:1-2 ispartof: location:England status: Published online

Impulsivity is a core feature of attention-deficit hyperactivity disorder (ADHD). It has been conceptualized in a number of different ways. In the current article, we examine how the new concept of "waiting impulsivity", which refers to premature responding before a scheduled target appears, adds to our understanding of impulsivity in ADHD. Sixty children (8-12 years old; 30 ADHD; 30 typically developing controls) completed the 4-choice serial reaction time task, a measure of waiting impulsivity, alongside tasks measuring inhibitory control and temporal discounting and questionnaires measuring behavioral disorder symptoms, delay aversion, and various aspects of impulsivity. A multiple logistic regression model was used to explore the contribution of the primary task outcomes to predict group membership. Children with ADHD displayed more waiting impulsivity and less inhibitory control; they did not differ in temporal discounting. There was no correlation between waiting impulsivity and inhibitory control. Waiting impulsivity was correlated with parent-reported ratings of hyperactivity/impulsivity, inattention, oppositional defiant disorder (ODD), and conduct disorder (CD) and with self-reported delay aversion ratings. Only waiting impulsivity was a significant predictor of ADHD status. In conclusion, waiting impulsivity is distinct from inhibitory control deficits and predicts ADHD status independently of it. Future research needs to examine the relationship with delay aversion and ODD/CD more thoroughly.

Introduction During the past years, an increasing number of articles has focused on comparing sleep in youths with and without ADHD. However, so far no meta-analysis has been conducted summarizing the findings. Therefore, the current study assesses sleep architecture (i.e. the basic sleep structure), sleep problems, and sleep hygiene. Sleep was assessed both subjectively and objectively and the two groups were compared on multiple variables. Methods Two researchers independently performed a literature search (1980–2020). Studies using a case-control design comparing sleep in youths (12–25 years) with and without ADHD were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Standardized mean differences were calculated for each outcome domain being reported by at least two studies. Results 10379 publications were screened, resulting in 11 studies and 52 effect sizes (nADHD=2377, ncontrol=21687). These effect sizes were summarized into 7 objective and 11 subjective variables measuring sleep. Two objective sleep variables were significantly worse in the ADHD group; total sleep time (z=2.16, p=.03) and sleep onset latency (z=2.39, p=.02). The two groups did not differ on sleep efficiency, sleep onset/offset time, and time in bed. Comparing the groups on subjective variables resulted in the same pattern, with total sleep time (z=21.27, p Conclusion In general, youths with ADHD have a disrupted sleep architecture and experience more sleep problems compared to their typically developing peers. Consequently, sleep assessment should become a routine part during the diagnostic process of ADHD. Additionally, more research is needed focusing on sleep architecture and sleep hygiene, and on the development of a sleep intervention for youths with ADHD. Support (if any)

Background: Attention-deficit/hyperactivity disorder (ADHD) is presumed to involve mental effort application difficulties. To test this assumption, we manipulated task difficulty and measured behavioral, as well as subjective and psychophysiological indices of effort.Methods: Fifteen adolescent ADHD boys and 16 controls performed two tasks. First, subjective estimates and behavioral and pupillary measures of effort were recorded across five levels of N-back task difficulties. Second, effort discounting was assessed. In the latter, participants made repeated choices between performing a difficult N-back task for a high reward versus an easier N-back task for a smaller reward.Results: Increasing task difficulty led to similar deteriorations in performance for both groups – although ADHD participants performed more poorly at all difficulty levels than controls. While ADHD and control participants rated the tasks equally difficult and discounted effort similarly, those with ADHD displayed slightly different pupil dilation patterns with increasing task difficulty.Conclusion: The behavioral results did not provide evidence for mental effort problems in adolescent boys with ADHD. The subtle physiological effects, however, suggest that adolescents with ADHD may allocate effort in a different way than controls.

Background Both the US FDA and the European Medicines Agency (EMA) have approved aripiprazole for use in adolescents for specific indications. Given the assumed favorable side-effect profile of aripiprazole, its use in children and adolescents has increased for both official and off-label indications (anxiety disorders, eating disorders, personality disorders). However, several cases of children and adolescents with new-onset extrapyramidal symptoms (EPS) after commencing treatment with aripiprazole have been reported, and a more systematic appraisal of this possible risk is lacking. Objective We conducted a systematic review and a meta-analysis to assess the evidence for acute EPS (acute dystonia, akathisia, Parkinsonism) associated with the use of aripiprazole in children and adolescents. Method We searched the MEDLINE and Embase databases (2003–10 April 2016) for clinical trials in pediatric patients (aged 0–18 years) using the keywords ‘aripiprazole’ (regardless of the formulation) and ‘extrapyramidal symptoms’. We evaluated the abstracts of papers using the following exclusion criteria: (1) study design: case report, letter to the editor, editorial, or poster presentation data; (2) unrelated PICOS (population, intervention, comparators, outcomes, study) structure. We performed a meta-analysis, in which we used effect sizes with 95 % confidence intervals (CIs). To examine the homogeneity of the effect size distribution, we used a Q-statistic. When we observed heterogeneity in effect sizes, we assessed the possible influence of moderator variables (age and sex, mean dose, study duration, and method of measuring EPS incidence) and evaluated the suitability of either a fixed or a random model. Finally, we assessed the incidence of EPS in children and adolescents treated with aripiprazole compared with placebo. Results An initial search via PubMed and Embase yielded 328 hits. A manual search of the reference lists of review papers revealed seven additional relevant articles. We included 41 studies, with 2114 pediatric patients, in the meta-analysis. For the analysis of the mean incidence of EPS, data were provided by 24 studies, with a total of 1446 pediatric patients. Meta-analysis revealed a mean EPS incidence of 17.1 % (95 % CI 0.128–0.223). In terms of the incidence of various extrapyramidal side effects, overall, no significant effects of age, sex, mean dose, study duration, or measuring method could be demonstrated. The side effects ‘EPS’, ‘parkinsonism’, and ‘tremor’ were significantly more common in children and adolescents treated with aripiprazole than in those treated with placebo. Conclusion Our meta-analysis provides evidence for a non-negligible incidence of acute EPS in children and adolescents treated with aripiprazole. Although the study has several limitations and further investigation is needed, these findings may help clinicians make more balanced treatment choices and more closely monitor the use of this drug in youth. Electronic supplementary material The online version of this article (doi:10.1007/s40263-016-0367-y) contains supplementary material, which is available to authorized users.

Dit artikel rapporteert over een gerandomiseerd gecontroleerde studie van een gedragsveranderende interventie in het reguliere lager onderwijs voor kinderen met symptomen van een aandachtstekortstoornis met hyperactiviteit (ADHD). De ADHD toolkit is een systematisch werkinstrument voor leerkracht en leerling dat probleemgedrag in kaart brengt en terugkoppelt naar de leerling, waarbij met toenemende intensiteit meer passend gedrag wordt ingeoefend, gekoppeld aan positieve bekrachtiging. Honderdenzes leerlingen tussen vijf en twaalf jaar oud werden gerekruteerd uit zeven Vlaamse scholen en werden via randomisatie over een interventiegroep en een wachtlijst-controlegroep verdeeld. De uitkomstmaten waren de beoordeling door de leerkracht van de ADHD-symptomen (primair) en de oppositioneel opstandige gedragsproblemen (secundair). Ondanks een positieve appreciatie van het instrument, kon de studie geen significant verschil aantonen tussen de interventie- en de controlegroep betreffende de primaire en secundaire uitkomstmaten. Deze pilotstudie draagt bij tot de vaststelling dat ADHD-gedrag moeilijk veranderbaar is, zoals recent ook uit meta-analyses is gebleken.

Contains fulltext : 194110.pdf (Publisher’s version ) (Open Access) Background: Experimental research supports delay aversion as a motivational feature of attention deficit/hyperactivity disorder (ADHD). To investigate the neurobiology of delay aversion in ADHD, this study examined whether adolescents with ADHD display an unusually strong activation in affective brain regions in response to cues predicting forthcoming delay and whether these effects are (a) delay‐dose dependent and (b) statistically mediate the association between ADHD and self‐reported delay aversion. Methods: Twenty‐nine right‐handed male adolescents with combined type ADHD and 32 typically developing controls (ages 10–18 years) performed a reaction time task in an MRI scanner. Pretarget cues indicated delay‐related response consequences. One indicated that delay would follow the response irrespective of response speed (CERTAIN DELAY), a second that delay would only follow if the response was too slow (CONDITIONAL DELAY), and a third that no delay would follow the response whatever its speed (NO DELAY). Delay levels were 2, 6, or 14 s. Participants also rated their own delay aversion in everyday life. Results: Individuals with ADHD rated themselves as more delay averse than controls. Significantly greater activation to CERTAIN DELAY cues relative to NO DELAY cues was found in participants with ADHD compared to controls (bilaterally) in amygdala, anterior insula, temporal pole, dorsolateral prefrontal cortex (DLPFC), and ventromedial prefrontal cortex. Amygdala and DLPFC activation strength were strongly and delay‐dose dependently correlated with delay aversion ratings, and statistically mediated the relationship between ADHD status and delay aversion. Conclusions: When presented with cues predicting impending delay, adolescents with ADHD, relative to controls, displayed a delay‐related increase in activation in amygdala and DLPFC, regions known to be implicated in the processing of aversive events. Future studies should examine the specificity of these effects to delay aversion compared to aversive events in general. 12 p.

ADHD is a common neurodevelopmental disorder that is underrecognized and underdiagnosed in many parts of the world but overdiagnosed in others. As there are presently no biological tests or markers available to support the diagnostic process, the cornerstone of case identification remains the clinical interview and assessment. Evidence suggests that a structured approach to assessment can foster good clinical practice and facilitate building a treatment plan that can be adequately monitored over time. Whilst there are several evidence-based clinical guidelines that describe the assessment process, these are not used in routine clinical practice as regularly as they should. This chapter describes the elements of a structured approach to assessment, including commentary on recognition, the clinical interview, observation, school information, questionnaires, diagnostic formulation, and cognitive and somatic examination. Special attention is needed to assess comorbidities and with special populations such as those in preschool and with intellectual impairments.

Objectives Emotional lability (EL) is an important trans-diagnostic concept that is associated with significant functional impairment in childhood and adolescence. EL is typically measured with questionnaires, although little is known about the ecological validity of these ratings. In this paper, we undertook 2 studies addressing this issue by examining the relationship between rating-based measures of EL and directly measured emotional expressions and experiences. Furthermore, the associations between directly measured emotional expressions and experiences and attention-deficit/hyperactivity disorder (ADHD) symptomatology were also examined, given the clear association of EL with ADHD in former research. Methods In Study 1, we examined the relationship between parental report of children's EL and ADHD, and children's emotional expressions in an experimental context (N = 67). In Study 2, we examined the relationship between parental ratings and real-time measures of emotional experiences in daily life in adolescents (N = 65). Results EL ratings were associated with different elements of real-time emotional experiences and expressions. Elements of emotional expressions but not emotional experiences were also associated with ADHD symptom reports. Conclusions These studies provide evidence for the ecological validity of EL ratings. Furthermore, they add evidence for the associations between EL and ADHD.

Background: Concerns have been raised over the safety of methylphenidate (MPH), with regard to adverse effects on growth and blood pressure. Our study investigates whether, and to what extent, methylphenidate use in boys with ADHD is associated with having low body mass index (BMI), having low height, and increased systolic and diastolic blood pressure.Methods: Data used for this study stem from the German KiGGS dataset. Three different groups of boys aged 6–15 years were included in the analysis: ADHD patients who used MPH for less than 12 months; ADHD patients who used MPH for 12 months or more; and ADHD patients without current MPH treatment. Each of these three groups was compared to a non-ADHD control group regarding low weight (BMI ≤ 3rd percentile), low height (≤3rd percentile) and raised systolic and diastolic blood pressure. For growth outcomes, boys were categorized according to age (Results: 4244 boys were included in the study; MPH n = 65 (n = 36 n = 53 (n = 22 n = 320 (n = 132 n = 3806 (n = 2003 Conclusion: The analyses of the KiGGS dataset showed that MPH use in boys with ADHD is associated with low BMI. However, this effect was only observed in certain groups. Furthermore, our analysis was unable to confirm that MPH use is also associated with low height (≤3rd percentile) and changes in blood pressure.

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

Central nervous system-directed prophylactic chemotherapy increases survival in childhood leukemia, but possible late neurocognitive sequelae remain a concern. We compared intellectual performance (WAIS IV), memory (AVLT), and executive functioning (ANT) between adult leukemia survivors (n = 31) and control individuals (n = 35). In survivors, cerebrospinal fluid (CSF) levels of phosphorylated Tau (p-Tau) during treatment and total intrathecal methotrexate dose correlated with adult intellectual performance (Pearson's and Spearman's coefficients, respectively). Long-term memory and attentional control, both maturing before survivors' mean age at diagnosis, were unaffected (P > .05 on all four subtests), in contrast to cognitive flexibility and information processing (P < .05 for eight of the subtests), which mature during adolescence. CSF p-Tau and methotrexate dose negatively correlated with intellectual performance (r = -0.414, P = .04 and r = -0.484, P = .007, respectively), but not with each other (r = 0.219, P = .29). These data identify CSF p-Tau as a predictor of late neurocognitive sequelae (in addition to methotrexate dose). Early identification of children at risk could inspire interventions to prevent or remediate chemotherapy-induced cognitive sequelae.

Background: Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be associated with cardiovascular effects. It is important to identify whether mean group effects translate into clinically relevant increases for some individual patients, and/or increase the risk for serious cardiovascular adverse events such as stroke or sudden death.Objectives: To evaluate potential cardiovascular effects of these treatments, we conducted a systematic review and meta-analysis of the effects of methylphenidate (MPH), amphetamines (AMP), and atomoxetine (ATX) on diastolic and systolic blood pressure (DBP, SBP) and heart rate (HR) in children and adolescents with ADHD.Methods: We conducted systematic searches in electronic databases (PsychINFO, EMBASE and Medline) to identify published trials which involved individuals who were (i) diagnosed with ADHD and were aged between 0–18 years; (ii) treated with MPH, AMP or ATX and (iii) had their DBP and SBP and/or HR measured at baseline (pre) and the endpoint (post) of the study treatment. Studies with an open-label design or a double-blind randomised control design of any duration were included. Statistical analysis involved calculating differences between pre- and post-treatment measurements for the various cardiovascular parameters divided by the pooled standard deviation. Further, we assessed the percentage of clinically relevant increased BP or HR, or documented arrhythmias.Results: Eighteen clinical trials met the inclusion criteria (10 for MPH, 5 for AMP, and 7 for ATX) with data from 5837 participants (80.7% boys) and average duration of 28.7 weeks (range 4–96 weeks). All three medications were associated with a small, but statistically significant pre–post increase of SBP (MPH: standard mean difference [SMD] 0.25, 95% confidence interval [CI] 0.08–0.42, p p p = 0.01). MPH did not have a pre–post effect on DBP and HR. AMP treatment was associated with a small but statistically significant pre–post increase of DBP (SMD 0.16, CI 0.03–0.29, p = 0.02), as was ATX treatment (SMD 0.22, CI 0.10–0.34, p p p F(1) = 19.55, p = 0.05). Further, MPH studies published before 2007 reported higher effect sizes on SBP than studies after 2007 (F(1) = 5.346, p = 0.05). There was no effect of the following moderators: type of medication, doses, sample size, age, gender, type of ADHD, comorbidity or dropout rate. Participants on medication reported 737 (12.6%) other cardiovascular effects. Notably, 2% of patients discontinued their medication treatment due to any cardiovascular effect. However, in the majority of patients, the cardiovascular effects resolved spontaneously, medication doses were changed or the effects were not considered clinically relevant. There were no statistically significant differences between the medication treatments in terms of the severity of cardiovascular effects.Conclusions: Statistically significant pre–post increases of SBP, DBP and HR were associated with AMP and ATX treatment in children and adolescents with ADHD, while MPH treatment had a statistically significant effect only on SBP in these patients. These increases may be clinically significant for a significant minority of individuals that experience larger increases. Since increased BP and HR in general are considered risk factors for cardiovascular morbidity and mortality during adult life, paediatric patients using ADHD medication should be monitored closely and regularly for HR and BP.

Item does not contain fulltext Individuals with ADHD appear to respond differently to incentives than their peers. This could be due to a general altered sensitivity to reinforcers. However, apart from differences in the degree of motivation, individuals with ADHD might also be motivated by qualitatively different factors. This study aimed to harvest a range of motivational factors and identify ADHD-related qualitative differences in motivation, from the adolescent's point of view. Semi-structured interviews allowing participants to describe what motivates them in daily life were conducted with young adolescents (9-16 years) with and without ADHD. Thematic analysis was undertaken using NVivo software. Major themes relating to motivation were identified from the interview data. These were: (1) achieving a sense of togetherness; (2) feeling competent; (3) fulfilling a need for variation; (4) gaining pleasure from applying effort to achieve a goal; (5) valuing social reinforcement; (6) desiring to be absorbed/forget problems; (7) feeling free and independent, (8) attaining material reinforcement; and (9) an enjoyment of bodily stimulation. The theme structure was very similar for both groups. However, individuals with ADHD differed in some specifics: their focus on the passing of time, the absence of preference for predictable and familiar tasks, and their less elaborate description of the togetherness theme. A broad range of motivational themes was identified, stretching beyond the current focus of ADHD research and motivational theories. Similarities and differences in motivational values of individuals with and without ADHD should be taken into account in reward sensitivity research, and in psychological treatment. 10 p.

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

Introduction The neural response towards cues signalling monetary gain and loss has been extensively studied through the Monetary Incentive Delay (MID) task [1]. Abnormalities in reward processing have been found in adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Anticipation of loss is often directly compared against anticipation of gain to represent the trade-off between positive and negative outcomes. In daily life situations, these events occur independently from each other and monetary loss can be escapable. We used an adaptation of the MID functional Magnetic Resonance Imaging (fMRI) task to assess the specific brain response pattern of typically developing adolescents and adolescents with ADHD towards monetary loss, representing a common social penalty. Methods Thirty-nine right-handed male adolescents with ADHD and 33 age-matched controls (9-18 years) performed a reaction time task under three conditions: (i) on Certain Loss trials, a monetary loss of €0.20, €1, or €5 occurred irrespective of response speed, (ii) on Conditional Loss trials, monetary loss could be avoided when responding in time, and (iii) on No Loss trials, no money could be lost. Participants started with €150 and were told that they could take home the remainder after 135 trials. The game was set that 4/5 of the start amount was lost. fMRI BOLD responses were acquired to compare anticipatory brain activation following the different cue types. Standard preprocessing and statistical analysis was performed in Statistical Parametric Mapping 12 (Wellcome department of Neuroimaging, London, UK). Repeated-measures ANOVA’s examined the effects of condition (certain loss, conditional loss, no loss) as a within subject factor and group (ADHD, controls) as a between subject factor on reaction time (RT). To examine the effects of monetary level on these variables further ANOVAs were conducted with monetary value (€0.20, €1, €5) and task condition (certain loss, conditional loss) as within-subject factors, and group as a between-subject factor. Post-hoc t-tests were used to explore significant interaction effects, when appropriate Results RTs were significantly (p No Loss contrast. In the ADHD group, conditional loss cues elicited an unusually strong pattern of activation within brain regions known, more generally, to be implicated in the processing of aversive events. Conclusions We provide some of the first evidence of a distinctive brain pattern between conditional and certain monetary loss in adolescents with ADHD compared to typically developing controls. The identification of such contingencies can provide more insight how adolescents respond to monetary loss in daily life.

Background: Medication is an important element of therapeutic strategies for ADHD. While medications for ADHD are generally well-tolerated, there are common, although less severe, as well as rare but severe adverse events AEs during treatment with ADHD drugs. The aim of this review is to provide evidence- and expert-based guidance concerning the management of (AEs) with medications for ADHD. Methods: For ease of use by practitioners and clinicians, the article is organized in a simple question and answer format regarding the prevalence and management of the most common AEs. Answers were based on empirical evidence from studies (preferably meta-analyses or systematic reviews) retrieved in PubMed, Ovid, EMBASE and Web of Knowledge through 30 June 2012. When no empirical evidence was available, expert consensus of the members of the European ADHD Guidelines Group is provided. The evidence-level of the management recommendations was based on the SIGN grading system. Results: The review covers monitoring and management strategies of loss of appetite and growth delay, cardiovascular risks, sleep disturbance, tics, substance misuse/abuse, seizures, suicidal thoughts/behaviours and psychotic symptoms. Conclusion: Most AEs during treatment with drugs for ADHD are manageable and most of the times it is not necessary to stop medication, so that patients with ADHD may continue to benefit from the effectiveness of pharmacological treatment. Keywords: ADHD, medication, adverse events, management, recommendations, European.

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

Background Catatonia is a motor dysregulation syndrome co-occurring with a variety of psychiatric and medical disorders. Response to treatment with benzodiazepines and electroconvulsive therapy suggests a neurobiological background. The genetic etiology however remains largely unexplored. Copy Number Variants (CNV), known to predispose to neurodevelopmental disorders, may play a role in the etiology of catatonia. Methods This study is exploring the genetic field of catatonia through CNV analysis in a cohort of psychiatric patients featuring intellectual disability and catatonia. Fifteen adults admitted to a psychiatric inpatient unit and diagnosed with catatonia were selected for array Comparative Genomic Hybridization analysis at 200 kb resolution. We introduced a CNV interpretation algorithm to define detected CNVs as benign, unclassified, likely pathogenic or causal with regard to catatonia. Results Co-morbid psychiatric diagnoses in these patients were autism, psychotic or mood disorders. Eight patients were found to carry rare CNVs, which could not be classified as benign, comprising 6 duplications and 2 deletions. Microdeletions on 22q13.3, considered causal for catatonia, were detected in 2 patients. Duplications on 16p11.2 and 22q11.2 were previously implicated in psychiatric disorders, but not in catatonia, and were therefore considered likely pathogenic. Driven by the identification of a rare 14q11.2 duplication in one catatonic patient, additional patients with overlapping duplications were gathered to delineate a novel susceptibility locus for intellectual disability and psychiatric disorders on 14q11.2, harboring the gene SUPT16H . Three remaining variants respectively on 2q36.1, 16p13.13 and 17p13.3 were considered variants of unknown significance. Conclusion The identification of catatonia-related copy number changes in this study, underscores the importance of genetic research in patients with catatonia. We confirmed that 22q13.3 deletions, affecting the gene SHANK3 , predispose to catatonia, and we uncover 14q11.2 duplications as a novel susceptibility factor for intellectual and psychiatric disorders.

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

OBJECTIVE: There is no questionnaire to specifically monitor perceived adverse events of methylphenidate (MPH) on cognition, motivation, and mood. The current study therefore had two goals. First, to harvest accounts of such putative events from transcripts of interviews in samples enriched for such potential experiences. Second, to use the derived data to generate items for a new questionnaire that can be used for monitoring such events in medication trials or routine clinical care. METHODS: Following a literature search aimed at identifying associations between MPH and cognition and/or motivation, a qualitative semistructured interview was designed to focus specifically on the domains of cognition (i.e., reasoning, depth/breadth of thinking, intellectual capacity, and creativity) and motivation (i.e., drive, effort, and attitudes toward rewards/incentives). Interviews were conducted with 45 participants drawn from the following four groups: (a) clinicians, child and adolescent psychiatrists, and pediatricians specializing in attention-deficit/hyperactivity disorder (ADHD) (n = 15); (2) teachers, with experience of teaching at least 10 medicated children with ADHD (n = 10); (3) parents of children with ADHD (n = 8) treated with MPH; and (4) adolescents/adults with ADHD (n = 12). Purposeful sampling was used to selectively recruit ADHD participants whose histories suggested a degree of vulnerability to MPH adverse events. Data were analyzed using a deductive approach to content analysis. RESULTS: While we probed purposefully for cognitive and motivational adverse events, a third domain, related to mood, emerged from the reports. Therefore, three domains, each with a number of subdomains, were identified from the interview accounts: (i) Cognition (six subdomains; attention/concentration, changes in thinking, reduced creativity, sensory overload, memory, slower processing speed); (ii) motivation (four subdomains; loss of intrinsic motivation for goal-directed activities, external locus of control, lack of effort/engagement in daily tasks, increased focus on incentives); and (iii) mood (three subdomains; dampening of spontaneity/flat affect, mood dysregulation, increased anxiety/edginess). On the basis of these reports, 34 items were specified and incorporated into a prototype questionnaire, which was piloted and refined on the basis of field-testing. CONCLUSIONS: Items were identified that capture potential/perceived cognitive, motivational, and mood-related adverse events of MPH. The items generated will allow us to further develop and psychometrically examine their prevalence, and the extent to which they are associated with medication adherence, treatment outcome, impairment, and other reported adverse events (e.g., loss of appetite/cardiovascular effects). ispartof: Journal of Child and Adolescent Psychopharmacology vol:26 issue:6 pages:1-11 ispartof: location:United States status: published

Working memory (WM) dysfunction and increased within-subject variability are known issues in attention deficit/hyperactivity disorder (ADHD) patients. Little is known about the electrophysiological characteristics of this variability. We evaluated behavioral and electrophysiological within-subject variability taking developmental aspects into account in a group of ADHD patients. Multichannel (n = 31) event-related potentials (ERP) were measured during a visuo-spatial backmatching task; 44 children (8-16 years old) were tested: 22 children with ADHD, combined (n = 17) and inattentive (n = 5) type, and 22 age- and intelligence-matched control children. One-backmatching (BM1) and two-backmatching (BM2) tasks were performed. Classical behavioral parameters and target and nontarget ERP were compared between groups. In addition, motor response variability and ERP amplitude variability were studied. Age-related changes in both motor response and ERP amplitude variability were analyzed in each group. Attention deficit/hyperactivity disorder children made more commission errors, which was more pronounced in the difficult (BM2) task. No difference between groups was found in ERP amplitude and in motor response variability. However, ADHD patients had higher ERP amplitude variability, which was again more pronounced in the difficult WM task. A delayed maturation of amplitude variability was seen in ADHD patients with a slower than in controls decrease in variability with age. This amplitude variability was correlated with the number of commissions, but in an opposite way for ADHD and control children. Our findings indicate an impaired visuo-spatial WM processing in ADHD children with greater ERP amplitude variability compared to controls. Our results also support the view of a delayed cortical development of visuo-spatial WM circuits in this disorder.

Clinical decision making is influenced by a range of factors and constitutes an inherently complex task. Here we present results from the decisions regarding ADHD management (DRAMa) study in which we undertook a thematic analysis of clinicians' experiences and attitudes to assessment, diagnosis and treatment of ADHD. Fifty prescribing child psychiatrists and paediatricians from Belgium and the UK took part in semi-structured interviews about their decisions regarding the assessment, diagnosis and treatment of ADHD. Interviews were transcribed and processed using thematic analysis and the principles of grounded theory. Clinicians described the assessment and diagnostic process as inherently complicated and requiring time and experience to piece together the accounts of children made by multiple sources and through the use of varying information gathering techniques. Treatment decisions were viewed as a shared process between families, children, and the clinician. Published guidelines were viewed as vague, and few clinicians spoke about the use of symptom thresholds or specific impairment criteria. Furthermore, systematic or operationalised criteria to assess treatment outcomes were rarely used. Decision making in ADHD is regarded as a complicated, time consuming process which requires extensive use of clinical impression, and involves a partnership with parents. Clinicians want to separate biological from environmental causal factors to understand the level of impairment and the subsequent need for a diagnosis of ADHD. Clinical guidelines would benefit from revisions to take into account the real-world complexities of clinical decision making for ADHD.

In recent years, the interest in the relationship between exposure to green spaces and children's and adolescents' mental health has risen. This systematic review aims to provide an overview of observational studies assessing the association between empirical green space exposure with standardized outcome measures of mental health problems, mental well-being and developmental problems in children, adolescents and young adults. The PRISMA statement guidelines for reporting systematic reviews were followed. A PubMed and Scopus search resulted in the inclusion of 21 studies. The evidence consistently suggests a beneficial association between green space exposure and children's emotional and behavioral difficulties, particularly with hyperactivity and inattention problems. Limited evidence suggests a beneficial association with mental well-being in children and depressive symptoms in adolescents and young adults. These beneficial associations are resistant to adjustment for demographic and socio-economic confounders, which thus may represent independent links. Mediating factors and the variability of this association between different age groups are discussed. From a precautionary principle, evidence up to now demands the attention of policy makers, urban planners and mental healthcare workers in order to protect children's and adolescents' mental health in light of rapid global urbanization by providing sufficient exposure to green spaces. ispartof: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH vol:15 issue:12 ispartof: location:Switzerland status: published