The short- and longer-term effects of brief behavioral parent training versus care as usual in children with behavioral difficulties: study protocol for a randomized controlled trial.

BACKGROUND: The access to and uptake of evidence-based behavioral parent training for children with behavioral difficulties (i.e., oppositional, defiant, aggressive, hyperactive, impulsive, and inattentive behavior) are currently limited because of a scarcity of certified therapists and long waiting lists. These problems are in part due to the long and sometimes perceived as rigid nature of most evidence-based programs and result in few families starting behavioral parent training and high dropout rates. Brief and individually tailored parenting interventions may reduce these problems and make behavioral parent training more accessible. This protocol paper describes a two-arm, multi-center, randomized controlled trial on the short- and longer-term effectiveness and cost-effectiveness of a brief, individually tailored behavioral parent training program for children with behavioral difficulties. METHODS: Parents of children aged 2-12 years referred to a child mental healthcare center are randomized to (i) three sessions of behavioral parent training with optional booster sessions or (ii) care as usual. To evaluate effectiveness, our primary outcome is the mean severity of five daily ratings by parents of four selected behavioral difficulties. Secondary outcomes include measures of parent and child behavior, well-being, and parent-child interaction. We explore whether child and parent characteristics moderate intervention effects. To evaluate cost-effectiveness, the use and costs of mental healthcare and utilities are measured. Finally, parents' and therapists' satisfaction with the brief program are explored. Measurements take place at baseline (T0), one week after the brief parent training, or eight weeks after baseline (in case of care as usual) (T1), and six months (T2) and twelve months (T3) after T1. DISCUSSION: The results of this trial could have meaningful societal implications for children with behavioral difficulties and their parents. If we find the brief behavioral parent training to be more (cost-)effective than care as usual, it could be used in clinical practice to make parent training more accessible. TRIAL REGISTRATION: The trial is prospectively registered at ClinicalTrials.gov (NCT05591820) on October 24th, 2022 and updated throughout the trial.

Methylphenidate dose-response in children with ADHD: evidence from a double-blind, randomized placebo-controlled titration trial.

Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally increased doses are found to result in better symptom control; however, it remains unclear whether this pattern can be observed at the individual level, given the large heterogeneity in individual dose-response relationships and observed placebo responses. A double-blind, randomized, placebo-controlled cross-over trial was used to compare weekly treatment with placebo and 5, 10, 15 and 20 mg of MPH twice daily on parent and teacher ratings of child ADHD symptoms and side effects. Participants were 5-13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). MPH response was assessed at group and individual levels and predictors of individual dose-response curves were examined. Mixed model analysis showed positive linear dose-response curves at group level for parent and teacher rated ADHD symptoms and parent rated side effects, but not for teacher rated side effects. Teachers reported all dosages to improve ADHD symptoms compared to placebo, while parents only reported > 5 mg/dose as effective. At the individual level, most (73-88%) children, but not all, showed positive linear dose-response curves. Higher severity of hyperactive-impulsive symptoms and lower internalizing problems, lower weight, younger age and more positive opinions towards diagnosis and medication partly predicted steeper linear individual dose-response curves. Our study confirms that increased doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose-response relationship was found and increased doses did not lead to greater symptom improvement for all children. This trial was registered in the Netherlands trial register (# NL8121).

Editorial: The need for more effective school-based youth mental health interventions.

An important setting to detect youth mental health problems and provide interventions is the school context, but effective and affordable school-based interventions are scarce and implementation of the available evidence-based interventions is limited. In this editorial, we highlight three issues and propose a research agenda. First, we emphasize that many of the mental health interventions currently used in school settings lack a solid evidence base. Second, we outline that high-quality studies are needed to determine what works, for whom it works and under which circumstances. This includes insight into the most effective intervention elements, subgroups of students who profit more or less from these interventions, and the most effective modes of delivery. These questions should drive our research agenda on school-based mental health interventions. Finally, while answering these pivotal questions, a collaborative multidisciplinary effort should be made to implement school-based interventions with a solid evidence base, which involves, among others, studying how this can be done most effectively.

Commentary: Why treatment is the best choice for childhood mental disorders - a commentary on Roest et al. (2022).

An important question in mental healthcare for children is whether treatments are effective and safe in the long run. Here, we comment on a recent editorial perspective by Roest et al. (2022), who argue, based on an overview of systematic reviews, 'that there is no convincing evidence that interventions for the most common childhood disorders are beneficial in the long term'. We believe that the available evidence does not justify this conclusion and express our concern regarding the harmful effects of their message. We show that there is evidence to suggest beneficial longer term treatment effects for each of the disorders and explain why evidence-based treatment should be offered to children with mental disorders.

The efficacy of a self-help parenting program for parents of children with externalizing behavior: a randomized controlled trial.

Parenting programs are effective for children with externalizing problems, but not always easily accessible for parents. In order to facilitate accessibility, we developed a self-help parenting program, consisting of a manual and online part. The efficacy of the program in reducing children's externalizing problems was compared to waitlist in a randomized controlled trial. In addition, two versions of the program were exploratively compared, one with and one without biweekly telephonic support. Candidate moderators (child and parent factors) and parental satisfaction were also examined. We randomly assigned 110 families to one of the following three conditions: the support condition, the no support condition, or the waitlist condition. Intervention duration was 15 weeks. Outcomes were collected at baseline (T0), 8 weeks (T1), 15 weeks (T2), and 28 weeks (T3) and included daily telephonic measurements of parent-rated externalizing behavior and the Intensity scale of the parent-rated Eyberg Child Behavior Inventory (ECBI). Main analyses compared outcomes at T2, using longitudinal regressions with T0 as fixed factor. Results showed that children improved significantly more on both outcomes in the intervention condition compared to waitlist, with small to medium effect sizes. Parental satisfaction was high. Neither differences in efficacy nor in parental satisfaction were found between the support and no support condition. No moderators were detected. The newly developed self-help parenting program is effective in reducing children's externalizing behavior problems and may help improve access to evidence-based care.

Review: Which components of behavioral parent and teacher training work for children with ADHD? - a metaregression analysis on child behavioral outcomes.

BACKGROUND: This metaregression analysis examined which behavioral techniques that are commonly used in behavioral parent and teacher training programs for children with attention-deficit/hyperactivity disorder (ADHD) were related to program effectiveness on children's behavioral outcomes. METHODS: We included 32 randomized controlled trials (N = 2594 children) investigating behavioral parent training, teacher training, or a combination, in children with ADHD under 18 years. Outcomes were symptom counts of total ADHD, inattention, and hyperactivity-impulsivity and behavioral problems. The dosage of techniques was extracted from the intervention manuals. Metaregression was used to assess which techniques and intervention characteristics (setting, delivery method, duration, and home-school collaboration) were associated with intervention effectiveness. RESULTS: Higher dosage of psycho-education for parents was associated with smaller effects on behavioral problems and, only in case of parent training, also with smaller effects on ADHD symptoms. Higher dosage of teaching parents/teachers to use negative consequences was associated with larger effects on behavioral problems. Individual training compared with group training was associated with larger effects on ADHD and hyperactivity-impulsivity symptoms. CONCLUSIONS: This study provides first insights into the specific techniques that are essential in behavioral parent and teacher training programs for children with ADHD. This knowledge can eventually be used to improve and tailor interventions.

Facial emotion recognition impairment predicts social and emotional problems in children with (subthreshold) ADHD.

Children with attention-deficit/hyperactivity disorder (ADHD) symptoms often experience social and emotional problems. Impaired facial emotion recognition has been suggested as a possible underlying mechanism, although impairments may depend on the type and intensity of emotions. We investigated facial emotion recognition in children with (subthreshold) ADHD and controls using a novel task with children's faces of emotional expressions varying in type and intensity. We further investigated associations between emotion recognition accuracy and social and emotional problems in the ADHD group. 83 children displaying ADHD symptoms and 30 controls (6-12 years) completed the Morphed Facial Emotion Recognition Task (MFERT). The MFERT assesses emotion recognition accuracy on four emotions using five expression intensity levels. Teachers and parents rated social and emotional problems on the Strengths and Difficulties Questionnaire. Repeated measures analysis of variance revealed that the ADHD group showed poorer emotion recognition accuracy compared to controls across emotions (small effect). The significant group by expression intensity interaction (small effect) showed that the increase in accuracy with increasing expression intensity was smaller in the ADHD group compared to controls. Multiple regression analyses within the ADHD group showed that emotion recognition accuracy was inversely related to social and emotional problems, but not prosocial behavior. Not only children with an ADHD diagnosis, but also children with subthreshold ADHD experience impairments in facial emotion recognition. This impairment is predictive for social and emotional problems, which may suggest that emotion recognition may contribute to the development of social and emotional problems in these children.

Parental experiences of homeschooling during the COVID-19 pandemic: differences between seven European countries and between children with and without mental health conditions.

The aim of the present study was to examine parental experiences of homeschooling during the COVID-19 pandemic in families with or without a child with a mental health condition across Europe. The study included 6720 parents recruited through schools, patient organizations and social media platforms (2002 parents with a child with a mental health condition and 4718 without) from seven European countries: the UK (n = 508), Sweden (n = 1436), Spain (n = 1491), Belgium (n = 508), the Netherlands (n = 324), Germany (n = 1662) and Italy (n = 794). Many parents reported negative effects of homeschooling for themselves and their child, and many found homeschooling to be of poor quality, with insufficient support from schools. In most countries, contact with teachers was limited, leaving parents with primary responsibility for managing homeschooling. Parents also reported increased levels of stress, worry, social isolation, and domestic conflict. A small number of parents reported increased parental alcohol/drug use. Some differences were found between countries and some negative experiences were more common in families with a child with a mental health condition. However, differences between countries and between families with and without a mental health condition were generally small, indicating that many parents across countries reported negative experiences. Some parents also reported positive experiences of homeschooling. The adverse effects of homeschooling will likely have a long-term impact and contribute to increased inequalities. Given that school closures may be less effective than other interventions, policymakers need to carefully consider the negative consequences of homeschooling during additional waves of the COVID-19 pandemic and future pandemics.

Neurocognitive markers of late-onset ADHD: a 6-year longitudinal study.

BACKGROUND: There is an increased interest in 'late-onset' attention-deficit/hyperactivity disorder (ADHD), referring to the onset of clinically significant ADHD symptoms after the age of 12 years. This study aimed to examine whether unaffected siblings with late-onset ADHD could be differentiated from stable unaffected siblings by their neurocognitive functioning in childhood. METHODS: We report findings from a 6-year prospective, longitudinal study of the Dutch part of the International Multicenter ADHD Genetics (IMAGE) study, including individuals with childhood-onset (persistent) ADHD (n = 193), their siblings with late-onset ADHD (n = 34), their stable unaffected siblings (n = 111) and healthy controls (n = 186). At study entry (mean age: 11.3) and follow-up (mean age: 17.01), participants were assessed for ADHD by structured psychiatric interviews and multi-informant questionnaires. Several neurocognitive functions were assessed at baseline and after 6 years, including time reproduction, timing variability (reaction time variability and time production variability), reaction time speed, motor control and working memory; intelligence was taken as a measure of overall neurocognitive functioning. RESULTS: Siblings with late-onset ADHD were similar to individuals with childhood-onset ADHD in showing longer reaction times and/or higher error rates on all neurocognitive measures at baseline and follow-up, when compared to healthy controls. They differed from stable unaffected siblings (who were similar to healthy controls) by greater reaction time variability and timing production variability at baseline. No significant group by time interaction was found for any of the tasks. CONCLUSIONS: For unaffected siblings of individuals with ADHD, reaction time variability and timing production variability may serve as neurocognitive marker for late-onset ADHD.

Effectiveness of Specific Techniques in Behavioral Teacher Training for Childhood ADHD: A Randomized Controlled Microtrial.

Objective: Behavioral teacher training is the most effective classroom-based intervention for children with attention-deficit/hyperactivity disorder (ADHD). However, it is currently unknown which components of this intervention add to its effectiveness and for whom these are effective.Method: In this microtrial, teachers of 90 children with impairing levels of ADHD symptoms (6-12 years) were randomly assigned to one of three conditions: a short (2 sessions), individualized intervention consisting of either (A) antecedent-based techniques (stimulus control), (B) consequent-based techniques (contingency management) or (C) waitlist. Primary outcome was the average of five daily assessments of four individualized problem behaviors, assessed pre and post intervention and three months later. Moderation analyses were conducted to generate hypotheses on child, teacher and classroom factors that may contribute to technique effectiveness.Results: Multilevel analyses showed that both antecedent- and consequent-based techniques were equally and highly effective in reducing problem behaviors compared to the control condition (Cohen's d =.9); effects remained stable up to three months later. Child's age and class size were moderators of technique effectiveness. For younger children, consequent-based techniques were more effective than antecedent-based techniques, whereas for older children the effect was in the opposite direction. Further, beneficial effects of antecedent-based techniques increased when the number of students per class decreased, whilst effectiveness of consequent-based techniques did not depend on class size.Conclusions: This study shows that both antecedent- and consequent-based techniques are highly effective in reducing problem behavior of children with ADHD. Interventions may be adapted to the child's age and class size.

Which Techniques Work in Behavioral Parent Training for Children with ADHD? A Randomized Controlled Microtrial.

OBJECTIVE: Behavioral parent training (BPT) is an evidence-based intervention for children with attention-deficit/hyperactivity disorder (ADHD), but little is known about the effects of separate techniques parents learn in BPT. METHOD: In a three-armed randomized controlled microtrial including parents of 92 children (4-12 years) with ADHD, we examined the efficacy of two sessions parent training involving either stimulus control techniques (antecedent-based condition (AC)) or contingency management techniques (consequent-based condition (CC)), compared to a waitlist. Primary outcome was daily parent-rated problem behaviors, secondary outcomes were parent-rated symptoms of ADHD and oppositional defiant disorder (ODD), and mental health-care consumption. Measures were completed at baseline (T0), immediately after the training (T1), at two weeks (T2) and three months (T3) follow-up. We also explored whether child and parent characteristics moderated treatment effects. RESULTS: Compared to the waitlist, in the AC, daily rated problem behaviors improved at T1 (d= .56) and T2 (d= .65); in the CC, these behaviors only improved at T2 (d= .53). Daily rated problem behaviors within both conditions remained stable between T2 and T3. In the AC compared to the other conditions, inattention symptoms decreased at T1 and T2. For both active conditions compared to waitlist, hyperactivity-impulsivity symptoms decreased only at T2 and ODD symptoms did not decrease. No moderators were identified. Mental health-care consumption after training was low and did not differ between the active conditions. CONCLUSIONS: Brief training of parents in antecedent- or consequent-based techniques improves problem behaviors of children with ADHD. Antecedent-based techniques appear to be especially important to target inattention.

Does methylphenidate improve academic performance? A systematic review and meta-analysis.

Academic improvement is amongst the most common treatment targets when prescribing stimulants to children with ADHD. Previous reviews on stimulant-related academic improvements are inconclusive and focus on task engagement. Recent literature suggests outcome-domain-specific medication effects that are larger for productivity than for accuracy. The aims of this study are quantifying methylphenidate effects on academic productivity and accuracy for math, reading, spelling; exploring the mediating or moderating effects of symptom improvements, demographic-, design- and disorder-related variables. PubMed, EMBASE, ERIC and PsycINFO were searched for articles reporting methylphenidate effects on academic productivity and accuracy. Thirty-four studies met entry criteria. Methylphenidate improved math productivity (7.8% increase, p < .001); math accuracy (3.0% increase, p = .001); increased reading speed (SMD .47, p < .001) but not reading accuracy. None of the mediators or moderators tested affected methylphenidate efficacy. Academic improvements were small compared to symptom improvements; qualitative changes limited to math. Clinicians should take this discrepancy into account when prescribing medication for ADHD.

Stimulant treatment profiles predicting co-occurring substance use disorders in individuals with attention-deficit/hyperactivity disorder.

Adolescents with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence (ND). It remains unclear whether and how stimulant treatment may affect this risk. We aimed to investigate how stimulant use profiles influence the risk of SUDs and ND, using a novel data-driven community detection analysis to construct different stimulant use profiles. Comprehensive lifetime stimulant prescription data and data on SUDs and ND were available for 303 subjects with ADHD and 219 controls, with a mean age 16.3 years. Community detection was used to define subgroups based on multiple indicators of treatment history, start age, treatment duration, total dose, maximum dose, variability, stop age. In stimulant-treated participants, three subgroups with distinct medication trajectories were distinguished (late-and-moderately dosed, n = 91; early-and-moderately dosed, n = 51; early-and-intensely dosed, n = 103). Compared to stimulant-naïve participants (n = 58), the early-and-intense treatment group had a significantly lower risk of SUDs and ND (HR = 0.28, and HR = 0.29, respectively), while the early-and-moderate group had a significantly lower risk of ND only (HR = 0.30). The late-and-moderate group was at a significantly higher risk of ND compared to the other two treatment groups (HR = 2.66 for early-and-moderate, HR = 2.78 for early-and-intense). Our findings show that in stimulant-treated adolescents with ADHD, long-term outcomes are associated with treatment characteristics, something that is often ignored when treated individuals are compared to untreated individuals.

Network-level assessment of reward-related activation in patients with ADHD and healthy individuals.

INTRODUCTION: Reward processing is a key aspect of cognitive control processes, putatively instantiated by mesolimbic and mesocortical brain circuits. Deficient signaling within these circuits has been associated with psychopathology. We applied a network discovery approach to assess specific functional networks associated with reward processing in participants with attention-deficit/hyperactivity disorder (ADHD). METHODS: To describe task-related processes in terms of integrated functional networks, we applied independent component analysis (ICA) to task response maps of 60 healthy participants who performed a monetary incentive delay (MID) task. The resulting components were interpreted on the basis of their similarity with group-level task responses as well as their similarity with brain networks derived from resting state fMRI analyses. ADHD-related effects on network characteristics including functional connectivity and communication between networks were examined in an independent sample comprising 150 participants with ADHD and 48 healthy controls. RESULTS: We identified 23 components to be associated with 4 large-scale functional networks: the default-mode, visual, executive control, and salience networks. The salience network showed a specific association with reward processing as well as the highest degree of within-network integration. ADHD was associated with decreased functional connectivity between the salience and executive control networks as well as with peripheral brain regions. CONCLUSIONS: Reward processing as measured with the MID task involves one reward-specific and three general functional networks. Participants with ADHD exhibited alterations in connectivity of both the salience and executive control networks and associated brain regions during task performance. Hum Brain Mapp 38:2359-2369, 2017. © 2017 Wiley Periodicals, Inc.

Short-Term Effects of Methylphenidate on Math Productivity in Children With Attention-Deficit/Hyperactivity Disorder are Mediated by Symptom Improvements: Evidence From a Placebo-Controlled Trial.

BACKGROUND: Although numerous studies report positive effects of methylphenidate on academic performance, the mechanism behind these improvements remains unclear. This study investigates the effects of methylphenidate on academic performance in children with attention-deficit/hyperactivity disorder (ADHD) and the mediating and moderating influence of ADHD severity, academic performance, and ADHD symptom improvement. METHODS: Sixty-three children with ADHD participated in a double-blind placebo-controlled crossover study comparing the effects of long-acting methylphenidate and placebo. Dependent variables were math, reading, and spelling performance. The ADHD group performance was compared with a group of 67 typically developing children. RESULTS: Methylphenidate improved math productivity and accuracy in children with ADHD. The effect of methylphenidate on math productivity was partly explained by parent-rated symptom improvement, with greater efficacy for children showing more symptom improvement. Further, children showing below-average math performance while on placebo profited more from methylphenidate than children showing above-average math performance. CONCLUSIONS: The results from this study indicate positive effects of methylphenidate on academic performance, although these were limited to math abilities. In light of these results, expectations of parents, teachers, and treating physicians about the immediate effects of methylphenidate on academic improvement should be tempered. Moreover, our results implicate that positive effects of methylphenidate on math performance are in part due directly to effects on math ability and in part due to reductions in ADHD symptoms.

Paediatric reference values for total homocysteine, tryptophan, tyrosine and phenylalanine in blood spots.

Determining blood concentrations of the amino acids homocysteine, tryptophan, tyrosine and phenylalanine in children is of value in the clinical practice. Over the past decades, the use of blood spot samples to examine amino acid concentrations is increasing rapidly. In children, the use of blood spot samples is especially of relevance, as this method is much less invasive than venous blood sampling. Currently, no paediatric reference values for amino acids in blood spots are available. The aim of the current study was to establish reference values for blood spot concentrations of total homocysteine, tryptophan, tyrosine and phenylalanine in school-age children. Dried blood spots were obtained in a community sample of 104 healthy children, aged 6-12 years old (52% males). Blood spot concentrations of total homocysteine, tryptophan, tyrosine and phenylalanine were determined by positive electrospray liquid chromatography-tandem mass spectrometry. Parents of participants completed questions regarding demographic characteristics. Our sample consisted of healthy children from various ethnic backgrounds, with varying levels of socioeconomic status, in line with the composition of the Dutch society. Blood spot concentrations of total homocysteine, tryptophan, tyrosine and phenylalanine were similar in males and females, and independent of age. In conclusion, paediatric reference values for blood spot concentrations of total homocysteine, tryptophan, tyrosine and phenylalanine were established, which could be of use in the clinical practice.

Risk factors for comorbid oppositional defiant disorder in attention-deficit/hyperactivity disorder.

Oppositional defiant disorder (ODD) is highly prevalent in attention-deficit/hyperactivity disorder (ADHD). Individuals with both ADHD and ODD (ADHD + ODD) show a considerably worse prognosis compared with individuals with either ADHD or ODD. Therefore, identification of risk factors for ADHD + ODD is essential and may contribute to the development of (early) preventive interventions. Participants were matched for age, gender, and ADHD-subtype (diagnostic groups), and did not differ in IQ. Predictors included pre- and perinatal risk factors (pregnancy duration, birth weight, maternal smoking during pregnancy), transgenerational factors (parental ADHD; parental warmth and criticism in diagnostic groups), and postnatal risk factors (parental socioeconomic status [SES], adverse life events, deviant peer affiliation). Three models were assessed, investigating risk factors for ADHD-only versus controls (N = 86), ADHD + ODD versus controls (N = 86), and ADHD + ODD versus ADHD-only (N = 90). Adverse life events and parental ADHD were risk factors for both ADHD + ODD and ADHD-only, and more adverse life events were an even stronger risk factor for comorbid ODD compared with ADHD-only. For ADHD + ODD, but not ADHD-only, parental criticism, deviant peer affiliation, and parental SES acted as risk factors. Maternal smoking during pregnancy acted as minor risk factor for ADHD-only, while higher birth weight acted as minor risk factor for ADHD + ODD. No effects of age were present. Findings emphasise the importance of these factors in the development of comorbid ODD. The identified risk factors may prove to be essential in preventive interventions for comorbid ODD in ADHD, highlighting the need for parent-focused interventions to take these factors into account.

A Systematic Review and Meta-analysis of Neuroimaging in Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) Taking Attention-Deficit Hyperactivity Disorder (ADHD) Into Account.

Oppositional defiant disorder (ODD) and conduct disorder (CD) are common behavioural disorders in childhood and adolescence and are associated with brain abnormalities. This systematic review and meta-analysis investigates structural (sMRI) and functional MRI (fMRI) findings in individuals with ODD/CD with and without attention-deficit hyperactivity disorder (ADHD). Online databases were searched for controlled studies, resulting in 12 sMRI and 17 fMRI studies. In line with current models on ODD/CD, studies were classified in hot and cool executive functioning (EF). Both the meta-analytic and narrative reviews showed evidence of smaller brain structures and lower brain activity in individuals with ODD/CD in mainly hot EF-related areas: bilateral amygdala, bilateral insula, right striatum, left medial/superior frontal gyrus, and left precuneus. Evidence was present in both structural and functional studies, and irrespective of the presence of ADHD comorbidity. There is strong evidence that abnormalities in the amygdala are specific for ODD/CD as compared to ADHD, and correlational studies further support the association between abnormalities in the amygdala and ODD/CD symptoms. Besides the left precuneus, there was no evidence for abnormalities in typical cool EF related structures, such as the cerebellum and dorsolateral prefrontal cortex. Resulting areas are associated with emotion-processing, error-monitoring, problem-solving and self-control; areas associated with neurocognitive and behavioural deficits implicated in ODD/CD. Our findings confirm the involvement of hot, and to a smaller extent cool, EF associated brain areas in ODD/CD, and support an integrated model for ODD/CD (e.g. Blair, Development and Psychopathology, 17(3), 865-891, 2005).

No objectively measured sleep disturbances in children with attention-deficit/hyperactivity disorder.

The main goal of this study was to gain more insight into sleep disturbances in children with attention-deficit/hyperactivity disorder, using objective measures of sleep quality and quantity. The evidence for sleep problems in children with attention-deficit/hyperactivity disorder thus far is inconsistent, which might be explained by confounding influences of comorbid internalizing and externalizing problems and low socio-economic status. We therefore investigated the mediating and moderating role of these factors in the association between attention-deficit/hyperactivity disorder and sleep problems. To control for the effects of stimulant medication use, all participants were tested free of medication. Sixty-three children with attention-deficit/hyperactivity disorder and 61 typically developing children, aged 6-13 years, participated. Sleep was monitored for one to three school nights using actigraphy. Parent and teacher questionnaires assessed symptoms of attention-deficit/hyperactivity disorder, internalizing behaviour, oppositional defiant disorder and conduct disorder. Results showed no differences between the attention-deficit/hyperactivity disorder and typically developing group in any sleep parameter. Within the attention-deficit/hyperactivity disorder group, severity of attention-deficit/hyperactivity disorder symptoms was not related to sleep quality or quantity. Moderation analyses in the attention-deficit/hyperactivity disorder group showed an interaction effect between attention-deficit/hyperactivity disorder symptoms and internalizing and externalizing behaviour on total sleep time, time in bed and average sleep bout duration. The results of our study suggest that having attention-deficit/hyperactivity disorder is not a risk factor for sleep problems. Internalizing and externalizing behaviour moderate the association between attention-deficit/hyperactivity disorder and sleep, indicating a complex interplay between psychiatric symptoms and sleep.

Dopamine and serotonin genetic risk scores predicting substance and nicotine use in attention deficit/hyperactivity disorder.

Individuals with attention deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence. The co-occurrence of ADHD and SUDs/nicotine dependence may in part be mediated by shared genetic liability. Several neurobiological pathways have been implicated in both ADHD and SUDs, including dopamine and serotonin pathways. We hypothesized that variations in dopamine and serotonin neurotransmission genes were involved in the genetic liability to develop SUDs/nicotine dependence in ADHD. The current study included participants with ADHD (n = 280) who were originally part of the Dutch International Multicenter ADHD Genetics study. Participants were aged 5-15 years and attending outpatient clinics at enrollment in the study. Diagnoses of ADHD, SUDs, nicotine dependence, age of first nicotine and substance use, and alcohol use severity were based on semi-structured interviews and questionnaires. Genetic risk scores were created for both serotonergic and dopaminergic risk genes previously shown to be associated with ADHD and SUDs and/or nicotine dependence. The serotonin genetic risk score significantly predicted alcohol use severity. No significant serotonin × dopamine risk score or effect of stimulant medication was found. The current study adds to the literature by providing insight into genetic underpinnings of the co-morbidity of ADHD and SUDs. While the focus of the literature so far has been mostly on dopamine, our study suggests that serotonin may also play a role in the relationship between these disorders.