Efficacy of a synbiotic in the management of adults with Attention-Deficit and Hyperactivity Disorder and/or Borderline Personality Disorder and high levels of irritability: Results from a multicenter, randomized, placebo-controlled, "basket" trial.

Irritability worsens prognosis and increases mortality in individuals with Attention-Deficit and Hyperactivity Disorder (ADHD) and/or Borderline Personality Disorder (BPD). However, treatment options are still insufficient. The aim of this randomized, double blind, placebo-controlled study was to investigate the superiority of a synbiotic over placebo in the management of adults with ADHD and/or BPD and high levels of irritability. The study was conducted between February 2019 and October 2020 at three European clinical centers located in Hungary, Spain and Germany. Included were patients aged 18-65 years old diagnosed with ADHD and/or BPD and high levels of irritability (i.e., an Affectivity Reactivity Index (ARI-S) ≥ 5, plus a Clinical Global Impression-Severity Scale (CGI-S) score ≥ 4). Subjects were randomized 1(synbiotic):1(placebo); the agent was administered each day, for 10 consecutive weeks. The primary outcome measure was end-of-treatment response (i.e., a reduction ≥ 30 % in the ARI-S total score compared to baseline, plus a Clinical Global Impression-Improvement (CGI-I) total score of < 3 (very much, or much improved) at week 10). Between-treatment differences in secondary outcomes, as well as safety were also investigated. Of the 231 included participants, 180 (90:90) were randomized and included in the intention-to-treat-analyses. Of these, 117 (65 %) were females, the mean age was 38 years, ADHD was diagnosed in 113 (63 %), BPD in 44 (24 %), both in 23 (13 %). The synbiotic was well tolerated. At week 10, patients allocated to the synbiotic experienced a significantly higher response rate compared to those allocated to placebo (OR: 0.2, 95 % CI:0.1 to 0.7; P = 0.01). These findings suggest that that (add-on) treatment with a synbiotic may be associated with a clinically meaningful improvement in irritability in, at least, a subgroup of adults with ADHD and/or BPD. A superiority of the synbiotic over placebo in the management of emotional dysregulation (-3.6, 95 % CI:-6.8 to -0.3; P = 0.03), emotional symptoms (-0.6, 95 % CI:-1.2 to -0.05; P = 0.03), inattention (-1.8, 95 % CI: -3.2 to -0.4; P = 0.01), functioning (-2.7, 95 % CI: -5.2 to -0.2; P = 0.03) and perceived stress levels (-0.6, 95 % CI: -1.2 to -0.05; P = 0.03) was also suggested. Higher baseline RANK-L protein levels were associated with a significantly lower response rate, but only in the synbiotic group (OR: 0.1, 95 % CI: -4.3 to - 0.3, P = 0.02). In the placebo group, higher IL-17A levels at baseline were significantly associated with a higher improvement in in particular, emotional dysregulation (P = 0.04), opening a door for new (targeted) drug intervention. However, larger prospective studies are warranted to confirm the findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03495375.

Are Genetic and Environmental Risk Factors for Psychopathology Amplified in Children with Below-Average Intelligence? A Population-Based Twin Study.

There is a negative association between intelligence and psychopathology. We analyzed data on intelligence and psychopathology to assess this association in seven-year-old Dutch twin pairs (ranging from 616 to 14,150 depending on the phenotype) and estimated the degree to which genetic and environmental factors common to intelligence and psychopathology explain the association. Secondly, we examined whether genetic and environmental effects on psychopathology are moderated by intelligence. We found that intelligence, as assessed by psychometric IQ tests, correlated negatively with childhood psychopathology, as assessed by the DSM-oriented scales of the Child Behavior Check List (CBCL). The correlations ranged between - .09 and - .15 and were mainly explained by common genetic factors. Intelligence moderated genetic and environmental effects on anxiety and negative affect, but not those on ADHD, ODD, and autism. The heritability of anxiety and negative affect was greatest in individuals with below-average intelligence. We discuss mechanisms through which this effect could arise, and we end with some recommendations for future research.

Study Protocol: Pegasus: psychotherapy incorporating horses for 'therapy-resistant' adolescents with autism spectrum disorders, a study with series of randomised, baseline controlled n-of-1 trials.

BACKGROUND: For people with autism spectrum disorder (ASD), daily life can be highly stressful with many unpredictable events that can evoke emotion dysregulation (ED): a strong difficulty with appropriately negative affect regulation. For some of the patients with ASD, treatment as usual does not prove to be effective for ED. They may be at risk of life-long impairment, development of other disorders and loss of motivation for most regular forms of therapy. A highly promising method that may prove effective for therapy-resistant individuals with ASD is Psychotherapy incorporating horses (PIH). PIH uses the interactions of the horse and the patients on the ground and does not include horseriding. While often met with prejudgment and scepticism, reports from parents and therapists as well as a recent systematic review suggest that PIH may have beneficial effects on youths with ASD. Therefore, we examine clinical outcomes both in the short and in the long terms of PIH offered to adolescents with ASD and severe ED despite regular therapy. METHODS: A total of 35 adolescents aged 11-18 years with ASD will receive PIH during 15 sessions once a week with randomization to five different groups differentiating in baseline phase from 2 to 6 weeks. PIH uses horses to promote social awareness and self-awareness as well as relationship management and self-management. The primary outcome is the response to treatment on the Emotion Dysregulation Index (EDI). The secondary outcome measures include ASD symptom severity, quality of life, self-esteem, global and family functioning, and goal attainment. Assessments take place at the baseline (T0), at the end of baseline phase A (T1), after completion of intervention phase B (T2), after the end of post-measurement phase C (T3) and after one year (T4). Qualitative interviews of participants, parents and therapists will be held to reveal facilitators and barriers of PIH and a cost-effectiveness study will be performed. DISCUSSION: This study aims at contributing to clinical practice for adolescents with ASD and persistent emotion regulation problems despite 1.5 year of treatment by offering Psychotherapy incorporating horses in a study with series of randomised, baseline controlled n-of-1 trials. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT05200351, December 10th 2021.

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 short and long-term effects of a lifestyle intervention in children with mental illnesses: a randomized controlled trial (Movementss study).

BACKGROUND: A lifestyle including poor diet, physical inactivity, excessive gaming and inadequate sleep hygiene is frequently seen among Dutch children. These lifestyle behaviors can cause long-term health problems later in life. Unhealthy lifestyle and poor physical health are even more prevalent among children with mental illness (MI) such as autism, attention-deficit/hyperactivity disorder, depression, and anxiety. However, research on lifestyle interventions among children with MI is lacking. As a result, there are currently no guidelines, or treatment programs where children with MI and poor lifestyle can receive effective support. To address these issues and to provide insight into the effectiveness of lifestyle interventions in children with MI and their families, the Movementss study was designed. This paper describes the rationale, study design, and methods of an ongoing randomized controlled trial (RCT) comparing the short-term (12 weeks) and long-term (1 year) effects of a lifestyle intervention with care as usual (CAU) in children with MI and an unhealthy lifestyle. METHODS: A total of 80 children (6-12 years) with MI according to DSM-V and an unhealthy lifestyle are randomized to the lifestyle intervention group or CAU at a specialized child and adolescent mental hospital. The primary outcome measure is quality of life measured with the KIDSCREEN. Secondary outcomes include emotional and behavior symptoms, lifestyle parameters regarding diet, physical activity, sleep, and screen time, cognitive assessment (intelligence and executive functions), physical measurements (e.g., BMI), parenting styles, and family functioning, prior beliefs, adherence, satisfaction, and cost-effectiveness. Assessments will take place at the start of the study (T0), after 12 weeks (T1), six months (T2), and 12 months of baseline (T3) to measure long-term effects. DISCUSSION: This RCT will likely contribute to the currently lacking knowledge on lifestyle interventions in children with MI. TRIAL REGISTRATION: trialsearch.who.int/ NL9822. Registered at November 2nd, 2021.

Short-term effects of an elimination diet and healthy diet in children with attention-deficit/hyperactivity disorder: a randomized-controlled trial.

An Elimination Diet (ED) may be effective in reducing symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), but has never been compared to an active control condition [i.e., Healthy Diet (HD)]. In a two-armed RCT, a total of N = 165 children (5-12 years) with ADHD were randomized by means of minimization (1:1) to either an ED (N = 84) or HD (N = 81) within two Dutch child and adolescent psychiatry centers. The design included a non-randomized comparator arm including N = 58 children being treated with Care as Usual (CAU). Treatment allocation was unblinded. The primary outcome was a 5-point ordinal measure of respondership based on a combination of parent and teacher ratings on ADHD and emotion regulation, determined after 5 weeks of treatment. Ordinal regression analyses were done on an intention-to-treat basis. Fewer ED (35%) than HD (51%) participants showed a partial to full response, despite overall good-to-excellent treatment adherence (> 88%) and comparable high parental prior believes. A younger age and higher problem severity predicted a better respondership. CAU-preferring participants responded more often favorably (56%) compared to ED-but not HD-participants. Small-to-medium improvements in physical health (blood pressure, heart rate, and somatic complaints) were found in response to ED/HD versus decrements in response to CAU (74% received psychostimulants). The lack of superiority of the ED versus HD suggests that for the majority of children, dietary treatment response is not rooted in food-allergies/-sensitivities. The comparable results for treatment with HD and CAU are remarkable given that CAU participants were probably 'easier to treat' than HD (and ED) participants with proportionally fewer with a (suboptimal/non-response to) prior treatment with medication (4% versus 20%). Further assessment of long-term effects is needed to evaluate the potential place of dietary treatment within clinical guidelines. The trial is closed and registered in the Dutch trial registry, number NL5324 ( https://www.onderzoekmetmensen.nl/en/trial/25997 ).

Characterizing the heterogeneous course of inattention and hyperactivity-impulsivity from childhood to young adulthood.

To advance understanding of the heterogeneity in the course of ADHD, joint symptom trajectories of inattention and hyperactivity-impulsivity from childhood to young adulthood were modelled and associated with genetic, demographic, and clinical characteristics. Data were obtained from the NeuroIMAGE cohort which includes 485 individuals with ADHD, their 665 siblings, and 399 typically developing children. Trajectories were based on scores of the Conners Parent Rating Scale Revised and estimated over seven homogeneous age bins (from 5 to 28 years) using parallel process latent class growth analysis on data collected across 2-4 time points. Multilevel multinomial logistic regression was used to identify characteristics that differentiated between the derived classes. A seven-class solution revealed "severe combined stable" (4.8%), "severe combined decreasing" (13%), "severe inattentive stable" (4.8%), "moderate combined increasing" (7.5%), "moderate combined decreasing" (12.7%), "stable mild" (12.9%), and "stable low" (44.3%) classes. Polygenic risk for depression, ADHD diagnosis, ADHD medication use, IQ, comorbid symptom levels (foremost oppositional behaviour), and functional impairment levels differentiated classes with similar ADHD symptom levels in childhood but a diverging course thereafter. The course of ADHD is highly heterogeneous, with stable, decreasing, and increasing trajectories. Overall, severe symptom levels in childhood are associated with elevated-to-severe symptom levels in adolescence and young adulthood, despite substantial symptom reductions. Beyond symptom severity in childhood, genetic, demographic, and clinical characteristics distinguish the heterogeneous course.

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.

A polygenic risk score analysis of ASD and ADHD across emotion recognition subtypes.

This study investigated the genetic components of ADHD and ASD by examining the cross-disorder trait of emotion recognition problems. The genetic burden for ADHD and ASD on previously identified emotion recognition factors (speed and accuracy of visual and auditory emotion recognition) and classes (Class 1: Average visual, impulsive auditory; Class 2: Average-strong visual & auditory; Class 3: Impulsive & imprecise visual, average auditory; Class 4: Weak visual & auditory) was assessed using ASD and ADHD polygenic risk scores (PRS). Our sample contained 552 participants: 74 with ADHD, 85 with ASD, 60 with ASD + ADHD, 177 unaffected siblings of ADHD or ASD probands, and 156 controls. ADHD- and ASD-PRS, calculated from the latest ADHD and ASD GWAS meta-analyses, were analyzed across these emotion recognition factors and classes using linear mixed models. Unexpectedly, the analysis of emotion recognition factors showed higher ASD-PRS to be associated with faster visual emotion recognition. The categorical analysis of emotion recognition classes showed ASD-PRS to be reduced in Class 3 compared to the other classes (p value threshold [pT] = 1, p = .021). A dimensional analysis identified a high ADHD-PRS reduced the probability of being assigned to the Class 1 or Class 3 (pT = .05, p = .028 and p = .044, respectively). Though these nominally significant results did not pass FDR correction, they potentially indicate different indirect causative chains from genetics via emotion recognition to ADHD and ASD, which need to be verified in future research.

A two arm randomized controlled trial comparing the short and long term effects of an elimination diet and a healthy diet in children with ADHD (TRACE study). Rationale, study design and methods.

BACKGROUND: Food may trigger Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. Therefore, an elimination diet (ED) might be an effective treatment for children with ADHD. However, earlier studies were criticized for the nature of the control group, potential confounders explaining the observed effects, unsatisfactory blinding, potential risks of nutritional deficiencies and unknown long term and cost-effectiveness. To address these issues, this paper describes the rationale, study design and methods of an ongoing two arm randomized controlled trial (RCT) comparing the short (5 week) and long term (1 year) effects of an elimination diet and a healthy diet compared with care as usual (CAU) in children with ADHD. METHODS: A total of N = 162 children (5-12 years) with ADHD will be randomized to either an ED or a healthy diet. A comparator arm including N = 60 children being solely treated with CAU (e.g. medication) is used to compare the effects found in both dietary groups. The two armed RCT is performed in two youth psychiatry centers in the Netherlands, with randomization within each participating center. The primary outcome measure is response to treatment defined as a ≥ 30% reduction on an ADHD DSM-5 rating scale (SWAN) and/or on an emotion dysregulation rating scale (SDQ: dysregulation profile). This is assessed after 5 weeks of dietary treatment, after which participants continue the diet or not. Secondary outcome measures include the Disruptive Behavior Diagnostic Observational Schedule (DB-DOS), parent and teacher ratings of comorbid symptoms, cognitive assessment (e.g. executive functions), school functioning, physical measurements (e.g. weight), motor activity, sleep pattern, food consumption, nutritional quality of the diet, adherence, parental wellbeing, use of health care resources and cost-effectiveness. Assessments take place at the start of the study (T0), after five weeks (T1), four months (T2), eight months (T3) and 12 months of treatment (T4). T0, T1 and T4 assessments take place at one of the psychiatric centers. T2 and T3 assessments consist of filling out online questionnaires by the parents only. DISCUSSION: This RCT will likely contribute significantly to clinical practice for ADHD by offering insight into the feasibility, nutritional quality, (cost-)effectiveness and long term effects of dietary treatments for ADHD. TRIAL REGISTRATION: www.trialregister.nl, NTR5434. Registered at October 11th, 2015.

Long-term effects of stimulant treatment on ADHD symptoms, social-emotional functioning, and cognition.

BACKGROUND: Methodological and ethical constraints have hampered studies into long-term lasting outcomes of stimulant treatment in individuals with attention-deficit/hyperactivity disorder (ADHD). Lasting effects may be beneficial (i.e. improved functioning even when treatment is temporarily ceased) or detrimental (i.e. worse functioning while off medication), but both hypotheses currently lack empirical support. Here we investigate whether stimulant treatment history predicts long-term development of ADHD symptoms, social-emotional functioning or cognition, measured after medication wash-out. METHODS: ADHD symptoms, social-emotional functioning and cognitive test performance were measured twice, 6 years apart, in two ADHD groups (stimulant-treated versus not stimulant-treated between baseline and follow-up). Groups were closely matched on baseline clinical and demographic variables (n = 148, 58% male, age = 11.1). A matched healthy control group was included for reference. RESULTS: All but two outcome measures (emotional problems and prosocial behaviour) improved between baseline and follow-up. Improvement over time in the stimulant-treated group did not differ from improvement in the not stimulant-treated group on any outcome measure. CONCLUSIONS: Stimulant treatment is not associated with the long-term developmental course of ADHD symptoms, social-emotional functioning, motor control, timing or verbal working memory. Adolescence is characterised by clinical improvement regardless of stimulant treatment during that time. These findings are an important source to inform the scientific and public debate.

Overweight in family members of probands with ADHD.

The widely reported association between ADHD and overweight may be attributable to genetic and environmental factors also present in unaffected family members. Therefore, the purpose of this study was to examine the association between ADHD and overweight within families. A cohort was used of families with at least one member with ADHD, recruited as part of the Dutch node of the International Multicenter ADHD Genetics (IMAGE) study, with assessments taking place between 2003 and 2006, 2009 and 2012, and 2013 and 2015. The three assessment waves yielded N = 1828 youth assessments and N = 998 parent assessments from N = 447 unique families. Overweight was defined as a body mass index (BMI) ≥ 85th percentile for youth of the same age and sex; overweight in adults as a BMI ≥ 25. Effects of age, gender, and medication use (psychostimulants, antipsychotics, and melatonin) were taken into account. Generalized estimation equations were used to correct for within-family and within-subject correlations. There was no difference in risk between ADHD-affected youth and their unaffected siblings (OR 0.92, 95% CI 0.78-1.09). However, compared to population prevalence data, all ADHD family members alike were at increased risk for being overweight: ADHD-affected youth (OR 1.33, 95% CI 1.13-1.59), unaffected siblings (OR 1.73, 95% CI 1.45-2.08), mothers (OR 1.74, 95% CI 1.40-2.17) and fathers (OR 1.78, 95% CI 1.46-2.15). Parental overweight-but not parental ADHD-was predictive of offspring overweight (mothers OR 1.40; 95% CI 1.14-1.73, fathers OR 1.83; 95% CI 1.41-2.36). Being overweight runs in ADHD families, yet is not specifically linked to ADHD within families. Shared unhealthy lifestyle factors (including nutrition, sleep, exercise, stress) as well as genetic factors shared by family members likely explain the findings.

Emotional valence detection in adolescents with oppositional defiant disorder/conduct disorder or autism spectrum disorder.

Oppositional defiant disorder, conduct disorder (ODD/CD), and autism spectrum disorder (ASD) share poor empathic functioning and have been associated with impaired emotional processing. However, no previous studies directly compared similarities and differences in these processes for the two disorders. A two-choice emotional valence detection task requiring differentiation between positive, negative, and neutral IAPS pictures was administered to 52 adolescents (12-19 years) with ODD/CD, 52 with ASD and 24 typically developing individuals (TDI). Callous-unemotional (CU) traits were assessed by self- and parent reports using the Inventory of callous-unemotional traits. Main findings were that adolescents with ODD/CD or ASD both performed poorer than TDI in terms of accuracy, yet only the TDI-not both clinical groups-had relatively most difficulty in discriminating between positive versus neutral pictures compared to neutral-negative or positive-negative contrasts. Poorer performance was related to a higher level of CU traits. The results of the current study suggest youth with ODD/CD or ASD have a diminished ability to detect emotional valence which is not limited to facial expressions and is related to a higher level of CU traits. More specifically, youth with ODD/CD or ASD seem to have a reduced processing of positive stimuli and/or lack a 'positive perception bias' present in TDI that could either contribute to the symptoms and/or be a result of having the disorder and may contribute to the comorbidity of both disorders.

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.

Examining the intertwined development of prosocial skills and ASD symptoms in adolescence.

Autism spectrum disorder (ASD) and reduced prosocial behaviour are strongly intertwined. However, social interactions with peers may be increasingly practiced over the course of development and may instigate a reduction in ASD symptoms and vice versa. We, therefore, sought to determine if, during adolescence, possible improvements in prosocial behaviours and ASD symptoms may benefit one another over time. Participants were 2773 adolescents from the Tracking Adolescents' Individual Lives Survey (TRAILS) cohorts. Measurements took place over three waves (mean ages: 11.1, 13.4, and 16.2 years). Longitudinal associations between teacher-rated classroom prosocial skills and parent-rated ASD symptoms were examined using the random intercept cross-lagged panel model (RI-CLPM). In addition to estimating the stable, between-person associations, the dynamical effects between prosocial skills and ASD symptoms over time were estimated at the within-person level. At the between-person level, prosocial skills and ASD symptoms were substantially negatively correlated. At the within-person level, a small and unexpected positive cross-lagged effect from wave 1 ASD symptoms on wave 2 prosocial skills was observed. We added to the existing literature by showing that, in addition to replicating the already firmly established between-person association between low prosocial skills and ASD, within-person gains in prosocial skills do not lead to subsequent reduction of ASD symptoms, and reductions in ASD symptoms do not lead to subsequent enhancement of prosocial skills. We, therefore, conclude from our findings that the inverse association between autistic symptoms and prosocial skills in adolescence is highly stable.

High intelligence and the risk of ADHD and other psychopathology.

BackgroundHigh intelligence may be associated with positive (adaptive, desired) outcomes, but may also come with disadvantages.AimsTo contribute empirically to the debate concerning whether a trade-off in IQ scores exists in relation to attention-deficit hyperactivity disorder (ADHD) and related problems, suggesting that high intelligence - like low intelligence - increases the risk of ADHD.MethodCurves of the relation between IQ score and ADHD problems were fitted to questionnaire data (parent, teacher, self-report} in a population-based study of 2221 children and adolescents aged 10-12 years. Externalising and internalising problems were included for comparison purposes.ResultsHigher IQ score was most strongly related to fewer attention problems, with more rater discrepancy in the high v. average IQ range. Attention problems - but only minimally hyperactivity/impulsivity problems - predicted functional impairment at school, also in the higher IQ range.ConclusionsAttention problems in highly intelligent children are exceptional and affect school performance; they are therefore a reason for clinical concern.

Structural brain imaging correlates of ASD and ADHD across the lifespan: a hypothesis-generating review on developmental ASD-ADHD subtypes.

We hypothesize that it is plausible that biologically distinct developmental ASD-ADHD subtypes are present, each characterized by a distinct time of onset of symptoms, progression and combination of symptoms. The aim of the present narrative review was to explore if structural brain imaging studies may shed light on key brain areas that are linked to both ASD and ADHD symptoms and undergo significant changes during development. These findings may possibly pinpoint to brain mechanisms underlying differential developmental ASD-ADHD subtypes. To this end we brought together the literature on ASD and ADHD structural brain imaging symptoms and particularly highlight the adolescent years and beyond. Findings indicate that the vast majority of existing MRI studies has been cross-sectional and conducted in children, and sometimes did include adolescents as well, but without explicitly documenting on this age group. MRI studies documenting on age effects in adults with ASD and/or ADHD are rare, and if age is taken into account, only linear effects are examined. Data from various studies suggest that a crucial distinctive feature underlying different developmental ASD-ADHD subtypes may be the differential developmental thinning patterns of the anterior cingulate cortex and related connections towards other prefrontal regions. These regions are crucial for the development of cognitive/effortful control and socio-emotional functioning, with impairments in these features as key to both ASD and ADHD.

Elimination diets' efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder.

Nutrition plays an important role in neurodevelopment. This insight has led to increasing research into the efficacy of nutrition-related interventions for treating neurodevelopmental disorders. This review discusses an elimination diet as a treatment for attention deficit hyperactivity disorder and autism spectrum disorder, with a focus on the efficacy of the food additives exclusion diet, gluten-free/casein-free diet and oligoantigenic diet. Furthermore, we discuss the potential mechanisms of elimination diets' effects in these neurodevelopmental disorders. The main candidate mechanism is the microbiome-gut-brain axis possibly involving complex interactions between multiple systems, including the metabolic, immune, endocrine, and neural system. We conclude with practical implications and future directions into the investigation of an elimination diet's efficacy in the treatment of attention deficit hyperactivity disorder and autism spectrum disorder.

Decision-making in social contexts in youth with ADHD.

This study examined reward-related decision-making in children and adolescents with ADHD in a social context, using economic games. We furthermore examined the role of individual differences in reward-related decision-making, specifically, the roles of reward sensitivity and prosocial skills. Children and adolescents (9-17 years) with ADHD-combined subtype (n = 29; 20 boys) and healthy controls (n = 38; 20 boys) completed the ultimatum game and dictator game as measures of reward-related decision-making in social contexts. Prosocial skills were measured with the Interpersonal Reactivity Index. The ADHD group had a larger discrepancy between ultimatum game and dictator game offers than controls, indicating strategic rather than fairness driven decisions. This finding was supported by self-reports showing fewer individuals with ADHD than controls who considered fairness as motive for the decisions. Perspective taking or empathic concern did not differ between groups and was not significantly associated with offers. In conclusion, the results suggest that rather than a failure to understand the perspective of others, children and adolescents with ADHD were less motivated by fairness than controls in simple social situations. Results encourage the use of economic games in ADHD research.