Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ...ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis.
In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156.
Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (Cohen's d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5).
With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes.
National Institutes of Health.
To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared with placebo for attention-deficit/hyperactivity disorder (ADHD), and the impact on substance treatment ...outcomes in adolescents concurrently receiving cognitive-behavioral therapy (CBT) for substance use disorders (SUD).
This was a 16-week, randomized, controlled, multi-site trial of OROS-MPH + CBT versus placebo + CBT in 303 adolescents (aged 13 through 18 years) meeting DSM-IV diagnostic criteria for ADHD and SUD. Primary outcome measures included the following: for ADHD, clinician-administered ADHD Rating Scale (ADHD-RS), adolescent informant; for substance use, adolescent-reported days of use in the past 28 days. Secondary outcome measures included parent ADHD-RS and weekly urine drug screens (UDS).
There were no group differences on reduction in ADHD-RS scores (OROS-MPH: -19.2, 95% confidence interval CI, -17.1 to -21.2; placebo, -21.2, 95% CI, -19.1 to -23.2) or reduction in days of substance use (OROS-MPH: -5.7 days, 95% CI, 4.0-7.4; placebo: -5.2 days, 95% CI, 3.5-7.0). Some secondary outcomes favored OROS-MPH, including lower parent ADHD-RS scores at 8 (mean difference = 4.4, 95% CI, 0.8-7.9) and 16 weeks (mean difference =6.9; 95% CI, 2.9-10.9) and more negative UDS in OROS-MPH (mean = 3.8) compared with placebo (mean = 2.8; p = .04).
OROS-MPH did not show greater efficacy than placebo for ADHD or on reduction in substance use in adolescents concurrently receiving individual CBT for co-occurring SUD. However, OROS-MPH was relatively well tolerated and was associated with modestly greater clinical improvement on some secondary ADHD and substance outcome measures. Clinical Trial Registration Information-Attention Deficit Hyperactivity Disorder (ADHD) in Adolescents with Substance Use Disorders (SUD); http://www.clinicaltrials.gov; NCT00264797.
The most common method used to evaluate child behavior and functioning is rating scales completed by parents and/or teachers. Given that executive functioning (EF) plays a fundamental role in the ...developing child's cognitive, behavioral, and social-emotional development, it would be ideal if ratings of EF and performance-based EF measures assess the same construct. However, most studies report a small to negligible association between performance-based measures and ratings of EF. There are few studies investigating this association for preschoolers, and most only include parent ratings. Teachers may be more reliable reporters of EF behaviors due to the higher demand for EF skills in the preschool setting than at home and because teachers may have a better sense of what behaviors are normative. In this study, we reviewed the associations between three EF rating scales completed by teachers on 243 preschool children. Results showed small to moderate correlations with EF measures of inhibition and cognitive flexibility/switching for all three scales, with the strongest associations observed between Child Behavior Rating Scale (CBRS) Behavioral Regulation subscale and child EF measures. Exploratory multivariate path analyses showed that, after controlling for age, sex, and socioeconomic status (SES), Behavioral Regulation significantly predicted performance-based measures of EF and accounted for incrementally more variance in the models. We conclude that in ideal situations, it is best to measure EF using both rating scales and performance-based measures of EF. The CBRS seems to be a sensitive measure of EF in preschoolers and may be a helpful brief screening tool for use with teachers.
Abstract Attention-Deficit/Hyperactivity Disorder (ADHD) frequently co-occurs with substance use disorder (SUD) and is associated with poor substance-use treatment outcomes. A trial evaluating ...osmotic-release oral system methylphenidate (OROS-MPH) for adolescents with ADHD and SUD, concurrently receiving behavioral therapy, revealed inconsistent medication effects on ADHD or SUD. Clinical care for this population would be advanced by knowledge of treatment outcome predictors. Data from the randomized placebo-controlled trial (n = 299) were analyzed. Significant treatment predictors included: 1) Substance use severity, associated with poorer ADHD and SUD outcomes, 2) ADHD severity, associated with better ADHD and SUD outcomes, 3) comorbid conduct disorder, associated with poorer ADHD outcomes, and 4) court-mandated status, associated with better SUD outcomes but poorer treatment completion. An interaction effect showed that OROS-MPH improved SUD outcomes in adolescents with comorbid conduct disorder compared to placebo. While severe SUD may require more intensive psychosocial treatment, OROS-MPH may improve substance treatment outcomes in adolescents with co-morbid attention and conduct problems.
One of the most salient long-term implications of a childhood diagnosis of ADHD is an increased risk for substance use, abuse, or dependence in adolescence and adulthood. The extent to which cannabis ...use affects ADHD-related alterations in brain functional organization is unknown, however. To address this research gap, we recruited a sample of 75 individuals aged 21-25 years with and without a childhood diagnosis of ADHD Combined Type, who were either frequent users or non-users of cannabis. These participants have been followed longitudinally since age 7-9.9 years as part of a large multi-site longitudinal study of ADHD, the Multimodal Treatment Study of Children with ADHD (MTA). We examined task-independent intrinsic functional connectivity (iFC) within 9 functional networks using a 2 × 2 design, which compared four groups of participants: (1) individuals with a childhood diagnosis of ADHD who currently use cannabis (
= 23); (2) individuals with ADHD who do not currently use cannabis (
= 22); (3) comparisons who currently use cannabis (
= 15); and (4) comparisons who do not currently use cannabis (
= 15). The main effects of childhood ADHD were primarily weakened iFC in networks supporting executive function and somatomotor control. Contrary to expectations, effects of cannabis use were distinct from those of diagnostic group and no interactions were observed. Exploratory brain-behavior analyses suggested that ADHD-related effects were primarily linked with poorer neurocognitive performance. Deficits in the integrity of functional networks supporting executive function and somatomotor control are consistent with the phenotypic and neurocognitive features of ADHD. Our data suggest that cannabis use does not exacerbate ADHD-related alterations, but this finding awaits replication in a larger sample. Longitudinal neuroimaging studies are urgently required to delineate the neurodevelopmental cascade that culminates in positive and negative outcomes for those diagnosed with ADHD in childhood.
Abstract Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with deficits in fluid reasoning, which may be related to self-regulation of cognition and behavior, and requires intact ...attention, working memory, and inhibition skills. No functional magnetic resonance imaging (fMRI) studies have directly examined fluid reasoning in ADHD which is surprising given that studies demonstrate a consistent network of brain regions involved in fluid reasoning that are also implicated in the pathogenesis of ADHD. Twenty-two right-handed, non-medicated children (12 ADHD, 10 controls) ages 8–12 years completed a fluid reasoning task during which fMRI data were collected. The primary comparison of interest was activation during the fluid reasoning compared to the control condition. Behavioral data showed that children with ADHD tended to be less accurate with faster reaction times in the fluid reasoning condition compared to controls, and were significantly less accurate in the control condition. Controls activated more than participants with ADHD in the right intraparietal sulcus and the left lateral cerebellum in the fluid reasoning condition. Results showed hypoactivation in ADHD in regions critical for fluid reasoning. These results add to the literature suggesting a role for parietal and cerebellar regions in cognition and ADHD.
There is limited literature examining the adaptive functioning of adolescents with autism spectrum disorder (ASD). This study aimed to (a) document Vineland Adaptive Behavior Scales (VABS-3) and ...Adaptive Behavior Assessment System (ABAS-3) adaptive behavior profiles of adolescents with ASD; (b) examine the comparability of the two measures; and (c) assess potential discrepancies between IQ and adaptive behaviors. Participants included 14- to 18-year-olds with ASD without intellectual disability. Significant adaptive skills deficits were observed with most scores at least one standard deviation below the mean. Relative weaknesses were observed for social and daily living skills. The absolute magnitude of VABS-3 and ABAS-3 scores differed. There were significant discrepancies between IQ and adaptive functioning. These findings have implications for clinicians and researchers.
Adolescents with autism spectrum disorder frequently experience social communication difficulties, executive functioning deficits, and anxiety and depressive symptoms, which are similar to the ...symptoms and correlates of sluggish cognitive tempo. Although sluggish cognitive tempo is related to, but distinct from, the inattentive and hyperactive-impulsive symptoms of attention-deficit/hyperactivity disorder that commonly co-occur with autism spectrum disorder, few studies have examined sluggish cognitive tempo in autism spectrum disorder. We examined whether sluggish cognitive tempo and attention-deficit/hyperactivity disorder were differentially associated with autism symptomatology, daily life executive functioning, and internalizing and externalizing symptoms in 51 adolescents (ages 13–18 years) with autism spectrum disorder without intellectual disability. Regression analyses controlling for age and IQ showed that sluggish cognitive tempo symptoms, but not attention-deficit/hyperactivity disorder symptoms, were associated with increased autism symptomatology and internalizing symptoms. Attention-deficit/hyperactivity disorder symptoms, but not sluggish cognitive tempo symptoms, were associated with increased externalizing behaviors and behavior regulation deficits. Both sluggish cognitive tempo and attention-deficit/hyperactivity disorder were independently associated with increased metacognitive deficits. This study provides preliminary evidence that sluggish cognitive tempo symptoms are elevated in autism spectrum disorder and associated with key clinical correlates, with implications for the assessment and treatment in adolescents with autism spectrum disorder.
Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The ...authors sought to identify cortical characteristics related to ADHD using large-scale studies.
Cortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707).
In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample.
Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.
Background
Shortened sleep and affective disturbances are both prevalent in adolescents with attention‐deficit/hyperactivity disorder (ADHD), yet the causal link between these domains has not been ...examined. This study investigated whether shortened sleep duration is causally linked to affective functioning in adolescents with ADHD.
Methods
Participants were 48 adolescents (75% male) aged 14–17 years with ADHD who successfully completed a three‐week sleep protocol using an experimental crossover design. The protocol included a phase stabilization week, followed, in randomized counterbalanced order, by one week of sleep restriction (6.5 hr in bed) and one week of sleep extension (9.5 hr in bed). Sleep was monitored with objective actigraphy, and all participants included in this study obtained ≥1 hr actigraphy‐measured sleep duration during extension compared to restriction. Parents and adolescents provided daily ratings of positive and negative affect during the extension and restriction conditions. Ratings of affect, internalizing symptoms, and emotion regulation were collected at laboratory visits conducted at the end of each week.
Results
Both parents and adolescents reported greater depressive symptoms and lower positive affect during restriction compared to extension. Parents also reported greater negative affect and emotion dysregulation among adolescents during sleep restriction than extension. No effects were found for parent‐ or adolescent‐reported anxiety symptoms or for adolescent‐reported emotion regulation or negative affect.
Conclusions
Findings from this study provide the first evidence that shortened sleep duration is a causal contributor to the affect and mood disturbances frequently experienced by adolescents with ADHD, particularly as observed by parents. Targeting sleep may be important to reduce affective disturbances in adolescents with ADHD.
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