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ObjectiveThis study aimed to evaluate attention-deficit hyperactivity disorder (ADHD) symptom patterns among children with Down syndrome (DS) with or without ADHD and typically developing (TD) children with ADHD.MethodsParents and teachers rated symptoms of inattention, hyperactivity, and general behavioral concerns for 22 children with DS and comorbid diagnoses of ADHD (DS + ADHD), 66 gender-matched and age-matched children with DS with no diagnosis of ADHD (DS - ADHD), and 66 gender-matched and age-matched TD children with ADHD (TD + ADHD). Children with DS were recruited from the community. TD children with ADHD were recruited from a specialty clinic evaluating for ADHD.ResultsParents tended to report higher scores of inattention and hyperactivity for TD children with ADHD compared with children with DS and no ADHD. Although mean ADHD symptom summary scores were not significantly different in DS + ADHD and DS - ADHD, specific parent-report items (e.g., distractibility and being "on the go") did tend to differentiate these groups. By contrast, teachers tended to report higher inattention and hyperactivity scores for DS + ADHD compared with both DS - ADHD and TD + ADHD. Specific teacher-reported items tending to differentiate DS + ADHD and DS - ADHD included difficulties following through on tasks, avoiding tasks, leaving one's seat, and excessive talking.ConclusionVariability in response patterns between parent and teacher reports for children with and without DS highlights the need to evaluate ADHD symptoms across environments. Our findings also suggest specific items that may particularly be helpful in distinguishing children with DS who do and do not have ADHD, although replication is needed.

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes.

ObjectiveSome studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Neuroanatomic heterogeneity limits our understanding of ADHD's etiology. This study aimed to parse heterogeneity of ADHD and to determine whether patient subgroups could be discerned based on subcortical brain volumes.MethodsUsing the large ENIGMA-ADHD Working Group dataset, four subsamples of 993 boys with and without ADHD and to subsamples of 653 adult men, 400 girls, and 447 women were included in analyses. We applied exploratory factor analysis (EFA) to seven subcortical volumes in order to constrain the complexity of the input variables and ensure more stable clustering results. Factor scores derived from the EFA were used to build networks. A community detection (CD) algorithm clustered participants into subgroups based on the networks.ResultsExploratory factor analysis revealed three factors (basal ganglia, limbic system, and thalamus) in boys and men with and without ADHD. Factor structures for girls and women differed from those in males. Given sample size considerations, we concentrated subsequent analyses on males. Male participants could be separated into four communities, of which one was absent in healthy men. Significant case-control differences of subcortical volumes were observed within communities in boys, often with stronger effect sizes compared to the entire sample. As in the entire sample, none were observed in men. Affected men in two of the communities presented comorbidities more frequently than those in other communities. There were no significant differences in ADHD symptom severity, IQ, and medication use between communities in either boys or men.ConclusionsOur results indicate that neuroanatomic heterogeneity in subcortical volumes exists, irrespective of ADHD diagnosis. Effect sizes of case-control differences appear more pronounced at least in some of the subgroups.

Parents of 30 school-age children with Down syndrome participated in a small-scale randomized clinical trial of a behavioral sleep treatment designed specifically for children with Down syndrome. The aim was to improve child sleep, child daytime behavior problems, caregiver sleep, and caregiver stress. The intervention spanned 5-8 weeks, and assessments occurred pre-treatment, immediately post-treatment, and three months post-treatment using a double-blinded design. Both the active treatment and a treatment-as-usual attention-controlled comparison group showed improvements in actigraphy and parent-report measures of child sleep, parent-reported child internalizing behaviors, and actigraphy measures of parent-sleep. The behavioral sleep treatment did not yield significantly different outcomes than a treatment-as-usual approach supplemented with non-sleep-specific behavioral or education sessions. Possible interpretations of study findings are discussed.

ObjectiveTo determine motor vehicle crash (MVC) risk in adults with a history of childhood attention-deficit/hyperactivity disorder (ADHD) and persistent ADHD symptoms.MethodParticipants with (n = 441) and without (n = 239; local normative comparison group) childhood ADHD from the Multimodal Treatment of Attention-Deficit/Hyperactivity Disorder (MTA) Study were included. Participants provided self-reports on total number of MVCs they had been involved in and the time of licensure. Driving experience was estimated as the number of months since licensure. Total number of MVCs by adulthood was regressed on baseline ADHD status adjusting for sex, age at follow-up, driving experience, baseline oppositional defiant disorder/conduct disorder comorbidity, baseline household income level, adult oppositional defiant disorder/conduct disorder symptoms, adolescent and adult substance use, and adult antisocial personality disorder symptoms. We repeated the analysis using adult ADHD status (persistent versus desistant versus local normative comparison group) and symptom level as the predictor variables. Results are presented as incidence rate ratio (IRR) and CI.ResultsChildhood ADHD was associated with a higher number of MVCs (IRR = 1.45, CI = 1.15-1.82), and adult ADHD symptom persistence was associated with more MVCs than desistance (IRR = 1.46, CI = 1.14-1.86). ADHD desistance was not associated with a significantly increased risk for MVCs compared with the local normative comparison group (IRR = 1.24, CI = 0.96-1.61). Concurrent symptoms of inattention and hyperactivity/impulsivity predicted MVC risk.ConclusionPersistence of ADHD into adulthood is a stronger predictor of MVC risk than childhood-limited ADHD.Clinical trial registration informationMultimodal Treatment of Attention Deficit Hyperactivity Disorder (MTA) Study; https://clinicaltrials.gov; NCT00000388.

Childhood attention-deficit/hyperactivity disorder (ADHD) is prospectively linked to substance use and disorder. Depression emerging in adolescence is an understudied risk factor that may explain some of this risk. In the present study, we considered mediating and moderating roles of adolescent depression in explaining this association by using longitudinal data from the prospective 16-year follow-up of the Multimodal Treatment Study of ADHD (MTA). Participants were 547 children diagnosed with DSM-IV ADHD Combined Type, and 258 age- and sex-matched comparison children. In adolescence, depressive symptoms did not exacerbate effects of childhood ADHD on any substance use. For both groups, time-varying and average depressive symptoms were associated with more frequent use of all substances. Prospectively, we found no evidence of depression mediation to adult substance use. However, adolescent depression moderated the association between childhood ADHD and adult marijuana use. Although adults without ADHD histories used marijuana more frequently if they had elevated depressive symptoms in adolescence, marijuana use by adults with ADHD histories was independent of their adolescent depression. In adulthood, depression diagnoses and ADHD persistence continued to operate as independent, additive correlates of substance use risk. Our findings suggest a circumscribed role for depression in substance use risk that adds to, but does not alter or explain, ADHD-related risk.

ObjectiveNeuroimaging 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.MethodsCortical 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).ResultsIn 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.ConclusionsSubtle 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.

Many students with reading difficulties and disabilities (RD) also have Attention Deficit/Hyperactivity Disorder (ADHD). This randomized clinical trial compared the effects of ADHD treatment alone (medication, parent training), intensive reading intervention alone, and their combination on the reading fluency and comprehension of students with both disorders. Students with ADHD and RD were randomly assigned to receive (a) Reading Intervention only (n = 74), (b) ADHD Treatment only (n = 78), or (c) simultaneous Combined ADHD and RD Treatment (n = 70). For phonemic decoding fluency, the Reading Intervention group and the Combined Treatment group both had significantly better outcomes than the ADHD Treatment group, but did not differ from one another. For passage comprehension, the ADHD Treatment group had significantly better outcomes than the Reading Intervention group, while the other groups did not differ from one another. ADHD treatment may support passage comprehension in this population, while fluent decoding is best supported through intensive reading intervention.

BACKGROUND:Inconsistent findings exist regarding long-term substance use (SU) risk for children diagnosed with attention-deficit/hyperactivity disorder (ADHD). The observational follow-up of the Multimodal Treatment Study of Children with ADHD (MTA) provides an opportunity to assess long-term outcomes in a large, diverse sample. METHODS:Five hundred forty-seven children, mean age 8.5, diagnosed with DSM-IV combined-type ADHD and 258 classmates without ADHD (local normative comparison group; LNCG) completed the Substance Use Questionnaire up to eight times from mean age 10 to mean age 25. RESULTS:In adulthood, weekly marijuana use (32.8% ADHD vs. 21.3% LNCG) and daily cigarette smoking (35.9% vs. 17.5%) were more prevalent in the ADHD group than the LNCG. The cumulative record also revealed more early substance users in adolescence for ADHD (57.9%) than LNCG (41.9%), including younger first use of alcohol, cigarettes, marijuana, and illicit drugs. Alcohol and nonmarijuana illicit drug use escalated slightly faster in the ADHD group in early adolescence. Early SU predicted quicker SU escalation and more SU in adulthood for both groups. CONCLUSIONS:Frequent SU for young adults with childhood ADHD is accompanied by greater initial exposure at a young age and slightly faster progression. Early SU prevention and screening is critical before escalation to intractable levels.

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

ObjectiveRecent results from the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (ADHD; MTA) have demonstrated impairments in several functioning domains in adults with childhood ADHD. The childhood predictors of these adult functional outcomes are not adequately understood. The objective of the present study was to determine the effects of childhood demographic, clinical, and family factors on adult functional outcomes in individuals with and without childhood ADHD from the MTA cohort.MethodRegressions were used to determine associations of childhood factors (age range 7-10 years) of family income, IQ, comorbidity (internalizing, externalizing, and total number of non-ADHD diagnoses), parenting styles, parental education, number of household members, parental marital problems, parent-child relationships, and ADHD symptom severity with adult outcomes (mean age 25 years) of occupational functioning, educational attainment, emotional functioning, sexual behavior, and justice involvement in participants with (n = 579) and without (n = 258) ADHD.ResultsPredictors of adult functional outcomes in ADHD included clinical factors such as baseline ADHD severity, IQ, and comorbidity; demographic factors such as family income, number of household members and parental education; and family factors such as parental monitoring and parental marital problems. Predictors of adult outcomes were generally comparable for children with and without ADHD.ConclusionChildhood ADHD symptoms, IQ, and household income levels are important predictors of adult functional outcomes. Management of these areas early on, through timely treatments for ADHD symptoms, and providing additional support to children with lower IQ and from households with low incomes, could assist in improving adult functioning.

BackgroundThe Multimodal Treatment Study (MTA) began as a 14-month randomized clinical trial of behavioral and pharmacological treatments of 579 children (7-10 years of age) diagnosed with attention-deficit/hyperactivity disorder (ADHD)-combined type. It transitioned into an observational long-term follow-up of 515 cases consented for continuation and 289 classmates (258 without ADHD) added as a local normative comparison group (LNCG), with assessments 2-16 years after baseline.MethodsPrimary (symptom severity) and secondary (adult height) outcomes in adulthood were specified. Treatment was monitored to age 18, and naturalistic subgroups were formed based on three patterns of long-term use of stimulant medication (Consistent, Inconsistent, and Negligible). For the follow-up, hypothesis-generating analyses were performed on outcomes in early adulthood (at 25 years of age). Planned comparisons were used to estimate ADHD-LNCG differences reflecting persistence of symptoms and naturalistic subgroup differences reflecting benefit (symptom reduction) and cost (height suppression) associated with extended use of medication.ResultsFor ratings of symptom severity, the ADHD-LNCG comparison was statistically significant for the parent/self-report average (0.51 ± 0.04, p

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 (n = 23); (2) individuals with ADHD who do not currently use cannabis (n = 22); (3) comparisons who currently use cannabis (n = 15); and (4) comparisons who do not currently use cannabis (n = 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.

Objective: Examine patterns and predictors of skill learning during multisession Enhanced FO rward C oncentration and A ttention L earning (FOCAL+) training. Background: FOCAL+ teaches teens to reduce the duration of off-road glances using real-time error learning. In a randomized controlled trial, teens with ADHD received five sessions of FOCAL+ training and demonstrated significant reductions in extended glances (>2-s) away from the roadway (i.e., long-glances) and a 40% reduced risk of a crash/near-crash event. Teens' improvement in limiting long-glances as assessed after each FOCAL+ training session has not been examined. Method: Licensed teen (ages 16–19) drivers with ADHD (n = 152) were randomly assigned to five sessions of either FOCAL+ or modified standard driver training. Teens completed driving simulation assessments at baseline, after each training session, and 1 month and 6 months posttraining. Naturalistic driving was monitored for one year. Results: FOCAL+ training produced a 53% maximal reduction in long-glances during postsession simulated driving. The number of sessions needed to achieve maximum performance varied across participants. However, after five FOCAL+ training sessions, number of long-glances was comparable irrespective of when teens achieved their maximum performance. The magnitude of reduction in long-glances predicted levels of long-glances during simulated driving at 1 month and 6 months posttraining but not naturalistic driving outcomes. FOCAL+ training provided the most benefit during training to teens who were younger and had less driving experience. Conclusion: FOCAL+ training significantly reduces long-glances beginning at the 1st training session. Application: Providing five FOCAL+ training sessions early on during teen driving may maximize benefit. [ABSTRACT FROM AUTHOR]

ObjectiveTo compare educational, occupational, legal, emotional, substance use disorder, and sexual behavior outcomes in young adults with persistent and desistent attention-deficit/hyperactivity disorder (ADHD) symptoms and a local normative comparison group (LNCG) in the Multimodal Treatment Study of Children with ADHD (MTA).MethodData were collected 12, 14, and 16 years postbaseline (mean age 24.7 years at 16 years postbaseline) from 476 participants with ADHD diagnosed at age 7 to 9 years, and 241 age- and sex-matched classmates. Probands were subgrouped on persistence versus desistence of DSM-5 symptom count. Orthogonal comparisons contrasted ADHD versus LNCG and symptom-persistent (50%) versus symptom-desistent (50%) subgroups. Functional outcomes were measured with standardized and demographic instruments.ResultsThree patterns of functional outcomes emerged. Post-secondary education, times fired/quit a job, current income, receiving public assistance, and risky sexual behavior showed the most common pattern: the LNCG group fared best, symptom-persistent ADHD group worst, and symptom-desistent ADHD group between, with the largest effect sizes between LNCG and symptom-persistent ADHD. In the second pattern, seen with emotional outcomes (emotional lability, neuroticism, anxiety disorder, mood disorder) and substance use outcomes, the LNCG and symptom-desistent ADHD group did not differ, but both fared better than the symptom-persistent ADHD group. In the third pattern, noted with jail time (rare), alcohol use disorder (common), and number of jobs held, group differences were not significant. The ADHD group had 10 deaths compared to one death in the LNCG.ConclusionAdult functioning after childhood ADHD varies by domain and is generally worse when ADHD symptoms persist. It is important to identify factors and interventions that promote better functional outcomes.

ObjectiveTo determine childhood factors that predict attention-deficit/hyperactivity disorder (ADHD) persistence and desistence in adulthood.MethodRegression analyses were used to determine associations between childhood factors and adult ADHD symptom persistence in 453 participants (mean age, 25 years) from the Multimodal Treatment Study of Children with ADHD (MTA). Childhood IQ, total number of comorbidities, child-perceived parenting practices, child-perceived parent-child relationships, parental mental health problems, marital problems of parents, household income levels, and parental education were assessed at a mean age of 8 years in all participants. Adult ADHD persistence was defined using DSM-5 symptom counts either with or without impairment, as well as mean ADHD symptom scores on the Conners' Adult ADHD Rating Scale (CAARS). Age, sex, MTA site, and childhood ADHD symptoms were covaried.ResultsThe most important childhood predictors of adult ADHD symptom persistence were initial ADHD symptom severity (odds ratio [OR] = 1.89, standard error [SE] = 0.28, p = .025), comorbidities (OR = 1.19, SE = 0.07, p = .018), and parental mental health problems (OR = 1.30, SE = 0.09, p = .003). Childhood IQ, socioeconomic status, parental education, and parent-child relationships showed no associations with adult ADHD symptom persistence.ConclusionInitial ADHD symptom severity, parental mental health, and childhood comorbidity affect persistence of ADHD symptoms into adulthood. Addressing these areas early may assist in reducing adult ADHD persistence and functioning problems.

Children diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for substance abuse. Response inhibition is a hallmark of ADHD, yet the combined effects of ADHD and regular substance use on neural networks associated with response inhibition are unknown. Task-based functional Magnetic Resonance Imaging (fMRI) data from young adults with childhood ADHD with (n = 25) and without (n = 25) cannabis use ≥ monthly in the past year were compared with a local normative comparison group (LNCG) with (n = 11) and without (n = 12) cannabis use. Go/NoGo behavioral and fMRI data were evaluated for main and interaction effects of ADHD diagnosis and cannabis use. ADHD participants made significantly more commission errors on NoGo trials than controls. ADHD participants also had less frontoparietal and frontostriatal activity, independent of cannabis use. No main effects of cannabis use on response inhibition or functional brain activation were observed. An interaction of ADHD diagnosis and cannabis use was found in the right hippocampus and cerebellar vermis, with increased recruitment of these regions in cannabis-using controls during correct response inhibition. ADHD participants had impaired response inhibition combined with less fronto-parietal/striatal activity, regardless of cannabis use history. Cannabis use did not impact behavioral response inhibition. Cannabis use was associated with hippocampal and cerebellar activation, areas rich in cannabinoid receptors, in LNCG but not ADHD participants. This may reflect recruitment of compensatory circuitry in cannabis using controls but not ADHD participants. Future studies targeting hippocampal and cerebellar-dependent function in these groups may provide further insight into how this circuitry is altered by ADHD and cannabis use.

Response inhibition deficits are widely believed to be at the core of Attention-Deficit Hyperactivity Disorder (ADHD). Several studies have examined neural architectural correlates of ADHD, but research directly examining structural correlates of response inhibition is lacking. Here we examine the relationship between response inhibition as measured by a Go/No Go task, and cortical surface area and thickness of the caudal inferior frontal gyrus (cIFG), a region implicated in functional imaging studies of response inhibition, in a sample of 114 young adults with and without ADHD diagnosed initially during childhood. We used multiple linear regression models to test the hypothesis that Go/No Go performance would be associated with cIFG surface area or thickness. Results showed that poorer Go/No Go performance was associated with thicker cIFG cortex, and this effect was not mediated by ADHD status or history of substance use. However, independent of Go/No Go performance, persistence of ADHD symptoms and more frequent cannabis use were associated with thinner cIFG. Go/No Go performance was not associated with cortical surface area. The association between poor inhibitory functioning and thicker cIFG suggests that maturation of this region may differ in low performing participants. An independent association of persistent ADHD symptoms and frequent cannabis use with thinner cIFG cortex suggests that distinct neural mechanisms within this region may play a role in inhibitory function, broader ADHD symptomatology, and cannabis use. These results contribute to Research Domain Criteria (RDoC) by revealing novel associations between neural architectural phenotypes and basic neurobehavioral processes measured dimensionally.

BackgroundBoth Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults.MethodsParticipants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness.ResultsAfter controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness.DiscussionYoung adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD.

Executive functioning (EF) abilities develop through childhood, but this development can be impacted by various psychosocial environmental influences. Using longitudinal data from the Health Outcome and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort study, we examined if psychosocial environmental factors were significant predictors of EF development. Study participants comprised 271 children and their primary caregivers (98.5% mothers) followed from birth to age 12. We identified four distinct EF developmental trajectory groups comprising a consistently impaired group (13.3%), a descending impairment group (27.7%), an ascending impairment group (9.95%), and a consistently not impaired group (49.1%). Higher levels of maternal ADHD and relational frustration appear to be risk factors for increased EF difficulty over time, while higher family income may serve as a protective factor delaying predisposed EF impairment. Important intervention targets might include teaching positive and effective parenting strategies to mothers whose children are at risk for EF dysfunction. [ABSTRACT FROM AUTHOR]

Evidence suggests that higher order linguistic functioning such as text comprehension is particularly vulnerable to emotional modulation. Gender has been identified as an important moderating variable in emotional expression such that girls tend toward internalizing emotions (e.g., sadness, anxiety) whereas boys tend toward externalizing emotions (e.g., anger, combativeness), which may influence the relationship between emotion and text comprehension. The present study examined whether gender moderates the relationship between emotional-behavioral problems and text comprehension among children (n = 187; boys = 115, girls = 72) with both word reading difficulties (RD) and attention-deficit/hyperactivity disorder (ADHD), a sample widely acknowledged to be at increased risk for developing emotional-behavioral problems such as anxiety, poor academic self-concept, and delinquency. A moderated regression analysis tested for the significance of two separate interaction terms (i.e., gender × externalizing problems, gender × internalizing problems) after controlling for gender, IQ, basic reading skills, cognitive-linguistic processes closely related to reading, attentional problems, internalizing problems, and externalizing problems. Results indicated that gender significantly and uniquely moderates the relationship between emotional-behavioral problems and text comprehension. Specifically, text comprehension was relatively lower among girls with relatively higher externalizing problems, whereas no such association was observed among boys. These results contribute to our understanding of cognition-emotion interactions within reading development and raise important implications.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) and cannabis use are each associated with specific cognitive deficits. Few studies have investigated the neurocognitive profile of individuals with both an ADHD history and regular cannabis use. The greatest cognitive impairment is expected among ADHD Cannabis Users compared to those with ADHD-only, Cannabis use-only, or neither.MethodsYoung adults (24.2±1.2 years) with a childhood ADHD diagnosis who did (n=42) and did not (n=45) report past year ≥ monthly cannabis use were compared on neuropsychological measures to a local normative comparison group (LNCG) who did (n=20) and did not (n=21) report past year regular cannabis use. Age, gender, IQ, socioeconomic status, and past year alcohol and smoking were statistical covariates.ResultsThe ADHD group performed worse than LNCG on verbal memory, processing speed, cognitive interference, decision-making, working memory, and response inhibition. No significant effects for cannabis use emerged. Interactions between ADHD and cannabis were non-significant. Exploratory analyses revealed that individuals who began using cannabis regularly before age 16 (n=27) may have poorer executive functioning (i.e., decision-making, working memory, and response inhibition), than users who began later (n=32); replication is warranted with a larger sample.ConclusionsA childhood diagnosis of ADHD, but not cannabis use in adulthood, was associated with executive dysfunction. Earlier initiation of cannabis use may be linked to poor cognitive outcomes and a significantly greater proportion of the ADHD group began using cannabis before age 16. Regular cannabis use starting after age 16 may not be sufficient to aggravate longstanding cognitive deficits characteristic of ADHD.

ObjectivesTo determine long-term effects on substance use and substance use disorder (SUD), up to 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the multisite Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA; n=436); to test whether (a) medication at follow-up, (b) cumulative psychostimulant treatment over time, or (c) both relate to substance use/SUD; to compare substance use/SUD in the ADHD sample to the non-ADHD childhood classmate comparison group (n=261).MethodMixed-effects regression models with planned contrasts were used for all tests except the important cumulative stimulant treatment question, for which propensity score matching analysis was used.ResultsThe originally randomized treatment groups did not differ significantly on substance use/SUD by the 8 year follow-up or earlier (M age = 17 years). Neither medication at follow-up (mostly stimulants) nor cumulative stimulant treatment was associated with adolescent substance use/SUD. Substance use at all time points, including use of two or more substances and SUD, were each greater in the ADHD than non-ADHD samples, regardless of sex.ConclusionsMedication for ADHD did not protect from, nor contribute to, visible risk of substance use or SUD by adolescence, whether analyzed as randomized treatment assignment in childhood, as medication at follow-up, or as cumulative stimulant treatment over an 8 year follow-up from childhood. These results suggest the need to identify alternative or adjunctive adolescent-focused approaches to substance abuse prevention and treatment for boys and girls with ADHD, especially given their increased risk for use and abuse of multiple substances that is not improved with stimulant medication. Clinical trial registration information—Multimodal Treatment Study of Children with Attention Deficit and Hyperactivity Disorder (MTA); http://clinical trials.gov/; NCT00000388.