Joint polygenic and environmental risks for childhood attention-deficit/hyperactivity disorder (ADHD) and ADHD symptom dimensions.

Background: attention-deficit/hyperactivity disorder (ADHD) is associated with both polygenic liability and environmental exposures, both intrinsic to the family, such as family conflict, and extrinsic, such as air pollution. However, much less is known about the interplay between environmental and genetic risks relevant to ADHD-a better understanding of which could inform both mechanistic models and clinical prediction algorithms. Methods: Two independent data sets, the population-based Adolescent Brain Cognitive Development Study (ABCD) (N = 11,876) and the case-control Oregon-ADHD-1000 (N = 1449), were used to examine additive (G + E) and interactive (GxE) effects of selected polygenic risk scores (PRS) and environmental factors in a cross-sectional design. Genetic risk was measured using PRS for nine mental health disorders/traits. Exposures included family income, family conflict/negative sentiment, and geocoded measures of area deprivation, lead exposure risk, and air pollution exposure (nitrogen dioxide and fine particulate matter). Results: ADHD PRS and family conflict jointly predicted concurrent ADHD symptoms in both cohorts. Additive-effects models, including both genetic and environmental factors, explained significantly more variation in symptoms than any individual factor alone (joint R 2 = .091 for total symptoms in ABCD; joint R 2 = .173 in Oregon-ADHD-1000; all delta-R 2 p-values <2e-7). Significant effect size heterogeneity across ancestry groups was observed for genetic and environmental factors (e.g., Q = 9.01, p = .011 for major depressive disorder PRS; Q = 13.34, p = .001 for area deprivation). GxE interactions observed in the full ABCD cohort suggested stronger environmental effects when genetic risk is low, though they did not replicate. Conclusions: Reproducible additive effects of PRS and family environment on ADHD symptoms were found, but GxE interaction effects were not replicated and appeared confounded by ancestry. Results highlight the potential value of combining exposures and PRS in clinical prediction algorithms. The observed differences in risks across ancestry groups warrant further study to avoid health care disparities.

Prediction of Attention-Deficit/Hyperactivity Disorder Diagnosis Using Brief, Low-Cost Clinical Measures: A Competitive Model Evaluation.

Proper diagnosis of ADHD is costly, requiring in-depth evaluation via interview, multi-informant and observational assessment, and scrutiny of possible other conditions. The increasing availability of data may allow the development of machine-learning algorithms capable of accurate diagnostic predictions using low-cost measures to supplement human decision-making. We report on the performance of multiple classification methods used to predict a clinician-consensus ADHD diagnosis. Methods ranged from fairly simple (e.g., logistic regression) to more complex (e.g., random forest), while emphasizing a multi-stage Bayesian approach. Classifiers were evaluated in two large (N>1000), independent cohorts. The multi-stage Bayesian classifier provides an intuitive approach consistent with clinical workflows, and was able to predict expert consensus ADHD diagnosis with high accuracy (>86%)-though not significantly better than other methods. Results suggest that parent and teacher surveys are sufficient for high-confidence classifications in the vast majority of cases, while an important minority require additional evaluation for accurate diagnosis.

The Oregon ADHD-1000: A new longitudinal data resource enriched for clinical cases and multiple levels of analysis.

The fields of developmental psychopathology, developmental neuroscience, and behavioral genetics are increasingly moving toward a data sharing model to improve reproducibility, robustness, and generalizability of findings. This approach is particularly critical for understanding attention-deficit/hyperactivity disorder (ADHD), which has unique public health importance given its early onset, high prevalence, individual variability, and causal association with co-occurring and later developing problems. A further priority concerns multi-disciplinary/multi-method datasets that can span different units of analysis. Here, we describe a public dataset using a case-control design for ADHD that includes: multi-method, multi-measure, multi-informant, multi-trait data, and multi-clinician evaluation and phenotyping. It spans > 12 years of annual follow-up with a lag longitudinal design allowing age-based analyses spanning age 7-19 + years with a full age range from 7 to 21. Measures span genetic and epigenetic (DNA methylation) array data; EEG, functional and structural MRI neuroimaging; and psychophysiological, psychosocial, clinical and functional outcomes data. The resource also benefits from an autism spectrum disorder add-on cohort and a cross sectional case-control ADHD cohort from a different geographical region for replication and generalizability. Datasets allowing for integration from genes to nervous system to behavior represent the "next generation" of researchable cohorts for ADHD and developmental psychopathology.

A preliminary study of white matter correlates of a laboratory measure of attention and motor stability in attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a complex behavioral disorder, often difficult and time consuming to diagnose. Laboratory assessment of ADHD-related constructs of attention and motor activity may be helpful in elucidating neurobiology; however, neuroimaging studies evaluating laboratory measures of ADHD are lacking. In this preliminary study, we assessed the association between fractional anisotropy (FA), a measure of white matter microstructure, and laboratory measures of attention and motor behavior using the QbTest, a widely used measure thought to improve clinician diagnostic confidence. This is the first look at neural correlates of this widely used measure. The sample included adolescents and young adults (ages 12-20, 35% female) with ADHD (n = 31) and without (n = 52). As expected, ADHD status was associated with motor activity, and cognitive inattention and impulsivity in the laboratory. With regard to MRI findings, laboratory observed motor activity and inattention were associated with greater FA in white matter regions of the primary motor cortex. All three laboratory observations were associated with lower FA in regions subserving fronto-striatal-thalamic and frontoparietal (i.e. superior longitudinal fasciculus) circuitry. Further, FA in white matter regions of the prefrontal cortex appeared to mediate the relationship between ADHD status and motor activity on the QbTest. These findings, while preliminary, suggest that performance on certain laboratory tasks is informative with regard to neurobiological correlates of subdomains of the complex ADHD phenotype. In particular, we provide novel evidence for a relationship between an objective measure of motor hyperactivity and white matter microstructure in motor and attentional networks.

Longitudinal network model of the co-development of temperament, executive functioning, and psychopathology symptoms in youth with and without ADHD.

Attention Deficit Hyperactivity Disorder (ADHD) is a common, chronic, and impairing disorder, yet presentations of ADHD and clinical course are highly heterogeneous. Despite substantial research efforts, both (a) the secondary co-occurrence of ADHD and complicating additional clinical problems and (b) the developmental pathways leading toward or away from recovery through adolescence remain poorly understood. Resolving these requires accounting for transactional influences of a large number of features across development. Here, we applied a longitudinal cross-lagged panel network model to a multimodal, multilevel dataset in a well-characterized sample of 488 children (nADHD=296) to test Research Domain Criteria initiative-inspired hypotheses about transdiagnostic risk. Network features included DSM symptoms, trait-based ratings of emotional functioning (temperament), and performance-based measures of cognition. Results confirmed that ADHD symptom domains, temperamental Irritability, and Working Memory are independent transdiagnostic risk factors for psychopathology based on their direct associations with other features across time. ADHD symptoms and working memory each had direct, independent associations with depression. Results also demonstrated tightly linked co-development of ADHD symptoms and temperamental Irritability, consistent with the possibility that this type of anger dysregulation is a core feature that is co-expressed as part of the ADHD phenotype for some children.

Is the Association of ADHD with Socio-Economic Disadvantage Explained by Child Comorbid Externalizing Problems or Parent ADHD?

It has been unclear whether an associations of child ADHD with socio-economic disadvantage (SES) could be accounted for by (a) parental ADHD explaining both low SES and child ADHD, and/or (b) the joint overlap of ODD or CD with low SES and ADHD. Study 1 used a community-recruited case-control sample with detailed evaluation of SES indicators, child ADHD, child externalizing, and parent ADHD symptoms (n = 931 children, 521 ADHD, 577 boys, 354 girls) in a path modeling analysis with latent variables. Study 2 evaluated ADHD and externalizing behavior in a regression model using a poverty index for SES, in 70,927 children (48.2% female) aged 5-17 years from the US 2011-2012 National Survey of Children's Health (NSCH). In Study 1, lower SES was related to the ADHD latent variable, ß = -.18, p < .001; 95%CI [-.25,-.12]. This effect held when parent ADHD and child ODD and CD were in the model, ß = -.11, p < .01, 95% CI [-.09,-.03], equivalent to OR = 1.50, 95% CI[1.12-2.04]). In Study 2, these results replicated. Adjusting only for age and sex, children from families who were below 200% of the federal poverty line were more likely to have moderate or severe ADHD than no ADHD, versus children above that line, OR = 2.13, 95% CI[1.79,2.54], p < .001. The effect held after adjusting for disruptive/externalizing problems, OR = 1.61, p < .01, 95%CI [1.32,1.96]. The effect size for comparable models was similar across both studies, lending higher confidence to the results. It is concluded that the SES association with child ADHD is not explained by artifact and requires a mechanistic explanation.

Heterogeneity in development of aspects of working memory predicts longitudinal attention deficit hyperactivity disorder symptom change.

The role of cognitive mechanisms in the clinical course of neurodevelopmental disorders is poorly understood. Attention Deficit Hyperactivity Disorder (ADHD) is emblematic in that numerous alterations in cognitive development are apparent, yet how they relate to changes in symptom expression with age is unclear. To resolve the role of cognitive mechanisms in ADHD, a developmental perspective that takes into account expected within-group heterogeneity is needed. METHOD: The current study uses an accelerated longitudinal design and latent trajectory growth mixture models in a sample of children ages 7-13 years carefully characterized as with (n = 437) and without (n = 297) ADHD to (a) identify heterogeneous developmental trajectories for response inhibition, visual spatial working memory maintenance, and delayed reward discounting and (b) to assess the relationships between these cognitive trajectories and ADHD symptom change. RESULTS: Best-fitting models indicated multiple trajectory classes in both the ADHD and typically developing samples, as well as distinct relationships between each cognitive process and ADHD symptom change. Developmental change in response inhibition and delayed reward discounting were unrelated to ADHD symptom change, while individual differences in the rate of visual spatial working memory maintenance improvement predicted symptom remission in ADHD. CONCLUSION: Characterizing heterogeneity in cognitive development will be crucial for clarifying mechanisms of symptom persistence and recovery. Results here suggest working memory maintenance may be uniquely related to ADHD symptom improvement. (PsycINFO Database Record

The Effects of Mindfulness-Based Intervention on Children's Attention Regulation.

OBJECTIVE: This article describes results from a randomized clinical trial of a mindfulness-based intervention for parents and children, Mindful Family Stress Reduction, on a behavioral measure of attention in youths, the Attention Network Task (ANT). METHOD: Forty-one parent-child dyads were randomly assigned to either the mindfulness-based intervention condition or a wait-list control. School-age youths completed the ANT before and after the intervention. RESULTS: Results demonstrate significant, medium-size ( f2 = -.16) intervention effects to the conflict monitoring subsystem of the ANT such that those in the intervention condition decreased in conflict monitoring more than those in the wait-list control. Youths in the intervention condition also showed improvements in their orienting subsystem scores, compared with controls. CONCLUSION: Mindfulness-based interventions for youths have potential utility to improve attentional self-regulation, and future research should consider incorporating measures of attention into interventions that use mindfulness training.

Peer contagion in child and adolescent social and emotional development.

In this article, we examine the construct of peer contagion in childhood and adolescence and review studies of child and adolescent development that have identified peer contagion influences. Evidence suggests that children's interactions with peers are tied to increases in aggression in early and middle childhood and amplification of problem behaviors such as drug use, delinquency, and violence in early to late adolescence. Deviancy training is one mechanism that accounts for peer contagion effects on problem behaviors from age 5 through adolescence. In addition, we discuss peer contagion relevant to depression in adolescence, and corumination as an interactive process that may account for these effects. Social network analyses suggest that peer contagion underlies the influence of friendship on obesity, unhealthy body images, and expectations. Literature is reviewed that suggests how peer contagion effects can undermine the goals of public education from elementary school through college and impair the goals of juvenile corrections systems. In particular, programs that "select" adolescents at risk for aggregated preventive interventions are particularly vulnerable to peer contagion effects. It appears that a history of peer rejection is a vulnerability factor for influence by peers, and adult monitoring, supervision, positive parenting, structure, and self-regulation serve as protective factors.