Nóra Bunford

The goal of this review is to provide an updated evaluation of the reliability and validity of ADHD assessment measures since the last comprehensive review. Using an empirical rationale for measure selection, we evaluated measures with a revised version of the Rubric for Evaluating Norms, Validity, and Utility. The ADHD-RS, Conners, SNAP, and Vanderbilt scales had at least adequate descriptive information and excellent sensitivity to treatment, with most also showing adequate internal reliability and construct validity. Few studies examined clinical interviews and information was insufficient on most indices; only the DISC and K-SADS demonstrated adequate construct validity. Neuropsychological tests generally had adequate descriptive information, reliability, and construct validity, but discriminative validity and treatment sensitivity varied, with BRIEF values possibly inflated. Findings on impairment rating scales were mixed, though the AAPC, COSS, and IRS showed excellent sensitivity to treatment, and the IRS demonstrated broader reliability and validity. Strikingly little work addressed interrater or retest reliability, content validity, or generalization of reliability or validity. Reporting of ethnicity/race, SES, and medication status was inconsistent. Although concerns about reporting design constraints were raised a decade ago, we found no improvement in this regard: internal reliability was reported in only 18% of studies and assumptions were rarely tested. We recommend more rigorous empirical research and further revisions to the rubric to advance reproducible science.

In attention-deficit/hyperactivity disorder (ADHD), emotional features account for heterogeneity and exacerbate severity of behavioral and functional impairments, beyond cognitive and comorbidity features. Yet, debate remains about the extent to which, in ADHD, such emotional features are a “core feature”, i.e. whether ADHD should be conceptualized as encompassing difficulties with regulating not only activity, attention, and impulses but also processing and regulating emotions. We aimed to address this issue by examining the extent to which in adolescents, ADHD polygenic scores (PGSs) are associated with electrophysiological indices of affective-motivational processing, measured during a monetary punishment/reward feedback paradigm. ADHD PGSs were negatively associated, in n = 166 adolescents (M _age = 15.76 years, SD = 1.07; 42.77% girls), with amplitude values of an occipitoparietal event-related potential (i.e. late positive potential) and were positively associated, in n = 84 adolescents (M _age = 15.76 years, SD = 1.05; 41.67% girls), with fronto-centro-parietal alpha event-related desynchronization. Across analyses, covariates were anxiety, depression, and ADHD with comorbid disruptive behavior disorder PGSs; ADHD, internalizing, and oppositional defiant disorder severity; childhood maltreatment; current ADHD medication; and baseline values of the outcome. Findings were replicated in sensitivity analyses with blocks of conceptually related covariates entered separately. In adolescents, electrophysiological indices of affective-motivational processing are associated principally with genetic liability for ADHD but not comorbidity genetic liability or comorbidity manifest symptoms.

A delay in brain maturation is a hypothesized pathomechanism of attention-deficit/hyperactivity disorder (ADHD). Differences in emotion regulation are associated with phenotypic and prognostic heterogeneity in ADHD. The development of emotion regulation is driven, in part, by brain maturation. Whether the difference between an individual’s brain age predicted by machine-learning algorithms trained on neuroimaging data and that individual’s chronological age, i.e. brain-predicted age difference (brain-PAD) predicts differences in emotion regulation, and whether ADHD problems add to this prediction is unknown. Using data from the Adolescent Brain Cognitive Development Study, we examined, in 2711 children (M _age = 120.09 months, SD = 7.61; 54.15% female; 61.23% white), whether adjusting for action cancellation (inhibition), age, sex assigned at birth, psychotropic treatment, and pubertal status, brain-PAD in late childhood predicts self-reported emotion regulation in early adolescence (at 3-year follow-up), and whether parent-reported ADHD problems predict self-reported emotion regulation above and beyond brain-PAD. Greater brain-PAD predicted greater expressive suppression (b = 0.172, SE = 0.051, p _FDR = 0.004), whereas ADHD problems did not (b = 0.041, SE = 0.022, p _FDR = 0.124), model marginal R ² = 0.020. This pattern of results was replicated across sensitivity tests. Neither brain-PAD, nor ADHD problems predicted cognitive reappraisal, p _FDRs = 0.734. Clinically, consistent with earlier findings linking greater brain-PAD to psychopathology, we observed that greater brain-PAD in childhood—but not ADHD problems—predicted expressive suppression in early adolescence. Expressive suppression is implicated in the etiology, maintenance, and treatment of numerous psychopathologies, highlighting the relevance of brain-PAD in understanding developmental risk mechanisms. Conceptually, these findings further validate brain-PAD as a valuable tool for advancing developmental neuroscience.

Attention-deficit/hyperactivity disorder (ADHD) is associated with emotion dysregulation (ED) and in ADHD, beyond ADHD and comorbidity severity, ED confers increased risk for negative outcomes. First- and second-line ADHD pharmacotherapy is effective at ameliorating core symptoms and improving cognitive functioning and accumulating evidence indicates primairly in children and adults, active ADHD pharmacotherapy has beneficial effects on emotional symptoms. Gaps in knowledge remain about whether in adolescents, ADHD pharmacotherapy has beneficial effects on ED or about the extent to which effects are apparent for discontinued/ past ADHD pharmacotherapy. Examined, in N = 297 adolescents (Mage=15.77 years, SD = 1.06; 39.06% girls; n = 86 classified as with ADHD), whether accounting for depression and oppositional symptoms, concurrent and 18-month prospective measures of parent- and self-reported ED (1) differ across adolescents without ADHD, medication-naïve adolescents with ADHD, and ever-medicated (currently or previously) adolescents with ADHD. In case of parent-reported ED, ever medicated adolescents with ADHD exhibited a decline in ED over time whereas adolescents without ADHD and never medicated adolescents with ADHD exhibited no changes in ED over time. In case of self-reported ED, ever-medicated adolescents with ADHD exhibited lower ED than never medicated adolescents with ADHD and never medicated adolescents with ADHD exhibited greater ED than adolescents without ADHD. Currently and previously (but not currently) medicated adolescents did not differ in ED. Across parent- and self-reported findings, observed pattern of results held when analyses focused on adolescents who did not change medication status between baseline and follow-up. ADHD pharmacotherapy may have a boosting effect on longitudinal changes in parent-reported ED and a normalizing effect on concurrent measures of self-reported ED in adolescents.

The attention-deficit/hyperactivity disorder (ADHD) clinical phenotype has limitations for deciphering ADHD etiology and predicting prognosis. Although relative to the clinical phenotype, intermediate phenotypes may have better explanatory and prognostic power, the extent to which ADHD intermediate phenotypes are associated with ADHD risk and prognosis is unknown. The aim of this study was to evaluate evidence for event-related potential (ERP) measures of reward anticipation as ADHD risk and prognostic biomarkers. We examined, whether (1) in a sample of adolescents (N = 304; M _age = 15.78 years, SD = 1.08; 39.5% female), accounting for the effects of age, sex, ADHD severity and depression, ERPs are associated with ADHD polygenic risk scores (PRSs) (ADHD risk) and (2) in a sample of adolescents at-risk for ADHD (n = 99; M _age = 15.78 years, SD = 1.08; 39.5% female), accounting for the effects of age, sex, ADHD severity, depression, and baseline outcome values, ERPs are associated, prospectively, with alcohol misuse (ADHD prognosis). In adolescents, greater ADHD PRSs were associated with lower electrophysiological anticipatory attention to motivationally relevant feedback (b = −0.115, p = .046 95%CI [−0.228; −0.002]). The predictors accounted for 5% of the variance in the outcome. In adolescents at-risk for ADHD, at 18-month follow-up, lower electrophysiological anticipatory attention to motivationally relevant feedback was associated with greater alcohol consumption (b = −7.454, p = .007, 95%CI [−12.873; −2.034]). The predictors accounted for 31% of the variance in this outcome. These findings were replicated in sensitivity analyses with behavioral performance variables added as covariates. The current findings support the hypothesis that ERP amplitudes of reward anticipation may be ADHD risk and prognostic biomarkers and suggest that intermediate phenotypes may confer advantages over the ADHD clinical phenotype in delineating etiology and predicting prognosis.

A compelling hypothesis about attention-deficit/hyperactivity disorder (ADHD) etiopathogenesis is that the ADHD phenotype reflects a delay in cortical maturation. Slow-wave activity (SWA) of non-rapid eye movement (NREM) sleep electroencephalogram (EEG) is an electrophysiological index of sleep intensity reflecting cortical maturation. Available data on ADHD and SWA are conflicting, and developmental differences, or the effect of pharmacological treatment, are relatively unknown. We examined, in samples (M_age= 16.4, SD = 1.2), of ever-medicated adolescents at risk for ADHD (n = 18; 72% boys), medication-naïve adolescents at risk for ADHD (n = 15, 67% boys), and adolescents not at risk for ADHD (n = 31, 61% boys) matched for chronological age and controlling for non-ADHD pharmacotherapy, whether ADHD pharmacotherapy modulates the association between NREM SWA and ADHD risk in home sleep. Findings indicated medication-naïve adolescents at risk for ADHD exhibited greater first sleep cycle and entire night NREM SWA than both ever-medicated adolescents at risk for ADHD and adolescents not at risk for ADHD and no difference between ever-medicated, at-risk adolescents, and not at-risk adolescents. Results support atypical cortical maturation in medication-naïve adolescents at risk for ADHD that appears to be normalized by ADHD pharmacotherapy in ever-medicated adolescents at risk for ADHD. Greater NREM SWA may reflect a compensatory mechanism in middle-later adolescents at risk for ADHD that normalizes an earlier occurring developmental delay.

Understanding atypicalities in ADHD brain correlates is a step towards better understanding ADHD etiology. Efforts to map atypicalities at the level of brain structure have been hindered by the absence of normative reference standards. Recent publication of brain charts allows for assessment of individual variation relative to age- and sex-adjusted reference standards and thus estimation not only of case-control differences but also of intraindividual prediction. Methods. Aim was to examine, whether brain charts can be applied in a sample of adolescents (N = 140, 38% female) to determine whether atypical brain subcortical and total volumes are associated with ADHD at-risk status and severity of parent-rated symptoms, accounting for self-rated anxiety and depression, and parent-rated oppositional defiant disorder (ODD) as well as motion. Results. Smaller bilateral amygdala volume was associated with ADHD at-risk status, beyond effects of comorbidities and motion, and smaller bilateral amygdala volume was associated with inattention and hyperactivity/impulsivity, beyond effects of comorbidities except for ODD symptoms, and motion. Conclusions. Individual differences in amygdala volume meaningfully add to estimating ADHD risk and severity. Conceptually, amygdalar involvement is consistent with behavioral and functional imaging data on atypical reinforcement sensitivity as a marker of ADHD-related risk. Methodologically, results show that brain chart reference standards can be applied to address clinically informative, focused and specific questions.