Bright light therapy versus physical exercise to prevent co-occurring depression in adolescents and young adults with attention-deficit/hyperactivity disorder: a multicentre, three-arm, randomised controlled, pilot phase-IIa trial.

Depression is common in attention-deficit/hyperactivity disorder (ADHD), but preventive behavioural interventions are lacking. This randomised controlled, pilot phase-IIa trial aimed to study a physical exercise intervention (EI) and bright light therapy (BLT)-both implemented and monitored in an individual, naturalistic setting via a mobile health (m-health) system-for feasibility of trial design and interventions, and to estimate their effects on depressive symptoms in young people with ADHD. Two hundred seven participants aged 14-45 years were randomised to 10-week add-on intervention of either BLT (10,000 lx; daily 30-min sessions) (n = 70), EI (aerobic and muscle-strengthening activities 3 days/ week) (n = 69), or treatment-as-usual (TAU) (n = 68), of whom 165 (80%) were retained (BLT: n = 54; EI: n = 52; TAU: n = 59). Intervention adherence (i.e. ≥ 80% completed sessions) was very low for both BLT (n = 13, 22%) and EI (n = 4, 7%). Usability of the m-health system to conduct interventions was limited as indicated by objective and subjective data. Safety was high and comparable between groups. Changes in depressive symptoms (assessed via observer-blind ratings, Inventory of Depressive Symptomatology) between baseline and end of intervention were small (BLT: -0.124 [95% CI: -2.219, 1.971], EI: -2.646 [95% CI: -4.777, -0.515], TAU: -1.428 [95% CI: -3.381, 0.526]) with no group differences [F(2,153) = 1.45, p = 0.2384]. These findings suggest that the m-health approach did not achieve feasibility of EI and BLT in young people with ADHD. Prior to designing efficacy studies, strategies how to achieve high intervention adherence should be specifically investigated in this patient group. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03371810, 13 December 2017.

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure.

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.

Event-related brain-oscillatory and ex-Gaussian markers of remission and persistence of ADHD.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) often persists into adolescence and adulthood, but the processes underlying persistence and remission remain poorly understood. We previously found that reaction time variability and event-related potentials of preparation-vigilance processes were impaired in ADHD persisters and represented markers of remission, as ADHD remitters were indistinguishable from controls but differed from persisters. Here, we aimed to further clarify the nature of the cognitive-neurophysiological impairments in ADHD and of markers of remission by examining the finer-grained ex-Gaussian reaction-time distribution and electroencephalographic (EEG) brain-oscillatory measures in ADHD persisters, remitters and controls. METHODS: A total of 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 age-matched controls were compared on ex-Gaussian (mu, sigma, tau) indices and time-frequency EEG measures of power and phase consistency from a reaction-time task with slow-unrewarded baseline and fast-incentive conditions ('Fast task'). RESULTS: Compared to controls, ADHD persisters showed significantly greater mu, sigma, tau, and lower theta power and phase consistency across conditions. Relative to ADHD persisters, remitters showed significantly lower tau and theta power and phase consistency across conditions, as well as lower mu in the fast-incentive condition, with no difference in the baseline condition. Remitters did not significantly differ from controls on any measure. CONCLUSIONS: We found widespread impairments in ADHD persisters in reaction-time distribution and brain-oscillatory measures. Event-related theta power, theta phase consistency and tau across conditions, as well as mu in the more engaging fast-incentive condition, emerged as novel markers of ADHD remission, potentially representing compensatory mechanisms in individuals with remitted ADHD.

Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments.

BACKGROUND: A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE). METHODS: The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8-40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses. RESULTS: When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, ß = 0.088, p = 0.02) but not for CE (R2 = 0.011, ß = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10). CONCLUSIONS: We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.

ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA): a multi-centre prospective cohort study protocol.

BACKGROUND: Emerging evidence points at substantial comorbidity between adult attention deficit hyperactivity disorder (ADHD) and cardiometabolic diseases, but our understanding of the comorbidity and how to manage cardiometabolic disease in adults with ADHD is limited. The ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) project uses remote measurement technology to obtain real-world data from daily life to assess the extent to which ADHD medication treatment and physical activity, individually and jointly, may influence cardiometabolic risks in adults with ADHD. Our second main aim is to obtain valuable real-world data on adherence to pharmacological treatment and its predictors and correlates during daily life from adults with ADHD. METHODS: ART-CARMA is a multi-site prospective cohort study within the EU-funded collaboration 'TIMESPAN' (Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients) that will recruit 300 adults from adult ADHD waiting lists. The participants will be monitored remotely over a period of 12 months that starts from pre-treatment initiation. Passive monitoring, which involves the participants wearing a wrist-worn device (EmbracePlus) and downloading the RADAR-base Passive App and the Empatica Care App on their smartphone, provides ongoing data collection on a wide range of variables, such as physical activity, sleep, pulse rate (PR) and pulse rate variability (PRV), systolic peaks, electrodermal activity (EDA), oxygen saturation (SpO2), peripheral temperature, smartphone usage including social connectivity, and the environment (e.g. ambient noise, light levels, relative location). By combining data across these variables measured, processes such as physical activity, sleep, autonomic arousal, and indicators of cardiovascular health can be captured. Active remote monitoring involves the participant completing tasks using a smartphone app (such as completing clinical questionnaires or speech tasks), measuring their blood pressure and weight, or using a PC/laptop (cognitive tasks). The ART system is built on the RADAR-base mobile-health platform. DISCUSSION: The long-term goal is to use these data to improve the management of cardiometabolic disease in adults with ADHD, and to improve ADHD medication treatment adherence and the personalisation of treatment.

Is association of preterm birth with cognitive-neurophysiological impairments and ADHD symptoms consistent with a causal inference or due to familial confounds?

BACKGROUND: Preterm birth is associated with an increased risk for cognitive-neurophysiological impairments and attention-deficit/hyperactivity disorder (ADHD). Whether the associations are due to the preterm birth insult per se, or due to other risk factors that characterise families with preterm-born children, is largely unknown. METHODS: We employed a within-sibling comparison design, using cognitive-performance and event-related potential (ERP) measures from 104 preterm-born adolescents and 104 of their term-born siblings. Analyses focused on ADHD symptoms and cognitive and ERP measures from a cued continuous performance test, an arrow flanker task and a reaction time task. RESULTS: Within-sibling analyses showed that preterm birth was significantly associated with increased ADHD symptoms (ß = 0.32, p = 0.01, 95% CI 0.05 to 0.58) and specific cognitive-ERP impairments, such as IQ (ß = -0.20, p = 0.02, 95% CI -0.40 to -0.01), preparation-vigilance measures and measures of error processing (ranging from ß = 0.71, -0.35). There was a negligible within-sibling association between preterm birth with executive control measures of inhibition (NoGo-P3, ß = -0.07, p = 0.45, 95% CI -0.33 to 0.15) or verbal working memory (digit span backward, ß = -0.05, p = 0.63, 95% CI -0.30 to 0.18). CONCLUSIONS: Our results suggest that the relationship between preterm birth with ADHD symptoms and specific cognitive-neurophysiological impairments (IQ, preparation-vigilance and error processing) is independent of family-level risk and consistent with a causal inference. In contrast, our results suggest that previously observed associations between preterm birth with executive control processes of inhibition and working memory are instead linked to background characteristics of families with a preterm-born child rather than preterm birth insult per se. These findings suggest that interventions need to target both preterm-birth specific and family-level risk factors.

Shared and Disorder-Specific Event-Related Brain Oscillatory Markers of Attentional Dysfunction in ADHD and Bipolar Disorder.

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) often present with overlapping symptoms and cognitive impairments, such as increased fluctuations in attentional performance measured by increased reaction-time variability (RTV). We previously provided initial evidence of shared and distinct event-related potential (ERP) impairments in ADHD and BD in a direct electrophysiological comparison, but no study to date has compared neural mechanisms underlying attentional impairments with finer-grained brain oscillatory markers. Here, we aimed to compare the neural underpinnings of impaired attentional processes in ADHD and BD, by examining event-related brain oscillations during a reaction-time task under slow-unrewarded baseline and fast-incentive conditions. We measured cognitive performance, ERPs and brain-oscillatory modulations of power and phase variability in 20 women with ADHD, 20 women with BD (currently euthymic) and 20 control women. Compared to controls, both ADHD and BD groups showed increased RTV in the baseline condition and increased RTV, theta phase variability and lower contingent negative variation in the fast-incentive condition. Unlike controls, neither clinical group showed an improvement from the slow-unrewarded baseline to the fast-incentive condition in attentional P3 amplitude or alpha power suppression. Most impairments did not differ between the disorders, as only an adjustment in beta suppression between conditions (lower in the ADHD group) distinguished between the clinical groups. These findings suggest shared impairments in women with ADHD and BD in cognitive and neural variability, preparatory activity and inability to adjust attention allocation and activation. These overlapping impairments may represent shared neurobiological mechanisms of attentional dysfunction in ADHD and BD, and potentially underlie common symptoms in both disorders.

Neurophysiological Correlates of Attentional Fluctuation in Attention-Deficit/Hyperactivity Disorder.

Cognitive performance in attention-deficit/hyperactivity disorder (ADHD) is characterised, in part, by frequent fluctuations in response speed, resulting in high reaction time variability (RTV). RTV captures a large proportion of the genetic risk in ADHD but, importantly, is malleable, improving significantly in a fast-paced, rewarded task condition. Using the temporal precision offered by event-related potentials (ERPs), we aimed to examine the neurophysiological measures of attention allocation (P3 amplitudes) and preparation (contingent negative variation, CNV), and their associations with the fluctuating RT performance and its improvement in ADHD. 93 participants with ADHD and 174 controls completed the baseline and fast-incentive conditions of a four-choice reaction time task, while EEG was simultaneously recorded. Compared to controls, individuals with ADHD showed both increased RTV and reduced P3 amplitudes during performance on the RT task. In the participants with ADHD, attenuated P3 amplitudes were significantly associated with high RTV, and the increase in P3 amplitudes from a slow baseline to a fast-paced, rewarded condition was significantly associated with the RTV decrease. Yet, the individuals with ADHD did not show the same increase in CNV from baseline to fast-incentive condition as observed in controls. ADHD is associated both with a neurophysiological impairment of attention allocation (P3 amplitudes) and an inability to adjust the preparatory state (CNV) in a changed context. Our findings suggest that both neurophysiological and cognitive performance measures of attention are malleable in ADHD, which are potential targets for non-pharmacological interventions.

Predictive validity of parent- and self-rated ADHD symptoms in adolescence on adverse socioeconomic and health outcomes.

There is scarcity of research investigating the validity of self-report of attention deficit hyperactivity disorder (ADHD) symptoms compared to other informants, such as parents. This study aimed to compare the predictive associations of ADHD symptoms rated by parents and their children across adolescence on a range of adverse socioeconomic and health outcomes in early adulthood. Parent- and self-rated ADHD symptoms were assessed in 2960 individuals in early (13-14 years) and late adolescence (16-17 years). Logistic regression analyses were used to compare the associations between parent- and self-rated ADHD symptoms at both time points and adverse life outcomes in young adulthood obtained from Swedish national registries. Both parent- and self-ratings of ADHD symptoms were associated with increased risk for adverse outcomes, although associations of parent-ratings were more often statistically significant and were generally stronger (OR = 1.12-1.49, p < 0.05) than self-ratings (OR = 1.07-1.17, p < 0.05). After controlling for the other informant, parent-ratings of ADHD symptoms in both early and late adolescence significantly predicted academic and occupational failure, criminal convictions and traffic-related injuries, while self-ratings of ADHD symptoms only in late adolescence predicted substance use disorder and academic failure. Our findings suggest that both parent- and self-ratings of ADHD symptoms in adolescence provides valuable information on risk of future adverse socioeconomic and health outcomes, however, self-ratings are not valuable once parent-ratings have been taken into account in predicting most outcomes. Thus, clinicians and researchers should prioritize parent-ratings over self-ratings.

Altered EEG spectral power during rest and cognitive performance: a comparison of preterm-born adolescents to adolescents with ADHD.

Preterm birth has been associated with an increased risk for ADHD-like behavioural symptoms and cognitive impairments. However, direct comparisons across ADHD and preterm-born samples on neurophysiological measures are limited. The aim of this analysis was to test whether quantitative EEG (QEEG) measures identify differences or similarities in preterm-born adolescents, compared to term-born adolescents with and without ADHD, during resting-state and cognitive task conditions. We directly compared QEEG activity between 186 preterm-born adolescents, 69 term-born adolescents with ADHD and 135 term-born control adolescents during an eyes-open resting-state condition (EO), which previously discriminated between the adolescents with ADHD and controls, and during a cued continuous performance task (CPT-OX). Absolute delta power was the only frequency range to demonstrate a significant group-by-condition interaction. The preterm group, like the ADHD group, displayed significantly higher delta power during EO, compared to the control group. In line with these findings, parent-rated ADHD symptoms in the preterm group were significantly correlated with delta power during rest. While the preterm and control groups did not differ with regard to absolute delta power during CPT-OX, the ADHD group showed significantly higher absolute delta power compared to both groups. Our results provide evidence for overlapping excess in the absolute delta range in preterm-born adolescents and term-born adolescents with ADHD during rest. During CPT-OX, preterm-born adolescents resembled controls. Increased delta power during rest may be a potential general marker of brain trauma, pathology or neurotransmitter disturbances.

Cognitive and neurophysiological markers of ADHD persistence and remission.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) persists in around two-thirds of individuals in adolescence and early adulthood. AIMS: To examine the cognitive and neurophysiological processes underlying the persistence or remission of ADHD. METHOD: Follow-up data were obtained from 110 young people with childhood ADHD and 169 controls on cognitive, electroencephalogram frequency, event-related potential (ERP) and actigraph movement measures after 6 years. RESULTS: ADHD persisters differed from remitters on preparation-vigilance measures (contingent negative variation, delta activity, reaction time variability and omission errors), IQ and actigraph count, but not on executive control measures of inhibition or working memory (nogo-P3 amplitudes, commission errors and digit span backwards). CONCLUSIONS: Preparation-vigilance measures were markers of remission, improving concurrently with ADHD symptoms, whereas executive control measures were not sensitive to ADHD persistence/remission. For IQ, the present and previous results combined suggest a role in moderating ADHD outcome. These findings fit with previously identified aetiological separation of the cognitive impairments in ADHD. The strongest candidates for the development of non-pharmacological interventions involving cognitive training and neurofeedback are the preparation-vigilance processes that were markers of ADHD remission.

The aetiological association between the dynamics of cortisol productivity and ADHD.

Attention-deficit/hyperactivity disorder (ADHD) has been linked to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, indexed by salivary cortisol. The phenotypic and aetiological association of cortisol productivity with ADHD was investigated. A selected twin design using 68 male twin-pairs aged 12-15, concordant or discordant for high ADHD symptom scores, or control twin-pairs with low ADHD symptoms, based on developmentally stable parental ADHD ratings. A genetic growth curve model was applied to cortisol samples obtained across three points during a cognitive-electroencephalography assessment, to examine the aetiological overlap of ADHD affection status (high versus low ADHD symptom scores) with latent intercept and slope factors. A significant phenotypic correlation emerged between ADHD and the slope factor, with cortisol levels dropping faster for the group with high ADHD symptom scores. The analyses further suggested this overlap was mostly driven by correlated genetic effects. We identified change in cortisol activity over time as significantly associated with ADHD affection status, primarily explained by shared genetic effects, suggesting that blunted cortisol productivity can be a marker of genetic risk in ADHD.

Editorial Perspective: How should child psychologists and psychiatrists interpret FDA device approval? Caveat emptor.

Recently several new tests have received US Federal Drug Administration (FDA) marketing approval as aids in the diagnostic process for attention deficit hyperactivity disorder (ADHD), including the Neuropsychiatric electroencephalogram (EEG)-Based ADHD Assessment Aid (NEBA) Health test. The NEBA test relies upon an EEG-based measure, called the theta to beta ratio (TBR). Although this measure has yielded large differences between ADHD and non-ADHD groups in studies prior to 2009, recent studies and a meta-analysis could not replicate these findings. In this article, we have used the NEBA device as an exemplar for a discussion that distinguishes between FDA de novo marketing approval for a device and any claims that that device is empirically supported, scientifically validated with replicated findings. It is understood that the aims of each differ; however, for many, including the lay public as well as some mental health professionals, these terms may be confused and treated as though they are synonymous. With regard to the TBR measure, there is no reliable association or replication for its clinical usage in the ADHD diagnostic process. The recommendation for potential consumers of the NEBA Health test (as well as perhaps for other existing FDA-approved diagnostic tests) is caveat emptor (let the buyer beware!).

Response time variability under slow and fast-incentive conditions in children with ASD, ADHD and ASD+ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) show significant behavioural and genetic overlap. Both ADHD and ASD are characterised by poor performance on a range of cognitive tasks. In particular, increased response time variability (RTV) is a promising indicator of risk for both ADHD and ASD. However, it is not clear whether different indices of RTV and changes to RTV according to task conditions are able to discriminate between the two disorders. METHODS: Children with ASD (n = 19), ADHD (n = 18), ASD + ADHD (n = 29) and typically developing controls (TDC; n = 26) performed a four-choice RT task with slow-baseline and fast-incentive conditions. Performance was characterised by mean RT (MRT), standard deviation of RT (SD-RT), coefficient of variation (CV) and ex-Gaussian distribution measures of Mu, Sigma and Tau. RESULTS: In the slow-baseline condition, categorical diagnoses and trait measures converged to indicate that children with ADHD-only and ASD + ADHD demonstrated increased MRT, SD-RT, CV and Tau compared to TDC and ASD-only. Importantly, greater improvement in MRT, SD-RT and Tau was demonstrated in ADHD and ASD + ADHD from slow-baseline to fast-incentive conditions compared to TDC and ASD-only. CONCLUSIONS: Slower and more variable RTs are markers of ADHD compared to ASD and typically developing controls during slow and less rewarding conditions. Energetic factors and rewards improve task performance to a greater extent in children with ADHD compared to children with ASD. These findings suggest that RTV can be distinguished in ASD, ADHD and ASD + ADHD based on the indices of variability used and the conditions in which they are elicited. Further work identifying neural processes underlying increased RTV is warranted, in order to elucidate disorder-specific and disorder-convergent aetiological pathways.

Commonalities in EEG Spectral Power Abnormalities Between Women With ADHD and Women With Bipolar Disorder During Rest and Cognitive Performance.

While attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) denote distinct psychiatric conditions, diagnostic delineation is impeded by considerable symptomatic overlap. Direct comparisons across ADHD and BD on neurophysiological measures are limited. They could inform us on impairments that are specific to or shared between the disorders and, therefore, potential biomarkers that may aid in the identification of the diagnostic boundaries. Our aim was to test whether quantitative EEG (QEEG) identifies differences or similarities between women with ADHD and women with BD during resting-state and task conditions. QEEG activity was directly compared between 20 ADHD, 20 BD and 20 control women during an eyes-open resting-state condition (EO) and a cued continuous performance task (CPT-OX). Both ADHD (t38 = 2.50, p = 0.017) and BD (t38 = 2.54, p = 0.018) participants showed higher absolute theta power during EO than controls. No significant differences emerged between the two clinical groups. While control participants showed a task-related increase in absolute theta power from EO to CPT-OX (t19 = -3.77, p = 0.001), no such change in absolute theta power was observed in the ADHD (t19 = -0.605, p = 0.553) or BD (t19 = 1.82, p = 0.084) groups. Our results provide evidence for commonalities in brain dysfunction between ADHD and BD. Absolute theta power may play a role as a marker of neurobiological processes in both disorders.

Testing for the mediating role of endophenotypes using molecular genetic data in a twin study of ADHD traits.

Family and twin studies have identified endophenotypes that capture familial and genetic risk in attention-deficit/hyperactivity disorder (ADHD), but it remains unclear if they lie on the causal pathway. Here, we illustrate a stepwise approach to identifying intermediate phenotypes. First, we use previous quantitative genetic findings to delineate the expected pattern of genetically correlated phenotypes. Second, we identify overlapping genetic associations with ADHD-related quantitative traits. Finally, we test for the mediating role of associated endophenotypes. We applied this approach to a sample of 1,312 twins aged 7-10. Based on previous twin model-fitting analyses, we selected hyperactivity-impulsivity, inattention, reading difficulties (RD), reaction time variability (RTV) and commission errors (CE), and tested for association with selected ADHD risk alleles. For nominally significant associations with both a symptom and a cognitive variable, matching the expected pattern based on previous genetic correlations, we performed mediation analysis to distinguish pleiotropic from mediating effects. The strongest association was observed for the rs7984966 SNP in the serotonin receptor gene (HTR2A), and RTV (P = 0.007; unadjusted for multiple testing). Mediation analysis suggested that CE (38%) and RTV (44%) substantially mediated the association between inattention and the T-allele of SNP rs3785157 in the norepinephrine transporter gene (SLC6A2) and the T-allele of SNP rs7984966 in HTR2A, respectively. The SNPs tag risk-haplotypes but are not thought to be functionally significant. While these exploratory findings are preliminary, requiring replication, this study demonstrates the value of this approach that can be adapted to the investigation of multiple genetic markers and polygenic risk scores. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

A Matter of Time: The Influence of Recording Context on EEG Spectral Power in Adolescents and Young Adults with ADHD.

Elevated theta or theta/beta ratio is often reported in attention deficit hyperactivity disorder (ADHD), but the consistency across studies and the relation to hypoarousal are increasingly questioned. Reports of elevated delta related to maturational lag and of attenuated beta activity are less well replicated. Some critical inconsistencies could relate to differences in recording context. We examined if resting-state EEG power or global field synchronization (GFS) differed between recordings made at the beginning and end of a 1.5 h testing session in 76 adolescents and young adults with ADHD, and 85 controls. In addition, we aimed to examine the effect of IQ on any potential group differences. Both regional and midline electrodes yielded group main effects for delta, trends in theta, but no differences in alpha or theta/beta ratio. An additional group difference in beta was detected when using regions. Group by time interactions in delta and theta became significant when controlling for IQ. The ADHD group had higher delta and theta power at time-1, but not at time-2, whereas beta power was elevated only at time-2. GFS did not differ between groups or condition. We show some ADHD-control differences on EEG spectral power varied with recording time within a single recording session, with both IQ and electrode selection having a small but significant influence on observed differences. Our findings demonstrate the effect of recording context on resting-state EEG, and highlight the importance of accounting for these variables to ensure consistency of results in future studies.

Genetics of preparation and response control in ADHD: the role of DRD4 and DAT1.

BACKGROUND: Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children. METHODS: Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N = 94) and controls without family history of ADHD (N = 31). Both groups were split for the presence of at least one DRD4 7-repeat allele and the DAT1 10-6 haplotype. RESULTS: Children with ADHD showed diminished performance and lower Cue-P3, CNV and Nogo-P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue-P3 and CNV, but Nogo-P3 was not reduced. Children with the DAT1 10-6 haplotype had no difficulties with performance or Cue-P3 and CNV, but contrary to expectations increased Nogo-P3. There were no Genotype by ADHD interactions. CONCLUSIONS: This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10-6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.

The effect of methylphenidate on very low frequency electroencephalography oscillations in adult ADHD.

Altered very low-frequency electroencephalographic (VLF-EEG) activity is an endophenotype of ADHD in children and adolescents. We investigated VLF-EEG case-control differences in adult samples and the effects of methylphenidate (MPH). A longitudinal case-control study was conducted examining the effects of MPH on VLF-EEG (.02-0.2Hz) during a cued continuous performance task. 41 untreated adults with ADHD and 47 controls were assessed, and 21 cases followed up after MPH treatment, with a similar follow-up for 38 controls (mean follow-up=9.4months). Cases had enhanced frontal and parietal VLF-EEG and increased omission errors. In the whole sample, increased parietal VLF-EEG correlated with increased omission errors. After controlling for subthreshold comorbid symptoms, VLF-EEG case-control differences and treatment effects remained. Post-treatment, a time by group interaction emerged; VLF-EEG and omission errors reduced to the same level as controls, with decreased inattentive symptoms in cases. Reduced VLF-EEG following MPH treatment provides preliminary evidence that changes in VLF-EEG may relate to MPH treatment effects on ADHD symptoms; and that VLF-EEG may be an intermediate phenotype of ADHD. Further studies of the treatment effect of MPH in larger controlled studies are required to formally evaluate any causal link between MPH, VLF-EEG and ADHD symptoms.

A Blended Intervention Targeting Emotion Dysregulation in Adults With Attention-Deficit/Hyperactivity Disorder: Development and Feasibility Study.

BACKGROUND: Many adults with attention-deficit/hyperactivity disorder (ADHD) experience difficulties related to emotion regulation. Such difficulties are known to substantially impact quality of life and overall functioning. Yet, there is a lack of treatment interventions specifically designed to address these challenges. OBJECTIVE: This study aimed to describe the development and assess the feasibility, along with the initial clinical outcomes, of a novel blended intervention for adults with ADHD. The blended intervention combines both face-to-face and digital components and is specifically designed to address emotion dysregulation in ADHD. METHODS: This intervention was an 8-week blended intervention combining weekly face-to-face group sessions with a supplementary digital companion app. The intervention is based on elements from dialectic behavioral therapy skills training and positive psychology. To evaluate its feasibility, we performed a 10-week feasibility study with an uncontrolled pre-post study design, including 16 adults with ADHD and co-occurring emotion dysregulation. The feasibility measures encompassed adherence, satisfaction, and perceived credibility of the intervention. Clinical outcomes were evaluated by self-reported symptoms of emotion dysregulation, inattention, hyperactivity-impulsivity, executive function, depression, anxiety, and a measure of quality of life. Paired sample 2-tailed t tests were used to analyze clinical outcomes with a Bonferroni-corrected significance level. RESULTS: Both treatment credibility and treatment satisfaction were rated favorably by the majority of the participants. In particular, the participants emphasized meeting others with ADHD as beneficial. In terms of adherence, 3 participants withdrew before initiating the intervention, while another 4 participants did not complete the intervention. On average, the participants who enrolled in the intervention attended 6.2 of the 8 group sessions and completed 6.7 of the 8 skills training modules in the companion app. In terms of clinical outcomes, there was a reduction in symptoms of emotion dysregulation from before to after the intervention (d=2.0). Significant improvements were also observed in measures of inattention (d=1.1) and hyperactivity-impulsivity (d=0.9). However, no significant improvements were found in the domains of depression, anxiety, quality of life, and executive functioning. CONCLUSIONS: The results are encouraging, both in terms of feasibility and the preliminary clinical results on emotion dysregulation. The blended format, combining digital and face-to-face elements, may also seem to offer some advantages: the group-based format was valued as it facilitated peer interaction, while a rather high completion of modules in the companion app highlights its potential to enhance skills training between the group sessions. Future randomized controlled trials are called for to further evaluate the clinical effectiveness of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05644028; https://clinicaltrials.gov/study/NCT05644028.