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Background: Cognitive control has been strongly linked to midfrontal theta (4-8 Hz) brain activity. Such control processes are known to be impaired in individuals with psychiatric conditions and neurodevelopmental diagnoses, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Temporal variability in theta, in particular, has been associated with ADHD, with shared genetic variance underlying the relationship. Here, we investigated the phenotypic and genetic relationships between theta phase variability, theta-related signals (the N2, error-related negativity, and error positivity), reaction time, and ADHD and ASD longitudinally in a large twin study of young adults to investigate the stability of the genetic relationships between these measures over time., Methods: Genetic multivariate liability threshold models were run on a longitudinal sample of 566 participants (283 twin pairs). Characteristics of ADHD and ASD were measured in childhood and young adulthood, while an electroencephalogram was recorded in young adulthood during an arrow flanker task., Results: Cross-trial theta phase variability in adulthood showed large positive phenotypic and genetic relationships with reaction time variability and both childhood and adult ADHD characteristics. Error positivity amplitude was negatively related phenotypically and genetically to ADHD and ASD at both time points., Conclusions: We showed significant genetic associations between variability in theta signaling and ADHD. A novel finding from the current study is that these relationships were stable across time, indicating a core dysregulation of the temporal coordination of control processes in ADHD that persists in individuals with childhood symptoms. Error processing, indexed by the error positivity, was altered in both ADHD and ASD, with a strong genetic contribution., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

This study explored whether high autistic traits, high attention deficit hyperactivity disorder (ADHD) traits and their interaction were associated with quality of life (QoL) in a sample of 556 of young-adult twins (Mean age 22 years 5 months, 52% Female). Four participant groups were created: high autistic traits, high ADHD traits, high autistic/ADHD traits, and low ADHD/autistic traits. High autistic traits were associated with lower QoL across domains (physical, psychological, social, and environmental). High ADHD traits associated with lower physical, psychological, and environmental QoL. The interaction of autistic and ADHD traits was not significant in any domain. While mental health difficulties were associated with lower QoL, after accounting for mental health, most relationships between autistic traits, ADHD traits and QoL remained., (© 2022. The Author(s).)

Background: Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) share impairments in top-down and bottom-up modulation of attention. However, it is not yet well understood if co-occurrence of ASD and ADHD reflects a distinct or additive profile of attention deficits. We aimed to characterise alpha oscillatory activity (stimulus-locked alpha desynchronisation and prestimulus alpha) as an index of integration of top-down and bottom-up attentional processes in ASD and ADHD., Methods: Children with ASD, ADHD, comorbid ASD+ADHD, and typically-developing children completed a fixed-choice reaction-time task ('Fast task') while neurophysiological activity was recorded. Outcome measures were derived from source-decomposed neurophysiological data. Main measures of interest were prestimulus alpha power and alpha desynchronisation (difference between poststimulus and prestimulus alpha). Poststimulus activity linked to attention allocation (P1, P3), attentional control (N2), and cognitive control (theta synchronisation, 100-600 ms) was also examined. ANOVA was used to test differences across diagnostics groups on these measures. Spearman's correlations were used to investigate the relationship between attentional control processes (alpha oscillations), central executive functions (theta synchronisation), early visual processing (P1), and behavioural performance., Results: Children with ADHD (ADHD and ASD+ADHD) showed attenuated alpha desynchronisation, indicating poor integration of top-down and bottom-up attentional processes. Children with ADHD showed reduced N2 and P3 amplitudes, while children with ASD (ASD and ASD+ADHD) showed greater N2 amplitude, indicating atypical attentional control and attention allocation across ASD and ADHD. In the ASD group, prestimulus alpha and theta synchronisation were negatively correlated, and alpha desynchronisation and theta synchronisation were positively correlated, suggesting an atypical association between attentional control processes and executive functions., Conclusions: ASD and ADHD are associated with disorder-specific impairments, while children with ASD+ADHD overall presented an additive profile with attentional deficits of both disorders. Importantly, these findings may inform the improvement of transdiagnostic procedures and optimisation of personalised intervention approaches., (© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

There is an urgent need to identify the mechanisms that contribute to atypical thinking and behavior associated with psychiatric illness. Behavioral and brain measures of cognitive control are associated with a variety of psychiatric disorders and conditions as well as daily life functioning. Recognition of the importance of cognitive control in human behavior has led to intensive research into behavioral and neurobiological correlates. Oscillations in the theta band (4-8 Hz) over medial frontal recording sites are becoming increasingly established as a direct neural index of certain aspects of cognitive control. In this review, we point toward evidence that theta acts to coordinate multiple neural processes in disparate brain regions during task processing to optimize behavior. Theta-related signals in human electroencephalography include the N2, the error-related negativity, and measures of theta power in the (time-)frequency domain. We investigate how these theta signals are affected in a wide range of psychiatric conditions with known deficiencies in cognitive control: anxiety, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and substance abuse. Theta-related control signals and their temporal consistency were found to differ in most patient groups compared with healthy control subjects, suggesting fundamental deficits in reactive and proactive control. Notably, however, clinical studies directly investigating the role of theta in the coordination of goal-directed processes across different brain regions are uncommon and are encouraged in future research. A finer-grained analysis of flexible, subsecond-scale functional networks in psychiatric disorders could contribute to a dimensional understanding of psychopathology., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Electrophysiological recording methods, including electroencephalography (EEG) and magnetoencephalography (MEG), have an unparalleled capacity to provide insights into the timing and frequency (spectral) composition of rapidly changing neural activity associated with various cognitive processes. The current chapter provides an overview of EEG studies examining alterations in brain activity in ADHD, measured both at rest and during cognitive tasks. While EEG resting state studies of ADHD indicate no universal alterations in the disorder, event-related studies reveal consistent deficits in attentional and inhibitory control and consequently inform the proposed cognitive models of ADHD. Similar to other neuroimaging measures, EEG research indicates alterations in multiple neural circuits and cognitive functions. EEG methods - supported by the constant refinement of analytic strategies - have the potential to contribute to improved diagnostics and interventions for ADHD, underlining their clinical utility., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objective: Previous studies in children with ADHD identified two partially separable familial factors underlying cognitive dysfunction, but evidence in adolescents and adults is lacking. Here, we investigate the etiological structure of cognitive-neurophysiological impairments in ADHD in adolescents and young adults. Method: Factor analyses and multivariate familial models were run in 356 participants from ADHD and control sibling pairs aged 11 to 27 years on data on IQ, digit span forward (DSF) and backward (DSB), and cognitive-performance and event-related potential (ERP) measures from three cognitive tasks. Results: Three familial factors (cF 1-3 ), showing substantial familial overlap with ADHD, captured the familial covariation of ADHD with nine cognitive-ERP measures. cF 1 loaded on IQ, mean reaction time (MRT), and reaction-time variability (RTV); cF 2 on DSF and DSB; and cF 3 on number of errors and ERPs of inhibition and error processing. Conclusion: These results identify three partially separable etiological pathways leading to cognitive-neurophysiological impairments in adolescent and adult ADHD.

Objective: This study investigates whether impairments associated with persistent ADHD-impaired attention allocation (P3 amplitude), peripheral hypoarousal (skin conductance level [SCL]), and adjustment in preparatory state (contingent negative variation [CNV])-reflect enduring deficits unrelated to ADHD outcome or are markers of ADHD remission. Method: Young people with childhood ADHD (73 persisters and 18 remitters) and 144 controls were compared on neurophysiological measures during two conditions (baseline and fast-incentive) of a four-choice reaction time task. Results: ADHD remitters differed from persisters, and were indistinguishable from controls, on baseline P3 amplitude and fast-incentive CNV amplitude ( p ≤ .05). ADHD remitters differed from controls ( p ≤ .01), and were indistinguishable from persisters ( p > .05), on baseline SCL. Conclusion: Preparation-vigilance measures were markers of ADHD remission, confirming previous findings with other measures. Yet, SCL-measured peripheral hypoarousal emerges as an enduring deficit unrelated to ADHD improvement. Future studies should explore potential compensatory mechanisms that enable efficient preparation-vigilance processes in ADHD remitters.

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 (β = 0.32, p = 0.01, 95% CI 0.05 to 0.58) and specific cognitive-ERP impairments, such as IQ (β = -0.20, p = 0.02, 95% CI -0.40 to -0.01), preparation-vigilance measures and measures of error processing (ranging from β = 0.71, -0.35). There was a negligible within-sibling association between preterm birth with executive control measures of inhibition (NoGo-P3, β = -0.07, p = 0.45, 95% CI -0.33 to 0.15) or verbal working memory (digit span backward, β = -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.

We investigated key event-related brain potential markers (ERPs) derived from a flanked continuous performance task (CPT) and whether these would show phenotypic associations with ADHD (attention-deficit/hyperactivity disorder) in a population-based sample. We further explored whether there was preliminary evidence that such ERPs could also index genetic risk for ADHD (depending on finding phenotypic associations). Sixty-seven male-only twin pairs (N = 134; aged 12-15) from a subsample of the Twins' Early Development Study, concordant and discordant for ADHD symptoms, performed the flanked CPT (or CPT-OX) while electroencephalography (EEG) was recorded. ERPs were obtained for cue (P3, CNV or contingency negative variation), go (P3, N2) and nogo trials (P3, N2). We found no phenotypic associations between CPT-derived ERPs and ADHD-the sizes of the estimated phenotypic correlations were nonsignificant and very small (r's = -.11 to .04). Twin-model fitting analyses using structural equation modelling provided preliminary evidence that some of the ERPs were heritable (with the most robust effect for go-P3 latency), but there was limited evidence of any genetic associations between ERPs and ADHD, although with the caveat that our sample was small and hence had limited power. Overall, unlike in previous research, there was no evidence of phenotypic (nor preliminary evidence for genetic) associations between ADHD and CPT-derived ERPs in this study. Hence, it may be currently premature for genetic analyses of ADHD to be guided by CPT-derived ERP parameters (unlike alternative cognitive-neurophysiological approaches which may be more promising). Further research with better-powered, population-based, genetically-informative and cross-disorder samples are required, which could be facilitated by emerging mobile EEG technologies., Competing Interests: The authors have declared that no competing interests exist.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common and impairing neurodevelopmental disorders that frequently co-occur. The neurobiological mechanisms involved in ASD and ADHD are not fully understood. However, alterations in large-scale neural networks have been proposed as core deficits in both ASD and ADHD and may help to disentangle the neurobiological basis of these disorders and their co-occurrence. In this study, we examined similarities and differences in large-scale oscillatory neural networks between boys aged 8-13 years with ASD (n = 19), ADHD (n = 18), ASD + ADHD (n = 29) and typical development (Controls, n = 26). Oscillatory neural networks were computed using graph-theoretical methods from electroencephalographic (EEG) data collected during an eyes-open resting-state and attentional control and social cognition tasks in which we previously reported disorder-specific atypicalities in oscillatory power and event-related potentials (ERPs). We found that children with ASD showed significant hypoconnectivity in large-scale networks during all three task conditions compared to children without ASD. In contrast, children with ADHD showed significant hyperconnectivity in large-scale networks during the attentional control and social cognition tasks, but not during the resting-state, compared to children without ADHD. Children with co-occurring ASD + ADHD did not differ from children with ASD when paired with this group and vice versa when paired with the ADHD group, indicating that these children showed both ASD-like hypoconnectivity and ADHD-like hyperconnectivity. Our findings suggest that ASD and ADHD are associated with distinct alterations in large-scale oscillatory networks, and these atypicalities present together in children with both disorders. These alterations appear to be task-independent in ASD but task-related in ADHD, and may underlie other neurocognitive atypicalities in these disorders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Preterm birth is associated with heightened risk for attention-deficit/hyperactivity disorder (ADHD)-like symptoms and neurocognitive impairments, including impairments in performance monitoring. Here, we investigate the cognitive and neurophysiological processes from a performance-monitoring task in preterm-born adolescents and examine whether these processes in preterm-born adolescents reflect identical neurophysiological impairments to those observed in term-born adolescents with ADHD. We compared 186 preterm-born individuals to 69 term-born individuals with ADHD and 135 term-born controls on cognitive-performance measures and event-related potentials (ERPs) of conflict monitoring (N2) and error processing (ERN, Pe) from a flanker task. Preterm-born adolescents demonstrated reduced N2, ERN and Pe amplitudes, compared to controls, and similar ERN and Pe impairments to term-born adolescents with ADHD. While ADHD symptoms correlated with ERN amplitude at FCz among the preterm-born, ERN amplitude at Fz, N2 and Pe amplitude were not associated with ADHD symptoms. Preterm-born individuals show impairments on neurophysiological indices of conflict monitoring (N2) and error processing (ERN and Pe). Early neurophysiological error processing may be a marker underlying the processes linked to the increased risk for ADHD among preterm-born individuals. Error detection processes are malleable and potential targets for non-pharmacological interventions. Preterm-born individuals are likely to benefit from early interventions., Competing Interests: Prof Jonna Kuntsi has given talks at educational events sponsored by Medice. All funds are received by King’s College London and used for studies of ADHD. Prof Asherson has received funding for research by Vifor Pharma, and has given sponsored talks and been an advisor for Shire, Janssen–Cilag, Eli-Lilly, Flynn Pharma and Pfizer, regarding the diagnosis and treatment of ADHD. All funds are received by King’s College London and used for studies of ADHD. Prof Banaschewski served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Medice, Novartis, Oxford outcomes, PCM scientific, Shire and Vifor Pharma. He received conference support or speaker’s fee by Medice, Novartis and Shire. He is/has been involved in clinical trials conducted by Shire and Vifor Pharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. Prof Brandeis reports no biomedical financial interests or potential conflicts of interest. He serves as an unpaid scientific advisor for an EU-funded Neurofeedback trial. Drs Rommel, James, Michelini and McLoughlin report no biomedical financial interests or potential conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Attention deficit/hyperactivity disorders (ADHD) and autism spectrum disorders (ASD) frequently co-occur. However, we know little about the neural basis of the overlaps and distinctions between these disorders, particularly in young adulthood - a critical time window for brain plasticity across executive and socioemotional domains. Here, we systematically review 75 articles investigating ADHD and ASD in young adult samples (mean ages 16-26) using cognitive tasks, with neural activity concurrently measured via electroencephalography (EEG) - the most accessible neuroimaging technology. The majority of studies focused on event-related potentials (ERPs), with some beginning to capitalise on oscillatory approaches. Overlapping and specific profiles for ASD and ADHD were found mainly for four neurocognitive domains: attention processing, performance monitoring, face processing and sensory processing. No studies in this age group directly compared both disorders or considered dual diagnosis with both disorders. Moving forward, understanding of ADHD, ASD and their overlap in young adulthood would benefit from an increased focus on cross-disorder comparisons, using similar paradigms and in well-powered samples and longitudinal cohorts., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Whilst preterm-born individuals have an increased risk of developing attention-deficit/hyperactivity disorder (ADHD), and are reported to have ADHD-like attention and arousal impairments, direct group comparisons are scarce., Methods: We directly compared preterm-born adolescents (n = 186) to term-born adolescents with ADHD (n = 69), and term-born controls (n = 135), aged 11-23, on cognitive-performance, event-related potential and skin conductance level (SCL) measures associated with attention and arousal. The measures are from baseline and fast-incentive conditions of a four-choice reaction time task, previously shown to discriminate between the individuals with ADHD and controls. We aimed to establish whether preterm-born adolescents show: (a) identical cognitive-neurophysiological impairments to term-born adolescents with ADHD (b) possible additional impairments, and whether (c) the observed impairments correlate with ADHD symptom scores., Results: The preterm group, like the term-born ADHD group, showed increased mean reaction time (MRT) and reaction time variability (RTV) in the baseline condition, and attenuated contingent negative variation (CNV) amplitude (response preparation) in the fast-incentive condition. The preterm group, only, did not show significant within-group adjustments in P3 amplitude (attention allocation) and SCL (peripheral arousal). Dimensional analyses showed that ADHD symptoms scores correlated significantly with MRT, RTV and CNV amplitude only., Conclusions: We find impairments in cognition and brain function in preterm-born adolescents that are linked to increased ADHD symptoms, as well as further impairments, in lack of malleability in neurophysiological processes. Our findings indicate that such impairments extend at least to adolescence. Future studies should extend these investigations into adulthood.

Altered power of resting-state neurophysiological activity has been associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. We compared resting-state neurophysiological power in children with ASD, ADHD, co-occurring ASD + ADHD, and typically developing controls. Children with ASD (ASD/ASD + ADHD) showed reduced theta and alpha power compared to children without ASD (controls/ADHD). Children with ADHD (ADHD/ASD + ADHD) displayed decreased delta power compared to children without ADHD (ASD/controls). Children with ASD + ADHD largely presented as an additive co-occurrence with deficits of both disorders, although reduced theta compared to ADHD-only and reduced delta compared to controls suggested some unique markers. Identifying specific neurophysiological profiles in ASD and ADHD may assist in characterising more homogeneous subgroups to inform treatment approaches and aetiological investigations.

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.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are associated with varied executive function (EF) difficulties. Callous-unemotional (CU) traits, a proposed antecedent of adult psychopathy, are often associated with intact or enhanced EF. Here we test whether CU traits may therefore modulate EF in ASD and ADHD, in which EF is typically impaired. We collected CU traits and measured event-related potentials (ERPs) that index EF during a cued-continuous performance test (CPT-OX) in boys with ASD, ADHD, comorbid ASD+ADHD and typical controls. We examined attentional orienting at cues (Cue-P3), inhibitory processing at non-targets (NoGo-P3) and conflict monitoring between target and non-target trials (Go-N2 vs. NoGo-N2). In children with ASD, higher CU traits were associated with an enhanced increase in N2 amplitude in NoGo trials compared to Go trials, which suggests relatively superior conflict monitoring and a potential cognitive strength associated with CU traits. The results emphasise the importance of considering the effects of co-occurring traits in the assessment of heterogeneity of EF profiles in neurodevelopmental disorders., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

Objective: Preterm birth has been associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD)-like symptoms and cognitive impairments similar to those seen in ADHD, including attention and inhibitory control difficulties. Yet data on direct comparisons across ADHD and preterm birth on cognitive-neurophysiological measures are limited., Method: We directly compared 186 preterm-born adolescents to 69 term-born adolescents with ADHD and 135 term-born controls on cognitive-performance and event-related potential measures associated with attentional and inhibitory processing from a cued continuous performance test (CPT-OX), which we have previously shown to discriminate between the adolescents with ADHD and controls. We aimed to elucidate whether the ADHD-like symptoms and cognitive impairments in preterm-born individuals reflect identical cognitive-neurophysiological impairments in term-born individuals with ADHD., Results: Go-P3 amplitude was reduced, reflecting impaired executive response control, in preterm-born adolescents compared to both controls and adolescents with ADHD. Moreover, in preterm-born adolescents, as in term-born adolescents with ADHD, contingent negative variation amplitude was attenuated, reflecting impairments in response preparation compared to controls. Although the ADHD group showed significantly increased NoGo-P3 amplitude at FCz compared to preterm group, at Cz preterm-born adolescents demonstrated significantly decreased NoGo-P3 amplitude compared to the control group, similar to term-born adolescents with ADHD., Conclusion: These findings indicate impairments in response preparation, executive response control, and response inhibition in preterm-born adolescents. Although the response preparation and response inhibition impairments found in preterm-born adolescents overlap with those found in term-born adolescents with ADHD, the preterm group also shows unique impairments, suggesting more wide-ranging impairments in the preterm group compared to the ADHD group., Competing Interests: Prof. Brandeis has served as an unpaid scientific advisor for an EU-funded neurofeedback trial. Prof. Banaschewski has served in an advisory or consultancy role for Actelion, Hexal Pharma, Eli Lilly and Co., Medice, Novartis, Oxford outcomes, PCM scientific, Shire, and Vifor Pharma. He has received conference support or speaker’s fee from Medice, Novartis, and Shire. He is/has been involved in clinical trials conducted by Shire and Vifor Pharma. He has received royalties from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. Prof. Asherson has received funding for research by Vifor Pharma, and has given sponsored talks and been an advisor for Shire, Janssen-Cilag, Eli Lilly and Co., Flynn Pharma, and Pfizer, regarding the diagnosis and treatment of ADHD. All funds are received by King’s College London and used for studies of ADHD. Drs. Rommel and McLoughlin, Prof. Kuntsi, and Ms. James report no biomedical financial interests or potential conflicts of interest., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The processes underlying persistence and remission of attention-deficit/hyperactivity disorder (ADHD) are poorly understood. We examined whether cognitive and neurophysiological impairments on a performance-monitoring task distinguish between ADHD persisters and remitters., Methods: On average 6 years after initial assessment, 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 age-matched control participants were compared on cognitive-performance measures and event-related potentials of conflict monitoring (N2) and error processing (error-related negativity and positivity) from an arrow flanker task with low-conflict and high-conflict conditions. ADHD outcome was examined with parent-reported symptoms and functional impairment measures using a categorical (DSM-IV) and a dimensional approach., Results: ADHD persisters were impaired compared with controls on all cognitive-performance and event-related potential measures (all p < .05). ADHD remitters differed from persisters and were indistinguishable from control participants on the number of congruent (low-conflict) errors, reaction time variability, error-related negativity, and error-related positivity (all p ≤ .05). Remitters did not differ significantly from the other groups on incongruent (high-conflict) errors, mean reaction time, and N2. In dimensional analyses on all participants with childhood ADHD, ADHD symptoms and functional impairment at follow-up were significantly correlated with congruent errors, reaction time variability, and error-related positivity (r = .19-.23, p ≤ .05)., Conclusions: Cognitive and neurophysiological measures of attention-vigilance and error detection distinguished ADHD remitters from persisters. These results extend our previous findings with other tasks and indicate that such measures are markers of remission and candidates for the development of nonpharmacological interventions., (Copyright © 2016 Society of Biological Psychiatry. All rights reserved.)

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., (© 2016 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Objective: A controversial issue is whether self-report of symptoms and impairment is sufficient for diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adolescents and adults in the absence of other informants, such as parents. The present study investigated how well self-report is reflected by cognitive-neurophysiological and actigraph measures, which we have previously shown to discriminate between ADHD persisters, remitters and controls using parent-report (Cheung et al., 2015; Brit J Psychiat http://dx.doi.org/10.1192/bjp.bp.114.145185)., Method: Parent- and self-reported ADHD symptoms and impairment, together with cognitive, electroencephalogram (EEG) frequency, event-related potential (ERP) and actigraph measures were obtained from 108 adolescents and young adults with childhood ADHD and 167 controls., Results: Participants reported lower levels of ADHD symptoms and impairments than parents (p < 0.05) and the ADHD persistence rate based on self-report was low at 44%, compared to the persistence rate of 79% previously reported based on parent-report. Regression analyses showed that the objective measures distinguished poorly between ADHD persistent and remittent groups based on self-report, in contrast to findings based on parent-report (Cheung et al., 2015), although the measures differentiated well between ADHD persisters and controls. Correlation analyses revealed that self-reported impairment significantly correlated with fewer of the objective measures, despite parent- and self-reported symptoms showing similar correlations with the measures., Conclusions: The findings show that self-reported ADHD outcome is not as well reflected by cognitive-neurophysiological and movement correlates as we previously found for parent-reported ADHD., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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 (t 38  = 2.50, p = 0.017) and BD (t 38  = 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 (t 19  = -3.77, p = 0.001), no such change in absolute theta power was observed in the ADHD (t 19  = -0.605, p = 0.553) or BD (t 19  = 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., Competing Interests: Philip Asherson has received funding for research by Vifor Pharma, and has given sponsored talks and been an advisor for Shire, Janssen–Cilag, Eli-Lilly, Flynn Pharma and Pfizer, regarding the diagnosis and treatment of ADHD. All funds are received by King’s College London and used for studies of ADHD. The other authors report no conflicts of interest.

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.

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 Royal College of Psychiatrists 2016.)

Objective: Overlapping symptoms can make the diagnostic differentiation of attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) challenging in adults using current clinical assessments. This study sought to determine if current clinical measures delineate ADHD from BD in adults, comparing relative levels of ADHD, BD and emotional lability (EL) symptoms., Methods: Sixty adult women with ADHD, BD or controls were compared on self-report and interview measures for ADHD symptoms, mania, depression, EL, and impairment., Results: ADHD interview measures and self-ratings of ADHD symptoms best discriminated between ADHD and BD. Self-report measures of EL and depression showed non-specific enhancement in both clinical groups. BD-specific items may distinguish BD from ADHD if a retrospective time-frame is adopted., Conclusions: Using measures which capture specific symptoms of ADHD and chronicity/episodicity of symptoms facilitates the delineation of ADHD from BD in adult women., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In adults, attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) have certain overlapping symptoms, which can lead to uncertainty regarding the boundaries of the two disorders. Despite evidence of cognitive impairments in both disorders separately, such as in attentional and inhibitory processes, data on direct comparisons across ADHD and BD on cognitive-neurophysiological measures are as yet limited., Method: We directly compared cognitive performance and event-related potential measures from a cued continuous performance test in 20 women with ADHD, 20 women with BD (currently euthymic) and 20 control women., Results: The NoGo-N2 was attenuated in women with BD, reflecting reduced conflict monitoring, compared with women with ADHD and controls (both p < 0.05). Both ADHD and BD groups showed a reduced NoGo-P3, reflecting inhibitory control, compared with controls (both p < 0.05). In addition, the contingent negative variation was significantly reduced in the ADHD group (p = 0.05), with a trend in the BD group (p = 0.07), compared with controls., Conclusions: These findings indicate potential disorder-specific (conflict monitoring) and overlapping (inhibitory control, and potentially response preparation) neurophysiological impairments in women with ADHD and women with BD. The identified neurophysiological parameters further our understanding of neurophysiological impairments in women with ADHD and BD, and are candidate biomarkers that may aid in the identification of the diagnostic boundaries of the two disorders.

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.

Background: Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood, but it remains unclear which childhood factors predict future outcome., Aim: To identify childhood predictors of ADHD outcome using both dimensional and categorical approaches., Methods: 116 adolescents and young adults with childhood ADHD were followed up on average 6.6 years later. ADHD outcome variables were interview-based parent-reported ADHD symptoms and impairment. Childhood predictors included parent- and teacher-rated ADHD symptoms and co-occurring behaviours; actigraph measures of activity level; socio-economic status (SES); and cognitive measures previously associated with ADHD., Results: Of the sample, 79% continued to meet clinical criteria of ADHD in adolescence and young adulthood. Higher parent-rated ADHD symptoms and movement intensity in childhood, but not teacher-rated symptoms, predicted ADHD symptoms at follow up. Co-occurring symptoms of oppositional behaviours, anxiety, social and emotional problems were also significant predictors, but these effects disappeared after controlling for ADHD symptoms. IQ and SES were significant predictors of both ADHD symptoms and impairment at follow up, but no other cognitive measures significantly predicted outcome., Conclusions: SES and IQ emerge as potential moderators for the prognosis of ADHD. Childhood severity of ADHD symptoms, as measured by parent ratings and actigraph movement intensity, also predicts later ADHD outcome. These factors should be considered when identifying ADHD children at most risk of poor long-term outcomes and for the development of interventions to improve prognosis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Attention-deficit/hyperactivity disorder (ADHD) is associated with cognitive performance and functional brain changes that are sensitive to task conditions, indicating a role for dynamic impairments rather than stable cognitive deficits. Prominent hypotheses consistent with this observation are a failure to optimise brain arousal or activation states. Here we investigate cortical activation during different conditions. Using a sample of 41 non-comorbid adults with ADHD and 48 controls, we examine quantitative EEG activity during a resting state, a cued continuous performance test with flankers (CPT-OX) and the sustained attention to response task (SART). We further investigate the effects of methylphenidate in a subsample of 21 ADHD cases. Control participants showed a task-related increase in theta activity when engaged in cognitive tasks, primarily in frontal and parietal regions, which was absent in participants with ADHD. Treatment with methylphenidate resulted in normalisation of the resting state to task activation pattern. These findings suggest that ADHD in adults is associated with insufficient allocation of neuronal resources required for normal cortical activation commensurate with task demands. Further work is required to clarify the causal role of the deficit in cortical activation and provide a clearer understanding of the mechanisms involved., (Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.)

There are high rates of overlap between autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Emotional impairment in the two disorders, however, has not been directly compared using event-related potentials (ERPs) that are able to measure distinct temporal stages in emotional processing. The N170 and N400 ERP components were measured during presentation of emotional face stimuli to boys with ASD (n=19), ADHD (n=18), comorbid ASD+ADHD (n=29) and typically developing controls (n=26). Subjects with ASD (ASD/ASD+ADHD) displayed reduced N170 amplitude across all stimuli, particularly for fearful versus neutral facial expressions. Conversely, subjects with ADHD (ADHD/ASD+ADHD) demonstrated reduced modulation of N400 amplitude by fearful expressions in parietal scalp regions and happy facial expressions in central scalp regions. These findings indicate a dissociation between disorders on the basis of distinct stages of emotion processing; while children with ASD show alterations at the structural encoding stage, children with ADHD display abnormality at the contextual processing stage. The comorbid ASD+ADHD group presents as an additive condition with the unique deficits of both disorders. This supports the use of objective neural measurement of emotional processing to delineate pathophysiological mechanisms in complex overlapping disorders., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Biological markers that are grounded in neuroscience may facilitate understanding of the pathophysiology of complex psychiatric disorders. One of the most consistent and robust neural abnormalities in attention deficit hyperactivity disorder (ADHD) is increased EEG power in the theta band at rest (4-8Hz). The present study used a twin design to estimate the extent of genetic overlap between increased theta power and risk for ADHD in order to validate theta power as a marker of genetic risk for ADHD. At rest, EEG was measured in 30 monozygotic and dizygotic adolescent twin pairs concordant or discordant for high ADHD symptom scores and 37 monozygotic and dizygotic control twin pairs with low ADHD symptom scores. Structural equation modelling was used to estimate the heritability of theta power and partition the genetic and environmental contributions to the overlap between ADHD and theta power. A significant phenotypic correlation between ADHD symptoms and elevated theta power was found. Theta power demonstrated moderate to high heritability estimates (0.77) and moderate genetic correlations with ADHD (0.35) suggesting shared genetic influences. Increased theta power is a candidate biological marker of genetic risk for ADHD, which warrants further investigation of the neurobiological mechanisms that underlie the genetic relationship., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Substantial overlap has been reported between attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Deficits in executive function (EF) are characteristic of both disorders but these impairments have not been compared directly across pure and co-morbid cases using event-related potentials (ERPs)., Method: Behavioural parameters and ERPs were recorded during a flankered cued-continuous performance test (CPT-OX) administered to 8-13-year-old boys with ASD (n = 19), ADHD (n = 18), co-morbid ASD + ADHD (n = 29) and typically developing controls (TD; n = 26). Preparatory processing (contingent negative variation, CNV) and attentional orienting (Cue-P3) at cues, response execution at targets (Go-P3), inhibitory processing at non-targets (NoGo-P3) and conflict monitoring between target and non-target trials (Go-N2 v. NoGo-N2) were examined., Results: Categorical diagnoses and quantitative trait measures indicated that participants with ADHD (ADHD/ASD + ADHD) made more omission errors and exhibited increased reaction-time (RT) variability and reduced amplitude of the Cue-P3 and NoGo-P3 compared to TD/ASD participants. Participants with ASD (ASD/ ASD + ADHD) demonstrated reduced N2 enhancement from Go to NoGo trials compared to TD/ADHD participants. Participants with ASD-only displayed enhanced CNV amplitude compared to ASD + ADHD and TD participants., Conclusions: Children with ADHD show deficits in attentional orienting and inhibitory control whereas children with ASD show abnormalities in conflict monitoring and response preparation. Children with co-morbid ASD + ADHD present as an additive co-occurrence with deficits of both disorders, although non-additive effects are suggested for response preparation. Measuring ERPs that index attention and inhibition is useful in disentangling cognitive markers of ASD and ADHD and elucidating the basis of co-occurring ASD + ADHD to guide clinical assessment.

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Electrophysiological and hemodynamic activity is altered in attention-deficit/hyperactivity disorder (ADHD) during tasks requiring cognitive control. Frontal midline theta oscillations are a cortical correlate of cognitive control influencing behavioral outcomes including reaction times. Reaction time variability (RTV) is consistently increased in ADHD and is known to share genetic effects with the disorder. The etiological relationship between the cognitive control system, RTV, and ADHD is unknown. In a sample of twins selected for ADHD and matched control subjects, we aimed to quantify the strength of the phenotypic, genetic, and environmental relationships between event-related midline theta oscillations, RTV, and ADHD., Methods: Our sample included 134 participants aged 12 to 15 years: 67 twin pairs (34 monozygotic; 33 dizygotic) with concordance or discordance for ADHD symptomatology assessed at 8, 10, and 12 years of age. Our main outcome measures were frontal midline theta activity, derived from both channel and source decomposed electroencephalographic data, and behavioral performance on a response-choice arrow flanker task known to elicit theta activity., Results: Variability in stimulus event-related theta phase from frontal midline cortex is strongly related to both RTV and ADHD, both phenotypically and genetically., Conclusions: This is the first finding to confirm the genetic link between the frontal midline cognitive control system and ADHD and the first to identify a genetically related neurophysiological marker of RTV in ADHD. Variability in the timing of the theta signal in ADHD may be part of a dysfunctional brain network that impairs regulation of task-relevant responses in the disorder., (Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Parent and teacher ratings of attention deficit hyperactivity disorder (ADHD) symptoms yield high estimates of heritability whereas self-ratings typically yield lower estimates. To understand why, the present study examined the etiological overlap between parent, teacher and self-ratings of ADHD symptoms in a population-based sample of 11-12-year-old twins. Method Participants were from the Twins Early Development Study (TEDS). ADHD symptoms were assessed using the Strengths and Difficulties Questionnaire (SDQ) hyperactivity scale completed by parents, teachers and children. Structural equation modeling was used to examine genetic and environmental contributions to phenotypic variance/covariance., Results: The broad-sense heritability of ADHD symptoms was 82% for parent ratings, 60% for teacher ratings and 48% for self-ratings. Post-hoc analyses revealed significantly higher heritability for same-teacher than different-teacher ratings of ADHD (76% v. 49%). A common pathway model best explained the relationship between different informant ratings, with common genetic influences accounting for 84% of the covariance between parent, teacher and self-rated ADHD symptoms. The remaining variance was explained by rater-specific genetic and non-shared environmental influences., Conclusions: Despite different heritabilities, there were shared genetic influences for parent, teacher and self-ratings of ADHD symptoms, indicating that different informants rated some of the same aspects of behavior. The low heritability estimated for self-ratings and different-teacher ratings may reflect increased measurement error when different informants rate each twin from a pair, and/or greater non-shared environmental influences. Future studies into the genetic influences on ADHD should incorporate informant data in addition to self-ratings to capture a pervasive, heritable component of ADHD symptomatology.

Children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) demonstrate face processing abnormalities that may underlie social impairment. Despite substantial overlap between ASD and ADHD, ERP markers of face and gaze processing have not been directly compared across pure and comorbid cases. Children with ASD (n=19), ADHD (n=18), comorbid ASD+ADHD (n=29) and typically developing (TD) controls (n=26) were presented with upright/inverted faces with direct/averted gaze, with concurrent recording of the P1 and N170 components. While the N170 was predominant in the right hemisphere in TD and ADHD, children with ASD (ASD/ASD+ADHD) showed a bilateral distribution. In addition, children with ASD demonstrated altered response to gaze direction on P1 latency and no sensitivity to gaze direction on midline-N170 amplitude compared to TD and ADHD. In contrast, children with ADHD (ADHD/ASD+ADHD) exhibited a reduced face inversion effect on P1 latency compared to TD and ASD. These findings suggest children with ASD have specific abnormalities in gaze processing and altered neural specialisation, whereas children with ADHD show abnormalities at early visual attention stages. Children with ASD+ADHD are an additive co-occurrence with deficits of both disorders. Elucidating the neural basis of the overlap between ASD and ADHD is likely to inform aetiological investigation and clinical assessment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background:   Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with a complex aetiology. The identification of candidate intermediate phenotypes that are both heritable and genetically linked to ADHD may facilitate the detection of susceptibility genes and elucidate aetiological pathways. Very low-frequency (VLF; <0.5 Hz) electroencephalographic (EEG) activity represents a promising indicator of risk for ADHD, but it currently remains unclear as to whether it is heritable or genetically linked to the disorder., Methods:   Direct-current (DC)-EEG was recorded during a cognitive activation condition in 30 monozygotic and dizygotic adolescent twin pairs concordant or discordant for high ADHD symptom scores, and 37 monozygotic and dizygotic matched-control twin pairs with low ADHD symptom scores. Structural equation modelling was used to quantify the genetic and environmental contributions to the phenotypic covariance between ADHD and VLF activity., Results:   Attention deficit hyperactivity disorder was significantly associated with reduced VLF power during cognitive activation, which suggests reduced synchronization of widespread neuronal activity. Very low-frequency power demonstrated modest heritability (0.31), and the genetic correlation (-0.80) indicated a substantial degree of overlap in genetic influences on ADHD and VLF activity., Conclusions:   Altered VLF activity is a potential candidate intermediate phenotype of ADHD, which warrants further investigation of underlying neurobiological and genetic mechanisms., (© 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.)

Attention deficit hyperactivity disorder (ADHD) is characterised by developmentally inappropriate and impairing levels of inattentive and hyperactive-impulsive behaviours. We aimed to investigate the differential effects of parent and teacher ratings on inattention and hyperactivity-impulsivity and the extent of genetic overlap between the two behavioural dimensions. Multivariate structural equation modelling was performed on DSM-IV based ADHD ratings by parents and teachers collected on a general population sample of 672 twin pairs, at ages 7-10 years. This study is the first to simultaneously use parent and teacher ratings in twin modelling to examine the effects of different raters on the two behavioural dimensions of ADHD. The findings indicated that hyperactivity-impulsivity and inattention load on to separate latent factors that represent a common behavioural view for both parents and teachers, although there are additional aspects to the observations of these behaviours that are unique to each type of rater. The findings further indicate some shared aetiology for hyperactivity-impulsivity and inattention as measured by both parent and teacher ratings, in agreement with previous findings on the aetiology of the two symptom dimensions of ADHD.

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that starts in childhood and frequently persists in adults. In a comparison of adults with ADHD and a matched control sample, we previously showed that abnormal inhibitory processing is typically preceded or accompanied by other processing deficits in adult ADHD. We now compare these data further to additional data from first-degree relatives (fathers) of children with ADHD to identify whether this pattern of abnormal processing shares familial influences with ADHD in adults., Methods: Using a family design, we compared 20 fathers of children with the combined subtype of ADHD with 21 adults with ADHD combined subtype and 20 controls in event-related potential indices of preparatory states and subsequent response inhibition processing as elicited by a cued continuous performance task., Results: Fathers of children with ADHD exhibited significantly weaker orienting attention to cues and inhibitory processing than the controls but not the ADHD sample., Conclusions: These findings provide evidence for the familial association of attentional orienting and response inhibition processes with ADHD in adults and indicate a familial and neurobiological link between ADHD in children and adults.

Background: Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ., Method: Multivariate familial models were run on data from 1265 individuals aged 6-18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice-delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI)., Results: Significant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41-0.71) and IQ (rF=-0.25 to -0.49). The association between ADHD and cognitive performance was largely independent (80-87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ., Conclusions: The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder with complex genetic aetiology. The identification of candidate intermediate phenotypes may facilitate the detection of susceptibility genes and neurobiological mechanisms underlying the disorder. Electroencephalography (EEG) is an ideal neuroscientific approach, providing a direct measurement of neural activity that demonstrates reliability, developmental stability and high heritability. This systematic review evaluates the utility of a subset of electrophysiological measures as potential intermediate phenotypes for ADHD: quantitative EEG indices of arousal and intraindividual variability, and functional investigations of attention, inhibition and performance monitoring using the event-related potential (ERP) technique. Each measure demonstrates consistent and meaningful associations with ADHD, a degree of genetic overlap with ADHD and potential links to specific genetic variants. Investigations of the genetic and environmental contributions to EEG/ERP and shared genetic overlap with ADHD might enhance molecular genetic studies and provide novel insights into aetiology. Such research will aid in the precise characterisation of the clinical deficits seen in ADHD and guide the development of novel intervention and prevention strategies for those at risk.

Context: Attention-deficit/hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots or separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations., Objectives: To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD., Design: An ADHD and control sibling-pair design., Setting: Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom., Participants: A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants., Main Outcome Measures: Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task., Results: The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit., Conclusions: The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models--a developmental model and an arousal-attention model--of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform developmentally sensitive interventions.

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that starts in childhood and frequently persists in adults. Several theories postulate deficits in ADHD that have effects across many executive functions or in more narrowly defined aspects, such as response inhibition. Electrophysiological studies on children, however, indicate that ADHD is not associated with a core deficit of response inhibition, as abnormal inhibitory processing is typically preceded or accompanied by other processing deficits. It is not yet known if this pattern of abnormal processing is evident in adult ADHD., Methods: The objective of this paper was to investigate event-related potential indices of preparatory states and subsequent response inhibition processing in adults with ADHD. Two cued continuous performance tasks were presented to 21 adults meeting current criteria for adult ADHD and combined type ADHD in childhood, and 20 controls., Results: The ADHD group exhibited significantly weaker orienting attention to cues, cognitive preparation processes and inhibitory processing. In addition, we observed a strong correlation between the resources allocated to orienting to cues and the strength of the subsequent response strength control processes, suggesting that orienting deficits partly predict and determine response control deficits in ADHD., Conclusions: These findings closely resemble those previously found in children with ADHD, which indicate that there is not a core response inhibition deficit in ADHD. These findings therefore suggest the possibility of developmental stability into adulthood of the underlying abnormal processes in ADHD.

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that starts in childhood and frequently persists in adults. Electrophysiological studies in children with ADHD provide evidence for abnormal performance monitoring processes and familial association of these processes with ADHD. It is not yet known whether these processes show the same abnormalities and familial effects in adults., Method: We investigated event-related potential (ERP) indices of performance monitoring in adults with ADHD compared to age matched control participants. We subsequently investigated whether the ERP indices showed a familial association with ADHD by investigating these processes in first degree relatives of children with ADHD. This was achieved using an arrow flanker task presented to 21 adults with ADHD, 20 fathers of children with ADHD and 20 control participants., Results: Compared to the control group, both adults with ADHD and fathers of children with ADHD displayed significantly weaker error and conflict monitoring, as indexed by the smaller error negativity (Ne) and the N2 components. These two components were highly correlated within each of the three groups (r=0.53-0.65). The groups did not differ on the error positivity (Pe)., Conclusions: These findings closely resemble those previously found in children with ADHD, suggesting that conflict monitoring and early error processing are also abnormal in adults with ADHD; and share familial influences with ADHD throughout the lifespan. The relationship between different indices of performance monitoring may suggest partly common underlying mechanisms or modulators.

Attention-deficit/hyperactivity disorder (ADHD) is a common and debilitating psychiatric disorder characterized by symptoms of inattention, impulsivity and motor restlessness. Consistently noted alongside these symptoms is mood instability in the form of irritability, volatility, swift changes in mood, hot temper and low frustration tolerance. The current diagnostic classification systems do not include mood instability as a core aspect of ADHD, but rather as an associated feature of the disorder. However, the literature suggests that overlapping cognitive deficits and neuroanatomical substrates may underlie both the classical ADHD symptoms and mood instability. Furthermore, common neurotherapeutic interventions in the form of stimulant medications or atomoxetine may help to alleviate both types of symptoms when they co-occur. This research suggests that mood instability and symptoms of ADHD may be interlinked and that mood instability may be better understood as a core feature of the ADHD syndrome.

Objective: Attention deficit hyperactivity disorder (ADHD) is a common, complex and highly heritable disorder, characterised by inattentive, impulsive and overactive behaviour. Evidence for the heritability of ADHD measures in twin population samples has come from the analysis of total scores that combine inattentive and hyperactive-impulsive symptoms subscales. This study investigated, in a community sample, the aetiology of ADHD-like traits and the aetiological overlap between the two dimensions that define the ADHD disorder., Materials and Methods: Parents of 6,222 approximately 8-year-old twin pairs from the Twins Early Development Study (TEDS) population sample completed the two subscales of the Conners' 18-item DSMIV checklist, a screening instrument for ADHD symptoms., Results: Both subscales were highly heritable (hyperactive-impulsive: 88%; inattentive: 79%). Bivariate genetic modelling indicated substantial genetic overlap between the two components; however, there were significant independent genetic effects., Conclusions: These findings suggest that many genes associated with the hyperactivity-impulsivity dimension will also be associated with the inattentive dimension but that there is significant genetic heterogeneity as well. These results provide genetic support for combining the two behavioural dimensions that define ADHD, but also suggest that some symptom-specific genes will also be identified.

Attention deficit hyperactivity disorder (ADHD) is a behavioral diagnosis based on the presence of developmentally inappropriate levels of impulsivity, overactivity, and inattentiveness. It is a familial condition with a complex pattern of inheritance. Variation of several genes involved in the regulation of dopamine, norepinephrine, and serotonin neurotransmission is associated with ADHD. We highlight the two most prominent findings with the dopamine D4 receptor (DRD4) gene and the dopamine transporter (DAT1) gene, and their implications for the understanding of the cellular and neurobiological basis for ADHD. Cognitive and functional studies using electrophysiology and brain imaging frequently indicate altered processing in ADHD during performance on cognitive tasks hypothesized to measure a "core" deficit, such as response inhibition. Yet, children with ADHD appear to suffer from a more general deficit, including impairment in attentional alerting, orienting, response preparation, and control. Reward processes are also altered and, further, a strong association emerges with intraindividual variability, with several causal hypotheses being proposed. Task performance correlates with underactivation of, especially, frontostriatal areas of the brain, but an extended network of brain regions is also implicated. Electroencephalography studies indicate abnormalities in ADHD in relation to slow-wave activity, linked to underarousal. These advances in the areas of genetics, cognitive function, neurophysiology, and neuroanatomy of ADHD give important leads for interdisciplinary research that aims to delineate the causal pathways. Such research is only at its beginning, but is illustrated by recent findings of an association between DAT1 and increased response variability in ADHD.