Publications by authors named "Philip Asherson"

284 Publications

The management of ADHD in children and adolescents: bringing evidence to the clinic: perspective from the European ADHD Guidelines Group (EAGG).

Eur Child Adolesc Psychiatry 2021 Oct 22. Epub 2021 Oct 22.

LWL-University Hospital for Child and Adolescent Psychiatry, Ruhr-University Bochum, Hamm, Germany.

ADHD is the most common neurodevelopmental disorder presenting to child and adolescent mental health, paediatric, and primary care services. Timely and effective interventions to address core ADHD symptoms and co-occurring problems are a high priority for healthcare and society more widely. While much research has reported on the benefits and adverse effects of different interventions for ADHD, these individual research reports and the reviews, meta-analyses and guidelines summarizing their findings are sometimes inconsistent and difficult to interpret. We have summarized the current evidence and identified several methodological issues and gaps in the current evidence that we believe are important for clinicians to consider when evaluating the evidence and making treatment decisions. These include understanding potential impact of bias such as inadequate blinding and selection bias on study outcomes; the relative lack of high-quality data comparing different treatments and assessing long-term effectiveness, adverse effects and safety for both pharmacological and non-pharmacological treatments; and the problems associated with observational studies, including those based on large national registries and comparing treatments with each other. We highlight key similarities across current international clinical guidelines and discuss the reasons for divergence where these occur. We discuss the integration of these different perspective into a framework for person/family-centered evidence-based practice approach to care that aims to achieve optimal outcomes that prioritize individual strengths and impairments, as well as the personal treatment targets of children and their families. Finally, we consider how access to care for this common and impairing disorder can be improved in different healthcare systems.
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http://dx.doi.org/10.1007/s00787-021-01871-xDOI Listing
October 2021

Alpha oscillatory activity during attentional control in children with Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD), and ASD+ADHD.

J Child Psychol Psychiatry 2021 Sep 3. Epub 2021 Sep 3.

Department of Child & Adolescent Psychiatry, King's College London, London, UK.

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.
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http://dx.doi.org/10.1111/jcpp.13514DOI Listing
September 2021

Early neurophysiological stimulus processing during a performance-monitoring task differentiates women with bipolar disorder from women with ADHD.

Psychiatry Res 2021 09 29;303:114088. Epub 2021 Jun 29.

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, UK. Electronic address:

Adults with attention-deficit/hyperactivity disorder (ADHD) or bipolar disorder (BD) may display similar cognitive impairments and clinical symptoms, which might reflect shared mechanisms. Initial evidence indicates disorder-specific and overlapping neurophysiological alterations using event-related potentials (ERPs) in individuals with BD or ADHD during attentional tasks, but it is unknown whether impairments generalize across other processes and tasks. We conduct the first comparison between women with ADHD (n = 20), women with BD (n = 20) and control women (n = 20) on ERPs from a performance-monitoring flanker task. The BD group showed a significantly attenuated frontal ERP of conflict monitoring (N2) compared to the ADHD group across both low-conflict (congruent) and high-conflict (incongruent) task conditions, and compared to controls in the high-conflict condition. However, when controlling for an earlier attentional ERP (frontal N1), which was significantly reduced in participants with BD compared to participants with ADHD and controls, N2 group differences were no longer significant. These results indicate that ERP differences in conflict monitoring may be attributable to differences in earlier attentional processes. These findings identify neural differences in early attention between BD and ADHD which precede conflict monitoring processes, potentially pointing to distinct neural mechanisms implicated in the two disorders.
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http://dx.doi.org/10.1016/j.psychres.2021.114088DOI Listing
September 2021

Transcranial direct current stimulation (tDCS) combined with cognitive training in adolescent boys with ADHD: a double-blind, randomised, sham-controlled trial.

Psychol Med 2021 Jul 6:1-16. Epub 2021 Jul 6.

Department of Child & Adolescent Psychiatry, King's College London, London, UK.

Background: Transcranial direct current stimulation (tDCS) could be a side-effect-free alternative to psychostimulants in attention-deficit/hyperactivity disorder (ADHD). Although there is limited evidence for clinical and cognitive effects, most studies were small, single-session and stimulated left dorsolateral prefrontal cortex (dlPFC). No sham-controlled study has stimulated the right inferior frontal cortex (rIFC), which is the most consistently under-functioning region in ADHD, with multiple anodal-tDCS sessions combined with cognitive training (CT) to enhance effects. Thus, we investigated the clinical and cognitive effects of multi-session anodal-tDCS over rIFC combined with CT in double-blind, randomised, sham-controlled trial (RCT, ISRCTN48265228).

Methods: Fifty boys with ADHD (10-18 years) received 15 weekday sessions of anodal- or sham-tDCS over rIFC combined with CT (20 min, 1 mA). ANCOVA, adjusting for baseline measures, age and medication status, tested group differences in clinical and ADHD-relevant executive functions at posttreatment and after 6 months.

Results: ADHD-Rating Scale, Conners ADHD Index and adverse effects were significantly lower at post-treatment after sham relative to anodal tDCS. No other effects were significant.

Conclusions: This rigorous and largest RCT of tDCS in adolescent boys with ADHD found no evidence of improved ADHD symptoms or cognitive performance following multi-session anodal tDCS over rIFC combined with CT. These findings extend limited meta-analytic evidence of cognitive and clinical effects in ADHD after 1-5 tDCS sessions over mainly left dlPFC. Given that tDCS is commercially and clinically available, the findings are important as they suggest that rIFC stimulation may not be indicated as a neurotherapy for cognitive or clinical remediation for ADHD.
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http://dx.doi.org/10.1017/S0033291721001859DOI Listing
July 2021

Using e-diaries to investigate ADHD - State-of-the-art and the promising feature of just-in-time-adaptive interventions.

Neurosci Biobehav Rev 2021 08 4;127:884-898. Epub 2021 Jun 4.

Mental mhealth Lab, Institute of Sports and Sports Science, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Wuerttemberg, Germany.

Attention-deficit/hyperactive disorder (ADHD) is characterized by symptoms which are dynamic in nature: states of hyperactivity, inattention and impulsivity as core symptoms, and emotion dysregulation as associated feature. Although tremendous work has been done to investigate between-subject differences (how patients with ADHD differ from healthy controls or patients with other disorders), little is known about the relationship between symptoms with triggers and contexts, that may allow us to better understand their causes and consequences. Understanding the temporal associations between symptoms and environmental triggers in an ecologically valid manner may be the basis to developing just-in-time adaptive interventions. Fortunately, recent years have seen advances in methodology, hardware and innovative statistical approaches to study dynamic processes in daily life. In this narrative review, we provide a description of the methodology (ambulatory assessment), summarize the existing literature in ADHD, and discuss future prospects for these methods, namely mobile sensing to assess contextual information, real-time analyses and just-in-time adaptive interventions.
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http://dx.doi.org/10.1016/j.neubiorev.2021.06.002DOI Listing
August 2021

Self-harm and Mental Health Characteristics of Prisoners with elevated rates of autistic traits.

Res Dev Disabil 2021 Jul 15;114:103987. Epub 2021 May 15.

King's College London, United Kingdom.

Background: Prevalence studies among prisoners have found rates of 1-4% for autism spectrum disorder (ASD) or autistic traits. However, little is known about those prisoners with high levels of autistic traits.

Aim: This aim of this study was to compare the mental health characteristics of prisoners with autistic traits with neurotypical prisoners not screening positive for neurodevelopmental disorders.

Method: The study recruited 240 male prisoners from a London prison and screened for autism spectrum disorder using the Autism Quotient (AQ) 20 and 10, and Autism Diagnostic Observation Schedule (ADOS). The Mini International Neuropsychiatric Interview was used to assess for depression, anxiety, self-harm behavior and suicide.

Results: Screening using the AQ identified 46 prisoners with significant autistic traits, with 12 meeting the diagnostic threshold for ASD using the ADOS. Those screening positive with autistic traits were significantly more likely to have thought about self-harm and suicide in the past month than neurotypical prisoners and have a comorbid mental disorder. They were also significantly more likely to report having attempted suicide during their lifetime compared to neurotypical peers at a rate of 64.9 % compared to 11.6 % for the neurotypical prisoners.

Conclusion: Prisoners with elevated levels of autistic traits were more likely to report self-harm, suicidal thoughts and were more vulnerable to a range of mental disorders than neurotypical prisoners. There is a need for more evidence on the experience of autistic prisoners to inform how pathways should work to improve health outcomes through increased awareness and access to screening and subsequent diagnosis which currently prisons are currently not set up for.
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http://dx.doi.org/10.1016/j.ridd.2021.103987DOI Listing
July 2021

Failure of Healthcare Provision for Attention-Deficit/Hyperactivity Disorder in the United Kingdom: A Consensus Statement.

Front Psychiatry 2021 19;12:649399. Epub 2021 Mar 19.

Cambridge Cognition, Cambridge, United Kingdom.

Despite evidence-based national guidelines for ADHD in the United Kingdom (UK), ADHD is under-identified, under-diagnosed, and under-treated. Many seeking help for ADHD face prejudice, long waiting lists, and patchy or unavailable services, and are turning to service-user support groups and/or private healthcare for help. A group of UK experts representing clinical and healthcare providers from public and private healthcare, academia, ADHD patient groups, educational, and occupational specialists, met to discuss shortfalls in ADHD service provision in the UK. Discussions explored causes of under-diagnosis, examined biases operating across referral, diagnosis and treatment, together with recommendations for resolving these matters. Cultural and structural barriers operate at all levels of the healthcare system, resulting in a de-prioritization of ADHD. Services for ADHD are insufficient in many regions, and problems with service provision have intensified as a result of the response to the COVID-19 pandemic. Research has established a range of adverse outcomes of untreated ADHD, and associated long-term personal, social, health and economic costs are high. The consensus group called for training of professionals who come into contact with people with ADHD, increased funding, commissioning and monitoring to improve service provision, and streamlined communication between health services to support better outcomes for people with ADHD. Evidence-based national clinical guidelines for ADHD are not being met. People with ADHD should have access to healthcare free from discrimination, and in line with their legal rights. UK Governments and clinical and regulatory bodies must act urgently on this important public health issue.
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http://dx.doi.org/10.3389/fpsyt.2021.649399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017218PMC
March 2021

Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets.

J Child Psychol Psychiatry 2021 10 22;62(10):1202-1219. Epub 2021 Mar 22.

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.

Objective: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.

Methods: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.

Results: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.

Conclusion: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
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http://dx.doi.org/10.1111/jcpp.13396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455726PMC
October 2021

Validation of the German Version of the Mind Excessively Wandering Scale (MEWS-G).

Fortschr Neurol Psychiatr 2021 Feb 26. Epub 2021 Feb 26.

Klinik für Psychiatrie und Psychotherapie, Zentralinstitut für Seelische Gesundheit Klinische Fakultät Mannheim, Universität Heidelberg.

Increasing evidence shows that unintentional mind wandering is linked to Attention Deficit Hyperactivity Disorder (ADHD) and that its frequency contributes to symptom severity and functional impairment in ADHD. However, empirical data on mind wandering in adult ADHD are still scarce, and a validated scale to assess mind wandering in German adult ADHD patients is lacking. The primary aim of this study is to assess the psychometric properties of the German version of the recently published Mind Excessively Wandering Scale (MEWS-G) in terms of factorial structure and factor stability, internal consistency and construct validity. Analyses were performed in 128 adults with ADHD, clinical and healthy controls. As described for the original English 15-item version of the scale, we found lowest item-total-correlations for items 6, 10 and 14 with item-total correlation of all: 0.54/ADHD: 0.32 (item 6), all: 0.55/ADHD: 0.39 (item 10) and all: 0.11/ADHD: -0.04 (item 14). Item-total correlations for the remaining items were 0.65-0.86 and Cronbach Alpha was 0.96 indicating good internal consistency of the 12-item version of scale, on which we based all further analyses. Principal component analysis indicated a one- and two- factorial scale structure respectively explaining 71.7 % and 78.7 % of variance. Both factors showed good stability with lower stability of the factor-2 solution if sample size was reduced. The two-factorial solution also had many cross-loadings and a strong correlation of both factors in confirmatory factorial analysis (rf1f2 = 0.87). It probably describes related and interdependent, but not distinct facets of mind wandering, which strongly argues for the one factorial structure of the scale. Mean MEWS-G score in ADHD was 23.77 ± 7.85 compared to 7.64 ± 7.27 in controls (p < .0001). According to ROC, the optimal cut-off point to discriminate ADHD and controls is at MEWS-G score = 13. On the symptom level, MEWS-G score was correlated with ADHD, depressive and total psychiatric symptom scores, on the personality level with neuroticsm and negatively with conscientiousness and on the functional level with social interaction difficulties and impaired self-efficacy. In summary, our study shows that MEWS-G is a reliable, valid instrument to assess spontaneous mind wandering in adult ADHD and to discriminate between ADHD and controls.
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http://dx.doi.org/10.1055/a-1362-9743DOI Listing
February 2021

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 17. Epub 2021 Feb 17.

Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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http://dx.doi.org/10.1002/hbm.25364DOI Listing
February 2021

Comparable emotional dynamics in women with ADHD and borderline personality disorder.

Borderline Personal Disord Emot Dysregul 2021 Feb 12;8(1). Epub 2021 Feb 12.

King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK.

Background: Emotional dysregulation (ED) is a core diagnostic symptom in borderline personality disorder (BPD) and an associated feature of attention-deficit/hyperactivity disorder (ADHD). We aimed to investigate differences in dynamical indices of ED in daily life in ADHD and BPD.

Methods: We used experience sampling method (ESM) and multilevel modelling to assess momentary changes in reports of affective symptoms, and retrospective questionnaire measures of ED in a sample of 98 adult females with ADHD, BPD, comorbid ADHD+BPD and healthy controls.

Results: We found marked differences between the clinical groups and healthy controls. However, the ESM assessments did not show differences in the intensity of feeling angry and irritable, and the instability of feeling sad, irritable and angry, findings paralleled by data from retrospective questionnaires. The heightened intensity in negative emotions in the clinical groups compared to controls was only partially explained by bad events at the time of reporting negative emotions, suggesting both reactive and endogenous influences on ED in both ADHD and BPD.

Conclusions: This study supports the view that ED is a valuable trans-diagnostic aspect of psychopathology in both ADHD and BPD, with similar levels of intensity and instability. These findings suggest that the presence or severity of ED should not be used in clinical practice to distinguish between the two disorders.
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http://dx.doi.org/10.1186/s40479-021-00144-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879647PMC
February 2021

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 11. Epub 2021 Feb 11.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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http://dx.doi.org/10.1002/hbm.25320DOI Listing
February 2021

The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder.

Neurosci Biobehav Rev 2021 09 4;128:789-818. Epub 2021 Feb 4.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Wuerzburg, Germany. Electronic address:

Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base.

Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder.

Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents.

Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.
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http://dx.doi.org/10.1016/j.neubiorev.2021.01.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328933PMC
September 2021

Recommendations for occupational therapy interventions for adults with ADHD: a consensus statement from the UK adult ADHD network.

BMC Psychiatry 2021 02 4;21(1):72. Epub 2021 Feb 4.

Psychology Services Limited, London, UK.

Background: ADHD is neurodevelopmental disorder which persists into adulthood. Presently, therapeutic approaches are mainly pharmacological and psychological whilst the role, scope and approaches of occupational therapists have not been adequately described.

Results: In this consensus statement we propose that by assessing specific aspects of a person's occupation, occupational therapists can deploy their unique skills in providing specialist interventions for adults with ADHD. We also propose a framework with areas where occupational therapists can focus their assessments and give practice examples of specific interventions.

Conclusions: Occupational therapists have much to offer in providing interventions for adults with ADHD. A unified and flexible approach when working with adults with ADHD is most appropriate and further research on occupational therapy interventions is needed.
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http://dx.doi.org/10.1186/s12888-021-03070-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863422PMC
February 2021

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

Psychol Med 2021 Feb 3:1-9. Epub 2021 Feb 3.

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

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, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 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.
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http://dx.doi.org/10.1017/S0033291720005218DOI Listing
February 2021

Electrophysiological modulation of sensory and attentional processes during mind wandering in attention-deficit/hyperactivity disorder.

Neuroimage Clin 2021 30;29:102547. Epub 2020 Dec 30.

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom. Electronic address:

We recently reported increased mind wandering (MW) frequency in adults with attention-deficit/hyperactivity disorder (ADHD) relative to controls during high demands on sustained attention, reflecting deficient context regulation of MW. Studies on community samples previously linked context regulation of MW with attenuation in brain sensory processes, reflecting perceptual decoupling, and attentional processes during MW compared to task focus. However, the association between deficient context regulation of MW and these neural processes has not been studied in ADHD. We addressed this question by comparing adults with ADHD (N = 23) and controls (N = 25) on event-related potentials of early sensory processes (P1) and attention allocation (P3) during tasks manipulating cognitive demands (high vs low) on working memory and sustained attention, and during periods of MW and task focus measured through experience-sampling. Compared to controls, adults with ADHD showed reduced P1 during high sustained attention demands, as well as reduced P3 during high working memory demands. These group differences were no longer significant after adding MW frequency as a covariate. Across tasks, adults with ADHD showed no differences from controls on the P1 during MW episodes, but attenuated P1 during task focus. P3 was reduced in adults with ADHD compared to controls during MW, but not during task focus during the sustained attention task. These findings converge to indicate that impairments in early sensory processing in individuals with ADHD seem parallel to increased MW frequency and might reflect inefficient adjustments from periods of MW to task focus.
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http://dx.doi.org/10.1016/j.nicl.2020.102547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808945PMC
June 2021

Emotion recognition and mind wandering in adults with attention deficit hyperactivity disorder or autism spectrum disorder.

J Psychiatr Res 2021 02 22;134:89-96. Epub 2020 Dec 22.

Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in adults are often undiagnosed and overlap in psychopathology. Here we investigated the transdiagnostic traits of emotion recognition and mind wandering in a sample of 103 adults (43 with ADHD and 14 with ASD). The ability to correctly identify a facial expression of anger, fear, disgust or surprise was no different between the adults with ADHD or ASD and neurotypical (NT) adults. However, adults with ADHD or ASD were on average almost 200 ms slower in making a correct decision, suggesting a larger speed-accuracy trade-off in facial emotion recognition compared to NT adults. General processing speed was associated with excessive mind wandering in adults with ADHD, but not with ASD. The deficits in emotional processing were independent from mind wandering in both adults with ADHD or ASD. Emotional dysregulation and functional impairment scales separated adults with ADHD and ASD from the NT adults, but not from each other. When controlling for self-reported ADHD and ASD symptom severity, mind wandering in ADHD was independent from both ADHD and ASD symptom severity. In ASD, mind wandering was related to ASD but not ADHD symptom severity. Our results suggest that ASD and ADHD share a slower ability to recognize emotions, which is exacerbated by excessive mind wandering in ADHD, and by decreased processing speed in ASD.
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http://dx.doi.org/10.1016/j.jpsychires.2020.12.059DOI Listing
February 2021

Greater male than female variability in regional brain structure across the lifespan.

Hum Brain Mapp 2020 Oct 12. Epub 2020 Oct 12.

FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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http://dx.doi.org/10.1002/hbm.25204DOI Listing
October 2020

Context Regulation of Mind Wandering in ADHD.

J Atten Disord 2021 Dec 18;25(14):2014-2027. Epub 2020 Sep 18.

King's College London, De Crespigny Park, UK.

Objective: We aimed to understand the association between MW frequency and clinical measures, context regulation of MW and group differences in task performance.

Method: 27 adults with ADHD and 29 controls performed tasks manipulating demand on working memory and sustained attention, and recorded their MW frequency using probes.

Results: A significant association between MW frequency and the clinical measures was demonstrated. Along with increased MW frequency, individuals with ADHD reported decreasing MW frequency during increasing demands on working memory (context regulation), but not on sustained attention (deficient context regulation). Controls, however, maintained continuous task focus across all conditions. Group differences in task performance were no longer significant after adding MW frequency as a covariate.

Conclusion: Deficient context regulation during increasing demands on sustained attention suggests that sustained attention deficits may play a more important role in regulation of MW in ADHD. MW frequency might also underpin performance deficits in ADHD.
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http://dx.doi.org/10.1177/1087054720956714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527550PMC
December 2021

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders.

JAMA Psychiatry 2021 Jan;78(1):47-63

Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University, the Netherlands.

Importance: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood.

Objective: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia.

Design, Setting, And Participants: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244.

Main Outcomes And Measures: Interregional profiles of group difference in cortical thickness between cases and controls.

Results: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders.

Conclusions And Relevance: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.2694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450410PMC
January 2021

Mapping UK mental health services for adults with attention-deficit/hyperactivity disorder: national survey with comparison of reporting between three stakeholder groups.

BJPsych Open 2020 Jul 29;6(4):e76. Epub 2020 Jul 29.

Department of Psychiatry, University of Cambridge, UK.

Background: UK clinical guidelines recommend treatment of attention-deficit hyperactivity disorder (ADHD) in adults by suitably qualified clinical teams. However, young people with ADHD attempting the transition from children's to adults' services experience considerable difficulties in accessing care.

Aims: To map the mental health services in the UK for adults who have ADHD and compare the reports of key stakeholders (people with ADHD and their carers, health workers, service commissioners).

Method: A survey about the existence and extent of service provision for adults with ADHD was distributed online and via national organisations (e.g. Royal College of Psychiatrists, the ADHD Foundation). Freedom of information requests were sent to commissioners. Descriptive analysis was used to compare reports from the different stakeholders.

Results: A total of 294 unique services were identified by 2686 respondents. Of these, 44 (15%) were dedicated adult ADHD services and 99 (34%) were generic adult mental health services. Only 12 dedicated services (27%) provided the full range of treatments recommended by the National Institute for Health and Care Excellence. Only half of the dedicated services (55%) and a minority of other services (7%) were reported by all stakeholder groups (P < 0.001, Fisher's exact test).

Conclusions: There is geographical variation in the provision of NHS services for adults with ADHD across the UK, as well as limited availability of treatments in the available services. Differences between stakeholder reports raise questions about equitable access. With increasing numbers of young people with ADHD graduating from children's services, developing evidence-based accessible models of care for adults with ADHD remains an urgent policy and commissioning priority.
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http://dx.doi.org/10.1192/bjo.2020.65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443899PMC
July 2020

Wandering minds in attention-deficit/hyperactivity disorder and borderline personality disorder.

Eur Neuropsychopharmacol 2020 09 20;38:98-109. Epub 2020 Jul 20.

King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, 16 DeCrespigny Park, London SE5 8AF, United Kingdom.

Attention-deficit/hyperactivity Disorder (ADHD) and borderline personality disorder (BPD) have overlapping symptoms. We proposed that excessive spontaneous mind wandering (MW-S) might reflect a component of psychopathology that distinguishes ADHD from BPD. Using a questionnaire measure of MW-S and an experience sampling method, we investigated MW-S in daily life, in 28 ADHD, 19 BPD, 22 comorbid ADHD+BPD, and 29 control females. The clinical groups reported heightened frequency and intensity of MW-S compared to controls, but no differences from each other. When controlling for depression and anxiety, significant differences only persisted between controls and ADHD, who also showed elevated intensity of MW-S compared to BPD and comorbid ADHD+BPD. We found no MW-S instability differences amongst clinical cases as well as cases versus controls. Negative content of MW-S was higher in BPD and comorbid ADHD+BPD compared to controls, with no differences between ADHD and controls. When controlling for depression/anxiety, the differences between BPD and comorbid ADHD+BPD and controls dissipated. MW-S is a trans-diagnostic process present in both ADHD and BPD. Yet, the underlying mechanisms of this experience may be driven by anxiety/depression in BPD but reflect a core process in ADHD.
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http://dx.doi.org/10.1016/j.euroneuro.2020.07.005DOI Listing
September 2020

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

Psychol Med 2020 Jul 2:1-10. Epub 2020 Jul 2.

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

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.
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http://dx.doi.org/10.1017/S0033291720002056DOI Listing
July 2020

Lateralization of attention in adults with ADHD: Evidence of pseudoneglect.

Eur Psychiatry 2020 06 29;63(1):e68. Epub 2020 Jun 29.

Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Background: We investigated whether adults with attention-deficit/hyperactivity disorder (ADHD) show pseudoneglect-preferential allocation of attention to the left visual field (LVF) and a resulting slowing of mean reaction times (MRTs) in the right visual field (RVF), characteristic of neurotypical (NT) individuals -and whether lateralization of attention is modulated by presentation speed and incentives.

Method: Fast Task, a four-choice reaction-time task where stimuli were presented in LVF or RVF, was used to investigate differences in MRT and reaction time variability (RTV) in adults with ADHD (n = 43) and NT adults (n = 46) between a slow/no-incentive and fast/incentive condition. In the lateralization analyses, pseudoneglect was assessed based on MRT, which was calculated separately for the LVF and RVF for each condition and each study participant.

Results: Adults with ADHD had overall slower MRT and increased RTV relative to NT. MRT and RTV improved under the fast/incentive condition. Both groups showed RVF-slowing with no between-group or between-conditions differences in RVF-slowing.

Conclusion: Adults with ADHD exhibited pseudoneglect, a NT pattern of lateralization of attention, which was not attenuated by presentation speed and incentives.
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http://dx.doi.org/10.1192/j.eurpsy.2020.68DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443776PMC
June 2020

Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups.

Am J Psychiatry 2020 09 16;177(9):834-843. Epub 2020 Jun 16.

The full list of authors in the ENIGMA working groups, author affiliations, author disclosures, and acknowledgments are provided in online supplements.

Objective: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.

Methods: Structural T-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).

Results: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.

Conclusions: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
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http://dx.doi.org/10.1176/appi.ajp.2020.19030331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296070PMC
September 2020

Reliability, Criterion and Concurrent Validity of the Farsi Translation of DIVA-5: A Semi-Structured Diagnostic Interview for Adults With ADHD.

J Atten Disord 2021 10 3;25(12):1666-1675. Epub 2020 Jun 3.

MRC Social Genetic and Developmental Psychiatry, Institute of Psychiatry, King's College London, UK.

This study evaluated the psychometrics of the Farsi translation of diagnostic interview for attention-deficit hyperactivity disorder (ADHD) in adults (DIVA-5) based on DSM-5 criteria. Referrals to a psychiatric outpatient clinic ( = 120, 61.7% males, mean age 34.35 ± 9.84 years) presenting for an adult ADHD (AADHD) diagnosis, were evaluated using the structured clinical interviews for DSM-5 (SCID-5 & SCID-5-PD) and the DIVA-5. The participants completed Conner's Adult ADHD Rating Scale-Self Report-Screening Version (CAARS-S-SV). According to the SCID-5 and DIVA-5 diagnoses, 55% and 38% of the participants had ADHD, respectively. Diagnostic agreement was 81.66% between DIVA-5/SCID-5 diagnoses, 80% between SCID-5/CAARS-S-SV, and 71.66% between DIVA-5/CAARS-S-SV. Test-retest and inter-rater reliability results for the DIVA-5 were good to excellent. Findings support the validity and reliability of the Farsi translation of DIVA-5 among the Farsi-speaking adult outpatient population.
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http://dx.doi.org/10.1177/1087054720930816DOI Listing
October 2021

Electrophysiological correlates of spontaneous mind wandering in attention-deficit/hyperactivity disorder.

Behav Brain Res 2020 08 30;391:112632. Epub 2020 Apr 30.

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, United Kingdom; Semel Institute for Neuroscience & Human Behavior, University of California Los Angeles, 760 Westwood Plaza, Los Angeles, CA, 9002/4, United States. Electronic address:

We recently hypothesised that increased spontaneous mind wandering (MW-S) reflects a core process underlying attention-deficit/hyperactivity disorder (ADHD). Previous studies show that individuals with ADHD and neurotypical individuals with increased MW-S display similar cognitive-performance and electrophysiological (EEG) impairments in attentional processes. However, the cognitive-EEG markers associated with increased MW-S in ADHD remain poorly understood. We therefore investigated such markers in a sample of 69 sex- and age-matched adults with ADHD and 29 controls during the Sustained Attention to Response Task. We compared task performance and EEG measures (P3, time-frequency brain-oscillations) of attentional processes between groups, and examined their association with a validated self-report questionnaire of MW-S. Finally, we tested the hypothesis that MW-S and ADHD diagnosis relate to the same cognitive-EEG impairments using a hierarchical regression model. Compared to controls, adults with ADHD showed attenuations in P3, event-related alpha and beta suppression during response inhibition (No-Go trials), and theta power activations during response execution (Go trials), as well as increased reaction time variability and more commission/omission errors. MW-S was also continuously associated with most cognitive-EEG measures related to ADHD. The hierarchical regressions on measures associated with both ADHD diagnosis and MW-S showed that MW-S did not explain additional variance in the cognitive-EEG markers (except for beta suppression) beyond ADHD diagnosis, and vice versa. These findings are consistent with our hypothesis that ADHD diagnosis and MW-S share common neural deficits, and that MW-S may reflect a core symptom of the disorder.
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http://dx.doi.org/10.1016/j.bbr.2020.112632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303944PMC
August 2020

Shared genetic background between children and adults with attention deficit/hyperactivity disorder.

Neuropsychopharmacology 2020 09 12;45(10):1617-1626. Epub 2020 Apr 12.

Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.
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http://dx.doi.org/10.1038/s41386-020-0664-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419307PMC
September 2020
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