Professor Philip Asherson
Future Directions in ADHD
In the first plenary session of Day 2, Professor Barbara Franke (Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands) gave an informative presentation on epigenetics as a window to understanding the contribution of the environment in ADHD. Professor Franke presented research showing that higher methylation status of the SLC6A4 serotonin transporter gene promoter has been associated with higher severity of hyperactive-impulsive symptoms in children with ADHD.1 She then discussed epigenetic research from her own laboratory, which compared DNA methylation between ADHD trajectories, reporting that children with remitted ADHD showed a level of methylation intermediate to cases and control patients.
The second lecture of this session was delivered by Professor Philip Asherson (MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK), who discussed DSM symptoms of ADHD and questioned whether they are sufficient to diagnose adult ADHD. Professor Asherson highlighted emotional impulsivity as an important symptom of ADHD,2 which is not adequately captured by current diagnostic criteria despite being a key contributor to impairment in ADHD. He also discussed task-unrelated thoughts and their correlation with Default Mode Network activity, and reported his own findings related to the measurement of mind wandering in adults with ADHD using the Mind Excessively Wandering Scale.3
In a thought-provoking presentation from Professor Edmund Sonuga-Barke (Department of Child and Adolescent Psychiatry Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK), the effect of extraordinary environments on the development of inattention and overactivity was discussed. Using data from a longitudinal study of English and Romanian adoptees, Professor Sonuga-Barke described how orphans who experienced severe deprivation for 1 to 43 months from birth, before being adopted by families in the UK, were compared with UK adoptees who had not experienced deprivation. Romanian adoptees who had experienced more than 6 months of deprivation showed higher rates of inattention and overactivity versus UK adoptees through to young adulthood.4
In the final lecture of this plenary session, Professor Alejandro Anrias Vásques (Radboud University Medical Centre, Groningen, the Netherlands) discussed preliminary unpublished data on the gut microbiome and how it may influence cognition and behaviour in ADHD. Professor Vásques described his study, in which mice were colonised with microbiota from individuals with and without ADHD, with behavioural and brain imaging tests conducted after 4 weeks. Mice colonised with microbiota from individuals with ADHD showed increased anxiety compared with control mice, with altered brain structure and connectivity in brain areas known to be altered in adults with ADHD. Professor Vásques concluded by talking about his plans for future research, which will eventually be conducted in humans.
Professor Asherson: “ADHD represents the extreme of one or more highly heritable quantitative traits…and we may never be able to define the boundary between having and not having ADHD.”
Professor Klaus W Lange and Professor David Coghill
Pros and cons: The treatment of ADHD patients has long-term effects
In a lively debate moderated by Katherine Ellison, Professor David Coghill (Department of Paediatrics and Psychiatry, University of Melbourne, Melbourne, Australia) opened the session by discussing whether the risks of long-term medication use outweigh the benefit; he concluded that there are significant risks associated with not treating ADHD and that treatment of ADHD did have long-term benefits. He described the results from several observational studies which highlighted that pharmacological treatment significantly reduced criminality rates, significantly reduced the number of trauma-related ER visits, decreased the risk of poor educational outcomes and substance use disorder, had a protective effect on comorbidity, and improved driving and obesity. Using results from the MTA study and Dundee study he went on to highlight that treatment effects don’t need to slip back over time if there is careful titration, and continued care and observation.
In his rebuttal, Professor Klaus W Lange (Department of Experimental Psychology, University of Regensburg, Regensburg, Germany) concluded that there is no proof that treatment of ADHD has long-term beneficial effects. He noted that the results presented by Professor Coghill were from observational studies and patients were not from the ‘general population’. He says that the paucity of long-term randomised trials makes it difficult to assess long-term treatment effects. He went on to explain that when new drugs are developed there is a need for 3-arm trials which include a placebo, an established drug and a new drug. He also advised that studies should be independent, rather than pharmaceutical company led to ensure there is no result bias.
Professor Coghill came back to the stage to highlight that 3-arm studies are now a requirement of the EMA, although still not for the FDA. He also went on to say that industry sponsored studies are more critically evaluated now than University studies, in that Investigators have to sign off results and Study Reports are published online in full. He also concluded that long-term randomised studies were not ethical and that the best approach would be to conduct more randomised withdrawal studies.
Professor Coghill: “Functional outcomes and real-world outcomes should be measured at every assessment, as well as positive and negative outcomes of treatment.”
Professor Lange: “A randomised controlled trial should only be conducted if you are not sure of the outcome.”
Dr Duncan Manders, Dr Kenny Handelman, Professor Peter Jensen and Professor David Coghill
Industry Sponsored Symposium
Sustaining the optimal management of ADHD in children and adolescents
Supported by an unrestricted educational grant from Shire, now part of Takeda
Dr Kenny Handelman (Oakville Trafalgar Memorial Hospital, Ontario, Canada) opened the symposium by highlighting that ADHD is a lifelong disorder which goes beyond core symptoms into functional outcomes. He noted that patients change over time, become non-compliant, etc; it is therefore imperative that management of patients with ADHD adapts alongside the patient.
Professor Peter Jensen (University of Arkansas for Medical Sciences & CEO of the REACH Institute, Arkansas, AR, USA) discussed how the key findings from the MTA study can be used to encourage optimal management of ADHD. The diverse real-world nature of the patient population was described and he highlighted the importance of monitoring throughout the 14-month study, especially during the titration period where in the MTA study the patient was assessed weekly. He described the percentage of normalised patients at 14-month endpoint , (68% combined, 56% medication only, 33% behavioural therapy only, 25% community care).5 He reported that the key differences between the medication only and community care results were due to the initial titration, dose, dose frequency, number of visits/year, length of visits and contact with schools. He went on to show that after the 14-month study period was over, and patients went back to their usual community care, the differences observed disappeared. He surmised this was because rating scales weren’t being used, there was no teacher input, lower number of visits, non-compliance etc, and he concluded that intensive medication management is more effective than community care treatment as long as it is continued.
Professor David Coghill (Department of Paediatrics and Psychiatry, University of Melbourne, Melbourne, Australia) explained that the only difference between the Dundee study and the MTA study was that they weren’t starting treatment with an intensive titration period and weren’t seeing the patient on a monthly basis, so in the Dundee study they switched to a nurse-led modified MTA protocol (initial 4-week titration which focused on symptom reduction and optimising treatment). They also used a fixed protocol of SNAP-IV (clinician delivered); SKAMP (teacher); height, weight, pulse, BP measured; adverse events (framed as ‘other symptoms’); and screened for ‘other problems’ and arranged treatment as required over the 4-week titration period, which continued on a monthly basis as continued care. SNAP-IV or ADHD-IV (total mean item score) was recorded as 2.5 at baseline, 0.7 at the end of titration, 1.0 during continuing care and 0.8 at the most recent visit (mean duration of treatment 43 months).6 This demonstrated that with the right support treatment effects do not need to dwindle over time.
In the discussion session moderated by Dr Duncan Manders (The Royal Hospital for Sick Children, Edinburgh, UK), the expert panel were unanimous in the opinion that it is important to use rating scales when assessing symptoms and functional outcomes; however, dialogue with the families, school, peers, and the patient themselves is just as important. When asked by the audience when they would switch treatment, Professor Luis Rohde (Federal University of Rio Grande do Sul, Porto Alegre, Brazil) emphasised the importance of thinking about dose before switching and Dr Javier Quintero (University Hospital Infanta Leonor, Madrid, Spain) said that it was important to manage the expectations of the family.
Dr Handelman: “There is no ‘one size fits all’ for each patient as we have to assess the individual needs of each patient…it is important to get to optimal management and sustain it over time.”
Professor Jensen: “If you don’t have those personal conversations you are going to miss the boat.”
Professor Coghill: “Need to individualise treatment but we don’t have a tool to predict response.”
Professor Martin Katzman
Industry Sponsored Symposium
Can the newest research in ADHD translate into better patient outcomes? A case-based examination
Supported by Purdue
In this industry sponsored session, a case-based examination was used to discuss recent research in ADHD and how it could translate into better patient outcomes. The session Chair, Professor Martin Katzman (START Clinic for Mood and Anxiety Disorders, Toronto, Ontario, Canada) began by familiarising the audience with the patient; Sarah, a marketing executive referred to his practice for the treatment of depression and anxiety. Sarah’s history had a number of features that led Professor Katzman to consider a diagnosis of ADHD; she was divorced, with a poor employment record, a history of risk behaviour as a teenager and a family history of ADHD. Professor Katzman presented unpublished data, which suggest that 34% of individuals with treatment-resistant depression could meet criteria for ADHD. Dr Timothy Bilkey (Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada) then went on to describe a number of psychosocial treatments that could be considered for a patient like Sarah, with ADHD. Dr Bilkey discussed the role of ‘critical moments’ and ‘peripheral brains’ (e.g. phone alarms and personal organisers) and the role of cognitive behavioural therapy, as described in his book, ‘FAST MINDS. How to Thrive If You Have ADHD’.7 The session concluded with a presentation from Dr Angelo Fallu (Clinique Woodward and Diex Research Inc., Sherbrooke, Québec, Canada), who provided a detailed overview of diagnostic interviews, symptom rating scales and the application of the latest inventories of executive function and functional impairment in clinical practice.8
Dr Bilkey: “There are multiple forms of ADHD contingent on a person’s constellation of strengths and challenges.”
Professor Katzman: “Critical moments are like the fork in the road, one way leading to a life that runs well, the other leading to default rhythms of activity – the moment before you make a bad choice.”
Hot Topic Symposium
Anxiety disorders and adult ADHD across the life cycle
In this hot topic symposium, comorbid anxiety disorders and adult ADHD were discussed across four engaging presentations. Dr Cesar Soutullo opened the session with an overview of anxiety disorders at different stages of childhood, and the estimated prevalence of anxiety in children with ADHD. Dr Soutullo then described the difficulties of differentiating between ADHD and anxiety, particularly where the symptoms of ADHD are masked by anxiety, e.g. when impulsivity is suppressed by social anxiety disorder.
Professor Frederick Reimherr (Mood Disorders Clinic, Department of Psychiatry, University of Utah Health Sciences Center, Salt Lake City, UT, USA) then went on to discuss his unpublished data, which looked at the prevalence of comorbid ADHD and anxiety in samples from: ADHD studies, anxiety studies (without ADHD), ADHD patients in clinical practice and patients with ADHD and/or generalised anxiety disorder referred to his clinic by US Federal Probation and Parole. Professor Reimherr found the prevalence of anxiety in each of these populations to be 30%, 24%, 24% and 24%, respectively. He also presented preliminary findings, which suggest that high anxiety is more frequent in individuals with combined subtype ADHD versus inattentive and hyperactive/impulsive subtypes.
Professor Manfred Dӧpfner (Department of Psychiatry, Psychosomatics and Psychotherapy in Childhood and Adolescence, Medical Faculty, University of Cologne, Cologne, Germany) then provided a comprehensive overview of psychosocial interventions in the treatment of ADHD and anxiety, both as separate and comorbid disorders. Professor Dӧpfner explained that psychosocial interventions in both anxiety and ADHD are patient focused, parent focused and school focused, with some evidence to suggest that family interventions may be more effective than child-only interventions in anxiety. He concluded that combined treatment with psychosocial and pharmacological treatments is likely to be the most appropriate approach in treating comorbid ADHD and anxiety.
The session concluded with a presentation from Professor Lenard Adler (Psychiatry and Child and Adolescent Psychiatry at New York University School of Medicine, New York, NY, USA), which provided a sneak preview of his research on the treatment of comorbid ADHD and anxiety disorders in adults.
Hot Topic Symposium
Comorbidity of adult ADHD with mood disorders? Mechanisms and genetics
Dr Eugenio Grevet (Faculty of Medicine, Federal University at Rio Grande do Sul, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil) opened the symposium by discussing depression as a red flag for adult ADHD, highlighting the relationship between ADHD, emotional dysregulation and depression, and explaining that there was a red thread linking depression to ADHD.
The second presentation by Dr Martin Katzman (START Clinic for Mood and Anxiety Disorders, Lakehead University, University of Toronto, The Northern Ontario School of Medicine, & Adler School of Professional Studies, Toronto, Ontario, Canada) began by emphasising that comobidity of depression and ADHD represents a common phenotypic presentation and that untreated comorbid ADHD is predictive of much poorer treatment outcomes in those patients who are depressed. During the presentation he explained that hedonic tone represents the capacity to experience reward, and anhedonia represents the state of reduced ability to experience pleasure, with low hedonic tone increasing the likelihood of experiencing anhedonia. He then went on to describe the involvement of neural circuits in bottom-up and top-down systems in the prefrontal cortex and neuromodulation of dopamine, noradrenaline and serotonin. He also elucidated that patients with lower hedonic tone may try to elevate this to reach euthymia through internalising activity, e.g. fantasy/day-dreaming or externalising activity, e.g. risky behaviour/self-medication. He concluded that low hedonic tone that represents a chronic anhedonia associated with lower catecholaminergic tone, and may be the connection between ADHD and depression; low hedonic tone as a manifestation of ADHD comorbidity with depression may explain a poor response to SSRIs and increased suicidality.
Dr Manuel Mattheisen (Department of Biomedicine and Center for Integrated Sequencing (iSEQ), Aarhus University, Aarhus, Denmark) provided the audience with an overview of the genetics of ADHD and MDD, shared heritability and risk loci. He described the shared heritability measures used such as genome-wide complex trait analysis (GCTA), LD score regression (LDSC) and polygenic risk scores (PRS) and their strengths and limitations. He noted that there were two key genes, SORC53 and NEGR1, involved in ADHD. Regarding the heritability of ADHD and comorbid MDD and ADHD he presented results from the Cross-Disorder Group of Psychiatric Genomics and his unpublished research from the iPSYCH study but concluded that more studies with increased sample size were required and results should be interpreted with caution.
The symposium was closed by a presentation from Dr Andreas Reif (Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany) who discussed the relationship between comorbid bipolar disorder (BD) and ADHD. He began by describing BD as a chronic and potentially lethal disorder with a lifetime prevalence of 1% (WHO data) and went on to describe the manic, hypomanic and depressive episodes and the different courses of bipolar I and II disorder. He also noted that ADHD diagnosis can be challenging because its symptoms are often mistakenly assumed to be part of BD; however, he did highlight the notable differences between ADHD and BD, for example, that ADHD starts in childhood, but BD usually starts in late adolescence/early adulthood. He described ADHD as a trait-like condition and BD as a phasic condition. He presented results from a meta-analysis of family genetic probands which found a significantly higher prevalence of ADHD among relatives of bipolar probands and a significantly higher prevalence of bipolar I disorder among relatives of ADHD probands.9
Dr Søren Dalsgaard
Meet the Experts
A missing window: The assessment and treatment of ADHD in the transition of adolescence to adulthood
In this Meet the Expert session, Dr Søren Dalsgaard (National Centre for Register-Based Research, NCRR, Aarhus University, Denmark) discussed his experience of adolescents with ADHD transitioning into adulthood. He began by emphasising that adolescence is a period of change for everyone and sometimes it can be difficult to disentangle the ADHD and normal development/puberty. He noted that when you have ADHD the transition from being an adolescent to becoming an independent adult is extra difficult. Adolescents with ADHD may get lost in the transition due to challenges of assessment and treatment, differing support systems, changes for the individual and their family.
When assessing adolescents and young adults clinicians face many challenges, such as core symptom changes (e.g. more procrastination, more problems with planning and prioritisation, hyperactive symptoms become less visible, the impact of executive dysfunctions become more evident and emotional dysregulations and impulsive behaviour become clearer), which informants should be trusted the most (scores from self-reports and parent/teacher reports often differ), and patterns of comorbidity change. It was also noted that during adolescence patients want to become more independent … and they should, but they have to learn that this can be more difficult. He highlighted that parents also face new frustrations in this transition period when many adolescents with ADHD don’t want help from their parents.
Dr Dalsgaard described the typical difficulties for adolescents with ADHD at home (e.g. going to bed late, very tired in the morning, disagreements and less interaction/communication with their parents), and in relation to treatment (discontinuation or skipping medication). One of the key issues for adolescents with ADHD is non-compliance with medication; poorer compliance can be related to higher severity of ADHD, older age at initiation of medication, family dysfunction, multi-dose administration and low starting dose. To encourage adolescents with ADHD to remain compliant it is important to let them know that compliance decreases the severity of ADHD symptoms and impairment, decreases conflict-level with adults and peers and also decreases the risk of substance use disorder, criminality, injuries, traffic accidents, depression and suicidal behaviour. Dr Dalsgaard also emphasised that if medication is discontinued, the rest of the treatment package is likely to be discontinued as well.
To facilitate transition from adolescent to adult services, the physician should be aware that patient-clinician relationships are important, to implement protocols for transition, to plan in collaboration with the patient and family at least 1 year ahead, to transfer medical records of the patient to adult services, and also ensure collaboration between both services with a temporal overlap. Dr Dalsgaard advocated continued use of mental health services or at least shared-care with GPs, the importance of clinician-patient relationships, communication with the patient and avoiding non-compliance as key to optimal follow-up of adolescents with ADHD.
Dr Dalsgaard: “When you see kids in the clinic it is important to be aware that those who need treatment the most will be the ones that are not compliant.”
Dr Wolfgang Retz
New assessment strategies of ADHD in adults
In this educational seminar, an engaged audience learned about assessment strategies in adults with ADHD. Katharina Bachmann (School of Medicine and Health Sciences, Medical Campus University of Oldenburg, Oldenburg, Germany) presented comprehensive information on the symptoms of adult ADHD and emphasised the importance of utilising multiple observations in the assessment of adults with suspected ADHD. She suggested that clinicians should consider the longitudinal history of symptoms, other potential differential diagnoses, coping strategies that might mask symptoms of ADHD, family history, school report cards and reports from other individuals in the patient’s life, e.g. partner or parents. Dr Wolfgang Retz (Department of Psychiatry and Psychotherapy, University Medical Center, Mainz, Germany) recommended the use of standardised instruments in the assessment of adult ADHD; however, he stressed the dangers of basing a diagnosis of ADHD purely on rating scales and recommended a complete psychiatric assessment. Although the patient should be considered the most important source of information, Dr Retz described the benefits of utilising reports from other informants (e.g. parents) can give a more accurate description of childhood symptoms. The audience asked a number of questions related to the use of standardised instruments in clinical practice. The difficulties of obtaining informant ratings were of particular interest, as were the problems associated with self-reporting, e.g. recall bias or health-seeking behaviour.
Dr Retz: “Don’t be too easily satisfied with an answer, e.g. if the patient only answers with a ‘yes’, ask the patient to give concrete examples from everyday life. Confront patients if they report conflicting information.”
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- Barkley RA, Fischer M. The unique contribution of emotional impulsiveness to impairment in major life activities in hyperactive children as adults. J Am Acad Child Adolesc Psychiatry 2010; 49: 503-513.
- Mowlem FD, Skirrow C, Reid P, et al. Validation of the Mind Excessively Wandering Scale and the Relationship of Mind Wandering to Impairment in Adult ADHD. J Atten Disord 2016 [Epub ahead of print].
- Sonuga-Barke EJS, Kennedy M, Kumsta R, et al. Child-to-adult neurodevelopmental and mental health trajectories after early life deprivation: the young adult follow-up of the longitudinal English and Romanian Adoptees study. Lancet 2017; 389: 1539-1548.
- MTA study group. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Arch Gen Psychiatry 1999; 56: 1073-1086.
- Coghill D, Seth S. Effective management of attention-deficit/hyperactivity disorder (ADHD) through structured re-assessment: the Dundee ADHD Clinical Care Pathway. Child Adolesc Psychiatry Ment Health 2015; 9: 52.
- Surman C, Bilkey T. FAST MINDS. How to Thrive If You Have ADHD. Penguin Group 2013.
- Ramsay JR. Assessment and monitoring of treatment response in adult ADHD patients: current perspectives. Neuropsychiatr Dis Treat 2017; 13: 221-232.
- Faraone SV, Biederman J, Wozniak J. Examining the comorbidity between attention deficit hyperactivity disorder and bipolar I disorder: a meta-analysis of family genetic studies. Am J Psychiatry 2012; 169: 1256-1266.