Professor Stephen Faraone
New advances in ADHD neurobiology
Supported by the Verein zur Durchführung Neurowissenschaftlicher Tagungen e.V., Germany, with an unrestricted grant
The first plenary session of Day 3 was opened by Professor Stephen Faraone (Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA), who provided an enthusiastic overview of genetic risk in ADHD. Professor Faraone concentrated on polygenic risk scores, explaining that they can indicate the number of ADHD risk alleles carried by an individual, but cannot tell us what genetic variants are truly associated with ADHD. Professor Faraone concluded by considering the future applications of genetic research in ADHD; he discussed the potential for personalised medicine and presented unpublished data from a meta-analysis investigating whether drug response can be predicted from gene variants in youths with ADHD.
In the second lecture of this plenary session, Professor Katya Rubia (Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK) discussed magnetic resonance imaging (MRI) studies in ADHD. Professor Rubia provided an overview of the existing literature, describing how differences in brain function and structure have been observed between individuals with and without ADHD. She also explained that, although disorders like obsessive compulsive disorder (OCD) and autism spectrum disorder (ASD) can affect overlapping areas of the brain, imaging studies have shown structural and functional differences between these brain areas in individuals with the different disorders.1 Professor Rubia concluded with a presentation of data from a real-time functional MRI neurofeedback study in adolescents with ADHD.2
Dr Kalina Christoff (Department of Psychology and Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada) then provided an engrossing presentation on the concept of ‘mind wandering’, a topic that has gained traction throughout the 21st century. Dr Christoff described the different definitions of mind wandering that are used in the literature, highlighting that the current usage of the term does not capture the spontaneous thoughts associated with mind wandering. Dr Christoff concluded by discussing how spontaneous thoughts arise from an absence of strong constraints on thought content and transition, with ADHD as a disorder marked by excessive variability in thought movement.
The session concluded with a novel presentation by Professor Joel Nigg (Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA) on big data and advanced analytics. Professor Nigg defined big data as having at least one of the following characteristics: high volume, high velocity and high variety; and explained how big data will be key to the future understanding of complex disease. In a discussion of the current and future applications of these concepts in ADHD research, Professor Nigg highlighted that novel analytical applications are possible even when big data are not available, and he presented data from a study investigating the utility of a random forest classification in the assessment and diagnosis of depression.3
Professor Faraone: “Patients in the highest 10% of polygenic risk have five-fold increased risk for ADHD…but polygenic risk factor is a very weak predictor of who does and doesn’t have ADHD.”
Dr Christoff: “Within a dynamic framework, ADHD can be understood as a disorder marked by excessive variability in thought movement.”
Professor Margaret Weiss
Grant-round: A case presentation of an adult with multiple comorbidities and ADHD symptoms
In this exciting and highly anticipated clinical session, Professor Paulo Mattos (Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil) presented a case video of an adult with a diagnosis of ADHD and comorbid generalised anxiety disorder from his clinical practice. The objective of this session was to disentangle the source of the impairment and to examine the risk:benefit ratio for treating ADHD symptoms in this context. He was joined on stage by Professor Thomas E Brown (Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA) and Professor Margaret Weiss. (Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada).
After watching the video, the panel discussed the importance of collateral reports, and investigating functional impairment and working memory. Professor Mattos also described the 3 areas of bias that a clinician should be aware of when discussing symptoms with their patients: anchoring bias (when only the chief complaint is discussed), verification bias (where all questions are aimed at the chief complaint), and confirmatory bias (when all questions are answered “yes” to the chief complaint).
When discussing treatment, the panel emphasised that as ADHD is a multidimensional disorder, clinicians need to make sure that they don’t treat everyone the same. Professor Mattos highlighted the importance of recognising that symptoms change from childhood to adulthood and that psychoeducation and support are required across the lifespan to ensure that the patients have the information they need to recognise the different symptoms. The discussion ended with the panel agreeing that a combination of pharmacological and non-pharmacological treatment should be used when treating patients with ADHD.
Professor Mattos concluded that it would not be appropriate to develop ADHD services where clinicians would only have expertise in ADHD. Anyone working with children, adolescents and adults with ADHD needs to have general neuropsychiatry experience.
Professor Weiss: “He has good treatment, he has good psychoeducation, but he needs education on how the two diagnoses are intertwined to allow him to succeed.”
Dr Larry Klassen
Recognising, diagnosing and treating ADHD in adults
Supported by Shire, now part of Takeda
In this industry sponsored session, a passionate panel chaired by Professor Martin Katzman (Stress, Trauma, Anxiety, Rehabilitation and Treatment [START] Clinic for Mood and Anxiety Disorders, Toronto, Ontario, Canada) discussed recognising, diagnosing and treating ADHD in adult patients. Dr Hugh Morgan (The Mindcare Centre, University of Sydney, Australia) began by highlighting the complex nature of ADHD in adults, with the majority of patients having a comorbid psychiatric condition,4 which can mask the symptoms of ADHD. In particular, Dr Morgan highlighted results from the National Comorbidity Survey Replication (NCS-R) which showed that over half of patients with ADHD have had previous treatment for a comorbid psychiatric disorder, while only 1 in 5 have received treatment for the underlying ADHD.6 He concluded by sharing his hopes that in the future, cynicism amongst physicians regarding the diagnosis of ADHD will be reduced, and that psychiatry registrars, psychiatrists, paediatricians, clinical psychologists and general practitioners will become comfortable with diagnosing and treating ADHD.
Dr Larry Klassen (Eden Mental Health Centre, University of Manitoba, Manitoba, Canada) followed by discussing differential diagnoses, explaining that the symptoms of ADHD overlap with a number of other psychiatric disorders; in particular, bipolar disorder. Taking major depressive disorder and bipolar disorder as examples, Dr Klassen described factors to consider when trying to differentiate between primary disorders and comorbid disorders. Moving on to comorbid substance use disorders, Dr Klassen conjectured that long-acting stimulants have less abuse potential compared with short-acting stimulants, and shared a patient video of a patient who had experienced taking both types of stimulant.
Dr Joel Young (Rochester Centre for Behavioural Medicine, Wayne State University School of Medicine, MI, USA) then discussed the pharmacological and non-pharmacological treatment of adults with ADHD. Dr Young provided a brief overview of the currently available pharmacological treatments, and their known adverse reactions, agreeing with Dr Klassen that long-acting stimulants are preferred by many over short-acting stimulants. Dr Young also briefly touched on the subject of counselling, coaching, accommodations and patient support groups. He concluded with some case studies to demonstrate the decision-making processes followed in practice.
The symposium finished with the panel answering a selection of questions from the audience on topics including screening for ADHD in the parents of affected children, the amount of time that clinicians require to spend with a patient before making a diagnosis of ADHD and encouraging compliance with pharmacological therapy.
Dr Klassen: “With ADHD, it’s just random thoughts popping out of nowhere…with bipolar disorder – you can follow the stream, but it’s going real fast.”
Professor Frederick Reimherr
Hot Topics Symposium
Advances in the treatment of adult ADHD
In this informative hot topics symposium, the speakers presented some advances in the treatment of ADHD in adult patients.
Katharina Bachmann (School of Medicine and Health Sciences, Medical Campus University of Oldenburg, Oldenburg, Germany) began with an overview of psychosocial therapies, highlighting that treatment guidelines recommend multimodal treatment, which includes non-pharmacological therapies. Bachmann discussed cognitive behavioural therapy (CBT) delivered in groups or to individuals, and also psychoeducation. She also touched on longitudinal data exploring the use of pharmacological treatment in combination with psychoeducation. She concluded by discussing unpublished data, which will report patient perceptions of the effectiveness of different treatment combinations.
Professor Craig Surman (Department of Psychiatry, Massachusetts, General Hospital, MA, USA) then provided an overview of pharmacological therapies and the evidence base. In particular, he focused on a recent meta-analysis, which included 40 systematic reviews and found that pharmacological therapy was significantly more effective than placebo in adults with ADHD, but less well accepted or tolerated.5 Professor Surman concluded with a discussion of the gaps in the research, emphasising that further research is required into tolerance to ADHD medications.
Professor Frederick Reimherr (Mood Disorders Clinic, Department of Psychiatry, University of Utah Health Sciences Center, Salt Lake City, UT, USA) then presented preliminary findings from his research investigating the effect of anxiety on treatment response in adults with ADHD. Professor Reimherr began by summarising the existing literature on the topic of treatment response in comorbid ADHD and anxiety, highlighting that the evidence to date is conflicting. Stressing the preliminary nature of his results, Professor Reimherr concluded that anxiety may not influence treatment response to ADHD medication as measured using DSM-based symptom criteria. Highly anxious patients may show an improvement in anxiety when their ADHD is treated.
The session concluded with a presentation from Professor Andreas Fallgatter (University of Tübingen, Tübingen, Germany) on near infra-red spectrum (NIRS)-neurofeedback in individuals with ADHD. After a brief overview of the concept of neurofeedback, Professor Fallgatter presented results from a pilot study conducted in children, which compared NIRS-neurofeedback with EEG-neurofeedback treatment and found a benefit to attention in the NIRS-NF treatment arm.6 He then described his future research, which will investigate neurofeedback within a 3D virtual reality classroom. Finally, Professor Fallgatter concluded by emphasising that further research is required in larger samples of patients.
Professor Reimherr: “Anxiety overlaps with emotional dysregulation in ADHD, but also represented alternative dimensions in ADHD.”
Dr Wolfgang Retz
Hot Topics Symposium
Impact of adult ADHD on the course of delinquent behaviour
Dr Wolfgang Retz (Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany) opened his presentation by stressing that conduct disorder (CD) is highly prevalent in patients with ADHD and described the relationship between CD and criminality, emphasising that CD is a risk factor for criminality. He highlighted that approximately 1 in 5 of the prison population had ADHD and that rates were similar between males and females, and discussed the findings from long-term follow-up studies in children with ADHD which showed that there was an increased risk of arrests, convictions, incarcerations, an earlier start of criminal careers and a higher rate of criminal recidivism (re-conviction, violent re-conviction, re-incarceration), compared with those without ADHD. He described results from an unpublished study which examined whether lifetime or persisting ADHD influenced the risk of criminal relapse upon release. Logistic regression analysis of the 13-year follow-up study showed that ADHD had a significant influence on criminal recidivism and he concluded that, in male offenders, ADHD did indeed predict criminal recidivism.
Dr Ylva Ginsberg (Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden) presented results from the Norrtälje Prison Study which was a 5-week randomised, double-blind, placebo-controlled trial of OROS-MPH followed by a 47-week open-label extension phase and long-term follow-up in an incarcerated population of adult males with ADHD. Results from the study showed that treatment significantly improved ADHD symptoms and global functioning, with no significant changes observed in safety parameters during the initial randomised controlled trial.7Effectiveness over the 52-week treatment period showed that overall symptomatic improvement translated into functional improvement and the majority attended and completed cognitive behavioural therapy programmes, educational activities and vocational training. She also noted that, after trial completion, regular prison psychiatrists were responsible for continued treatment and when inmates were conditionally released they were referred. She also described the improvements in both verbal and visuospatial working memory and normalisation of inattention, impulsivity and reaction time variability rates. Effects gained during the 52-week study were maintained in completers at 1- and 3-year follow-up with poorer outcomes observed in the non-medicated group compared with the medicated group.8 She concluded that multimodal treatment in offenders with ADHD could substantially reduce the individual and societal burden of criminality.
The final presentation of this hot topic symposium was by Dr Florence Philipp-Wiegmann (Institute for Forensic Psychology and Psychiatry, Saarland University, Germany) who presented results from an unpublished 10-year follow-up study of female incarcerated offenders, which examined rates of recidivism in female prisoners. Results from the study showed that ADHD did not predict criminal recidivism in female offenders.
Dr Retz: “ADHD is associated with an increased risk for criminal behaviour and this association appears early in life as conduct disorder.”
Professor Iris Manor and Dr Mark Stein
Diagnostic process and treatment planning for children
In this interactive educational seminar, Dr Mark Stein (Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA) and Professor Iris Manor (Geha Mental Health Center, Peta Tikva, Israel) collected questions from the audience on the diagnosis and treatment of children with ADHD, and aimed to address these questions throughout their joint presentation. A wide range of topics were discussed, including the assessment of ADHD in children with autism spectrum disorder or intellectual disabilities; improving compliance in adolescents; and identifying ADHD in girls with the inattentive subtype.
Dr Stein focused on the components of an optimal diagnosis, emphasising that ratings scales are no substitution for a comprehensive medical history. Dr Stein recommended assessing symptoms, impairment, differential diagnoses, comorbid conditions and protective factors, e.g. environmental aspects that may confound the appearance of ADHD. Dr Stein presented a number of case studies to show that ADHD is usually complex.
Professor Manor explained that it is important to look beyond the child with ADHD, and to treat the entire family. She highlighted that it is very common for the parents of children with ADHD to also meet diagnostic criteria. It is therefore important to consider the impact that a parent with ADHD can have on the child’s treatment, e.g. who will make sure the child takes their medication each morning?
The seminar ended with a discussion on improving medication compliance in adolescents with ADHD, with both speakers emphasising the importance of communicating with the patient, and ultimately accepting their decision, even if it is to discontinue treatment.
Professor Manor: “You don’t treat the individual with ADHD, you treat the family with ADHD.”
Dr Stein: “Rating scales can’t replace a comprehensive clinical history…people confuse having symptoms with having the disorder.”
- Norman LJ, Carlisi C, Lukito S, et al. Structural and Functional Brain Abnormalities in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder: A Comparative Meta-analysis. JAMA Psychiatry 2016; 73: 815-825.
- Alegria AA, Wulff M, Brinson H, et al. Real-time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder. Hum Brain Mapp 2017 [Epub ahead of print].
- Gibbons RD, Weiss DJ, Frank E, et al. Computerized Adaptive Diagnosis and Testing of Mental Health Disorders. Annu Rev Clin Psychol 2016; 12: 83-104.
- Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006; 163: 716-723.
- De Crescenzo F, Cortese S, Adamo N, et al. Pharmacological and non-pharmacological treatment of adults with ADHD: a meta-review. Evid Based Ment Health 2017; 20: 4-11.
- Marx AM, Ehlis AC, Furdea A, et al. Near-infrared spectroscopy (NIRS) neurofeedback as a treatment for children with attention deficit hyperactivity disorder (ADHD) – a pilot study. Front Hum Neurosci 2015 ; 8: 1038.
- Ginsberg Y, Lindefors N. Methylphenidate treatment of adult male prison inmates with attention-deficit hyperactivity disorder: randomised double-blind placebo-controlled trial with open-label extension. Br J Psychiatry 2012; 200: 68-73.
- Ginsberg Y, Långström N, Larsson H, et al. Long-Term Treatment Outcome in Adult Male Prisoners with Attention-Deficit/Hyperactivity Disorder: Three-Year Naturalistic Follow-Up of a 52-Week Methylphenidate Trial. J Clin Psychopharmacol 2015; 35: 535-543.