Professor Joseph Biederman
New advances in ADHD diagnosis
The final morning of the 6th World Congress on ADHD began with an exciting plenary session which examined advances in ADHD diagnosis. Professor Joseph Biederman (Massachusetts General Hospital, Boston, MA, USA) gave a presentation on the clinical relevance of recognising subthreshold ADHD. He opened his presentation by explaining that, although the diagnosis of the fully syndromatic form of ADHD has been well-validated, much less is known about subsyndromal ADHD as such cases are excluded from clinical trials. He highlighted that available literature is based on community samples, making it unclear whether similar findings would apply to clinical samples and that the definition of subthreshold ADHD is based solely on insufficient numbers of ADHD symptoms. He noted that subthreshold ADHD can also stem from an atypical age of onset, even in the presence of an adequate number of symptoms. He went on to describe results from a meta-analysis of current literature which highlighted that, compared with full ADHD patients, those with subthreshold ADHD were more likely to be female, older, come from families with higher socio-economic status, have less family conflict and fewer perinatal complications. However, patients with subthreshold ADHD were similar to full ADHD patients in that both differed from control patients on a number of comorbid disorders; clinical and social functioning scales; and cognitive achievement and school functioning scores.
Professor Jan Buitelaar (Radboud University, Nijmegen, the Netherlands) gave a presentation on the relationship between ADHD, autism spectrum disorder (ASD) and schizophrenia. He highlighted that ADHD is a risk factor for schizophrenia with females being at a much higher risk than males; he also noted higher rates of childhood ADHD, oppositional defiant disorder (ODD)/conduct disorder (CD), anxiety and depression in patients with schizophrenia versus those without schizophrenia. He emphasised that psychosis plus childhood ADHD was associated with poorer premorbid function, earlier onset of illness and poorer clinical and functional outcomes at 1-year follow-up. He reported that data are inconsistent regarding whether stimulant treatment in ADHD is a risk factor for schizophrenia. He explained that there was also a genetic overlap between ASD and schizophrenia, and ASD and ADHD, but the exact nature of this association is currently unclear. However, common genetic risk factors, environmental factors, shared endophenotypes and dysregulation in the dopamine system could underlie these associations.
The third presentation by Dr Stephen Becker (Division of Behavioural Medicine and Clinical Psychology, Cincinnati Children’s Hospital Medical Center, OH, USA) centred around disentangling differences between sluggish cognitive tempo (SCT) and ADHD without hyperactivity. He began his presentation by stating that SCT is not a disorder in any past or current diagnostic nosology; however, there is increasing interest in the SCT construct. Dr Becker presented results from a meta-analysis of available research which highlighted that SCT is clearly linked to greater internalising problems, e.g. depression compared with anxiety, and that SCTs are associated with sensitivity to punishment, whereas ADHD is associated with sensitivity to reward and SCT is associated with suicide risk in psychiatrically hospitalised children. However, SCT was found not to be associated with or linked to fewer externalising problems, e.g. fewer ADHD hyperactive-impulsive and ODD symptoms and decreased aggression. He went on to explain that, in most studies, SCT remained associated with functional impairment after controlling for ADHD and other mental health symptoms. He also noted that SCT is increasingly linked to poor academic functioning but with mixed results and consistently associated with social functioning such as general social problems, increased peer withdrawal and isolation, increased peer problems and poorer perception of social cues. Dr Becker summarised by concluding that SCT is consistently associated with greater ADHD inattention, depression and anxiety, SCT was not associated with hyperactive-impulsive and externalising behaviours, and that SCT is clearly linked with impairment; however, much more research is needed.
Professor Luis Rohde (Federal University of Rio Grando do Sul, Department of Psychiatry, Porto Alegre, Brazil) closed this plenary session with a presentation entitled: “Is there a real adult-onset ADHD disorder?” He began by posing the question: “Which onset are we talking about?”, particularly noting two possible interpretations: 1) the aetiological origin of the disorder, and 2) the age of onset of the phenotypic presentation for a disorder with complex and heterogeneous phenotype where multiple genes determine biological vulnerability. He described research which investigated whether young adults with ADHD symptoms always have a childhood-onset disorder. Conclusions from this longitudinal study showed the existence of two syndromes that have distinct developmental trajectories. He also described the biological plausibility of adult-onset ADHD, concluding that ADHD onset varied during childhood and adulthood. He closed the symposium by briefly describing the prospect of personalised medicine to predict both persistent and later-onset ADHD.
Professor Biederman: “Both subthreshold ADHD and full ADHD subjects had significantly higher rates of all comorbidities compared with controls.”
Dr Jeffrey Newcorn
New advances in treatment of ADHD
In the final plenary session of the Congress, Dr John Mitchell (Duke University Medical Center, Department of Psychiatry and Behavioral Sciences, Durham, NC, USA) delivered a novel presentation on the use of mindfulness-based interventions in the treatment of ADHD. Mindfulness can be defined as paying attention in the present to the unfolding of experiences moment to moment. Dr Mitchell briefly described the available evidence on mindfulness-based interventions in anxiety and depression, before presenting the evidence base supporting their use in ADHD in children and adults. He presented results from a meta-analysis of 10 studies on the effect of mindfulness-based interventions, which gave effect sizes of d=-0.66 on inattention, and d=0.53 on hyperactivity/impulsivity.1 Dr Mitchell concluded with some thoughts for the future, recommending randomised controlled trials with active treatment comparison groups, conducted over a longer period of time.
This was followed by a presentation from Dr Mark Stein (Department of Psychiatry and Behavioral Sciences, Seattle Children’s Hospital and University of Washington School of Medicine, Seattle, WA, USA), who shared his thoughts on the need for personalised treatment of patients with ADHD. Dr Stein discussed the problems experienced by patients who do not respond to treatment, and hypothesised that refining the ADHD phenotype will allow improved treatment of these patients. Dr Stein concluded by discussing the importance of study design, suggesting that clinical trials investigating unique populations will allow clinicians to predict treatment response in the future. He described his own current research, which will look at the effects of treatment in a population of mothers with ADHD, who have children at risk of ADHD.
In a fascinating presentation, Dr Damien Fair (Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA), discussed the effect of psychostimulants on network structure in brains of patients with ADHD. In his introduction, Dr Fair provided an explanation of functional connectivity in the human brain, and how it can be studied by functional magnetic resonance imaging (MRI). He followed this with a discussion of data showing subtle differences in brain network organisation between individuals with and without ADHD. The differences appeared to be driven by patients with severe symptoms of ADHD. Patients with mild symptoms of ADHD appeared to have differences in network organisation compared with patients with severe symptoms, suggesting that brain changes may not simply increase proportionally with ADHD severity.
In the final presentation of the Congress, Dr Jeffrey Newcorn (Icahn School of Medicine, Mount Sinai Hospital, New York, NY, USA) delivered a thought-provoking lecture on biomarkers in ADHD, and their potential uses in the future. Dr Newcorn explained that patients can respond differently to the same drug based on genetic variations, e.g. mutations in drug-metabolising enzymes. He explained that personalised treatment is about selecting the right treatment for a patient, and then using this treatment in the right way. Differential treatment response is a key area for future research, and is currently being explored in the MACRO study. Preliminary results from 36 children with ADHD suggest that increased caudate activation observed with fMRI can predict differential response to methylphenidate over atomoxetine.
Dr Jeffrey Newcorn: “A ‘one size fits all’ approach to treatment of ADHD is not sufficient…use of non-stimulants would be aided by the identification of predictors of response/non-response.”
Cairncross M, Miller CJ. The Effectiveness of Mindfulness-Based Therapies for ADHD: A Meta-Analytic Review. J Atten Disord 2016 [Epub ahead of print].