ADHD, Author Interviews, Genetic Research, Pediatrics / 01.11.2016
Specific Genetic Mutations Present in Many Children With ADHD
MedicalResearch.com Interview with:
Dr. Josephine Elia, M.D.
Neuroscience Center
Department of Child and Adolescent Psychiatry
Nemours/Alfred I. DuPont Hospital for Children
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Glutamate neurotransmission may play an important role in ADHD and other neuropsychiatric disorders. The purpose of this study is to determine the frequency of genetic mutations involving specific genes (GRM network genes) which influence glutamatergic neurotransmission. A total of 23 study sites across the USA enrolled 1,013 children, aged 6-17 years who had been previously diagnosed with ADHD. Saliva samples were submitted to The Center for Applied Genomics (CAG) at CHOP for analysis of mutations of interest. Information on medical history, including other neuropsychiatric diagnoses and family history as well as areas of academic and social concern were also collected.
Overall, the mutation frequency was 22%, with a higher prevalence of 25% observed in patients aged 6-12. When compared to mutation negative ADHD patients, the patients with the mutations of interest were more likely to have concerns about anger control and disruptive behaviors.

Dr. Katya Rubia[/caption]
Katya Rubia, PhD
Department of Child and Adolescent Psychiatry
Institute of Psychiatry, Psychology, and Neuroscience
King’s College London
London, England
MedicalResearch.com: What are the main findings?
Dr. Rubia: ADHD and OCD patients both suffer from poor inhibitory control and in both disorders this has been associated with structural and functional deficits in fronto-striatal networks. However, it is not clear to what extent the two disorders differ in their underlying neural substrates. This study therefore conducted a meta-analysis of all published whole brain structural and functional MRI studies of inhibitory control in both disorders.
MedicalResearch.com: What are the main findings?
Dr. Rubia: The main findings are that ADHD and OCD patients differ quite fundamentally in their structural and functional brain abnormalities. OCD patients have enlarged volume in basal ganglia and insula, while ADHD patients have reduced volumes in these regions. In fMRI, in the left hemisphere this was also observed for the left insula and putamen, which were increased in OCD and reduced in ADHD. In addition both disorders have different frontal deficits. OCD patients have deficits in rostro-dorsal medial frontal regions that are important for top-down control of affect while ADHD patients had reduced activation in lateral inferior frontal cortex, a key area of attention and cognitive control. The findings fit into the notion of fronto-striatal dysregulation in OCD where basal ganglia are overactive and poorly controlled by medial frontal regions and a delayed fronto-striatal maturation in ADHD where both lateral frontal regions and the basal ganglia/insula are smaller, and presumably less developed in structure and in function in ADHD.
Dr. Nicole Pratt[/caption]
Nicole Pratt PhD
Senior Research Fellow
Quality Use of Medicines and Pharmacy Research Centre
Sansom Institute, School of Pharmacy and Medical Sciences
University of South Australia
Adelaide South Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Pratt: The cardiac safety of methylphenidate has been debated. This study aimed to measure the risk of cardiac events in a large population of children treated with these medicines. We found that there was a significantly raised risk of arrhythmia in time periods when children were treated with methylphenidate compared to time periods when they were not. While the relative risk of cardiac events was significant the absolute risk is likely to be low as cardiac events are rare in children.
Prof. Luis. Rohde[/caption]
Luis Augusto Rohde MD, PhD
Full Professor
Department of Psychiatry
Federal University of Rio Grande do Sul
Director
ADHD Program
Hospital de Clínicas de Porto Alegre
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The idea that Attention-deficit/Hyperactivity Disorder always begins in childhood has been held for decades even without proper testing. The main manuals of psychiatric diagnoses require age at onset in childhood as a core feature of the disorder. In a large birth cohort followed until age 18, we identified many young adults presenting with a full impairing ADHD syndrome. They had consistently worse outcomes - criminality, substance abuse, traffic accidents, among others - than their counterparts without ADHD. However, most of these young adults (84.6%) presenting with a full impairing syndrome did not have a prior diagnosis in their childhood years. This surprising observation held after many secondary analyses exploring possible biases, like comorbidities in young adulthood, subthreshold ADHD in childhood and change of information source.

Dr. Storebø[/caption]
MedicalResearch.com Interview with:
Dr. Ole Jakob Storebø
Region Zealand, Child and Adolescent Psychiatric Department, Roskilde
Region Zealand Psychiatry
Psychiatric Research Unit, Slagelse
University of Southern Denmark
Department of Psychology
Faculty of Health Science,
Odense Denmark
Medical Research: What is the background for this study? What are the main findings?
Dr. Storebø: Despite widespread use of methylphenidate for the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD), a comprehensive systematic review of its benefits and harms has not yet been conducted. Over the past 15 years, several reviews investigating the efficacy of methylphenidate for ADHD (with or without meta-analyses) have been published. Each of these reviews, however, has several shortcomings and these are described in detail in the review. The most important concerns are that none of these reviews are based on a pre-published protocol, and most assessed neither the risk of bias (systematic errors) of included trials nor adverse events. Moreover, none of these reviews considered the risk of random errors. Therefore, their interpretation of findings is unlikely to have taken into account the poor reporting of adverse events, the impact of combining data from small trial samples, or the impact of risk of bias on their analyses; information about adverse events is also missing from several RCTs. Because of this it is our opinion that these previous reviews might have overestimated the true treatment effect.
We found that Methylphenidate may improve ADHD symptoms, general behaviour and quality of life in children and adolescents aged 18 years and younger with ADHD. We rated the evidence to be of very low quality and, as a result, we cannot be certain about the magnitude of the effects from the meta-analyses. The evidence is limited by serious risk of bias in the included trials, under-reporting of relevant outcome data, and a high level of statistical variation between the results. We found no evidence for serious adverse events, but a lot of non-serious adverse events. Most of these are well known but the number of adverse events might even be higher than the number we found due to underreporting of adverse events. We know very little about the long term effects or harms as most of the trials in our review did not measure outcomes beyond 6 months. The risk of rare, serious adverse events seem low over the short duration of follow-up of the trials that reported on harms, but in general there was inadequate reporting of adverse events in many trials.












