Prof. Pell[/caption]
Professor Jill Pell MD
Director of Institute (Institute of Health and Wellbeing)
Associate (School of Medicine, Dentistry and Nursing)
University of Glasgow
MedicalResearch.com: What is the background for this study?
Response: The novelty of our study lies in its scale and scope. In terms of scope, it reported on six educational outcomes and three health outcomes in the same group of children.
In terms of scale, it is the first study of a whole country to compare educational outcomes of children with treated ADHD with their unaffected peers and is more than 20 times larger than previous studies on similar educational outcomes. The only previous countrywide study on health outcomes, included only children with very severe ADHD who were in psychiatric hospitals.
Dr. Vigod[/caption]
Simone Vigod, MD, MSc, FRCPC
Psychiatrist and Lead, Reproductive Life Stages Program
Women’s Mental Health Program
Women’s College Hospital
Toronto, ON
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Depression is one of the most common problems that can complicate a pregnancy. Untreated, or incompletely treated, it can be associated with significant harm to mother and child. While psychotherapies alone may be effective for women with mild (or even moderate) severity symptoms, sometimes antidepressant medication is required. In these cases, the benefits of treatment must be weighed against potential risks. Previous research suggested that there may be an increased risk for autism in children exposed to antidepressant medication during pregnancy. However, previous studies were limited in their ability to account for other potential causes of autism in their analyses. In our study, we used several different strategies to try to compare children whose pregnancy exposures were very similar, except for exposure to an antidepressant.
The main finding was that after using these strategies, there was no longer a statistically significant association between in-utero antidepressant exposure and autism.
Dr. Lisa Meeks[/caption]
Dr. Chorniy[/caption]
Anna Chorniy PhD
Postdoctoral Research Associate
Center for Health and Wellbeing
Princeton University
Princeton NJ 08544
MedicalResearch.com: What is the background for this study?
Response: Attention-deficit/hyperactivity disorder (ADHD) is one of the common chronic mental conditions affecting children. In the U.S., 11% of children ages 4–17 (6.4 million) are estimated to have an ADHD diagnosis and almost 70% of them report taking medication for the condition (e.g. Visser et al., 2014). However, little evidence exists on the effects of ADHD treatment on children’s outcomes.
We use a panel data set of South Carolina Medicaid claims paid out in 2003–2013 to investigate the effects of ADHD medication treatment on a seldom studied set of outcomes associated with this condition: adolescent risky behaviors and the incidence of injuries.
The occurrence of injuries allows us to evaluate short-term effects of ADHD treatment, while substance abuse and risky sexual behavior outcomes speak for the long-term effects of medication. Second, we use Medicaid spending on treatment of these negative events to evaluate the impact of ADHD drugs on the severity of ADHD, and compare the cost of ADHD treatment with the costs of negative health events.
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. Kenneth Koblan[/caption]
Dr. Kenneth Koblan PhD
Sunovion Pharmaceuticals Inc.
Fort Lee, NJ and Marlborough, MA
Medical Research: What is the background for this study?
Dr. Koblan: Assessing abuse potential is important in the clinical development process for any therapy affecting the central nervous system, especially those that may act on dopamine and norepinephrine neurotransmitter systems. Human abuse liability studies are conducted to evaluate the abuse potential associated with drugs that affect the central nervous system.
Drugs that increase dopamine levels may be associated with stimulant effects and abuse (e.g., cocaine and amphetamine), whereas drugs that increase serotonin and/or norepinephrine levels are not generally associated with recreational abuse (e.g., selective serotonin reuptake inhibitors). Among drugs with effects on dopamine neurotransmission, slowing the rate of absorption is thought to reduce abuse potential, and increasing the rate of elimination is thought to reduce rewarding effects and abuse liability due to sustained elevations in drug concentrations resulting in sustained inhibition of dopamine transporters (DAT).
Dasotraline is an investigational dopamine and norepinephrine reuptake inhibitor from Sunovion in late-stage development to evaluate its use in treating the symptoms of attention deficit hyperactivity disorder (ADHD) and binge-eating disorder (BED). Dasotraline has slow absorption and elimination that supports the potential for plasma concentrations yielding a continuous therapeutic effect over the 24-hour dosing interval at steady state.
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.
Dr. Michael Halassa[/caption]
MedicalResearch.com Interview with:
Michael M. Halassa, MD, PhD, Assistant professor
Departments of Psychiatry and Neuroscience and Physiology
The Neuroscience Institute Depts. of Psychitatry
Langone Medical Center
New York, NY 10016
Medical Research: What is the background for this study? What are the main findings?
Dr. Halassa: Attention is a vital aspect of our daily life and our minds are not merely a reflection of the outside world, but rather a result of careful selection of inputs that are relevant. In fact, if we indiscriminately open up our senses to what’s out there, we would be totally overwhelmed. Selecting relevant inputs and suppressing distractors is what we call attention, and as humans we are able to attend in a highly intentional manner. Meaning, we choose what to pay attention to, and we do so based on context. If you’re driving and getting directions from your GPS, you’ll be intentionally splitting your attention between your vision and hearing. Now, in one context, you might have just updated the GPS software, so you know it’s reliable; this would allow you to intentionally pay attention more to the voice coming from the GPS. In another context, the GPS software may be outdated making voice instructions unreliable. This context would prompt you to direct your attention more towards using visual navigation cues and less to the GPS voice. How the brain intentionally and dynamically directs attention based context is unknown.
The main strength of our study is that we were able to study context-dependent attention in mice. Mice are unique models because they provide genetic tools to study brain circuits. Meaning, we can turn circuits on and off very precisely in the mouse, and in a way we cannot do in other experimental animals. The inability to do these types of manipulations has been the major roadblock for progress in understanding what brain circuits mediate attention and its intentional allocation.
Because we couldn’t train mice to drive and listen to the GPS, we decided to do something much simpler. Based on context (the type of background noise in the experimental enclosure), a mouse had to select between conflicting visual and auditory stimuli in order to retrieve a milk reward. Mice love milk; it turns out, and will work tirelessly to do well on getting it. Each trial, the mouse is told ‘you need to pick the light flash’ or ‘you need to pick the auditory sweep’; these stimuli appeared on either side of the mouse randomly so the animal really had to pay attention in order to get its reward. It also had to take the context into account. We found that mice did this task, and as humans would do, they were reliant on the prefrontal cortex for determining the appropriate context. The major finding was that the prefrontal cortex changed the sensitivity of the brain to incoming stimuli (meaning, made the visual stimulus brighter when the mouse cared about vision and made the auditory stimulus louder when the mouse cared about hearing), by influencing activity in the thalamus. The thalamus is the major early relay station in the brain. The prefrontal cortex does that by instructing the brain’s switchboard, known as the thalamic reticular nucleus (TRN) to control how much visual or auditory information the thalamus was letting through. So in a sense, we discovered that executive function, represented by the prefrontal cortex, can talk to ‘attentional filters’ in the thalamus to determine what ultimately is selected from the outside environment to build our internal world.
MedicalResearch.com Interview with:
Dr. Graham Murray PhD
University Lecturer
Department of Psychiatry
Addenbrooke's Hospital
Cambridge UK
Medical Research: What is the background for this study? What are the main findings?
Dr. Murray: There is debate about the extent to which ADHD persists into adulthood, with estimates suggesting that between 10-50% of children still have ADHD in adulthood. Diagnosis (whether in childhood or adulthood) is currently reliant on meeting symptom checklists (such as the American Psychiatric Association’s Diagnostic and Statistical Manual), and a current diagnosis is often the prerequisite to access health care from psychiatric services. We decided to follow up a sample of 49 teens who all had a confirmed diagnosis of ADHD at age 16. We also followed a control group made up of comparison healthy volunteers from the same social, ethnic and geographical background.
When we used the symptom checklist criteria of persistence, only 10% of patients still met ADHD diagnostic criteria in adulthood. However, there is more to ADHD than this. When it comes to adult brain structure and function, it didn’t make any difference whether symptom checklists were still met or not. On reaching adulthood, the adolescent ADHD group show reduced brain volume in the caudate nucleus - a key brain region that supports a host of cognitive functions, including working memory function. When we assessed working memory ability, we noted persistent problems in the adolescent ADHD group, with a third of the adolescent ADHD sample failing the memory test. The poor memory scores seemed to relate to a lack of responsiveness in the activity of the caudate nucleus that we could detect using functional MRI scans. In the control group, when the memory questions became more difficult, the caudate nucleus became more active, and this appeared to help the control group perform well; in the adolescent ADHD group, the caudate nucleus kept the same level of activity throughout the test. It was as if, for the controls, when the test got harder, the caudate nucleus went up a gear in its activity, and this is likely to have helped solve the memory problems. But for the adolescence ADHD group, the caudate couldn’t go up a gear when the test became harder, and this likely resulted in poorer performance.
MedicalResearch.com Interview with:
Susanna N. Visser, DrPH
Epidemiologist at the National Center on Birth Defects and Developmental Disabilities
CDC
Medical Research: What is the background for this study? What are the main findings?
Dr. Visser: Attention-Deficit/Hyperactivity Disorder, or ADHD is one of the most common chronic conditions of childhood. It often persists into adulthood. When children diagnosed with ADHD receive proper treatment, they have the best chance of thriving at home, doing well at school, and making and keeping friends.
In 2011, the American Academy of Pediatrics (AAP) updated their guidelines for ADHD treatment. The new guidelines give this advice to healthcare providers, psychologists, educators, and parents of children with ADHD:
MedicalResearch.com Interview with: Dr Søren Dalsgaard National Centre for Register-based Research Aarhus University Denmark Medical Research: What is the background for this study? What are the main findings? Response: This is the first large-scale prospective study of all-cause-mortality in people with ADHD. The nationwide Danish registers offer unique research possibilities. We followed a cohort of almost...
MedicalResearch.com Interview with:
William Brinkman, MD, MEd, MSc
Associate Professor of Pediatrics
Director, Research Section, Division of General & Community Pediatrics
Research Director, Cincinnati Pediatric Research Group
James M. Anderson Center for Health Systems Excellence
Cincinnati Children’s Hospital Medical Center
MedicalResearch.com: What is the background for this study?
Dr. Brinkman: Early onset of substance use is a significant public health concern as those who use substances before the mid-teen years are more likely to develop dependence than those who start later. The association of attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) with tobacco and alcohol use has not been assessed in a young adolescent sample representative of the U.S. population.
MedicalResearch.com Interview with:
Dr. Henrik Larsson PhD
Associate Professor
Department of Medical Epidemiology and Biostatistics
Karolinska Institute
Stockholm, Sweden
MedicalResearch: What are the main findings of the study?
Dr. Larrson: We found no evidence for an overall increased rate of suicide related events associated with the use of stimulant or non-stimulant drug treatment for ADHD. If anything, the results pointed to a potential protective effect of drugs for ADHD on suicidal behaviour, particularly for stimulant drugs.
MedicalResearch.com Interview with:
Dr. Anders Nykjaer MD, PhD
Mayo Clinic in Florida and
Aarhus University in Denmark
MedicalResearch: What are the main findings of the study?
Dr. Nykjaer: It is well known that ADHD is a complex condition caused by a number of factors including genetic and environment. However, approximately 75% etiology is considered to be genetic and a large body of investigations suggests that it is multiple genes each with a moderate effect that is responsible for conferring susceptibility to ADHD. We have here found one single gene the dysfunction of which is sufficient to trigger the disease. The gene encodes a receptor, SorCS2, which ensures correct wiring our reward system during embryonic development. Malfunction of the receptor causes ADHD-like symptoms in mice. It is well accepted that ADHD predisposes to psychiatric disorders and genetic reports have linked variations in the SorCS2 gene with schizophrenia. Studies are currently ongoing to evaluate if mutations disrupting the function of SorCS2 may also result in schizophrenia. If this is the case we have come closer to an explanation for the link between ADHD and psychiatric disorders. In the future when prenatal genetic screening becomes established, non-sense mutations in the SorCS2 gene can be used to predict that the child will develop ADHD with 100% certainty.
MedicalResearch.com Interview with:
Jørn Olsen, M.D., Ph.D.
Professor Institute of Public Health, Department of Epidemiology UCLA
Aarhus University
Aarhus,Denmark
MedicalResearch.com: What are the main findings of the study?
Dr. Olsen: Acetaminophen (paracetamol) is drug being used by many, including pregnant women. In our data about half of all pregnant women in 1995 to 2002 had used the drug all least once during their pregnancy. The drug has shown hormonal disruptor properties in animal studies.
We found that women who used this drug during pregnancy gave birth to children who 5 – 10 years later slightly more often had behavioral problems or were treated for ADHD. The risk was highest for those who took the medication late in pregnancy and/or had taken the drug several times. The increased risk was about 10-30%.
MedicalResearch.com Interview with:
Dr. Vitria Adisetiyo, Ph.D.
Postdoctoral Research Fellow
Medical University of South Carolina
Center for Biomedical Imaging Charleston, SC 29425
MedicalResearch.com: What are the main findings of the study?
Dr. Adisetiyo: Using a non-invasive MRI method called magnetic field correlation imaging, we detected significantly reduced striatal and thalamic brain iron in medication-naive children and adolescents with ADHD compared to age-, gender- and IQ-matched typically developing controls. ADHD patients who had a history of psychostimulant medication treatment (e.g. Ritalin, Aderrall) had brain iron levels comparable to controls, suggesting brain iron may normalize with psychostimulants. Blood iron measures did not differ between patients and controls.
MedicalResearch.com Interview with:
Professor Desiree Silva MB BS, FRACP, MPH
Consultant Paediatrician
Suite 210 Specialist Centre, Joondalup Health Campus
60 Shenton Avenue, Joondalup WA 6027
MedicalResearch.com: What are the main findings of the study?
Prof. Silva: Our study is one of the largest population based studies of 12,991 children with ADHD. We found that smoking in pregnancy, maternal urinary infections, preeclampsia, being induced and threatened pre-term labour increases the risk of ADHD with little gender differences. Prematurity also increased the risk of ADHD including babies born late preterm and early term marginally increased the risk of ADHD.
MedicalResearch.com eInterview with Kathryn L. Humphreys, M.A., Ed.M.
Clinical Psychology Doctoral Student
UCLA Department of Psychology
1285 Franz Hall, Box 951563
Los Angeles, CA 90095
MedicalResearch.com: What are the main findings of the study?
Response: Our primary question was to answer whether the use of stimulant medication in the treatment of ADHD was associated with increased or decreased risk for a variety of substance use (ever tried) and substance use disorder (abuse or dependence) outcomes (alcohol, cocaine, marijuana, nicotine, and non-specific drug use).
Prior research from individual studies of children have provided mixed evidence (i.e., some found medication increased later risk, some found medication decreased risk, and still others found no difference in risk). We examined available longitudinal studies (i.e., medication treatment preceded measurement of substance outcome) together using meta-analysis, a technique that aggregates findings from a number of studies, in order to examine this question in a much larger sample of individuals.
Our main finding was that children with ADHD who received medication treatment did not differ in risk for lifetime substance use or abuse or dependence compared to those children with ADHD who did not receive medication treatment.