MedicalResearch.com Interview with:Sneha Vaddadi, BS
Department of Medical Education
Geisinger Commonwealth School of Medicine
Scranton, Pennsylvania
MedicalResearch.com: What is the background for this study?Response: The prescription stimulants methylphenidate, amphetamine, and lisdexamfetamine, classified as Schedule II substances, are sympathomimetic drugs with therapeutic use widely used in the US for Attention Deficit Hyperactivity Disorder. Changes in criteria for diagnosis of Attention Deficit Hyperactivity Disorder in 2013 and approval of lisdexamfetamine for binge eating disorder in 2015 may have impacted usage patterns.
The goal of this study1 was to extend upon past research2 to compare the pharmacoepidemiology of these stimulants in the United States from 2010–2017, including consideration to variation within geographic regions, the Hispanic population, and the Medicaid population.
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MedicalResearch.com Interview with:
Jeremy Brown BA MScRESEARCH DEGREE STUDENT IN PHARMACOEPIDEMIOLOGY
London School of Hygiene & Tropical Medicine
MedicalResearch.com: What is the background for this study? Response: Given the way schools typically work, children in the same year as each other can be almost a whole year apart in terms of age. We’ve known for a while that children who are young in their year at school are also more likely to be diagnosed as having hyperactivity disorders and tend to do less well academically than the older children in the year. They also seem to be at increased risk of suicide. This is thankfully an extremely rare occurrence in children, but there is little evidence about whether younger children are more likely to be diagnosed with depression.
We used electronic health records for just over a million children in the UK to see if there was any association between how old the children were in their year and whether they got diagnosed with ADHD, intellectual disability and depression. (more…)
MedicalResearch.com Interview with:
Tianyang Zhang, MSc
Centre for Psychiatry Research, Department of Clinical NeuroscienceStockholm Health Care Services, Stockholm County Council
Department of Medical Epidemiology and Biostatistics
Karolinska Institutet
Stockholm, Sweden
MedicalResearch.com: What is the background for this study? Response: We know that births by caesarean delivery are linked to several negative health outcomes in the children, such as obesity, asthma, allergy, and type 1 diabetes. However, the association between c-section and neurodevelopmental and psychiatric disorders has been less studied. In addition, it is unclear whether the extent of this association is different if a caesarean section is performed planned in advance or urgently due to medical reasons during a delivery.
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MedicalResearch.com Interview with:
Dr. Angela Lupattelli, PhD
School of Pharmacy
University of Oslo
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Between 1-4% of pregnant women take at least once a benzodiazepine and/or a z-hypnotic medication during the course of gestation. These medications are generally used intermittently in pregnancy, mainly for treatment of anxiety disorders and sleeping problems, which are not uncommon conditions among pregnant women.
However, data regarding the safety of benzodiazepine and/or a z-hypnotic in pregnancy on child longer-term development are sparse. For instance, studies on child motor skills are only available up to toddler age, and little is known in relation to other child developmental domains. So, there is an urgent need to better understand whether prenatal use of benzodiazepine and/or a z-hypnotic medication may pose detrimental longer-term child risks. (more…)
MedicalResearch.com Interview with:
Silvia Alemany, PhD first author
Barcelona Institute for Global Health (ISGlobal), a centre supported by "la Caixa".
In collaboration with co-authors:
Philip Jansen,MD, MSc and
Tonya White, MD, PhD
Erasmus University Medical Center, Rotterdam
MedicalResearch.com: What is the background for this study? Response: Individuals affected by psychiatric disorders can demonstrate morphological brain abnormalities when compared to healthy controls. Although both genetic and environmental factors can account for these brain abnormalities, we expect that genetic susceptibility for psychiatric disorders has the greatest influence on the development of the brain.
Genetic susceptibility for psychiatric disorders can be estimated at the individual level by generating polygenic risk scores. Using this methodology, genetic susceptibility to psychiatric disorders and cognition has been associated with behavior problems in childhood. These findings suggest that heritable neurobiological mechanisms are at play in very early in the course of the illnesses.
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MedicalResearch.com Interview with:
Meghan Miller, Ph.D.
Assistant Professor
Department of Psychiatry & Behavioral Sciences
UC Davis MIND Institute
Sacramento, CA 95817
MedicalResearch.com: What is the background for this study? What are the main findings?Response: This study evaluated within-diagnosis sibling recurrence and sibling cross-aggregation of ADHD and autism spectrum disorder among later-born siblings of diagnosed children. We specifically chose to include only families who had at least one subsequent child after the diagnosis of an older child because failing to do so could bias recurrence risk estimates.
We found that, compared to later-born siblings of non-diagnosed children, later-born siblings of children with autism were more likely to be diagnosed with autism or with ADHD. Likewise, compared to later-born siblings of non-diagnosed children, later-born siblings of children with ADHD were more likely to be diagnosed with ADHD or with autism.
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MedicalResearch.com Interview with:
George J. DuPaul, PhD
Department of Education and Human Services
Lehigh University
Charles Barrett. Ph.D.
School Psychologist
Loudon County Virginia
Public Schools
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Numerous studies have shown that Black children are more likely to receive ratings that are more indicative of displaying externalizing behavior difficulties, including Attention Deficit Hyperactivity Disorder (ADHD). However, many of these studies included teachers as the informants. Consistent with most teachers in the United States, raters have typically been White females. For this reason, it is unclear if these outcomes would exist if the rater and child shared the same racial/ethnic background. Additionally, most research in the United States that involved cross-cultural comparisons has used White and Hispanic boys. Few empirical studies have examined differences between Black and White boys.
The present study sought to address several limitations in the field. Most notably, cross-cultural comparisons between Black and White boys were included instead of Hispanic and White children. Next, maternal figures, rather than teachers, were included as the informants.
The present study was developed using a similar methodology that examined Hispanic and White boys’ behavior from the perspective of Hispanic and White teachers (Dominguez de Ramirez & Shapiro, 2005). In sum, we sought to determine if there were differences in how Black and White maternal figures rated Black and White boys who were demonstrating the same level/type of behavior (i.e., sub-clinical levels of ADHD). Notably, although the boys’ behaviors were the same, maternal ratings were not identical.
Specifically, using the ADHD Rating Scale, Fourth Edition (ARS-4), Black mothers assigned higher ratings to both Black and White boys.
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MedicalResearch.com Interview with:
Holly White, PhD
Research Scientist
Basic and Applied Cognition Laboratory
Department of Psychology
University of Michigan
MedicalResearch.com: What is the background for this study? What are the main findings?Response: This study was inspired by my previous findings of higher originality and creative achievement among adults with ADHD, as well as my personal observations of individuals with ADHD choosing non-traditional approaches to problem solving. College students with ADHD sometimes ignore task instructions and examples, and while this may lead to errors, it may also lead to extraordinarily unique answers and solutions. I was curious as to whether this tendency of ADHD individuals to think in an unconventional and expansive manner might lead to resistance to conformity during creative tasks.
In the present study, college students with ADHD were less likely to copy experimenter-provided task examples, compared to non-ADHD peers, on a product label invention task. ADHD participants were also less likely to create imaginary fruits that resembled typical Earth fruit, compared to non-ADHD participants. Students with ADHD were less likely to conform to pre-existing prototypes of fruit and therefore invented more original creations.
Individuals with ADHD may be more flexible in tasks which require creating something new, and less likely to rely on examples and previous knowledge. As a result, the creative products of individuals with ADHD may be more innovative, relative to creations of non-ADHD peers.(more…)
MedicalResearch.com Interview with:
Marianthi-Anna Kioumourtzoglou ScD
Assistant Professor
Environmental Health Sciences
Mailman School of Public Health
Columbia UniversityMedicalResearch.com: What is the background for this study? Response: The prevalence of neurodevelopmental disorders, like attention deficit/hyperactivity disorder (ADHD) has been increasing. One of the hypothesized risk factors for increased risk for neurodevelopmental disorders is a class of chemicals known as endocrine disrupting chemicals (EDCs). These chemicals are known to interfere with the endocrine system, i.e. the system that uses hormones to control and coordinate metabolism, reproduction and development. Several high production volume chemicals, ubiquitously present in commercial products, are known or suspected endocrine disruptors. Because of their widespread use in consumer products, the population-wide exposure to known and suspected EDCs is very high.
Recently, there has been increased attention in the potential effects of EDCs on neurodevelopment that span multiple generations. Animal studies have provided evidence that exposure to EDCs, such as phthalates and bisphenol A (BPA), alter the behavior and social interactions in mice in three to five generations after exposure. However, evidence of such multi-generational impacts of EDC exposure on neurodevelopment in humans is unavailable, likely because of the lack of detailed information on exposures and outcomes across generations.
For this study we leveraged information from a nationwide cohort, the Nurses’ Health Study II (NHSII), to investigate the potential link between exposure to diethylstilbestrol (DES) and third generation ADHD, i.e. ADHD among the grandchildren of the women who used DES while pregnant. DES is a very potent endocrine disruptor that was prescribed between 1938 and 1971 to pregnant women thought to prevent pregnancy complications. In the United States, between 5 and 10 million women are estimated to have used DES, although the exact number is not known. DES was banned in 1971, when was linked to vaginal adenocarcinomas (a rare cancer of the reproductive system) in the daughters of the women who had used it during pregnancy. Since then, DES has been also linked to multiple other reproductive outcomes in DES daughters, as well as with some reproductive outcomes in the grandchildren of the women who used it, such as hypospadias and delated menstrual regularization. However, to our knowledge, no study to date has evaluated the association between DES, or any other EDC, and multigenerational neurodevelopment. (more…)
MedicalResearch.com Interview with:
Dr. Megan E. Narad, PhD
Division of Behavioral Medicine and Clinical Psychology
Cincinnati Children's Hospital Medical Center | CCHMC
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Previous research has shown that children with a history of traumatic brain injury (TBI) demonstrate difficulties with attention following injury; however, most studies only follow children 2-3 years after injury. Our study followed a group of children with a history of TBI 7-10 years after injury.
The main finding is that those with severe TBI were at greater risk for developing secondary attention deficit hyperactivity disorder (SADHD) than those with orthopedic injury; however, it should also be noted that kids with less severe injuries were also at risk of developing SADHD. In addition to injury severity, environmental factors (maternal education and family functioning) also played a role in SADHD development. It should also be noted that a number of kids developed SADHD >3.5 years after injury suggesting that these difficulties may not surface until many years after injury.
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MedicalResearch.com Interview with:
Krista F. Huybrechts, MS PhD
Assistant Professor of Medicine
Division of Pharmacoepidemiology and Pharmacoeconomics
Brigham and Women's Hospital
Harvard Medical School
Boston, MA 02120 MedicalResearch.com: What is the background for this study? What are the main findings?Response: In recent years, use of stimulant medications in adults, including women of reproductive age, has increased substantially.
However, data regarding the safety of stimulant medications in early pregnancy are sparse and conflicting. For example, two recent cohort studies failed to detect an association between use of methylphenidate in early pregnancy and overall or cardiac malformations, while another found an 81% increased risk of cardiac malformations, although the estimate was imprecise.
Given the rapidly increasing use of stimulant medications during pregnancy and among women of reproductive age who may become pregnant inadvertently, there is an urgent need to better understand their safety.
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MedicalResearch.com Interview with:
Dr. Adriana Di Martino, MD
Associate Professor, Department of Child and Adolescent Psychiatry
NYU Langone Health
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: While there has been an increased awareness of the co-occurrence of symptoms of Attention Deficit/Hyperactivity Disorder (ADHD) in children with a primary diagnosis of ASD, only recently has there been an appreciation that a substantial proportion of children with ADHD may also have ASD traits. These symptom domains overlap pose a challenge for accurate recognition and targeted treatments, yet their underlying mechanisms have been unknown.
With more traditional diagnostic group comparisons we detected a significant influence of ASD on white matter organization, but our analyses of the severity of symptoms across individuals revealed an association between autistic traits and white matter organization, regardless of the individual's diagnosis. These findings were mostly centered around the corpus callosum, a structure that enables communication between the left and right cerebral hemispheres.
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MedicalResearch.com Interview with: Professor Ian Chi Kei Wong and Kenneth KC Man, Senior Research Assistant
Department of Social Work and Social Administration, Faculty of Social Science
Department of Pharmacology and Pharmacy, LKS Faculty of Medicine
The University of Hong Kong
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Patients with attention-deficit/hyperactivity disorder (ADHD) are at higher risk of various mental health problems. Previous studies suggested that individuals with ADHD are having a higher chance of both attempted and completed suicide. Methylphenidate is a psychostimulant that is recommended for the treatment of ADHD. With the increasing usage of methylphenidate over the past decade, there are concerns about the safety of the medication, in particular, psychiatric adverse effects such as suicide attempt.
The current study looked into over 25,000 patients aged 6 to 25 years in Hong Kong who were receiving methylphenidate in 2001 to 2015. Using the self-controlled case series design, in which the patients act as their own control, we found that the risk of suicide attempt was 6.5 fold higher during a 90-day period before methylphenidate was initiated, remained elevated 4-fold during the first 90 days of treatment, and returned to the normal level during ongoing treatment.
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MedicalResearch.com Interview with: Zheng Chang PhD MSc
Department of Medical Epidemiology and Biostatistics (MEB)
Karolinska Institutet
Stockholm Sweden
MedicalResearch.com: What is the background for this study? What are the main findings?Response: About 1.25 million people worldwide die annually because of motor vehicle crashes (MVCs). ADHD is a prevalent neurodevelopmental disorder with symptoms that include poor sustained attention, impaired impulse control and hyperactivity. ADHD affects 5 percent to 7 percent of children and adolescent and for many people it persists into adulthood. Prior studies have suggested people with ADHD are more likely to experience MVCs. Pharmacotherapy is a first-line treatment for the condition and rates of ADHD medication prescribing have increased over the last decade in the United States and in other countries.
Among the more than 2.3 million patients with ADHD (average age 32.5), we found patients with ADHD had a higher risk of an MVC than a control group of people without ADHD. The use of medication in patients with ADHD was associated with reduced risk for motor vehicle crashes in both male and female patients.
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MedicalResearch.com Interview with:
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.
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MedicalResearch.com Interview with:
M. (Martine) Hoogman PhD.
Postdoc and PI of ENIGMA-ADHD
Radboud universitair medisch centrum
Department of Human Genetics
Nijmegen, The Netherlands
MedicalResearch.com: What is the background for this study? What are the main findings?Response: There are many neuro-imaging studies aimed at investigating structural brain changes related to ADHD, but the results are often inconclusive.
There are two main reasons for this:
1) the small sample size of the studies and
2) the heterogeneous methods used.
We tried to address these issues by forming an international collaboration to provide a sample size sufficient to detect even small effects in volume differences. And in addition, we analyzed all the raw scans again using homogenized methods. There are data of more than 1700 patients (aged 4-63 years of age) and more than 1500 healthy controls in our dataset, coming from 23 sites around the world. We studied the possible volume differences between cases and controls of 7 subcortical regions and intracranial volume by performing mega- and meta-analysis.
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Lisa Meeks , PhD
Director, Medical Student Disability
UCSF Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This was the first study to include students with AD/HD, learning, psychological, and chronic health conditions. This study found that the prevalence of students with disabilities is up to four times higher than previous studies indicated.
AD/HD, learning, and psychological disabilities were the most prevalent, suggesting that most students with disabilities in medicine have non-apparent disabilities. Within MD granting programs, the number of students self-reporting disability varied between 0% and 12%. Explanations for the high variability between programs are unknown, however, anecdotal reports suggest the degree to which programs have dedicated resources and inclusive practices for students with disabilities influence student disclosure.
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MedicalResearch.com Interview with:Gustavo Sudre, PhD
Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch
National Human Genome Research Institute
Bethesda, Maryland
MedicalResearch.com: What is the background for this study? What are the main findings?Response: ADHD is the most common childhood neuropsychiatric disorder, affecting 7-9% of school age children. It is highly heritable (h2=0.7), but few risk genes have been identified. In this study, we aimed to provide quantitative brain-based phenotypes to accelerate gene discovery and understanding.
ADHD is increasingly viewed as resulting from anomalies of the brain’s connectome. The connectome is comprised of the structural connectome (white matter tracts joining different brain regions) and the functional connectome (networks of synchronized functional activity supporting cognition). Here, we identified features of the connectome that are both heritable and associated with ADHD symptoms.
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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.
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MedicalResearch.com Interview with: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. (more…)
MedicalResearch.com Interview with: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.
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MedicalResearch.com Interview with: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.
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MedicalResearch.com Interview with:
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 AlegreMedicalResearch.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.
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MedicalResearch.com Interview with:
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.
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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.
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MedicalResearch.com Interview with:
Michael M. Halassa, MD, PhD, Assistant professorDepartments 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.
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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.(more…)
MedicalResearch.com Interview with:
Scott A. Adler, Ph.D.
Associate Professor Coordinator
Developmental Science Graduate Program Dept. of Psychology & Centre for Vision Research
Visual and Cognitive Development Project
York University
Toronto, Ontario Canada
Medical Research: What is the background for this study?
Dr. Adler: Experiences that we have early in life clearly have an impact on our brain development and behavior as we get older. Numerous studies have detailed these experiences, ranging from how we were fed as a baby to how many languages we hear to traumatic events. These experiences have been shown to influence formation, maintenance, and pruning of the networks of synaptic connections in our brain's that impact all manner of thought and behavior. Yet, the impact of one of the earliest experiences, that of being born, on brain and psychological behavior has not before been explored. A recent study with rat pups has strongly suggested that the birth process has a definite impact on initial brain development. If that is the case, what happens if the infant's birth is one in which she does not experience the natural birth process, such as occurs with caesarean section births?
Medical Research: What are the main findings?
Dr. Adler: There were two main findings from this study. We measured the speed and timing of infants' saccadic eye movements, which are overt indicators of attention, relative to the onset of visual events on a computer monitor. Moving attention and eye movements can occur through two general classes of processes. The first is bottom-up mechanisms in which attention is moved reactively and automatically to the appearance or existence of unique and salient events in the world. In this case, where attention goes is essentially controlled by the events in the world.
The second is top-down mechanisms in which we move attention voluntarily to what we determine to be relevant event in the world based on our own cognitive biases and goals.
This study found that 3-month-old infants born by caesarean section were significantly slower to move attention and make eye movements in reaction to the occurrence of visual events on the basis of bottom-up mechanisms than were infants born vaginally. In contrast, there was difference between infants in moving attention and making eye movements in anticipation of the appearance of visual events on the basis of top-down mechanisms. Additionally, maternal age, which has been shown to be related to the occurrence of caesarean sections, was found not to be related to the current effects.
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