Addiction, ADHD, Author Interviews, Eating Disorders / 29.01.2016
Dasotraline Explored For Treatment of ADHD and Binge Eating Disorders
MedicalResearch.com Interview with:
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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. 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. Richard Deth[/caption]
MedicalResearch.com Interview with:
Dr. Richard Deth PhD
Professor of Pharmacology
Department of Pharmaceutical Sciences
Nova Southeastern University
Medical Research: What is the background for this study?
Dr. Deth: Vitamin B12 plays a crucial role in regulating and promoting methylation reactions (the attachment of a carbon atom to molecules), including DNA methylation. Recent research has identified methylation of DNA and consequential changes in gene expression as crucial factors in brain development, as well as in memory formation and maintenance of brain function during aging. More specifically, the cause(s) of neurodevelopmental disorders such as autism remain obscure, although numerous studies have demonstrated oxidative stress and low plasma levels of the antioxidant glutathione (GSH) in autism.
Medical Research: What are the main findings?
Dr. Deth: We found that brain levels of vitamin B12, especially the methylation-regulating form known as methylB12, decrease significantly with age, even though blood levels don’t show a similar decrease. Importantly, much lower levels of methylB12 were found in subjects with autism and schizophrenia compared to normal subjects of a similar age. Animal studies showed that impaired GSH formation is associated with decreased brain B12 levels.
Dr. Christoph Correll[/caption]
More on Mental Health on MedicalResearch.com
MedicalResearch.com Interview with:
Christoph U. Correll, MD
Professor of Psychiatry and Molecular Medicine
Hofstra Northwell School of Medicine
Hempstead, New York, USA
Investigator, Center for Psychiatric Neuroscience
Feinstein Institute for Medical Research
Manhasset, New York,
Medical Director, Recognition and Prevention
The Zucker Hillside Hospital,
Department of Psychiatry
Medical Research: What is the background for this study?
Dr. Correll: Antipsychotics have been used increasingly for psychotic, but also for many non-psychotic conditions, including for disorders and conditions for which they have not received regulatory approval. Moreover, antipsychotics have been associated with weight gain and abnormalities in blood fat and blood glucose levels. Although data in youth have been less available than in children and adolescents, youth appear to be more sensitive to the cardiometabolic adverse effects of antipsychotics than adults in whom significant weight gain might have already occurred due to long-term prior antipsychotic treatment. Nevertheless, type 2 diabetes, which is related to weight gain, overweight and obesity, seemed to be more common in adults than youth, likely due to the fact that it takes a long time for the body to develop diabetes. Recently, several individual epidemiologic or database studies with sufficient long-term follow-up durations suggested that the type 2 diabetes risk was higher in youth exposed to antipsychotics than healthy control youth and, possibly, even compared to psychiatrically ill patients treated with non-antipsychotic medications. However, a meta-analytic pooling of all available data has not been available to estimate the absolute and relative risk of type 2 diabetes in youth receiving antipsychotic treatment.
Medical Research: What are the main findings?
Dr. Correll: The main findings of the study that meta-analyzed data from 13 studies with 185,105 youth exposed to antipsychotics (average age 14.1 and 59.5 percent male) are that the absolute rates of type 2 diabetes are fortunately still relatively low, i.e. a cumulative type 2 diabetes risk of 5.7/1,000 patients and an exposure adjusted incidence rate of 3.1/1,000 patient-years. Nevertheless, the cumulative risk of 
Prof. Dimitrios Karussis[/caption]
MedicalResearch.com Interview with:
Prof. Dimitrios Karussis M.D., Ph.D.
Professor of Neurology
Head, Multiple Sclerosis Center
Hadassah BrainLabs
Medical Research: What is the background for this study? What are the main findings?
Prof. Karussis: BrainStorm Cell Therapeutics is developing innovative, autologous stem cell therapies for highly debilitating neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson’s Disease (PD). Our technology, NurOwn™ is a first-of-its-kind approach that induces autologous bone marrow-derived Mesenchymal Stem Cells (MSCs) to secrete Neurotrophic Growth Factors (NTFs). These MSC-NTF cells have been shown to be protective in several animal models of neurodegenerative diseases.
Data from the clinical trials described in the recent issue of the Journal of American Medicine – Neurology (JAMA Neurology), suggest that NurOwn can help patients with 
Dr. Aaron Dawes[/caption]
MedicalResearch.com Interview with:
Aaron J. Dawes, MD
Fellow, VA/RWJF Clinical Scholars Program
Division of Health Services Research
University of California Los Angeles
Los Angeles, CA 90024
Medical Research: What is the background for this study? What are the main findings?
Dr. Dawes: We reviewed the published literature to answer three basic questions about bariatric surgery and mental health conditions.
First, how common are mental health conditions among patients being referred for or undergoing bariatric surgery?
Dr. Diana Schendel[/caption]
MedicalResearch.com Interview with:
Diana Schendel, Professor MSO
Department of Public Health
Institute of Epidemiology and Social Medicine and
Department of Economics and Business National Centre for Register-based Research
Aarhus University
Denmark
Medical Research: What is the background for this study? What are the main findings?
Dr. Schende: Elevated mortality has been reported in persons with autism spectrum disorder (ASD), especially with comorbid epilepsy and intellectual disability. The effect of comorbidity on the risk for mortality in ASD, however, has not been rigorously examined in large, population-based studies. Our study aim was to investigate ASD mortality patterns overall and to assess the specific effects of comorbid mental, behavioral, and neurologic disorders on ASD mortality into young adulthood. Our study comprised a nation-wide Danish cohort of 1.9 million children of whom 20,492 were diagnosed with ASD. We observed 68 deaths in persons with ASD; 83% of the persons with ASD who died had comorbid mental/behavioral or neurologic disorders. The risk for mortality was two-fold higher in persons with 
Dr. Mayur Patel[/caption]
MedicalResearch.com Interview with:
Mayur Patel, MD, MPH, FACS
Assistant Professor of Surgery & Neurosurgery
Vanderbilt University Medical Center
Staff Surgeon and Surgical Intensivist
Nashville VA Medical Center
Medical Research: What is the background for this study?
Dr. Patel: Post-traumatic stress disorder (PTSD) can occur in patients after the traumatizing events of critical illness. Survivors of critical illness have reported PTSD symptoms months to even years after critical illness, possibly related to nightmare-like experiences, safety restraints creating communication barriers, and protective mechanical ventilation causing feelings of breathlessness and fear of imminent death. But, the epidemiology of PTSD after critical illness is unclear with wide ranging estimates (0-64%) and largely fails to distinguish past PTSD from new PTSD specifically resulting from the critical care experience.
Our study provides estimates on new cases of 
Dr. Silvia Sara Canetto[/caption]
MedicalResearch.com Interview with:
Silvia Sara Canetto, Ph.D., Professor
Faculty in the Department of Psychology, and
Affiliate Faculty in the
Center for Women's Studies and Gender Research,
Department of Ethnic Studies, and in the
Human Development and Family Studies Department
Colorado State University
Medical Research: What is the background for this study?
Dr. Canetto: In the United States, older men of European descent (so called white men) have significantly higher suicide rates than any other demographic group. For example, their suicide rates are significantly higher than those of older men of African, Latino or Indigenous descent, as well as relative to older women across ethnicities.
Behind these facts there is a cultural story, not just individual journeys of psychological pain and despair. Colorado State University’s Silvia Sara Canetto has spent a large portion of her research career seeking to uncover cultural stories of suicide.
A professor in the College of Natural Sciences’ Department of Psychology, Canetto adds a new chapter to that story in an article recently published in the journal Men and Masculinities. The article features a critical review of theories and research on suicide among older men.
Dr. Anick Bérard[/caption]
MedicalResearch.com Interview with:
Anick Bérard PhD FISPE
Research chair FRQ-S on Medications and Pregnancy
and Director, Réseau Québécois de recherche sur le médicament (RQRM)
and Professor, Research Chair on Medications, Pregnancy and Lactation
Faculty of Pharmacy University of Montreal
and Director, Research Unit on Medications and Pregnancy
Research Center
CHU Ste-Justine
Medical Research: What is the background for this study? What are the main findings?
Dr. Bérard: Paroxetine (one of the most used antidepressant during pregnancy) has been studied extensively over the past 10-12 years. In 2005, a black box warning was put on the Paxil label to caution against use during pregnancy due to the increased risk of cardiac defects. The ACOG 2010 guidelines also suggested switching to other antidepressants during pregnancy. Over the past decade, many studies, including meta-analyses, were performed on on paroxetine use during pregnancy and the risk of cardiac malformations - but results were sometimes statistically significant or not, although a consistent increased risk was observed. It was thought that these variations could be explained by different study designs, patient populations, and because maternal depression was not always taken into account correctly. Hence, we undertook another meta-analysis (the most recent and updated) to quantify the risk of cardiac defects overall as well as specific cardiac defects associated with paoxetine use during pregnancy and to assess the impact of study designs, maternal depression and patient population on the effect of the risk.
We found that women using paroxetine during the first trimester of pregnancy (critical time-window for malformations) were 23% more at risk of having a child with malformations (15 studies combined) - baseline risk of malformation is 3-5% and thus a 23% increased risk is 3.69-6.15% absolute risk; women using paroxetine during the first trimester of pregnancy were 28% more at risk of having a child with cardiac malformations (18 studies combined) - baseline risk of cardiac malformation is 1% and thus a 28% increased risk is 1.28% absolute risk. We found that paroxetine was increasing the risk of many specific cardiac defects as well. Although the estimates varied depending on the comparator group, study design, and malformation detection period, a trend towards increased risk was observed.
Josephine Mollon[/caption]
MedicalResearch.com Interview with:
Josephine Mollon MSc
Department of Psychosis Studies
Institute of Psychiatry, Psychology, and Neuroscience
King’s College London
London, England
Medical Research: What is the background for this study? What are the main findings?
Dr. Mollon: Psychotic symptoms, such as hallucinations and delusions, are core features of psychotic disorders. A significant minority of the general population also reports subclinical psychotic experiences. Evidence suggests that these experiences may lie on a continuum with clinically significant psychotic symptoms. For example, cognitive deficits, which are a hallmark of psychotic disorders, are also seen in people with subclinical psychotic experiences. We used population-based survey data to characterize cognitive functioning in adults with psychotic experiences while adjusting for important sociodemographic characteristics and investigating the effect of age.
The 171 (9.7%) adults with psychotic experiences showed significant memory and verbal deficits, but not IQ or processing speed deficits. Only participants 50 years and older with psychotic experiences showed medium to large impairments in general IQ, verbal knowledge, working memory and memory after adjusting for socioeconomic status, cannabis use, and common mental disorders.
Dr. Chugani[/caption]
MedicalResearch.com Interview with:
Diane C. Chugani, PhD
Director, Nemours Neuroscience Research
Nemours—AI DuPont Hospital for Children
Wilmington, DE 19803
Medical Research: What is the background for this study? What are the main findings?
Dr. Chugani: This clinical trial was performed at 5 sites throughout the country and was lead by our team at Wayne State University and Children’s Hospital of Michigan in Detroit. The study was sponsored by the National Institutes of Health through an Autism Centers of Excellence Network grant. Based upon our previous PET scanning studies showing low serotonin synthesis in the brains of young children with autism, we tested whether the serotonin-like drug buspirone would be beneficial in treating young children with Autism Spectrum Disorder. We found that low doses of buspirone were effective in reducing repetitive behaviors with no significant side effects in this group of children.
Dr. Zoltan Sarnyai[/caption]
MedicalResearch.com Interview with:
Zoltan Sarnyai, M.D., Ph.D.
Associate Professor of Pharmacology
Head, Laboratory of Psychiatric Neuroscience
Australian Institute of Tropical Health and Medicine (AITHM)
Comparative Genome Centre
Centre for Biodiscovery and Molecular Development of Therapeutics
James Cook University
Townsville, Australia
Medical Research: What is the background for this study?
Dr. Sarnyai: Schizophrenia has long been conceptualized as a disease contributed by the increased activity of the neurotransmitter system that provides dopamine for the brain. All clinically used antipsychotic drugs inhibit dopamine transmission in the brain by blocking dopamine receptors. These drugs have only a limited efficacy on a certain set of symptoms associated with schizophrenia. More recent research has uncovered that abnormal glucose and energy metabolism in the brain may contribute in the development of schizophrenia. This is not altogether surprising considering that our brain is using a disproportionately high amount of glucose to fuel neurotransmission (cell-to-cell communication in the brain), to maintain normal electrical activity of nerve cells and to deal with damaging free oxygen radicals. Therefore, even relatively small changes in the machinery that is required to provide energy for the brain cells can have very significant impact on brain function. In fact, recent studies have identified altered expression of genes and proteins that are responsible for enzymatic breakdown of glucose and proper handling of the metabolites to create the energy-rich molecule ATP. In addition, recent research shows decreased number and impaired function of the mitochondria, the powerhouses of the cell, in the brain of individuals with schizophrenia.
These recent results that show abnormal energy metabolism in schizophrenia raise the possibility of targeting metabolic pathways for therapeutic benefit in this condition. Ketogenic diet provides and alternative source of energy to the brain through fatty acids. Furthermore, since this diet is very low in carbohydrates, almost all the energy needs of the cells comes from breaking down fat (fatty acids) as opposed to glucose. This can circumvent the classic glucose metabolic pathways that maybe impaired in the disease. Also, breaking down fatty acids produces 40% more of the energy-rich molecule ATP than breaking down the carbohydrate glucose. Altogether, ketogenic diet may provide extra energy and can help neurotransmission in the brain, leading to the improvement of neurobiological processes underlying schizophrenia.
Dr. Rashmi Patel[/caption]
MedicalResearch.com Interview with:
Dr. Rashmi Patel
MA (Cantab) MA BM BCh PGDip (Oxon) MRCPsych
Psychiatry
King's College Londo
Dr. Martin[/caption]
MedicalResearch.com Interview with:
Dr Anne Martin PhD
Research Associate/Research Fellow
Physical Activity for Health Research Centre (PAHRC)
Institute for Sport, PE & Health Sciences
University of Edinburgh
TeleScot Research Group
Usher Institute for Population Health Sciences and Informatics
Edinburgh
Medical Research: What is the background for this study? What are the main findings?
Dr. Martin: Impairments in cognitive development during childhood can have detrimental effects on health behaviour, educational attainment, and socio-economic status later in life. Epidemiological evidence indicates an association between childhood obesity and cognition and educational attainment. Knowledge of when obesity related deficits in cognition and attainment emerge, and how large the deficits are at various ages, may be useful to support arguments for school-based obesity prevention initiatives and in translating evidence on this topic into policy aimed at preventing obesity.
In this study we explored whether the adverse association between obesity and cognition emerges in early childhood. Measures of cognitive abilities included visuo-spatial skills, expressive language skills and reasoning skills. Our findings indicated that obesity in the pre-school years may be weakly associated with some poorer cognitive outcomes at age 5 years in boys, independently of socioeconomic status.
Stronger relationships between obesity and 
Dr. De Brito[/caption]
MedicalResearch.com Interview with:
Stephane De Brito, PhD
Birmingham Fellow
School of Psychology
Robert Aitken Building, Room 337a
University of Birmingham UK
Medical Research: What is the background for this study? What are the main findings?
Dr. De Brito: In the last decade, an increasing number of neuroimaging studies have used structural magnetic resonance imaging (sMRI) to examine the brains of youths who show behavioural problems that include antisocial and aggressive behaviour. Those studies have mostly relied on a method called voxel-based morphometry (or VBM), which is a whole-brain and automated technique that allows researchers to objectively assess the local composition of brain tissue, such as grey matter volume. The main problem is that the findings from those sMRI studies have been quite disparate and few have been replicated, partly due to differences in sample sizes and characteristics across studies. Therefore, we set out to carry out a meta-analysis of the available data to provide a clearer account of the literature on this topic. A particular strength of our meta-analysis is that we used the original brain imaging maps (also referred to as statistical parametric maps) from 11 of the 13 studies, which makes our analysis more accurate and reliable. The final sample comprised of 394 youths with behavioural problems and 350 typically developing youths, making it the largest study on this topic to date.
Our results showed that, compared to typically developing youths, those with behavioural problems show reduced grey matter volume in the amygdala, the insula, and the prefrontal cortex. These brain areas have been shown to be important for decision-making, empathic responses, processing facial expressions and emotion regulation; key cognitive and affective processes that are shown to be deficient in youths with behavioural problems.
Dr. Eileen Shinn[/caption]
MedicalResearch.com Interview with:
Dr. Eileen H. Shinn PhD
Assistant Professor, Department of Behavioral Science
Cancer Prevention and Population Sciences
MD Anderson Cancer Center
The University of Texas
Houston, TX
Medical Research: What is the background for this study? What are the main findings?
Dr. Shinn: Recent studies with leukemia, breast, lung, renal and liver cancer patients have shown that patients with depression have worsened survival. These effect sizes are small, but independent of any of the traditional factors that are known to impact survival, such as extent of cancer, types of treatment administered and baseline health and age of the patient. The current thinking is that cancer patients who are depressed have chronically heightened responses to stress; the constant release of stress hormones trigger changes in the tumor itself (such as noradrenergically-driven tumor angiogenesis) or may weakens the body’s immune function and ability to resist tumor growth.
When we measured depression in newly diagnosed patients with oropharyngeal cancer (cancer of the base of tongue and tonsil), we found that those patients who scored as depressed were 3.5 times more likely to have died within the five year period after their diagnosis, compared to nondepressed patients. We also found that patients who were depressed were also 3.8 times more likely to have their cancer recur within the first five years after diagnosis. We also found that patients who continued to smoke after diagnosis were more likely to recur within the first five years. These effect sizes were larger than those typically found in recent studies. We believe that the larger effect size may be due to the tight eligibility criteria ( e.g., we did not include patients who already had recurrent disease, we only included patients with one specific type of head and neck cancer, oropharyngeal) and also due to controlling other known factors (all patients completed individualized treatment regimens of radiation/ chemoradiation at a comprehensive cancer center and patients with more advanced disease stage were more likely to have received treatment intensification compared to patients with early stage disease). In all, we had 130 patients, one of the largest prospective studies with oropharyngeal cancer to examine the effect of depression on cancer outcome.
Dr. Frans Boch Waldorff[/caption]
Dr. Kevin Nead[/caption]
MedicalResearch.com Interview with:
Kevin T. Nead, MD, MPhil
Dept. of Radiation Oncology
Perelman School of Medicine
University of Pennsylvania
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Nead: There are a growing number of studies suggesting that the use of Androgen Deprivation Therapy (ADT) may be associated with cognitive changes and some of these changes overlap with characteristic features of Alzheimer’s disease. In addition, low testosterone levels have been associated with Alzheimer’s disease risk and ADT lowers testosterone levels. Despite these findings, we could not identify any studies examining the association between ADT and Alzheimer’s disease risk. We therefore felt this study could make an important contribution in guiding future research to fully understand the relative risks and benefits of ADT.
We examined electronic medical record data from Stanford University and Mt. Sinai hospitals to identify a cohort of 16,888 patients with prostate cancer. We found that men with prostate cancer who received Androgen Deprivation Therapy were more likely to develop Alzheimer’s disease than men who did not receive 
Dr. Douglas A. Mata Harvard Medical School[/caption]
Douglas A. Mata, M.D., M.P.H.
Anatomic and Clinical Pathology
Resident Physician, Brigham & Women’s Hospital
Clinical Fellow, Harvard Medical School
Boston, MA 02115
Marco A. Ramos, M.Phil., M.S.Ed.
History of Science and Medicine
M.D./Ph.D. Candidate, Yale School of Medicine
New Haven, CT 06511
Medical Research: What is the background for your study?
Dr. Mata: Training to be a doctor is clearly stressful, but the prevalence of depression among trainees is not well known. They may get especially depressed during their grueling years of residency, when young physicians are learning their craft by working long hours and taking care of critically ill patients. Coming up with a reliable estimate of the prevalence of depression among graduate medical trainees would help us identify causes of resident depression and begin to treat or prevent it. We thus aimed to find answers to two questions:
Halle Amick[/caption]
MedicalResearch.com Interview with:
Halle Amick, research associate
Sheps Center for Health Services Research
University of North Carolina at Chapel Hill
Chapel Hill, NC
Medical Research: What is the background for this study? What are the main findings?
Response: Major depressive disorder (MDD) affects more than 32 million Americans and millions more worldwide. Many patients first seek care from a primary care provider, and the most common treatment initiated in that setting is medication. Although there is an evidence base that shows certain psychotherapies to be effective treatments, primary care providers may not be familiar enough with psychotherapy to present it as a treatment option. We conducted a full review of clinical trials that compared antidepressant medication—specifically second-generation antidepressants (SGAs)—with cognitive behavioral therapy (CBT).
We found that symptom improvement and rate of remission were similar between SGAs and CBT, whether they were used alone or in combination with each other. We also found no difference in the rates of withdrawal from the clinical trials either overall or due to adverse events.