Author Interviews, Autism, Genetic Research, Nature, Pediatrics, Schizophrenia / 04.01.2017

MedicalResearch.com Interview with: Dr. Beate St Pourcain MSc, PhD(Cardiff) Genetic Epidemiology School of Oral and Dental Sciences MRC Integrative Epidemiology Unit University of Bristol MedicalResearch.com: What is the background for this study? What are the main findings? Response: People with autism and with schizophrenia both have problems interacting and communicating with other people, because they cannot easily initiate social interactions or give appropriate responses in return. On the other hand, the disorders of autism and schizophrenia develop in very different ways. The first signs of Autism Spectrum Disorder (ASD) typically occur during infancy or early childhood, whereas the symptoms of schizophrenia usually do not appear until early adulthood. The researchers asked whether it is possible to disentangle the apparent symptom overlap in ASD and schizophrenia through genetic analyses. As clinical diagnoses relate to the age of onset of a disorder and do not capture multiple developmental stages, the researchers used a trick. They assumed that there is a continuum between normal and abnormal behaviour and captured social communicative competence - the ability to socially engage with other people successfully - in participants of a population-based birth cohort during development. Specifically, the researchers studied the genetic overlap between the risk of having these psychiatric disorders and these measures of social communicative competence. Investigating thousands of genetic variants with small effects across the genome, they showed that genes influencing social communication problems during childhood overlap with genes conferring risk for autism, but that this relationship wanes during adolescence. In contrast, genes influencing risk for schizophrenia were most strongly interrelated with genes affecting social competence during later adolescence, in line with the natural history of the disorder. "The findings suggest that the risk of developing these contrasting psychiatric conditions is strongly related to distinct sets of genes, both of which influence social communication skills, but exert their maximum influence during different periods of development", explained Beate St Pourcain, senior investigator at the Max Planck Institute and lead author of the study. This is consistent with studies showing that genetic factors underlying social communication behaviour also change to some degree during childhood and adolescence. (more…)
Author Interviews, Autism, Emory, Pediatrics / 25.11.2016

MedicalResearch.com Interview with: Warren Jones, PhD Director of Research, Marcus Autism Center Children's Healthcare of Atlanta CHOA Distinguished Chair in Autism Asst. Professor, Dept. of Pediatrics Emory University School of Medicine Atlanta, Georgia 30329 MedicalResearch.com: What is the background for this study? What are the main findings? Response: These results help clarify an important and longstanding question in autism: why do children with autism look less at other people’s eyes? Two ideas for reduced eye contact in autism have been proposed: - One idea is that children with autism avoid eye contact because they find it stressful and negative. - The other idea is that children with autism look less at other people’s eyes because the social cues from the eyes are not perceived as particularly meaningful or important. This study is important because each idea reflects a very different understanding of what autism is. And maybe even more importantly, each idea reflects a very different view about the right treatment approach to autism and to reduced eye contact in autism. To answer this question, we used eye-tracking technology to study how 86 children with and without autism paid attention to other people’s eyes. Children were tested when they were just two years old, at their time of initial diagnosis. (more…)
Author Interviews, Autism, JAMA, Pediatrics / 20.11.2016

MedicalResearch.com Interview with: Dr. Melanie Penner, MD FRCP (C) Clinician investigator and developmental pediatrician Holland Bloorview Kids Rehabilitation Hospital  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Studies have shown that accessing intensive behavioral intervention (IBI) services at younger ages is associated with improved outcomes for children with autism spectrum disorder (ASD). In Ontario, Canada, children wait years to access publicly-funded IBI. This analysis estimated costs and projected adult independence for three IBI wait time scenarios: the current wait time, a wait time reduced by half, and an eliminated wait time. The model inputs came from published literature. The main findings showed that eliminating the wait time generated the most independence and cost the least amount of money to both the government and society. With no wait time for intensive behavioral intervention, the government would save $53,000 (2015 Canadian dollars per person) with autism spectrum disorder over their lifetime, and society would save $267,000 (2015 Canadian dollars). (more…)
Author Interviews, Autism, Gender Differences / 08.11.2016

MedicalResearch.com Interview with: Dr. John Strang, PsyD Division of Pediatric Neuropsychology Children's National Health System. MedicalResearch.com: What is the background for this study? What are the main findings Response: Gender dysphoria or transgenderism (GD) and autism spectrum disorders (ASD) often co-occur. Between 9 and 25% of youth referred for gender dysphoria concerns have co-occurring ASD. Autistic transgender youth often require significant supports; their autism symptoms alone present challenges, but when combined with gender dysphoria, the clinical needs and complexities increase significantly. For example, an autism spectrum disorder, with its resulting social and communication challenges, can make it more difficult for a transgender teen to advocate for their needs around gender. Specialists from youth gender clinics from around the world have years of experience working with autistic transgender youth. This study used an international search process to identify experts in co-occurring ASD and GD. Twenty-two experts were identified and participated in this multi-stage consensus building study. A set of initial clinical guidelines for the evaluation and care of youth with co-occurring ASD and GD were produced. (more…)
Author Interviews, Autism, Education, Lancet, Pediatrics / 26.10.2016

MedicalResearch.com Interview with: Prof. Tony Charman Chair in Clinical Child Psychology King's College London, Institute of Psychiatry, Psychology & Neuroscience (IoPPN) Department of Psychology PO77, Henry Wellcome Building De Crespigny Park Denmark Hill London MedicalResearch.com: What is the background for this study? What are the main findings? Response: The study is a follow-up of a treatment trial on which we have previous reported. In the original Preschool Autism Communication Trial (PACT), 152 children aged 2-4 with autism were randomised to receive the 12 month early intervention or treatment as usual. The type of early intervention used in this study focuses specifically on working with parents. Through watching videos of themselves interacting with their child and receiving feedback from therapists, parents are able to enhance their awareness and response to their child’s unusual patterns of communication; they become better able to understand their child and communicate back appropriately in a focused way. Parents take part in 12 therapy sessions over 6 months, followed by monthly support sessions for the next 6 months. In addition, parents agree to do 20-30 minutes per day of planned communication and play activities with the child. The study published today is the follow-up analysis of the same children approximately 6 years after the end of treatment. The main findings are that children who had received the PACT intervention aged 2-4 had less severe overall symptoms six years later, compared to children who only received ’treatment as usual’ (TAU) with improved social communication and reduced repetitive behaviours, although no changes were seen in other areas such as language or anxiety. These findings on an international recognised and blind rated observational measure of autism symptoms were accompanied by improvements in children’s communication with their parents for the intervention group, but no differences in the language scores of children. Additionally, parents in the intervention group reported improvements in peer relationships, social communication and repetitive behaviours. However, there was no significant difference between the two groups on measures of child anxiety, challenging behaviours (eg, conduct/oppositional disorder) or depression. (more…)
Author Interviews, Autism, Genetic Research, Kidney Disease, Nature / 28.09.2016

MedicalResearch.com Interview with: Prof Adrian S. Woolf Chair, Professor of Paediatric Science University of Manchester, UK MedicalResearch.com: What is the background for this study? Response: Several years ago, Laurent Fasano discovered that the Drosophila teashirt gene was needed to pattern the body of embryonic flies. He then found that this transcription factor had three similar genes in mammals. Working with Adrian Woolf in the UK, they found that Teashirt-3 (Tshz3) was needed in mice to make muscle form in the ureter When the gene was mutated, mice were born with ureters that were 'blown-up' and they failed to milk urine from the kidney with the bladder. (more…)
Author Interviews, Autism, Biomarkers, JAMA, NIH, Pediatrics / 21.09.2016

MedicalResearch.com Interview with: Dr. Yong Cheng, PhD Postdoctoral Fellow NIH MedicalResearch.com: What is the background for this study? Response: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders which affect about 1 in 68 children in the United States, according to data from the Centers for Disease Control and Prevention. Brain-derived neurotrophic factor (BDNF) is an important moderator in neurodevelopment and neuroplasticity, and studies have suggested the involvement of BDNF in ASD. Although some clinical studies show abnormal expression of BDNF in children with ASD, findings have been inconsistent. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood BDNF levels in children with ASD, compared with healthy peers. (more…)
Author Interviews, Autism, Diabetes, Mental Health Research / 25.08.2016

MedicalResearch.com Interview with: Evdokia Anagnostou MD Canada Research Chair (Tier II) in Translational Therapeutics in Autism Senior Clinician Scientist and co-lead of the Autism Research Centre Holland Bloorview Kids Rehabilitation Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Researchers from Holland Bloorview Kids Rehabilitation Hospital / University of Toronto (Canada), Ohio State University, University of Pittsburgh, Columbia University, and Vanderbilt University, led a double-blind, placebo-controlled randomized clinical trial to examine whether metformin, a common type-2 diabetes drug, may be effective in counteracting weight gain commonly seen with the use of atypical antipsychotic medications, indicated by the FDA for the treatment of irritability in children and youth with autism spectrum disorder (ASD). Results showed that metformin was effective in helping overweight children and adolescents with autism spectrum disorder (ASD) who take antipsychotic medications lower their body mass index (BMI). Both FDA-approved antipsychotic medications for treating irritability and agitation symptoms in children and adolescents with ASD can cause a significant increase in weight gain, which in addition to increasing BMI, enhances long-term risk of diabetes. This complicates an already challenging issue as adolescents with autism spectrum disorder are ~ two times more likely to be obese than adolescents without developmental disabilities. Findings of this research are important, especially for families of children with ASD, as managing long-term physical health while also treating irritability/agitation symptoms, can help ensure that their child can participate fully in life (school, etc.). (more…)
Author Interviews, Autism, Genetic Research, NIH / 16.08.2016

MedicalResearch.com Interview with: Karen Usdin, Ph. D. Senior Investigator Chief, Gene Structure and Disease Section Laboratory of Cell and Molecular Biology National Institute of Diabetes, Digestive and Kidney Diseases National Institutes of Health Bethesda MD 20892 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our laboratory is interested in the causes and consequences of the unusual repeat expansion mutation that causes the Fragile X-related disorders. However these disorders are challenging to study, in part because the repeat tract is difficult to amplify by PCR. This makes monitoring of repeat length, as well as other factors we are interested in such as methylation status and the presence of AGG interruptions, quite difficult. In our experience, both repeat number and methylation status are very variable in patient stem cells and in disease-relevant cell types derived from them. This variability arises because the repeat is prone to both expansion and contraction and because at different times there can be selection for smaller alleles or against unmethylated ones. Thus the frequent monitoring of repeat length and methylation status is critical for work with patient cells, particularly when those cells are to be used for drug screening or to examine the consequences of expansion. While other assays are available to determine one or more of these parameters, some are cumbersome to use or lack the necessary robustness and sensitivity, whilst others are prohibitively expensive for routine laboratory work. We thus saw a need for assays that are robust, sensitive and cost-effective for preclinical studies. (more…)
Author Interviews, Autism, OBGYNE / 04.07.2016

MedicalResearch.com Interview with: Dr-Claudia-Avella-GarcíaClaudia Avella-García MD, MPH, PhD ISGlobal - Institut de Salut Global Barcelona Unitat Docent de Medicina Preventiva i Salut Publica H.Mar-UPF-ASPB MedicalResearch.com: What is the background for this study? Response: Acetaminophen (paracetamol) is used by around half of all pregnant women in developed countries and is currently the recommended treatment for fever and pain during gestation. However, evidence linking exposure to this medication with negative changes in neurodevelopment has been coming to light, warranting further study. Therefore, our objective was to evaluate whether prenatal exposure to acetaminophen was adversely associated with child neurodevelopment at 1 and 5 years of age. For this reason, we evaluated 2644 mother-child pairs recruited during pregnancy as part of the INfancia y Medio Ambiente – Childhood and Environment (INMA) project, a Spanish general population-based cohort. We collected information on acetaminophen use prospectively up until week 32 of gestation. We evaluated neurodevelopment at 1 year of age using the Bayley Scales of Infant Development. At 5 years of age we applied a battery of tests evaluating different aspects of neurodevelopment including both cognitive and behavioural aspects. (more…)
Author Interviews, Autism, Genetic Research / 09.06.2016

MedicalResearch.com Interview with: David Beversdorf, M.D. Associate professor in the departments of radiology, neurology and psychological sciences University of Missouri and Missouri University Thompson Center for Autism and Neurodevelopmental DisordersDavid Beversdorf, M.D. Associate professor in the departments of radiology, neurology and psychological sciences University of Missouri and Missouri University Thompson Center for Autism and Neurodevelopmental Disorders MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Beversdorf: Our previous work had demonstrated in retrospective surveys a higher incidence of prenatal psychosocial stress exposure during the late 2nd and early 3rd trimester in pregnancies where the offspring had developed autism spectrum disorder (ASD). This had been confirmed in other studies, including a study examining the timing of exposure to tropical storms during pregnancy. However, not everyone exposed to stress during pregnancy has a child with ASD, so we began to look at genetic risk for augmented stress reactivity. This initial exploration involved examination of the interaction between stress exposure during ASD-associated pregnancies and the maternal presence of variations in one gene well known to affect stress reactivity. Variations in this gene were also targeted as they have been associated with ASD in some studies. We found in two independent groups of patients (one in Missouri, one in Ontario, Canada) that maternal presence of at least one copy of the stress-susceptible variant of this gene is associated with the link between maternal stress exposure during this time window of pregnancy and subsequent development of ASD in the offspring. (more…)
Author Interviews, Autism, Pediatrics, Toxin Research / 01.05.2016

MedicalResearch.com Interview with: Steven Daniel Hicks, M.D., Ph.D. Penn State Hershey Medical Group Hope Drive, Pediatrics Hershey, PA 17033  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Hicks:  This research was inspired by results of the CHARGE study (examining environmental influences on autism) which showed that specific pesticides (including pyrethroids) increased the risk of autism and developmental delay, particularly when mothers were exposed in the 3rdtrimester. We recognized that the department of health sprayed pyrethroids from airplanes in a specific area near our regional medical center every summer to combat mosquito borne illnesses. We asked whether children from those areas had increased rates of autism and developmental delay. We found that they were about 25% more likely to be diagnosed with a developmental disorder at our medical center than children from control regions without aerial spraying of pyrethroids. (more…)
Author Interviews, Autism, Brigham & Women's - Harvard, PLoS / 09.04.2016

MedicalResearch.com Interview with: Ya Wen PhD TRANSCEND Research, Neurology Department Massachusetts General Hospital, Charlestown, Massachusetts, Harvard Medical School, Harvard University, Boston, Massachusetts Higher Synthesis Foundation, Cambridge, Massachusetts MedicalResearch.com: What is the background for this study? Dr. Ya Wen: At the time of this study (December 2014), the SFARI (Simons Foundation Autism Research Initiative) Gene-Human Gene Module recorded 667 human genes implicated as relevant to Autism spectrum disorders (ASDs). Now the number is close to 800. We sought to address the challenge of making sense of this large list of genes by identifying coherent underlying biological mechanisms that link groups of these genes together. To do this, we used information from several existing and well established databases and created a “demographics” of autism genes and pathways. MedicalResearch.com: What are the main findings? Dr. Ya Wen: From these hundreds of autism genes, we first found the relatively most important pathways, and then we generated a pathway network by mapping the pathway-pathway interactions into an Autism Pathway Network. Our systems analyses of this network converged upon an important role in autism pathophysiology for two pathways: MAPK signaling and calcium signaling, and specifically the process where they overlap, “calcium-protein kinase C-Ras-Raf-MAPK/ERK”. Our study also illuminated genetic relationships between autism and several other kinds of illness, including cancer, metabolic and heart diseases. Many of the significant genes and pathways were associated with vulnerability in the processing of challenging environmental influences. (more…)
Abuse and Neglect, Autism, Depression / 14.03.2016

MedicalResearch.com Interview with: Dr. Rebecca A. Charlton PhD Senior Lecturer in Psychology; Undergraduate Admissions Tutor Department of Psychology Goldsmiths, University of London New Cross London, UK MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Charlton: Although Autism Spectrum Disorders are classified as developmental disorders, they last throughout life. Autism Spectrum Disorders were first identified in the 1940s, but it was only from the 1960s onwards that awareness of the condition began to increase. Initial research into Autism focused on the area of greatest need, i.e. childhood and education. Only now that those individuals first diagnosed with Autism are reaching old age are studies able to examine what happens in late-life. Although there are an increasing number of older adults with a diagnosis of Autism Spectrum Disorders, it is often difficult to identify individuals willing to participate in research. One alternative is to explore Autism traits in the general population, this is known as the Broad Autism Phenotype (BAP). These BAP traits occur in relatives of those with Autism and in the general population. By examining the BAP in community-dwelling older adults, we can begin to understand whether these traits confer additional risk to in ageing. MedicalResearch.com: What did you do in the study? What are the main findings? Dr. Charlton: Adults aged over 60 years old were recruited to take part in the study. They completed questionnaires reporting on presences of  Broad Autism Phenotype traits, executive functions (the ability to plan and organise behaviour), mood (depression and anxiety), and social support. Of the 66 individuals who participated, 20 individuals reported significant BAP traits – classified as the  Broad Autism Phenotype group. Individuals in the BAP group reported more problems with executive functions, higher rates of depression and anxiety, and less social support than those in the non-BAP group. Further analyses demonstrated that having  Broad Autism Phenotype traits was the factor that most explained presence of depression and anxiety symptoms among these older adults. (more…)
Author Interviews, Autism, Genetic Research / 23.02.2016

MedicalResearch.com Interview with: Li ZENG, Ph.D. Principal Investigator Neural Stem Cell Research Lab National Neuroscience Institute Singapore Medical Research: What is the background for this study? What are the main findings? Dr. Zeng: Autism Spectrum Disorders (ASDs) are a group of highly inheritable behavioural disorders that pose major personal and public health concerns. Patients with ASDs have mild to severe communication difficulties, repetitive behaviour and social challenges. Such disorders significantly challenge an individual’s ability to conduct daily activities and function normally in society. Currently there are very few medication options that effectively treat ASDs. Therefore, there is a need to better understand the biology of that produces Autism Spectrum Disorder symptoms. In the study, we found how one brain-specific microRNA (miR-128) plays a key role in causing abnormal brain development. MicroRNAs are small molecules that regulate gene expression in the human body to ensure proper cellular functions. Although it was known that miR-128 is misregulated in some patients with autism, what that meant and how it functioned was not known. We showed that miR-128 targets a protein called PCM1 that is critical to the cell division of neural precursor cells (NPCs). NPCs during early brain development have two fates - they either stay as NPCs and undergo self-renewal or become neurons through differentiation. The dysfunctional regulation of PCM1 by misregulated miR-128 impairs brain development, which may underlie brain size changes in people with Autism Spectrum Disorders. (more…)
Author Interviews, Autism, JAMA, Pediatrics / 18.02.2016

MedicalResearch.com Interview with: Dr. David Grossman MD MPH Vice chair of the U.S. Preventive Services Task Force Professor at the University of Washington Schools of Public Health and Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Grossman: The Task Force cares deeply about the challenges that children affected by autism and their families face in getting the care and support they need. This was the first time that we assessed the evidence around screening young children for autism, and our recommendation was informed by a review of the most up-to-date science, which included randomized trials, observational studies, and research from a number of Federal health agencies. We concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for autism spectrum disorder in children for whom no concerns of autism have been raised by their parents or a clinician. This is an I statement, which is not a recommendation against screening, but a call for more research on screening and treatment in young children who don’t have obvious symptoms. It is important to note that this recommendation will not affect insurance coverage for autism screening, which is currently covered under the Affordable Care Act as a result of the American Academy of Pediatrics’ Bright Futures Guidelines. (more…)
Author Interviews, Autism, Genetic Research, JAMA, Schizophrenia / 30.01.2016

MedicalResearch.com Interview with: Andrea J. Gonzalez-Mantilla, M.D. Postdoctoral Fellow Andres Moreno-De-Luca, M.D. Investigator I Autism & Developmental Medicine Institute Department of Radiology Geisinger Health System Danville, PA 17822 Medical Research: What is the background for this study? What are the main findings? Response: Developmental brain disorders (DBD), such as autism, intellectual disability, and schizophrenia are a group of heterogeneous conditions characterized by deficits that affect multiple functional domains, such as cognition, behavior, communication, and motor skills. Previous studies provide strong evidence of common underlying molecular pathways and shared genetic causes among apparently different DBDs. Large-scale genomic studies of individuals with developmental brain disorders have found that identifying multiple, independent de novo pathogenic loss-of-function (pLOF) variants in the same gene among unrelated individuals is a powerful statistical approach to reliably identify disease-causing genes. However, genomic data from smaller cohorts and case reports are not routinely pooled with data from larger studies. Moreover, most previous studies have been restricted to cohorts of individuals ascertained based on a single diagnosis (e.g., a study will focus on only individuals with a diagnosis of autism and not consider other genomic data from individuals with a different diagnosis). Therefore, genomic data from individuals across DBD are not being jointly analyzed in search of pLOF variants in the same gene that may help build evidence for a causative role in developmental brain disorders. In this study, we carried out data mining of previously published data to identify genes related to the DBD phenotype. We expanded the aforementioned method and developed a multilevel data-integration approach, which capitalizes on three genotype-phenotype data sources: (1) genomic data from structural and sequence pLOF variants, (2) phenotype data from six apparently distinct DBD (autism, intellectual disability, epilepsy, schizophrenia, bipolar disorder and attention-deficit/hyperactivity disorder), and (3) data from large scale studies, smaller cohorts, and case reports. We identified 241 candidate genes for developmental brain disorders, including 17 genes that had not previously been associated with developmental brain disorders. (more…)
Aging, Author Interviews, Autism, Mental Health Research, PLoS, Schizophrenia / 25.01.2016

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. (more…)
Accidents & Violence, Author Interviews, Autism, JAMA / 12.01.2016

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 autism spectrum disorder overall. An elevated risk for mortality was also seen in persons who had ASD only, or had both ASD and other neurologic or mental/behavioral disorders, compared to persons without these other morbidities and no ASD. However, the co-occurrence of ASD in persons with neurologic, or with mental/behavioral disorders, added no additional mortality risk compared to persons with these disorders and no autism spectrum disorder. These results suggest that the mechanisms underlying mortality risk in ASD in part may be shared with these other disorders, although what might be the specific shared mechanisms cannot be determined with these data. (more…)
Author Interviews, Autism, Pediatrics, Pharmacology / 02.01.2016

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. (more…)
Author Interviews, Autism, Pediatrics, PNAS / 21.11.2015

MedicalResearch.com Interview with: Lauren Kenworthy, PhD Associate professor of Neurology, Pediatrics, and Psychiatry George Washington University School of Medicine Director of the Center for Autism Spectrum Disorders Children’s National Health System Medical Research: What is the background for this study? What are the main findings? Dr. Kenworthy: Connectivity among brain regions may account for variability in autism outcomes not explained by age or behavioral measures, according to a study. We have previously shown that behavioral assessments of intelligence, baseline adaptive behavior and executive functions in people with autism can explain some of the variation in outcomes and function, but we have not been able to explain all of the variance in outcome (e.g. Pugliese et al 2015a, 2015b). In this study, we found that 44% of the study group experienced significant change in scores on adaptive behavior between the initial scan and follow-up. Connectivity between three resting-state networks, including the salience network, the default-mode network, and the frontoparietal task control network, was linked not only to future autistic behaviors but also to changes in autistic and adaptive behaviors over the post-scan period. Further, connectivity involving the salience network and associated brain regions was associated with improvement in adaptive behaviors, with 100% sensitivity and around 71% precision. (more…)
Author Interviews, Autism, Radiology, UCLA / 16.10.2015

MedicalResearch.com Interview with: Kay Jann, PhD, Department of Neurology Danny JJ Wang, Prof., Department of Neurology Laboratory of Functional MRI Technology Ahmanson-Lovelace Brain Mapping Center Department of Neurology University of California Los Angeles Los Angeles  Medical Research: What is the background for this study? What are the main findings? Response: The brain controls most of our behavior and thus changes in how brain areas function and communicate with each other can alter this behavior and lead to impairments associated with mental disorders. Higher cognitive functions are controlled by brain areas that form complex interconnected networks and alterations in these networks can lead to cognitive impairments. In autism, one such network is the so called default mode network. This network controls self-referential thoughts, reasoning past and future and is involved in understanding mental states of others (i.e. Theory of Mind). Functional MRI based functional connectivity is a research tool to understand the interrelations between brain areas and how separate, distributed areas can be organized into brain networks that serve specific cognitive functions. In autism, local hyperconnectivity along with hypoconnectivity in long range connections between anterior and posterior cingulate cortices has been discussed to be one of the physiological underpinnings of the behavioral symptoms in social interaction and cognition observed in austism. It is hypothesized to be due to a developmental delay and disbalance of the balance between neuronal excitation/inhibition in brain areas that lead to oversynchronized strong short-range (local) networks while long-range connections that develop later in neurodevelopment are less well established. In our study, we used a non-invasive MRI technique called arterial spin labeling (ASL) perfusion MRI for the first time in autism research. Similarly to Positron Emission Tomography (PET) this technique allows measuring cerebral blood flow (CBF), however without the need to inject radioactive tracers. ASL MRI uses magnetically labeled blood water as an endogenous tracer to quantify CBF. Accordingly, our approach enabled us to combine information about how brain areas are functionally connected, as well as their associated metabolic energy consumption in autism spectrum disorder.  We found that in typically developing children, the known relation between how strongly an area is connected to other areas in a brain network, the more energy it requires holds. In children with autism spectrum disorder this relation, however, was disrupted in a major brain area (the dorsal anterior cingulate cortex) that is relevant to social interactions and in Theory of Mind. Both are cognitive processes that are to some extent impaired in persons with autism spectrum disorders. (more…)
Author Interviews, Autism, Medical Imaging, OBGYNE / 14.10.2015

MedicalResearch.com Interview with: Alex Ure MPsych(Clin) PhD Psychologist & Postdoctoral Fellow, CRE in Newborn Medicine Research Officer, VIBeS Group, Clinical Sciences Murdoch Childrens Research Institute The Royal Children’s Hospital Flemington Road Parkville Victoria 3052 AUS Medical Research: What is the background for this study? What are the main findings? Dr. Ure: Children born very preterm (<30 weeks gestation) are at increased risk of autism spectrum symptoms and disorder (ASD) compared with their term born peers. It has been suggested that this increased prevalence is due to abnormal brain development or injury associated with preterm birth.   But, until now, there has been limited research using neonatal brain imaging, a period of key brain development, and later ASD diagnosis. Our study included 172 children born very preterm who were recruited at birth and underwent structural brain imaging at term equivalent age (40 weeks gestation). We used a standardized diagnostic interview with parents to diagnose children with autism spectrum symptoms and disorder during their 7 year follow up visit. The diagnoses were confirmed via an independent assessment. Our results suggest there are subtle differences in the brain structure of very preterm newborns later diagnosed with autism spectrum symptoms and disorder, compared with very preterm children without autism spectrum symptoms and disorder. Specifically, we found newborns later diagnosed with ASD had more cystic lesions in the cortical white matter and smaller cerebellums. This latter result is consistent with findings from previous research, including studies that have used positive ASD screening tools with very preterm toddlers, and others who have reported reduced cerebellar volumes in older children with ASD. (more…)
Author Interviews, Autism, JAMA, OBGYNE / 25.06.2015

MedicalResearch.com Interview with: Ali S. Khashan, Ph.D. Irish Centre for Fetal and Neonatal Translational Research (INFANT) Cork, Ireland Medical Research: What is the background for this study? What are the main findings? Dr. Khashan: The Caesarean section rate is increasing worldwide reaching 30% in some western countries and 50% in China and Brazil. As a result, it is becoming increasingly important to understand the long-term effects this procedure may have on both mother and child. Previously, our group conducted a systematic review and meta-analysis of published literature and found birth by Caesarean to be associated with approximately 20% increased risk of autism spectrum disorder (ASD), compared to birth by vaginal delivery. This means if the risk of ASD in children born by vaginal delivery were 1%, and the association was causal, the risk of autism spectrum disorder in children born by Caesarean section is 1.2% i.e. two additional ASD cases per 1000 births. However, studies were limited, and we were unable to determine what was driving this association. In our new study, now published in JAMA Psychiatry, we investigated this issue further with the largest study on this subject to date, including all children born in Sweden between 1982 and 2010. Our study included data on over 2.9 million people and accounted for variety of factors known to be associated with both Caesarean section and autism spectrum disorder. After controlling for known confounders, such as maternal age and psychiatric history as well as various other perinatal and socio-demographic factors, we confirmed our previous findings that birth by Caesarean was associated with approximately 20% increased risk of autism spectrum disorder, compared to birth by vaginal delivery. However, with this analysis it remained unclear whether the increased risk was due to the Caesarean section itself, or some genetic or environmental factor that we were unable to measure. To determine if it was birth by Caesarean section or another unknown factor which led to an increased risk of ASD, we compared children with autism spectrum disorder to their non-diagnosed brothers and sisters. In other words, we analysed pairs of siblings in which one was diagnosed with ASD and one was not, to determine if birth by Caesarean was associated with increased risk of ASD within families. In this way, we attempted to indirectly account for genetic and family environment factors that are shared by siblings but we were unable to measure in the general population. In this analysis, which included data on over 13,000 sibling pairs, there was no longer any association between birth by Caesarean section and ASD. Overall, these results indicate that though birth by Caesarean section may be associated with an increased risk of ASD, it is likely due to family factors such as genetics or environment, rather than the Caesarean section itself. These findings are more informative than many previous studies as we had the largest sample size on this topic to date and estimated the association between Caesarean section and the risk of autism spectrum disorder while comparing siblings born by different methods of delivery. This allowed us to control for many factors that other studies did not. (more…)
Author Interviews, Autism, Education / 10.06.2015

Annette Estes, Ph.D. Research Associate Professor of Speech and Hearing Sciences Adjunct Research Associate Professor of Psychology Director, University of Washington Autism Center Susan & Richard Fade Endowed Chair Center on Human Development and Disability University of WashingtonMedicalResearch.com Interview with: Annette Estes, Ph.D. Research Associate Professor of Speech and Hearing Sciences Adjunct Research Associate Professor of Psychology Director, University of Washington Autism Center Susan & Richard Fade Endowed Chair Center on Human Development and Disability University of Washington Medical Research: What is the background for this study? What are the main findings? Dr. Estes: Although a number of studies have shown the positive effects of early intervention on children’s abilities during the preschool period, there have been few studies to date that have followed children longitudinally to find out if these gains are sustained.  We found that two years after completing the intervention, children maintained their gains in cognitive and adaptive behavior skills and also showed a reduction in autism symptoms.  The results suggest that early intervention results in long term benefits for children across a wide range of skills.  Children who received the ESDM intervention as toddlers later showed fewer autism symptoms at school age. Medical Research: What should clinicians and patients take away from your report? Dr. Estes: Early intensive behavioral intervention has been found to be efficacious in improving developmental outcomes for young children with autism spectrum disorder. Children were able to maintain the developmental gains that they made in early, intensive, in-home intervention over a 2-year follow-up period. These children did not exhibit developmental regression or lose skills, even after substantial reductions in services. Intellectual, language, and adaptive functioning gains made as a result of early intervention may generalize to new domains of functioning, such as reduced Autism Spectrum Disorder symptom severity, 2 years later. (more…)
Author Interviews, Autism, Education, Emory, JAMA, Pediatrics / 22.04.2015

MedicalResearch.com Interview with: Lawrence Scahill, MSN, PhD and Karen Bearss, PhD Department of Pediatrics, Marcus Autism Center Children’s Healthcare of Atlanta and Emory University Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Response: Autism spectrum disorder (ASD) affects an estimated 0.6 to 1% of children worldwide. In young children with ASD (e.g. 3 to 7 years of age) up to 50% also have disruptive behaviors such as tantrums, aggression, self-injury and noncompliance. When present, these disruptive behaviors interfere with the child’s readiness to make use of educational and other supportive services. The presence of disruptive behaviors also hinders the acquisition of routine daily living skills. Parent Training has been shown to be effective for young children with disruptive behaviors who do not have Autism spectrum disorder – but it has not be well-studied in children with ASD. The current multisite study shows that parent training is effective in reducing serious behavioral problems in young children with ASD. This is the largest randomized trial of a behavioral intervention in children with ASD.  180 children were randomly assigned to parent training or parent education. Both treatments were delivered individually to parents over 24 weeks. Serious behavioral problems were reduced by almost 50% in the parent-training group compared to about 30% for parent education. A clinician who was blind to treatment assignment rated positive response in 69% of children in the parent training group compared to 40% for parent education. In addition, 79% of children who showed a positive response to parent training at the end of the 24-week trial maintained benefit at 6 months post treatment. Parent training provided parents with specific strategies on how to manage tantrums, aggression, self-injury and noncompliance in children with autism spectrum disorder. Parent education provided up-to-date and useful information about ASD, but no instruction on how to address behavioral problems. Parents were engaged in the study treatments as evidenced by the low drop-out rate of 10% . (more…)
Author Interviews, Autism, Biomarkers / 17.02.2015

Alisa G. Woods, Ph.D., MSMedicalResearch.com Interview with: Alisa G. Woods, Ph.D., MS Assistant Professor Biochemistry & Proteomics Group Department of Chemistry & Biomolecular Science Clarkson University, Potsdam, NY, 13699 Medical Research: What is the background for this study? What are the main findings? Dr. Woods: Objective assessments for autism are greatly needed in order to understand autism cause and also to diagnose autism. Currently autism is diagnosed based on behavior, despite theories that autism may have a biological cause. We sought to develop a non-invasive biological test for autism, using saliva and mass spectrometry-based proteomics. We found nine statistically significant proteins that were elevated in the saliva of children with autism relative to typically developing controls and three proteins that were significantly decreased or absent. (more…)
Author Interviews, Autism, Radiology / 27.01.2015

Gabriel S. Dichter, PhD Associate Professor UNC Departments of Psychiatry and Psychology Carolina Institute for Developmental Disabilities MedicalResearch.com Interview with: Gabriel S. Dichter, PhD Associate Professor UNC Departments of Psychiatry and Psychology Carolina Institute for Developmental Disabilities Medical Research: What is the background for this study? What are the main findings? Dr. Dichter: The background for this study is that although most brain imaging research in autism spectrum disorders has focused on understanding the brain basis of social communication impairments, we know that autism symptoms are pervasive and may include difficulties with irritability, anxiety, mood, and even in some instances aggression or self injurious behaviors.  Additionally, these types of associated features are among the first that prompt parents to bring their child to a pediatrician for an evaluation for a neurodevelopmental disorder, and so we know these symptoms can be deeply troubling to parents.  All of these associated symptoms of autism suggest difficulty with regulating emotional responses, and so our team set out to investigate the brain basis of these difficulties.  We taught participants with and without autism simple strategies to change their emotion responses and then scanned them using functional MRI to measure brain activity when they actively tried to change their emotional responses to pictures of faces.  Our central finding was that although they reported they were able to change their emotional responses, brain imaging findings told us something quite different.  The dorsolateral prefrontal cortex, a part of the brain that controls emotional responses, was underactive in the participants with autism.  Consequently, they were less able to modulate parts of the brain’s limbic system that produces strong emotional responses.  In other words, they had difficulty “turning on the brakes” to control emotional responses.  Finally, the differences we observed in their brain activity predicted the severity of their overall autism symptoms, suggestion a direct linkage between emotion regulation impairments and autism severity. (more…)
Author Interviews, Autism, Pediatrics, Pediatrics / 13.01.2015

Terisa P. Gabrielsen, PhD, NCSP Assistant Professor, School Psychology Dept. of Counseling Psychology and Special Education Brigham Young University, Provo, UT 84602MedicalResearch.com Interview with: Terisa P. Gabrielsen, PhD, NCSP Assistant Professor, School Psychology Dept. of Counseling Psychology and Special Education Brigham Young University, Provo, UT 84602 Medical Research: What is the background for this study? What are the main findings? Dr. Gabrielsen: One of the keys to improving outcomes for individuals with outcomes is to begin intervention as early as possible, which means we need to identify autism symptoms as early as possible, preferably during the early toddler years.  The current study grew out of a screening feasibility study to see what would happen if pediatricians followed the AAP guidelines for screening every child for autism at ages 18 and 24 months as part of their regular pediatric care appointments.  That study  was conducted in a large, independent community pediatrics practice.  We found that universal screening of 796 patients helped to identify 10 toddlers with autism who had not previously been referred for evaluations.  Physicians had previously identified 3 others with autism in the group, and toddlers with other delays, such as language delays, were also identified through the screening process.  We wondered what some possible causes were for the low rate of autism referrals and designed the current study to look for what information was available to a pediatrician during the timespan of a typical pediatric exam.  We found that even in toddlers with autism, a brief (10-minute) sample contains an overwhelming ratio of typical behaviors (averaging 89%) compared to infrequent atypical behaviors (11%)  that would indicate the presence of autism.  We had autism experts identifying the behaviors from videos of the evaluations of children in the previous study, so they had many luxuries that a clinician doesn't have during an exam (i.e., ability to focus on one aspect of development, ability to rewind and re-view behaviors).  After watching the 10-minute video observations, we asked our experts, "Would you refer this child for an autism evaluation?"  We found that even the experts missed referring a child for an autism evaluation 39% of the time when the only data available were the brief observations. (more…)