http://www.ucdmc.ucdavis.edu/mindinstitute/events/dls/index.html A monthly lecture series from the UC Davis M.I.N.D. Institute featuring some of the greatest minds in medicine discussing research and developments in the study of autism and other neurodevelopmental disorders. Copyright 2006/2007 UC Davis M.I.N.D. Institute Mon, 25 June 2007 10:00:00 PST en-us http://media.mindinstitute.org/video/dls/2007/wmv/pauls_dls_01_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/pauls_dls_01_hi.wmv Wed, 11 Oct 2006 16:00:00 PST Abstract: Tourette Disorder (TD) is a neuropsychiatric disorder with a complex mode of inheritance characterized by waxing and waning multiple motor and phonic tics. This talk will report results of the largest genetic linkage study yet undertaken for TD. The sample analyzed includes 238 nuclear families yielding 304 “independent” sib-pairs and 18 separate multigenerational families; a total of 2,040 individuals. A whole genome screen using 390 microsatellite markers was completed. Analyses were completed using two diagnostic classifications: 1) only individuals with TD were included as affected; and 2) individuals with TD or chronic tics (CT) were included as affected. Significant evidence for linkage was observed for a region on chromosome 2p [-log(p) = 4.42, p = 3.8 x 10-5] in the analyses which included individuals with TD or CT as affected. Results in several other regions also provide suggestive evidence for additional susceptibility loci for TD. http://media.mindinstitute.org/video/dls/2007/wmv/pauls_dls_02_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/pauls_dls_02_hi.wmv Wed, 11 Oct 2006 18:00:00 PST Abstract: Tourette Disorder (TD) and Obsessive Compulsive Disorder (OCD) are complex neuropsychiatric disorders TD is characterized by waxing and waning multiple motor (seemingly purposeless movements) and phonic tics (seemingly purposeless sounds and utterances) while OCD is characterized by recurrent intrusive thoughts (obsessions) and complex repetitive, seemingly purposeful movements (compulsions). Individuals with TD have symptoms of OCD much more frequently than expected by chance. Similarly, individuals with OCD that had its onset in childhood have a history of tics much more frequently than would be expected. Family data suggest that the two disorders may be alternative expressions of some shared familial etiology. This talk will summarize those studies and discuss how such seemingly disparate conditions could be genetically related. http://media.mindinstitute.org/video/dls/2007/wmv/beaudet_dls_01_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/beaudet_dls_01_hi.wmv Wed, 08 Nov 2006 16:00:00 PST Abstract: The genetic contribution to autism is often attributed to the combined effects of many loci (ten or more). This conclusion is based in part on the much lower concordance for dizygotic than for monozyotic twins, and is consistent with the failure to find strong evidence for linkage in genome-wide studies. We propose that the twin data are compatible with oligogenic inheritance (two or more loci) combined with a major, genetic or epigenetic, de novo component to the etiology. Based on evidence that maternal but not paternal duplications of chromosome 15q cause autism, we attempted to test the hypothesis that autism involves oligogenic inheritance and that the Angelman gene, which encodes the E6-AP ubiquitin ligase, is one of the contributing genes. Based on evidence for allele sharing in 15q among sib-pairs, abnormal DNA methylation downstream from Angelman gene coding region in one of 17 autism brains, and decreased E6-AP protein in some autism brains, we propose a mixed epigenetic and genetic model for autism with both de novo and inherited contributions. A mixed epigenetic and genetic and mixed de novo and inherited (MEGDI) model could also be relevant to other “complex disease traits.” http://media.mindinstitute.org/video/dls/2007/wmv/beaudet_dls_02_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/beaudet_dls_02_hi.wmv Wed, 08 Nov 2006 18:00:00 PST Abstract: Reports of a dramatic increase in the incidence of autism over the last 30 years have led to considerable debate as to whether the apparent increase is real or artifact. Some researchers believe that more children per capita are being born with autism. Other researchers agree that many more children are receiving a diagnosis of autism, but argue that this is a reflection of changing use of diagnostic categories, greater awareness of autism, and increased services available to children with a diagnosis of autism. I will review this debate and address some of the relevant issues, including whether a final answer to this controversy is currently available. Whether or not a real increase exists has very important implications for research and prevention, and possibly for treatment. For example, a real increase in autism would point to some environmental change/factor, probably produced by human activities, which is interacting with the genetic makeup of infants. Along these lines, I will discuss a number of possible factors, including the intake of folic acid by the population and exposure to prenatal ultrasound. http://media.mindinstitute.org/video/dls/2007/wmv/suomi_dls_01_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/suomi_dls_01_hi.wmv Wed, 13 Dec 2006 16:00:00 PST Abstract: Recent research with both humans and rhesus monkeys has provided compelling evidence of gene-environment interactions (G x E) throughout development. For example, a specific polymorphism (“short” allele) in the promoter region of the serotonin transporter (5-HTT) gene is associated with deficits in neurobehavioral functioning during infancy and in poor control of aggression and low serotonin metabolism throughout juvenile and adolescent development in monkeys who experienced insecure early social attachments but not in monkeys who developed secure attachment relationships with their mothers during infancy. In contrast, monkeys possessing the “long” allele of the 5-HTT gene exhibit normal neurobehavioral functioning, control of aggression, and serotonin metabolism regardless of the relative security of their early attachment relationships. One interpretation of these G x E interaction data is that the long 5-HTT allele somehow confers resiliency to adverse early attachment relationships on those individuals who carry it (“good genes”). An alternative interpretation of the same data is that secure attachment relationships somehow confer resiliency to individuals who carry alleles that may otherwise increase their risk for adverse developmental outcomes (“maternal buffering”). These two interpretations are not mutually exclusive, but the differences in their respective implications for developing effective strategies for successful intervention in and even prevention of adverse developmental outcomes in affected individuals are considerable. Moreover, genetic analyses of several other macaque species, as well as all of the great ape species, have revealed that although all of these species possess the 5-HTT gene, they do not have any of the functional polymorphisms found in humans and rhesus monkeys, i.e., in each case there is no within-species functional allelic variability for this gene. Implications of these recent findings will be discussed. http://media.mindinstitute.org/video/dls/2007/wmv/suomi_dls_02_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/suomi_dls_02_hi.wmv Wed, 13 Dec 2006 18:00:00 PST Abstract: Recent research has found marked individual differences in patterns of rhesus monkey biobehavioral development throughout the life span. Approximately 20% of monkeys growing up in naturalistic settings consistently display unusually fearful and anxious-like behavioral reactions to novel, mildly stressful social situations throughout development; another 5-10% are likely to exhibit impulsive and/or inappropriately aggressive responses under similar circumstances. These distinctive behavioral patterns and their biological correlates appear early in life and remain remarkably stable from infancy to adulthood. Both genetic and experiential mechanisms are implicated not only in the expression of these patterns but also in their transmission across successive generations of monkeys. For example, a specific polymorphism in the serotonin transporter gene is associated with deficits in infant neurobehavioral functioning and in juvenile and adolescent control of aggression and serotonin metabolism in monkeys who experienced insecure early attachments but not in monkeys who developed secure attachment relationships with their mothers during infancy (“maternal buffering”). Moreover, because the attachment style of a monkey mother is typically “copied” by her daughters when they grow up and become mothers themselves, similar buffering is likely to occur for the next generation of infants carrying that specific polymorphism. http://media.mindinstitute.org/video/dls/2007/wmv/scahill_dls_01_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/scahill_dls_01_hi.wmv Wed, 10 Jan 2007 16:00:00 PST Lawrence Scahill, MSN, PhD., is professor of Nursing and Child Psychiatry at Yale. For the past 9 years, he has served as the Director of the Research Unit on Pediatric Psychopharmacology (RUPP) at Yale, one of three centers in the RUPP Autism Network. The aim of this mulitsite network is to evaluate psychopharmacological and behavioral interventions in children with adolescents with autism and related developmental disorders. In addition to his work in autism, Dr. Scahill is also involved in psychopharmacological and behavioral interventions for children and adults with Tourette syndrome. He serves on the Medical Advisory Board of the Tourette Syndrome Association and is a principal investigator on two multisite studies evaluating the efficacy of a behavioral intervention for tics in children and adults with Tourette syndrome. Dr. Scahill is an active clinician specializing in the care of children with Tourette syndrome and children with autism. The author of over 130 journal articles and numerous book chapters, Dr. Scahill is also a teacher in the graduate School of Nursing at Yale. http://media.mindinstitute.org/video/dls/2007/wmv/scahill_dls_02_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/scahill_dls_02_hi.wmv Wed, 10 Jan 2007 18:00:00 PST Lawrence Scahill, MSN, PhD., is professor of Nursing and Child Psychiatry at Yale. For the past 9 years, he has served as the Director of the Research Unit on Pediatric Psychopharmacology (RUPP) at Yale, one of three centers in the RUPP Autism Network. The aim of this mulitsite network is to evaluate psychopharmacological and behavioral interventions in children with adolescents with autism and related developmental disorders. In addition to his work in autism, Dr. Scahill is also involved in psychopharmacological and behavioral interventions for children and adults with Tourette syndrome. He serves on the Medical Advisory Board of the Tourette Syndrome Association and is a principal investigator on two multisite studies evaluating the efficacy of a behavioral intervention for tics in children and adults with Tourette syndrome. Dr. Scahill is an active clinician specializing in the care of children with Tourette syndrome and children with autism. The author of over 130 journal articles and numerous book chapters, Dr. Scahill is also a teacher in the graduate School of Nursing at Yale. http://media.mindinstitute.org/video/dls/2007/wmv/grandin_dls_01_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/grandin_dls_01_hi.wmv Wed, 14 Feb 2007 16:00:00 PST Abstract: During this technical presentation, Dr. Grandin discusses how the minds of visual thinkers, like herself, work. Included in her discussion is how she uses concrete visual metaphors – including a nonverbal “video library” of particular people, places and associations – to make sense of the world around her, along with the many ways that individuals with autism think. http://media.mindinstitute.org/video/dls/2007/wmv/grandin_dls_02_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/grandin_dls_02_hi.wmv Wed, 14 Feb 2007 18:00:00 PST Abstract: In this community-interest lecture, Dr. Grandin provides a personal account of what it is like to live with autism. She will discuss the value of early intervention, her sensory sensitivities and how she manages them, ways of thinking among individuals with autism, social relationships, medications and careers. http://media.mindinstitute.org/video/dls/2007/wmv/piven_dls_01_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/piven_dls_01_hi.wmv Wed, 14 Mar 2007 16:00:00 PST Abstract: In his early descriptions of autism, Professor Leo Kanner noted an increase in the occurrence of particular behaviors in non-autistic family members that, although milder, were qualitatively similar to the defining features of autism. The twin study by Folstein and Rutter established that these characteristics, later referred to as constituting a ‘broad autism phenotype,’ were likely to be related to the underlying genetic liability for autism. This presentation will review the results of several studies of the broad autism phenotype as well as other potentially relevant aspects of the ‘autism phenotype’ that may be useful in future studies aiming to elucidate the pathogenesis of this condition. Recorded March 14, 2007 16:00:00 PST. http://media.mindinstitute.org/video/dls/2007/wmv/piven_dls_02_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/piven_dls_02_hi.wmv Wed, 14 Mar 2007 18:00:00 PST Abstract: Converging evidence from brain imaging, head circumference and post-mortem studies support the observation that brain enlargement is associated with autism. In this presentation data from an ongoing longitudinal MRI study of early brain development in autism will be reviewed and the findings will be related to results from parallel studies of the behavioral development in infant siblings of autistic individuals to suggest a new paradigm for understanding brain and behavioral development in autism. Recorded March 14, 2007 18:00:00 PST. http://media.mindinstitute.org/video/dls/2007/wmv/bookheimer_dls_01_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/bookheimer_dls_01_hi.wmv Wed, 11 Apr 2007 16:00:00 PST Abstract: Research using fMRI has indicated several areas of systems-level brain dysfunction that may underlie many features of autism. This talk will present a series of studies in our lab examining fMRI during social-emotional tasks. Using data from face recognition, emotional face processing, gaze direction, reward processing and imitation/observation studies, we will argue that a commonality underlying the major features of autism is dysfunction in the mirror neuron system. This system, found originally in monkey single unit recording studies, involves brain areas that respond both during the execution and observation of behavior. Neurons in these regions communicate with subcortical systems involved in affect and reward processing via the insula. A dysfunction in this system would account for a range of symptoms including imitation, joint attention, affect processing, gaze following, and response to reward. Variations in the degree to which this system is dysfunctional appear to correlate with symptom severity. Focusing on this system may allow us to tailor treatments that may affect a range of behaviors. Recorded April 11, 2007 16:00:00 PST. http://media.mindinstitute.org/video/dls/2007/wmv/bookheimer_dls_02_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/bookheimer_dls_02_hi.wmv Wed, 11 Apr 2007 18:00:00 PST Abstract: Why do children develop autism? Although it is known that genetics plays a major role in risk for autism, these genes must affect the brain before influencing behavior. The discovery of functional magnetic resonance imaging (FMRI) in the early 1990’s has revolutionized the study of childhood disorders generally and autism specifically. FMRI allows us to observe brain activity while children perform mental tasks we know are affected in autism. These studies have shown that portions of the human brain are specialized for different aspects of social behaviors, including following eye gaze, responding to human faces, and imitating the behaviors of others. Abnormalities in some of these brain systems appear to be pervasive in children with autism, even those who are high functioning. Underlying these brain abnormalities are very subtle differences in brain structure that changes in development. Recent data has shown that the environment can influence many aspects of brain development. This talk will review recent findings in brain structure and function in autism and will suggest ways that brain imaging may help future studies of intervention in autism. Recorded April 11, 2007 18:00:00 PST. http://media.mindinstitute.org/video/dls/2007/wmv/abbeduto_dls_01_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/abbeduto_dls_01_hi.wmv Wed, 9 May 2007 16:00:00 PST Abstract: Fragile X syndrome is the leading inherited cause of intellectual disabilities and is often associated with serious language problems. My colleagues and I are interested in developing a more nuanced characterization of language problems in fragile X syndrome by examining (1) the extent of impairment in the various components of language and in prerequisite skills (such as hearing), (2) the relationships between language and nonlinguistic dimensions of the behavioral phenotype, and (3) possible environmental contributions. We have found a profile of relative strengths and weaknesses in the various components of language that distinguishes fragile X syndrome from Down syndrome and, perhaps, other disorders. We also find that variation in language skill among affected individuals is related to cognitive ability, autism status, and other nonlinguistic dimensions of the phenotype. And finally, we have preliminary results suggesting that mothers of children with fragile X syndrome display relatively low levels of psychological well-being, which may have implications for their children’s language learning. In this presentation, I will share our findings to date and present a model of the organismic and environmental factors affecting language learning in fragile X syndrome. Recorded May 9, 2007 16:00:00 PST. http://media.mindinstitute.org/video/dls/2007/wmv/abbeduto_dls_02_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/abbeduto_dls_02_hi.wmv Wed, 9 May 2007 18:00:00 PST Abstract: Fragile X syndrome is the leading inherited cause of intellectual disabilities and is often associated with serious problems in communication. In this presentation, I will summarize findings from several completed and ongoing studies designed to understand the extent and nature of the communication challenges facing older children, adolescents, and young adults – both males and females – with fragile X syndrome. I will focus on the foundations for communication, barriers to effective communication, and the process of communication itself. I will also discuss some of the factors that are associated with more or less severe communication challenges in individuals with fragile X syndrome, and make recommendations for assessing communication challenges in affected individuals. And finally, I will briefly describe strategies for facilitating communication development that can be implemented by parents and professionals. Recorded May 9, 2007 18:00:00 PST. http://media.mindinstitute.org/video/dls/2007/wmv/charman_dls_01_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/charman_dls_01_hi.wmv Wed, 13 Jun 2007 16:00:00 PST Abstract: Diagnosis of autism spectrum disorders relies largely on behavioral and developmental characteristics. While subtypes within this disorder have been explored for many years, the boundaries between strictly defined autism and other autism spectrum disorders remain ill-defined. Further, it is well known that the behavioral phenotype of autism and the broader autism spectrum disorders includes individuals with different ultimate etiologies, so even when biological or genetic markers are found they will not be present in all individuals with the phenotype. The fact that autism is not a unitary ‘disorder’ presents a significant challenge to epidemiological, genetic, biological, neurological and psychological research. In several areas of investigation people are attempting to define subgroups – at the behavioral, cognitive and biological level. Drawing on data from our population-representative sample of children with autism in the UK we are attempting to determine whether any of the suggested ‘subtypes’ hold up to scrutiny and whether apparent subgroups exist in our dataset. This talk will outline our initial attempts to join others in identifying meaningful subgroups that might aid scientific inquiry into autism. Recorded June 13, 2007 16:00:00 PST. http://media.mindinstitute.org/video/dls/2007/wmv/charman_dls_02_hi.wmv http://media.mindinstitute.org/video/dls/2007/wmv/charman_dls_02_hi.wmv Wed, 13 Jun 2007 18:00:00 PST Abstract: Until a decade ago, best estimate prevalence rates for autism spectrum disorders were 5 per 10,000 for autism and 20 per 10,000 for the broader spectrum. Recent reports have suggested that the prevalence of autism and related spectrum disorders is considerably higher than previously recognized. A number of recent studies, including our own study in the UK, have suggested that the rates for the broad autism spectrum may be as high as one percent. Whilst ICD-10 and DSM-IV diagnostic criteria and standard diagnostic instruments have been used in recent prevalence studies, they still allow scope for variation in interpretation and different severity thresholds applied within the same qualitative domains of impairment, resulting in different prevalence rates. Increased recognition, the broadening of the diagnostic concept over time and methodological differences across studies may account for most or all of the apparent increase in prevalence but other explanations cannot be ruled out, including a true rise in incidence. In this talk I will review recent evidence on the prevalence of autism spectrum disorders, discuss whether we can rule out or rule in a ‘real’ increase and highlight some directions for future epidemiological work. Notwithstanding these scientific challenges, services in health, education and social care will need to recognize the needs of children with some form of autism who constitute 1% of the child population. Recorded June 13, 2007 18:00:00 PST.