From the 2006/2007 Distinguished Lecturer Series. 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.

From the 2006/2007 Distinguished Lecturer Series. 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.

From the 2006/2007 Distinguished Lecturer Series. 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.

From the 2006 Summer Institute on Neurodevelopmental Disorders. Recorded Fri, 11 Aug 2006 15:30:00 PST.

From the 2006/2007 Distinguished Lecturer Series. Abstract: Reports of a dramatic increase in the incidence of autism over the last 30 years have lead 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.

From the 2006/2007 Distinguished Lecturer Series. 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."

From the 2006 Summer Institute on Neurodevelopmental Disorders. Recorded Thu, 10 Aug 2006 09:25:00 PST.

From the 2006/2007 Distinguished Lecturer Series. 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.

From the 2006/2007 Distinguished Lecturer Series. 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.

From the 2006 Summer Institute on Neurodevelopmental Disorders. Recorded Thu, 10 Aug 2006 11:00:00 PST.