James Leckman

..This study was carried out to investigate whether cytokines associated with the innate immune response or T cell activation were altered under baseline conditions and during periods of symptom exacerbation...

..This annotation reviews recent evidence that points to the likely role of aberrant neural oscillations in the pathogenesis of Tourette syndrome (TS)...

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..Future progress may also be expected as endophenotypes, and possibly genetic markers, are identified that are associated with specific comorbid conditions and etiologically distinct forms of TS...

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..A group of children with Tourette syndrome and/or OC disorder without a PANDAS history served as the comparison (non-PANDAS) group...

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..Finally, existing assessment methods are inadequate and new dimensional scales are needed to take full advantage of a dimensional approach in clinical and population-based studies...

..This study was designed to evaluate the psychometric properties of the YCGSI...

..It is likely that the research paradigms utilized in these studies and many of the empirical findings resulting from them, will be relevant to other disorders of childhood onset and to our understanding of normal development...

..Third, the authors evaluate the hypothesis that these highly conserved behavioral and neural systems and the genetic messages that guide their development are intimately involved in the pathogenesis of OCD...

..This seminar focuses on these changing views and offers a new perspective on our understanding of the pathogenesis of Tourette's syndrome and on principles for treatment of patients with this disorder...

..This article reviews the available scientific literature concerning the neurobiological substrates of Tourette's disorder (TD)...

..We conclude that familial factors contribute significantly to OC symptom dimension phenotypes in GTS families. This familial contribution could be genetic or environmental...

..It is timely to reconsider the nosology of this disorder, assessing whether changes to diagnostic criteria as well as subtypes and specifiers may improve diagnostic validity and clinical utility...

..CONCLUSION: Obsessive-compulsive disorder symptoms in children with TS became more severe at a later age and were more likely to persist than tic symptoms...

..We then examined the power of GABHS infections and measures of psychosocial stress to predict future tic, obsessive-compulsive (OC), and depressive symptom severity...

..We hypothesize that performance on the Purdue Pegboard test may serve as a useful endophenotype in the study of TS and provide a rough measure of the degree of basal ganglia dysfunction present in TS patients...

..This study provides compelling evidence that morphologic disturbances of the caudate nucleus within cortico-striatal-thalamo-cortical circuits are central to the persistence of both tics and obsessive-compulsive symptoms into adulthood...

..Childhood onset OCD is a highly familial disorder. Some early-onset cases may represent a valid subgroup, with higher genetic loading and shared vulnerability with chronic tic disorders...

..When disruptive behavior problems are present, there is an additional burden on children's social and family functioning...

..Wild-type SLITRK1, but not the frameshift mutant, enhanced dendritic growth in primary neuronal cultures. Collectively, these findings support the association of rare SLITRK1 sequence variants with TS...

..Our objective was to replicate these results in OCD patients who participated in one of four randomized, placebo-controlled, clinical trials (RCT)...

..We examined neuropsychological functioning in relatively large and well-characterized samples of children categorized as TS, TS-plus-ADHD, ADHD, and unaffected controls...

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..To examine the role of aberrant neural oscillatory activity in the pathophysiology of co-occurring Tourette Syndrome (TS) and Attention-Deficit/Hyperactivity Disorder (ADHD)...

..We also postulated that group A beta hemolytic streptococcal infections could promote autoimmune responses by releasing exotoxins (streptococcal pyrogenic exotoxins [SPE])...

..Future therapy and pharmacotherapy studies in trichotillomania should employ larger sample sizes and intention-to-treat analysis and seek to validate clinical rating scales of trichotillomania severity...

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..Further meta-analyses based on individual patient data would be helpful in determining whether age of OCD onset, gender and the presence of comorbid illness (e.g., tics) moderates the relationship between 5-HTTLPR and OCD...

..The aim of the study was to investigate how perfectionism and sensory phenomena (SP) interact as possible phenotypic components of obsessive-compulsive disorder (OCD)...

..We sought to determine the relative efficacy of different medications in treating ADHD and tic symptoms in children with both Tourette's syndrome and ADHD...

..To evaluate the efficacy of a 10-session individually administered anger control training (ACT) for adolescents with Tourette's syndrome (TS) and disruptive behavior...

..The goal of this article was to review the long-term clinical course of tics and comorbid conditions in children with TS...

..To review the contributions of research on nonhuman primates, specifically macaque monkeys, to the understanding of early social stress and its effects on behavior and neurophysiology...

..We hypothesized that antineuronal antibodies may be elevated in patients (reflecting autoimmune processes), and levels of total immunoglobulins (Igs) may be decreased (reflecting immune deficiency)...

..The United States is facing a severe shortage of academic child and adolescent psychiatrists. This article reviews a model integrated pathway to improve recruitment...

..The authors conducted a meta-analysis to determine the factor structure of the Yale-Brown Obsessive Compulsive Scale Symptom Checklist...

..Efforts are needed to reduce the frequency of these risk factors in high-risk populations. Future studies, using genetically sensitive designs, are also needed to sort out the causal pathways...

..Second, independent of mode of delivery, parental worries and mood are related to specific brain activations in response to own baby-cry...

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..We view our different programs as seamlessly interconnected with one another but present them as separate entities to facilitate the incorporation of different components into local realities...

..Future studies of genetic and environmental influences on maternal behavior have the potential to inform models of disease pathogenesis...

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..Antidepressant drug therapy can precipitate mania in vulnerable individuals, but little is known about the effects of age on this phenomenon...

..5, during early gastrulation stage, BEN is localized in the cytoplasm. At later stages, BEN retains an extensive expression pattern in a variety of developing systems implicating its involvement in tissue development and organogenesis...

..We apply a duplication-degeneration-complementation model to explain how this family of genes has evolved...

..Obsessive-compulsive disorder (OCD) is a heterogeneous disorder with emerging data suggesting that age of onset and/or the presence of tics may define clinically important subgroups...

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..A second major aim was to assess whether fluctuations in tic and OC symptom severity covaried with one another...

..000003. Although P values were not adjusted for multiple comparison, nearly all were much smaller than the customary significance level of.0001 for genomewide scans...

..The imbalance in striatal and GPi inhibitory neuron distribution suggests that the functional dynamics of cortico-striato-thalamic circuitry are fundamentally altered in severe, persistent TS...

..This is a review of progress made in the understanding of Tourette syndrome (TS) during the past decade including models of pathogenesis, state-of-the-art assessment techniques, and treatment...

..CONCLUSIONS: The results suggest no clear relationship between new GABHS infections and symptom exacerbations in an unselected group of patients with TS and/or OCD...

..Although the importance of immunologic confirmation of infection is widely accepted, the immediate and long-term immunokinetics of the human antibody response are incompletely documented and poorly understood...

..The selective deficit of PV+ and cholinergic striatal interneurons in TS subjects may result in an impaired cortico/thalamic control of striatal neuron firing in TS...

..Genotyping the affected and unaffected members of these pedigrees has the potential to identify rare recessive contributions to this disorder...

..Autism spectrum disorders (ASD) are neurodevelopmental disorders of complex etiology, with a recognized substantial contribution of heterogeneous genetic factors; one of the core features of ASD is a lack of affiliative behaviors...

..Community samples and recent investigations in clinical samples confirm that the presence of ADHD predicts greater disability than that associated with tic disorders alone...

..These neural systems are also likely to underlie aspects of religious experience and ritual as well as the wonders of romantic and early parental love...

..These findings suggest that maternal care in childhood may be associated with anatomy and functions in brain regions implicated in appropriate responsivity to infant stimuli in human mothers...

..CONCLUSIONS: The results are consistent with an autoimmune etiology in a subset of cases of Tourette's syndrome...

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..The purpose of this study was to conduct an exploratory principal components analysis of obsessive-compulsive (OC) symptoms in children and adolescents with OCD to identify improved phenotypes for future studies...

..CONCLUSIONS: TD and ADHD are not alternate phenotypes of a single underlying genetic cause. There is an increased risk of comorbid ADHD and TD in affected families, possibly reflecting some overlapping neurobiology or pathophysiology...

..However, approximately 40% of patients do not have a significant improvement, suggesting that new medications are needed. This study was designed to investigate the treatment response to escitalopram in OCD patients...

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..Identification of a category-based OCD symptom dimension structure that is validated for use across child, adolescent, and adult age groups is necessary to guide ongoing translational research...

..These data suggest that PK can function as an autoimmune target and that this immunoreactivity may be associated with Tourette syndrome, OCD, and associated disorders...

..We examined the type and frequency of characteristic OCD obsessions and compulsions in a large sample of AN patients...

..Reduced inhibitory input may in turn enhance prefrontal excitation, thus helping to control tics and possibly contributing to the cortical hyperexcitatibility reported previously in patients with Tourette's disorder...

..No significant relationship was observed between OCS in TS or ASD probands and OCS of their parents. Further studies on OCD and OCS including a dimensional approach within ASD families are needed...

..The need for a dimensional rating scale and suggestions for future research aimed at reducing the burden of this disorder are discussed...

..Future studies should investigate the interactions of genetics, environment, infectious agents, and immunity on symptom expression in families with tic disorders...

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..A diverse program of multidisciplinary research is recommended to reduce the burden on children and families affected with these conditions...

..Funds are also requested to support the national independent evaluation of both the KGT Foundation Medical Student Fellowship (at six sites) and the Integrated Research Pathway Program (at two sites). ..

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..These insights may be relevant to our understanding of other diseases including AIDS. ..