Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein–protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.

Background The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families. Method OCD and ADHD symptom patterns were examined in TS patients and their family members ( N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed. Results EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders). Conclusions Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.

Cross-sectional studies of adolescent suicidal thoughts/behaviors (STBs) (ideation or attempts) have long demonstrated a strong association with a wide range of contemporaneous risk factors (such as Axis I and II psychiatric diagnoses, subsyndromal behavioral difficulties, and educational problems), as well as pre-existing family background factors (such as economic adversity, poor family functioning, and parental psychopathology). In recent years, the steady accretion of data from several long-running prospective, population-based studies has shed new light on the lifespan implications and long-term sequelae of adolescent suicidality and provided a corrective to what has been described as the “strangely a-developmental” nature of much earlier suicide research, which paid little regard to the complex interaction of systems across development.1King R.A. Ruchkin V.V. Schwab-Stone M. Suicide and the “continuum of adolescent self-destructiveness”: is there a connection?.in: King R.A. Apter A. Suicide in Children and Adolescents. Cambridge University Press, Cambridge, UK2003: 41-62Crossref Google Scholar, 2Glenn C.R. Cha C.B. Kleiman E.M. Nock M.K. Understanding suicide risk within the Research Domain Criteria (RDoC) Framework: insights, challenges, and future research considerations.Clin Psychol Sci. 2017; 5: 568-592Crossref PubMed Scopus (47) Google Scholar Among the most productive community-based prospective studies in this regard have been the Christchurch, Dunedin, and Great Smoky Mountains studies. In this issue of the Journal, the report by Copeland et al.3Copeland W.E. Goldston D.B. Costello E.J. Adult associations of childhood suicidal thoughts and behaviors: a prospective, longitudinal analysis.J Am Acad Child Adolesc Psychiatry. 2017; 56: 958-965Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar of the latest findings from the Great Smoky Mountains Study exemplifies the power of this methodology and highlights several important conclusions: (1) adolescent STBs are an ongoing risk factor for future suicidal behaviors and a broader host of psychosocial difficulties in adulthood; (2) the worrisome long-term prognostic implications of adolescent STBs are likely not due to adolescent STB per se but rather the host of background family and childhood factors that predisposed youngsters to adolescent STB in the first place; (3) youngsters with only suicidal ideation/plan (but no attempts) fared as poorly as those who had made an actual suicide attempt in adolescence; (4) the combination of childhood depression and adolescent STB poses an especially high risk for adult suicidal behavior; but (5) most participants with adult suicidality had neither childhood depression nor childhood suicidal behavior. The Great Smoky Mountains Study has now followed the vicissitudes of a population-based sample of 1,420 youngsters, originally ages 9 to 13 years, up through the age of 30, using periodic structured interviews and other data collection. In this most recent examination of the data, STB in adolescence was associated with adult anxiety disorder or STB in adulthood, as well as poor adult functioning in the areas of finance, health, social relations, and risky/illegal behaviors. Once adjustments were made, however, for background factors (gender, race, low socioeconomic status, childhood maltreatment, family instability/dysfunction, and peer victimization; and diagnosis of a childhood depression, anxiety, disruptive behavior, or substance abuse disorder), the power of adolescent STB to predict poor adult functioning disappeared, suggesting that it is these background factors, rather than the occurrence of adolescent STB itself, that predispose youngsters to compromised adult functioning. Strikingly, however, even after adjusting for these childhood risk factors, childhood adolescent STB remained a significant predictor of adult suicidal behaviors. For youngsters with suicidal ideation/plans but no attempt, the presence of childhood depression conferred a particularly high risk for STB in adulthood, compared to those with ideation/plans but no depression. On the other hand, underlining the fact that there are multiple pathways into adult suicidality, the large majority of participants showing suicidal behavior in adulthood had not had prior adolescent STBs. Other prospective studies support the notion of adolescent STB as an “‘early warning signal’ for persistent vulnerability to poor outcomes.”4Goldman-Mellor S.J. Caspi A. Harrington H. et al.Suicide attempt in young people: a signal for long-term health care and social needs.JAMA Psychiatry. 2014; 71: 119-127Crossref PubMed Scopus (166) Google Scholar Following adolescent suicide attempters into their late 30s, the Dunedin study found significantly increased levels of persistent mental health problems, engagement in violence, need for social supports, and health problems (such as metabolic syndrome and inflammation), even after correcting for youth psychiatric diagnoses and social class.4Goldman-Mellor S.J. Caspi A. Harrington H. et al.Suicide attempt in young people: a signal for long-term health care and social needs.JAMA Psychiatry. 2014; 71: 119-127Crossref PubMed Scopus (166) Google Scholar What are the implications of these findings for prevention? Case finding and treating youngsters with identified suicidal behavior is clearly important to reduce the near-term and lifespan risk for recurrent STBs. However, despite the ubiquity of adolescent STB,5Kann L. McManus T. Harris W.A. et al.Youth risk behavior surveillance—United States, 2015.MMWR Surveillance Summary. 2016; 65: 1-174Crossref Scopus (778) Google Scholar a meta-analysis of randomized clinical trials (RCTs) of interventions for adolescent self-harm (which did not differentiate between suicidal and nonsuicidal self-injury) found efficacy for only 3 interventions: cognitive-behavioral therapy, mentalization-based therapy, and dialectic-behavioral therapy.6Ougrin D. Tranah T. Stahl D. Moran P. Asarnow J.R. Therapeutic nterventions for suicide attempts and self-harm in adolescents: systematic review and meta-analysis.J Am Acad Child Adolesc Psychiatry. 2015; 54: 97-107Abstract Full Text Full Text PDF PubMed Scopus (220) Google Scholar Commenting on this study, Brent7Brent D. Some promising news about psychosocial interventions for adolescent self-harm.Evid Based Ment Health. 2015; 18: 93Crossref PubMed Scopus (2) Google Scholar noted that although there is some indication of greater effectiveness for interventions that involve the family and last more than a single session, the heterogeneity of these treatment models, the lack of replicated findings, and the absence of psychopharmacological RCTs using suicidal behavior as an outcome all point to the need for further research into effective interventions. Among the unresolved questions regarding the optimal choice of treatment focus is whether psychosocial and behavioral interventions that address suicidal behavior/ideation directly are more effective in preventing recurrence than indirect interventions that address only associated symptoms, such as hopelessness, depression, anxiety, or quality of life; the effectiveness and durability of these different approaches may vary over different follow-up periods.8Meerwijk E.L. Parekh A. Oquendo M.A. Allen I.E. Franck L.S. Lee K.A. Direct versus indirect psychosocial and behavioural interventions to prevent suicide and suicide attempts: a systematic review and meta-analysis.Lancet Psychiatry. 2016; 3: 544-554Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar Difficult as it is to identify effective treatments for youth depression and suicidal behavior per se, the converging findings of the Great Smoky Mountains Study and other prospective studies pose an even more daunting challenge: the risk of recurrent suicidal behavior is merely the tip of the iceberg of morbid risk for such youngsters as they reach adulthood. Not only is adolescent STB a marker for many forms of concurrent individual and family psychopathology and adversity that need prompt intervention in childhood and adolescence, but the occurrence of adolescent STB signals high future risk for various forms of adult dysfunction (STB aside) that, in turn, provide the soil for a successive generation’s difficulties.9Brent D.A. Melhem N.M. Mann J.J. Pathways to offspring suicidal behavior may begin with maternal suicide attempt.J Am Acad Child Adolesc Psychiatry. 2015; 54 ([letter]): 868Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Because the nexus of risk factors for adolescent STB is so broad and often long-standing, it seems likely that equally broad, time-extended interventions may be needed to change this trajectory of risk. Brent10Brent D. Prevention programs to augment family and child resilience can have lasting effects on suicidal risk.Suicide Life Threat Behav. 2016; 46: S39-S47Crossref PubMed Scopus (17) Google Scholar points to evidence suggesting that several family-based preventive programs focused on augmenting family and child resilience, originally designed to prevent psychopathology such as substance abuse, may also show long-term effectiveness in reducing suicide risk for parents and/or offspring. The developmental perspective provided by studies such as Copeland et al.3Copeland W.E. Goldston D.B. Costello E.J. Adult associations of childhood suicidal thoughts and behaviors: a prospective, longitudinal analysis.J Am Acad Child Adolesc Psychiatry. 2017; 56: 958-965Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar underlines the need to go beyond gate-keeper, school-based, or other “suicide-specific” interventions to broader interventions that can mitigate negative developmental trajectories by promoting healthier and more adaptive parent–child interactions. Adult Associations of Childhood Suicidal Thoughts and Behaviors: A Prospective, Longitudinal AnalysisJournal of the American Academy of Child & Adolescent PsychiatryVol. 56Issue 11PreviewSuicidal thoughts and behavior (STBs) have their peak period of onset in adolescence, but little is known about how such behavior is associated with later functioning. The aim of this study is to test whether childhood STBs are related to adult psychiatric, suicidal, and functional outcomes. Full-Text PDF

The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) have not been well characterized.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by recurrent motor and vocal tics, often accompanied by obsessive–compulsive disorder and/or attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet to be clarified fully. There is now mounting evidence that the genetic risks for TS include both common and rare variants and may involve complex multigenic inheritance or, in rare cases, a single major gene. Based on recent progress in many other common disorders with apparently similar genetic architectures, it is clear that large patient cohorts and open-access repositories will be essential to further advance the field. To that end, the large multicenter Tourette International Collaborative Genetics (TIC Genetics) study was established. The goal of the TIC Genetics study is to undertake a comprehensive gene discovery effort, focusing both on familial genetic variants with large effects within multiply affected pedigrees and on de novo mutations ascertained through the analysis of apparently simplex parent–child trios with non-familial tics. The clinical data and biomaterials (DNA, transformed cell lines, RNA) are part of a sharing repository located within the National Institute for Mental Health Center for Collaborative Genomics Research on Mental Disorders, USA, and will be made available to the broad scientific community. This resource will ultimately facilitate better understanding of the pathophysiology of TS and related disorders and the development of novel therapies. Here, we describe the objectives and methods of the TIC Genetics study as a reference for future studies from our group and to facilitate collaboration between genetics consortia in the field of TS.

Objective: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method: The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results: Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p = .09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p = .08 in the current study, p = .025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). Conclusion: Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.

m T he article by Bridge and colleagues 1 in this issue of the Journal examines vulnerability to adolescent suicidal behavior through the lens of the Iowa Gambling Task. The IGT is among a newer generation of empirically operationalized neuropsychological tasks that are advancing our understanding of cognitiveemotional styles and how they may link basic neurobiological processes to psychopathology. The study found that, compared with demographically matched psychiatric controls, adolescents with a history of attempted suicide showed impaired learning from experience on the IGT; furthermore, this difference in impaired decision making persisted even after controlling for affective disorder, current medication, hostility, and impulsivity. This study stands as an exemplar of newer dimensional paradigms that shed light on underlying pathogenic mechanisms—and that cut across categorical diagnostic boundaries. Each era’s understanding of maladies such as adolescent suicidality reflects its prevalent theoretical models and available investigative methodologies. Brent recently summarized the impressive progress made over the past 30 years in the empirical understanding of youth suicide and suicidal behavior. This progress reflected important developments in psychiatry and child psychiatry as a whole. In addition to the DSM’s standardization of a categorical approach, the development of reliable diagnostic assessments and sophisticated epidemiologic methods made possible a rich body of psychological postmortem, case control, and population studies that demonstrated the major role played by mood, conduct, and substance-abuse disorders and of Axis II cluster B traits in the occurrence of suicidal behavior. Large-scale epidemiologic studies also have shown the overlap between suicidal behavior and other health risk behaviors (fightc

Objective: The objective of this blinded, prospective, longitudinal study was to determine whether new group A beta hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). A group of children with Tourette syndrome and/or OC disorder without a PANDAS history served as the comparison (non-PANDAS) group. Method: Consecutive clinical ratings of tic and OC symptom severity were obtained for 31 PANDAS subjects and 53 non-PANDAS subjects. Clinical symptoms and laboratory values (throat cultures and streptococcal antibody titers) were evaluated at regular intervals during a 25-month period. Additional testing occurred at the time of any tic or OC symptom exacerbation. New GABHS infections were established by throat swab cultures and/or recent significant rise in streptococcal antibodies. Laboratory personnel were blinded to case or control status, clinical (exacerbation or not) condition, and clinical evaluators were blinded to the laboratory results. Results: No group differences were observed in the number of clinical exacerbations or the number of newly diagnosed GABHS infections. On only six occasions of a total of 51(12%), a newly diagnosed GABHS infection was followed, within 2 months, by an exacerbation of tic and/or OC symptoms. In every instance, this association occurred in the non-PANDAS group. Conclusions: This study provides no evidence for a temporal association between GABHS infections and tic/OC symptom exacerbations in children who meet the published PANDAS diagnostic criteria. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(2): 108-118.

Background: The goals of this prospective longitudinal study were to monitor levels of psychosocial stress in children and adolescents with Tourette syndrome (TS) and/or obsessive-compulsive disorder (OCD) compared to healthy control subjects and to examine the relationship between measures of psychosocial stress and fluctuations in tic, obsessive-compulsive (OC), and depressive symptom severity. Methods: Consecutive ratings of tic, OC and depressive symptom severity were obtained for 45 cases and 41 matched healthy control subjects over a two-year period. Measures of psychosocial stress included youth self-report, parental report, and clinician ratings of long-term contextual threat. Structural equation modeling for unbalanced repeated measures was used to assess the temporal sequence of psychosocial stress with the severity of tic, OC and depressive symptoms. Results: Subjects with TS and OCD experienced significantly more psychosocial stress than did the controls. Estimates of psychosocial stress were predictive of future depressive symptoms. Current levels of psychosocial stress were also a significant predictor of future OC symptom severity, but not vice versa. Current OC symptom severity was a predictor of future depressive symptom severity, but not vice versa. Current levels of psychosocial stress and depression were independent predictors of future tic severity, even after controlling for the effect of advancing chronological age. Conclusions: The impact of antecedent psychosocial adversity is greater on future depressive symptoms than for tic and/or OC symptoms. Worsening OC symptoms are also a predictor of future depressive symptoms. Advancing chronological age is robustly associated with reductions in tic severity.

AbstractThe psychodynamic approach to suicide examines the meaning and origins of suicidal behaviour in terms of the vicissitudes of feelings, motives, self-concept, and interpersonal relationships. Negative or poorly differentiated self-concept; maladaptive defensive or attachment style; and isolative, avoidant, or self-critical personality traits appear to be important risk factors for suicidality in youth.Across diverse national contexts, adolescent suicidality is associated with family factors such as parental psychopathology, negative life events, family discord, negative parent–child relationship (including abuse and neglect), and low perceived family support. Further research is needed to understand the intervening variables linking such family factors to suicide, including delineating the relative contributions of shared genetic risk (e.g. for psychopathology or maladaptive traits) versus the negative developmental impact of adverse family environment.The developmental challenges of adolescence increase the vulnerability to suicidal ideation and behaviour. How specific national or cultural contexts mitigate or exacerbate these factors remains an important area for further study.

The objective of this study is examine the similarities and differences between adolescent suicide completers, adolescents with non-fatal suicidal symptoms, and non-suicidal psychiatric controls in an epidemiologic sample. Using the central Israeli military medical registry, 214 18-21 year old males from the same national service cohort were identified, consisting of 43 consecutive completed suicides and 171 consecutive central psychiatric clinic outpatients presenting with near-fatal suicide attempts, serious suicide attempts, para-suicidal gestures, threats, ideation, or other non-suicidal complaints. Systematic pre-induction and service data were available for all subjects, with detailed postmortem inquest data for suicides. Systematic clinical data, including the Kiddie-Schedule for Affective Disorders and Schizophrenia (K-SADS), Hamilton Depression Scale, and Eysenck Personality Inventory were obtained on all clinic subjects. Major depression was present in half of completers, near-lethal attempters, and ideators, but absent in the other clinic groups, whose commonest diagnosis was adjustment disorder. Depression scores increased across groups with increasing intent; ideators also had high scores. Completers and near-lethal attempters had higher I.Q. and medical fitness ratings and were in more demanding assignments than other groups. Prior attempts were commonest in completers, near-lethal attempters, and gesturers. Disciplinary history, ethnicity, family intactness, immigrant status, and Eysenck Personality Inventory scores did not differentiate the groups. The findings may not be generalizable to female adolescents or to other countries or time periods. The findings thus point to contrasts, as well as similarities, between groups of adolescents with different types of suicidal symptoms.

BACKGROUND:Tourette Syndrome is a neuropsychiatric disorder characterized by chronic motor and phonic tics. Affected individuals and their family members are at an increased risk for other neuropsychiatric conditions including obsessive-compulsive disorder and attention deficit hyperactivity disorder. While there is consistent evidence that genetic factors play a significant etiologic role, no replicable susceptibility alleles have thus far been identified.DESCRIPTION:Here we discuss a sharing resource of clinical and genetic data, the New Jersey Center for Tourette Syndrome Sharing Repository, whose goal is to provide clinical data, DNA, and lymphoblastoid cell lines to qualified researchers.CONCLUSION:Opening access to the data and patient material to the widest possible research community will hasten the identification of causal genetic factors and facilitate better understanding and treatment of this often impairing disorder.

A 48-year-old man with severe, lifelong Tourette's syndrome (TS) characterized by forceful self-injurious motor tics and, obsessive-compulsive disorder was treated with bilateral deep brain stimulation (DBS). The decision to treat was based on his progressive neurological impairment (left sided weakness secondary to spinal cord injury) because of his relentless, violent head jerks. Electrodes were implanted at the level of the medial part of the thalamus (centromedian nucleus, the substantia periventricularis, and the nucleus ventro-oralis interims). DBS resulted in a substantial reduction of tics. These data show that bilateral DBS of the thalamus can have a good effect on severe ties in adult patients suffering from intractable TS. (c) 2007 Movement Disorder Society

Objective The aim of this study was to analyze the cultivable oral microbiota of patients with obstructive sleep apnea (OSA) and its association with the periodontal condition. Methods The epidemiology profile of patients and their clinical oral characteristics were determined. The microbiota was collected from saliva, subgingival plaque, and gingival sulcus of 93 patients classified into four groups according to the periodontal and clinical diagnosis: Group 1 ( n = 25), healthy patients; Group 2 ( n = 17), patients with periodontitis and without OSA; Group 3 ( n = 19), patients with OSA and without periodontitis; and Group 4 ( n = 32), patients with periodontitis and OSA. Microbiological samples were cultured, classified, characterized macroscopically and microscopically, and identified by MALDI-TOF-MS. The distribution of complexes and categories of microorganisms and correlations were established for inter- and intra-group of patients and statistically evaluated using the Spearman r test ( p -value <0.5) and a multidimensional grouping analysis. Result There was no evidence between the severity of OSA and periodontitis ( p = 0.2813). However, there is a relationship between the stage of periodontitis and OSA ( p = 0.0157), with stage III periodontitis being the one with the highest presence in patients with severe OSA (prevalence of 75%; p = 0.0157), with more cases in men. The greatest distribution of the complexes and categories was found in oral samples of patients with periodontitis and OSA (Group 4 P-OSA); even Candida spp. were more prevalent in these patients. Periodontitis and OSA are associated with comorbidities and oral conditions, and the microorganisms of the orange and red complexes participate in this association. The formation of the dysbiotic biofilm was mainly related to the presence of these complexes in association with Candida spp. Conclusion Periodontopathogenic bacteria of the orange complex, such as Prevotella melaninogenica , and the yeast Candida albicans , altered the cultivable oral microbiota of patients with periodontitis and OSA in terms of diversity, possibly increasing the severity of periodontal disease. The link between yeasts and periodontopathogenic bacteria could help explain why people with severe OSA have such a high risk of stage III periodontitis. Antimicrobial approaches for treating periodontitis in individuals with OSA could be investigated in vitro using polymicrobial biofilms, according to our findings.

Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal tics—rapid, repetitive, stereotyped movements or vocalizations. Tourette syndrome typically has a prepubertal onset, and boys are more commonly affected than girls. Symptoms usually begin with transient bouts of simple motor tics. By age 10 years, most children are aware of nearly irresistible somatosensory urges that precede the tics. These urges likely reflect a defect in sensorimotor gating because they intrude into the child's conscious awareness and become a source of distraction and distress. A momentary sense of relief typically follows the completion of a tic. Over the course of hours, tics occur in bouts, with a regular intertic interval. Tics increase during periods of emotional excitement and fatigue. Tics can become ``complex'' in nature and appear to be purposeful. Tics can be willfully suppressed for brief intervals and can be evoked by the mere mention of them. Tics typically diminish during periods of goal-directed behavior, especially those that involve both heightened attention and fine motor or vocal control, as occur in musical and athletic performances. Over the course of months, tics wax and wane. New tics appear, often in response to new sources of somatosensory irritation, such as the appearance of a persistent vocal tic (a cough) following a cold. Over the course of years, tic severity typically peaks between 8 and 12 years of age. By the end of the second decade of life, many individuals are virtually tic free. Less than 20% of cases continue to experience clinically impairing tics as adults. Tics rarely occur in isolation, and other coexisting conditions—such as behavioral disinhibition, hypersensitivity to a broad range of sensory stimuli, problems with visual motor integration, procedural learning difficulties, attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, depression, anxiety, and emotional instability—are often a greater source of impairment than the tics themselves. Emerging behavioral treatments of Tourette syndrome are based in part on an understanding of the moment-to-moment experience of somatosensory urges and motor response. With identification of specific genes of major effect and advances in our understanding of the neural circuitry of sensorimotor gating, habit formation, and procedural memory—together with insights from postmortem brain studies, in vivo brain imaging, and electrophysiologic recordings—we might be on the threshold of a deeper understanding of the phenomenology and natural history of Tourette syndrome. (J Child Neurol 2006;21:642—649; DOI 10.2310/7010.2006.00167).

Obsessive–compulsive disorder (OCD) encompasses a broad range of symptoms representing multiple domains. This complex phenotype can be summarized using a few consistent and temporally stable symptom dimensions. The objective of this study was to assess the psychometric properties of the Dimensional Yale–Brown Obsessive–Compulsive Scale (DY-BOCS). This scale measures the presence and severity of obsessive–compulsive (OC) symptoms within six distinct dimensions that combine thematically related obsessions and compulsions. The DY-BOCS includes portions to be used as a self-report instrument and portions to be used by expert raters, including global ratings of OC symptom severity and overall impairment. We assessed 137 patients with a Diagnostic and Statistical Manual-IV diagnosis of OCD, aged 6–69 years, from sites in the USA, Canada and Brazil. Estimates of the reliability and validity of both the expert and self-report versions of the DY-BOCS were calculated and stratified according to age (pediatric vs. adult subjects). The internal consistency of each of the six symptom dimensions and the global severity score were excellent. The inter-rater agreement was also excellent for all component scores. Self-report and expert ratings were highly intercorrelated. The global DY-BOCS score was highly correlated with the total Yale–Brown Obsessive–Compulsive Scale score (Pearson r =0.82, P <0.0001). Severity scores for individual symptom dimensions were largely independent of one another, only modestly correlated with the global ratings, and were also differentially related to ratings of depression, anxiety and tic severity. No major differences were observed when the results were stratified by age. These results indicate that the DY-BOCS is a reliable and valid instrument for assessing multiple aspects of OCD symptom severity in natural history, neuroimaging, treatment response and genetic studies when administered by expert clinicians or their highly trained staff.