Phenomenology of OCD: Lessons from a large multicenter study and implications for ICD-11

This study aimed to investigate the phenomenology of obsessive compulsive disorder (OCD), addressing specific questions about the nature of obsessions and compulsions, and to contribute to the World Health Organization's (WHO) revision of OCD diagnostic guidelines. Data from 1001 patients from the Brazilian Research Consortium on Obsessive Compulsive Spectrum Disorders were used. Patients were evaluated by trained clinicians using validated instruments, including the Dimensional Yale Brown Obsessive Compulsive Scale, the University of Sao Paulo Sensory Phenomena Scale, and the Brown Assessment of Beliefs Scale. The aims were to compare the types of sensory phenomena (SP, subjective experiences that precede or accompany compulsions) in OCD patients with and without tic disorders and to determine the frequency of mental compulsions, the co-occurrence of obsessions and compulsions, and the range of insight. SP were common in the whole sample, but patients with tic disorders were more likely to have physical sensations and urges only. Mental compulsions occurred in the majority of OCD patients. It was extremely rare for OCD patients to have obsessions without compulsions. A wide range of insight into OCD beliefs was observed, with a small subset presenting no insight. The data generated from this large sample will help practicing clinicians appreciate the full range of OCD symptoms and confirm prior studies in smaller samples the degree to which insight varies. These findings also support specific revisions to the WHO's diagnostic guidelines for OCD, such as describing sensory phenomena, mental compulsions and level of insight, so that the world-wide recognition of this disabling disorder is increased. (C) 2014 Elsevier Ltd. All rights reserved.

Separation anxiety disorder in adult patients with obsessive-compulsive disorder: prevalence and clinical correlates

Objective: Individuals with obsessive-compulsive disorder (OCD) and separation anxiety disorder (SAD) tend to present higher morbidity than do those with OCD alone. However, the relationship between OCD and SAD has yet to be fully explored.Method: This was a cross-sectional study using multiple logistic regression to identify differences between OCD patients with SAD (OCD + SAD, n = 260) and without SAD (OCD, n = 695), in terms of clinical and socio-demographic variables. Data were extracted from those collected between 2005 and 2009 via the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders project.Results: SAD was currently present in only 42 (4.4%) of the patients, although 260 (27.2%) had a life-time diagnosis of the disorder. In comparison with the OCD group patients, patients with SAD + OCD showed higher chance to present sensory phenomena, to undergo psychotherapy, and to have more psychiatric comorbidities, mainly bulimia.Conclusion: In patients with primary OCD, comorbid SAD might be related to greater personal dysfunction and a poorer response to treatment, since sensory phenomena may be a confounding aspect on diagnosis and therapeutics. Patients with OCD + SAD might be more prone to developing specific psychiatric comorbidities, especially bulimia. Our results suggest that SAD symptom assessment should be included in the management and prognostic evaluation of OCD, although the psychobiological role that such symptoms play in OCD merits further investigation. (C) 2014 Elsevier Masson SAS. All rights reserved.

Clinical features of tic-related obsessive-compulsive disorder: results from a large multicenter study

Objective. To evaluate the clinical features of obsessive-compulsive disorder (OCD) patients with comorbid tic disorders (TD) in a large, multicenter, clinical sample. Method. A cross-sectional study was conducted that included 813 consecutive OCD outpatients from the Brazilian OCD Research Consortium and used several instruments of assessment, including the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Yale Global Tic Severity Scale (YGTSS), the USP Sensory Phenomena Scale, and the Structured Clinical Interview for DSM-IV Axis I Disorders. Results. The sample mean current age was 34.9 years old (SE 0.54), and the mean age at obsessive-compulsive symptoms (OCS) onset was 12.8 years old (SE 0.27). Sensory phenomena were reported by 585 individuals (72% of the sample). The general lifetime prevalence of TD was 29.0% (n=236), with 8.9% (n=72) presenting Tourette syndrome, 17.3% (n=5141) chronic motor tic disorder, and 2.8% (n=523) chronic vocal tic disorder. The mean tic severity score, according to the YGTSS, was 27.2 (SE 1.4) in the OCD1TD group. Compared to OCD patients without comorbid TD, those with TD (OCD1TD group, n=236) were more likely to be males (49.2% vs. 38.5%, p<005) and to present sensory phenomena and comorbidity with anxiety disorders in general: separation anxiety disorder, social phobia, specific phobia, generalized anxiety disorder, post-traumatic stress disorder, attention-deficit hyperactivity disorder, impulse control disorders in general, and skin picking. Also, the "aggressive," "sexual/religious," and "hoarding" symptom dimensions were more severe in the OCD+TD group. Conclusion. Tic-related OCD may constitute a particular subgroup of the disorder with specific phenotypical characteristics, but its neurobiological underpinnings remain to be fully disentangled.

Evidence that a single bioluminescent system is shared by all known bioluminescent fungal lineages

Since the early 20th century, many researchers have attempted to determine how fungi are able to emit light. The first successful experiment was obtained using the classical luciferin-luciferase test that consists of mixing under controlled conditions hot (substrate/luciferin) and cold (enzyme/luciferase) water extracts prepared from bioluminescent fungi. Failures by other researchers to reproduce those experiments using different species of fungi lead to the hypothesis of a non-enzymatic luminescent pathway. Only recently, the involvement of a luciferase in this system was proven, thus confirming its enzymatic nature. Of the 100 000 described species in Kingdom Fungi, only 71 species are known to be luminescent and they are distributed unevenly amongst four distantly related lineages. The question we address is whether the mechanism of bioluminescence is the same in all four evolutionary lineages suggesting a single origin of luminescence in the Fungi, or whether each lineage has a unique mechanism for light emission implying independent origins. We prepared hot and cold extracts of numerous species representing the four bioluminescent fungal lineages and performed cross-reactions (luciferin x luciferase) in all possible combinations using closely related non-luminescent species as controls. All cross-reactions with extracts from luminescent species yielded positive results, independent of lineage, whereas no light was emitted in cross-reactions with extracts from non-luminescent species. These results support the hypothesis that all four lineages of luminescent fungi share the same type of luciferin and luciferase, that there is a single luminescent mechanism in the Fungi, and that fungal luciferin is not a ubiquitous molecule in fungal metabolism.

Clinical features of obsessive-compulsive disorder with hoarding symptoms: A multicenter study

Background: Factor analyses indicate that hoarding symptoms constitute a distinctive dimension of obsessive-compulsive disorder (OCD), usually associated with higher severity and limited insight. The aim was to compare demographic and clinical features of OCD patients with and without hoarding symptoms. Method: A cross sectional study was conducted with 1001 DSM-IV OCD patients from the Brazilian Research Consortium of Obsessive-Compulsive Spectrum Disorders (CTOC), using several instruments. The presence and severity of hoarding symptoms were determined using the Dimensional Yale-Brown Obsessive-Compulsive Scale. Statistical univariate analyses comparing factors possibly associated with hoarding symptoms were conducted, followed by logistic regression to adjust the results for possible confounders. Results: Approximately half of the sample (52.7%, n = 528) presented hoarding symptoms, but only four patients presented solely the hoarding dimension. Hoarding was the least severe dimension in the total sample (mean score: 3.89). The most common lifetime hoarding symptom was the obsessive thought of needing to collect and keep things for the future (44.0%, n = 440). After logistic regression, the following variables remained independently associated with hoarding symptoms: being older, living alone, earlier age of symptoms onset, insidious onset of obsessions, higher anxiety scores, poorer insight and higher frequency of the symmetry-ordering symptom dimension. Concerning comorbidities, major depressive, posttraumatic stress and attention deficit/hyperactivity disorders, compulsive buying and tic disorders remained associated with the hoarding dimension. Conclusion: OCD hoarding patients are more likely to present certain clinical features, but further studies are needed to determine whether OCD patients with hoarding symptoms constitute an etiologically discrete subgroup. (C) 2012 Elsevier Ltd. All rights reserved.

Social phobia in obsessive-compulsive disorder: Prevalence and correlates

Background: Social Phobia (SP) is an anxiety disorder that frequently co-occurs with obsessive-compulsive disorder (OCD); however, studies that evaluate clinical factors associated with this specific comorbidity are rare. The aim was to estimate the prevalence of SP in a large multicenter sample of OCD patients and compare the characteristics of individuals with and without SP. Method: A cross-sectional study with 1001 patients of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders using several assessment instruments, including the Dimensional Yale-Brown Obsessive-Compulsive Scale and the Structured Clinical Interview for DSM-IV Axis I Disorders. Univariate analyses were followed by logistic regression. Results: Lifetime prevalence of SP was 34.6% (N=346). The following variables remained associated with SP comorbidity after logistic regression: male sex, lower socioeconomic status, body dysmorphic disorder, specific phobia, dysthymia, generalized anxiety disorder, agoraphobia, Tourette syndrome and binge eating disorder. Limitations: The cross-sectional design does not permit the inference of causal relationships; some retrospective information may have been subject to recall bias; all patients were being treated in tertiary services, therefore generalization of the results to other samples of OCD sufferers should be cautious. Despite the large sample size, some hypotheses may not have been confirmed due to the small number of cases with these characteristics (type 2 error). Conclusion: SP is frequent among OCD patients and co-occurs with other disorders that have common phenomenological features. These findings have important implications for clinical practice, indicating the need for broader treatment approaches for individuals with this profile. (C) 2012 Elsevier B.V. All rights reserved.

BODY DYSMORPHIC DISORDER IN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER: PREVALENCE AND CLINICAL CORRELATES

Background The prevalence, sociodemographic aspects, and clinical features of body dysmorphic disorder (BDD) in patients with obsessivecompulsive disorder (OCD) have been previously addressed in primarily relatively small samples. Methods We performed a cross-sectional demographic and clinical assessment of 901 OCD patients participating in the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders. We used the Structured Clinical Interview for DSM-IV Axis I Disorders; Yale-Brown Obsessive-Compulsive Scale; Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS); Brown Assessment of Beliefs Scale; Clinical Global Impression Scale; and Beck Depression and Anxiety Inventories. Results The lifetime prevalence of BDD was 12.1%. The individuals with comorbid BDD (OCD-BDD; n = 109) were younger than were those without it. In addition, the proportions of single and unemployed patients were greater in the OCD-BDD group. This group of patients also showed higher rates of suicidal behaviors; mood, anxiety, and eating disorders; hypochondriasis; skin picking; Tourette syndrome; and symptoms of the sexual/religious, aggressive, and miscellaneous dimensions. Furthermore, OCD-BDD patients had an earlier onset of OC symptoms; greater severity of OCD, depression, and anxiety symptoms; and poorer insight. After logistic regression, the following features were associated with OCD-BDD: current age; age at OCD onset; severity of the miscellaneous DY-BOCS dimension; severity of depressive symptoms; and comorbid social phobia, dysthymia, anorexia nervosa, bulimia nervosa, and skin picking. Conclusions Because OCD patients might not inform clinicians about concerns regarding their appearance, it is essential to investigate symptoms of BDD, especially in young patients with early onset and comorbid social anxiety, chronic depression, skin picking, or eating disorders. Depression and Anxiety 29: 966-975, 2012. (C) 2012 Wiley Periodicals, Inc.

Clinical correlates of social adjustment in patients with obsessive-compulsive disorder

Background: Patients with obsessive-compulsive disorder (OCD) frequently show poor social adjustment, which has been associated with OCD severity. Little is known about the effects that age at symptom onset, specific OCD symptoms, and psychiatric comorbidities have on social adjustment. The objective of this study was to investigate the clinical correlates of social functioning in OCD patients. Methods: Cross-sectional study involving 815 adults with a primary DSM-IV diagnosis of OCD participating in the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders. Patients were assessed with the Social Adjustment Scale, the Medical Outcomes Study 36-item Short-Form Health Survey, the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, and the Structured Clinical Interview for DSM-IV Axis I Disorders. Clinical correlates of social adjustment were assessed with generalized linear models with gamma distribution. Results: Poor overall social functioning was associated with greater OCD severity (p = 0.02); hoarding symptoms (p = 0.004); sexual/religious obsessions (p = 0.005); current major depressive disorder (p = 0.004); current post-traumatic stress disorder (p = 0.002); and current eating disorders (p = 0.02). Poor social adjustment was also associated with impaired quality of life. Conclusions: Patients with OCD have poor social functioning in domains related to personal relationships and professional performance. Hoarding symptoms and sexual/religious obsessions seem to have the strongest negative effects on social functioning. Early age at OCD symptom onset seems to be associated with professional and academic underachievement and impairment within the family unit, whereas current psychiatric comorbidity worsen overall social functioning. In comparison with quality of life, social adjustment measures seem to provide a more comprehensive overview of the OCD-related burden. (C) 2012 Elsevier Ltd. All rights reserved.

Identification of unannotated exons of low abundance transcripts in Drosophila melanogaster and cloning of a new serine protease gene upregulated upon injury

Abstract Background The sequencing of the D.melanogaster genome revealed an unexpected small number of genes (~ 14,000) indicating that mechanisms acting on generation of transcript diversity must have played a major role in the evolution of complex metazoans. Among the most extensively used mechanisms that accounts for this diversity is alternative splicing. It is estimated that over 40% of Drosophila protein-coding genes contain one or more alternative exons. A recent transcription map of the Drosophila embryogenesis indicates that 30% of the transcribed regions are unannotated, and that 1/3 of this is estimated as missed or alternative exons of previously characterized protein-coding genes. Therefore, the identification of the variety of expressed transcripts depends on experimental data for its final validation and is continuously being performed using different approaches. We applied the Open Reading Frame Expressed Sequence Tags (ORESTES) methodology, which is capable of generating cDNA data from the central portion of rare transcripts, in order to investigate the presence of hitherto unnanotated regions of Drosophila transcriptome. Results Bioinformatic analysis of 1,303 Drosophila ORESTES clusters identified 68 sequences derived from unannotated regions in the current Drosophila genome version (4.3). Of these, a set of 38 was analysed by polyA+ northern blot hybridization, validating 17 (50%) new exons of low abundance transcripts. For one of these ESTs, we obtained the cDNA encompassing the complete coding sequence of a new serine protease, named SP212. The SP212 gene is part of a serine protease gene cluster located in the chromosome region 88A12-B1. This cluster includes the predicted genes CG9631, CG9649 and CG31326, which were previously identified as up-regulated after immune challenges in genomic-scale microarray analysis. In agreement with the proposal that this locus is co-regulated in response to microorganisms infection, we show here that SP212 is also up-regulated upon injury. Conclusion Using the ORESTES methodology we identified 17 novel exons from low abundance Drosophila transcripts, and through a PCR approach the complete CDS of one of these transcripts was defined. Our results show that the computational identification and manual inspection are not sufficient to annotate a genome in the absence of experimentally derived data.

Avaliação do stent coronário eluidor de everolimus XIENCE TM V na cpopulação feminina latino-americana do estudo de braço único SPIRIT Women: acompanhamento clínico de um ano

INTRODUÇÃO: Os estudos com stents farmacológicos têm avaliado predominantemente populações masculinas de descendência europeia. O estudo de braço único SPIRIT Women avalia o stent eluidor de everolimus XIENCE TM V em lesões de novo complexas em uma população feminina do mundo real, incluindo pacientes latino-americanas. Esta análise permite compreender como essa população responde ao implante de stent, comparativamente a pacientes não-latino-americanas. MÉTODOS: Das 1.572 pacientes matriculadas em 73 locais fora dos Estados Unidos, 138 (9%) foram recrutadas na Argentina, no Brasil e na Venezuela. RESULTADOS: As lesões-alvo tinham diâmetro de referência do vaso entre 2,25 mm e 4 mm e extensão da lesão ≤ 28 mm. As características basais foram semelhantes entre os grupos, com exceção de maior prevalência de hipertensão arterial, infarto do miocárdio (IM) de parede anterior e história familiar de doença arterial coronária na coorte latino-americana. As lesões tendiam a ser mais complexas em mulheres latino-americanas, com menor diâmetro de referência do vaso-alvo, maior extensão da lesão, maior excentricidade e angulação e mais lesões tipo B2/C. Os eventos foram adjudicados de acordo com as definições do Academic Research Consortium. Em um ano, o desfecho combinado de morte por todas as causas, IM e revascularização do vaso-alvo (RVA) foi de 12,1% na população não-latino-americana e de 10,1% na população latino-americana (P = 0,58). CONCLUSÕES: Em um ano, os baixos índices de eventos cardíacos adversos, incluindo trombose do stent, falha da lesão-alvo, morte cardíaca, IM e RVA nas mulheres latino-americanas foram comparáveis aos das mulheres não-latino-americanas, apesar da maior complexidade das lesões. Esses resultados demonstram a segurança e a eficácia do stent XIENCE TM V nessa pequena coorte de pacientes latino-americanas, à semelhança do que é observado com populações maiores e mais variadas.

Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review

As part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation of the gastrointestinal tract, which affects 2.2 million people in Europe and 1.4 million people in North America. We systematically reviewed all published genetic studies on populations of European ancestry (67 studies on Crohn's disease [CD] and 37 studies on ulcerative colitis [UC]) to identify critical genomic regions associated with IBD. We developed a computer algorithm to map the 807 P/PI genes with exact genomic locations listed in the MEROPS database of peptidases onto these critical regions and to rank P/PI genes according to the accumulated evidence for their association with CD and UC. 82 P/PI genes (75 coding for proteases and 7 coding for protease inhibitors) were retained for CD based on the accumulated evidence. The cylindromatosis/turban tumor syndrome gene (CYLD) on chromosome 16 ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4), all located on chromosome 3. For UC, 18 P/PI genes were retained (14 proteases and 4 protease inhibitors), with a considerably lower amount of accumulated evidence. The ranking of P/PI genes as established in this systematic review is currently used to guide validation studies of candidate P/PI genes, and their functional characterization in interdisciplinary mechanistic studies in vitro and in vivo as part of IBDase. The approach used here overcomes some of the problems encountered when subjectively selecting genes for further evaluation and could be applied to any complex disease and gene family.

Clinical end points in coronary stent trials: a case for standardized definitions

BACKGROUND: Although most clinical trials of coronary stents have measured nominally identical safety and effectiveness end points, differences in definitions and timing of assessment have created confusion in interpretation. METHODS AND RESULTS: The Academic Research Consortium is an informal collaboration between academic research organizations in the United States and Europe. Two meetings, in Washington, DC, in January 2006 and in Dublin, Ireland, in June 2006, sponsored by the Academic Research Consortium and including representatives of the US Food and Drug Administration and all device manufacturers who were working with the Food and Drug Administration on drug-eluting stent clinical trial programs, were focused on consensus end point definitions for drug-eluting stent evaluations. The effort was pursued with the objective to establish consistency among end point definitions and provide consensus recommendations. On the basis of considerations from historical legacy to key pathophysiological mechanisms and relevance to clinical interpretability, criteria for assessment of death, myocardial infarction, repeat revascularization, and stent thrombosis were developed. The broadly based consensus end point definitions in this document may be usefully applied or recognized for regulatory and clinical trial purposes. CONCLUSION: Although consensus criteria will inevitably include certain arbitrary features, consensus criteria for clinical end points provide consistency across studies that can facilitate the evaluation of safety and effectiveness of these devices.