Academic literature on the topic 'Obsessive-compulsive spectrum disorders'

ABSTRACTIt has been proposed that certainDiagnostic and Statistical Manual of Mental Disorders, Fourth EditionAxis I disorders share overlapping clinical features, genetic contributions, and treatment response and fall within an “obsessive-compulsive” spectrum. Obsessive-compulsive personality disorder (OCPD) resembles obsessive-compulsive disorder (OCD) and other spectrum disorders in terms of phenomenology, comorbidity, neurocognition, and treatment response.This article critically examines the nosological profile of OCPD with special reference to OCD and related disorders. By viewing OCPD as a candidate member of the obsessive-compulsive spectrum, we gain a fresh approach to understanding its neurobiology, etiology, and potential treatments.

Pathological gambling has been proposed to belong to the obsessive-compulsive spectrum of disorders. Disorders on this spectrum are thought to share similar clinical features, neurobiology, and responses to treatment as Obsessive-Compulsive Disorder. A total of 18 studies were included in a meta-analysis to assess the strength of the association between these disorders. A strong relationship (effect size = 1. 01) was found between pathological gambling and obsessive-compulsive traits. A weak relationship was found between pathological gambling and Obsessive-Compulsive Disorder (.07) and Obsessive-Compulsive Personality Disorder (effect size = .23). These results suggest pathological gambling and Obsessive-Compulsive Disorder are distinct disorders. However, pathological gamblers do appear to show high rates of obsessive-compulsive traits relative to controls. These findings are only moderately supportive of the inclusion of pathological gambling within the obsessive-compulsive spectrum of conditions.

In the DSM IV-TR, Obsessive-Compulsive Disorder (OCD) is categorized as an anxiety disorder. A wide range of psychiatric and medical disorders, not included in this category, has been hypothesized to be related to OCD and to form a family of disorders known as obsessive compulsive spectrum disorders (OCSD). OCSD would include several clinically heterogeneous disorders such as Body Dysmorphic Disorder, Tourette's Syndrome or Pathological Gambling. This construct is based on disorders’ similarities with OCD in a variety of domains such as phenomenology, comorbidity, neurotransmitter or peptide systems, neurocircuitry, family history, genetic factors and treatment response. This presentation provides an overview of the existing literature regarding the concept of the OCD spectrum and the relationships between the disorders included in OCSD. Although there are data supporting the inclusion of some disorders in the OC spectrum, more research is needed to clarify the relationships and the boundaries between these disorders. Ultimately, a better understanding of OC spectrum may have significant implications for clinical practice.

The obsessive-compulsive disorders spectrum concept has grown in recent years because of the common clinical features, such as obsessive thinking and compulsive rituals, biological markers, presumed etiology, and treatment response, that these disorders may share with obsessive-compulsive disorder (OCD). This concept has important implications in regard to diagnosis, nosology, neurobiology, and treatment of a wide group of diverse disorders affecting up to 10% of the population. New insights in central nervous system (CNS) mechanisms that drive the repetitive behaviors of the obsessive-compulsive spectrum disorders have heightened interest in the spectrum in researchers, clinicians, and those involved in drug development.An important approach in neuropsychiatry centers on employing a dimensional classification of psychopathology. Psychiatric phenomena often fall on a continuum. A dimensional approach allows for the classification of patients who fall at the border of classical entities or who are otherwise atypical. Diagnostic categories are considered along a spectrum if there is considerable overlap in symptoms and in etiology, as demonstrated by familial linkage biological markers, and pharmacological dissection. Categorical and dimensional approaches to the OCD spectrum could have significant implications for diagnosis, nosology, neurobiology, and treatment of a wide group of disorders affecting a sizable percentage of the population.Recent interest has focused on spectrums in movement disorders, affective disorders, schizophrenia, epileptic and impulsive disorders, and obsessive-compulsive disorders (which we will examine here); in addition, there has been interest in the overlap between these spectrums. Viewing disorders in terms of overlapping spectrums provides researchers and clinicians a framework with which to better understand and treat these disorders.

Obsessive-compulsive disorder (OCD) and the spectrum of associated conditions, affect 2-4% of the population worldwide. Although heritability studies in OCD have shown a 3 - 12 times increased risk for first degree relatives, the identification of the underlying risk-conferring genetic variation using classic genetic association studies has proven to be difficult. The possibility of a larger contribution of rare genetic variants to the risk of psychiatric disorder has been suggested by several successful studies. We expect that a spectrum of risk allele frequencies exists, which includes not only common variation but also a substantial amount of rare genetic variants that contribute to OCD. This thesis is aimed at identifying and functionally characterizing rare genetic variation in the OCD spectrum. Identified statistically significant variants were scrutinized for changes related to synaptic function using high content screening and subsequent functional analyses. Identifying the genetic profile of rare variants found in the OCD spectrum cohort combined with the functional impact that these variants have has provided insight into the etiology of the OCD spectrum. With these approaches a foundation can be laid for the development of a predictive model of the OCD spectrum.

Autism Spectrum Disorder (ASD) and Obsessive-Compulsive Disorder (OCD) are frequently comorbid and share deficits in executive function, highlighting a need to understand the shared and/or disorder-specific neurofunctional abnormalities underlying these behaviours. First, a comparative, multimodal meta-analysis between ASD and OCD was conducted on whole-brain voxel-based morphometry structural magnetic resonance imaging (MRI) studies and functional MRI studies of cognitive control. Second, functional MRI (fMRI) was used to scan adolescent boys with ASD or OCD, and control boys while they performed tasks measuring sustained attention and reward-based decision-making, including temporal discounting and gambling. Shared abnormalities were observed in the meta-analysis, where both clinical groups had reduced structure and function during cognitive control in medial prefrontal and anterior cingulate regions. During fMRI, shared abnormalities were also observed during executive function tasks of reward-based decision-making, where both clinical groups had reduced activation in ventromedial, inferior frontal and orbitofronto-striatal as well as temporo-parietal regions compared to controls. Disorder-specific abnormalities, on the other hand, were seen predominantly during tasks of non-emotional executive function. OCD patients had disorder-specific increases in striato-insular structure and function, whereas ASD individuals had increased structure but decreased function in dorsolateral prefrontal cortex during cognitive control. Temporo-parietal underactivation during sustained attention was uniquely associated with OCD compared to ASD and controls. These results present novel evidence that neurofunctional abnormalities, including temporo-parietal underactivation and striato-insular overactivation during non-emotional tasks of executive function may be mostly disorder-specific to OCD compared with ASD, whereas abnormalities during emotionally-driven tasks of reward-based decision-making are predominantly shared between ASD and OCD, particularly in ventromedial, inferior and orbitofronto-striatal regions. These studies provide preliminary indication that both shared and disorder-specific neurostructural and neurofunctional biomarkers underpin cognitive dysfunction in these disorders that may have implications for future diagnosis and treatment.

Le trouble obsessionnel-compulsif (TOC) se caractérise par la présence d’obsessions et/ou de compulsions. À la lumière de l’hétérogénéité du TOC et de la présence de styles de pensées et de comportements de type TOC chez des personnes présentant d’autres problèmes de santé mentale, certains ont fait valoir la nécessité de créer une catégorie des troubles du spectre obsessionnel-compulsif et d’identifier les processus cognitifs communs qui sous-tendent ces troubles afin d’élaborer des théories et des traitements plus parcimonieux. Une tendance générale à douter de ses sens et de ses facultés cognitives semble être le pivot des troubles obsessionnels. Selon l’approche basée sur les inférences, le doute obsessionnel est suscité par un processus de raisonnement erroné, soit la confusion inférentielle (CI). La CI implique (1) une méfiance vis-à-vis des sens et (2) une importance indue accordée aux possibilités imaginaires. La faible confiance cognitive (CC), un processus cognitif similaire, renvoie à une méfiance par rapport à son attention, sa perception et sa mémoire. Cette thèse a visé à étudier la CI et la faible CC en tant que potentiels facteurs cognitifs transdiagnostiques dans le spectre de l’obsessionnalité. Le premier article constitue une revue systématique avec méta-analyse destinée à évaluer le rôle de la CC pour différents sous-types du TOC et à examiner à quel degré la faible CC est associée aux symptômes du TOC. On a constaté que les individus atteints d’un TOC présentent une plus faible CC que les témoins sains, mais que celle-ci ne semble pas spécifique au TOC. L’article a aussi souligné la nécessité d’employer des tâches idiosyncratiques, ciblant les distorsions de la pensée propres au TOC, afin de bien mesurer la CC. Dans le cadre du deuxième article, le but a été d’approfondir cette piste de recherche en examinant le rôle commun de la faible CC et de la CI pour les différents sous-types du TOC, en procédant à des analyses de grappes avec un échantillon de 128 patients atteints d’un TOC. Alors qu’il a été constaté que la faible CC correspondait davantage aux sous-types de vérification et « tout à fait juste », la CI semble pertinente pour un plus large éventail de profils TOC. Le troisième article examine le rôle de la CI chez les troubles des conduites alimentaires (TCAs) en provoquant la CI expérimentalement. Des participantes atteintes d’un TA (n = 18) et des femmes témoins saines (n = 18) ont été assignées à l’une des deux conditions expérimentales : pour la condition CI élevée, les participantes ont visionné des vidéos où des séquences clés étaient manquantes, ce qui suscitait la CI; pour la condition CI faible, les participantes ont visionné les vidéos intégrales. Chez le groupe TA assigné à la condition CI élevée, on a observé une tendance à présenter un état de CI post-vidéos supérieur, un recours accru au comportement de neutralisation et, enfin, davantage de symptômes TOC. En somme, les résultats de cette thèse soulignent la pertinence de la CI et de la faible CC en tant que facteurs cognitifs transdiagnostiques sur le spectre obsessionnel-compulsif.<br>Obsessive-compulsive disorder (OCD) is a severe mental health disorder that involves obsessions and/or compulsions. In light of the heterogeneity of OCD and of the presence of OCD-like thinking and behaviors in several disorders, some have argued for the necessity of a new category of obsessive-compulsive spectrum disorders. Considering the overlap between various disorders characterized by obsessionality, there is a need for the identification of common cognitive processes that underpin these disorders in order to formulate more parsimonious explanations and treatments for these conditions. A general tendency to doubt the senses and cognitive faculties appears as central to obsessional disorders. According to the inference-based approach, the obsessional doubt is elicited by a faulty reasoning process known as inferential confusion (IC), that implicates (1) a distrust of the senses, and (2) an investment in imaginary possibilities. A similar construct is low cognitive confidence, which is defined as a distrust of one’s attention, perception and memory. The overarching goal of this thesis was to examine IC and low cognitive confidence as potential transdiagnostic cognitive factors across the spectrum of obsessionality. The first thesis article evaluated the role of cognitive confidence across OCD subtypes and examined the extent to which poor cognitive confidence is associated with OCD symptomatology by conducting a systematic review with a meta-analysis. This article led to the conclusion that individuals with OCD have lower cognitive confidence than healthy controls, but that it is unclear if cognitive confidence is specific to OCD, such that the use of idiosyncratic tasks appears to be required in order to correctly capture cognitive confidence in OCD. The second thesis article furthered this investigation by examining the joint role of low cognitive confidence and IC across OCD subtypes by performing cluster analyses using a sample of 128 individuals with OCD. While cognitive confidence was found to more relevant to the checking and “just right” subtypes, IC appeared to be relevant to a wider range of OCD profiles. The third thesis article sought to examine the role of IC in eating disorders by inducing IC experimentally. Female participants with an eating disorder (n = 18) and healthy controls participants (n = 18) were recruited. Participants were assigned to one of two experimental conditions: in the High IC condition, participants watched videos with key sequences missing – provoking a distrust of the senses and lending more space for the imagination, thus triggering IC. In the Low IC condition, participants watched videos without sequences missing. The eating disorder group assigned to the High IC condition demonstrated a trend for higher levels of state IC, greater neutralization behavior and higher OCD symptoms than those who were assigned to the Low IC condition. Taken together, the results of the present thesis underline the relevance of IC and cognitive confidence as transdiagnostic cognitive factors across the obsessive-compulsive spectrum.

Tese de doutoramento em Biociências, no ramo de Neurociências, apresentada ao Departamento de Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra<br>As doenças neuropsiquiátricas abrangem um largo espectro de distúrbios comportamentais, incluindo auto-flagelação, défices cognitivos, problemas de interacção social e emocional, entre outros. Dada a ausência de biomarcadores concretos e a sobreposição de sintomas comportamentais, o diagnóstico das doenças neuropsiquiátricas é por vezes efectuado por exclusão relativamente a outras causas subjacentes. Estudos genómicos em larga escala revelaram uma sobreposição de genes e vias de sinalização envolvidas em diferentes transtornos neuropsiquiátricos. Proteínas relacionadas com a sinaptogénese ou com a transmissão sináptica excitatória/inibitória, parecem estar implicadas, assim como os circuitos córtico-estriado-tálamo-corticais (CETC). Hipóteses recentes sugerem que uma disfunção estriatal possa estar na génese de padrões repetitivos e estereotipados de comportamento associados a doenças neuropsiquiátricas, tais como a Perturbação Obsessiva-Compulsiva (POC) e as Perturbações do Espectro Autista (PEA). As PEA afectam uma em cada 68 crianças nos Estados Unidos e são caracterizadas clinicamente por dificuldades ao nível da socialização e a pela existência de interesses repetitivos/estereótipados. A Perturbação Obsessiva-Compulsiva (POC) afecta 2-3% da população mundial e é caracterizada pela manifestação de preocupações excessivas (obsessões) associadas a rituais específicos (compulsões). Aproximadamente 30-40% dos doentes com PEA apresentam comorbidade com POC, sugerindo alguma sobreposição ao nível dos circuitos neuronais envolvidos. O gene Shank3, um dos principais candidatos em PEA que contribui possivelmente para ~1% de todos os casos, encontra-se enriquecido em sinapses cortico-estriatais glutamatérgicas e interage directamente com proteínas da família SAPAP. Ao nível das sinapses glutamatérgicas cortico-estriatais, as proteínas SAPAP3 e SHANK3 apresentam um padrão de expressão único, sendo os únicos membros das respectivas famílias proteicas enriquecidos nesta localização. A delecção do gene Sapap3 em murganhos resulta em comportamentos semelhantes a POC e a delecção do gene Shank3 resulta em lesões devido a grooming repetitivo e problemas de interacção social, assemelhando-se aos comportamentos observados em PEA. O trabalho experimental descrito nesta tese aprofunda o conhecimento relacionado com as bases neurais (e genéticas) do comportamento compulsivo e da ansiedade, utilizando murganhos Sapap3 e Shank3-KO como modelos de comportamento animal semelhante a POC e PEA. Os resultados sugerem que uma insuficiência de inibição estriatal pode causar uma hiperactividade do estriado nos murganhos Sapap3-KO, conduzindo a grooming excessivo. Demonstra-se que os interneurónios do estriado que expressam parvalbumina são necessários para o estabelecimento de hábitos nos murganhos WT, indicando-os como elementos-chave do perfil comportamental determinado pelo estriado. No trabalho descrito nesta tese foram também utilizados murganhos Shank3-cKI para demonstrar que o grooming patológico e problemas de interacção social, mas não a ansiedade, podem ser revertidos no estado adulto. Isto corrobora a hipótese de que diferentes dimensões sintomatológicas podem não só estar associadas com substratos neuronais distintos, como também ser independentes entre si. O trabalho realizado permitiu também observar que duas linhas distintas de murganhos transgénicos, contendo mutações associadas a PEA e esquizofrenia no exão 21 do gene Shank3, apresentam défices distintos e outros partilhados entre elas. Este estudo ilustra ao nível molecular, sináptico, bem como ao nível de circuitos neuronais e comportamental, como diferentes mutações no gene Shank3 podem contribuir para sintomas distintos e perturbações associadas. Embora os murganhos Sapap3- e Shank3-KO apresentem um fenótipo de lesões devido a grooming repetitivo com origem biológica distinta, ambos os genes partilham um padrão de expressão elevado ao nível cortico-estriatal. Relativamente à patologia humana, propomos que um comportamento patológico em comum possa na verdade emergir de diferentes perturbações afectando os mesmo circuitos neuronais. Estes resultados ilustram também a forma como uma disrupção de proteínas com uma função sináptica pode afectar os circuitos neuronais e ao mesmo tempo promover a descoberta de elos importantes na compreensão de doenças neuropsiquiátricas.<br>Neuropsychiatric disorders encompass a wide range of diseases that manifest as one or many altered behaviors, including but not limited to self-injurious behavior, impaired social-emotional communication and cognitive deficits. Due to the lack of biomarkers and overlapping behavioral symptoms, diagnosis of neuropsychiatric disorders sometimes relies on exclusion of other underlying conditions. Current data from large scale genomic studies, suggests overlapping genes and pathways for different neuropsychiatric disorders. Proteins that play a role in synaptogenesis or excitatory/inhibitory synaptic transmission are implicated as well as cortico-striato-thalamocortical circuits (CSTC). In recent years striatal dysfunction has been hypothesized in repetitive and stereotyped behaviors associated with neuropsychiatric disorders, such as obsessive compulsive disorder (OCD) and autism spectrum disorders (ASD). Autism spectrum disorders (ASD) are clinically defined by the symptoms of social impairment and repetitive behavior/restricted interests, affecting 1 in 68 children in the United States. OCD (Obsessive Compulsive Disorder) affects 2-3% of the worldwide population and is characterized by excessive preoccupations (obsessions) associated to specific rituals (compulsions). Approximately 30-40% ASD patients have comorbidity with OCD, suggesting some degree of overlapping circuitry. Shank3, one of the most prominent ASD genes that is estimated to contribute to ~1% of all ASD cases, is enriched at corticostriatal glutamatergic synapses and directly interacts with SAPAP protein-family. At corticostriatal glutamatergic synapses SAPAP3 and SHANK3 proteins show a unique expression pattern, being the only members of their protein-family highly enriched at this location. Deletion of the Sapap3 gene in mice leads to striking OCD-like behavior and mice with Shank3 deletion exhibit self-injurious repetitive grooming and social interaction deficits, reminiscent of autistic-like behaviors. Experimental work described on this thesis deepens our knowledge on the neural (and genetic) basis of compulsive behavior and anxiety, using Sapap3 and Shank3-KO mice as animal models of OCD and ASD-like behaviors. Results suggest that insufficient striatal inhibition might be causing striatum hyperactivity in the Sapap3-KO mice and leading to repetitive overgrooming. Parvalbumin interneurons within the striatum are shown to be required for proper habit formation in WT mice, implicating them as key players in determining striatum behavioral output. Experimental work described on this thesis also takes advantage of a Shank3 cKI mouse to show that pathological grooming and social interaction deficits can be reversed in adulthood, but not anxiety. This supports the idea that different symptom dimensions might be associated with distinct neural substrates and might be independent of one another. Further experimental work shows that two mutant mice lines carrying exon 21 Shank3 mutations linked to ASD and schizophrenia, display both shared and distinct defects. This study provides an explanation at the molecular, synaptic, circuit and behavioral level, on how different mutations in the Shank3 gene may contribute to different symptoms and hence disorders. Although Sapap3- and Shank3-KO mice have self-injurious grooming phenotypes that are unique in their biological origins, both genes share an enriched corticostriatal expression. In regards to human pathology, we suggest that a commonly shared pathological behavior, compulsivity, may arise from different causal insults that impact the same brain circuits. Moreover these results illustrate how disruption of scaffolding proteins can affect brain circuitry and are able to provide insightful links to neuropsychiatric disorders.<br>Fundação para a Ciência e Tecnologia - SFRH/BD/33894/2009

This chapter reviews the literature on obsessive compulsive spectrum disorders (i.e., obsessive compulsive disorder, body dysmorphic disorder, trichotillomania, Tourette syndrome, and varied body-focused repetitive behaviors) in children and adolescents. For each disorder, data on phenomenology, associated clinical characteristics, etiology, and treatment are reviewed. The chapter concludes with a discussion of future research and clinical directions, such as novel augmentation strategies, diagnostic classification of obsessive compulsive spectrum disorders, and methods of maximizing treatment outcome.

The current chapter provides an overview of psychoanalytic and behavioral theories of obsessive compulsive disorder and related conditions (i.e., hoarding, hypochondriasis, body dysmorphic disorder, trichotillomania, and tic disorders), and reviews the empirical support for these psychological theories. While Freud correctly ascribed compulsive rituals to an anxiety-reducing role, the more fundamental tenets of his drive model of obsessional development, and the subsequent focus on the role of defense mechanisms, have remained largely untested. In contrast, behavioral theories of obsessive compulsive and spectrum disorders revolutionized the psychological conceptualization and treatment of these disorders, and there is strong evidence accumulated over the past 40 years demonstrating the seminal role of operant conditioning processes in the maintenance of obsessive compulsive and related spectrum disorders. The evidence supporting the role of classical conditioning in symptom development is less clear; however, learning theory has contributed a partial understanding of the etiology of these conditions.