Genetic and Environmental Risk factors associated with Obsessive-Compulsive Disorder and its symptom dimensions: A twin study
There is an incomplete understanding of the heritability and the specific genetic bases of Obsessive-Compulsive Disorder (OCD). It has a complex multifactorial etiology comprising both biological as well as psychosocial components not clearly elucidated. Moreover, OCD is clinically heterogeneous and...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/311415 |
| Acceso en línea: | http://hdl.handle.net/10803/311415 |
| Access Level: | acceso abierto |
| Palabra clave: | Neurosi obsessiva Obsesión Obsessive-compulsive disorder Ansietat Ansiedad Anxiety Genètica de la conducta Genética de la conducta Behavior genetics Bessons Gemelos Twins Ciències de la Salut 616 |
| Sumario: | There is an incomplete understanding of the heritability and the specific genetic bases of Obsessive-Compulsive Disorder (OCD). It has a complex multifactorial etiology comprising both biological as well as psychosocial components not clearly elucidated. Moreover, OCD is clinically heterogeneous and it is unknown whether this complex phenotypic reflects distinct or partially distinct etiology mechanisms. Until recently OCD was designated as an anxiety disorder (AD) due to the similarities in phenomenology, comorbidity and aggregation in families suffering from various ADs. In this context, it was implicitly understood that OCD was sharing common etiological factors with other ADs. However, the idea that disorders not classified in the anxiety group could also be associated with OCD has generated an intense and controversial debate about whether OCD is indeed and AD or, in fact, more closely related to other disorders, with the anxiety merely as a consequence of OCD symptoms. Twin studies are considered a key tool in behavioral genetics used to dissect the nature (genetic) versus the nurture (environmental) contributions to individual phenotypes. Also, twin studies are one of the best ways of identifying genetic markers relevant to understand the etiological factors that underlie complex psychopathologies. Unfortunately, there is a lack of empirical twin studies that have actually directly compared the OCD, obsessive-compulsive and related disorders (OCRDs) and ADs together. OBJECTIVES: To clarify biological components of OCD etiology by examining specific and shared genetic factors between Obsessive-Compulsive (OC) symptom dimensions (forbidden thoughts, checking, symmetry/ordering and washing) anxiety disorders (social phobia (SP), generalized anxiety disorder (GAD) and panic disorder (PD)) and OC spectrum disorders (body-dysmorphic disorder (BDD), hoarding disorder (HD) and hypochondriasis (HYP)). As a second aim this thesis would like to study the patter of causation relationships between OCD, the ADs and the OCRDs, using a new statistical approach to infer causation in twin data (ICE FALCON). A non-clinical sample of 2,495 male and female twins of 18 to 45 years old was used to address these objectives. The results of the present thesis show for the first time that the patterns of heritability of hypochondriasis, BDD and HD symptoms present genetic sex differences. Moreover, it shows that anxiety makes an essential contribution to the complex etiology of OCD. In the causation inference analysis it was demonstrated that OCD symptoms increase an individual’s probability to develop GAD, PD and HD symptoms, but not revers; and that social phobia increases an individual probability to develop OCD symptoms. Regarding OCD dimensions this thesis found that forbidden thoughts and washing show the highest association with the AD symptoms while symmetry/ordering shows the highest genetic specificity. On the other hand, checking dimension is genetically associated with other OCRDs (specifically BDD) and AD symptoms. Finally, only checking and symmetry/ordering dimensions share environmental factors with the ADs. In summary, this thesis answers questions of high clinical and diagnostic relevance for OCD, one of the most prevalent mental disorders (2-3%) and one of the largest generators of chronic suffering and cost in the current health programs. All the results from this thesis are related to the biological basis underlying the disorder and are aimed to elucidate more stable endophenotypes of analysis. This could have a large impact on both, improving patients’ quality of life and in the reduction of costs associated with the handling of a complex and heterogeneous disorder. |
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