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Obsessive-compulsive disorder phenotypes: implications for genetic studies

Abstract

Obsessive-compulsive disorder (OCD) clinical presentation is remarkably diverse, and can vary both within and across patients over time. This variability in the phenotypic expression has led to the hypothesis that OCD is a heterogeneous disorder and that this heterogeneity obscures the findings of clinical, natural history and treatment response studies and complicates the search for vulnerability genes. A complete understanding of what comprises OCD and the underlying etiological mechanisms will require a dramatic change in how the disorder is conceptualized. In this review, several different approaches that may represent the first steps in this reconceptualization are discussed. These approaches include (1) narrowing the phenotype to identify categorically defined more homogeneous and mutually exclusive subtypes of OCD, (2) considering OC symptom dimensions as quantitative components of the more complex OCD phenotype and (3) broadening the phenotype to include other etiologically related conditions. A combined dimensional approach within distinctive subgroups is proposed as probably the most effective in helping to identify the heritable components of OCD. By identifying heritable components of OCD, it should be possible to find genes for these separate components. The review continues with the illustration of the possible role of some epigenetic risk and protective factors in the OCD presentation and the relevance of examining associated traits and/or endophenotypes to enhance our ability to understand the genetic basis of OCD. To conclude, we discuss the variability in treatment outcome and the significance of the development of specific pharmacological and/or behavioral based therapies tailored to each of these phenotypes.

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Acknowledgements

This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP): #99/08560-6 to Dr Miguel, #99/08560-6 to Dr Mercadante, #98/15013-9 to Dr Hounie, #03/07451-6 to Dr Rosario-Campos and #06697-6 to Dr Chacon. This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ), Brazil (grant #521369/96-7) to Dr Miguel and MackPesquisa to Dr Mercadante.

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Miguel, E., Leckman, J., Rauch, S. et al. Obsessive-compulsive disorder phenotypes: implications for genetic studies. Mol Psychiatry 10, 258–275 (2005). https://doi.org/10.1038/sj.mp.4001617

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  • DOI: https://doi.org/10.1038/sj.mp.4001617

Keywords

  • obsessive-compulsive disorder
  • obsessive behaviors
  • compulsive behaviors
  • genetics
  • molecular genetics

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