Browsing by Subject "Obsessive-compulsive disorder"

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    Open Access
    Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture
    (Public Library of Science, 2013) Davis, Lea K; Yu, Dongmei; Keenan, Clare L; Gamazon, Eric R; Konkashbaev, Anuar I; Derks, Eske M; Neale, Benjamin M; Yang, Jian; Lee, S Hong; Evans, Patrick
    Author Summary Family and twin studies have shown that genetic risk factors are important in the development of Tourette Syndrome (TS) and obsessive compulsive disorder (OCD). However, efforts to identify the individual genetic risk factors involved in these two neuropsychiatric disorders have been largely unsuccessful. One possible explanation for this is that many genetic variations scattered throughout the genome each contribute a small amount to the overall risk. For TS and OCD, the genetic architecture (characterized by the number, frequency, and distribution of genetic risk factors) is presently unknown. This study examined the genetic architecture of TS and OCD in a variety of ways. We found that rare genetic changes account for more genetic risk in TS than in OCD; certain chromosomes contribute to OCD risk more than others; and variants that influence the level of genes expressed in two regions of the brain can account for a significant amount of risk for both TS and OCD. Results from this study might help in determining where, and what kind of variants are individual risk factors for TS and OCD and where they might be located in the human genome.
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    Open Access
    Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative
    (2020-02-14) Simpson, Helen B; van den Heuvel, Odile A; Miguel, Euripedes C; Reddy, Y. C J; Stein, Dan J; Lewis-Fernández, Roberto; Shavitt, Roseli G; Lochner, Christine; Pouwels, Petra J W; Narayanawamy, Janardhanan C; Venkatasubramanian, Ganesan; Hezel, Dianne M; Vriend, Chris; Batistuzzo, Marcelo C; Hoexter, Marcelo Q; de Joode, Niels T; Costa, Daniel L; de Mathis, Maria A; Sheshachala, Karthik; Narayan, Madhuri; van Balkom, Anton J L M; Batelaan, Neeltje M; Venkataram, Shivakumar; Cherian, Anish; Marincowitz, Clara; Pannekoek, Nienke; Stovezky, Yael R; Mare, Karen; Liu, Feng; Otaduy, Maria C G; Pastorello, Bruno; Rao, Rashmi; Katechis, Martha; Van Meter, Page; Wall, Melanie
    Background Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. Methods We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. Discussion Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.