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Metrics details. 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.

We will study medication-free adults with OCD, unaffected adult siblings of individuals with OCD, and healthy control subjects at five expert research sites across five countries Brazil, India, Netherlands, South Africa, and the U. All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging MRI.

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. 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.

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