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.

Loss and abuse in children can lead to unresolved–disorganized (UD) attachment. How this condition relates to brain structure and functional connectivity (FC) is unknown. We therefore aimed to investigate gray matter volume (GMV) and resting state functional connectivity (RSFC) correlates of UD attachment in adolescents. Based on previous neuroimaging studies of trauma effects, we hypothesized that the structure of the amygdala and hippocampus and the FC of the latter would be linked to UD attachment. Anatomical and RSFC data were collected from a mixed group of adolescents (N = 74) with symptoms of posttraumatic stress disorder (PTSD) related to childhood sexual abuse (CSA), anxiety/depressive symptoms, and without psychiatric disorder as part of the Emotional Pathways’ Imaging Study in Clinical Adolescents (EPISCA). Bilateral volumes of the amygdala and hippocampus were measured using the FMRIB Software Library, and RSFC of the hippocampus was assessed using seed‐based correlation. UD attachment was measured using the Adult Attachment Interview. Hierarchical regression and correlation were used to assess the associations between UD status (continuous and categorical), brain structure, and FC, adjusting for a general psychopathology factor, puberty stage, gender, age, and IQ. UD attachment was associated with a smaller left hippocampal volume, R 2 = .23, and a higher level of FC between the hippocampus and the middle temporal gyrus and lateral occipital cortex. The associations among UD attachment, specific brain structure, and FC across psychopathological classifications shows promise for dimensional complements to the dominant classificatory approach in clinical research and practice.

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