Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative

Abstract

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.

The state of psychiatric research in the Asia Pacific region

“…Another emerging field is neuroscience (eg, biological markers, genetics, and neuroimaging) research (Patra & Kar, 2020; Ramesh, Venkatesan, Chellathai, & Silamban, 2020; E. Sharma, Vaidya, et al, 2020; Simpson et al, 2020; V. Singh, Mishra, Prajapati, Ampapathi, & Thakur, 2020), as well as research into newer treatment modalities and novel interventions such as yoga (Choudhary et al, 2019; Gandhi et al, 2019; Varambally, George, & Gangadhar, 2020).…”

Genome-wide association study identifies new locus associated with OCD

“…Age at onset is usually in early to late adolescence but diagnosis and initiation of treatment are often delayed by several years 3;4 . OCD frequently co-occurs with other disorders, particularly tic disorders, eating disorders, depressive disorders, and anx-D R A F T iety disorders [5][6][7][8] . Although anxiety is a common symptom of OCD, OCD is currently considered to be distinct from anxiety disorders in terms of its epidemiological, clinical and pathophysiological presentation.…”

Cross-national harmonization of neurocognitive assessment across five sites in a global study.

“…This project is part of an ongoing, cross-sectional, global multicentre study involving five countries across five continents (Brazil, India, the Netherlands, South Africa, and the USA) that aims to identify brain biomarkers of OCD profiles in adults. For this purpose, sociodemographic, clinical, neuroimaging, and neurocognitive data on volunteers with OCD and age, sex, and education-matched healthy controls are still being collected (https://global-ocd.org; Simpson et al, 2020). The parent study was designed to tap into different brain circuits with computerized and standardized tasks that are in line with the National Institute of Mental Health’s (NIMH’s) RDoC, with negligible reliance on language and known to reflect cognitive domains affected by obsessive-compulsive symptoms (Abramovitch et al, 2015; Benzina et al, 2016; Goodman et al, 2021; Robbins et al, 2019).…”