Global Initiative for Harmonized Functional MRI in Psychiatry - ABSTRACT The global burden of mental illness is immense, costing the global economy over $6 trillion USD annually. Even so, neuropsychiatry is still in severe need of reliable biosignatures - to improve diagnosis and disease subtyping, and to better evaluate treatments. Resting-state functional MRI (rs-fMRI) opens up a vast landscape of discovery by approximating large-scale intrinsic brain networks. Even so, most individual rs-fMRI studies focus on single disorders with limited power, constrained by a complex analysis decision tree resulting in highly heterogeneous methods, with no global forum to verify or replicate discoveries. Here we launch an unprecedented Global fMRI Initiative in Psychiatry - with the goal of transforming functional neuroimaging in psychiatry by addressing long-standing roadblocks of reproducibility and standardization. We leverage the success of 15 years of work in the ENIGMA consortium to bring together over 1,000 laboratories from 45 countries to conduct the largest fMRI study in the literature. In doing so, we will harmonize international data sets across 8 psychiatric and neurodevelopmental disorders including: schizophrenia (SCZ), bipolar disorder (BD), post-traumatic stress disorder (PTSD), major depression disorder (MDD), obsessive compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and anorexia nervosa (AN). In Aim 1, our novel AI tools will create a global framework for transdiagnostic research by accelerating analysis and image quality control, quantifying methods-related variance and reliability. In Aim 2, we will isolate and rigorously validate biosignatures of mental illness on 15,719 cases and 20,225 controls. We then identify shared and distinct functional connectivity patterns across the 8 disorders, mirroring genetic findings from GWAS studies. This project includes a foreign subaward to MPI Dr. Clara Moreau’s team at Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada. The foreign effort is limited to analysis and creation of fMRI workflows; no data collection of any kind is supported by this award, and the project instead leverages already-collected data at no cost to U.S. taxpayers. This work cannot be conducted in the U.S.: Dr. Moreau chairs the ENIGMA fMRI Working Group and her team leads and architected HALFpipe, the primary analysis pipeline now in wide use across ENIGMA, an expertise that is not substitutable. The clear benefit to the U.S. is decisive: this is the largest, best-powered psychiatric neuroimaging study ever conducted, validating brain biomarkers across 8 disorders of urgent U.S. public-health importance and directly serving the U.S. biotech, pharmaceutical, and healthcare economy. As our Letters of Support show, a vast and growing community will benefit from this rigorous framework with efficient tools to replicate and validate their findings, galvanizing the field to address the replication crisis in neuroscience and psychiatry.
