Multidimensional Investigation of Neurobiological, Demographic, and Psychological Factors in Depression

Global Burden of Mental Illness

Serious mental illnesses significantly contribute to global disability. By 2030, it is expected that mental health disorders will surpass cancer, diabetes, and respiratory diseases in terms of economic costs. In the United States, major depressive disorder incurs an annual cost of $326 billion and affects over 21 million adults, with approximately 45,000 lives lost to suicide each year.

Depression is a clinically heterogeneous disorder, manifesting in various ways and often accompanied by comorbidities such as anxiety, substance use, and chronic medical conditions, all of which complicate treatment. The chronic nature of depression is evident, with 60- 70% of patients experiencing recurrent episodes. Many individuals suffering from depression are at a higher risk of suicide, highlighting the urgent need for better treatment options.

Unfortunately, the drug development process is fraught with challenges, including high costs, lengthy timelines, and a 45% failure rate. Furthermore, most current treatments focus on managing symptoms rather than addressing the underlying causes of depression.

A Paradigm Shift Through Precision Psychiatry

The FNIH is establishing the Multidimensional Investigation of Neurobiological, Demographic, and Psychological Factors in Depression to conduct a transformative study aimed at understanding the complexities and diverse nature of depression. This longitudinal, observational study will reflect real-world clinical settings and promote personalized treatment approaches by using multimodal biomarkers to identify the factors that influence treatment outcomes.

The study will be carried out in several stages. Stage 1 will involve a small cohort to test the feasibility of the study across multiple sites. In Stage 2, the participant pool will expand to a size sufficient to generate reliable and informative data, which will help refine biomarkers and identify subtypes of depression. The Confirmatory Stage will validate the findings from Stage 2. This stepwise approach ensures a comprehensive understanding of depression and progressively refines strategies with each stage.

A notable aspect of this study is including participants aged 15 and older, which will allow for a deeper understanding of youth mental health and the unique challenges faced by younger populations. Data will be collected from a wide range of sources, including biomarkers (e.g., genomics, molecular data, neuroimaging, and digital markers), clinical assessments, and patient-reported outcomes. A data fusion approach will integrate these diverse data types, ensuring efficient storage and processing to support the study’s objectives. Additionally, minimizing the burden on patients through remote assessments will enhance engagement, and inclusivity, and reduce bias, making the findings broadly applicable. This prospective study has the potential to identify endophenotypes associated with depression, develop personalized care strategies, and accelerate drug development. Its primary goal is to improve symptom management, enhance clinical outcomes, and ensure applicability to diverse patient populations, including those with comorbidities. Furthermore, the collaboration fostered by the FNIH’s public-private partnership aims to improve access to high-quality data, promote open collaboration, and broaden the study’s impact on other serious mental illnesses, ultimately advancing the field of precision psychiatry.

Resources

Project Overview Document

The FNIH is actively engaging public, private, and philanthropic partners for the study Design Phase as we look ahead to implementation of this public-private partnership. To learn more about becoming a scientific and funding partner, please contact Liz Mesmer.