Unraveling the Neural Landscape of Mental Disorders Using Double Functional Independent Primitives

Background Mental illnesses extract personal and societal costs, leading to significant challenges in cognitive function, emotional regulation, and social behavior. These disorders are thought to result from disruptions in how different brain regions communicate with each other. Despite advances in neuroimaging, current methods are not always precise enough to permit a full understanding of the complexity of these disruptions. More advanced approaches are needed to better identify and characterize the specific brain network alterations linked to different psychiatric conditions. Methods We used a hierarchical approach to derive double functional independent primitives (dFIPs) from resting-state functional magnetic resonance imaging data. dFIPs represent independent patterns of functional network connectivity across the brain. Our study utilized a large multisite dataset comprising 5805 individuals diagnosed with schizophrenia (SCZ), autism spectrum disorder (ASD), bipolar disorder, and major depressive disorder and healthy control individuals. We analyzed how combinations of dFIPs differentiated psychiatric diagnoses. Results Distinct dFIP patterns emerged for each disorder. SCZ was characterized by heightened cerebellar connectivity and reduced cerebellar-subcortical connectivity. In ASD, sensory domain hyperconnectivity was prominent. Some dFIPs displayed disorder-specific connectivity patterns, while others exhibited commonalities across multiple conditions. These findings underscore the utility of dFIPs in revealing neural connectivity alterations unique to each disorder, serving as unique fingerprints for different mental disorders. Conclusions Our study demonstrates that dFIPs provide a novel, data-driven method for identifying disorder-specific functional connectivity patterns in psychiatric conditions. These distinct neural signatures offer potential biomarkers for mental illnesses, contributing to a deeper understanding of the neurobiological underpinnings of these disorders.