Transdiagnostic connectome signatures from resting-state fMRI predict individual-level intellectual capacity

Medication and other therapies for psychiatric disorders show unsatisfying efficacy, in part due to the significant clinical/ biological heterogeneity within each disorder and our over-reliance on categorical clinical diagnoses. Alternatively, dimensional transdiagnostic studies have provided a promising pathway toward realizing personalized medicine and improved treatment outcomes. One factor that may influence response to psychiatric treatments is cognitive function, which is reflected in one’s intellectual capacity. Intellectual capacity is also reflected in the organization and structure of intrinsic brain networks. Using a large transdiagnostic cohort ( n = 1721), we sought to discover neuroimaging biomarkers by developing a resting-state functional connectome-based prediction model for a key intellectual capacity measure, Full-Scale Intelligence Quotient (FSIQ), across the diagnostic spectrum. Our cross-validated model yielded an excellent prediction accuracy (r = 0.5573, p < 0.001). The robustness and generalizability of our model was further validated on three independent cohorts ( n = 2641). We identified key transdiagnostic connectome signatures underlying FSIQ capacity involving the dorsal-attention, frontoparietal and default-mode networks. Meanwhile, diagnosis groups showed disorder-specific biomarker patterns. Our findings advance the neurobiological understanding of cognitive functioning across traditional diagnostic categories and provide a new avenue for neuropathological classification of psychiatric disorders.