Functional connectome-based predictive modeling of suicidal ideation

Suicide represents an egregious threat to society despite major advancements in medicine, in part due to limited knowledge of the biological mechanisms of suicidal behavior. We apply a connectome predictive modeling machine learning approach to identify a reproducible brain network associated with suicidal ideation in the hopes of demonstrating possible targets for novel anti-suicidal therapeutics. Patients were recruited from an inpatient facility at The Menninger Clinic, in Houston, Texas (N = 261; 181 with active and specific suicidal ideation) and had a current major depressive episode and recurrent major depressive disorder, underwent resting-state functional magnetic resonance imaging. The participants' ages ranged from 18 to 70 (mean ± SEM = 31.6 ± 0.8 years) and 136 (52 %) were males. Using this approach, we found a robust and reproducible biomarker of suicidal ideation relative to controls without ideation, showing that increased suicidal ideation was associated with greater internal connectivity and reduced internetwork external connectivity in the central executive, default mode, and dorsal salience networks. We also found evidence for higher external connectivity between ventral salience and sensorimotor/visual networks as being associated with increased suicidal ideation. Overall, these observed differences may reflect reduced network integration and higher segregation of connectivity in individuals with increased suicide risk. Our findings provide avenues for future work to test novel drugs targeting these identified neural alterations, for instance drugs that increase network integration.