Suicidal risk is associated with hyper-connections between frontal-parietal and limbic networks in patients with depression

Abstract Suicide is a complex behavior strongly associated with depression. Despite extensive research, an objective biomarker for evaluating the suicide risk precisely and timely is still lacking. Using the precision resting-state fMRI method, we studied 61 depressive patients with suicide ideation (SI) or suicide attempt (SA), and 35 patients without SI to explore functional biomarkers of suicide risk. Among them, 21 participants also completed electroconvulsive therapy (ECT) treatment, allowing the examination of functional changes across different risk states within the same individual. Functional networks were localized in each subject using resting-state fMRI and then an individualized connectome was constructed to represent the subject’s functional brain organization. Compared to patients without SI, patients with suicide risk showed hyper-connectivity involving the frontoparietal network (FPN, p = 0.001). ECT treatment normalized these hyper-connections, with connectivity between the FPN and limbic system (LMB) showing the most significant reduction (p < 0.001). Post-hoc analysis indicated that the FPN-LMB connectivity was also significantly altered in the SA group compared to the SI group (p = 0.001), which may reflect the elevation of suicide risk across these two groups. These findings suggest that functional coupling between the FPN and LMB may constitute an important biomarker for evaluating suicide risk and may provide potential targets for interventions such as non-invasive brain stimulation.